| 2021 | Differentiating multisystem inflammatory syndrome in children: a single-centre retrospective cohort study. | Arch Dis Child | Features of multisystem inflammatory syndrome in children (MIS-C) overlap with other febrile illnesses, hindering prompt and accurate diagnosis. The objectives of this study were to identify clinical and laboratory findings that distinguished MIS-C from febrile illnesses in which MIS-C was considered but ultimately excluded, and to examine the diseases that most often mimicked MIS-C in a tertiary medical centre.We identified all children hospitalised with fever who were evaluated for MIS-C at our centre and compared clinical signs and symptoms, SARS-CoV-2 status and laboratory studies between those with and without MIS-C. Multivariable logistic LASSO (least absolute shrinkage and selection operator) regression was used to identify the most discriminative presenting features of MIS-C.We identified 50 confirmed MIS-C cases (MIS-C) and 68 children evaluated for, but ultimately not diagnosed with, MIS-C (MIS-C). In univariable analysis, conjunctivitis, abdominal pain, fatigue, hypoxaemia, tachypnoea and hypotension at presentation were significantly more common among MIS-C patients. MIS-C and MIS-C patients had similar elevations in C-reactive protein (CRP), but were differentiated by thrombocytopenia, lymphopenia, and elevated ferritin, neutrophil/lymphocyte ratio, BNP and troponin. In multivariable analysis, predictors of MIS-C included age, neutrophil/lymphocyte ratio, platelets, conjunctivitis, oral mucosa changes, abdominal pain and hypotension.Among hospitalised children undergoing evaluation for MIS-C, children with MIS-C were older, more likely to present with conjunctivitis, oral mucosa changes, abdominal pain and hypotension, and had higher neutrophil/lymphocyte ratios and lower platelet counts. These data may be helpful for discrimination of MIS-C from other febrile illnesses, including bacterial lymphadenitis and acute viral infection, with overlapping features. |
| 2021 | Critical illness-related corticosteroid insufficiency in dogs with systemic inflammatory response syndrome: A pilot study in 21 dogs. | Vet J | Critical illness-related corticosteroid insufficiency (CIRCI) refers to a lack of adequate corticosteroid activity, which occurs in up to 48% of dogs with sepsis. However, data regarding the occurrence of CIRCI in critically-ill dogs are still scarce. This study aimed to assess: (1) the relationship between CIRCI and clinicopathological inflammatory markers, hypotension and mortality; and (2) the impact of low-dose hydrocortisone treatment on survival. Twenty-one dogs diagnosed with systemic inflammatory response syndrome (SIRS) were enrolled in a prospective case-control study. All dogs were initially evaluated for adrenal function with an ACTH stimulation test and dogs with Δcortisol ≤ 3 μg/dL were diagnosed with CIRCI. Mean arterial pressure (MAP), white blood cell (WBC), band neutrophils (bNs), c-reactive protein (CRP), and 28-day mortality rate were assessed. Fourteen dogs were treated with low-dose hydrocortisone. The relationships between CIRCI and MAP, WBC, bN, CRP, basal cortisol and mortality were investigated, as was the association between mortality and hydrocortisone treatment. Ten of 21 (48%) dogs were diagnosed with CIRCI. Increased bNs were associated with the presence of CIRCI (P = 0.0075). CRP was higher in dogs with CIRCI (P = 0.02). Fourteen of 21 (66%) dogs died during the study (6/14 had CIRCI). Basal hypercortisolemia (>5 μg/dL) was associated with increased risk of mortality (P = 0.025). Based on our diagnostic criteria, CIRCI occurs frequently in dogs with SIRS and was associated with increased bNs and increased CRP. In this study, CIRCI and low-dose hydrocortisone treatment were not significantly associated with mortality, but basal hypercortisolemia was associated with increased mortality. |
| 2021 | Acute kidney injury in children with COVID-19: a retrospective study. | BMC Nephrol | Acute kidney injury (AKI) is a complication of coronavirus disease 2019 (COVID-19). The reported incidence of AKI, however, varies among studies. We aimed to evaluate the incidence of AKI and its association with mortality and morbidity in children infected with severe acute respiratory distress syndrome coronavirus 2 (SARS-CoV-2) who required hospital admission.This was a multicenter retrospective cohort study from three tertiary centers, which included children with confirmed COVID-19. All children were evaluated for AKI using the Kidney Disease Improving Global Outcomes (KDIGO) definition and staging.Of 89 children included, 19 (21 %) developed AKI (52.6 % stage I). A high renal angina index score was correlated with severity of AKI. Also, multisystem inflammatory syndrome in children (MIS-C) was increased in children with AKI compared to those with normal kidney function (15 % vs. 1.5 %). Patients with AKI had significantly more pediatric intensive care admissions (PICU) (32 % vs. 2.8 %, p < 0.001) and mortality (42 % vs. 0 %, p < 0.001). However, AKI was not associated with prolonged hospitalization (58 % vs. 40 %, p = 0.163) or development of MIS-C (10.5 % vs. 1.4 %, p = 0.051). No patient in the AKI group required renal replacement therapy. Residual renal impairment at discharge occurred in 9 % of patients. This was significantly influenced by the presence of comorbidities, hypotension, hypoxia, heart failure, acute respiratory distress, hypernatremia, abnormal liver profile, high C-reactive protein, and positive blood culture.AKI occurred in one-fifth of children with SARS-CoV-2 infection requiring hospital admission, with one-third of those requiring PICU. AKI was associated with increased morbidity and mortality, and residual renal impairment at time of discharge. |
| 2021 | Atherosclerosis-calcification score and predictors of intra-dialytic hypotension. | Clin Nephrol | Intra-dialytic hypotension episodes (ID-Hypos) cause significant reduction of dialysis efficiency and increased cardiovascular morbimortality. Atherosclerosis and vascular calcification are two closely inter-related processes that occur prematurely and progress aggressively in maintenance hemodialysis (MHD) patients.To study the predictors of ID-Hypos, particularly a novel combined atherosclerosis-calcification score (CACS) (0 to 6) obtained by adding the atherosclerosis score (AS) to a modified abdominal aortic calcification score (AACS), each ranging 0 to 3.In 60 adult MHD patients, AS was derived from ankle-brachial index and carotid ultrasound. AACS was modified from Kauppila score applied on lateral abdominal plain radiographs. The number of sessions complicated by ≥ 1 ID-Hypos over 14 weeks was recorded and correlated with CACS, ultrafiltration rate (UFR), and other hemodynamic and laboratory parameters.Patients developed a median of 10.5 ID-Hypos (IQR 5.75 - 14). The number of ID-Hypos had a statistically significant positive correlation with CACS (r = 0.291, p = 0.024), but not with its individual components. AACS had a statistically significant positive correlation with s. phosphorus and calcium-phosphorus product. On multivariate analysis, the most significant independent predictors of ID-Hypos were high UFR, high CACS, and low hemoglobin. Serum C-reactive protein had a positive correlation with ID-Hypos that was lost in the adjusted models.High UFR, CACS, and anemia are significant predictors of ID-Hypos. CACS may help in quantifying vascular pathology and characterizing MHD patients at highest risk for ID-Hypos, those who would be prioritized for potential preventive measures like biocompatible membranes or hemodiafiltration. A background of chronic inflammation may underlie and link patient-related ID-Hypos risk factors. |
| 2021 | Multisystem Inflammatory Syndrome in Infants <12 months of Age, United States, May 2020-January 2021. | Pediatr Infect Dis J | Multisystem inflammatory syndrome in children (MIS-C), temporally associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been identified in infants <12 months old. Clinical characteristics and follow-up data of MIS-C in infants have not been well described. We sought to describe the clinical course, laboratory findings, therapeutics and outcomes among infants diagnosed with MIS-C.Infants of age <12 months with MIS-C were identified by reports to the CDC's MIS-C national surveillance system. Data were obtained on clinical signs and symptoms, complications, treatment, laboratory and imaging findings, and diagnostic SARS-CoV-2 testing. Jurisdictions that reported 2 or more infants were approached to participate in evaluation of outcomes of MIS-C.Eighty-five infants with MIS-C were identified and 83 (97.6%) tested positive for SARS-CoV-2 infection; median age was 7.7 months. Rash (62.4%), diarrhea (55.3%) and vomiting (55.3%) were the most common signs and symptoms reported. Other clinical findings included hypotension (21.2%), pneumonia (21.2%) and coronary artery dilatation or aneurysm (13.9%). Laboratory abnormalities included elevated C-reactive protein, ferritin, d-dimer and fibrinogen. Twenty-three infants had follow-up data; 3 of the 14 patients who received a follow-up echocardiogram had cardiac abnormalities during or after hospitalization. Nine infants had elevated inflammatory markers up to 98 days postdischarge. One infant (1.2%) died after experiencing multisystem organ failure secondary to MIS-C.Infants appear to have a milder course of MIS-C than older children with resolution of their illness after hospital discharge. The full clinical picture of MIS-C across the pediatric age spectrum is evolving. |
| 2021 | Septic Shock Due to Capnocytophaga canimorsus Infection in a Splenectomized Patient. | Cureus | is a gram-negative rod that is part of the commensal flora of dogs' mouths. Among splenectomized patients who maintain close contact with dogs, the bacteria can lead to infection and fulminant sepsis even without evidence of a skin breach. In this report, we describe the case of a 71-year-old woman who had undergone splenectomy 35 years ago. She came to our emergency department complaining of back pain, myalgia, asthenia, and a fever of 40.2ºC. No other symptoms were noted upon her admission. Blood workup revealed hyperlacticaemia, increased C-reactive protein, and lymphopenia. A urinalysis and chest radiography were ordered, with no abnormal findings, and the SARS-CoV-2 test was negative. The patient developed persistent hypotension and drowsiness that did not improve with intravenous fluids. Therefore, she was started on a norepinephrine infusion. Cultures were collected, and intravenous antibiotic therapy was started with amoxicillin/clavulanic acid 2.2 mg and azithromycin 500 mg. Besides all the diagnostic tests, no infectious cause was found. On the second day of hospitalization, she started to deteriorate, and antibiotic therapy was escalated to piperacillin/tazobactam 4.5 g, resulting in a good clinical response. On the third day after admission, thanks to a group discussion, we were able to identify in the patient's blood cultures. A review of history revealed that the patient was in close contact with her pet dog. This case highlights the importance of a multidisciplinary discussion, including the microbiology team, in order to reach an uncommon diagnosis. When dealing with splenectomized individuals presenting with the septic shock of unclear origin, a history of close contact with dogs must lead clinicians to consider as a causative agent. |
| 2021 | Effects of high-flux hemodialysis combined with levocarnitine on vascular calcification, microinflammation, hepcidin, and malnutrition of elderly patients on maintenance hemodialysis. | Ann Palliat Med | This study was to investigate the effect of high-flux hemodialysis (HD) combined with levocarnitine on vascular calcification, microinflammation, hepcidin, and malnutrition in elderly patients on maintenance HD (MHD).75 MHD elderly patients admitted to hospital between 1st September 2017 and 31st August 2019 were selected as the study subjects. They were randomly divided by digital table into three groups: low-flux group (n=25), high-flux group (n=25) and joint group (n=25). In the low-flux group, dialyzer had an ultrafiltration coefficient 12 mL/(h·mmHg) and effective surface area of 1.4 m2 compared with 59 mL/(h·mmHg) and 1.8 m2 in the high-flux group. After treatment, the calcification of blood vessels was examined by lateral X-ray, pelvic plain film and bilateral positive position. For patients in all groups, the concentrations of parathyroid hormone (PTH) and β 2-microglobulin (β 2-MG) in serum were measured by automatic chemiluminescence; levels of interleukin-6, C-reactive protein (CRP), and tumor necrosis factor alpha (TNF-α) were measured by ELISA before and after treatment; and the level of hepcidin was measured by ELISA. Before and 12 weeks after the treatment, the nutritional status of the patients was evaluated by modified quantitative subjective global assessment (MQSGA), hemoglobin (Hb) and red blood cell count (RBC). Complications in the three groups were recorded, including nausea, chest pain, hypotension, hypertension, pruritus, dry heat, muscle spasm, arrhythmia, and restless legs.Vascular calcification in the joint group was better than the low-flux and high-flux groups (P<0.05). After treatment, the serum PTH and β 2-mg concentrations in the joint group were lower than those in the other two groups (P<0.05), and the levels of IL-6, CRP, TNF-α and hepcidin in the joint group were significantly lower than those before treatment (P<0.05). After treatment, the MQSGA scores in the joint group were lower than those in the low-flux and high-flux groups (P<0.05), and Hb and RBC were higher (P<0.05).The combination of high-flux HD and levocarnitine in elderly patients on MHD can increase the clearance of medium and large molecular toxins, effectively correct malnutrition, alleviate microinflammation, delay the progress of vascular calcification, and is safe. |
| 2021 | Coronavirus Disease Clinical and Laboratory Parameters: Dismembering the Values Reveals Outcomes. | Cureus | Background The medical community's understanding of the novel coronavirus disease (COVID-19) was limited initially, and many laboratory investigations were performed to observe effects of the virus on the body, its complications, and outcomes. We observed that some laboratory investigations provided redundant information regarding outcomes, and, therefore, were not necessary. Therefore, the extent of laboratory investigations may need to be pared down to not only avoid issues related to repeated blood sampling but also to minimize the financial burdens in poor socioeconomic countries. Objective This study aimed to observe trends of clinical and laboratory values in COVID-19 patients and their relationship to outcomes, including disease severity, length of hospital stay, and mortality. Methods We conducted an observational cohort study of COVID-19 patients treated as inpatients at the Shifa International Hospital (SIH) in Islamabad in April 2020. Patients were included if they were nonsurgical, adult inpatients of SIH diagnosed with COVID-19 via positive polymerase chain reaction test. We monitored study participants' clinical and laboratory values (including hypoxia) on admission and throughout the study period. We used IBM SPSS Statistics for Windows, Version 23.0 (IBM Corp., Armonk, NY, USA) for data entry and analysis. Descriptive statistics were calculated for qualitative and quantitative data. We determined the effect of all variables on outcomes through chi-squared or Fisher's exact test, and p-values <0.05 with 95% confidence interval were considered statistically significant. Results A total of 51 patients with COVID-19 were enrolled. Most of the study participants were men older than age 50 with multiple comorbidities and resided in Khyber Pakhtunkhwa. Length of hospital stay ranged from eight to 14 days, and most patients had severe disease and survived. Factors such as patient age, gender, comorbid conditions, residence, and medication did not significantly affect outcomes. Hypotension during the height of symptoms and oxygen saturations <80% on admission was associated with prolonged hospital stays. Two complete blood count (CBC) parameters (platelet counts and mean corpuscular volume, MCV) were strongly associated with mortality and severity in our patients. Four non-CBC parameters (alanine transaminase, ALT; D-dimer; C-reactive protein, CRP; and lactate dehydrogenase, LDH) had strong statistical impact on disease severity, length of hospital stay, and mortality in our patients. Conclusion In a resource-limited country, laboratory testing must be chosen wisely and used appropriately. Patient age, gender, comorbid conditions, drugs, residence, and ferritin levels did not affect COVID-19 outcomes. Hemoglobin, platelet count, MCV, CRP, D-dimer, ALT, LDH, hypoxia, and hypotension were all correlated to disease outcomes. Therefore, these factors are useful laboratory examinations for COVID-19 patients, especially in poor countries. |
| 2021 | Coronavirus disease in children: A multicentre study from the Kingdom of Saudi Arabia. | J Infect Public Health | The COVID-19 global pandemic caused by severe acute respiratory syndrome coronavirus 2 infection, warranted attention for whether it has unique manifestations in children. Children tend to develop less severe disease with a small percentage present with clinical manifestations of paediatric multisystem inflammatory syndrome and have poor prognosis. We studied the characteristics of COVID-19 in children requiring hospitalisation in the Kingdom of Saudi Arabia and assessed the clinical presentation and the risk factors for mortality, morbidity, and paediatric intensive care (PICU) admission.We conducted a retrospective analysis of COVID-19 patients under 15 years hospitalised at three tertiary academic hospitals between 1 March and 30 June 2020.Eighty-eight children were enrolled (>20% were infants). Seven (8%) were in critical condition and required PICU admission, and 4 (4.5%) died of which 3 met the full diagnostic criteria of multi-system inflammatory syndrome and had a high Paediatric Risk of Mortality (PRISM) score at the time of admission. The initial polymerase chain reaction (PCR) test result was positive for COVID-19 in most patients (97.7%), and the remaining two patients had positive result in the repeated confirmatory test. In a subset of patients (20 subjects), repeated PCR testing was performed until conversion to negative result, and the average duration for conversion was 8 (95% CI: 5.2-10.5) days Children requiring PICU admission presented with signs of respiratory distress, dehydration, and heart failure. Most had fever (71.4%) and tonsillitis; 61.4% were discharged within 7 days of hospitalisation. Risk factors for mortality included skin rash, hypotension, hypoxia, signs of heart failure, chest radiograph suggestive of acute respiratory distress syndrome, anaemia, leucocytosis, hypernatraemia, abnormal liver enzymes, and high troponin I, and risk factors for prolonged hospitalisation (>7 days) included the presence of comorbidities, leucopaenia, hyponatraemia, and elevated C-reactive protein.The majority of hospitalised children had a brief febrile illness and made a full recovery, but a minority had severe disease. |
| 2021 | Hypotension Associated with MTS is Aggravated by Early Activation of TEA During Open Esophagectomy. | Local Reg Anesth | A mesenteric traction syndrome (MTS) is elicited by prostacyclin (PGI)-induced vasodilation and identified by facial flushing, tachycardia, and hypotension during abdominal surgery. We evaluated whether thoracic epidural anesthesia (TEA) influences the incidence of MTS.Randomized, blinded controlled trial.Single-center university hospital.Fifty patients undergoing open esophagectomy.Patients were randomized to either early (EA, after induction of general anesthesia) or late activation of TEA (LA, after re-established gastric continuity). Plasma 6-keto-PGF, a stable metabolite of PGI and interleukine-6 (IL6) were measured in plasma during surgery along with hemodynamic variables and MTS graded according to facial flushing together with plasma C-reactive protein on the third post-operative day.Forty-five patients met the inclusion criteria. Development of MTS tended to be more prevalent with EA (n=13/25 [52%]) than with LA TEA (n=5/20 [25%], p=0.08). For patients who developed MTS, there was a transient increase in plasma 6-keto-PGF by 15 min of surgery and plasma IL6 (p<0.001) as C-reactive protein (P<0.009) increased. EA TEA influenced the amount of phenylephrine needed to maintain mean arterial pressure >60 mmHg in patients who developed MTS (0.16 [0.016-0.019] mg/min vs MTS and LA TEA 0.000 [0.000-0.005] mg/min, p<0.001).The incidence of MTS is not prevented by TEA in patients undergoing open esophagectomy. On the contrary, the risk of hypotension is increased in patients exposed to TEA during surgery, and the results suggest that it is advantageous to delay activation of TEA. Also, MTS seems to be associated with a systemic inflammatory response, maybe explaining the aggravated post-operative outcome. |
| 2021 | Multisystem inflammatory syndrome in pediatric COVID-19 patients: a meta-analysis. | World J Pediatr | We aimed to systematically review the clinical and laboratory features of patients with the multisystem inflammatory syndrome in pediatrics diagnosed during the COVID-19 pandemic.A literature search in Web of Science, PubMed, Scopus, and Science Direct was made up to June 29, 2020.Analysis of 15 articles (318 COVID-19 patients) revealed that although many patients presented with the typical multisystem inflammatory syndrome in pediatrics, Kawasaki-like features as fever (82.4%), polymorphous maculopapular exanthema (63.7%), oral mucosal changes (58.1%), conjunctival injections (56.0%), edematous extremities (40.7%), and cervical lymphadenopathy (28.5%), atypical gastrointestinal (79.4%) and neurocognitive symptoms (31.8%) were also common. They had elevated serum lactic acid dehydrogenase, D-dimer, C-reactive protein, procalcitonin, interleukin-6, troponin I levels, and lymphopenia. Nearly 77.0% developed hypotension, and 68.1% went into shock, while 41.1% had acute kidney injury. Intensive care was needed in 73.7% of cases; 13.2% were intubated, and 37.9% required mechanical ventilation. Intravenous immunoglobulins and steroids were given in 87.7% and 56.9% of the patients, respectively, and anticoagulants were utilized in 67.0%. Pediatric patients were discharged after a hospital stay of 6.77 days on average (95% CI 4.93-8.6).Recognizing the typical and atypical presentation of the multisystem inflammatory syndrome in pediatric COVID-19 patients has important implications in identifying children at risk. Monitoring cardiac and renal decompensation and early interventions in patients with multisystem inflammatory syndrome is critical to prevent further morbidity. |
| 2021 | Hemoperitoneum due to splenic injury after colonoscopy, a complication perhaps not so uncommon. | Rev Esp Enferm Dig | Mr. Editor, We have read with interest in your journal the article "Splenic rupture as an endoscopic complication: as rare as it appears?" (1) and we would like to contribute a case handled in our hospital. Clinical case We present the case of a 72-year-old male smoker. His medical history showed a right lobectomy and adjuvant chemotherapy for lung adenocarcinoma. He was not under any kind of antiplatelet or anticoagulant medication. He had no history of abdominal surgery. An elective colonoscopy was performed with conscious sedation (midazolam and pethidine). The bowel preparation was appropriate. Diverticula and several pedunculated polyps were observed. After injection of diluted adrenaline (1/50000), a tubular adenoma with low-grade dysplasia measuring 20 millimeters in size was successfully removed using a diathermic loop at the splenic flexure. Post-resection mucosal defect was closed prophylactically with clip. 24 horas later, the patient was admitted to the emergency department due to abdominal pain and hypotension. There were no signs of peritoneal irritation. Laboratory analysis showed creatinine of 2.6 mg/dl, and C-reactive protein of 20 mg/L. Hemoglobin dropped from an initial level of 12.0 g/dL to 6.2 g/dL. A computerized tomography was performed (Fig. 1) after hemodynamic stabilization. The patient was treated with urgent splenectomy. He needed blood transfusion (six units of packed red blood cells). Postoperative course was uneventful and the patient was discharged home on day 5 after admission. Histopathological examination of his spleen revealed partial decapsulation. There was no evidence of underlying splenic disease. Discussion Our case presented tobacco consumption, oncological history and polypectomy (1,2) as risk factors for splenic injury after colonoscopy. Due to pedunculated polyp morphology wall damage was minimal. Management was optimal due to a high degree of clinical suspicion (3). Computed tomography should be performed immediately after resuscitation of the patient even if the abdominal X-ray is negative (2). The treatment of choice is urgent surgery (3,4,5) when there is hemodynamic instability. This complication has been described as very rare, with an incidence of 0.004% (4). Interestingly the cases presented here and before (1,4) suggest that the incidence of this complication could be higher. |
| 2021 | The Association of COVID-19 With Acute Kidney Injury Independent of Severity of Illness: A Multicenter Cohort Study. | Am J Kidney Dis | Although coronavirus disease 2019 (COVID-19) has been associated with acute kidney injury (AKI), it is unclear whether this association is independent of traditional risk factors such as hypotension, nephrotoxin exposure, and inflammation. We tested the independent association of COVID-19 with AKI.Multicenter, observational, cohort study.Patients admitted to 1 of 6 hospitals within the Yale New Haven Health System between March 10, 2020, and August 31, 2020, with results for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing via polymerase chain reaction of a nasopharyngeal sample.Positive test for SARS-CoV-2.AKI by KDIGO (Kidney Disease: Improving Global Outcomes) criteria.Evaluated the association of COVID-19 with AKI after controlling for time-invariant factors at admission (eg, demographic characteristics, comorbidities) and time-varying factors updated continuously during hospitalization (eg, vital signs, medications, laboratory results, respiratory failure) using time-updated Cox proportional hazard models.Of the 22,122 patients hospitalized, 2,600 tested positive and 19,522 tested negative for SARS-CoV-2. Compared with patients who tested negative, patients with COVID-19 had more AKI (30.6% vs 18.2%; absolute risk difference, 12.5% [95% CI, 10.6%-14.3%]) and dialysis-requiring AKI (8.5% vs 3.6%) and lower rates of recovery from AKI (58% vs 69.8%). Compared with patients without COVID-19, patients with COVID-19 had higher inflammatory marker levels (C-reactive protein, ferritin) and greater use of vasopressors and diuretic agents. Compared with patients without COVID-19, patients with COVID-19 had a higher rate of AKI in univariable analysis (hazard ratio, 1.84 [95% CI, 1.73-1.95]). In a fully adjusted model controlling for demographic variables, comorbidities, vital signs, medications, and laboratory results, COVID-19 remained associated with a high rate of AKI (adjusted hazard ratio, 1.40 [95% CI, 1.29-1.53]).Possibility of residual confounding.COVID-19 is associated with high rates of AKI not fully explained by adjustment for known risk factors. This suggests the presence of mechanisms of AKI not accounted for in this analysis, which may include a direct effect of COVID-19 on the kidney or other unmeasured mediators. Future studies should evaluate the possible unique pathways by which COVID-19 may cause AKI. |
| 2020 | Systemic inflammation and oxidative stress contribute to acute kidney injury after transcatheter aortic valve implantation. | Cardiol J | Acute kidney injury (AKI) is a frequent complication of transcatheter aortic valve implantation (TAVI) and has been linked to preexisting comorbidities, peri-procedural hypotension, and systemic inflammation. The extent of systemic inflammation after TAVI is not fully understood. Our aim was to characterize the inflammatory response after TAVI and evaluate its contribution to the mechanism of post-procedural AKI.One hundred and five consecutive patients undergoing TAVI at our institution were included. We analyzed the peri-procedural inflammatory and oxidative stress responses by measuring a range of biomarkers (including C-reactive protein [hsCRP], cytokine levels, and myeloperoxidase [MPO]), before TAVI and 6, 24, and 48 hours post-procedure. We correlated this with changes in renal function and patient and procedural characteristics.We observed a significant increase in plasma levels of pro-inflammatory cytokines (hsCRP, interleukin 6, tumor necrosis factor alpha receptors) and markers of oxidative stress (MPO) after TAVI. The inflammatory response was significantly greater after trans-apical (TA) TAVI compared to trans-femoral (TF). This was associated with a higher incidence of AKI in the TA cohort compared to TF (44% vs. 8%, respectively, p < 0.0001). The incidence of AKI was significantly lower when N-acetylcysteine (NAC) was given peri-procedurally (12% vs. 38%, p < 0.005). In multivariate analysis, only the TA approach and no use of NAC before the procedure were independent predictors of AKI.TAVI creates a significant post-procedural inflammatory response, more so with the TA approach. Mechanisms of AKI after TAVI are complex. Inflammatory response, hypoperfusion, and oxidative stress may all play a part and are potential therapeutic targets to reduce/prevent AKI. |
| 2021 | Association and predictive value of geriatric nutritional risk index, body composition, or bone mineral density in haemodialysis patients. | Nephrology (Carlton) | Assess the association and predictive value of geriatric nutritional risk index (GNRI), body composition, and bone mineral density (BMD) in haemodialysis (HD) patients.Laboratory data, body composition parameters measured via body composition monitor, and radius, lumbar spine, femoral neck BMD measured using dual energy X-ray absorptiometry were assessed in all subjects on HD or online haemodiafiltration (HDF) at baseline. Regression analysis for GNRI, Cox proportional hazard analyses and comparison of multiple receiver operating characteristic (ROC) curves were performed.Among all 264 patients, age was 65 ± 12 years and dialysis vintage was 79 (39-144) months. GNRI tertile (T)1, T2, and T3 were 88 (85-91), 94 (93-95), and 98 (97-101), respectively. Patients in GNRI T1 had lower fat tissue index (FTI), lean tissue index, and femoral neck, lumbar spine, and distal mid-third radius BMD, but higher overhydration/extracellular fluid than patients in GNRI T2 or T3 (P < .05). GNRI was significantly associated with FTI, lean tissue index, and femoral neck, lumbar spine, and distal mid-third radius BMD (P < .01). GNRI was a significant predictor of 2-year all-cause mortality (HR 0.92, P < .05). Area under the ROC curve for all-cause mortality using traditional risk factors (age, sex, diabetes mellitus, cardiovascular disease, use of vasopressors for dialysis-related hypotension, and C-reactive protein) was 0.67 and changed by adding GNRI (0.78, P < .05), FTI (0.75), or femoral neck BMD (0.66), respectively.Associations between GNRI, body composition, and BMD were confirmed in HD patients. Combining GNRI with traditional risk factors improved mortality prediction in HD patients. |
| 2020 | Effect of a Supervised Peridialytic Exercise Program on Serum Asymmetric Dimethylarginine in Maintenance Hemodialysis Patients. | Int J Nephrol | End-stage renal disease (ESRD) patients treated with maintenance haemodialysis (MHD) have alarmingly high atherosclerotic cardiovascular disease morbidity and mortality. Nitric oxide (NO) is the principal endogenous antiatherosclerotic molecule. Increased asymmetric dimethylarginine (ADMA), an endogenous NO synthase inhibitor, was strongly implicated in endothelial dysfunction, premature atherosclerosis, vascular events, and mortality. Regular physical exercise effectively decreased serum ADMA in several patient cohorts, but this potential benefit has not been specifically explored among MHD patients. Forty-four middle-aged ESRD patients treated with thrice-weekly MHD for ≥6 months completed a 6-months regimen of peridialytic lower limb exercise comprising predialytic 10-12 stretching cycles and 20-30 minutes of intradialytic pedaling cycles. Before and after the study, predialytic haemoglobin, serum ADMA, urea, creatinine, calcium, phosphorus, and C-reactive protein (CRP) were measured. Dialysis adequacy was assessed by single-pool Kt/V. The average total physical activity (PA) level was assessed by the International Physical Activity Questionnaire (IPAQ). values <0.05 denoted a statistical significance. The overall level of PA, on both categorical and continuous scales, has significantly increased after application of the exercise program. However, S. ADMA increased from a median of 2375 to 3000 ng/mL (=0.016). Thirty-one patients sustained an increase in S. ADMA (ADMA_Inc), whereas 13 patients had a declining or stable S. ADMA (ADMA_Dec). Compared with ADMA_Inc, ADMA_Dec patients had significantly higher Kt/V (=0.02), higher grade of the basal general PA level (=0.017), and significantly fewer intradialytic hypotension episodes (IDHs) (=0.019). The increase in the S. ADMA and the poststudy S. ADMA level had statistically significant positive correlations with the number of IDHs ( = 0.401, =0.007 and = 0.305, =0.044, respectively). A 6-month program of combined aerobic and resistance peridialytic exercise failed to reduce S. ADMA in most MHD patients studied. A modest S. ADMA decline, however, occurred in patients with higher basal PA levels, higher Kt/V, and less IDHs. A potential exercise benefit may be promoted by a multidisciplinary approach targeting increased PA, improved dialysis efficiency, and prevention of IDHs. |
| 2020 | Peritoneal Dialysis in a Patient with Acute Kidney Injury, Thrombocytopenia, Urosepsis, and Liver Cirrhosis: A Case Report. | Am J Case Rep | BACKGROUND We present the possibility of successful peritoneal dialysis (PD) treatment in acute kidney injury (AKI) patients with multiple comorbidities. CASE REPORT A 60-year-old woman with chronic kidney disease (CKD, stage G3b), liver cirrhosis (Child-Pugh class A score), and thrombocytopenia developed AKI due to urosepsis. Laboratory tests showed serum creatinine 430.5 µmol/L, urea 44.0 mmol/L, potassium 5.7 mmol/L, C-reactive protein 208 mg/L, procalcitonin 8 ng/mL, platelets 14×10⁹/L, hemoglobin 5.83 mmol/L, and albumin 30 g/L. Due to hemodynamic instability with profound hypotension and the potentially high bleeding risk when doing central venous catheter insertion or using anticoagulants, PD was selected as the AKI treatment. The PD catheter was implanted by the surgical method after the transfusion of platelet concentrate. Automated PD in tidal mode was implemented using 1.5% and 2.3% glucose: basic inflow volume 1200 mL and a tidal volume of 700 mL. Effective dialysis with ultrafiltration up to 1200 mL/day was achieved. The patient was discharged home in good condition. After 1 month, PD was discontinued due to the renal function returning to its pre-septic state of CKD category G3b. The PD catheter was removed 3 weeks later. CONCLUSIONS PD can be an effective method for AKI treatment in patients with sepsis, hemodynamic instability, thrombocytopenia, and liver cirrhosis. |
| 2020 | Jejunal Diverticulosis Probably Leading to Pylephlebitis of the Superior Mesenteric Vein. | Case Rep Surg | Thrombophlebitis of the portal vein (pylephlebitis) is a rare but serious condition with a high mortality rate of 11-50%. A 56-year-old male patient presented with a two-day history of postprandial, colic-like epigastric pain, nausea, fever, chills, and diarrhea. Clinical workup showed peritonism, leukocytosis, and elevated C-reactive protein (CRP). A computed tomography (CT) scan revealed a long-segment, partial thrombosis of the superior mesenteric vein as well as gas in the portal venous system. Additionally, extensive jejunal diverticulosis was present. Pylephlebitis mostly results from intestinal infections, e.g., appendicitis or diverticulitis. We assumed that the patient had suffered from a self-limiting episode of jejunal diverticulitis leading to septic thrombosis. Initially, antibiotic therapy and anticoagulation with heparin were administered. The patient deteriorated, and due to increasing abdominal defense, fever, and hypotension, a diagnostic laparoscopy was performed. Bowel ischemia could be ruled out, and after changing antibiotic therapy, the patient's condition improved. He was discharged without any further complications and without complaints on day 13. An underlying coagulopathy like myeloproliferative neoplasm or antiphospholipid syndrome could be ruled out. |
| 2020 | Emphysematous Pyelonephritis in a Diabetic Patient with Remarkable Radiological Findings and Excellent Outcome without Surgical Intervention or Drainage. | Am J Case Rep | BACKGROUND Emphysematous pyelonephritis (EPN) is a life-threatening infection of the renal parenchyma. The purpose of this report is to present a case of EPN with distinctive imaging. CASE REPORT An 87-year-old man with a history of type 2 diabetes mellitus presented to the ER with fever and shivering, hypotension, and anuria, which is a clinical presentation of septic shock. He had recently been hospitalized at another hospital due to myocardial infarction and ischemic stroke, where a temporary urinary catheter was placed. Upon physical examination, he had right lateral abdominal pain with extension to the right renal region. Laboratory studies showed leucocytosis (WBC: 24 320/μl with 94.4% polymorphonuclear), elevated C-reactive protein 340 mg/l (NV <3.45), and acute renal failure (urea 155mg/dl NV <50 mg/dl, creatinine 4.4 mg/dl NV <1.2 mg/dl). A plain X-ray showed air was present peripheral to the right kidney, while the abdominal CT revealed air inside the right kidney and bilateral nephrolithiasis. The patient was initially put on aggressive hydration, vasoconstrictors, and hydrocortisone to treat the septic shock, and an advanced antibiotic treatment (meropenem) was initiated immediately. Blood culture grew Escherichia coli. After 3 days of treatment, he showed significant improvement in diuresis and renal function (urea 90 mg/dl, creatinine 1.0 mg/dl), with a concomitant decrease in inflammatory markers (CRP 36.7 mg/l). The antibiotic treatment was tapered to cefuroxime and metronidazole. The patient's condition improved, and he was discharged with per os antibiotic treatment. Subsequently, surgical assessment for the nephrolithiasis was suggested. CONCLUSIONS Emphysematous pyelonephritis, although rare, should be included in the differential diagnosis of fever in a diabetic patient with renal pain. |
| 2020 | Development and validation of a simple and robust model to predict 30-day mortality in patients with -associated enterocolitis. | BMJ Open Gastroenterol | infection (CDI) is a common healthcare-associated infection and associated with high morbidity and mortality. As current guidelines recommend treatment stratified for disease severity, this study aimed to identify predictors of 30-day mortality in order to develop a robust prediction model.This was a retrospective analysis of 207 inpatients with CDI who were treated at the Jena University Hospital between September 2011 and December 2015. In a training cohort (n=127), predictors of 30-day mortality were identified by receiver operating characteristics analysis and logistic regression. The derived model was validated in an independent cohort of 80 inpatients with CDI.Within 30 days, 35 (28%) patients in the training cohort died from any cause. C-reactive protein (CRP) of ≥121 mg/L (OR 3.80; 95% CI 1.64 to 7.80; p=0.003) and lower systolic blood pressure of ≤104 mm Hg (OR 3.73; 95% CI 1.63 to 8.53; p=0.002) at diagnosis as well as development of renal impairment (serum creatinine >1.5×baseline; OR 5.61; 95% CI 1.94 to 16.26; p=0.035) within the first 6 days were associated with 30-day mortality in univariate analysis. The use of these parameters enabled correct mortality prediction in 73% of cases on the day of diagnosis and in 76% at day 6. In the validation cohort, 30-day mortality was 18/80 (23%). Our model enabled a 73.7% correct prediction concerning 30-day mortality on day 6 after diagnosis of CDI.Hypotension and CRP elevation on the day of diagnosis as well as occurrence of kidney dysfunction during the first 6 days are suitable parameters to predict 30-day mortality in patients with CDI who need to be treated in the hospital. |
| 2020 | Severe clinical spectrum with high mortality in pediatric patients with COVID-19 and multisystem inflammatory syndrome. | Clinics (Sao Paulo) | To assess the outcomes of pediatric patients with laboratory-confirmed coronavirus disease (COVID-19) with or without multisystem inflammatory syndrome in children (MIS-C).This cross-sectional study included 471 samples collected from 371 patients (age<18 years) suspected of having severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The study group comprised 66/371 (18%) laboratory-confirmed pediatric COVID-19 patients: 61 (92.5%) patients tested positive on real-time reverse transcription-polymerase chain reaction tests for SARS-CoV-2, and 5 (7.5%) patients tested positive on serological tests. MIS-C was diagnosed according to the criteria of the Center for Disease Control.MIS-C was diagnosed in 6/66 (9%) patients. The frequencies of diarrhea, vomiting, and/or abdominal pain (67% vs. 22%, p=0.034); pediatric SARS (67% vs. 13%, p=0.008); hypoxemia (83% vs. 23%, p=0.006); and arterial hypotension (50% vs. 3%, p=0.004) were significantly higher in patients with MIS-C than in those without MIS-C. The frequencies of C-reactive protein levels >50 mg/L (83% vs. 25%, p=0.008) and D-dimer levels >1000 ng/mL (100% vs. 40%, p=0.007) and the median D-dimer, troponin T, and ferritin levels (p<0.05) were significantly higher in patients with MIS-C. The frequencies of pediatric intensive care unit admission (100% vs. 60%, p=0.003), mechanical ventilation (83% vs. 7%, p<0.001), vasoactive agent use (83% vs. 3%, p<0.001), shock (83% vs. 5%, p<0.001), cardiac abnormalities (100% vs. 2%, p<0.001), and death (67% vs. 3%, p<0.001) were also significantly higher in patients with MIS-C. Similarly, the frequencies of oxygen therapy (100% vs. 33%, p=0.003), intravenous immunoglobulin therapy (67% vs. 2%, p<0.001), aspirin therapy (50% vs. 0%, p<0.001), and current acute renal replacement therapy (50% vs. 2%, p=0.002) were also significantly higher in patients with MIS-C. Logistic regression analysis showed that the presence of MIS-C was significantly associated with gastrointestinal manifestations [odds ratio (OR)=10.98; 95%CI (95% confidence interval)=1.20-100.86; p=0.034] and hypoxemia [OR=16.85; 95%CI=1.34-211.80; p=0.029]. Further univariate analysis showed a positive association between MIS-C and death [OR=58.00; 95%CI=6.39-526.79; p<0.0001].Pediatric patients with laboratory-confirmed COVID-19 with MIS-C had a severe clinical spectrum with a high mortality rate. Our study emphasizes the importance of investigating MIS-C in pediatric patients with COVID-19 presenting with gastrointestinal involvement and hypoxemia. |
| 2020 | Imaging features, clinicopathological analysis and diagnostic strategy of IgG4-related hypertrophic pachymeningitis. | Ann Palliat Med | This study was conducted to summarize the clinical, magnetic resonance imaging (MRI) and pathological features of IgG4-realated hypertrophic pachymeningitis (IgG4-RHP) and its differential diagnosis from similar diseases.Data of IgG4-RHP patients admitted to Department of Neurology, Neurosurgery and Infection, the First Affiliated Hospital of Medical School of Zhejiang University from January 1, 2015 to July 31, 2019 were collected and their clinical symptoms, laboratory examinations, imaging and pathological features were investigated. At the same time, the clinicopathological and imaging findings of other dura thickening diseases diagnosed in our hospital were compared and analyzed.The clinical symptoms of 4 IgG4-RHP patients include chronic headache and cranial nerves injury, etc. Levels of serum IgG4 and cerebrospinal fluid (CSF) IgG4 increased in all patients. Focal enhancement of dura mater could be seen on plain and enhanced cranial MRI. Pathological results were consistent with IgG4-RHP symptoms. Among other diseases that cause dural thickening, the content of serum C-reactive protein in patients with Rosai-Dorfman disease declined. Patients with intracranial hypotension syndrome often have postural headache. Patients with tuberculous meningitis can have previous pulmonary tuberculosis. The diagnosis of patients with atypical meningioma depends on the results of operation and pathology. Patients with central nervous system leukemia can be diagnosed with reference to the results of laboratory results.The clinicopathological and imaging manifestations of IgG4-RHP are summarized in this study. Meanwhile, the clinical data of several other diseases with similar imaging characteristics are analyzed in order to clarify the diagnostic strategy of IgG4-RHP and provide help for the next treatment. |
| 2020 | A Systematic Review of COVID-19 and Myocarditis. | Am J Med Case Rep | The COVID-19 infection which emerged in December 2019, is caused by the virus SARS-CoV-2. Infection with this virus can lead to severe respiratory illness, however, myocarditis has also been reported. The purpose of this study is to identify the clinical features of myocarditis in COVID-19 patients.A systematic review was conducted to investigate characteristics of myocarditis in patients infected with COVID-19 using the search term "Coronavirus" or "COVID" and "myocarditis," "heart," or "retrospective." Case reports and retrospective studies were gathered by searching Medline/Pubmed, Google Scholar, CINAHL, Cochrane CENTRAL, and Web of Science databases. 11 articles were selected for review.COVID-19 myocarditis affected patients over the age of 50 and incidences among both genders were equally reported. Patients presented with dyspnea, cough, fever with hypotension and chest pain. Laboratory tests revealed leukocytosis with increased C-reactive protein, while arterial blood gas analysis demonstrated respiratory acidosis. All cardiac markers were elevated. Radiographic imaging of the chest showed bilateral ground glass opacities or bilateral infiltrates, while cardiac magnetic resonance imaging produced late gadolinium enhancements. Electrocardiography demonstrated ST-segment elevation or inverted T waves, while echocardiography revealed reduced left ventricular ejection fraction with cardiomegaly or increased wall thickness. Management with corticosteroids was favored in most cases, followed by antiviral medication. The majority of studies reported either recovery or no further clinical deterioration.Current available data on COVID-19 myocarditis is limited. Further research is needed to advance our understanding of COVID-19 myocarditis. |
| 2020 | Clinical characteristics of COVID-19 in children: A systematic review. | Pediatr Pulmonol | Limited pediatric cases with coronavirus disease 2019 (COVID-19) have been reported and the clinical profiles regarding COVID-19 in children remain obscure. Our aim was to investigate the clinical characteristics of COVID-19 in children.PUBMED and EMBASE were searched through 20 June 2020, for case reports and case series reporting pediatric COVID-19 cases. Epidemiological, clinical, laboratory, and radiological data were collected and analyzed to compare by age.Our search identified 46 eligible case reports and case series. A total of 114 pediatric cases with COVID-19 were included. The main clinical features were mild symptoms including fever (64%), cough (35%), and rhinorrhea (16%), or no symptoms (15%). Ground-like opacities were common radiological findings (54%). The main laboratory findings were lymphopenia (33%) and elevated D-dimer (52%) and C-reactive protein (40%) levels. We identified 17 patients (15%) with multisystem inflammatory syndrome in children (MIS-C) manifesting with symptoms overlapping with, but distinct from, Kawasaki disease, including gastrointestinal symptoms, left ventricular systolic dysfunction, shock, and marked elevated inflammatory biomarkers. Twelve percent of the patients including 65% of the MIS-C cases required intensive care because of hypotension. No deaths were reported.This systematic review found that children with COVID-19 are generally less severe or asymptomatic. However, infants might be seriously ill and older children might develop MIS-C with severe illness. Early detection of children with mild symptoms or an asymptomatic state and early diagnosis of MIS-C are mandatory for the management of COVID-19 and the prevention of transmission and a severe inflammatory state. |
| 2020 | Acute myocarditis and multisystem inflammatory emerging disease following SARS-CoV-2 infection in critically ill children. | Ann Intensive Care | A recent increase in children admitted with hypotensive shock and fever in the context of the COVID-19 outbreak requires an urgent characterization and assessment of the involvement of SARS-CoV-2 infection. This is a case series performed at 4 academic tertiary care centers in Paris of all the children admitted to the pediatric intensive care unit (PICU) with shock, fever and suspected SARS-CoV-2 infection between April 15th and April 27th, 2020.20 critically ill children admitted for shock had an acute myocarditis (left ventricular ejection fraction, 35% (25-55); troponin, 269 ng/mL (31-4607)), and arterial hypotension with mainly vasoplegic clinical presentation. The first symptoms before PICU admission were intense abdominal pain and fever for 6 days (1-10). All children had highly elevated C-reactive protein (> 94 mg/L) and procalcitonin (> 1.6 ng/mL) without microbial cause. At least one feature of Kawasaki disease was found in all children (fever, n = 20, skin rash, n = 10; conjunctivitis, n = 6; cheilitis, n = 5; adenitis, n = 2), but none had the typical form. SARS-CoV-2 PCR and serology were positive for 10 and 15 children, respectively. One child had both negative SARS-CoV-2 PCR and serology, but had a typical SARS-CoV-2 chest tomography scan. All children but one needed an inotropic/vasoactive drug support (epinephrine, n = 12; milrinone, n = 10; dobutamine, n = 6, norepinephrine, n = 4) and 8 were intubated. All children received intravenous immunoglobulin (2 g per kilogram) with adjuvant corticosteroids (n = 2), IL 1 receptor antagonist (n = 1) or a monoclonal antibody against IL-6 receptor (n = 1). All children survived and were afebrile with a full left ventricular function recovery at PICU discharge.Acute myocarditis with intense systemic inflammation and atypical Kawasaki disease is an emerging severe pediatric disease following SARS-CoV-2 infection. Early recognition of this disease is needed and referral to an expert center is recommended. A delayed and inappropriate host immunological response is suspected. While underlying mechanisms remain unclear, further investigations are required to target an optimal treatment. |
| 2020 | Predictors of Acute Kidney Injury After Hip Fracture in Older Adults. | Geriatr Orthop Surg Rehabil | This study aimed to investigate the prevalence of acute kidney injury (AKI) following hip fracture surgery in geriatric patients and to identify predictors for development of AKI with a focus on possible preventable risk factors.In this retrospective cohort study, we reviewed electronic medical records of all patients above 65 years of age who underwent hip fracture surgery at Copenhagen University Hospital, Bispebjerg, Denmark, in 2018. Acute kidney injury was assessed according to the Kidney Disease Improving Global Outcomes guidelines. Multivariate logistic regression analyses were used to identify independent risk factors for AKI.Postoperative AKI developed in 28.4% of the included patients (85/299). Acute kidney injury was associated with increased length of admission (11.3 vs 8.7 days, < .001) and 30-day mortality (18/85 vs 16/214, = .001). In multivariable analysis, higher age (odds ratio [OR]: 1.05, 95% confidence interval [CI]: 1.01-1.08, = .004), heart disease (OR: 1.78, 95% CI: 1.01-3.11, = .045), and postoperative blood transfusion (OR: 1.84, 95% CI: 1.01-3.36, = .048) were associated with AKI. Moreover, a higher postoperative C-reactive protein (199.0 ± 99.9 in patients with AKI, 161.3 ± 75.2 in patients without AKI) and lower postoperative diastolic blood pressure were observed in patients developing AKI.Acute kidney injury was common following hip fracture surgery and associated with longer admissions and increased mortality. Patients developing AKI were older and showed several postoperative similarities, including higher C-reactive protein, lower postoperative diastolic pressure, and the need for blood transfusion. |
| 2020 | A case report of fulminant cytokine release syndrome complicated by dermatomyositis after the combination therapy with immune checkpoint inhibitors. | Medicine (Baltimore) | Immune-related adverse events (ir-AEs) are increasingly becoming a concern, as immune checkpoint inhibitors (ICIs) are used more frequently. Herein, we present a case of fulminant cytokine release syndrome (CRS) complicated by dermatomyositis after the combination therapy with ICIs.A 70-year-old male developed dermatomyositis during the course of treatment with two ICIs, nivolumab and ipilimumab. He was treated by steroid pulse therapy, but the effect was limited. Afterwards, he had acute-onset high fever, hypotension, respiratory failure, impaired consciousness, renal failure, and coagulation abnormality at the same time. C reactive protein (CRP), creatinine kinase (CK), D-dimer, and ferritin levels were considerably elevated: CRP, 24 mg/dL; CK, 40,500 U/L; D-dimer, 290 μg/mL; ferritin, 329,000 ng/mL.CRS induced by ICI combination therapy.Given that high fever and elevated CRP level indicated potential sepsis, an antibiotic was used until the confirmation of negative blood cultures. All the simultaneous acute symptoms were supposed to be CRS. He was admitted to the intensive care unit (ICU), and temporary intubation and hemodialysis were needed. Immunosuppressive therapy was reinforced by mycophenolate mofetil together with steroid, and plasma exchange was performed for the elimination of abnormal proteins.The patient's clinical symptoms and laboratory parameters gradually improved and he was discharged from the ICU in a month.Fulminant CRS can be induced by ICI combination therapy. As the initial symptoms of CRS resemble sepsis, it is important to consider CRS as a differential diagnosis and to initiate immunosuppressive therapy early when needed. In steroid-resistant cases, early introduction of other immunosuppressive therapy and plasma exchange can be effective. |
| 2020 | Early Initiation of Sacubitril/Valsartan in Patients with Chronic Heart Failure After Acute Decompensation: A Case Series Analysis. | Clin Drug Investig | Sacubitril/valsartan improved the prognosis of patients with heart failure with reduced ejection fraction in the PARADIGM-HF study. Recently, the TRANSITION and PIONEER-HF studies demonstrated the safety and efficacy of sacubitril/valsartan in patients hospitalized for acute decompensated heart failure, with treatment initiated after hemodynamic and clinical stabilization. In this case series study, we assessed the short-term effects of sacubitril/valsartan on exercise capacity, inflammation, and biomarkers in patients with acute decompensated heart failure.Patients admitted for acute decompensated heart failure to the Department of Internal Medicine of Telese Terme Hospital and Cardiovascular Department, University of Bari, from 9 March, 2017 to 9 June, 2018 were enrolled. Following hemodynamic stabilization, patients initiated sacubitril/valsartan 24/26 mg twice a day for 4 weeks, with up-titration to 49/51 mg twice a day based on tolerability after 1 week. Efficacy outcomes included the 6-min walking test, N-terminal pro-B-type natriuretic peptide, high-sensitivity C-reactive protein, and lymphocyte count. Safety outcomes included renal function, hyperkalemia, and symptomatic hypotension.In total, 40 patients completed the study and 27 (67.5%) patients were up-titrated. Compared with baseline, exercise capacity and relative lymphocyte count increased significantly after 4 weeks of treatment, while N-terminal pro-B-type natriuretic peptide and high-sensitivity C-reactive protein decreased significantly. N-terminal pro-B-type natriuretic peptide and relative lymphocyte count independently predicted the 6-min walking test distance (p = 0.021). No patients experienced any relevant side effects.Early initiation of sacubitril/valsartan in patients with heart failure with reduced ejection fraction after acute decompensated heart failure may be safe and effective in terms of functional capacity and biomarkers. |
| 2020 | Association of Body Composition and Intradialytic Hypotension in Hemodialysis Patients. | Blood Purif | The relationship between body mass index (BMI) and intradialytic hypotension (IDH) has been inconsistently reported, but no further research has investigated the correlation between body composition and IDH so far. This study aimed to determine whether the lean tissue index (LTI), fat tissue index (FTI), or both derived from body composition monitoring (BCM) is associated with IDH defined as a nadir intradialytic systolic blood pressure of <90 mm Hg and ≥3 episodes hypotension per 10 hemodialysis (HD) treatments in patients undergoing prevalent HD.The observational cohort study comprised 1,463 patients receiving thrice-weekly HD from 13 dialysis centers. LTI and FTI were assessed using a BCM machine, a multifrequency bioimpedance spectroscopy device. Unadjusted and multivariable adjusted logistic regression models were fit to estimate the association of body composition with the odds of developing IDH.One hundred and seven patients (7.3%) were diagnosed as IDH. The difference in dialysis vintage, BMI, FTI, LTI, high-density lipoprotein cholesterol, and C-reactive protein between IDH and non-IDH groups was statistically significant (all p < 0.05). The prevalence of diabetes among IDH patients was slightly higher than among non-IDH patients. In logistic regression models, low LTI and high FTI, but not high BMI were associated with greater odds of IDH ("high" as above median and "low" as below median). When patients were further stratified into 4 distinct body composition groups based on both the LTI and FTI, only the low LTI/high FTI group was connected with a significantly higher odds of IDH (OR 2.686, 95% CI 1.072-6.734; reference: low LTI/low FTI group).The LTI and FTI can provide better correlation of IDH occurrence than the BMI alone in prevalent HD patients. The low LTI/high FTI appears to be most associated with IDH. An optimal body composition for preventing the occurrence of IDH needs to be determined. |
| 2020 | Effects of the dual sodium-glucose linked transporter inhibitor, licogliflozin vs placebo or empagliflozin in patients with type 2 diabetes and heart failure. | Br J Clin Pharmacol | Explore the efficacy, safety and tolerability of the dual sodium-glucose cotransporter (SGLT) 1 and 2 inhibitor, licogliflozin in patients with type-2 diabetes mellitus (T2DM) and heart failure.This multicentre, parallel-group phase IIA study randomized 125 patients with T2DM and heart failure (New York Heart Association II-IV; plasma N-terminal pro b-type natriuretic peptide [NT-proBNP] >300 pg/mL) to licogliflozin (2.5 mg, 10 mg, 50 mg) taken at bedtime, empagliflozin (25 mg) or placebo (44 patients completed the study). The primary endpoint was change from baseline in NT-proBNP after 12 weeks. Secondary endpoints included change from baseline in glycated haemoglobin, fasting plasma glucose, weight, blood pressure, fasting lipid profile, high-sensitivity c-reactive protein, and safety and tolerability.Licogliflozin 10 mg for 12 weeks significantly reduced NT-proBNP vs placebo (Geometric mean ratio 0.56 [95% confidence interval: 0.33, 0.95], P = .033). A trend was observed with 50 mg licogliflozin (0.64 [95% confidence interval: 0.40, 1.03], P = .064), with no difference between licogliflozin and empagliflozin. The largest numerical decreases in glycated haemoglobin were with licogliflozin 50 mg (-0.58 ± 0.34%) and empagliflozin (-0.44 ± 1.18%) vs placebo (-0.04 ± 0.91%). The reduction in body weight was similar with licogliflozin 50 mg (-2.15 ± 2.40 kg) and empagliflozin (-2.25 ± 1.89 kg). A numerical reduction in systolic blood pressure was seen with licogliflozin 50 mg (-9.54 ± 16.88 mmHg) and empagliflozin (-6.98 ± 15.03 mmHg) vs placebo (-2.85 ± 11.97 mmHg). Adverse events (AEs) were mild, including hypotension (6.5%), hypoglycaemia (8.1%) and inadequate diabetes control (1.6%). The incidence of diarrhoea (4.9%) was lower than previously reported.The reduction in NT-proBNP with licogliflozin suggests a potential benefit of SGLT1 and 2 inhibition in patients with T2DM and heart failure. |
| 2020 | [Meningococcemia: Different Serotypes in the Same Region]. | Mikrobiyol Bul | Meningococcal infections are important health problems causing high morbidity and mortality. Neisseria meningitidis have 13 serogroups. A, B, C, Y and W135 are the most common causes of invasive disease among those serogroups. The distribution of the serogroups differs according to the geographical regions and the age groups. In this case report, two cases of meningococcemia infected with serogroup C and Y of N.meningitidis rarely seen in our country were presented. First case was a two and a half year-old female patient who has admitted to our pediatric emergency unit with fever and rash spreading from lower extremities to her body. The patient had diffuse purpuric rash with generalized weakness and tendency to sleep at admission. The patient has been suspected as meningococcemia because of the skin rash, tendency to sleep and hypotension. Antibiotics treatment was started immediately and lumber puncture was performed. In blood tests, leukocyte count: 3600/mm3 (61% neutrophils), hemoglobin: 11.1 g/ dl, platelet count: 127.000/mm3 , C-reactive protein: 10 mg/dl, erythrocyte sedimentation rate: 6 mm/ hour, prothrombin time: 28.8 seconds (normal value= 11-16), prothrombin activity: 36%, international normalized ratio (INR): 2.13 (normal value= 1-1.5), activated partial thromboplastin time: 57.7 seconds (normal value= 25-35 sec), fibrinogen: 246 mg/dl (normal value= 200-400 mg/dl) and in cerebrospinal fluid protein: 21 mg/dl and glucose: 62 mg/dl were found. There were eight cells in the microscopic examination. Skin rashes were increased and the patient became hypotensive. No microorganisms were isolated in blood and cerebrospinal cultures. N.meningitidis serogroup C was isolated from the cerebrospinal fluid of the patient using polymerase chain reaction (PCR). The patient suffered from immune-mediated arthritis in the sixth day of treatment and nonsteroidal anti-inflammatory drugs were given. The patient has recovered with antibiotics, fresh frozen plasma and inotropic treatment. Second case was a 13 year-old male patient who has admitted three days after the first case with a pre-diagnosis of malignancy because of pancytopenia and fever. The patient had generalized weakness and a few petechial purpuric rashes at the facial region at admission. After the admission general status of the patient has worsened rapidly and he has died as a result of cardiovascular arrest. Blood tests in admission showed leukocyte count: 6000/mm3 (79% neutrophils), hemoglobin: 17.3 mg/dl, platelet count: 16.000/mm3 , C-reactive protein: 8.63 mg/dl, prothrombin time: 92.6 seconds, prothrombin activity: 10%, INR: 6.78, activated partial thromboplastin time: 231.5 seconds. Cerebrospinal fluid obtained from postmortem lumbar puncture showed no growth (protein: 95 mg/dl, glucose: 35 mg/dl) and N.meningitidis serogroup Y was detected by PCR. Two meningococcemia cases caused by two different serogroups which are rarely seen in our region in recent years were presented at the same time period in the same hospital. This case report pointed out that surveillance has a great importance in such diseases. |
| 2020 | Neonatal exchange transfusion: Experience in Korea. | Transfus Apher Sci | Exchange transfusion (ET) is an established, efficacious, and reliable practice for severe neonatal hyperbilirubinemia, hemolytic disease of the newborn, and neonatal sepsis. This study assessed the indications and clinical outcomes of ET performed in a tertiary hospital in Korea.We studied 64 ET sessions performed on 23 neonates between March 1999 and March 2018. ET was performed based on estimated double volume exchange transfusion using fresh red blood cells and fresh frozen plasma. Patients' clinical information, including demographic data and ET indication, and laboratory data were collected pre- and post-ET.The most common ET indication was hyperbilirubinemia with hemolytic anemia due to non-ABO maternal blood group discrepancies. In three preterm babies, ETs were performed for severe anemia, leukocytosis, and hyperkalemia cases. Before ET, the patients showed slightly high WBC counts, low hemoglobin levels, and low platelet counts. After ET, blood examination revealed normal WBC counts, increased hemoglobin levels, and decreased platelet counts (all P < 0.001). Bilirubin levels decreased immediately after ET (P < 0.001). Electrolyte and C-reactive protein levels showed no significant changes after ETs. Adverse events occurred in 11 (47.8 %) patients; the most common were hypoxemia and hypotension. One infant experienced cardiorespiratory arrest due to hypercalcemia and was successfully resuscitated. No one died within 24 h of ET. However, five infants showed hyperbilirubinemia aggravation.ET is an effective treatment modality for leukocytosis and hyperbilirubinemia with low mortality but involves common adverse events post-ET. This report provides an overview of current ET practices in Korea. |
| 2020 | Persistent severe post-operative hypotension after pancreaticoduodenectomy is related to increased inflammatory response. | Acta Anaesthesiol Scand | Hypotension during major surgery is frequent, resulting in increased need for observation in the post-anaesthesia care unit and treatment including vasopressors and fluids. However, although severe hypotension in the immediate post-operative recovery phase after major surgery is suggested to be related to increased morbidity and mortality, the underlying risk factors are not well described, hindering advancements in prevention and treatment.We performed a retrospective study assessing factors (age, gender, body-mass index, cardiac co-morbidity, haemoglobin, absolute and increase in c-reactive protein on the first post-operative day, bleeding, fluid balance at the end of surgery and the first post-operative day) related to severe persistent hypotension (SPH) (SPH: need for noradrenaline to maintain a mean arterial blood pressure (MAP) >65.0 mm Hg on the morning after surgery) and occurrence of other early (24 hours) complications. One hundred patients undergoing pancreaticoduodenectomy (PD) with pre-operative high-dose glucocorticoid and goal-directed fluid therapy were enrolled and perioperative data collected from anaesthetic and medical records.Forty-five patients had SPH, who had a significantly higher increase in CRP levels the morning after surgery (median 50 mg L vs 41 mg L , SPH vs non-SPH, respectively, P = .028), and a significantly more positive fluid balance at discharge (median 1457 ml vs 1031 ml, respectively, P = .027) vs patients without SPH.Severe persistent hypotension after PD was associated with significantly increased inflammatory response and increased need for fluids. Future studies should investigate the effect of further inflammatory control in PD to improve haemodynamics and morbidity. |
| 2020 | [Predictive factors of bacteraemia in the patients seen in emergency departments due to infections]. | Rev Esp Quimioter | The aim of the study was to analyze predictive factors of bacteraemia in patients seen in the emergency department (ED) for an episode of infectious disease.Observational, retrospective and descriptive analytical study of all blood cultures extracted in an ED in adult patients (≥ 18 years) seen in ED due to infec-tious disease from 1-1-2019 to 1-7-2019. The follow-up was carried out during 30 days. Thirty-eight variables for predicting bacteraemia were assessed. They covered epidemiological, comorbidity, functional, clinical and analytical factors. Univariate and multivariate logistic regression analysis was performed.A total of 1,425 blood cultures were finally enrolled in the study. Of those were considered true bacteremia 179 (12.6 %) and as negative blood cultures 1,246 (87.4 %). Amongst negatives, 1,130 (79.3%) without growth and 116 (8.1%) as contaminants blood cultures. Five variables were significantly associated with true bacteraemia: serum procalcitonin (PCT) ≥ 0.51 ng/ml [odds ratio (OR): 4.52; 95% confidence interval (CI): 4.20-4.84, P <.001], temperature > 38.3°C [OR:1.60; 95% CI:1.29-1.90, P <.001], systolic blood pressure (SBP) < 100 mmHg [OR:3.68; 95% CI:2.78-4.58, P <.001], septic shock [OR:2.96; 95% CI:1.78-4.13, P <.001] and malignancy [OR:1.73; 95% CI:1.27-2.20, P <.001].Several factors evaluated in an initial assessment in the ED, including serum PCT, temperature, hypotension (with/without septic shock) and being malignancy, were found to predict true bacteraemia. |
| 2019 | Sepsis Care Pathway 2019. | Qatar Med J | Sepsis, a medical emergency and life-threatening disorder, results from abnormal host response to infection that leads to acute organ dysfunction. Sepsis is a major killer across all ages and countries and remains the most common cause of admission and death in the Intensive Care Unit (ICU). The true incidence remains elusive and estimates of the global burden of sepsis remain a wild guess. One study suggested over 19 million cases and 5 million sepsis-related deaths annually. Addressing the challenge, the World Health Assembly of the World Health Organisation (WHO) passed a resolution on better prevention, diagnosis, and management of sepsis. Despite thousands of articles and hundreds of trials, sepsis remains a major killer. The cornerstones of sepsis care remain early recognition, adoption of a systematic evidence-based bundle of care, and timely escalation to higher level of care. The bundle approach has been advocated since 2004 but underwent major modifications in subsequent years with more emphasis on the time-critical nature of sepsis and need to restore physiological variables within one hour of recognition. A shift from a three and six-hour bundle to one-hour bundle has been recommended. This single hour approach has been faced with an outcry and been challenged. Over several decades, the individual components of the sepsis bundle have not changed. Encountering a patient with suspected sepsis, one should measure lactate, obtain blood cultures, swiftly administer broad spectrum antimicrobials and fluids, and infuse vasopressors. A critical question arises: should we do this for all patients? Sepsis is not septic shock and guidelines did not make distinctive recommendations for each. Septic patients will present differently with some having more subtle signs and symptoms. Phenotypically, we do not know which patient with infection will develop a dysregulated host response and will succumb to sepsis and/or shock. The existing bundle lacks high quality evidence to support its recommendations and a blanket implementation for all patients with 'suspected' sepsis could be harmful. Indeed, a significant reduction of sepsis and septic shock in Australia and New Zealand was observed in a bundle-free region. Upon arrival in the ED, patients will be triaged. This is 'time zero'. Those with hypotension and hypoperfusion will be easily recognised and at most need to receive emergent care. Sepsis, per se, may not manifest clear cut signs and expertise to identify it is required. Those with non-specific symptoms may trigger an early warning scoring system and receive unnecessary antimicrobials and a large volume of intravenous (IV) fluids. Both therapies are not without significant side effects. Putting pressure on ED physicians to implement the 60-minute bundle without individualisation of care puts our patients at risk. Given the heterogenous nature and diverse pathobiological pathways, sepsis diagnosis can be challenging and both over and under-treatment can result. Established biomarkers such as procalcitonin and C-reactive protein lack specificity to rule out infection as the cause of inflammation. Currently, no laboratory test or biomarker helps predict which patients with infection or inflammation will develop organ dysfunction. A dire need for a specific sepsis biomarker exists. Modern molecular-based technologies are evolving and utilise polymerase chain reaction (PCR), nanotechnology, and microfluidics for point-of-care testing. Some devices identify causative microorganisms and their sensitivity in less than an hour. Catecholamines along with IV fluids are indicated to restore perfusion. However, inadvertent side effects may arise, especially at higher doses. Anti-adrenergic ß-blockers improve cardiac performance, enhance receptor responsiveness, and possess anti-inflammatory action. All are desirable in patients with septic shock. One randomised trial showed beneficial and protective effects of ß-blockers in septic shock. Rapidly acting titratable agents should be used in conjunction with appropriate hemodynamic monitoring and after adequate volume resuscitation. There is no consensus on target heart rate but an arbitrary cut off of 80-95 beats per minute is reasonable. Fluid resuscitation is the cornerstone of sepsis management. There is also compelling evidence that too much fluid is bad. Starch-based colloids should not be used in septic shock. Albumin is an alternative when large volumes are required but is not appropriate in traumatic brain injury. Balanced, less chloride and less acidic crystalloids are safer for the kidneys and are preferred over normal saline. Doses of IV fluids should be tailored to the patient's condition and a 30 ml/kg recommendation should be reviewed. Effective sepsis management requires adequate dosing of antimicrobials. Significant alteration of pharmacokinetics and pharmacodynamics is characteristic of septic shock. Accurate and effective dosing is challenging particularly in patients with multiple comorbidities and those receiving extracorporeal organ support. Underdosing results in treatment failure, whilst overdosing leads to toxicity and the risk of developing multi-drug resistant organisms. An individualised approach supported by therapeutic drug monitoring is suggested to ensure clinical efficacy. The search for a cure for sepsis is ongoing. A large prospective, randomised two-arm, parallel group study aims to recruit over 200 patients with septic shock across critical care units in Qatar. Evaluation of Hydrocortisone, Vitamin C, and Thiamine (HYVITS) examines the safety and efficacy of this triple therapy. Children are particularly vulnerable to sepsis. 1 in 6 children admitted with septic shock to ICU will die. As the majority of paediatric sepsis cases are community acquired, there is a strong need to raise awareness both for families and primary healthcare providers. Akin to adults, a bundle-approach to paediatric sepsis is strongly encouraged. National programs for paediatric sepsis have been established. The Qatar paediatric multidisciplinary sepsis program was established under the umbrella of the adult programme in 2017. A structured and standardised approach to sepsis across all neonate and paediatric facilities has been developed and implemented. Improvement in timely sepsis recognition and administration of antimicrobials within the golden hour has been observed. The program aims to achieve a 95% compliance to the paediatric sepsis bundle by the end of 2019. A screening tool and order set have been put in place and are presented in this special issue of Qatar Medical Journal. Pregnancy and childbirth are risk factors for sepsis. Multi-organ failure and death can result from puerperal sepsis. Sepsis is the direct and leading cause of maternal mortality in the UK. Attention to maternal sepsis with a tailored approach is encouraged. The Qatar National Sepsis Program developed a sepsis care pathway for pregnant women and during their early post-partum period. A broader, national -or better yet- a global approach to further sepsis management and outcome should be considered. There are a number of significant challenges to address. One such challenge is the inconsistency of the operational definition and diagnostic approaches for sepsis including coding and documentation. Significant deficiencies in healthcare systems have been highlighted by sepsis. This is most obvious in medium- and low-income countries. A major limitation to effective sepsis management is inadequate medical staffing and poor knowledge and awareness of sepsis. Both have a negative impact on sepsis outcome. Poor medical facilities in many countries pose significant challenges to sepsis care. Lack of critical care capacity - a global phenomenon - has been linked to poor outcome of sepsis cases and septic shock. This could be attributed to provision of suboptimal critical care, monitoring and critical interventions outside of the ICU. ICU availability is subject to inconsistency and inequity. Lack of adequate surgical capacity to accomplish timely source control adversely affects sepsis management. This, unfortunately, in medium- and low-income countries, is accompanied by inadequate medical supplies, diagnostic capacity, and manpower which increases sepsis mortality and morbidity. Antimicrobials are critical for sepsis care. A global concern is the development of multi-drug resistant organisms and the lack of novel antimicrobials and this adds pressure on those caring for septic patients. Effective antimicrobials should be utilised to eradicate infections. Misuse, inadequacy, inferior agents, and lack of timely access to effective and affordable agents significantly hinders patient's recovery from sepsis. Optimum sepsis outcome mandates attention to acute sepsis complications (e.g. acute renal or respiratory failure) as well as addressing post-discharge complications and disability. These challenging issues remain poorly studied or addressed. Sepsis and septic shock are major global health concerns. Progress has been achieved in understanding this life-threatening syndrome at a biological, metabolic, and cellular level. Efforts should be coordinated to improve sepsis care. Better and more accurate diagnostics are needed and governments are encouraged to invest in sepsis research and care. More integrated, inclusive, and focused research is desperately needed. Public education and increased awareness among primary healthcare providers are also critical to improve sepsis outcome. |
| 2019 | [Application of Narcotrend index and Richmond agitation-sedation score in sedation assessment of patients with short-term mechanical ventilation after pancreatoduodenectomy: a randomized controlled trial]. | Zhonghua Wei Zhong Bing Ji Jiu Yi Xue | To explore the feasibility of Narcotrend index (NTI) for digital monitoring of light sedation depth in patients undergoing short-term mechanical ventilation after pancreaticoduodenectomy.A prospective randomized controlled trial was conducted. Patients with mechanical ventilation for 12-48 hours after pancreaticoduodenectomy admitted to department of critical care medicine of the First Affiliated Hospital of Wannan Medical College from January 2016 to December 2018 were enrolled. They were randomly divided into two groups, and NTI and Richmond agitation-sedation score (RASS) were used to guide light sedation treatment respectively. The implementation effect of light sedation, duration of mechanical ventilation, dosage of sedative drugs, occurrence of adverse events (accidental extubation, delirium, cardiovascular events) and stress response [cortisol, epinephrine, norepinephrine, C-reactive protein (CRP)] were compared between the two groups.A total of 87 patients were enrolled in this study, of whom 45 received NTI-guided sedation assessment and 42 received RASS-guided sedation assessment. There were no significant differences in gender, age, body mass index (BMI), liver function classification, operation time, blood loss, conversion to laparotomy and acute physiology and chronic health evaluation II (APACHE II) score between the two groups. During sedation treatment, the light sedation compliance rate after light sedation, 2, 4, 6 hours and cumulative compliance period number (Dt) in NTI group were higher than those in RASS group [71.1% (32/45) vs. 50.0% (21/42), 80.0% (36/45) vs. 54.8% (23/42), 88.9% (40/45) vs. 59.5% (25/42), 83.9% (642/765) vs. 62.8% (475/756), all P < 0.05]. The dosage of dexmedetomidine in NTI group was higher than that in RASS group (μg×kg×h: 0.60±0.10 vs. 0.54±0.12, P < 0.01), but more patients in RASS group receiveda larger dose of propofol to maintain sedation [ratio of use of propofol: 64.3% (27/42) vs. 37.8% (17/45), dose of propofol (mg/h): 47.82±7.31 vs. 30.83±10.35, both P < 0.05]. The sedation duration and duration of mechanical ventilation in NTI group were lower than those in RASS group (hours: 15.68±2.43 vs. 17.29±2.43, 16.27±2.42 vs. 18.25±2.04, both P < 0.01). There were no significant differences in hypertension, bradycardia, accidental extubation and delirium between the two groups during sedation treatment, but the incidence of hypotension in RASS group was higher than that in NTI group [35.7% (15/42) vs. 13.3% (6/45), P < 0.05]. Compared with RASS group, epinephrine, norepinephrine and the levels of CRP at treatment of 6 hours with light sedation and 2 hours after tracheal catheter removal in NTI group were decreased [epinephrine (pg/L): 138.35±18.60 vs. 157.50±19.91, 136.24±40.40 vs. 150.46±20.22; norepinephrine (pg/L): 347.34±45.46 vs. 393.75±49.77, 340.59±50.95 vs. 376.37±49.70; CRP (μg/L): 62.26±18.78 vs. 71.31±10.32, 53.30±14.47 vs. 64.26±14.69, all P < 0.05], and cortisol level 6 hours after treatment with light sedation was lower than that of RASS group (nmol/L: 327.03±41.04 vs. 358.12±70.01, P < 0.05).The application of NTI monitoring to guide light sedation therapy for patients with short-term mechanical ventilation after pancreaticoduodenectomy can better achieve the goal of light sedation. |
| 2019 | Prognostic Role of Admission C-Reactive Protein Level as a Predictor of In-Hospital Mortality in Type-A Acute Aortic Dissection: A Meta-Analysis. | Vasc Endovascular Surg | Acute aortic dissection (AD) is a lethal vascular disease, accounting for over 90% cases of acute aortic syndrome. Despite advances in understanding associated risk factors, the long-term prognosis for AD patients is still poor. Several prognostic biomarkers have been used for AD as per the IRAD, such as older age (>70 years), onset of chest pain and hypotension, but they are not effective in all patients. Instead, C-reactive protein (CRP) is a consistent inflammatory marker. CRP levels are abnormally increased in AD. However, the prognostic value of serum CRP level in AD remains unclear.To perform a systematic review and meta-analysis (registration no CRD42017056205) to evaluate whether CRP is a biomarker associated with in-hospital mortality in type-A AD.PubMed, Web of Science, CNKI, SciELO, and EMBASE were searched for papers published from January 2000 to October 2017 for studies on the prognostic role of CRP at admission in type-A AD patients. Outcome data were extracted and pooled hazard ratios (HRs) were calculated.18 (N = 2875 patients) studies met the inclusion criteria. Elevated CRP level was associated with a significantly increased risk of in-hospital mortality in patients with type-A AD (HR = 1.15, 95% CI: 1.06-1.25, = 0.001). The pooled sensitivity of CRP in type-A AD patients was 77% (95% CI 69%-84%, < 0.001), and the specificity was 72% (95% CI 66%-78%, < 0.001).Elevated CRP level is significantly associated with increased risks of in-hospital mortality in patients with type-A AD. CRP is a convenient prognostic factor in type-A AD patients. |
| 2019 | Kawasaki disease shock syndrome: A report of two cases and literature review. | Pediatr Investig | Kawasaki disease shock syndrome (KDSS) is a rare Kawasaki disease (KD) manifestation. The pediatricians are not aware of the full range of clinical characteristics of KDSS.We aimed to investigate the clinical features, diagnosis and treatment of KDSS in two patients and we included a literature review.We collected and analyzed the clinical data for two patients with KDSS. Additionally, using "Kawasaki diseases shock syndrome" as a key phrase, we searched PubMed, Biotechnology Information and Wanfang Data Knowledge Service Platform databases for any similar reports between January 2009 and March 2017.Both of our patients diagnosed with KD developed sustained hypotension during the course of intravenous immunoglobulin treatment, as well as hypoalbuminemia, and increased C-reactive protein and brain natriuretic peptide levels during hypotension. Both patients responded well to fluid resuscitation and inotropic support. No aneurysms formed in either patient during follow-up. We reviewed two related studies in Chinese and 11 studies in English.KD may present with severe shock, and requires proper diagnosis and rapid treatment. The prognosis for most patients with KDSS is excellent. |
| 2019 | Orthostatic Hypotension in Asymptomatic Patients with Chronic Kidney Disease. | Medicina (Kaunas) | : Orthostatic hypotension (OH) is a decrease in systolic blood pressure (BP) of 20 mm Hg and in diastolic BP of 10 mm Hg when changing the position from lying to standing. Arterial hypertension (AH), comorbidities and polypharmacy contribute to its development. The aim was to assess the presence of OH and its predictors in asymptomatic chronic kidney disease (CKD) patients. : 45 CKD patients with estimated glomerular filtration rate (eGFR) ≤ 60 mL/min/1.73 m (CKD+) were examined for signs of OH and its predictors. The results were compared with the control group of 22 patients with eGFR > 60 mL/min/1.73 m (CKD-). Asymptomatic patients without ischemic heart disease and previous stroke were qualified. Total blood count, serum creatinine, eGFR, urea, phosphates, calcium, albumins, parathyroid hormone, uric acid, C reactive protein, N-terminal pro b-type natriuretic peptide, lipid profile, and urine protein to creatinine ratio were assessed. Simultaneously, patients underwent echocardiography. To detect OH, a modified Schellong test was performed. : OH was diagnosed in 17 out of 45 CKD+ patients (average age 69.12 ± 13.2) and in 8 out of 22 CKD- patients (average age 60.50 ± 14.99). The CKD+ group demonstrated significant differences on average values of systolic and diastolic BP between OH+ and OH- patients, lower when standing. In the eGFR range of 30-60 mL/min/1.73 m correlation was revealed between OH and β-blockers ( = 0.04), in the entire CKD+ group between β-blockers combined with diuretics ( = 0.007) and ACE-I ( = 0.033). Logistic regression test revealed that chronic heart failure (CHF, OR = 15.31), treatment with β-blockers (OR = 13.86) were significant factors influencing the presence of OH. : Predictors of OH in CKD may include: CHF, treatment with β-blockers, combined with ACE-I and diuretics. |
| 2019 | Clinical presentation and early predictors for poor outcomes in pediatric myocarditis: A retrospective study. | World J Clin Cases | Myocarditis is an important cause of morbidity and mortality in children, leading to long-term sequelae including chronic congestive heart failure, dilated cardiomyopathy, heart transplantation, and death. The initial diagnosis of myocarditis is usually based on clinical presentation, but this widely ranges from the severe sudden onset of a cardiogenic shock to asymptomatic patients. Early recognition is essential in order to monitor and start supportive treatment prior to the development of severe adverse events. Of note, many cases of fulminant myocarditis are usually misdiagnosed as otherwise minor conditions during the weeks before the unexpected deterioration.To provide diagnostic clues to make an early recognition of pediatric myocarditis. To investigate early predictors for poor outcomes.We conducted a retrospective cross-sectional single-center study from January 2008 to November 2017 at the Pediatric Department of our institution, including children < 18-years-old diagnosed with myocarditis. Poor outcome was defined as the occurrence of any of the following facts: death, heart transplant, persistent left ventricular systolic dysfunction or dilation at hospital discharge (early poor outcome), or after 1 year of follow-up (late poor outcome). We analyzed different clinical features and diagnostic test findings in order to provide diagnostic clues for myocarditis in children. Multivariable stepwise logistic regression analysis was performed using all variables that had been selected by univariate analysis to determine independent factors that predicted a poor early or late outcome in our study population.A total of 42 patients [69% male; median age of 8 (1.5-12) years] met study inclusion criteria. Chest pain (40%) was the most common specific cardiac symptom. Respiratory tract symptoms (cough, apnea, rhinorrhea) (38%), shortness of breath (35%), gastrointestinal tract symptoms (vomiting, abdominal pain, diarrhea) (33%), and fever (31%) were the most common non-cardiac initial complaints. Tachycardia (57%) and tachypnea (52%) were the most common signs on the initial physical exam followed by nonspecific signs of respiratory tract infection (44%) and respiratory distress (35%). Specific abnormal signs of heart failure such as heart murmur (26%), systolic hypotension (24%), gallop rhythm (20%), or hepatomegaly (20%) were less prevalent. Up to 43% of patients presented an early poor outcome, and 16% presented a late poor outcome. In multivariate analysis, an initial left ventricular ejection fraction (LVEF) < 30% remained the only significant predictor for early [odds ratio (OR) (95%CI) = 21 (2-456), = 0.027) and late [OR (95%CI) = 8 (0.56-135), = 0.047) poor outcome in children with myocarditis. LVEF correlated well with age ( = 0.51, = 0.005), days from the initiation of symptoms ( = -0.31, = 0.045), and N-terminal pro-brain natriuretic peptide levels ( = 0.66, < 0.001), but not with troponin T ( = -0.05, = 0.730) or C-reactive protein levels ( = -0.13, = 0.391). N-terminal pro-brain natriuretic peptide presented a high diagnostic accuracy for LVEF < 30% on echocardiography with an area under curve of 0.931 (95%CI: 0.858-0.995, < 0.001). The best cut-off point was 2000 pg/mL with a sensitivity of 90%, specificity of 81%, positive predictive value of 60%, and negative predictive value of 96%.The diagnosis of myocarditis in children is challenging due to the heterogeneous and unspecific clinical presentation. The presence of LVEF < 30% on echocardiography on admission was the major predictor for poor outcomes. Younger ages, a prolonged course of the disease, and N-terminal pro-brain natriuretic peptide levels could help to identify these high-risk patients. |
| 2019 | [Association of inflammatory indices with the severity of urinary sepsis: analysis of 70 cases]. | Nan Fang Yi Ke Da Xue Xue Bao | To analyze the association of the clinical inflammatory indices with the severity of urinary sepsis.We reviewed the clinical data of 70 patients with urinary sepsis treated in our hospital between January, 2013 and April, 2018. All the patients were diagnosed in line with the Guidelines for Diagnosis and Treatment of Urological Diseases in China (2014 edition), including 22 patients with sepsis, 12 with hypotension and severe sepsis, 17 with septic shock, and 19 with critical septic shock. White blood cell count (WBC), neutrophil percentage (N%), platelets (PLT), fibrinogen (FIB), Ddimer, interleukin-6 (IL-6), procalcitonin (PCT) and C-reactive protein (CRP) were examined in all the cases and compared among the 4 groups. The correlations of these inflammatory markers with the severity of sepsis were analyzed using logistic regression analysis.The 4 groups of patients showed significant differences in N%, PLT, D-dimer, and PCT ( < 0.05) but not in CRP (>0.05). Kruskal-Wallis Pairwise comparisons showed that the N% and PCT in patients with sepsis differed significantly from those in the other 3 groups; platelets in patients with sepsis differed significantly from those in patients with septic shock and critical septic shock; D-dimer differed significantly between patients with sepsis and those with septic shock. Among the 4 groups, the median levels of PLT decreased and PCT and N% increased with the worsening of sepsis. Logistic regression analysis indicated that PCT (=0.186, =0.000), N% (=0.047, =0.035) and PLT (=-0.012, =0.003) were significantly correlated with the severity of sepsis in these patients.PCT, PLT and N% are all significantly correlated with the severity of sepsis, and their combined detection can be informative for assessing the severity of sepsis to facilitate clinical decisions on treatment. |
| 2019 | Food protein-induced enterocolitis syndrome: guidelines summary and practice recommendations. | Med J Aust | Food protein-induced enterocolitis syndrome (FPIES) is a poorly understood non-IgE gastrointestinal-mediated food allergy that predominantly affects infants and young children. Cells of the innate immune system appear to be activated during an FPIES reaction. Acute FPIES typically presents between one and 4 hours after ingestion of the trigger food, with the principal symptom being profuse vomiting, and is often accompanied by pallor and lethargy. Additional features can include hypotension, hypothermia, diarrhoea, neutrophilia and thrombocytosis. In Australia, the most commonly reported foods responsible for FPIES are (in descending order) rice, cow's milk, egg, oats and chicken. Most children with FPIES react to only one food trigger, and thus, avoidance of multiple foods is often not indicated. FPIES is often misdiagnosed as sepsis or gastroenteritis. However, a diagnosis of FPIES is favoured if there is rapid resolution of symptoms within hours of presentation, an absence of fever, and a lack of a significant rise in C-reactive protein at presentation. Diagnosis is often hampered by the lack of awareness of FPIES, absence of reliable biomarkers, the non-specific nature of the presenting symptoms, and the delay between allergen exposure and symptoms. Although some national peak allergy bodies have attempted to improve the diagnosis and management of FPIES, up until 2017 there were no internationally agreed guidelines for its diagnosis and management. |
| 2018 | Clinical significance of analysis of the level of blood fat, CRP and hemorheological indicators in the diagnosis of elder coronary heart disease. | Saudi J Biol Sci | To investigate the levels of blood fat, C-reactive protein (CRP) and hemorheological indicators in the elder patients with coronary heart disease (CHD), so as to provide evidence for prospective study and treatment of elder CHD.We collected the clinical data of 127 elder CHD patients who admitted to this hospital between July 2016 and December 2017 to detect the levels of blood fat, CRP and hemorheological indicators.In elder CHD patients, levels of the total cholesterol (TC), triglyceride (TG) and low density lipoprotein cholesterin (LDL-C) were significantly higher than the normal reference, and comparison with the control group also showed significant increases ( < 0.01); average levels of the high-density lipoprotein cholesterin (HDL-C), phospholipid (PL), lipoprotein a [LP (a)] and free fatty acid were in the range of normal reference. Abnormal levels of TC, TG, LDL-C and HDL-C were identified in 59.06%, 58.27%, 51.18% and 18.11% of the elder CHD patients, most of which were concomitant with obesity or hypertension, and levels of these indicators were significantly higher than those in the control group with statistically significant differences ( < 0.01). Comparisons of the age, gender distribution, hypotension, exercise and sleep showed that differences had no statistical significance ( > 0.05). In comparison with the control group, the levels of CRP, the whole blood viscosities at high and low shears, plasma viscosity, hematocrit value, aggregation index and rigidity index of red blood cells (RBC) were all higher than those in the control group, and the differences had statistical significance ( < 0.01). However, the erythrocyte sedimentation rate (ESR), deformity index of RBC, blood flow rates in the bilateral middle cerebral arteries (MCA), anterior cerebral arteries (ACA), terminal internal carotid artery (TICA), posterior cerebral arteries (PCA), vertebral arteries (VA) and basilar artery (BA) were significantly lower than those in the control group, and the differences had statistical significance ( < 0.05 or 0.01).In elder CHD patients, anomaly is mainly seen in levels of TC, TG and LDL-C with concentrated, adhesive and aggregating blood. |
| 2018 | Assessment of acute kidney injury in canine parvovirus infection: Comparison of kidney injury biomarkers with routine renal functional parameters. | Vet J | Dogs with naturally occurring canine parvovirus (CPV) infection are at risk of developing acute kidney injury (AKI) due to several factors, including severe dehydration, hypotension and sepsis. Serum creatinine (sCr) and serum urea are insensitive markers for the assessment of early kidney injury. Therefore, the aim of this study was to investigate potential kidney injury in dogs with CPV infection using both routine renal functional parameters and several kidney injury biomarkers. Twenty-two dogs with CPV infection were prospectively enrolled and compared with eight clinically healthy control dogs. Urinary immunoglobulin G (uIgG) and C-reactive protein (uCRP) were measured to document glomerular injury, whereas urinary retinol-binding protein (uRBP) and neutrophil gelatinase-associated lipocalin (uNGAL) served as markers for tubular injury. These biomarkers were compared to routine renal functional parameters, including sCr, serum urea, urinary protein:creatinine ratio (UPC) and urine specific gravity (USG). Dogs with CPV infection had significantly higher concentrations of uIgG, uCRP, uRBP and uNGAL compared to healthy dogs. In contrast, sCr was significantly lower in dogs with CPV infection compared to controls, while serum urea was not significantly different. UPC and USG were both significantly higher in CPV-infected dogs. This study demonstrated that dogs with CPV infection had evidence of AKI, which remained undetected by the routine functional markers sCr and serum urea, but was revealed by UPC, uIgG, uCRP, uRBP and uNGAL. These results emphasize the added value of novel urinary kidney injury biomarkers to detect canine patients at risk of developing AKI. |
| 2019 | Comparison of diagnostic accuracy for nonocclusive mesenteric ischemia in models with biomarkers including intestinal fatty acid-binding protein in addition to clinical findings. | J Trauma Acute Care Surg | Nonocclusive mesenteric ischemia (NOMI) is an acute and life-threatening gastrointestinal disorder, requiring rapid therapeutic intervention for ischemic bowel. However, its rapid detection remains challenging. This retrospective, observational study was aimed at comparing the diagnostic accuracy for NOMI in models of biomarkers, including intestinal fatty acid-binding protein (I-FABP), and clinical findings.All consecutive patients who presented to the emergency department of the study hospital with suspected NOMI were prospectively enrolled. Receiver operating characteristic analysis compared the diagnostic accuracy of I-FABP with traditional biomarkers (white blood cell count, C-reactive protein, lactate, creatine kinase, and D-dimer) alone and in combination with the baseline model established from clinical findings.Of 96 patients with suspected NOMI, 25 (26.0%) were clinically diagnosed with NOMI. In-hospital mortality was higher in patients with NOMI than those with other conditions (56.0% vs. 4.2%, p < 0.001). Receiver operating characteristic analyses revealed that the I-FABP model had the highest area under the curve (0.805) in the diagnosis of NOMI, compared with other biomarkers. The diagnostic model of clinical findings including age, cardiovascular disease history, undergoing hemodialysis, hypotension, and consciousness disturbance in combination with I-FABP showed the best discrimination (area under the curve, 0.883), compared with other biomarkers. The bootstrap optimism estimate showed the lowest discrimination among the other models with other biomarkers (0.006).The usefulness of I-FABP for final diagnosis of NOMI in patients with clinically suspected NOMI at the emergency department was internally validated. Further external validation study is warranted.Diagnostic test, level III. |
| 2019 | The C-Reactive Protein to Albumin Ratio Predicts Acute Kidney Injury in Patients With ST-Segment Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention. | Heart Lung Circ | The relationship between acute kidney injury (AKI) and C-reactive protein (CRP) and albumin has been previously demonstrated in patients with ST elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (pPCI). However, to our knowledge, CRP to albumin ratio (CAR), a newly introduced inflammation-based risk score, has not yet been studied. In this study, we aimed to investigate the possible relationship between the CAR and AKI.A total of 815 consecutive STEMI patients treated with pPCI were reviewed.One hundred ten 110 (13.5%) patients developed AKI in the study population. The subjects were divided into two groups according to AKI development. The in-hospital mortality rate was higher in patients with AKI than those without AKI (15.5% vs. 1.3%; p<0.001). The patients with AKI had significantly higher mean value of CRP and CAR (0.29 [0.16-0.50] vs. 0.55 [0.37-1.05]; p<0.001) and lower mean levels of albumin than those without AKI. Age, diabetes mellitus, haematocrit, left ventricular ejection fraction, hypotension, and CAR (Odds ratio [OR]2.307, 95% confidence interval [CI] 1.397-3.809, p=0.001) were independent predictors of AKI.The CAR may be a useful inflammation-based risk score to predict AKI development in STEMI patients treated with pPCI. |
| 2018 | The role of extra-pancreatic infections in the prediction of severity and local complications in acute pancreatitis. | Pancreatology | The aim of our study was to determine the risk factors for extrapancreatic infection (EPI) occurrence and its predictive power for assessing severity and local complications in acute pancreatitis including infected pancreatic necrosis (IPN).Clinical data of 176 AP patients prospectively enrolled were analysed. EPI analysed were bacteraemia, lung infection, urinary tract infection and catheter line infection. Risk factors analysed were: Leukocyte count, C-reactive protein, liver function test, serum calcium, serum glucose, Blood urea nitrogen, mean arterial pressure at admission, total parenteral nutrition (TPN), enteral nutrition, hypotension, respiratory, cardiovascular and renal failure at admission, persistent systemic inflammatory response (SIRS) and intrapancreatic necrosis. Severity outcomes assessed were defined according to the Atlanta Criteria definition for acute pancreatitis. The predictive accuracy of EPI for morbidity and mortality was measured using area-under-the-curve (AUC) receiver-operating characteristics.Forty-four cases of EPI were found (25%). TPN (OR:9.2 CI95%: 3.3-25.7), APACHE-II>8 (OR:6.2 CI95%:2.48-15.54) and persistent SIRS (OR:2.9 CI95%: 1.1-7.8), were risk factors related with EPI. Bacteraemia, when compared with others EPI, showed the best accuracy in predicting significantly persistent organ failure (AUC:0.76, IC95%:0.64-0.88), ICU admission (AUC:0.80 IC95%:0.65-0.94), and death (AUC:0.73 CI95%:0.54-0.91); and for local complications including IPN (AUC:0.72 CI95%:0.53-0.92) as well. Besides, it was also needed for an interventional procedure against necrosis (AUC:0.74 IC95%: 0.57-0.91). When bacteraemia and IPN occurs, bacteraemia preceded infected necrosis in all cases. On multivariate analysis, risk factor for IPN were lung infection (OR:6.25 CI95%1.1-35.7 p = 0.039) and TPN (OR:22.0CI95%:2.4-205.8, p = 0.007), and for mortality were persistent SIRS at first week (OR: 22.9 CI95%: 2.6-203.7, p = 0.005) and Lung infection (OR: 9.7 CI95%: 1.7-53.8).In our study, EPI, played a role in predicting the severity and local complications in acute pancreatitis. |
| 2019 | Multiple balloon-like lesions in the small intestine of an adult with chronic diarrhoea. | Gut | A 28-year-old woman presented with a 3-year history of chronic watery diarrhoea along with abdominal pain and bloating, which could mostly be alleviated after defecation. Her symptom of diarrhoea, at least three times a day, could be relieved by neither probiotics nor antidiarrhoeal agents. She had also lost 5 kg in the last month. She denied family history, poor vaccine responses or significant infections in early childhood except for an allergy history to intravenous immunoglobulin (Ig) with immediate dyspnoea, palpitations and hypotension. Laboratory investigations suggested that the stool specimens were negative for viruses, parasites or bacteria. Laboratory evaluation revealed a low serum globulin level, 14.5 (reference range, 20-30 g/L); serum Ig levels were significantly abnormal: IgA <0.27 (0.7-4 g/L), IgM 0.24 (0.4-2.3 g/L), IgG 1.3 (7-16 g/L); white cell count 15.4×10/L (3.69-9.16×10/L); C-reactive protein (CRP) 20.5 (normal <10 mg/L); CD4+ lymphocyte/CD8+ lymphocyte 1.09% (1.5%-2%). Other laboratory findings were unremarkable, for example, tumour markers, autoantibodies and HIV, and so on. CT showed mesenteric nodule-like images and thickening of the wall and mucosa in small intestine. Peroral and transanal enteroscopy respectively demonstrated swelling mucosa and continuous granular lesions from duodenum to middle jejunum, and from middle ileum to terminal ileum (figure 1A-D).gutjnl;68/3/452/F1F1F1Figure 1Endoscopic images show swelling mucosa, dense nodular lesions in duodenum (A), upper jejunum (B), upper ileum (C) and terminal ileum (D).What is the most likely diagnosis? |
| 2018 | Effect of pre-operative methylprednisolone on orthostatic hypotension during early mobilization after total hip arthroplasty. | Acta Anaesthesiol Scand | Orthostatic hypotension (OH) and intolerance (OI) are common after total hip arthroplasty (THA) and may delay early mobilization. The pathology of OH and OI includes a dysregulated post-operative vasopressor response, by a hitherto unknown mechanism. We hypothesized that OI could be related to the inflammatory stress response which is inhibited by steroid administration. Consequently, this study evaluated the effect of a pre-operative high-dose methylprednisolone on OH and OI early after THA.Randomized, double-blind, placebo-controlled study in 59 patients undergoing elective unilateral THA with spinal anesthesia and a standardized multimodal analgesic regime. Patients were allocated (1 : 1) to pre-operative intravenous (IV) methylprednisolone (MP) 125 mg or isotonic saline (C). OH, OI and cardiovascular responses to sitting and standing were evaluated using a standardized mobilization protocol pre-operatively, 6, and 24 h after surgery. Systolic and diastolic arterial pressure and heart rate were measured non-invasively (Nexfin ). The systemic inflammation was monitored by the C-reactive protein (CRP) response.At 6 h post-operatively, 11 (38%) versus 11 (37%) patients had OH in group MP and group C, respectively (RR 1.02 (0.60 to 1.75; P = 1.00)), whereas OI was present in 9 (31%) versus 13 (43%) patients (RR 0.76 (0.42 to 1.36; P = 0.42)), respectively. At 24 h post-operatively, the prevalence of OH and OI did not differ between groups, though CRP levels were significantly reduced in group MP (P < 0.001).Pre-operative administration of 125 mg methylprednisolone IV did not reduce OH or OI compared with placebo despite a reduced inflammatory response. |
| 2017 | Cardiac tamponade in a patient with autoimmune polyglandular syndrome type 2. | Endocrinol Diabetes Metab Case Rep | We describe a case of a 40-year-old woman who was admitted to the intensive care unit with a rapid onset of dyspnea and orthopnea. She presented progressive weakness, weight loss and secondary amenorrhea during last year, while intermittent fever was present for the last two months. Initial biochemical evaluation showed anemia, hyponatremia and increased C-reactive protein levels. Clinical and echocardiographic evaluation revealed cardiac tamponade, which was treated with pericardiocentesis. Pleural fluid samples were negative for malignancy, tuberculosis or bacterial infection. Hormonal and serologic evaluation led to the diagnosis of autoimmune polyglandular syndrome (APS) type 2 (including primary adrenal insufficiency and autoimmune thyroiditis), possibly coexisting with systemic lupus erythematosus. After symptomatic rheumatologic treatment followed by replacement therapy with hydrocortisone and fludrocortisone, the patient fully recovered. In patients with the combination of polyserositis, cardiac tamponade and persistent hyponatremia, possible coexistence of rheumatologic and autoimmune endocrine disease, mainly adrenal insufficiency, should be considered. Early diagnosis and non-invasive treatment can be life-saving.In patients with the combination of polyserositis, cardiac tamponade and persistent hyponatremia, possible coexistence of rheumatologic and autoimmune endocrine disease, mainly adrenal insufficiency, should be considered.Early diagnosis and non-invasive treatment can be life-saving for these patients.Primary adrenal insufficiency requires lifelong replacement therapy with oral administration of 15-25 mg hydrocortisone in split doses and 50-200 µg fludrocortisone once daily. |
| 2017 | The inhibition of inducible nitric oxide synthase and oxidative stress by agmatine attenuates vascular dysfunction in rat acute endotoxemic model. | Environ Toxicol Pharmacol | Vascular dysfunction leading to hypotension is a major complication in patients with septic shock. Inducible nitric oxide synthase (iNOS) together with oxidative stress play an important role in development of vascular dysfunction in sepsis. Searching for an endogenous, safe and yet effective remedy was the chief goal for this study. The current study investigated the effect of agmatine (AGM), an endogenous metabolite of l-arginine, on sepsis-induced vascular dysfunction induced by lipopolysaccharides (LPS) in rats. AGM pretreatment (10mg/kg, i.v.) 1h before LPS (5mg/kg, i.v.) prevented the LPS-induced mortality and elevations in serum creatine kinase-MB isoenzyme (CK-MB) activity, lactate dehydrogenase (LDH) activity, C-reactive protein (CRP) level and total nitrite/nitrate (NOx) level after 24h from LPS injection. The elevation in aortic lipid peroxidation illustrated by increased malondialdehyde (MDA) content and the decrease in aortic glutathione (GSH) and superoxide dismutase (SOD) were also ameliorated by AGM. Additionally, AGM prevented LPS-induced elevation in mRNA expression of iNOS, while endothelial NOS (eNOS) mRNA was not affected. Furthermore AGM prevented the impaired aortic contraction to KCl and phenylephrine (PE) and endothelium-dependent relaxation to acetylcholine (ACh) without affecting endothelium-independent relaxation to sodium nitroprusside (SNP).AGM may represent a potential endogenous therapeutic candidate for sepsis-induced vascular dysfunction through its inhibiting effect on iNOS expression and oxidative stress. |
| 2017 | Procalcitonin level as a surrogate for catheter-related blood stream infection among hemodialysis patients. | J Vasc Access | Catheter-related bloodstream infection (CRBSI) is a frequent complication among hemodialysis patients who usually are presented with nonspecific signs such as fever, rigors, and hypotension. Blood culture will take up to 5 days and antimicrobials will be started. Procalcitonin (PCT) is a valid marker in sepsis. Our goal in this study is to evaluate its usefulness as a diagnostic marker in detecting CRBSI among hemodialysis patients who present with suspected CRBSI.Thirty-one hemodialysis patients with suspected CRBSI were enrolled in this study. PCT level was measured at the time of presentation. Patients were divided into two groups according to blood culture results: positive and negative groups. PCT level and other markers for inflammation: white blood cell count (WBC), C-reactive protein (CRP), and ferritin were compared between the two groups. Statistical analysis of variables was performed using the t-test or Mann-Whitney test together with Spearman correlation test.Thirty-one patients had median age 44.7 ± 2.1 years. They comprised 16 males (52%) and 15 females (48%). Sixteen patients had a positive blood culture result while in 15 it was negative. PCT level was significantly higher in the positive blood culture group (40.0 ± -21.9) (95% confidence interval [CI] 28.4-51.8) while its level was 1.1 ± 1 (95% CI 0.54-1.8) in the negative blood culture group [t(15) = -7, p<0.001). In the positive culture group, there was a correlation between CRP and ferritin (r = -0.58, p = 0.01, n = 16), while no correlation between PCT and other markers of inflammation.PCT is a useful marker for diagnosis of CRBSI among hemodialysis patients. |
| Predictors of mortality of severe sepsis among adult patients in the medical Intensive Care Unit. | Lung India | Sepsis is an important cause of mortality in the Intensive Care Units (ICUs) worldwide. Information regarding early predictive factors for mortality and morbidity is limited.The primary objective of the study was to estimate the mortality of severe sepsis among adult patients admitted into the medical ICU. The secondary objective was to identify the predictors associated with mortality.Adult patients admitted with severe sepsis in the medical ICU were studied. The primary outcome was the mortality among the study population. Baseline demographic, clinical, and laboratory data were recorded upon inclusion into the study. Risk factors associated with mortality were studied by univariate analysis. The variables having statistical significance were further included in multivariate analysis to identify the independent predictors of mortality.Out of eighty patients, 54 (67.5%) died. Univariate analysis showed that age >60 years, tachycardia, hypotension, elevated C-reactive protein (CRP) and lactate, thrombocytopenia, need of mechanical ventilation, and high Acute Physiology and Chronic Health Evaluation (APACHE) II and Sequential Organ Failure Assessment scores were variables associated with high mortality. The independent predictors of mortality identified by multivariate regression analysis were platelet count below 1 lakhs, serum levels of CRP >100, APACHE II score >25 on the day of admission to the ICU with severe sepsis, and the need for invasive mechanical ventilation.Low platelet count, elevated serum levels of CRP, APACHE score >25, and the need for invasive mechanical ventilation were found to be independent predictors of mortality of severe sepsis among adult patients with severe sepsis in the medical ICU. |
| 2016 | Successful therapy of Clostridium difficile infection with fecal microbiota transplantation. | J Physiol Pharmacol | Clostridium difficile infection (CDI) is the most common cause of infectious diarrhea and represents an important burden for healthcare worldwide. Symptoms of severe CDI include watery, foul-smelling diarrhea, peripheral leucocytosis, increased C-reactive protein (CRP), acute renal failure, hypotension and pseudomembranous colitis. Recent studies indicate that the main cause of CDI is dysbiosis, an imbalance in the normal gut microbiota. The restoration of a healthy gut microbiota composition via fecal microbiota transplantation (FMT) recently became more popular. The aim of the present study was to assess the effect of FMT on the healing of CDI and to analyze the changes in the level of pro-inflammatory markers (C-reactive protein, fecal calprotectin) and pro-inflammatory cytokines. Eighteen patients with CDI were included in our study (6 males and 12 females) with recurrent and/or severe CDI. The FMT was performed in 17 patients using colonoscopy, including 16 patients receiving a one-time FMT and 1 patient who needed 2 additional FMTs. One patient was treated with a single round of FMT using push-and-pull enteroscopy. In all CDI patients, before and 3 weeks after FMT, the following parameters were analyzed: C-reactive protein, fecal calprotectin, and plasma interleukin (IL)-6, IL-8 and IL-12, and tumor necrosis factor-alpha (TNF-α). In addition, the plasma level of LL-37, a cathelicidine peptide was assessed by fluorescence-activated cell sorting (FACS) before and 3 months after FMT. Finally, in 7 patients a microbiome analysis was performed by sequencing of 16SrRNA in stool probes obtained before and 3 weeks after FMT. The healing rate of CDI was 94%. In all successfully treated patients no recurrent CDI was observed during follow-up (16 months). The serum level of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6, IL-8 and IL-12) significantly decreased after FMT. Similarly, CRP and fecal calprotectin normalized after FMT. 3 months after FMT a significant increase of LL-37 in the plasma of successfully treated patients was monitored. The sequencing analysis demonstrated an elevated abundance of beneficial bacterial species such as Lactobacillaceae, Ruminococcaceae, Desulfovibrionaceae, Sutterellaceae and Porphyromonodacea after FMT. No serious side effects were observed. We concluded that FMT represented a very effective and safe treatment of recurrent and/or severe CDI and led to favorable shifts in the composition of gut microbiome. |
| 2017 | Role of Combined Post-Operative Venous Lactate and 48 Hours C-Reactive Protein Values on the Etiology and Predictive Capacity of Organ-Space Surgical Site Infection after Elective Colorectal Operation. | Surg Infect (Larchmt) | C-reactive protein (CRP) has been assessed to detect organ-space surgical site infection (OSI). Nevertheless, data about peri-operative oxygen debt and surgical stress-elicited biologic markers to explain and allow for the early detection of OSI are lacking. We analyzed immediate post-operative venous lactate, early CRP levels, and intra-operative hemodynamic values on the capacity to predict OSI after elective colorectal operation.Patients undergoing an elective colorectal surgical procedure with anastomosis between March 2013 and August 2014 were included and assessed prospectively. Post-operative lactate values at L-0, L-6, and L-24 hours, CRP (basal and 48 h), and the percentage of operative time (POT) with systolic blood pressure below 100 mm Hg and heart rate above 90 beats per minute in patients with and without OSI were compared. Binary logistic regression was constructed for L-0 and CRP-48, and receiver-operating characteristic (ROC) was analyzed for sensitivity (S), specificity (Sp), positive (PPV) and negative (NPV) predictive values.Patients with OSI (11 of 100) showed higher L-0 and L-24 (3.2 ± 2.5 vs. 1.6 ± 0.8; p = 0.025 and 1.9 ± 1.2 vs. 1.2 ± 0.4 mmol/L; p = 0.025) and CRP-48 (188 ± 80 vs. 74 ± 52 mg/L; p = 0.001). The ROC from logistic regression showed area under the curve of 0.899 (95% confidence interval [CI] 0.805-0.992), S of 72% (95% CI 43.2%-90.5%), Sp of 95% (95% CI 88.6%-98.4%), PPV of 66% (95% CI 38.9%-86.4%) and NPV of 0.96 (95% CI 90%-99%). L-0 was higher in those patients with hypotension during more than 60% of the POT (2.4 ± 2.1 vs. 1.6 ± 0.8; p = 0.038). Patients with OSI had a higher POT with hypotension (50 ± 28% vs. 30 ± 28%; p = 0.032) and tachycardia (18 ± 27% vs. 5 ± 16%; p = 0,024).The combination of immediate post-operative lactate and CRP at 48 hours proved to be useful in predicting OSI after elective colorectal operation. Assessment of peri-operative lactate is a potential target for intra-operative goal-oriented management aimed at improving post-operative outcomes. |
| The evaluation of the relationship between serum levels of Interleukin-6 and Interleukin-10 and metabolic acidosis in hemodialysis patients. | Saudi J Kidney Dis Transpl | Chronic kidney disease is defined as progressive kidney dysfunction. The levels of various cytokines increase in hemodialysis (HD) patients. High levels of interleukins (ILs) and presence of metabolic acidosis are described as independent risk factors for morbidity and mortality in these patients. This study was designed to evaluate the relationship between IL-6 and IL-10 and serum bicarbonate and metabolic acidosis in HD patients. In this analytical crosssectional study, patients referred to the HD units of Loghman Hakim and Shahid Ashrafi Esfahani Hospitals were randomly selected. Demographic and laboratory data, such as albumin, creatinine, calcium, phosphorus, parathormone, C-reactive protein, complete blood count, ferritin, ILs-6 and -10, and arterial blood gas analysis, were recorded for each patient. The correlation between IL and serum bicarbonate and other variables were evaluated by SPSS software. The patients were compared for the presence of acidosis and positivity for IL. A total of 84 patients with a mean age of 60.98 years and mean body mass index of 24.86 kg/m[2] were evaluated (53% male and 57% female). The mean dialysis duration was 24.86 ± 3.98 months. Overall, 41.7% of the patients had diabetes mellitus and 36.9% of them had hypotension. The mean serum levels of IL-6 and IL-10 were 6.036 and 17.46 pg/ml, respectively. There was a significant correlation between IL-6 and IL-10 levels and serum bicarbonate and the incidence of metabolic acidosis (P <0.05). Based on the results, metabolic acidosis and bicarbonate could be considered prognostic factors to differentiate the increased levels of IL-6 and IL-10 and associated morbidity and mortality. |
| 2016 | The Surgical Treatment of Toxic Megacolon in Hirschsprung Disease. | Pediatr Emerg Care | Enterocolitis remains the most significant cause of morbidity and mortality in Hirschsprung disease (HD). It could progress into toxic megacolon (TM)-acute dilatation of the colon as accompanying toxic complication of Hirschsprung enterocolitis. It is a devastating complication, especially in infants with so far undiagnosed HD.A retrospective analysis of medical records of 4 infants with TM was performed. The diagnosis TM was determined on the basis of clinical information (abdominal pain or tenderness, abdominal distension, diarrhea, bloody diarrhea, and constipation), plain x-rays of the abdomen (segmental or total colonic dilation), and the presence of such criteria (fever, high heart rate, increased white blood cell count, C reactive protein, anemia, dehydration, electrolyte disturbances, hypotension). Surgical management and outcome was evaluated by retrospective chart review.The median duration of symptoms characteristic for TM was 3 days. Toxic megacolon was seen as the first manifestation of previously unknown HD in 3 patients; in 1 newborn, the contrast radiograph was suggestive of HD. In all patients, conservative treatment was failed. Three patients were treated with surgical decompression and ileostomy only. In all these cases, severe complications occurred, consequently 2 of them died. In 1 patient, a resection of the transverse dilated colon additionally was performed. This patient had no complications in postoperative period and survived.Because of the high mortality in patients with TM that were treated medically or with colonic decompression, a resection of massively distended part of the colon should be performed. |
| 2016 | New role of biomarkers: mid-regional pro-adrenomedullin, the biomarker of organ failure. | Ann Transl Med | Mid-regional pro-adrenomedullin (MR-proADM) has a good biomarker profile: its half-life is several hours, and its plasma concentrations can be determined in clinical practice, it is essentially irrelevant, but proportionally represents the levels and activity of adrenomedullin (ADM). ADM synthesis is widely distributed in tissues, including bone, adrenal cortex, kidney, lung, blood vessels and heart. Its fundamental biological effects include vasodilator, positive inotropic, diuretic, natriuretic and bronchodilator. It has been described high levels in septic patients, interacting directly with the relaxation of vascular tone, triggering hypotension of these patients. It is also found high levels in other diseases such as hypertension, heart failure, respiratory failure, renal failure, cirrhosis and cancer. MR-proADM has been identified as a prognostic marker, stratifying the mortality risk in patients with sepsis in emergency department (ED) and ICU. Evolutionary MR-proADM levels and clearance marker to the 2nd-5th days of admission help to determine the poor performance and the risk of mortality in patients with severe sepsis admitted to the ICU. The MR-proADM levels are more effective than procalcitonin (PCT) and C-reactive protein (CRP) levels to determine an unfavorable outcome and the risk of mortality in patients with sepsis admitted to the ICU. It has also proved useful in patients diagnosed with organ dysfunction of infectious etiology. MR-proADM levels are independent of the germ conversely it is related to the magnitude of organ failure and therefore severity. We consider advisable incorporating the MR-proADM the panel of biomarkers necessary for the diagnosis and treatment of critically ill patients admitted to the ICU with severe sepsis. The combined PCT and MR-proADM levels could represent a valid tool in the clinical practice to timely identify patients with bacterial infections and guide the diagnosis and treatment of sepsis and septic shock. |
| 2016 | Delirium as a complication of the surgical intensive care. | Neuropsychiatr Dis Treat | The aim of this study was to examine the impact of somatic illnesses, electrolyte imbalance, red blood cell count, hypotension, and antipsychotic and opioid treatment on the duration of delirium in Central Intensive Care Unit for Surgery.Patients who were admitted to the Department of Central Intensive Care Unit for Surgery in the University Hospital Olomouc from February 2004 to November 2008 were evaluated using Riker sedation-agitation scale. Their blood pressure, heart rate, respiratory rate, and peripheral blood oxygen saturation were measured continually, and body temperature was monitored once in an hour. The laboratory blood tests including sodium, potassium, chlorides, phosphorus, urea and creatinine, hemoglobin, hematocrit, red and white blood cell count, and C-reactive protein, albumin levels and laboratory markers of renal and liver dysfunction were done every day. All measurements were made at least for ten consecutive days or longer until the delirium resolved.The sample consisted of 140 consecutive delirious patients with a mean age of 68.21±12.07 years. Delirium was diagnosed in 140 of 5,642 patients (2.48%) admitted in CICUS in the last 5 years. The median duration of delirium was 48 hours with a range of 12-240 hours. Statistical analysis showed that hyperactive subtype of delirium and treatment with antipsychotics were associated with prolonged delirium duration (hyperactive 76.15±40.53 hours, hypoactive 54.46±28.44 hours, mixed 61.22±37.86 hours; Kruskal-Wallis test: 8.022; <0.05). The duration of delirium was significantly correlated also with blood potassium levels (Pearson's =0.2189, <0.05), hypotension (hypotension 40.41±30.23 hours versus normotension 70.47±54.98 hours; Mann-Whitney =1,512; <0.05), administration of antipsychotics compared to other drugs (antipsychotics 72.83±40.6, benzodiazepines 42.00±20.78, others drugs, mostly piracetam 46.96±18.42 hours; Kruskal-Wallis test: 17.39, <0.0005), and history of alcohol abuse (with a history of abuse 73.63±45.20 hours, without a history of abuse 59.54±30.61 hours; Mann-Whitney =1,840; <0.05). One patient had suffered from complicated postoperative hypostatic pneumonia and died due to respiratory failure (patient with hypoactive subtype). According to the backward stepwise multiple regression, the best significant predictors of duration of the delirium were the hypotension, type of psychopharmacs, type of delirium, the daily dose of opioids, a combination of psychopharmacs, history of alcohol abuse, plasma level of potassium, anemia, hyperpyrexia, and plasma level of albumin, reaching statistical significance (analysis of variance: =5.205; =24; <0.005; adjusted =0.637).The hyperactive type of delirium, hypotension, usage of antipsychotics, the higher daily dose of opioids, a combination of psychopharmacs, history of alcohol abuse, low blood levels of potassium, anemia, hyperpyrexia, and hypoalbuminemia in the CICUS were associated with longer duration of delirium. |
| 2016 | Protective effects of kolaviron and gallic acid against cobalt-chloride-induced cardiorenal dysfunction via suppression of oxidative stress and activation of the ERK signaling pathway. | Can J Physiol Pharmacol | Cobalt (Co) toxicity is a potential public health problem due to recent renewed use of Co in orthopedic implants, dietary supplements, and blood doping in athletes and horses. We investigated the protective roles of kolaviron (KV), a bi-flavonoid of Garcinia kola, and gallic acid (GA) on cobalt chloride (CoCl)-induced cardiorenal damage in rats. CoCl caused significant increases (p < 0.05) in serum creatine kinase-myocardial band (CK-MB), lactate dehydrogenase (LDH), aspartate transaminase (AST), xanthine oxidase (XO), urea, creatinine, malondialdehyde, HO, nitric oxide, as well as C-reactive protein expression, along with significant (p < 0.05) reduction in cardiac and renal expression of extracellular signal regulated kinase (ERK) and the activities of superoxide dismutase, catalase, and glutathione S-transferase. KV and GA prevented the toxic effects of CoCl by stimulating ERK expression and reversing Co-induced biochemical changes. Administration of CoCl alone did not significantly alter ECG patterns in the rats, although co-treatment with KV (200 mg/kg) produced QT-segment prolongation and also appeared to potentiate Co hypotension. Histopathology of the heart and kidneys of rats treated with KV and GA confirmed the biochemical data. KV and GA thus protected against cardiac and renal damage in Co intoxication via antioxidant and (or) cell survival mechanisms, possibly involving ERK activation. |
| 2016 | [A sepsis case caused by a rare opportunistic pathogen: Bacillus pumilus]. | Mikrobiyol Bul | The high prevalence of Bacillus species in nature and the detection of these bacteria as contaminant in cultures may lead diagnostic dilemma, however they should still be considered as a pathogen particularly in case of repeated positive cultures from patients with risk factors. Bacillus pumilus is a bacteria, though rarely, been reported as the causative agent of various infections such as sepsis, endocarditis, skin infections and food poisoning in human. In this report, a sepsis case in an immunocompetent patient caused by B.pumilus was presented. A 38-year-old female patient was admitted to emergency service of our hospital with the complaints of headache, dizziness and diarrhea. She had not any risk factors except a history of heart valve replacement operation two years ago. In physical examination, she had abdominal retention, high fever and hypotension, together with the high levels of sedimentation rate (ESR) and C-reactive protein (CRP). The patient was hospitalized with the preliminary diagnosis of sepsis. Three sets of blood samples at two different periods were taken for the culture. All blood culture vials had a positive signal at the second day of incubation in BD BACTEC™ 9050 system, therefore subcultures were performed in sheep blood agar, chocolate agar and MacConkey agar, and incubated in aerobic and anaerobic conditions. Beta-haemolytic, gray-colored large colonies were isolated from anaerobic culture at the end of 18-24 hours incubation, and Gram staining from colonies showed gram-positive rods. The isolate was identified as B.pumilus with 99% accuracy rate by using BD Phoenix™ 100 identification system. This result was also confirmed by MALDI-TOF based VITEK® MS system and 16S rRNA sequencing by Illumina MiSeq® platform. Antibiotic susceptibility test performed by BD Phoenix™ 100 system and the isolate was found to be resistant against penicillin, while it was susceptible to vancomycin, erythromycin, clindamycin, levofloxacin, and trimethoprim-sulfamethoxazole. Initial treatment of patient was started with intravenous ceftriaxone and metronidazole empirically. Hypotension and fever returned to normal levels at the second and third days of the treatment, respectively. Metronidazole treatment was stopped at seventh day, and treatment was completed to 14 day with ceftriaxone alone. At the end of the treatment course, general condition of the patient was completely good, ESR and CRP were also decreased to normal levels. In conclusion, although most of the reported bloodstream infections that are caused by B.pumilus are intravascular catheter-related, artificial heart valves should also be considered as a risk factor even though vegetation was not detected in our patient. |
| 2016 | Discontinuation of empirical antifungal therapy in ICU patients using 1,3-β-d-glucan. | J Antimicrob Chemother | Empirical antifungal therapy in high-risk ICU patients is an attractive strategy, but overuse of antifungal agents is a potential problem.We evaluated if ICU patients at high risk to develop candidaemia identified by a prediction rule could discontinue empirical antifungal therapy on the basis of repeatedly negative 1-3-β-d-glucan (BDG) tests.We conducted a multicentre cohort study in 85 ICU patients receiving antibiotics or with central venous catheter plus two additional factors (dialysis, parenteral nutrition, surgery, pancreatitis or receipt of corticosteroids or other immunosuppressive agents) plus either fever, hypothermia, hypotension, acidosis, elevated C-reactive protein or leucocytosis. Blood cultures (days 1 and 2) and BDG (days 1-3, baseline period) were performed and anidulafungin was given. On day 4, patients with negative blood cultures and BDG discontinued antifungal therapy. Registered in ClinicalTrials.gov (NCT01734525).The incidence of candidaemia was 8.2% in patients selected versus 0.5% in patients without entry criteria (16.9 times higher). Sixty-four patients (75.3%) had baseline positive BDG, including 7 with candidaemia. All 21 patients with baseline negative BDG discontinued anidulafungin on day 4. None developed candidaemia until day 30.Early discontinuation of empirical echinocandin therapy in high-risk ICU patients based on consecutive negative BDG tests may be a reasonable strategy, with great potential to reduce the overuse of echinocandins in ICU patients. Prospective studies with a higher number of patients are needed. |
| 2017 | Describing Kawasaki shock syndrome: results from a retrospective study and literature review. | Clin Rheumatol | Kawasaki shock syndrome (KSS) is a rare manifestation of Kawasaki disease (KD) characterized by systolic hypotension or clinical signs of poor perfusion. The objectives of the study are to describe the main clinical presentation, echocardiographic, and laboratory findings, as well as the treatment options and clinical outcomes of KSS patients when compared with KD patients. This is a retrospective study. All children referred to two pediatric rheumatology units from January 1, 2012, to December 31, 2014, were enrolled. Patients were divided into patients with or without KSS. We compared the two groups according to the following variables: sex, age, type of KD (classic, with less frequent manifestations, or incomplete), clinical manifestations, cardiac involvement, laboratory findings, therapy administered, response to treatment, and outcome. Eighty-four patients with KD were enrolled. Of these, five (6 %) met the criteria for KSS. Patients with KSS had higher values of C-reactive protein (p = 0.005), lower hemoglobin levels (p = 0.003); more frequent hyponatremia (p = 0.004), hypoalbuminemia (p = 0.004), and coagulopathy (p = 0.003); and increase in cardiac troponins (p = 0.000). Among the KSS patients, three had a coronary artery involvement, but none developed a permanent aneurysm. Intravenous immunoglobulin resistance was more frequent in the KSS group, although not significantly so (3/5, 60 % vs. 23/79, 30 %, P = NS). None of the five cases was fatal, and all recovered without sequelae. KSS patients are more likely to have higher rates of cardiac involvement. However, most cardiovascular abnormalities resolved promptly with therapy. |
| 2016 | Association between Elevated Alanine Aminotransferase and Urosepsis in Children with Acute Pyelonephritis. | Pediatr Gastroenterol Hepatol Nutr | The aim of this study is to investigate the association between elevated alanine aminotransferase (ALT) and urosepsis in children with acute pyelonephritis (APN).We retrospectively identified all children who were managed in our hospital with APN during a decade period. In our study a diagnosis of APN was defined as having a positive urine culture and a positive (99m)Tc-dimercaptosuccinic acid scintigraphy. We compared those with elevated ALT and those with normal ALT according to the following variables: age, gender, duration of fever prior to admission, presence of hypotension, C-reactive protein (CRP), creatinine, presence of anemia, white blood cells count, platelet count, blood culture result, and grades of vesicoureteral reflux. In addition, the correlation between elevated ALT and positive blood culture was analyzed in detail.A total of 996 children were diagnosed with APN, of which 883 were included in the study. ALT was elevated in 81 children (9.2%). In the analysis of demographic characteristics, the number of children with elevated ALT was higher in children between 0 to 3 months, boys, and in those with positive blood culture (p=0.002, 0.036, and 0.010, respectively). In multivariate analysis of variables associated with positive blood culture, age younger than 3 months, elevated ALT, elevated CRP, and elevated creatinine showed statistical significance (p=0.004, 0.030, 0.043, and 0.044, respectively).Our study demonstrates the association between elevated ALT and increased prevalence of urosepsis in addition to elevated CRP, elevated creatinine, and age younger than 3 months in children with APN. |
| 2016 | Severe non-infective systemic inflammatory response syndrome, shock, and end-organ dysfunction after zoledronic acid administration in a child. | Osteoporos Int | Zoledronic acid is an intravenous bisphosphonate used to increase bone mineral density and reduce the risk of fractures. Its safety profile compares well with pamidronate in pediatric patients. We describe an acute, severe, life-threatening, inflammatory reaction in a child.A 7-year-old boy with complex medical problems and chronic ventilator requirements was admitted to the pediatric intensive care unit (due to ventilator needs) for zoledronic acid infusion and subsequent monitoring. His history was significant for osteoporosis secondary to immobilization with multiple fractures since 2 years of age, hypoxic-ischemic encephalopathy, quadriplegic cerebral palsy, seizure disorder, ventilator dependence, and pulmonary hypertension. He had previously been treated with four cycles of pamidronate without adverse events. He received 0.013 mg/kg of zoledronic acid infused over 30 minutes. Beginning 3 hours after completion of the infusion, he developed progressive tachycardia, fever, hypotension requiring vasopressor infusion, and increasing oxygen requirements. Laboratory studies revealed leukopenia, thrombocytopenia, elevated C-reactive protein, abnormal coagulation profile, metabolic acidosis, and negative cultures. The following day, he developed moderate acute respiratory distress syndrome and pulmonary hemorrhage requiring higher ventilatory settings, and subsequently diarrhea and abdominal distension. Initial clinical resolution was noted from the third day onward, and he was discharged on the sixth day after zoledronate administration.Our pediatric patient demonstrated an acute, severe, life-threatening reaction to zoledronic acid requiring intensive cardiorespiratory support without an underlying pre-existing inflammatory disorder.Our case highlights the importance of careful monitoring of children following zoledronic acid therapy. We recommend inpatient observation after an initial infusion of zoledronic acid in medically complex children. Children and their parents should be thoroughly counseled on the potential risks of bisphosphonate treatment, which can sometimes be severe and life threatening. |
| 2015 | A study of the clinical profile of acute pancreatitis and its correlation with severity indices. | Int J Health Sci (Qassim) | Acute pancreatitis is a common disease with wide clinical variation and its incidence is increasing. Acute pancreatitis may vary in severity, from mild self-limiting pancreatic inflammation to pancreatic necrosis with life-threatening sequelae. Severity of acute pancreatitis is linked to the presence of systemic organ dysfunctions and/or necrotizing pancreatitis.The present study was aimed to assess the clinical profile of acute pancreatitis and to assess the efficacy of various severity indices in predicting the outcome of patients.This was a prospective study done in Sri Ramachandra Medical College and Hospital from April 2012-September 2014. All patients with a diagnosis of acute pancreatitis were included in this study. Along with routine lab parameters, serum amylase, lipase, lipid profile, calcium, CRP, LDH, CT abdomen, CXR and 2D Echo was done for all patients.A total of 110 patients were analysed. 50 patients required Intensive care, among them 9 patients (18%) died. 20 patients (18.2%) had MODS, 15 patients (13.6%) had pleural effusion, 9 patients (8.2%) had pseudocyst, 2 patients(1.8%) had hypotension, 2 patients(1.8%) had ARDS and 2 patients(1.8%) had DKA. In relation to various severity indices, high score of CRP, LDH and CT severity index was associated with increased morbidity and mortality. 15 patients (13.6%) underwent open necrosectomy surgery, 3 patients (2.7%) underwent laparoscopic necrosectomy and 7 patients (6.4%) were tried step up approach but could not avoid surgery. Step up approach and surgery did not have a significant reduction in the mortality.Initial assessment of severity by CRP, LDH and lipase could be reliable indicators of outcome in acute pancreatitis. |
| 2016 | Inflammatory indices in meconium aspiration syndrome. | Pediatr Pulmonol | Meconium aspiration syndrome (MAS) is linked to inflammation, but data on the patterns of hematological indices and C-reactive protein (CRP) in MAS are lacking. The aim of the study was to evaluate CRP, white blood cell count (WBC), absolute neutrophil count (ANC), and immature-to-total neutrophil ratio (IT-ratio) in MAS and to assess their association with disease severity.Retrospective cross-sectional study including 239 consecutively admitted neonates with MAS to a level III NICU. Neonates with early onset sepsis were excluded. Results Neonates with severe MAS (invasive mechanical ventilation for <7 days) and very severe MAS (invasive mechanical ventilation for ≥7 days or high frequency ventilation or ECMO) had higher CRP and IT-ratio compared to neonates with non-severe MAS (no invasive mechanical ventilation) during the first 2 days of life (CRP: 13.0 and 40.9 vs. 9.5 mg/L, P = 0.039 and <0.001, respectively) and neonates with very severe MAS had lower WBC and ANC. All four inflammatory indices correlated significantly with duration of invasive mechanical ventilation, duration of respiratory support and with length of hospital stay, arterial hypotension, and persistent pulmonary hypertension. Neonates with all four inflammatory indices beyond the normal range had a more than 20-fold increase in risk for very severe MAS.High CRP and IT-ratio and low WBC and ANC values were closely linked to a more severe course of MAS during the early phases of the disease. These findings reflect the role of inflammation in the pathogenesis of MAS. Pediatr Pulmonol. 2016;51:601-606. 2015 Wiley Periodicals, Inc. |
| 2015 | Secondary stroke in patients with polytrauma and traumatic brain injury treated in an Intensive Care Unit, Karlovac General Hospital, Croatia. | Injury | Traumatic brain injury (TBI) is divided into primary and secondary brain injury. Primary brain injury occurs at the time of injury and is the direct consequence of kinetic energy acting on the brain tissue. Secondary brain injury occurs several hours or days after primary brain injury and is the result of factors including shock, systemic hypotension, hypoxia, hypothermia or hyperthermia, intracranial hypertension, cerebral oedema, intracranial bleeding or inflammation. The aim of this retrospective analysis of a prospective database was to determine the prevalence of secondary stroke and stroke-related mortality, causes of secondary stroke, treatment and length of stay in the ICU and hospital. This study included patients with TBI with or without other injuries who were hospitalised in a general ICU over a five-year period. The following parameters were assessed: demographics (age, sex), scores (Glasgow Coma Score, APACHE II, SOFA), secondary stroke (prevalence, time of occurrence after primary brain injury, causes of stroke and associated mortality), length of stay in the ICU and hospital, vital parameters (state of consciousness, cardiac function, respiration, circulation, thermoregulation, diuresis) and laboratory values (leukocytes, C-reactive protein [CRP], blood glucose, blood gas analysis, urea, creatinine). Medical data were analysed for 306 patients with TBI (median age 56 years, range 18-93 years) who were treated in the general ICU. Secondary stroke occurred in 23 patients (7.5%), 10 of whom died, which gives a mortality rate of 43.4%. Three patients were excluded as the cause of the injury was missile trauma. The study data indicate that inflammation is the most important cause of secondary insults. Levels of CRP were elevated in 65% of patients with secondary brain injury; leukocytosis was present in 87% of these patients, and blood glucose was elevated in 73%. The lungs and urinary tract were the most common sites of infection. In conclusion, elevated inflammatory markers (white blood cell count and CRP) and hyperglycaemia are associated with secondary brain injury. The lack of routine use of intracranial pressure (ICP) monitoring may explain the high mortality rate and the occurrence of secondary stroke in patients with TBI. |
| 2015 | Predictors of Bacteraemia in Patients with Suspected Community-Acquired Pneumonia. | PLoS One | The diagnostic yield of blood cultures is limited in patients with community-acquired pneumonia (CAP). Yet, positive blood culture results provide important information for antibiotic treatment and for monitoring epidemiologic trends. We investigated the potential of clinical predictors to improve the cost-benefit ratio of obtaining blood cultures.Data from two prospective cohort studies of adults with suspected CAP, admitted to non-ICU wards, were combined. Two models were created, one using readily available parameters and one additionally including laboratory parameters.3,786 patients were included (2,626 (69%) with X-ray confirmed CAP). Blood cultures were obtained from 2,977 (79%) patients (and from 2,107 (80%) with X-ray confirmed CAP). 266 (8.9%) of the patients with a blood culture had bacteraemia. Clinical predictors of bacteraemia were absence of pre-admission antibiotic treatment, pleuritic pain, gastro-intestinal symptoms, tachycardia, tachypnea, hypotension and absence of hypoxia. After including laboratory results in the model, younger age, C-reactive protein, leukocytosis or leukopenia, low thrombocyte count, low sodium level, elevated urea and elevated arterial pH were added, while gastro-intestinal symptoms and hypotension were no longer significant. The area under the receiver operating characteristics curve was 0.66 (95% confidence interval 0.63-0.70) for the first model and 0.76 (95% confidence interval 0.73-0.79) for the second model.In conclusion, in patients hospitalized with CAP, bacteraemia was moderately predictable using clinical parameters only. We recommend against the use of a risk prediction model for the decision to obtain blood cultures. |
| 2016 | A prospective randomized trial comparing the clinical effectiveness and biocompatibility of heparin-coated circuits and PMEA-coated circuits in pediatric cardiopulmonary bypass. | Perfusion | We compared the clinical effectiveness and biocompatibility of poly-2-methoxyethyl acrylate (PMEA)-coated and heparin-coated cardiopulmonary bypass (CPB) circuits in a prospective pediatric trial.Infants randomly received heparin-coated (n=7) or PMEA-coated (n=7) circuits in elective pediatric cardiac surgery with CPB for ventricular septum defects. Clinical and hematologic variables, respiratory indices and hemodynamic changes were analyzed perioperatively.Demographic and clinical variables were similar in both groups. Leukocyte counts were significantly lower 5 minutes after CPB in the PMEA group than the heparin group. Hemodynamic data showed that PMEA caused hypotension within 5 minutes of CPB. The respiratory index was significantly higher immediately after CPB and 1 hour after transfer to the intensive care unit (ICU) in the PMEA group, as were levels of C-reactive protein 24 hours after transfer to the ICU.Our study shows that PMEA-coated circuits, unlike heparin-coated circuits, cause transient leukopenia during pediatric CPB and, perhaps, systemic inflammatory respiratory syndrome after pediatric CPB. |
| 2015 | [Clinical predictors of bacteremia in immunocompetent adult patients hospitalized for community-acquired pneumonia]. | Rev Med Chil | The clinical usefulness of blood cultures in the management of patients hospitalized with community-acquired pneumonia (CAP) is controversial.To determine clinical predictors of bacteremia in a cohort of adult patients hospitalized for community-acquired pneumonia.A prospective cohort of 605 immunocompetent adult patients aged 16 to 101 years (54% male) hospitalized for CAP was studied. The clinical and laboratory variables measured at admission were associated with the risk of bacteremia by univariate and multivariate analysis using logistic regression models.Seventy seven percent of patients had comorbidities, median hospital stay was 9 days, 7.6% died in hospital and 10.7% at 30 days. The yield of the blood cultures was 12.6% (S. pneumoniae in 69 patients, H. influenzae in 3, Gram negative bacteria in three and S. aureus in one). These results modified the initial antimicrobial treatment in one case (0.2%). In a multivariate analysis, clinical and laboratory variables associated with increased risk of bacteremia were low diastolic blood pressure (Odds ratio (OR): 1.85, 95% confidence intervals (CI) 1.02 to 3.36, p < 0.05), leukocytosis e" 15,000/mm³ (OR: 2.18, 95% CI 1.22 to 3.88, p < 0.009), serum urea nitrogen e" 30 mg/dL (OR: 2.23, 95% CI 1.22 to 4.05, p < 0.009) and serum C-reactive protein e" 30 mg/dL (OR: 2.20, 95% CI 1.22 to 3.97, p < 0.01). Antimicrobial use before hospital admission significantly decreased the blood culture yield (OR: 0.14, 95% CI 0.04 to 0.46, p < 0.002).Blood cultures do not contribute significantly to the initial management of patients hospitalized for community-acquired pneumonia. The main clinical predictors of bacteremia were antibiotic use, hypotension, renal dysfunction and systemic inflammation. |
| 2015 | Marked elevation of procalcitonin level can lead to a misdiagnosis of anaphylactic shock as septic shock. | Int J Infect Dis | The case of a 74-year-old woman who presented with hyperthermia and hypotension is reported. Laboratory test results revealed marked elevation of C-reactive protein (CRP) and procalcitonin (PCT) levels. The clinical presentation and laboratory test results were suggestive of septic shock. No infectious focus was identified. The shock recurred after what was subsequently understood to be an unintended re-challenge with risedronate sodium. Drug-induced anaphylactic shock was finally diagnosed. Anaphylactic shock may be misdiagnosed as septic shock in patients who present with markedly elevated PCT levels. |
| 2015 | Neutrophil-Lymphocyte Ratio Is Significantly Decreased in Preemptive Renal Transplant Patients. | Transplant Proc | Cardiovascular diseases and infections are the leading two causes of morbidity and mortality in end-stage renal disease (ESRD) patients. Kidney transplantation is the preferred method for renal replacement owing to better survival. There are reports of irreversibly damaged immune system in dialysis patients, which did not return to normal even after kidney transplantation. The neutrophil-lymphocyte ratio (NLR) is an easily applicable method for evaluation of inflammation. We hypothesized that preemptive kidney transplantation can improve inflammatory state compared with nonpreemptive recipients. To test our hypothesis, we retrospectively investigated pretransplant and posttransplant NLR and C-reactive protein (CRP) levels of ESRD patients and compared them with values in healthy controls.We retrospectively analyzed NLR, CRP, and other hematologic parameters of ESRD patients who were transplanted between January 2005 and January 2014 on the day of transplantation and at the end of first year. We grouped the patients as preemptive and nonpreemptive ones. We excluded patients with coronary artery disease, obesity, hypotension, hyperthyroidism, uncontrolled diabetes mellitus, hematologic or solid organ cancers, and active documented infection at any evaluation period.We included 137 ESRD patient and 34 healthy control individual in our study. Of the 137 ESRD patients, 52 (38%) were transplanted preemptively. Of the patients, 85 were already on either hemodialysis or peritoneal dialysis therapy at the time of transplantation. The white blood cell count value of the patient and control group (7246.72 ± 1460.26 and 76661.76 ± 1286.29, respectively; P = .43), NLR of the control group was significantly lower than patient group (1.98 ± 0.94 and 3.47 ± 2.33, respectively; P = .007). The NLR of the preemptive group was decreased substantially at the end of first year posttransplantation, the NLR of the preemptive group was significantly lower than the nonpreemptive group (3.08 ± 1.32 and 3.71 ± 2.33; P = .01).We showed that all ESRD patients had an increased inflammation rate according to CRP and NLR when compared with healthy controls. We also found that improvement of inflammatory state in preemptive patients is significantly better than nonpreemptive patients at the end of first year evaluation. |
| 2015 | Bouveret syndrome: A fatal diagnostic dilemma of gastric outlet obstruction. | Ulus Travma Acil Cerrahi Derg | The patient presented in this study was a 54-year-old woman complaining of nausea and vomiting, onset preceding four days, with no significant past medical history and an unremarkable surgical history. The patient was afebrile and hypertensive. Physical examination revealed a non-tender abdomen, and initial laboratory evaluation revealed elevated blood glucose level, ketonuria, leukocytosis, elevated C-reactive protein, gamma glutamyl transferase, lactate dehydrogenase, and total bilirubin. The patient was admitted to the internal medicine ward due to new onset of diabetes mellitus. Due to persistent nausea and vomiting, gastroscopy revealed a healed duodenal ulcer, and abdominal ultrasonography revealed cholelithiasis. The medical condition of the patient deteriorated further in the internal medicine ward, with impending hypotension, tachycardia, leukocytosis, and acute renal failure, and she was admitted to the intensive care unit due to septic shock. A computerized tomography was obtained, which revealed an impacted gallstone in the distal duodenum. The patient was taken to the operating room. The gallstone was encountered in proximal jejunum immediately distal to the ligament of Treitz. A longitudinal enterotomy was made, and the stone was extracted. Her drains were cleared on postoperative day 5, and gastrointestinal function returned to normal. Unfortunately, the patient developed an overwhelming sepsis due to bacteremia and fungemia, and died on post-operative day 19. |
| 2015 | Orthostatic Blood Pressure Changes and Subclinical Markers of Atherosclerosis. | Am J Hypertens | Using a simple standing-up test in normotensive subjects, we evaluated orthostatic upright postural blood pressure (BP) changes and autonomic nervous function, as well as the relationship between orthostatic BP changes and subclinical markers of atherosclerosis.A total of 515 normotensive subjects aged 35-75 years (58.4±10.0 years) were enrolled. We measured body mass index (BMI), systolic BP (SBP) and diastolic BP (DBP), serum lipids, hemoglobin A1c (HbA1c), high-sensitivity C-reactive protein (hs-CRP), and urinary albumin-to-creatinine ratio. Brachial to ankle pulse wave velocity (baPWV) and carotid mean intima-media thickness (IMT) were measured. Participants underwent a simple standing-up test involving sitting then standing for 2 minutes each, followed again by sitting. To evaluate autonomic fluctuations, we calculated the coefficient of variation of the R-R interval, the ratio of low to high frequency heart rate variability (LF/HF), and the coefficient of component variance of high frequency.SBP and DBP decreased when standing, with a reduction of SBP when changing position of -8.0±10.2mm Hg. Orthostatic hypotension (OH) produced a significantly higher SBP than without OH. The baPWV was significantly higher in OH than in without OH. Stepwise regression analysis adjusted for age, sex, BMI, baseline SBP, triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, fasting glucose, HbA1c, hs-CRP, IMT, late systolic peak of the pressure wave form (SBP2), and baPWV confirmed that baPWV, SBP2, and triglycerides were independently related to orthostatic BP changes. Multiple regression analyses showed that a decrease in SBP as well as baseline SBP, age, BMI, and fasting glucose were independent determinants of PWV.We have shown that increased arterial stiffness was associated with OH during a standing-up test. Arterial stiffness may contribute to greater BP responses to postural changes from standing. |
| 2014 | Shenfu injection for intradialytic hypotension: a systematic review and meta-analysis. | Evid Based Complement Alternat Med | Objective. To evaluate the effectiveness and safety of Shenfu injection (SFI) for intradialytic hypotension (IDH). Methods. A systematic review of data sources published as of April 2014 was conducted. These included the Cochrane Central Register of Controlled Trials (2014 issue 4), Pubmed, Embase, CBM, CNKI, VIP, and Wangfang Data. Randomized controlled trials (RCTs) involving SFI for treatment and prevention of IDH were identified. Two researchers independently selected articles, extracted data, assessed quality, and cross checked the results. Revman 5.2 was used to analyze the results. Results. Eight RCTs were included. The meta-analysis indicated that compared with conventional therapies alone, SFI could elevate systolic blood pressure (SBP), increase the clinical effective rate, decrease the incidence of hypotension, increase serum albumin (ALB) levels, and reduce C-reactive protein (CRP) levels without serious adverse effects. GRADE Quality of Evidence. the quality of SBP, the effective rate, ALB, and CRP were low, and hypotension incidence and DBP were very low. Conclusions. SFI is more effective than conventional therapies for prevention and treatment of IDH. However, a clinical recommendation is not warranted due to the small number of studies included and low methodology quality. Multi-center and high-quality RCTs with large sample sizes are needed to provide stronger evidence. |
| 2014 | [Septic arthritis in adult patients in a general hospital in Chile]. | Rev Chilena Infectol | Septic arthritis is an infrequent condition of prolonged morbidity and there is no previous publications in Chile that allow orientate therapy.To characterize a group of adult patients with septic arthritis confirmed by culture.Descriptive study of a case series.From 2003 to august 2013, 24 patients with 25 events of septic arthritis were identified in a general hospital. Mean age was 68.3 years old (range 24-94). Predisposing conditions were harbored by 91.7%. Predominant clinical manifestations were pain (92%) and impaired joint movement (95.7%). Fever was present in 64%, hypotension in 28% of events, and C-reactive protein > 100 mg/L in 90.6%. Gram positive cocci were the most frequently isolated microorganisms (81.5%), predominating S. aureus (48.1%), and with 4 isolates methicillin resistant isolates (26.7%). Resistant isolates trend to be associated with previous surgery (p = 0.055) and all cases caused by non-fermentative Gram negative bacilli had recent hospitalization or surgery, a feature that did not reach a significant difference. Nine events were associated to bacteremia (36%). Outcome analysis indicated 32% of events with full recovery, 28% with a favorable evolution, 20% with therapy failure and 16.7% patients that died. A total of 24% of the series remained with significant sequels.Septic arthritis is an infrequent disease that affects in most cases patients with predisposing conditions. Associated symptoms include pain and impaired joint movement, sometimes fever, hypotension, positive blood cultures and frequently a C-reactive protein > 100 mg/L. Predominant agents are Gram positive cocci, specially S. aureus, including methicillin resistant isolates. Case-fatality ratio, treatment failure and sequels are important. |
| 2014 | [Effects of different anesthesia depth on stress response in elderly patients undergoing elective laparoscopic surgery for colorectal cancer]. | Nan Fang Yi Ke Da Xue Xue Bao | To investigate the effects of different anesthesia depth on stress response in elderly patients undergoing elective laparoscopic surgery for colorectal cancer.A total of 105 ASA I-III patients aged 60-91 years undergoing elective laparoscopic surgery for colorectal cancer with general anesthesia were randomized into 3 groups, namely group A with a target Narcotrend index (NI) maintained at D0 level, group B with a NI at D2 level, and group C with a NI at E1 level. The anesthetics (profopol and remifentanil) were adjusted according to Narcotrend monitoring results to maintain the specified anesthesia depth. The patients' heart rate (HR) and mean artery pressure (MAP) were recorded before anesthesia (T0), before intubation (T1), immediately after intubation (T2), at 2 min before pneumoperitoneum (T3), 2 min after pneumoperitoneum (T4), at the end of the surgery (T5) and extubation (T6). Serum levels of cortisol, adrenocorticotropic hormone (ACTH), endothelin-1 (ET-1), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and C-reactive protein (CRP) were measured by standard ELISA and radioimmunoassay before anesthesia (Ta), at the end of the surgery (Tb) and 1 day after the surgery (Tc).HR and MAP in group A increased significantly at T2, T4, and T6 compared to those at T0 (P<0.05), and were higher than those in group B and group C (P<0.05). The MAP in all the 3 groups all decreased at T1 and T3 (P<0.05 or P<0.01), and was markedly lower in group C than in groups A and B (P<0.05). The incidence of hypertension was significantly higher in group A than in groups B and C (P<0.05), while the incidence of hypotension was much higher in group C (P<0.01). There were no obvious differences in serum levels of cortisol, ACTH, CRP, IL-6, TNF-a, or ET-1 among the groups at Ta (P>0.05). The serum levels of ACTH in the 3 groups all significantly increased at Tb and Tc (P<0.01). CRP, IL-6 and TNF-a levels in group A were increased at Tb and Tc (P<0.05 or P<0.01) and significantly higher than those in groups B and C (P<0.05 or P<0.01). Cortisol in groups A and B increased at Tb and Tc (P<0.05) to a significantly higher level than that in group C (P<0.01). ET-1 level in group C at Tb and Tc was lower than those in groups A and B (P<0.05 or P<0.01).Maintaining the anesthesia depth for a NI at the D2 and E1 level can both attenuate the stress response in elderly patients undergoing laparoscopic surgery for colorectal cancer, but the hemodynamic stability can be better at a D2 level. |
| 2014 | [Saccharomyces cerevisiae fungemia in an elderly patient following probiotic treatment]. | Mikrobiyol Bul | Saccharomyces cerevisiae, known as baker's yeast, is also used as a probiotic agent to treat gastroenteritis by modulating the endogenous flora and immune system. However, since there have been increasing reports of fungemia due to S.cerevisiae and its subspecies S.boulardii, it is recommended that probiotics should be cautiously used in immunosuppressed patients, people with underlying diseases and low-birth weight babies. To emphasize this phenomenon, in this report, a case of S.cerevisiae fungemia developed in a patient given probiotic treatment for antibiotic-associated diarrhea, was presented. An 88-year-old female patient was admitted to our hospital with left hip pain, hypotension, and confusion. Her medical history included hypertension, chronic renal failure, left knee replacement surgery, and recurrent urinary tract infections due to neurogenic bladder. She was transferred to the intensive care unit with the diagnosis of urosepsis. After obtaining blood and urine samples for culture, empirical meropenem (2 x 500 mg) and linezolid (1 x 600 mg) treatment were administered. A central venous catheter (CVC) was inserted and after one day of inotropic support, her hemodynamic parameters were stabilized. The urine culture obtained on admission yielded extended-spectrum beta-lactamase-producing Klebsiella pneumoniae and Escherichia coli. Urine culture was repeated after three days and no bacteria were isolated. On the 4th day of admission she developed diarrhea. Toxin A/B tests for Clostridium difficile were negative. To relieve diarrhea, S.boulardii (Reflor 250 mg capsules, Sanofi Aventis, Turkey) was administered twice a day, without opening capsules. Two days later, her C-reactive protein (CRP) level increased from 23.2 mg/L to 100 mg/L without fever. Her blood culture taken from the CVC yielded S.cerevisiae. Linezolid and meropenem therapies were stopped on the 13th and 14th days, respectively, while prophylactic fluconazole therapy was replaced with caspofungin 1 x 50 mg on the fifth day. After seven days of therapy CRP and serum creatinine levels decreased to 9.1 mg/L and 1.2 mg/dl, respectively; and she was discharged from the hospital with improvement. The probiotic capsules were used unopen, thus, it was proposed that S.cerevisiae fungemia originated from translocation from the intestinal mucosa. Since it was not possible to investigate the molecular genetics of the strain isolated from the blood culture and the strain present in the probiotic, a definite conclusion about the origin of the strain could not be reached. It was thought that old age and underlying disease of the patient were the related predisposing factors for S.cerevisiae fungemia. This case emphasized that clinicians should be cautious in case of probiotic application even though in encapsulated form, even in immunocompetent patients with a history of long-term hospital stay and use of broad-spectrum antimicrobials since there may be a risk of S.cerevisiae fungemia development. |
| 2014 | Clinical and inflammatory response to bloodstream infections in octogenarians. | BMC Geriatr | Given the increasing incidence of bacteraemia causing significant morbidity and mortality in older patients, this study aimed to compare the clinical features, laboratory findings and mortality of patients over the age of 80 to younger adults.This study was a retrospective, observational study. Participants were taken to be all patients aged 18 and above with confirmed culture positive sepsis, admitted to a large metropolitan hospital in the year 2010. Measurements taken included patient demographics (accommodation, age, sex, comorbidities), laboratory investigations (white cell count, neutrophil count, C-reactive protein, microbiology results), clinical features (vital signs, presence of localising symptoms, complications, place of acquisition).A total of 1367 patient episodes were screened and 155 met study inclusion criteria. There was no statistically significant difference between likelihood of fever or systolic blood pressure between younger and older populations (p-values of 0.81 and 0.64 respectively). Neutrophil count was higher in the older cohort (p = 0.05). Higher Charlson (J Chronic Dis 40(5):373-383, 1987) comorbidity index, greater age and lower systolic blood pressure were found to be statistically significant predictors of mortality (p-values of 0.01, 0.02 and 0.03 respectively).The findings of this study indicate older patients are more likely to present without localising features. However, importantly, there is no significant difference in the likelihood of fever or inflammatory markers. This study also demonstrates the importance of the Charlson Index of Comorbidities (J Chronic Dis 40(5):373-383, 1987) as a predictive factor for mortality, with age and hypotension being less important but statistically significant predictive factors of mortality. |
| 2014 | Infection and inflammation leading to clozapine toxicity and intensive care: a case series. | Ann Pharmacother | To describe 3 cases of clozapine toxicity associated with infectious and/or inflammatory processes.Three patients stable on clozapine therapy prior to a medical hospital admission developed clozapine toxicity. It was suspected that an acute infectious and/or inflammatory process in each patient was related to abrupt mental status changes, onset of sialorrhea, myoclonus, and/or need for ventilatory support. Investigations of altered mental status did not reveal alternative causes and presentations were not consistent with neuroleptic malignant syndrome, other acute neurologic complications, or psychiatric decompensation. All patients improved after clozapine dose reductions allowing for transfer from intensive care units. Using the Naranjo ADR Probability Scale for each case, a probable relation between clozapine toxicity and the infectious and/or inflammatory process was determined.Clozapine toxicity may manifest with multiple symptoms, including sedation, sialorrhea, and hypotension. In addition to overdose and drug interactions; infection and/or inflammation may precipitate clozapine toxicity. This may be related to cytokine-mediated inhibition of cytochrome P450 1A2. The likelihood of toxicity via this mechanism has not been well characterized, thus careful monitoring is required for medically ill patients receiving clozapine. Clozapine is extensively bound to the acute phase reactant, α-1 acid glycoprotein, which may unpredictably protect against clinical toxicity. C-reactive protein has also been investigated to relate clozapine toxicity to infection and/or inflammation.Clozapine toxicity developed in 3 patients admitted to a medical setting suspected to be related to infection and/or inflammation. Clinicians should be aware of this potential adverse drug event with clozapine. |
| 2014 | Infliximab for intensification of primary therapy for Kawasaki disease: a phase 3 randomised, double-blind, placebo-controlled trial. | Lancet | Kawasaki disease, the most common cause of acquired heart disease in developed countries, is a self-limited vasculitis that is treated with high doses of intravenous immunoglobulin. Resistance to intravenous immunoglobulin in Kawasaki disease increases the risk of coronary artery aneurysms. We assessed whether the addition of infliximab to standard therapy (intravenous immunoglobulin and aspirin) in acute Kawasaki disease reduces the rate of treatment resistance.We undertook a phase 3, randomised, double-blind, placebo-controlled trial in two children's hospitals in the USA to assess the addition of infliximab (5 mg per kg) to standard therapy. Eligible participants were children aged 4 weeks-17 years who had a fever (temperature ≥38·0°C) for 3-10 days and met American Heart Association criteria for Kawasaki disease. Participants were randomly allocated in 1:1 ratio to two treatment groups: infliximab 5 mg/kg at 1 mg/mL intravenously over 2 h or placebo (normal saline 5 mL/kg, administered intravenously). Randomisation was based on a randomly permuted block design (block sizes 2 and 4), stratified by age, sex, and centre. Patients, treating physicians and staff, study team members, and echocardiographers were all masked to treament assignment. The primary outcome was the difference between the groups in treatment resistance defined as a temperature of 38·0°C or higher at 36 h to 7 days after completion of the infusion of intravenous immunoglobulin. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, NCT00760435.196 patients were enrolled and randomised: 98 to the infliximab group and 98 to placebo. One patient in the placebo group was withdrawn from the study because of hypotension before receiving treatment. Treatment resistance rate did not differ significantly (11 [11·2%] for infliximab and 11 [11·3%] for placebo; p=0·81). Compared with the placebo group, participants given infliximab had fewer days of fever (median 1 day for infliximab vs 2 days for placebo; p<0·0001). At week 2, infliximab-treated patients had greater mean reductions in erythrocyte sedimentation rate (p=0·009) and a two-fold greater decrease in Z score of the left anterior descending artery (p=0·045) than did those in the placebo group, but this difference was not significant at week 5. Participants in the infliximab group had a greater mean reduction in C-reactive protein concentration (p=0·0003) and in absolute neutrophil count (p=0·024) at 24 h after treatment than did those given placebo, but by week 2 this difference was not significant. At week 5, none of the laboratory values differed significantly compared with baseline. No significant differences were recorded between the two groups at any timepoint in proximal right coronary artery Z scores, age-adjusted haemoglobin values, duration of hospital stay, or any other laboratory markers of inflammation measured. No reactions to intravenous immunoglobulin infusion occurred in patients treated with infliximab compared with 13 (13·4%) patients given placebo (p<0·0001). No serious adverse events were directly attributable to infliximab infusion.The addition of infliximab to primary treatment in acute Kawasaki disease did not reduce treatment resistance. However, it was safe and well tolerated and reduced fever duration, some markers of inflammation, left anterior descending coronary artery Z score, and intravenous immunoglobulin reaction rates.US Food and Drug Administration, Robert Wood Johnson Foundation, and Janssen Biotech. |
| 2014 | [A multicenter randomized controlled trial of sufentanil for analgesia/sedation in patients in intensive care unit]. | Zhonghua Wei Zhong Bing Ji Jiu Yi Xue | To evaluate the sedation and analgesia power and security of sufentanil in intensive care unit (ICU), and to compare the effect with fentanyl.A multicenter randomized controlled trial was conducted. Critical adult patients in ICU from 11 hospitals in Henan Province from June 2011 to January 2012 who needed analgesia based sedation were enrolled. These patients were randomly divided into two groups with 300 cases in each group using the envelope method according to the hospital number and time sequence number of inclusion. Exclusion criteria included the time of analgesia duration < 48 hours and who were under continuous renal replacement therapy (CRRT) treatment during analgesia. 544 cases were enrolled finally, and there were 282 cases in sufentanil group and 262 in fentanyl group. Before using the drug, there was no statistically significant difference in age, body weight, acute physiology and chronic health evaluation II (APACHEII) score, Glasgow coma scale (GCS) between sufentanil group and fentanyl group, and were comparable. The goal of analgesia was faces pain scale (FPS)≤2. If the dosage of sufentanil and fentanyl exceeded the upper limited dose (sufentanil 0.3 μg×kg(-1)×h(-1), fentanyl 2 μg×kg(-1)×h(-1)) but FPS could not meet (still>2), and maintained the upper limited doses of sufentanil and fentanyl and added midazolam, and FPS≤2 or Ramsay 3 could meet the standard. The analgesia duration of all cases was 48-168 hours. Related data were collected for statistical analysis.(1) Compared with the data before the analgesia, the mean arterial pressure (MAP) of sufentanil analgesia after analgesia at different time points were significantly decreased (F=6.061, P<0.001) and closed to the normal level, FPS at different time point score were decreased significantly after analgesia (F=259.389, P<0.001), and the changes in pulse oxygen saturation (SpO(2)), respiratory rate and pulse were not found. (2) Compared with before the analgesia, the white blood cell count (WBC), neutrophil percentage (N), platelet count (PLT), aspartate transaminase (AST), creatinine (Cr), arterial partial pressure of carbon dioxide (PaCO(2)), blood lactic acid, blood sugar, C-reactive protein (CRP) were markedly reduced after sufentanil analgesia (WBC: 10.8 ± 4.2 ×10(9)/L vs. 14.2 ± 11.5×10(9)/L, F=49.879, P<0.001; N: 0.806 ± 0.104 vs. 0.815 ± 0.128, F=5.768, P=0.017; PLT: 160.4 ± 77.0 ×10(9)/L vs. 166.1 ± 89.0×10(9)/L, F=6.568, P=0.011; AST: 61.3 ± 10.1 U/L vs. 90.9 ± 26.9 U/L, F=6.706, P=0.010; Cr: 86.7 ± 71.8 μmol/L vs. 119.6 ± 56.0 μmol/L, F=30.303, P<0.001; PaCO(2): 39.4 ± 7.2 mmHg vs. 41.7 ± 22.6 mmHg, F=4.389, P=0.037; blood lactic acid: 1.9 ± 1.2 mmol/L vs. 2.7 ± 2.5 mmol/L, F=4.883, P=0.028; blood sugar: 8.0 ± 5.4 mmol/L vs. 9.7 ± 7.6 mmol/L, F=9.724, P=0.002; CRP: 64.8 ± 20.7 mg/L vs. 114.0 ± 55.9 mg/L, F=4.883, P=0.028). But there were no statistically significant differences in red blood cell count (RBC), prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen (FIB), thrombin time (TT), alanine aminotransferase (ALT), total bilirubin (TBil), albumin (ALB), total protein (TP) blood urea nitrogen (BUN), and arterial partial pressure of oxygen (PaO(2)) before and after sufentanil analgesia (all P>0.05). (3)There was no statistically significant difference in effectiveness of sufentanil and five times dose of fentanyl (P>0.05). There was no statistically significant difference in the proportion of sedative drugs midazolam usage [18.4% (52/282) vs. 24.8% (65/262), χ(2)=1.151, P=0.283] and the rate of analgesia success [44.3% (125/282) vs. 48.9% (128/262), χ(2)=0.571, P=0.450] and analgesia success [16.3% (46/282) vs. 15.3% (40/262), χ(2)=0.066, P=0.798] between sufentanil and fentanyl group. (4) Comparison of adverse reactions: the incidence of hypotension in sufentanil group was significantly lower than that in fentanyl group [3.2% (9/282) vs. 6.9% (18/262), χ(2)=3.900, P=0.048], and other common adverse reactions, such as respiratory depression/pause, nausea/vomiting and dizziness, pruritus, allergy, slow heart beat (bradycardia) and metabolic reactions had no statistically significant difference. Addiction or tetanus of skeletal muscles was not found in both groups.Compared with fentanyl, the analgesia efficacy of sufentanil is stronger. Sufentanil has less physiological interference and lower incidence of adverse reactions for ICU patients. |
| 2014 | Phase I safety trial of intravenous ascorbic acid in patients with severe sepsis. | J Transl Med | Parenterally administered ascorbic acid modulates sepsis-induced inflammation and coagulation in experimental animal models. The objective of this randomized, double-blind, placebo-controlled, phase I trial was to determine the safety of intravenously infused ascorbic acid in patients with severe sepsis.Twenty-four patients with severe sepsis in the medical intensive care unit were randomized 1:1:1 to receive intravenous infusions every six hours for four days of ascorbic acid: Lo-AscA (50 mg/kg/24 h, n = 8), or Hi-AscA (200 mg/kg/24 h, n = 8), or Placebo (5% dextrose/water, n = 8). The primary end points were ascorbic acid safety and tolerability, assessed as treatment-related adverse-event frequency and severity. Patients were monitored for worsened arterial hypotension, tachycardia, hypernatremia, and nausea or vomiting. In addition Sequential Organ Failure Assessment (SOFA) scores and plasma levels of ascorbic acid, C-reactive protein, procalcitonin, and thrombomodulin were monitored.Mean plasma ascorbic acid levels at entry for the entire cohort were 17.9 ± 2.4 μM (normal range 50-70 μM). Ascorbic acid infusion rapidly and significantly increased plasma ascorbic acid levels. No adverse safety events were observed in ascorbic acid-infused patients. Patients receiving ascorbic acid exhibited prompt reductions in SOFA scores while placebo patients exhibited no such reduction. Ascorbic acid significantly reduced the proinflammatory biomarkers C-reactive protein and procalcitonin. Unlike placebo patients, thrombomodulin in ascorbic acid infused patients exhibited no significant rise, suggesting attenuation of vascular endothelial injury.Intravenous ascorbic acid infusion was safe and well tolerated in this study and may positively impact the extent of multiple organ failure and biomarkers of inflammation and endothelial injury.ClinicalTrials.gov identifier NCT01434121. |
| 2013 | Treating inflammation by blocking interleukin-1 in humans. | Semin Immunol | IL-1 is a master cytokine of local and systemic inflammation. With the availability of specific IL-1 targeting therapies, a broadening list of diseases has revealed the pathologic role of IL-1-mediated inflammation. Although IL-1, either IL-1α or IL-1β, was administered to patients in order to improve bone marrow function or increase host immune responses to cancer, these patients experienced unacceptable toxicity with fever, anorexia, myalgias, arthralgias, fatigue, gastrointestinal upset and sleep disturbances; frank hypotension occurred. Thus it was not unexpected that specific pharmacological blockade of IL-1 activity in inflammatory diseases would be beneficial. Monotherapy blocking IL-1 activity in a broad spectrum of inflammatory syndromes results in a rapid and sustained reduction in disease severity. In common conditions such as heart failure and gout arthritis, IL-1 blockade can be effective therapy. Three IL-1blockers have been approved: the IL-1 receptor antagonist, anakinra, blocks the IL-1 receptor and therefore reduces the activity of IL-1α and IL-1β. A soluble decoy receptor, rilonacept, and a neutralizing monoclonal anti-interleukin-1β antibody, canakinumab, are also approved. A monoclonal antibody directed against the IL-1 receptor and a neutralizing anti-IL-1α are in clinical trials. By specifically blocking IL-1, we have learned a great deal about the role of this cytokine in inflammation but equally important, reducing IL-1 activity has lifted the burden of disease for many patients. |
| Correlation of serum magnesium with cardiovascular risk factors in maintenance hemodialysis patients--a cross-sectional study. | Magnes Res | Changes in serum magnesium (Mg) may affect some clinical features of patients on maintenance hemodialysis (HD). The aims of our study were to evaluate the correlation between serum Mg concentration and clinical characteristics in Chinese HD patients, and to determine whether it has any relevance for cardiovascular outcomes.98 chronic HD patients were recruited, and clinical features related to cardiovascular disease (CVD) were measured: the correlation between Mg and these characteristics was analyzed.In patients who were hypomagnesemic, serum Mg, creatinine (Scr), albumin (Alb), pre-albumin (pre-Alb) levels, protein catabolic rate per normalized body weight (nPCR), dietary protein intake (DPI), triceps skin fold (TSF) thickness, mid-arm circumference (MAC), mean mid-arm circumference (MAMC), subjective global assessment (SGA) scores and Kt/V were lower than in hypermagnesemic patients. On the other hand, the incidence of intradialytic hypotension (IDH), levels of serum calcium (Ca), phosphorus (P), intact parathyroid hormone (iPTH), C reactive protein (CRP), high-density lipoprotein cholesterol (HDL-c) levels, carotid artery plaque (CAP), and carotid intima-media thickness (CIMT) (all p<0.05, respectively) were higher in patients with low serum magnesium. Correlation analysis showed Mg to be not only positively associated with the nutritional status index, but also negatively correlated with other characteristics, such as IDH incidence, Kt/V, Ca, P, iPTH, CRP, HDL-c, CAP, CIMT (p<0.05, respectively). There was no significant correlation between Mg and low-density lipoprotein cholesterol (LDL-c), lipoprotein-a (LP-a), cholesterol (TC), serum triglycerides (TG), or subjective global assessment (SGA) scores (p>0.05, respectively). Multiple linear regression analysis showed that Mg was negatively associated with CIMT, a direct predictor of CVD (β coefficient=-0.260, p=0.009).It is suggested that lower serum Mg reflects poorer nutritional status and that it is also associated with other risk factors for cardiovascular disease in hemodialysis patients, such as greater incidence of IDH, poorer HD adequacy, deteriorating calcium-phosphate metabolism, inflammation and CIMT. |
| 2015 | Clinical manifestations of Kawasaki disease shock syndrome: a case-control study. | J Microbiol Immunol Infect | Kawasaki disease shock syndrome (KDSS) is a severe condition related to Kawasaki disease (KD), and sometimes it is difficult to diagnose. This is a case-control study to ascertain the clinical presentations, risk factors, and clinical outcomes of children who had KDSS.Children who were hospitalized during 2001-2011 with the diagnosis of KD combined with hypotension, sepsis, or shock were retrospectively reviewed and were defined as case patients. For each case patient, three season-matched patients diagnosed as having KD with normal blood pressure were identified to serve as control patients. Demographic characteristics, clinical presentations, laboratory features, therapies, and outcomes were analyzed.Nine KDSS patients and 27 control patients were identified. The average age of patients with KDSS was 3.2 ± 3.2 years. Compared with controls, KDSS patients were less likely to have a diagnosis of KD at admission (22.2% vs. 66.7%) and had a higher risk of coronary artery dilatation (77.8% vs. 11.1%). Risk factors for KDSS included higher neutrophil counts and proportions of bands, higher C-reactive protein (CRP), and lower platelet counts. All case patients received aspirin therapy; eight patients received intravenous immunoglobulin therapy, with two receiving more than one course. Seven KDSS patients required fluid resuscitation, and eight patients required vasoactive infusions.Patients with KDSS may have uneven clinical course and may be misdiagnosed in the beginning. They may have more prominent inflammatory markers in the early phase and higher risk of coronary artery dilatation. |
| 2013 | Diagnostic usefulness of procalcitonin as a marker of bacteremia in patients with acute pyelonephritis. | Scand J Clin Lab Invest | Acute pyelonephritis (APN) is one of the most common community-acquired infections and frequently accompanies bacteremia. The purpose of this study was to investigate the diagnostic role of procalcitonin in predicting bacteremia in patients with APN.We conducted a retrospective study of patients with APN who visited the emergency department (ED) at Samsung Medical Center, Seoul. Predictors of bacteremia were analyzed and receiver operating characteristics (ROC) curves were plotted for procalcitonin, C-reactive protein (CRP), and leukocytes.During the study period, a total of 147 patients who had microbiologically proven APN and available initial procalcitonin concentrations were identified. Of these, bacteremia was present in 84 patients. Multivariate analysis showed that age, hypotension, and higher procalcitonin concentrations independently predicted the presence of bacteremia. Procalcitonin had better discriminative power than CRP, as reflected by area under the ROC curve analysis (0.746 [95% CI, 0.667-0.826] vs. 0.602 [95% CI, 0.509-0.694], p = 0.02). At a cut-off value of 1.63 μg/L, procalcitonin predicted bacteremia with a sensitivity, specificity, positive predictive value, negative predictive value and accuracy of 61.9, 81.0, 81.3, 61.4 and 70.1%, respectively.Procalcitonin concentration could be used as a reliable marker to predict bacteremia in patients with APN in the ED. |
| 2013 | Serum procalcitonin level for the prediction of severity in women with acute pyelonephritis in the ED: value of procalcitonin in acute pyelonephritis. | Am J Emerg Med | Predicting medical outcomes for acute pyelonephritis (APN) in women is difficult. Delay in diagnosis and treatment often results in rapid progression to circulatory collapse, multiple-organ failure, and death. The aim of this study was to investigate the value of procalcitonin (PCT) level in women with APN at ED.We conducted a prospective study of women with APN presenting to the ED. The authors measured inflammatory biomarkers, and the severity of pyelonephritis was assessed by 4 severity of disease classification system and stage of sepsis. We performed an analysis to assess the value of PCT for the prediction of 28-day mortality and disease severity.A total of 240 female patients with APN are included. Patients were divided into 4 groups on the basis of systemic inflammatory response syndrome criteria, organ dysfunction, and persistent hypotension. The median PCT level was higher in the septic shock group compared with other groups. Of the other inflammatory markers, only white blood cell count was significantly different among the groups, whereas high-sensitivity C-reactive protein level and erythrocyte sedimentation rate revealed no differences. The area under the curve for PCT in predicting 28-day mortality was 0.68. For predicting mortality, a cutoff value of 0.42 ng/mL had a sensitivity of 80% and a specificity of 50%. However, the disease classification systems were demonstrated to be superior to PCT in predicting 28-day mortality.Relative to other classic markers of inflammation, by distinguishing the severity of sepsis related to APN, PCT levels can provide additional aid to clinicians in disease severity classification and their decision of treatment at ED. |
| 2012 | The malnutrition-inflammation-depression-arteriosclerosis complex is associated with an increased risk of cardiovascular disease and all-cause death in chronic hemodialysis patients. | Nephron Clin Pract | In chronic hemodialysis patients, malnutrition, inflammation, depression and arteriosclerosis are pathogenetically associated suggesting the presence of malnutrition-inflammation-depression-arteriosclerosis (MIDA) complex acting as a risk factor for cardiovascular disease (CVD).Nutritional status was assessed by serum albumin, subjective global assessment and normalized protein catabolic rate (nPCR). Inflammation was assessed by serum high-sensitivity C-reactive protein (hsCRP). Depression was assessed with the Beck Depression Inventory and DSM-IV criteria. The severity of arteriosclerosis was measured by pulse wave velocity (PWV).Among 81 hemodialysis patients, 44 (54.3%) had malnutrition (albumin <4.0 mg/dl with subjective global assessment score <6 and/or nPCR <1.0) and 39 (48.1%) had inflammation (hsCRP >1 mg/l). The prevalence of depression was 50.6% (n = 41). Fifty-nine (73.8%) had arteriosclerosis (measured PWV > expected PWV based on age/blood pressure/gender adjustment). The severity of the all four individual MIDA components correlated well with each other. The average number of the MIDA complication (MIDA score) was 2.27 ± 1.33. -During the 5-year follow-up, 40 cases of CVD and 26 cases of all-cause death occurred. In Cox analysis adjusted for -previous CVD, age, diabetes, blood pressure, pulse pressure, intradialytic hypotension, B-type natriuretic peptide, -hemoglobin and hemodialysis incompliance, the MIDA score was an independent predictor of CVD and all-cause death: hazard ratio (95% confidence interval); 1.89 (1.13-3.17) and 3.48 (1.32-9.21) for an increase of 1 MIDA score.This study suggests the presence of MIDA complex, which is composed of malnutrition, inflammation, depression and arteriosclerosis. The MIDA complex syndrome was an independent risk factor for CVD and all-cause death in chronic hemodialysis patients. |
| 2013 | C-reactive protein exacerbates renal ischemia-reperfusion injury. | Am J Physiol Renal Physiol | Renal ischemia-reperfusion injury (IRI) is a common cause of acute kidney injury (AKI), occurring with hypotension and cardiovascular surgery and inevitably during kidney transplantation. Mortality from AKI is high due to incomplete knowledge of the pathogenesis of IRI and the lack of an effective therapy. Inflammation accompanies IRI and increases the blood level of C-reactive protein (CRP), a biomarker of worsened outcomes in AKI. To test if CRP is causal in AKI we subjected wild-type mice (WT) and human CRP transgenic mice (CRPtg) to bilateral renal IRI (both pedicles clamped for 30 min at 37°C then reperfused for 24 h). Serum human CRP level was increased approximately sixfold after IRI in CRPtg (10.62 ± 1.31 μg/ml at baseline vs. 72.01 ± 9.41 μg/ml at 24 h) but was not elevated by sham surgery wherein kidneys were manipulated but not clamped. Compared with WT, serum creatinine, urine albumin, and histological evidence of kidney damage were increased after IRI in CRPtg mice. RT-PCR analysis of mRNA isolated from whole kidneys of CRPtg and WT subjected to IRI revealed that in CRPtg kidneys 1) upregulation of markers of macrophage classical activation (M1 markers) was blunted, 2) downregulation of markers of macrophage alternative activation (M2 markers) was more robust, and 3) expression of the activating receptor FcγRI was increased. Our finding that CRP exacerbates IRI-induced AKI, perhaps by shifting the balance of macrophage activation and FcγR expression towards a detrimental portfolio, might make CRP a promising therapeutic target for the treatment of AKI. |
| 2013 | The effect of immunosuppression on manifestations of sepsis in an animal model of cecal ligation and puncture. | Transplant Proc | The diagnosis of sepsis is difficult in immunocompromised patients owing to their modified response to infection. Our experiment in minipigs was designed to compare responses to sepsis between experimental groups of septic minipigs with and without immunosuppression.Minipigs with identical baseline parameters were randomized into 3 groups: Sepsis (n = 10); immunosuppression (n = 11), including cyclosporine, methylprednisolone, and mycophenolate mofetil treatment before surgery, and a sham group (n = 6). Sepsis was induced by cecal ligation and puncture (CLP). We recorded selected clinical and laboratory parameters up to 24 hours postoperatively.All CLP animals developed septic shock with a febrile response, tachycardia, and hypotension requiring noradrenaline administration. The hemodynamic responses to sepsis in septic groups with and without immunosuppression were similar. Noradrenaline infusion was started on average later in the immunosuppression than in the group without immunosuppression; however, the difference was not significant. The kinetics of the plasma levels of most selected cytokines and C-reactive protein were similar in both septic groups. At 10 hours after surgery, the immunosuppression group showed significantly lower interleukin (IL)-6 levels compared with the sepsis group. At 19, 22, and 25 hours after surgery immunosuppressed animals displayed significantly greater increases in IL-10 levels compared with the cohort without immunosuppression.CLP is a simple, reproducible model of sepsis in minipigs. All CLP animals developed sepsis within 24 hours on average. Significant differences in IL-6 and IL-10 plasma levels were recorded between septic animals with versus without immunosuppression. |
| 2012 | Risk factors and incidence of acute pyogenic cholangitis. | Hepatobiliary Pancreat Dis Int | Acute cholangitis varies from mild to severe form. Acute suppurative cholangitis (ASC), the severe form of acute cholangitis, is a fatal disease and requires urgent biliary decompression. Which patients are at a high risk of ASC and need emergency drainage is still unclear. The present study aimed to identify the factors for determining early-stage ASC and distinguishing ASC from acute cholangitis.We analyzed 359 consecutive patients with acute cholangitis who had been admitted to the First Affiliated Hospital, Zhejiang University School of Medicine from January 2004 to May 2011. Emergency endoscopic retrograde cholangiopancreatography (ERCP) was carried out in all patients to decompress or clear the stones by experienced endoscopists. Clinical and therapeutic data were collected, and univariate and multivariate analyses were performed to identify the potential risk factors of ASC.Of the 359 patients, 1 was excluded because of failure of ERCP drainage. Of the remaining 358 patients with an average age of 62.7 years (range 17-90), 162 were diagnosed with ASC, and 196 with non-ASC. ENBD catheters were placed in 343 patients (95.8%), of whom 182 patients had stones removed at the same time, and plastic stent was placed in 25 patients (7.0%). Clinical conditions were improved quickly after emergency biliary drainage in all patients. Complications were identified in 11 patients (3.1%): mild pancreatitis occurred in 8 patients and hemorrhage in 3 patients. There was no mortality. Univariate analysis showed that several variables were associated with ASC: age, fever, decreased urine output, hypotension, tachycardia, abnormal white blood cell count (WBC), low platelet, high C reactive protein (CRP), and duration of the disease. Multivariate analysis revealed that advanced age, hypotension, abnormal WBC, high CRP, and duration of the disease were independent risk factors for ASC.This study demonstrates that advanced age, hypotension, abnormal WBC, high CRP, and long duration of antibiotic therapy are significantly associated with ASC. We recommend decompression by ERCP should be carried out in patients as early as possible. |
| 2012 | Can hantavirus infections be predicted on admission to hospital? | J Med Virol | The aim of this study was to investigate the predictive factors which contribute to diagnosis of hantavirus infection. One hundred patients from rural areas hospitalized with a preliminary diagnosis of hantavirus infection from different hospitals in Turkey were investigated. Hantavirus infection was confirmed in 20 patients (Group 1) using immunofluorescence and immunoblot assays at the Refik Saydam National Public Health Agency. Hantaviruses were not detected in the serum of the remaining 80 patients, other infectious and non-infectious diseases being diagnosed in this group (Group 2). Patients' demographic characteristics and clinical and laboratory data on admission were examined and compared between the two groups. Fever, proteinuria, hematuria, lethargy-weakness, and nausea-vomiting were the most frequent symptoms and findings in Group 1, seen in almost all patients. Proteinuria, hematuria, muscle pain, diarrhea/abdominal pain, hypotension, shock, and sweating were observed at significantly higher levels in Group 1 compared to Group 2. Serum urea, creatinine, uric acid, lactate dehydrogenase (LDH), aspartate transaminase (AST), alkaline phosphatase (ALP), and C-reactive protein (CRP) were significantly higher, but serum platelet counts were lower in Group 1 patients. Area beneath the receiver operating characteristics (ROC) curve analysis was used to calculate the discriminative ability of various laboratory values to identify patients with hantavirus infection. This analysis revealed that, serum CRP had a 100% negative predictive value, whilst, platelet, and creatinine had 75% and 70% positive predictive values for the diagnosis of hantavirus infection. In summary, laboratory markers used in clinical practice are of great importance predicting hantavirus infections. |
| 2012 | [A severe falciparum malaria case successfully treated by exchange transfusion as an adjunct therapy]. | Mikrobiyol Bul | Plasmodium falciparum malaria is a type of malaria with high fatality rate despite optimal antimalarial treatment. Exchange transfusion (ET) is successfully used as a means of supportive therapy in severe P. falciparum malaria cases with hyperparasitemia. Herein, we present a case with hyperparasitemia, who received erythrocyte ET therapy due to lack of clinical response to antimalarial treatment. A 24-year-old male patient was admitted to our emergency clinic with the complaints of fever that persisted for 10 days, headache, nausea-vomiting, and impaired consciousness. Medical history revealed that he had been working in Sudan, Africa and returned back 12 days ago. On physical examination; he had fever, hypotension, tachycardia, subicterus and impaired cooperation. Laboratory examination revealed pancytopenia, elevated C-reactive protein, hyperbilirubinemia, hyponatremia, elevated creatinine level and hematuria. On thick blood smear and thin blood smear examinations, multiple (> 5%) trophozoites and gametocytes indicating P.falciparum species were observed. The case was diagnosed as P.falciparum malaria and parenteral fluid support, dopamine infusion, meropenem (IV), doxycycline (PO) and quinine sulphate (PO) were initiated in the intensive care unit. On reevaluation of the patient on the third day of hospitalization, it was observed that arterial hypotension and fever were persistent, anemia and trombocytopenia deteriorated and on thick blood smear parasitemiea was not decreased. It was decided to apply automated erythrocyte ET. After ET, patient's medical status was quickly improved and patient was discharged on the 7th day of hospitalization. In conclusion, it was noted that in addition to antimalarial treatment, erythrocyte ET may provide dramatic improvement in severe cases of P.falciparum malaria with hyperparasitemia. |
| 2012 | Apelin, plasmatic osmolality and hypotension in dialyzed patients. | Blood Purif | To evaluate the balance between arginine-vasopressin (AVP) and apelin during hemodialysis and its role in hypotension onset and in the inflammation status.We enrolled 50 patients chronically treated with hemodialysis. We assessed plasmatic osmolality, AVP, apelin, mean blood pressure (BP), high-sensitivity C-reactive protein (hsCRP) and β(2)-microglobulin.Apelin rises during dialytic treatment (from 0.68 ± 0.34 to 1.89 ± 0.56 pg/ml, p < 0.0001), while plasmatic osmolality (from 325 ± 4.54 to 311 ± 1.20 mosm/kg H(2)O, p < 0.0001), AVP (from 4.28 ± 1.12 to 2.48 ± 0.50 pg/ml, p < 0.0001) and mean BP (from 124 ± 6 to 110 ± 7 mm Hg, p < 0.0001) decrease. At multivariate regression with respect to apelin, only mean BP remains (r = -0.95, p < 0.0001). We also correlated the AVP/apelin ratio with BP. Moreover, apelin is inversely related to hsCRP (r = -0.79, p < 0.0001).The AVP/apelin balance changes with plasmatic osmolality variations induced by hemodialytic sessions and could represent a physiopathological marker of arterial hypo- and hypertension. Finally, apelin appears inversely related to inflammation markers. |
| 2012 | Phase II trial of hu14.18-IL2 for patients with metastatic melanoma. | Cancer Immunol Immunother | Phase I testing of the hu14.18-IL2 immunocytokine in melanoma patients showed immune activation, reversible toxicities, and a maximal tolerated dose of 7.5 mg/m(2)/day. In this phase II study, 14 patients with measurable metastatic melanoma were scheduled to receive hu14.18-IL2 at 6 mg/m(2)/day as 4-h intravenous infusions on Days 1, 2, and 3 of each 28 day cycle. Patients with stable disease (SD) or regression following cycle 2 could receive two additional treatment cycles. The primary objective was to evaluate antitumor activity and response duration. Secondary objectives evaluated adverse events and immunologic activation. All patients received two cycles of treatment. One patient had a partial response (PR) [1 PR of 14 patients = response rate of 7.1 %; confidence interval, 0.2-33.9 %], and 4 patients had SD and received cycles 3 and 4. The PR and SD responses lasted 3-4 months. All toxicities were reversible and those resulting in dose reduction included grade 3 hypotension (2 patients) and grade 2 renal insufficiency with oliguria (1 patient). Patients had a peripheral blood lymphocytosis on Day 8 and increased C-reactive protein. While one PR in 14 patients met protocol criteria to proceed to stage 2 and enter 16 additional patients, we suspended stage 2 due to limited availability of hu14.18-IL2 at that time and the brief duration of PR and SD. We conclude that subsequent testing of hu14.18-IL2 should involve melanoma patients with minimal residual disease based on compelling preclinical data and the confirmed immune activation with some antitumor activity in this study. |
| 2012 | Beneficial role of spironolactone, telmisartan and their combination on isoproterenol-induced cardiac hypertrophy. | Acta Cardiol | Although spironolactone and telmisartan are reported to reduce the risk of morbidity and death, direct studies on their effects on isoproterenol-induced cardiac hypertrophy are scanty. Hence the present investigation was carried out to study the effect of spironolactone, telmisartan and their combination on isoproterenol-induced cardiac hypertrophy.Isoproterenol was administered intra-peritoneally in a dose of 5 mg/kg once daily for 10 days to Wistar rats. Spironolactone (20 mg/kg/ day) (SL), telmisartan (5 mg/kg/day) (TM) or their combination (SLTM) was administered for 10 days after which various biochemical and cardiac parameters were measured.Isoproterenol produced dyslipidaemia, hypertension, elevated cardiac enzyme and C-reactive protein levels (CRP), worsened haemodynamic parameters and produced cardiac hypertrophy, left ventricular (LV) hypertrophy and oxidative stress. Chronic treatment with SL,TM or SLTM significantly controlled dyslipidaemia and produced a significant reduction in the elevated creatine-kinase (CK) and CRP levels. TM or SLTM produced a decrease in elevated lactate de-hydrogenase levels; however, SL failed to produce this effect. Hypotension, tachycardia, and decreased rate of pressure development and decay were prevented by SL, TM and SLTM treatment. Chronic treatment with SL, TM or SLTM also produced significant reduction in LV collagen levels, cardiac and LV hypertrophy index and prevented oxidative stress.Our data suggests that SL, TM and SLTM produced a beneficial effect on cardiac hypertrophy. |
| 2012 | Effects of secondary amyloidosis on arteriovenous hemodialysis fistula outcomes and intradialytic hypotension: a case-control study. | Hemodial Int | Amyloid fibrils can affect vascular structure through deposition and by causing nitric oxide depletion and increase of asymmetric dimethyl arginine. Patients with amyloidosis are prone to development of hypotension. Hypotension may also affect the maturation of arteriovenous fistula (AVF) and may set the stage for formation of thrombosis and fistula failure. Thus, we aimed to evaluate effects of secondary amyloidosis on AVF outcomes and intradialytic hypotension. This is a case-control study which included 20 hemodialysis patients with amyloidosis and 20 hemodialysis patients without amyloidosis as control group. All patients underwent Doppler ultrasound of AVF. A thorough fistula history and baseline laboratory values along with episodes of intradialytic hypotension and blood pressure measurements were recorded. There was no difference between the groups regarding age, gender, body mass index, presence of comorbidities, hypertension, and drug use. Systolic and diastolic blood pressures were similar (119 ± 28/75 ± 17 and 120 ± 14/75 ± 10 mmHg for patients with and without amyloidosis, respectively). Intradialytic hypotension episodes were also similar. Patients with amyloidosis had significantly lower serum albumin and higher C-reactive protein values compared to control hemodialysis patients. AVF sites and total number of created fistulas were similar in both groups. Flow rates of current functional AVFs were not different between the groups (1084 ± 875 and 845 ± 466 mL/minute for patients with and without amyloidosis, respectively, p:0.67). Patency duration of first AVF was not different between the groups. Clinical fistula outcomes and rate of intradialytic hypotension episodes were not significantly different between patients with and without secondary systemic amyloidosis. |
| 2012 | Autopsy cases of fulminant bacterial infection in adults: clinical onset depends on the virulence of bacteria and patient immune status. | J Infect Chemother | To assist physicians in recognizing the potentially fatal onset of symptoms in cases of fulminant bacterial infection, we analyzed 11 autopsy cases of such infection (four caused by Streptococcus pneumoniae, four by S. pyogenes, one by S. dysgalactiae subsp. equisimilis, one by Staphylococcus aureus, and one by Vibrio vulnificus). Clinicohistopathologic features were evaluated. All patients experienced sudden onset of hypotension and multiple organ failure, leading to unexpected death. Blood culture confirmed bacteremia. The main chief complaints were gastrointestinal symptoms (45%) and limb pain (36%). All had an underlying chronic illness (82%), e.g., a hematologic disorder (36.3%) or liver cirrhosis (27.2%). Necrotizing fasciitis occurred in only 55% of cases, with none involving pneumococcal infection. Laboratory tests typically showed C-reactive protein elevation but without leukocytosis, indicating a high-level inflammatory state. In ten cases, death was attributed to circulatory collapse due to sepsis; severe pulmonary congestion and hemorrhage were present in these cases. The onset of fulminant bacterial infection depends on both virulence of the bacterium and status of the host defense system. |
| 2012 | Tocilizumab improves cardiac disease in a hemodialysis patient with AA amyloidosis secondary to rheumatoid arthritis. | Amyloid | A 58-year-old Japanese woman on hemodialysis (HD) was admitted for intractable rheumatoid arthritis. Even after HD was started due to end-stage renal failure in 2004, her arthropathy worsened. A soluble tumor necrosis factor receptor inhibitor (etanercept at 25 mg twice weekly), tacrolimus (2 mg daily), and prednisolone (10 mg daily) had been administered since 2005, but high disease activity had persisted. She was admitted to our hospital in July 2007. C-reactive protein (CRP) was 6.8 mg/dL, and the DAS-CRP score was calculated to be 8.3. The cardiothoracic ratio (CTR) was 62% on a chest radiograph, but dialysis hypotension was remarkable. Left ventricular mass (LVM) was calculated as 320 g using echocardiography. Endoscopic biopsy of the stomach and duodenum revealed heavy deposition of AA amyloid. Etanercept was discontinued and tocilizumab was started at a dose of 320 mg (8 mg/kg) monthly. Even after predonisolone and tacrolimus were tapered gradually and discontinued because of her good response, CRP and DAS-CRP became 0.0 mg/dL and 1.5, respectively. In September 2011, re-evaluation was performed. CTR was reduced to 51% and LVM was decreased to 180 g. Endoscopic biopsy of the stomach and duodenum revealed disappearance of AA amyloid. Although AA amyloidosis of the gastrointestinal tract has already been reported to be improved by tocilizumab, this is the first report on improvement of myocardial hypertrophy as well as dialysis hypotension. |
| 2012 | Deferoxamine attenuates lipid peroxidation, blocks interleukin-6 production, ameliorates sepsis inflammatory response syndrome, and confers renoprotection after acute hepatic ischemia in pigs. | Artif Organs | We have previously shown that deferoxamine (DFO) infusion protected myocardium against reperfusion injury in patients undergoing open heart surgery, and reduced brain edema, intracranial pressure, and lung injury in pigs with acute hepatic ischemia (AHI). The purpose of this research was to study if DFO could attenuate sepsis inflammatory response syndrome (SIRS) and confer renoprotection in the same model of AHI in anesthetized pigs. Fourteen animals were randomly allocated to two groups. In the Group DFO (n=7), 150mg/kg of DFO dissolved in normal saline was continuously infused in animals undergoing hepatic devascularization and portacaval anastomosis. The control group (Group C, n=7) underwent the same surgical procedure and received the same volume of normal saline infusion. Animals were euthanized after 24h. Hematological, biochemical parameters, malondialdehyde (MDA), and cytokines (interleukin [IL]-1β, IL-6, IL-8, IL-10, and tumor necrosis factor-α) were determined from sera obtained at baseline, at 12h, and after euthanasia. Hematoxylin-eosin and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling were used to evaluate necrosis and apoptosis, respectively, in kidney sections obtained after euthanasia. A rapid and substantial elevation (more than 100-fold) of serum IL-6 levels was observed in Group C reaching peak at the end of the experiment, associated with increased production of oxygen free radicals and lipid peroxidation (MDA 3.2±0.1nmol/mL at baseline and 5.5±0.9nmol/mL at the end of the experiment, P<0.05) and various manifestations of SIRS and multiple organ dysfunction (MOD), including elevation of high-sensitivity C-reactive protein, severe hypotension, leukocytosis, thrombocytopenia, hypoproteinemia, and increased serum levels of lactate dehydrogenase (fourfold), alkaline phosphatase (fourfold), alanine aminotransferase (14-fold), and ammonia (sevenfold). In sharp contrast, IL-6 production and lipid peroxidation were completely blocked in DFO-treated animals offering remarkable resistance to the development of SIRS and MOD. Profound proteinuria, strips of extensive necrosis of tubular epithelial cells, and occasional apoptotic tubular epithelial cells were already present in Group C, but not in Group DFO animals at the time of euthanasia. DFO infusion attenuated lipid peroxidation, blocked IL-6 production, and substantially diminished SIRS and MOD, including tubulointerstitial damage in pigs after acute ischemic hepatic failure. This finding shows that iron, IL-6, and lipid peroxidation are important participants in the pathophysiology of renal injury in the course of generalized inflammation and provides novel pathways of therapeutic interventions for renal protection. |
| 2012 | Absolute blood eosinophil count and 1-year mortality risk following hospitalization with acute heart failure. | Eur J Emerg Med | In acute heart failure (AHF), hemoglobin, red cell distribution width, mean platelet volume, leukocytes, and relative lymphocyte count have been associated with mortality. It is not known whether absolute blood neutrophil, eosinophil, and monocyte counts are mortality predictors.One hundred and seventy-six patients hospitalized due to AHF were enrolled. Treatment modalities and comorbidities influencing leukocyte counts were excluded. Hemogram, pro-brain natriuretic peptide, D-dimer, biochemistry, thyroid hormones, sensitive C-reactive protein, and echocardiography were obtained. Cardiovascular deaths during the first year after hospitalization were determined.Leukocyte and absolute neutrophil count were significantly higher and absolute lymphocyte count and absolute eosinophil count (AEC) were significantly lower in deceased patients than patients who survived. Groups were similar in terms of monocyte counts. BMI albumin, estimated glomerular filtration rate, free T3, ejection fraction were significantly lower, and ferritin, uric acid, D-dimer, pro-brain natriuretic peptide were significantly higher in deceased patients. Mitral regurgitation, hypotension, hyponatremia, and acute renal failure were also significantly more frequent among the deceased group. Binary logistic regression analysis employing significant variables showed that lower BMI, lower ejection fraction, hyponatremia, lower free T3, and lower AEC were independent predictors of death and as a whole were responsible from 81.8% of cardiovascular deaths. Death rate among patients with an AEC of 0.02 n/l×10 or less was 4.4-fold higher than patients with an AEC of more than 0.02 n/l×10.AEC of AHF patients measured at admission was found to be a stronger predictor of mortality than all other hemogram parameters and this is consistent with the increased sympatho-adrenal activity theory. |
| 2011 | The usefulness of procalcitonin and C-reactive protein as early diagnostic markers of bacteremia in cancer patients with febrile neutropenia. | Cancer Res Treat | Procalcitonin (PCT) and C-reactive protein (CRP) are well known inflammatory markers. This study was designed to determine whether PCT and CRP are useful as early diagnostic markers for bacteremia in cancer patients with febrile neutropenia (FN) in the emergency department (ED).In this retrospective study, 286 episodes of FN in the ED were consecutively included between June 2009 and August 2010. From medical records, clinical characteristics including PCT and CRP were extracted and analyzed.Bacteremia was identified in 38 (13.3%) of the 286 episodes. The median values of PCT (2.8 ng/mL vs. 0.0 ng/mL, p=0.000) and CRP (15.9 mg/dL vs. 5.6 mg/dL, p=0.002) were significantly higher in the group with bacteremia compared to the group without bacteremia. In univariate analysis, elevated PCT (>0.5 ng/mL) and CRP (>10 mg/dL) as well as older age, hypotension, tachycardia, tachypnea, and high body temperature were significantly associated with bacteremia. On multivariate analysis, elevated PCT (>0.5 ng/mL) (odds ratio [OR], 3.6; 95% confidence interval [CI], 1.4 to 9.2; p<0.01) and tachypnea (OR, 3.4; 95% CI, 1.4 to 8.5; p<0.01) were independent early diagnostic markers for bacteremia in FN patients. The area under the curve of PCT was 74.8% (95% CI, 65.1 to 84.6%) and that of CRP was 65.5% (95% CI, 54.8 to 76.1%). With a PCT cut-off value of 0.5 ng/mL, sensitivity and specificity were 60.5% and 82.3%, respectively, while the sensitivity and specificity were 57.6% and 67.3%, respectively, with a CRP cutoff of 10 mg/dL.These findings suggest that PCT is a useful early diagnostic marker for the detection of bacteremia in FN at the ED and has better diagnostic value than CRP. |
| 2012 | Procalcitonin and valuable clinical symptoms in the early detection of neonatal late-onset bacterial infection. | Acta Paediatr | To evaluate which clinical symptoms indicate proven neonatal bacterial infection (NBI) and whether measuring procalcitonin aside from C-reactive protein and interleukin 6 improves sensitivity and specificity in diagnosis.In a prospective observational study, clinical symptoms and procalcitonin, C-reactive protein and interleukin 6 were simultaneously determined from the 4th day of life in 170 preterm and term neonates at the first time of suspicion of NBI. Proven NBI was defined as a positive culture of otherwise sterile body fluids or radiologically verified pneumonia in combination with elevated inflammatory markers.Fifty-eight (34%) patients were diagnosed with proven late-onset NBI. In case of proven NBI, odds ratio and 95% confidence intervals were 2.64 (1.06-6.54) for arterial hypotension, 5.16 (2.55-10.43) for feeding intolerance and 9.18 (4.10-20.59) for prolonged capillary refill. Sensitivity of combined determination of C-reactive protein (>10 mg/L) and interleukin 6 (>100 pg/mL) was 91.4%, specificity 80.4%, positive predictive value 70.7% and negative predictive value 94.7%. The additional determination of procalcitonin (>0.7 ng/mL) resulted in 98.3%, 65.2%, 58.8% and 98.6%, respectively.Arterial hypotension, feeding intolerance and especially prolonged capillary refill indicate proven neonatal late-onset bacterial infection, even at the time of first suspicion. Additional measurement of procalcitonin does indeed improve sensitivity to nearly 100%, but is linked to a decline in specificity. Nevertheless, in the high-risk neonatal population, additional procalcitonin measurement can be recommended because all infants with NBI have to be identified. |
| 2011 | Impact of volume status on blood pressure and left ventricle structure in patients undergoing chronic hemodialysis. | Ren Fail | In this study, we aimed to examine the impact of volume status on blood pressure (BP) and on left ventricular mass index (LVMI) in chronic hemodialysis (HD) patients. This study enrolled 74 patients (F/M: 36/38, mean age 53.5 ± 15.3 years, mean HD time 41.5 ± 41 months) that were on HD treatment for at least 3 months. Demographics, biochemical tests, hemogram and C-reactive protein levels, mean interdialytic weight gain (IDWG), mean percentage of ultrafiltration (UF), and intradialytic complications such as hypotension and cramps were determined. Mean values of predialysis and postdialysis BP measurements were recorded a month before echocardiographic examination. On the day after a midweek dialysis session, 24 h ambulatory BP monitoring (ABPM) and echocardiographic examination were made concurrently. The patients were classified into two groups according to volume status: normovolemic (group 1; 14F/24M, mean age 50 ± 16.7 years, mean dialysis time 47.7 ± 47.7 months) and hypervolemic (group 2; 15F/21M, mean age 57.3 ± 12.7 years, mean dialysis time 34.9 ± 32 months). HD duration, IDWG, UF, and interdialytic complication rates were similar between the two groups (p < 0.05). Eleven patients (28.9%) of group 1 and 8 patients (22.2%) of group 2 showed dipper (p = 0.50). Valvular damage was more common in group 2 (p = 0.002). Whereas 33 patients (91.7%) had left ventricular hypertrophy (LVH) in group 2, 21 patients of the group 1 (55.3%) had LVH (p < 0.001). Although LVMI showed a significant positive correlation with cardiothoracic index, predialysis and postdialysis BP, IDWG, UF, daytime and nighttime BP measurements of 24 h ABPM, a significant negative correlation was seen with Kt/V urea and serum albumin levels. In conclusion, increased IDWG and UF and elevated BP are independent predictors of LVH for HD patients. Increased volume status leads to IDWG and elevated BP and eventually causes severe LVMI increases. |
| 2011 | Serum C-reactive protein level is a predictive factor for 14-day mortality of patients with advanced cancer who present to the emergency department with acute symptoms. | Acad Emerg Med | This study aimed to investigate the potential of C-reactive protein (CRP) as a predictor of death within 14 days in acutely symptomatic patients with advanced cancer admitted to the emergency department (ED).A prospective observational study was conducted of 126 consecutive patients with advanced cancer who were admitted to the ED because of acute symptoms. The patients were categorized into two groups according to serum CRP levels (cutoff 9.2 mg/dL). Demographic characteristics, disease-related factors, clinical symptoms and signs, and laboratory data were collected. Univariate and multivariate analyses were performed to evaluate the relationship between clinical findings and 14-day mortality.Median survival was 26.5 days (interquartile range = 8.0-79.5 days). In univariate analysis, serum CRP level (≥9.2 mg/dL), chemotherapy, age (≥65 years), altered mental status, hypotension, and leukocytosis were significant. Multivariate regression analysis revealed that among these variables, serum CRP level (hazard ratio [HR] = 2.444, 95% confidence interval [CI] = 1.298 to 4.603, p = 0.006) and chemotherapy (HR = 0.452, 95% CI = 0.236 to 0.863, p = 0.016) were independent prognostic factors for 14-day mortality.Serum CRP levels may provide information on death within 14 days after the ED visit in patients with advanced cancer. |
| 2011 | High plasma level of long pentraxin 3 (PTX3) is associated with fatal disease in bacteremic patients: a prospective cohort study. | PLoS One | Long pentraxin 3 (PTX3) is an acute-phase protein secreted by various cells, including leukocytes and endothelial cells. Like C-reactive protein (CRP), it belongs to the pentraxin superfamily. Recent studies indicate that high levels of PTX3 may be associated with mortality in sepsis. The prognostic value of plasma PTX3 in bacteremic patients is unknown.Plasma PTX3 levels were measured in 132 patients with bacteremia caused by Staphylococcus aureus, Streptococcus pneumoniae, β-hemolytic streptococcae and Escherichia coli, using a commercial solid-phase enzyme-linked immunosorbent assay (ELISA). Values were measured on days 1-4 after positive blood culture, on day 13-18 and on recovery.The maximum PTX3 values on days 1-4 were markedly higher in nonsurvivors compared to survivors (44.8 vs 6.4 ng/ml, p<0.001) and the AUC(ROC) in the prediction of case fatality was 0.82 (95% CI 0.73-0.91). PTX3 at a cut-off level of 15 ng/ml showed 72% sensitivity and 81% specificity for fatal disease. High PTX3 (>15 ng/ml) was associated with hypotension (MAP <70 mmHg)(OR 7.9;95% CI 3.3-19.0) and high SOFA score (≥4)(OR 13.2; 95% CI 4.9-35.4). The CRP level (maximum value on days 1 to 4) did not predict case fatality at any cut-off level in the ROC curve (p = 0.132). High PTX3 (>15 ng/ml) remained an independent risk factor for case fatality in a logistic regression model adjusted for potential confounders.PTX3 proved to be a specific independent prognostic biomarker in bacteremia. PTX3 during the first days after diagnosis showed better prognostic value as compared to CRP, a widely used biomarker in clinical settings. PTX3 measurement offers a novel opportunity for the prognostic stratification of bacteremia patients. |
| 2011 | A case of femoral hemorrhage in a patient with microscopic polyangiitis with low levels of myeloperoxidase-antineutrophil cytoplasmic autoantibody. | Clin Exp Nephrol | We present the case of a 67-year-old female with femoral hemorrhage accompanied by microscopic polyangiitis. She was admitted to our hospital with symptoms of general fatigue, fever, and edema of the lower limbs. She was diagnosed with microscopic polyangiitis on the basis of the cardinal symptoms of the condition, including rapidly progressive glomerulonephritis and the presence of myeloperoxidase-antineutrophil cytoplasmic autoantibody (MPO-ANCA), albeit at a low titer. Renal biopsy demonstrated the presence of fibrocellular crescent-shaped glomeruli with interstitial infiltration. No immune deposits were detected in immunofluorescence studies. The patient was treated with steroids and anti-platelet agents; subsequently, the inflammatory reaction subsided and MPO-ANCA and C-reactive protein titers decreased. However, on day 14, the patient experienced sudden onset of swelling in the left femoral region accompanied by hypotension. Her hemoglobin level dropped from 8.8 to 4.5 g/dl in the subsequent hours. Although computed tomography of the legs revealed an extensive hematoma in the left quadriceps femoris muscle, the patient recovered after receiving a transfusion and supportive therapy with discontinuation of dipyridamole. Thereafter, her renal function improved, and she was discharged. To our knowledge, this is the first report of a case of microscopic polyangiitis accompanied by femoral hemorrhage. |
| 2011 | Circulating endotoxemia: a novel factor in systemic inflammation and cardiovascular disease in chronic kidney disease. | Clin J Am Soc Nephrol | Translocated endotoxin derived from intestinal bacteria has a wide range of adverse effects on cardiovascular (CV) structure and function, driving systemic inflammation, atherosclerosis and oxidative stress. This study's aim was to investigate endotoxemia across the spectrum of chronic kidney disease (CKD).Circulating endotoxin was measured in 249 patients comprising CKD stage 3 to 5 and a comparator cohort of hypertensive patients without significant renal impairment. Patients underwent extended CV assessment, including pulse wave velocity and vascular calcification. Hemodialysis (HD) patients also received detailed echocardiographic-based intradialytic assessments. Patients were followed up for 1 year to assess survival.Circulating endotoxemia was most notable in those with the highest CV disease burden (increasing with CKD stage), and a sharp increase was observed after initiation of HD. In HD patients, predialysis endotoxin correlated with dialysis-induced hemodynamic stress (ultrafiltration volume, relative hypotension), myocardial stunning, serum cardiac troponin T, and high-sensitivity C-reactive protein. Endotoxemia was associated with risk of mortality.CKD patients are characteristically exposed to significant endotoxemia. In particular, HD-induced systemic circulatory stress and recurrent regional ischemia may lead to increased endotoxin translocation from the gut. Resultant endotoxemia is associated with systemic inflammation, markers of malnutrition, cardiac injury, and reduced survival. This represents a crucial missing link in understanding the pathophysiology of the grossly elevated CV disease risk in CKD patients, highlighting the potential toxicity of conventional HD and providing a novel set of potential therapeutic strategies to reduce CV mortality in CKD patients. |
| 2010 | The additive blood pressure lowering effects of exercise intensity on post-exercise hypotension. | Am Heart J | Evidence contends lower levels of physical exertion reduce blood pressure (BP) as effectively as more rigorous levels. We compared the effects of low (40% peak oxygen consumption, Vo(2)peak), moderate (60% Vo(2)peak), and vigorous (100% Vo(2)peak) exercise intensity on the BP response immediately following aerobic exercise. We also examined clinical correlates of the BP response.Subjects were 45 men (mean +/- SEM, 43.9 +/- 1.4 years) with elevated awake ambulatory BP (ABP, 144.5 +/- 1.5/85.4 +/- 1.2 mm Hg). Men completed four randomly assigned experiments: non-exercise control and three exercise bouts at low, moderate, and vigorous intensity. All experiments began with a baseline period of seated rest. Subjects left the laboratory wearing an ABP monitor.Systolic ABP increased 2.8 +/- 1.6 mm Hg less after low, 5.4 +/- 1.4 mm Hg less after moderate, and 11.7 +/- 1.5 mm Hg less after vigorous than control over 9 h (P < .001). Diastolic ABP decreased 1.5 +/- 1.2 mm Hg more after low, 2.0 +/- 1.0 mm Hg more after moderate, and 4.9 +/- 1.3 mm Hg more after vigorous versus control over 9 h (P < .010). Baseline correlates of the systolic ABP post-exercise response to vigorous were fasting glucose (r = -0.415), C-reactive protein (r = -0.362), renin (r = -0.348), fasting insulin (r = 0.310), and fasting low density lipoprotein (r = -0.298) (R(2) = 0.400, P = .002). Baseline correlates of the diastolic ABP post-exercise response to vigorous were Vo(2)peak (r = -0.431), fasting low density lipoprotein (r = -0.431), renin (r = -0.411), fibrinogen (r = 0.369), and fasting glucose (r = -0.326) (R(2) = 0.429, P < .001).The antihypertensive effects of exercise intensity occurred in dose response fashion. Clinicians should weigh the benefits and risks of prescribing vigorous exercise intensity for those with hypertension on an individual basis. |
| 2010 | Relation of serum albumin and C-reactive protein to hypotensive episodes during hemodialysis sessions. | Saudi J Kidney Dis Transpl | To evaluate the effect of albumin serum levels and C-reactive protein (CRP) on the course of dialysis induced hypotension (DIH) in chronic hemodialysis (HD) patients, we studied 58 chronic hemodialysis patients in our center during 2007. We investigated the correlation between serum albumin, highly sensitive CRP (hs-CRP) and DIH. The mean of the serum albumin levels was 4.2 +/- 0.5 g/dL, and 32.8% of the patients revealed hypoalbuminemia. Occurrence of DIH among HD patients was 27.6%. The mean of serum albumin levels in the DIH group was significantly lower compared with the normotensive group (3.9 +/- 0.4 vs 4.3 +/- 0.5 g/dL, respectively, P= 0.008). The mean of the hs-CRP levels was significantly higher in the DIH group compared with the normotensive group (12.9 +/- 12 vs. 7.2 +/- 5.2 mg/dL, respectively, P= 0.01). We conclude that high level of CRP and hypoalbuminemia may be predictors of DIH. |
| 2010 | Clinical signs and CRP values associated with blood culture results in neonates evaluated for suspected sepsis. | Acta Paediatr | To identify which clinical signs at presentation are most predictive of sepsis subsequently confirmed by blood culture and to investigate whether the predictive power of the clinical signs varies by gestational age.Among 401 newborn infants < 28 days of age with suspected sepsis, nine signs of sepsis and C-reactive protein (CRP) values were prospectively recorded. Logistic regression assessed the association of these signs and laboratory values with a subsequently confirmed diagnosis of sepsis by positive blood culture. The analysis was stratified by gestational age with mutual simultaneous adjustment for the signs and sex.Five of the nine clinical signs (feeding intolerance, distended abdomen, blood pressure, bradycardia and apnoea), along with CRP were statistically significantly associated with a positive blood culture. After simultaneous adjustment for all of the signs, apnoea, hypotension and CRP were independently predictive of positive blood culture. When the material was stratified by gestational age, differences in the association with positive blood culture were found for bradycardia, tachypnea and irritability/seizures.In this selected population of infants with suspected sepsis, apnoea and hypotension are independently predictive of a confirmed diagnosis, while bradycardia is more predictive among preterm infants and tachypnea among term infants. |
| 2011 | Predictive factors of poor prognosis in cancer patients with chemotherapy-induced febrile neutropenia. | Support Care Cancer | We intended to determine the predictive factors of poor prognosis in cancer patients with chemotherapy-induced febrile neutropenia (FN).From January 1, 2007 to December 31, 2008, 396 episodes of FN in 346 cancer patients were retrospectively analyzed. Clinical and laboratory findings and Multinational Association of Supportive Care in Cancer (MASCC) risk-index score were analyzed and correlated with outcome.Of the 396 episodes, 73 (18.4%) had serious medical complications including 15 (3.8%) deaths. There was significant difference between unfavorable and favorable outcomes in age, gender, hypotension, tachypnea, duration of fever ≤24 h before admission (44.4% vs. 61.3%), interval of ≤7 days since last chemotherapy (34.2% vs. 16.1%), and duration of neutropenia ≥4 days (34.2% vs. 15.8%; P < 0.05 each), as did C-reactive protein (CRP; 15.0 vs. 7.5 mg dL(-1)) and platelet count (66.4 × 10(3) vs. 123.7 × 10(3) mm(-3);P < 0.001 each). MASCC score was significantly lower in unfavorable outcomes than favorable outcomes (19.0 vs. 24.6, P < 0.001). However, prophylactic antibiotics, treatment with granulocyte colony-stimulating factor (G-CSF), and history of FN were not associated with outcome. On multivariate analysis, MASCC risk-index score (OR 23.2, 95% CI 10.48-51.37), tachypnea (OR 3.61, 95% CI 1.44-9.08), thrombocytopenia (OR 3.41, 95% CI 1.69-6.89), increased CRP (OR 3.23, 95% CI 1.62-6.45), and prolonged neutropenia (OR 2.52, 95% CI 1.21-5.25) were independent predictors of unfavorable outcomes.MASCC risk-index score <21, tachypnea, thrombocytopenia, increased CRP, and prolonged neutropenia may be strongly associated with poor outcomes in cancer patients with FN. |
| 2010 | Evaluation of six risk factors for the development of bacteremia in children with cancer and febrile neutropenia. | Curr Oncol | Febrile neutropenia is a well-known entity in children with cancer, being responsible for the high risk for infection that characterizes this population. For this reason, cancer patients are hospitalized so that they can receive prophylactic care. Risk factors have been used to classify patients at a high risk for developing bacteremia. The present study evaluates whether those risk factors (C-reactive protein, hypotension, leukemia as the cancer type, thrombocytopenia, recent chemotherapy, and acute malnutrition) apply to patients at the Unidad Nacional de Oncología Pediátrica. We evaluated 102 episodes in 88 patients, in whom risk factors and blood cultures were tested. We observed no statistical relationship between the six risk factors and bacteremia. There was also no relationship between bacteremia and the simultaneous presence of two, three, or more risk factors. A significant relationship of C-reactive protein and platelet count with other outcome factors was observed. |
| 2010 | Recurrent syncope and chronic ear pain. | BMJ Case Rep | An elderly gentleman presented to hospital with recurrent blackout episodes consistent with syncope and a 3-month history of right ear pain. Significant postural hypotension was recorded. White cell count and C reactive protein were elevated. MRI of the head and neck revealed a soft tissue abnormality in the right nasopharynx and base of skull. Tissue biopsies were obtained and microbiology specimens revealed a mixed growth of pseudomonas and diphtheroids. There was no histological evidence of malignancy. A diagnosis of skull base infection was made. Infective involvement of the carotid sinus was considered to be the cause of the recurrent syncope and postural hypotension. The patient responded well to a 12-week course of intravenous meropenem. Inflammatory markers returned to normal and a repeat MRI after 3 months of treatment showed significant resolution of infection. The syncopal episodes and orthostatic hypotension resolved in parallel with treatment of infection. |
| 2009 | [Case of tuberculosis-associated hemophagocytic syndrome in a hemodialysis patient under steroid therapy]. | Nihon Jinzo Gakkai Shi | A 70-year-old woman was referred and admitted to our hospital with fever of unknown etiology. She had a past medical history of pulmonary tuberculosis. Ten weeks before admission she was diagnosed with acute renal failure caused by crescentic glomerulonephritis. Oral steroid therapy was not effective and she required dialysis. On admission, she was started on empiric antibiotic treatment, with the suspicion of bacterial infection. On the 3rd hospital day, she developed sudden hypotension and underwent direct hemoperfusion with a polymyxin B immobilized fiber. Soon after, her blood pressure normalised. Her inflammatory level apparently then improved in terms of white blood cell count and C-reactive protein, although severe fatigue and liver dysfunction persisted. On the 17th hospital day, her blood pressure went down again, accompanied by progressive pancytopenia and significant increase in serum vitamin B12, lactate dehydrogenase and uric acid. The patient was transmitted to the intensive care unit where she received bone marrow aspiration. The result revealed marked hemophagocytosis. Suspecting lymphoma-associated hemophagocytic syndrome (HPS), we administered high-dose steroid and combination chemotherapy. The treatment had no effect, and the patient died on the 21st hospital day. The autopsy demonstrated a large number of tuberculous bacilli, marked hemophagocytosis and necrosis without granuloma formation in multiple organs, leading to the pathological diagnosis of tuberculosis-associated HPS. Tuberculosis in one of the major causes for morbidity and mortality in hemodialyzed patients. It often shows atypical clinical manifestation and is difficult to diagnose. HPS in general runs a mild course unless it is lymphoma or EB virus-associated. This case seemed like bacterial infection improved with antibiotics but turned out to be a rapidly progressive tuberculosis-associated HPS. A careful examination and extensive laboratory workup is necessary to rule out tuberculosis, particularly in patients undergoing hemodialysis. |
| [Myocarditis exacerbation in a child undergoing inguinal herniopasty after viral infection]. | Srp Arh Celok Lek | Immunosuppressive effects of general anaesthesia and surgery could have unexpected consequences in a child with recent infection. The incidence of myocarditis in childhood is unknown.During general anaesthesia for inguinal hernia repair, a seven-year-old boy suddenly developed heart failure. Clinical presentation included hypotension, pulmonary oedema, drop in haemoglobin oxygen saturation, ST segment elevation and premature ventricular contractions. Haemodynamic stability and adequate oxygenation were achieved with dopamine and furosemide. Preoperative history, physical examination and complete blood count were unremarkable. Moderate cardiomegaly and pulmonary oedema were present on chest radiography. Diminished left ventricular contractility found on echocardiography increased troponin I and CK-MB levels suggested myocardial injury. Increased C-reactive protein with lymphocytosis suggested inflammation as its cause. Parents failed to report rubella 10 days before the operation. A clinical diagnosis of myocarditis as a complication of rubella was based on increased titer of IgM to rubella. With intravenous immunoglobulin, corticosteroids and symptomatic treatment for heart failure, his condition improved and ejection fraction reached 68% one month after operation.In future, we need protocols with instructions for paediatric patients undergoing elective surgery and anaesthesia after viral infections. |
| 2009 | Heparin-binding protein: an early marker of circulatory failure in sepsis. | Clin Infect Dis | The early detection of circulatory failure in patients with sepsis is important for successful treatment. Heparin-binding protein (HBP), released from activated neutrophils, is a potent inducer of vascular leakage. In this study, we investigated whether plasma levels of HBP could be used as an early diagnostic marker for severe sepsis with hypotension.A prospective study of 233 febrile adult patients with a suspected infection was conducted. Patients were classified into 5 groups on the basis of systemic inflammatory response syndrome criteria, organ failure, and the final diagnosis. Blood samples obtained at enrollment were analyzed for the concentrations of HBP, procalcitonin, interleukin-6, lactate, C-reactive protein, and the number of white blood cells.Twenty-six patients were diagnosed with severe sepsis and septic shock, 44 patients had severe sepsis without septic shock, 100 patients had sepsis, 43 patients had an infection without sepsis, and 20 patients had an inflammatory response caused by a noninfectious disease. A plasma HBP level > or = 15 ng/mL was a better indicator of severe sepsis (with or without septic shock) than any other laboratory parameter investigated (sensitivity, 87.1%; specificity, 95.1%; positive predictive value, 88.4%; negative predictive value, 94.5%). Thirty-two of the 70 patients with severe sepsis were sampled for up to 12 h before signs of circulatory failure appeared, and in 29 of these patients, HBP plasma concentrations were already elevated.In febrile patients, high plasma levels of HBP help to identify patients with an imminent risk of developing sepsis with circulatory failure. |
| 2009 | [Autopsy case of PR3-ANCA-associated vasculitis complicated with rectus muscle hematoma]. | Nihon Jinzo Gakkai Shi | A 80-year-old man was admitted to our hospital because of coughing, hemosputum and dyspnea. As a chest X-ray showed infiltrates of the right lung, he was diagnosed as bacterial pneumonia and treated with antibiotics. However, after a few days, he exhibited hemoptysis and developed severe dyspnea, while laboratory findings showed rapid elevation of the serum creatinine level (5.55 mg dL). Computed tomography (CT) revealed large areas of ground glass opacity in the right lung, hence the hemoptysis was considered to be due to alveolar hemorrhage. As he had been diagnosed as chronic renal failure a few years before this admission and we also noticed that interstitial pneumonia with a slightly elevated level of C-reactive protein had existed from that time, ANCA-associated vasculitis was suspected to be the underlying pathogenesis. Accordingly, he was started on methylprednisolone pulse therapy and temporary hemodialysis resulted in improvement of dyspnea and renal function. PR3-ANCA was 12.4 EU, so he was diagnosed as PR3-ANCA-associated vasculitis. After a few days, he suddenly complained of abdominal pain, developing hypotension and anemia. Abdominal CT showed an irregular low-density mass in the right muscle, so he was diagnosed as rectus muscle hematoma. Surgery was performed and a massive hematoma was found in the rectus muscle without any ruptures of macroscopic vessels in the abdomen. Bleeding could not be stopped followed by multiple organ failure and the patient died four days postoperatively. Rectus muscle hematoma is an uncommon cause of acute abdomen, and has been reported in about 100 cases in Japan. It occurs because of a tear in epigastric vessels and is usually managed conservatively with a good prognosis, although hemodynamically unstable cases require surgery. To the best of the authors' knowledge, this is the first case of rectus muscle hematoma complicated with ANCA-associated vasculitis. |
| 2009 | Recognition of a Kawasaki disease shock syndrome. | Pediatrics | We sought to define the characteristics that distinguish Kawasaki disease shock syndrome from hemodynamically normal Kawasaki disease.We collected data prospectively for all patients with Kawasaki disease who were treated at a single institution during a 4-year period. We defined Kawasaki disease shock syndrome on the basis of systolic hypotension for age, a sustained decrease in systolic blood pressure from baseline of > or =20%, or clinical signs of poor perfusion. We compared clinical and laboratory features, coronary artery measurements, and responses to therapy and analyzed indices of ventricular systolic and diastolic function during acute and convalescent Kawasaki disease.Of 187 consecutive patients with Kawasaki disease, 13 (7%) met the definition for Kawasaki disease shock syndrome. All received fluid resuscitation, and 7 (54%) required vasoactive infusions. Compared with patients without shock, patients with Kawasaki disease shock syndrome were more often female and had larger proportions of bands, higher C-reactive protein concentrations, and lower hemoglobin concentrations and platelet counts. Evidence of consumptive coagulopathy was common in the Kawasaki disease shock syndrome group. Patients with Kawasaki disease shock syndrome more often had impaired left ventricular systolic function (ejection fraction of <54%: 4 of 13 patients [31%] vs 2 of 86 patients [4%]), mitral regurgitation (5 of 13 patients [39%] vs 2 of 83 patients [2%]), coronary artery abnormalities (8 of 13 patients [62%] vs 20 of 86 patients [23%]), and intravenous immunoglobulin resistance (6 of 13 patients [46%] vs 32 of 174 patients [18%]). Impairment of ventricular relaxation and compliance persisted among patients with Kawasaki disease shock syndrome after the resolution of other hemodynamic disturbances.Kawasaki disease shock syndrome is associated with more-severe laboratory markers of inflammation and greater risk of coronary artery abnormalities, mitral regurgitation, and prolonged myocardial dysfunction. These patients may be resistant to immunoglobulin therapy and require additional antiinflammatory treatment. |
| 2009 | Clinical features of neonatal sepsis caused by resistant Gram-negative bacteria. | Pediatr Int | Clinical features and outcomes of neonatal sepsis caused by resistant Gram-negative bacteria are not well described in Jordan. The aim of the present study was therefore to describe microbiology and clinical features, laboratory findings and outcomes of early- and late-onset Gram-negative neonatal sepsis.All patients with Gram-negative bacteremia between July 2003 and June 2005 were retrospectively included. Resistance profiles, clinical features and outcomes of early and late-onset neonatal sepsis were compared.A total of 79 patients (after excluding all nine cases of Gram-positive bloodstream infection (BSI) were identified as having Gram-negative BSI (25 had early-onset and 54 had late-onset neonatal sepsis). Respiratory distress, metabolic acidosis and requirement of ventilation were found in 74.7%, 40.5%, and 58.2%, respectively. Hypotension was found in 22.9% of patients. Klebsiella pneumoniae was responsible for 43 cases (54.4.2%). Klebsiella pneumoniae resistance rates to ampicillin and ceftazidime were 100% and 50%, respectively. Mortality rate was 30.9%. Forty-eight percent of deaths occurred within 3 days of sepsis. Meningitis was diagnosed in five cases. Elevated C-reactive protein (CRP) and thrombocytopenia were seen in 28% and 24% of infants with early-onset sepsis, respectively, and in 79.6%, 59.3% of infants with late-onset sepsis respectively.Both early- and late-onset neonatal sepsis are caused by highly resistant Gram-negative bacteria. Mortality of sepsis is high. Elevated CRP and thrombocytopenia is seen more commonly in late-onset neonatal sepsis. |
| 2009 | On-line hemodiafiltration in Southeast Asia: a three-year prospective study of a single center. | Ther Apher Dial | Growing evidence suggests the superiority of on-line hemodiafiltration (HDF) compared with the conventional hemodialysis technique in many aspects; however, on-line HDF is still not used worldwide, including in Southeast Asia. The purpose of this study is to compare various clinical outcomes between on-line HDF and high-flux hemodialysis (HFHD). This was a single-center three-year prospective observational study that demonstrated the clinical parameters after switching from HFHD to on-line HDF in 22 HDF patients, whose average age was 58.1 +/- 13.3 years. The incidence of intradialytic undesired events, including hypotension, decreased and an apparent increase in appetite and an improvement in overall well-being were recorded by most patients after switching to on-line HDF. The data for dry weight, body mass index, and normalized protein nitrogen appearance, which represent nutritional status, showed a significant improvement while still maintaining a satisfactory albumin level. The adequacy in terms of urea reduction ratio significantly increased. The serum predialysis beta(2)-microglobulin levels were reduced by 25.7% from 31.1 +/- 3.1 to 23.1 +/- 4.8 mg/L (P < 0.05) at six months and remained constant during the three years of follow-up. The patients' lipid profile was well controlled, and the mean C-reactive protein value was still maintained in the normal range. In conclusion, our three-year experience showed that on-line HDF is a well-tolerated treatment with a lower incidence of intradialytic undesired events. The potential benefits may include the effective removal of higher molecular weight uremic toxins and an improved nutritional status, along with a low inflammatory state. |
| 2009 | GYY4137, a novel hydrogen sulfide-releasing molecule, protects against endotoxic shock in the rat. | Free Radic Biol Med | GYY4137 (morpholin-4-ium-4-methoxyphenyl(morpholino) phosphinodithioate) is a slow-releasing hydrogen sulfide (H(2)S) donor. Administration of GYY4137 (50 mg/kg, iv) to anesthetized rats 10 min after lipopolysaccharide (LPS; 4 mg/kg, iv) decreased the slowly developing hypotension. GYY4137 inhibited LPS-induced TNF-alpha production in rat blood and reduced the LPS-evoked rise in NF-kappaB activation, inducible nitric oxide synthase/cyclooxygenase-2 expression, and generation of PGE(2) and nitrate/nitrite in RAW 264.7 macrophages. GYY4137 (50 mg/kg, ip) administered to conscious rats 1 or 2 h after (but not 1 h before) LPS decreased the subsequent (4 h) rise in plasma proinflammatory cytokines (TNF-alpha, IL-1beta, IL-6), nitrite/nitrate, C-reactive protein, and L-selectin. GYY4137 administration also decreased the LPS-evoked increase in lung myeloperoxidase activity, increased plasma concentration of the anti-inflammatory cytokine IL-10, and decreased tissue damage as determined histologically and by measurement of plasma creatinine and alanine aminotransferase activity. Time-expired GYY4137 (50 mg/kg, ip) did not affect the LPS-induced rise in plasma TNF-alpha or lung myeloperoxidase activity. GYY4137 also decreased the LPS-mediated upregulation of liver transcription factors (NF-kappaB and STAT-3). These results suggest an anti-inflammatory effect of GYY4137. The possibility that GYY4137 and other slow-releasing H(2)S donors exert anti-inflammatory activity in other models of inflammation and in humans warrants further study. |
| 2009 | Serum vascular endothelial growth factor in adult haematological patients with neutropenic fever: a comparison with C-reactive protein. | Eur J Haematol | Vascular endothelial growth factor (VEGF) is considered to be of importance in patients with sepsis. No data are available on VEGF kinetics in haematological patients with neutropenic fever.Forty-two haematological patients were included into this prospective study. Median age was 57 yr (range 18-70). Fifteen patients received therapy for acute myeloid leukaemia and 27 patients received autologous stem cell transplantation for haematological malignancy. Laboratory samples for the determination of C-reactive protein (CRP) and VEGF were collected at the start of fever (d0) and then daily.The median serum VEGF concentrations were low in all study patients. In patients with severe sepsis (n = 5) the median VEGF on d0 was higher than in septic patients without signs of hypoperfusion or hypotension (n = 37) (77 pg/mL vs. 52 pg/mL, P = 0.061). Also on d1 the median VEGF concentration was higher in patients with severe sepsis (82 pg/mL vs. 56 pg/mL, P = 0.048). There were no statistically significant differences in CRP values on any day during the study period between patients with severe sepsis and those without. Time from d0 to the peak VEGF concentration (mean 1.02, SE 0.18 d) was shorter than that to the peak CRP concentration (mean 1.93, SE 0.15 d) (P = 0.002).Compared to CRP, serum VEGF was a more rapid indicator for sepsis in our haematological patients with neutropenic fever. Those with severe sepsis had higher VEGF concentrations than those without on d0 and d1 after the onset of fever. Further studies on VEGF are warranted in haematological patients. |
| 2009 | Systemic inflammatory responses in dogs experimentally infected with Babesia canis; a haematological study. | Vet Parasitol | A detailed haematological study of dogs that were infected with low, moderate or high numbers of Babesia canis-infected red blood cells was performed in an attempt to elucidate the pathogenesis early after B. canis infection. Results showed that upon infection the C-reactive protein (CRP) level in plasma increased prior to the detection of parasites in the blood indicative of an acute phase reaction. The response was further characterised by fever, fibrinogenaemia, thrombocytopenia and leucopoenia. Thrombocytopenia was associated with increased coagulation time. Infected dogs also developed life threatening hypotension, and dogs that were infected with the highest dose of B. canis-infected red blood cells had to be treated chemotherapeutically. Hypotension was associated with a reduced packed cell volume (PCV). This reduction of PCV correlated with reduced plasma creatinin concentration, suggesting that the plasma volume was increased, affecting both the erythrocyte and creatinin concentration in the plasma. Importantly, the onset of the response but not the dynamics of the response was dependent on the infectious dose i.e. curves obtained with different doses of infected erythrocytes appeared to be shifted in time but had a similar shape. This indicates that infection triggered a preset inflammatory response. |
| 2009 | Severe hyponatraemia during therapy with ramipril. | BMJ Case Rep | An older patient who was being treated with ramipril, chlorpromazine and aspirin presented with hypotension and serum sodium of 119 mmol/litre. The patient was treated with intravenous saline and all drug therapy was stopped. Serum sodium rose following fluid therapy. Ramipril was restarted as the patient's blood pressure increased. Serum sodium dropped to 112 mmol/litre. The patient's thyroid and adrenal functions were within normal limits, as were liver function tests and C-reactive protein. The hyponatraemia corrected when the patient was placed on fluid restriction and treatment with ramipril stopped. |
| 2008 | A patient with penicillin-resistant viridans group streptococcal endocarditis and unusual reactions to vancomycin. | Southeast Asian J Trop Med Public Health | There is a paucity of data regarding the treatment of endocarditis caused by penicillin-resistant viridans group streptococci (PR-VGS). We report a 16-year-old girl who had native-valve endocarditis due to PR-VGS which was identified as Streptococcus mitis. She also had unusual reactions to vancomycin. Eighteen hours after initiation of 50 mg/kg/day vancomycin, she developed a maculopapular rash, then at 48 hours she developed an intermittent high fever and a progressive decrease in peripheral leukocytes and platelets. She developed hypotension on Day 8. Her serum C-reactive protein and procalcitonin levels were high. All reactions improved after vancomycin was discontinued and oral prednisolone was started. This unusual combination of reactions to vancomycin was likely caused by immune and nonimmune mechanisms. Her endocarditis was successfully treated with cefotaxime 200 mg/kg/ day for 4 weeks. |
| 2008 | Pediatric myth: fever and petechiae. | CJEM | A child presenting with petechiae and fever is assumed to have meningococcemia or another form of bacterial sepsis and therefore to require antibiotics, blood cultures, cerebrospinal fluid analysis and hospital admission. A review of the literature challenges this statement and suggests that a child presenting with purpura (or petechiae), an ill appearance and delayed capillary refill time or hypotension should be admitted and treated for meningococcal disease without delay. Conversely, a child with a petechial rash, which is confined to the distribution of the superior vena cava, is unlikely to have meningococcal disease. Outpatient therapy in this context is appropriate. In other children, a reasonable approach would be to draw blood for culture and C-reactive protein (CRP) while administering antibiotics. If the CRP is normal, these children could be discharged to follow-up in 1 day, whereas children with CRP values greater than 6 mg/L would be admitted. |
| 1998 | Regional administration of recombinant tumour necrosis factor-alpha in cancer, with special reference to melanoma. | BioDrugs | Recombinant tumour necrosis factor-alpha (rTNFalpha) possesses the unique property of activating and selectively destroying the tumour-associated microvasculature. Systemic application of rTNFalpha has shown that the maximum tolerated dose (MTD) is 10 times lower than the efficient dose in animals. The main toxicity corresponds to the systemic inflammatory response syndrome (SIRS), with a decrease of vascular resistance and hypotension. We found that it is possible to administer rTNFalpha at 10 times the MTD in an isolated limb perfusion system, using a heart-lung machine, for advanced melanoma and sarcoma of the limbs. Our results, using the combination of high dose rTNFalpha, interferon-gamma and melphalan (TIM), produced an overall objective response rate of 100% in 2 successive studies on melanoma, with 90% and 78% complete response, respectively. In sarcoma, there was an overall response rate of 64%, with 36% complete response. Angiographic and immunohistological studies demonstrated selective and early damage of the tumour-associated microvasculature, preceded by upregulation of adhesion molecules and intratumoural leak of von Willebrand factor. Tumour invasion by platelets and, in some cases, by polymorphonuclear cells, appeared within hours after the application of rTNFalpha, long before the lysis of the tumour. Systemic changes after rTNFalpha treatment included the production of soluble TNFalpha receptors and of interleukin-6. A typical acute phase reaction was observed within 3 days, with increase of C-reactive protein parallelled by an increase of tenascin-C. A selective effect on intratumoural endothelial cells seems to be involved in the mechanism of the impressive antitumour effect of rTNFalpha, but the role of acute phase protein production is not fully understood. In selected cases of melanoma, specific cytotoxic T lymphocytes were increased after perfusion. |
| 2007 | Admission clinical and laboratory factors associated with death in children with cancer during a febrile neutropenic episode. | Pediatr Infect Dis J | Early identification of children with cancer at risk for death during a febrile neutropenic (FN) episode may increase their possibility for survival. Our aim was to identify at the time of admission, clinical and laboratory variables differing significantly among children who survived or died during a FN episode.In a prospective, multicenter study, children admitted with a high-risk FN episode were uniformly evaluated at enrollment and managed according to a national consensus protocol. Medical charts of children who died were evaluated to determine whether the death could be associated with an infection. Admission clinical and laboratory variables significantly associated with death were identified.A total of 393 (70%) of 561 FN episodes evaluated from June 2004 to December 2005 were classified as high risk for invasive bacterial infection, of which 14 (3.6%) resulted in an infectious-related death. Deaths occurred from 2 to 27 days after admission, and most dying children were admitted with relapse of acute lymphocytic leukemia (36%), hypotension (71%), and a diagnosis of sepsis (79%), compared with surviving children (16%, 20%, and 5% respectively, P < 0.001). Children who died were admitted with lower absolute neutrophil count (P < 0.001) and absolute monocytes count levels (P = 0.008), higher blood urinary nitrogen (P = 0.03) and C-reactive protein values (P < 0.001), and had more positive cultures (79% versus 32%, P = 0.008).We identified early clinical and laboratory findings significantly associated with death occurring at a later stage. Routine evaluation of these variables may prove to be useful in the early identification of children with a high-risk FN episode at risk for death. |
| 2007 | Uraemic itching: do polymethylmethacrylate dialysis membranes play a role? | Nephrol Dial Transplant | Patients undergoing chronic renal replacement therapy by haemodialysis (HD) suffer from chronic itching, the prevalence of which is very high. Many of the available treatment options are ineffective, but, as it has been shown that Polymethylmethacrylate based dialysis membranes (PMMA) membranes remove a wide range of 'middle molecules' and improve such long-term complications of HD as carpal tunnel syndrome and malnutrition, they may also have an effect on uraemic itching.This prospective study enrolled eight patients undergoing standard HD with low-flux synthetic membranes and suffering from chronic itching. The strength and duration of itching was evaluated by the patients themselves at each study time-point using a visual analogue scale (VAS). After a baseline evaluation, the patients were switched to a PMMA membrane for 6 months during which their pre-dialysis haemoglobin, haematocrit, total protein, albumin, urea, creatinine, phosphate, intact parathyroid hormone (i-PTH), serum bile acid, beta2-microglobulin, C-reactive protein (CRP) levels, and eKt/V were measured, and any general complaints were recorded.The self-assessed VAS itching strength scores decreased by 15% after 1 month, 30% after 2 months, and 55% after 6 months, and itching duration decreased by, respectively, 10, 22 and 44% at the same time; 2 months after the end of the study, both scores had slightly increased. There were no statistically significant differences in the pre-dialysis blood chemistry values or eKt/V at the four study time-points, but beta2-microglobulin levels significantly decreased (P < 0.03); the decrease in CRP levels was not significant (P < 0.06). Furthermore, four patients showed a trend towards a lower incidence of intradialytic hypotension.These findings support the hypothesis that a PMMA dialyser may improve renal itching in ESRD patients. This effect is not mediated by increased dialysis efficiency or an improvement in other biochemical parameters, but we can speculate that ionic substances may be directly or indirectly adsorbed into the polymer composition of BG-U series (PMMA membrane dialyser). We are currently undergoing further studies using a proteomic approach. |
| 2006 | Underestimated abdominal vascular pathology in a patient with Takayasu arteritis. | Interact Cardiovasc Thorac Surg | To describe a 31-year-old female with symptomatic Takayasu disease who was operated for aortic valve replacement. Although she had no preoperative abdominal vascular symptoms, she died on the first postoperative day due to extensive ischemia bowel syndrome.Echocardiography and computed tomography revealed progressive dilatation and thickening of the ascending aorta, severe aortic regurgitation and diminished left ventricular function from 1998 onwards. In 2000 she was operated and a prosthesis was placed end-to-end distally of the sinutubular junction with combined reduction plasty of this junction. After the operation, in time echocardiography and computed tomography showed progressive irregularities and dilatation of the thoracoabdominal aorta and progressive aortic regurgitation. A staged approach of aortic valve replacement and surgery for the thoracoabdominal aorta was planned. At the time of the reoperation in September 2004 the Takayasu inflammation was, after treatment with a maintenance dosage of prednisone and imuran, in a relative quiescent phase. The aortic valve was uneventfully replaced by a mechanical valve.Medical treatment for Takayasu disease never resulted in the patient in completely normal blood values of white blood cell count, C-reactive protein or erythrocyte sedimentation rate. In August 2004, she was admitted because of severe non-specific thoracic pain and hypertension. During hypertension management, she had a short period of diplégia that was assumed to be due to periods of relapsed relative hypotension. Although the computed tomography revealed severe stenosis of the superior mesenteric artery and the celiac trunk, she was free of abdominal complaints and without further abnormal laboratory findings. One day after the aortic valve replacement a dramatic increase of transaminase and lactate-dehydrogenase with extreme metabolic acidosis appeared. Urgent abdominal surgery was performed and extensive ischemia of the liver, gallbladder, small intestine and the proximal part of the colon were found. Because of the extensive regions of ischemia, no surgical interventions were optional. The patient died one day after abdominal exploration.We conclude that in Takayasu disease scheduled for on pump cardiac surgery, vascular workup should be done, and interventional treatment of asymptomatic but potentially critical lesions should be considered. |
| 2007 | Delayed presentation of an isolated gallbladder rupture following blunt abdominal trauma: a case report. | J Med Case Rep | Blunt injuries to the gallbladder occur rarely, and the incidence of isolated damage to the gallbladder is even smaller. We report a case of delayed presentation of isolated rupture of the gallbladder following blunt trauma to the abdomen.A 65 year old lady presented through the Emergency Department with a 1 week history of blunt trauma to her abdomen. She complained of continued epigastric pain which radiated through to her back and right upper quadrant. On presentation, the patient had a low grade temperature, hypotension and mild tachycardia. Abdominal examination revealed right upper quadrant tenderness with no localised peritonism. C-reactive protein was 451. An abdominal CT showed a moderate amount of ascitic fluid in the perihepatic space. The patient underwent a laparotomy, which revealed a ruptured gallbladder with free bile. There was no evidence of any associated injuries to the surrounding organs. Partial cholecystectomy was done in view of the friable nature of the gallbladder. Post operatively, a persistent bile leak was managed successfully with endoscopic sphincterotomy and stenting.Rupture of the gallbladder due to blunt injuries to the abdomen occurs from time to time and may constitute a diagnostic challenge especially with delayed presentation. Partial cholecystectomy is a safe option in cases where friability of the wall renders formal cholecystectomy inadvisable. Endoscopic sphincterotomy and stenting is a safe and effective treatment for persistent post operative bile leaks. |
| 2007 | [Toxic shock syndrome: experience in a pediatric intensive care unit]. | An Pediatr (Barc) | To review patients with toxic shock syndrome (TSS) in a pediatric intensive care unit.We performed a retrospective study of patients with TSS admitted to the intensive care unit in the previous 15 years. The patients included were those that met the clinical and microbiological criteria for TSS proposed by the Centers for Disease Control and Prevention.There were nine patients (four boys). The mean age was 7 years. The most frequent findings were fever (100 %), hypotension (100 %), erythroderma (100 %), multisystem organ failure [coagulopathy (100 %), lethargy (89 %), hypertransaminasemia (89 %), increased creatine phosphokinase levels (78 %), renal failure (66 %)] and cutaneous desquamation (100 %). Laboratory studies showed changes in the leukocyte count and C-reactive protein value in all patients. The etiology was as follows: Staphylococcus was detected in six patients (S. epidermidis in three and S. aureus in three) and Streptococcus was detected in two patients (S. pyogenes in one and S. pneumoniae in one); no microorganisms were detected in only one patient. The origin of the infection was identified in seven patients (cutaneous in six patients and tonsillar in one). All patients received life support and antibiotic treatment. Six patients received corticosteroid treatment and one received intravenous immunoglobulins. Patients with TSS secondary to Streptococcus showed the greatest severity, exhibiting renal failure and requiring greater respiratory and circulatory support. All patients recovered well from the infection, without serious long-term sequelae. CONCLUSION. TSS should be included in the differential diagnosis of patients with fever, exanthema and shock, since early diagnosis has been shown to improve outcomes. S. pneumoniae should be included among the microorganisms that cause TSS. Treatment is based on life support measures and antibiotic therapy. |
| 2007 | Lactate dehydrogenase as a prognostic factor for survival time of terminally ill cancer patients: a preliminary study. | Eur J Cancer | This study evaluated lactate dehydrogenase (LDH) as a prognostic factor for survival time in terminal cancer patients. We prospectively followed 93 consecutive inpatients with terminal cancer in one general hospital. Cox's proportional hazard model was used to adjust the influence of some clinical and laboratory variables on survival time. For 25 patients, LDH levels at 2 weeks and 1 week before death were compared by paired t test. In multivariate analysis, elevated LDH level (313 IU/L) was confirmed as an unfavourable indicator for survival time (hazard ratio=2.087, p=0.002). Serum LDH levels were significantly increased as the patients approached death. A combined index comprising LDH levels, C reactive protein levels, uric acid levels, presence of moderate to severe pain, fatigue, hypotension and performance status demonstrated a good stratification value for predicting survival time. Our results showed that serum LDH level can be a useful predictor of survival time of terminally ill cancer patients. |
| 2007 | [Low-doses dobutamine and fluids in high-risk surgical patients: effects on tissue oxygenation, inflammatory response and morbidity]. | Rev Bras Ter Intensiva | Dobutamine is an inotropic agent with predominant beta1- adrenergic properties frequently used to increase blood flow in critically ill patients. Dobutamine may have a role in increasing splanchnic perfusion, thereby protecting this area from further injury. We investigated the effects of low doses dobutamine (5 mug/kg/min) on tissue oxygenation, inflammatory response and postoperative complications in high-risk surgical patients.Prospective, randomized, blinded and placebo-controlled study. One hundred surgical patients admitted in a step-down unit were evaluated and 82 patients were enrolled, 42 in the control group (saline) and 40 in the treatment group (5 mug/kg/h) during 24 hours. Similar therapeutic goals were applied to both groups. Fluids were given whenever tachycardia or hypotension developed after study drug infusion.The total volume of fluids given was significantly higher in treatment than in control group (7351 ± 2082 mL versus 6074 ± 2386 mL, respectively, p < 0.05). Central venous oxygen saturation (ScvO2), serum lactate and C-reactive protein were similar in both groups. Complications occurred in 35% and 50% of the patients in the treatment and control groups, respectively (RR 0, 70 IC 95% 0.41 - 1.17; NS).Low-doses dobutamine and fluids after surgical trauma has no effects on the prevalence of postoperative complications in high-risk surgical patients. |
| 2006 | Severe acute pancreatitis--outcome following a primarily non-surgical regime. | Pancreatology | Severe acute pancreatitis (SAP) is associated with a high morbidity and mortality. The aim was to evaluate treatment, risk factors and outcome in SAP in a centre with a restrictive attitude to surgery.All cases of acute pancreatitis admitted 1994-2003 were analysed retrospectively. SAP was defined as organ failure and/or hospital stay >7 days together with one or more of: C-reactive protein >150 mg/l within 72 h after admission, necrosis on computed tomography and need for treatment in the intensive care unit.185 (22%) of patients with acute pancreatitis fulfilled the criteria for SAP. 175 patients were included, mean age 61 +/- 17 years. Hospital stay was in median 13 days. Forty-six patients had some surgical intervention, in 14 cases directed at the pancreas (8%). Hospital mortality was 9% (n = 16), in 88% (n = 14) associated with multiple organ dysfunction and 50% (n = 8) of the deaths occurred within the first week after admission. Of the parameters registered on admission, age and hypotension (systolic blood pressure <100 mm Hg) were identified as risk factors for death.The present treatment regime for SAP as defined above resulted in a 9% mortality rate, with age and hypotension at admission as predictive factors for death. |
| 2006 | Values of C-reactive protein, procalcitonin, and Staphylococcus-specific PCR in neonatal late-onset sepsis. | Acta Paediatr | To evaluate the predictive value of relevant clinical and laboratory parameters (complete blood count (CBC), C-reactive protein (CRP), procalcitonin (PCT) and Staphylococcus-specific polymerase chain reaction (PCR)) in neonates with suspected late-onset sepsis (LOS).NICU neonates were prospectively followed for septic events. One hundred and eleven neonates developed 148 suspected septic events beyond 3 d of age. We recorded the clinical signs and laboratory abnormalities at onset of sepsis, serum CRP and PCT, Staphylococcus-specific PCR, microbiological data, and empiric antimicrobial therapy.Variables significantly associated with subsequently confirmed LOS included hypotension (relative risk (RR) = 5.6, 95% CI 3.29-9.53), mechanical ventilation (RR = 2.46, 95% CI 1.24-4.86), immature/total neutrophil ratio (I/T) > 0.2 (RR = 5.13, 95% CI 2.54-10.31), CRP > 1.0 mg/dl (RR = 2.85, 95% CI 1.32-6.15), and small-for-gestational-age (SGA) status (RR = 2.13, 95% CI 1.03-4.38). PCT was not significantly associated with LOS. For detection of staphylococcal bacteremia, Staphylococcus-specific PCR showed: sensitivity 57.1%, specificity 94.7%, positive predictive value 53.3%, and negative predictive value 95.4%.Hypotension, mechanical ventilation, I/T > 0.2, CRP > 1.0 mg/dl, and SGA status at onset of sepsis are significant predictors of proven neonatal LOS. Staphylococcus-specific PCR might be of value in ruling out staphylococcal sepsis. |
| 2006 | Macrophage serum markers in pneumococcal bacteremia: Prediction of survival by soluble CD163. | Crit Care Med | Soluble CD163 (sCD163) is a new macrophage-specific serum marker. This study investigated sCD163 and other markers of macrophage activation (neopterin, ferritin, transcobalamin, and soluble urokinase plasminogen activator receptor [suPAR]) as prognostic factors in patients with pneumococcal bacteremia.Observational cohort study.Five university hospitals in Denmark.A total of 133 patients with Streptococcus pneumoniae bacteremia (positive blood culture) and 133 age- and gender-matched controls.Samples were collected for biochemical analyses at the time of first positive blood culture.sCD163 was highly correlated with other macrophage markers and was significantly elevated (median [25-75 percentiles], 4.6 mg/L [2.8-8.9]) compared with healthy controls (2.7 mg/L [2.1-3.3], p < .0001). Increased levels were observed in patients who needed intensive care (hemodialysis, p = .0011; hypotension, p = .0014; mechanical ventilation, p = .0019). Significantly lower levels of sCD163, ferritin, transcobalamin, and suPAR (but not C-reactive protein) were measured in patients > or =75 yrs. In patients <75 yrs, all macrophage markers were increased in patients who died from their infection compared with survivors, whereas no change was observed in any of the markers in the very old age. At cutoff levels of 9.5 mg/L (sCD163) and 1650 nmol/L (C-reactive protein), the relative risk for fatal outcome in patients <75 yrs was 10.1 (95% confidence interval 3.4-31.0) and 7.0 (95% confidence interval 2.4-21.6) for sCD163 and C-reactive protein, respectively. In a multivariate logistic regression model for patients <75 yrs, ferritin, transcobalamin, neopterin, and suPAR contained no significant information on the probability of survival when sCD163 and CRP were known (p = .25).Macrophage marker response in pneumococcal bacteremia was compromised in old age. In patients <75 yrs old, sCD163 was superior to other markers, including C-reactive protein, in predicting fatal disease outcome. |
| 2006 | Early prognostic factors in patients with acute renal failure requiring dialysis. | Ren Fail | Despite improvements in renal therapy and technology, the mortality rate of patients with acute renal failure (ARF) remains high. Because ARF is a heterogeneous syndrome, occurring in patients with diverse etiologies and comorbid conditions, predicting its outcome is difficult. This study aims to identify early clinical and laboratory prognostic factors, including acute-phase reactants such as C-reactive protein (CRP), fibrinogen, and albumin, in ARF patients requiring dialysis.From June 2002 to March 2004, 61 patients with ARF requiring dialysis at Chang Gung Memorial Hospital, Chiayi, were prospectively analyzed. For each patient, the worst values of prognostic variables 24 hr before starting dialysis were prospectively assessed.Oliguria, low plasma fibrinogen levels, hypotension, cardiac disease, and neoplastic disease were statistically significant in predicting hospital mortality. Using Youden's index, the best cut-off value for plasma fibrinogen in predicting mortality was 300 mg/dL with a sensitivity and specificity of 61% and 96%, respectively. Serum CRP and serum albumin were not predictive of hospital mortality.Early prognostic factors in predicting mortality for patients with ARF requiring dialysis identified by multivariate logistic regression were oliguria, low plasma fibrinogen, hypotension, cardiac disease, and neoplastic disease. Serum CRP and albumin were not predictive of hospital mortality, whereas a plasma fibrinogen level < or =300 mg/dL had 61% sensitivity and 96% specificity in predicting mortality. |
| 2005 | Vascular dementia prevention: a risk factor analysis. | Cerebrovasc Dis | Brain injury from ischemic or hemorrhagic cerebrovascular disease (CVD) produces decline in cognitive functions and vascular dementia (VaD). Likewise, CVD may cause VaD from hypoperfusion of susceptible brain areas. CVD may also worsen degenerative dementias such as Alzheimer's disease. Significant advances have been made in the identification and control of risk factors for stroke and cardiovascular disease. The main risk factors for VaD include age, hypertension and absence of antihypertensive medication, diabetes, cigarette smoking, history of cardiovascular disease (coronary heart disease, congestive heart failure, peripheral vascular disease), atrial fibrillation, left ventricular hypertrophy, hyperhomocysteinemia, orthostatic hypotension, cardiac arrhythmias, hyperfibrinogenemia, and sleep apnea. Recently identified risk factors include chronic infection and elevation of C-reactive protein, particularly in patients with diabetes. Evidence from controlled clinical trials strongly suggests that control of vascular risk factors, in particular hypertension, could prevent the development of dementia. |
| 2005 | Inflammatory markers and hepatocyte growth factor in sustained hemodialysis hypotension. | Artif Organs | Hypotension is an important complication of hemodialysis. The pathogenesis of this complication remains unclear. The role of chronic inflammation in chronic dialysis-associated hypotension has not been investigated. A total of 38 dialysis patients with chronic hypotension were identified. Their demographic and biochemical data, inflammatory markers (high sensitivity C-reactive protein [hs-CRP] and interleukin-6 [IL-6]), hepatocyte growth factor (HGF), leptin, and adiponectin levels were measured and compared with those of another 87 nonhypotensive dialysis patients. No between-group differences in their clinical features, underlying renal disease were found. Levels of serum albumin, leptin, adiponectin, and HGF were similar between the two groups. The serum albumin levels were inversely correlated with hs-CRP and IL-6. Adiponectin was negatively correlated with hs-CRP and leptin. HGF showed a positive relation with hs-CRP. No association was found between adiponectin and HGF. Therefore, chronic inflammation is prevalent in the dialysis population, and serum HGF level is associated with inflammation but not with chronic dialysis hypotension. |
| 2005 | Hepatic over-expression of TGF-beta1 promotes LPS-induced inflammatory cytokine secretion by liver cells and endotoxemic shock. | Immunol Lett | Transforming growth factor-beta (TGF-beta) is an important suppressor of inflammation. However, TGF-beta has also been found to promote secretion of inflammatory cytokines, and transgenic mice, which constitutively express TGF-beta in liver, have been found to be more susceptible to endotoxemia. To approach this apparent paradox, we investigated the role of hepatic TGF-beta1 in endotoxemia by utilising inducible TGF-beta1-transgenic mice that express TGF-beta1 under control of the C-reactive protein promoter. In contrast to non-transgenic littermates, administration of lipopolysaccharide (LPS) induced strongly increased expression of TGF-beta and acute phase proteins in the TGF-beta1-transgenic mice. Hepatic TGF-beta1-expression in the transgenic mice started an inflammatory cytokine cascade, marked by increased and prolonged secretion of TNF-alpha and IL-6 by hepatocytes. The inflammatory response of the TGF-beta1-transgenic mice to LPS was associated with high rates of mortality due to endotoxemic shock, marked by systemic hypotension and hypothermia. Endotoxemic shock was primarily mediated by TNF-alpha and IL-6, since inhibitory antibody to TNF-alpha or, more effectively, to IL-6 could reduce mortality in these mice. In conclusion, while TGF-beta-signalling to immune cells may suppress inflammatory effector function, TGF-beta-signalling to liver cells seems to promote LPS-stimulated secretion of inflammatory cytokines and to predispose for lethal endotoxemic shock. |
| 2005 | Hemorrhagic fever with renal syndrome in the Pomurje region of Slovenia--an 18-year survey. | Wien Klin Wochenschr | To determine the etiology of hemorrhagic fever with renal syndrome (HFRS) in the north-eastern part of Slovenia (Pomurje region) together with demographic, epidemiological and clinical data on 25 patients from this region who were diagnosed and treated at the General Hospital in Murska Sobota between 1986 and 2003.Medical records of patients with a discharge diagnosis of HFRS who were either hospitalized or referred to an infectiologist as outpatients were included in this retrospective study. Data on demographic characteristics, clinical manifestations and laboratory parameters were collected from the patients' records. In addition, all available follow-up records were examined and information on general health, blood pressure, basic blood and biochemical examination and urine analysis was collected.Infection with Puumala virus (PUUV) was indicated in 23 patients and Dobrava virus (DOBV) infection in two patients. The median age of patients was 39 years; 19 were male. The patients primarily had outdoor occupations. Most of the HFRS cases occurred between May and August. The most common findings were fever, vomiting, headache, myalgia, chills, cough, back and abdominal pain, and blurred vision. The most prominent laboratory abnormalities were elevated erythrocyte sedimentation rate and C-reactive protein concentration, thrombocytopenia, and leucocytosis with neutrophilia. The signs of renal dysfunction were observed in 24 of the 25 patients. Oliguric renal failure was seen in 13 of 23 (57%) PUUV-infected patients. Six of 23 (26%) patients infected with PUUV and one of two (50%) patients from the DOBV group had hypotension or developed signs of shock. Seven out of 15 (47%) patients had elevated protein concentration in cerebrospinal fluid (CSF). Sinus bradycardia was documented in 7 of 17 (41%) patients with PUUV infection.HFRS is endemic in the north-eastern part of Slovenia; PUUV and DOBV infections coexist, with PUUV being the main causative agent of HFRS. Demographic, clinical and laboratory findings in our patients with HFRS caused by PUUV were mostly in accordance with those published previously, but the ratio of patients with sinus bradycardia, oliguric renal failure and mildly elevated CSF protein concentration was rather high. |
| 2004 | Vascular dementia. Advances in nosology, diagnosis, treatment and prevention. | Panminerva Med | Ischemic or hemorrhagic cerebrovascular disease (CVD) produces injury of brain regions important for executive function, behavior, and memory leading to decline in cognitive functions and vascular dementia (VaD). Cardiovascular disease may cause VaD from hypoperfusion of susceptible brain areas. CVD may worsen degenerative dementias such as Alzheimer disease (AD). Currently, the global diagnostic category for cognitive impairment of vascular origin is vascular cognitive disorder (VCD). VCD ranges from vascular cognitive impairment (VCI) to VaD. The term VCI is limited to cases of cognitive impairment of vascular etiology, without dementia; VCI is equivalent to vascular mild cognitive impairment (MCI). Risk factors for VaD include age, hypertension, diabetes, smoking, cardiovascular disease (coronary heart disease, congestive heart failure, peripheral vascular disease), atrial fibrillation, left ventricular hypertrophy, hyperhomocysteinemia, orthostatic hypotension, cardiac arrhythmias, hyperfibrinogenemia, sleep apnea, infection, and high C-reactive protein. Research on biomarkers revealed increased CSF-NFL levels in VaD, whereas CSF-tau was normal. CSF-TNF-alpha, VEGF, and TGF-beta were increased in both AD and VaD. VaD shows low CSF acetylcholinesterase levels. This condition responds to acetylcholinesterase inhibitors, confirming the central role of cholinergic deficit in its pathogenesis. Evidence strongly suggests that control of vascular risk factors, in particular hypertension, could prevent VaD. |
| 2005 | [Procalcitonin as a marker for severe sepsis in an immunosuppressed patient]. | Anasthesiol Intensivmed Notfallmed Schmerzther | A 22 year old female was admitted to the emergency department with high fever up to 41,5 degrees C, tachycardia, and arterial hypotension. Clinically, she presented with bilateral pulmonary coarse crackles. Diagnosis on admission was pneumonia with septic shock. Intriguingly, procalcitonin (PCT) was increased early, reaching up to 435 ng/mL, while C-reactive protein levels were only moderately increased, with several days delay. The sepsis was originated from a multi-resistant pseudomonas aeruginosa pneumonia. Remarkably, the course of PCT levels reflected the severity of septic shock in that it paralleled noradrenaline demand. Ten months previously, the patient had been diagnosed with acute disseminated brainstem encephalitis (ADEM), and had received two cycles of intravenous cyclophosphamide. Our case illustrates that PCT is an early marker for sepsis and it indicates that PCT may also be a valuable marker for the severity of sepsis in immunosuppressed patients. |
| 2005 | Role of carnitine in modulating acute-phase protein synthesis in hemodialysis patients. | J Ren Nutr | Increased serum levels of C-reactive protein (CRP) in uremic and dialysis patients are associated with low serum prealbumin and albumin concentrations and increased mortality and greater risk of cardiovascular disease. Proinflammatory cytokines may cause malnutrition by increasing protein catabolism. Many studies have shown that L-carnitine supplementation leads to improvements in several conditions seen in uremic patients, including cardiac complications, impaired exercise and functional capacities, muscle symptoms, increased symptomatic intradialytic hypotension, and erythropoietin-resistant anemia. L-carnitine therapy may either suppress the inflammatory response or act independently on both inflammation and appetite and/or anabolic processes. Moreover, L-carnitine may suppress proinflammatory cytokines in sick individuals without renal disease and may improve protein synthesis or nitrogen balance in patients without renal disease and in hemodialysis and peritoneal dialysis patients. In a pilot study, we provided preliminary evidence that treatment with L-carnitine, 20 mg/kg 3 times weekly at the end of each hemodialysis treatment, was associated with a reduction in serum CRP levels and improvement in anabolic status. The improvement or normalization of serum concentrations of serum CRP also was correlated with increased serum concentrations of albumin, transferrin, and blood hemoglobin. The possibility that some or all of these changes may have been caused by improved nutritional intake cannot be ruled out. Further randomized clinical trials will be necessary to confirm the role of L-carnitine as a modulator of inflammatory protein synthesis in hemodialysis patients. |
| 2004 | Plasma endothelin-1 and clinical manifestations of neonatal sepsis. | J Perinat Med | To determine whether plasma endothelin-1 (ET-1) relates to clinical manifestations of sepsis in the newborn, especially with systemic hypotension, acidosis, severe hypoxemia (which may represent pulmonary hypertension) and oliguria.Prospective study of 35 consecutive newborns with clinical sepsis: 22 with hemoculture-positive (HC+) sepsis and 13 hemoculture-negative (HC-). Plasma ET-1 concentrations were measured within 2 days of the diagnosis of sepsis. SNAP-II severity score was performed at the time of highest clinical severity.Newborns with HC+ sepsis had higher plasma ET-1 concentrations and SNAP-II scores (especially PO 2 /FiO 2 ratio) than HC- septic children. Plasma ET-1 concentrations increased linearly with each item of the SNAP-II score, but only reached significant differences in lowest mean blood pressure (P=0.030), lowest pH (P=0.048), multiple seizures (P=0.010) and lowest urine output (P=0.013). Leukocyte count, immature/total neutrophil ratio and C-reactive protein value were not different. Each item of the SNAP-II score was independently related only to ET-1 level. Oliguria, acidosis and systemic hypotension were more correlated (R 2 >0.5).Plasma ET-1 levels in neonatal sepsis are related to the severity of clinical manifestations, especially oliguria, acidosis and systemic hypotension. |
| 2004 | Carnitine system in uremic patients: molecular and clinical aspects. | Semin Nephrol | Carnitine is a small water-soluble molecule that is present in almost all animal species. It plays an indispensable role in fatty acid metabolism, where it is involved in the transport of activated fatty acids between different cellular compartments. Uremic patients, as well as patients with chronic renal failure, appear to have abnormal renal handling of carnitine leading to dyslipidemia, lethargy, muscular weakness, hypotension, cardiac dysfunction and arrhythmias, and recurrent cramps. It often is difficult to distinguish these symptoms from similar ones related to uremia and dialysis. Many investigators have advocated L-carnitine supplementation in an attempt to alleviate carnitine deficiencies, and good results from this therapy have been reported. Moreover, several studies have shown that L-carnitine supplementation improves the response to erythropoietin. Chronic inflammation is another particular aspect affecting these patients. Anti-inflammatory properties of L-carnitine in hemodialysis patients have been shown by our group. Treatment with L-carnitine (20 mg/kg, given intravenously at the end of each dialysis session for 6 mo), significantly decreased serum C-reactive protein (CRP) levels, a proinflammatory cytokine known to inhibit erythropoiesis. Moreover, data from published literature are indicative of L-carnitine modulation of the immune system by the activation of glucocorticoid receptors and the modulation of the transcription of glucocorticoid-responsive genes. Our study showed that in these patients, treatment with L-carnitine has been able to improve their body mass index, likely by promoting a positive protein balance. This aspect is strictly correlated with the status of insulin resistance, which is well described in patients with renal diseases. Many studies showed that carnitine allowed mitochondrial fatty acid usage to link to the rate of glucose usage, thus improving insulin resistance. In conclusion, clinical beneficial effects of L-carnitine treatment on patients suffering from renal diseases are supported by molecular evidence involving both inflammatory and metabolic aspects of the disease. |
| 2004 | The plasma level of soluble urokinase receptor is elevated in patients with Streptococcus pneumoniae bacteraemia and predicts mortality. | Clin Microbiol Infect | This multicentre prospective study was conducted to investigate whether the level of the soluble form of urokinase-type plasminogen activator receptor (suPAR) is elevated during pneumococcal bacteraemia and is of predictive value in the early stage of the disease. Plasma levels of suPAR were increased significantly (median 5.5; range 2.4-21.0 ng/mL) in 141 patients with pneumococcal bacteraemia, compared to 31 healthy controls (median 2.6, range 1.5-4.0 ng/mL, p 0.001). Furthermore, suPAR levels were elevated significantly in patients who died from the infection (n = 24) compared to survivors (n = 117; p < 0.001). No correlation was found between suPAR levels and C-reactive protein. In univariate logistic regression analysis, hypotension, renal failure, cerebral symptoms and high serum concentrations of protein YKL-40 and suPAR were associated significantly with mortality (p < 0.05). In multivariate analysis, only suPAR remained a significant predictor of death (mortality rate of 13 for suPAR levels of > 10 ng/mL; 95% CI: 1.1-158). The increase in suPAR levels may reflect increased expression by vascular or inflammatory cells in the setting of pneumococcal sepsis. This plasma protein may be used to identify patients who are severely ill with pneumococcal bacteraemia. |
| 2004 | The prognostic virtue of inflammatory markers during late-onset sepsis in preterm infants. | J Perinat Med | Late-onset sepsis (occurring after the first three days of life) is a serious complication in preterm infants. In order to assess the possible prognostic virtues of the acute phase inflammatory response in the disease, we compared the inflammatory response of preterm infants who died within 72 hours (h) (fulminant sepsis) to infants who recovered from the disease (non-fulminant sepsis).Of 42 preterm infants that were evaluated: 10 had fulminant sepsis and 32 non-fulminant sepsis. Acute phase inflammatory response markers-C-reactive protein (CRP), serum amyloid A (SAA), interleukin (IL)-6 levels and white blood cell (WBC) counts were measured at the first suspicion of LOS and after 8, 24 and 48 h.Small for gestational age (SGA) infants who were treated with fewer days of antibiotics characterized the fulminant sepsis group. The initial high levels of inflammatory markers were similar in both groups, but as early as 8 h after onset significantly lower levels of SAA, CRP and WBC counts were documented in the fulminant sepsis group. The inflammatory response remained low at 24 and 48 h in the fulminant sepsis group, while in the survivors, significantly increased inflammatory markers were measured. Decreases in the levels of the inflammatory markers preceded episodes of metabolic acidosis and arterial hypotension that were more common in the fulminant sepsis group. Infant mortality correlated inversely with SAA levels at 8 h and with CRP and WBC counts at 24 h after onset.SAA, CRP and WBC counts can be used as prognostic markers in LOS in preterm infants, with SAA being the earliest prognostic marker. |
| 2004 | Gram-negative bacteraemia (GNB) after 428 unrelated donor bone marrow transplants (UD-BMT): risk factors, prophylaxis, therapy and outcome. | Bone Marrow Transplant | Gram-negative infection is an important cause of morbidity and mortality after unrelated donor-bone marrow transplantation (UD-BMT). We performed a retrospective case-control study to examine the risk factors, prophylaxis, therapy and outcome of Gram-negative bacteraemia (GNB) in 428 patients undergoing UD-BMT. The incidence of GNB was 3.6% in children and 19% in adults. Of the adults, 11% developed GNB >60 days post UD-BMT. Predisposing risk factors for GNB included 'high-risk' disease status, chronic graft-versus-host disease and use of systemic steroids. Fever, a raised C-reactive protein (CRP) and hypotension were common findings at presentation. Patients were routinely given prophylactic ciprofloxacin: resistance to this antibiotic was seen in 33% of isolates. We identified an age-matched control group undergoing UD-BMT over the same time period as the study group. Gram-positive bacteraemia was significantly more common in cases than controls. Mortality from GNB was 17% in children and 24% in adults. We conclude that GNB is a common complication of UD-BMT with a high associated mortality. Patients should be educated further to present rapidly with symptoms suggestive of infection. |
| 2003 | A phase I study of recombinant human leukemia inhibitory factor in patients with advanced cancer. | Clin Cancer Res | Leukemia inhibitory factor (LIF) is a pleiotropic molecule of the interleukin 6 family of cytokines. We aimed to examine the safety, pharmacokinetics, and biological effects of recombinant human LIF (rhLIF, emfilermin) in patients with advanced cancer.In stage 1 of the study, 34 patients received rhLIF or placebo (3:1 ratio) at doses of 0.25-16.0 micro g/kg/day or 4.0 micro g/kg three times daily for 7 days. In stage 2, 40 patients received rhLIF or placebo, either once daily for 14 days commencing the day after chemotherapy (0.25-8.0 micro g/kg/day) or for 7 days commencing the day before chemotherapy (4.0 micro g/kg three times daily). The chemotherapy was cisplatin 75 mg/m(2) and paclitaxel 135 mg/m(2).In stage 1, platelet counts increased in most patients, including those who received placebo. Blood progenitor cells increased in response to rhLIF. In stage 2, platelet recovery to baseline levels was earlier for patients receiving higher doses of rhLIF (>/=4.0 micro g/kg/day; P = 0.02). The neutrophil nadir after chemotherapy was less severe in patients receiving >/=4.0 micro g/kg/day of rhLIF. In stages 1 and 2, increases in C reactive protein were seen at higher doses. Several patients developed evidence of autonomic dysfunction, in particular impotence and episodic hypotension. The dose-limiting toxicities were hypotension and rigors. Pharmacokinetic studies demonstrated a short half-life (1-5 h) independent of dose.We demonstrated a biological effect of rhLIF on blood progenitor cells, C reactive protein levels, and hemopoietic recovery after chemotherapy. |
| 2003 | Bioartificial kidney ameliorates gram-negative bacteria-induced septic shock in uremic animals. | J Am Soc Nephrol | The bioartificial kidney (BAK) consists of a conventional hemofiltration cartridge in series with a renal tubule assist device (RAD) containing 10(9) porcine renal proximal tubule cells. BAK replaces filtration, transport, and metabolic and endocrinologic activities of a kidney. Previous work in an acutely uremic dog model demonstrated that BAK ameliorated endotoxin (lipopolysaccharide [LPS])-induced hypotension and altered plasma cytokine levels. To further assess the role of BAK in sepsis in acute renal failure, dogs were nephrectomized and 48 h later administered intraperitoneally with 30 x 10(10) bacteria/kg of E. coli. One hour after bacterial administration, animals were placed in a continuous venovenous hemofiltration circuit with either a sham RAD without cells (n = 6) or a RAD with cells (n = 6). BP, cardiac output, heart rate, pulmonary capillary wedge pressure, and systemic vascular resistance were measured throughout the study. All animals tested were in renal failure, with blood urea nitrogen and serum creatinine concentrations greater than 60 and 6 mg/dl, respectively. RAD treatment maintained significantly better cardiovascular performance, as determined by arterial BP (P < 0.05) and cardiac output (P < 0.02), for longer periods than sham RAD therapy. Consistently, all sham RAD-treated animals, except one, expired within 2 to 9 h after bacterial administration, whereas all RAD-treated animals survived more than 10 h. Plasma levels of TNF-alpha, IL-10, and C-reactive protein (CRP) were measured during cell RAD and sham RAD treatment. IL-10 levels were significantly higher (P < 0.01) during the entire treatment interval in the RAD animals compared with sham controls. These data demonstrated in a pilot large animal experiment that the BAK with RAD altered plasma cytokine levels in acutely uremic animals with septic shock. This change was associated with improved cardiovascular performance and increased survival time. These results demonstrate that the addition of cell therapy to hemofiltration in an acutely uremic animal model with septic shock ameliorates cardiovascular dysfunction, alters systemic cytokine balance, and improves survival time. |
| 2002 | Efficacy and safety of G-CSF mobilized granulocyte transfusions in four neutropenic children with sepsis and invasive fungal infection. | Infection | Bacterial and fungal infections are serious complications of cancer therapy. Especially during longstanding neutropenia, patients are at risk for life-threatening infections. The aim of this study was to assess the effect and safety of G-CSF mobilized granulocyte transfusions (GTX) in four neutropenic pediatric patients with sepsis.The patients were between 4.6-17.5 years old and their diagnoses included very severe aplastic anemia, non-Hodgkin's lymphoma (NHL) and acute myeloid leukemia. Before GTX, all patients had fever despite antibiotic and antimycotic therapy, neutropenia (absolute neutrophil count ANC < 500/microl), increasing C-reactive protein (CRP) values, hypotension requiring dopamine infusion and three patients needed supplemental oxygen. The granulocyte donors received G-CSF (Neupogen, 5 microg/kg body weight) 12 h prior to granulocyte apheresis.In total, 40 GTX were performed (range 2-28 per patient). The mean increase of the granulocyte count 1 h after GTX was 1,310/microl (range 200-2,950/microl). Within the period of GTX the CRP values decreased in all patients. During or 24 h after the last GTX, the hypotension resolved and supplemental oxygen was stopped. One GTX was discontinued because of oxygen desaturation.GTX were a safe therapeutic measure with beneficial effects on serious infections in neutropenic children. |
| 2002 | Prospective evaluation of a model of prediction of invasive bacterial infection risk among children with cancer, fever, and neutropenia. | Clin Infect Dis | A risk prediction model for invasive bacterial infection (IBI) was prospectively evaluated among children presenting with cancer, fever, and neutropenia. The model incorporated assessment of 5 previously identified risk factors: serum level of C-reactive protein (CRP) >/=90 mg/L, hypotension, identification of relapse of leukemia as the cancer type, platelet count of |
| 2001 | The bradykinin response and early hypotension at the introduction of continuous renal replacement therapy in the intensive care unit. | Artif Organs | We assessed the relationship of certain clinical variables (including bradykinin [BK] release and dialysis membrane) to initial mean arterial pressure (MAP) reduction in 47 patients requiring continuous renal replacement therapy (CRRT) in an intensive care unit. The pretreatment MAP was 84 +/- 14 mm Hg for the group as a whole. The initial MAP reduction was 11.5 (7-20) mm Hg, occurring 4 to 8 min after connection. MAP reduction was 9 (6-15) mm Hg with polyacryonitrile (PAN) membranes versus 14 (5-19) mm Hg with polysulfone (PS) (not significant). There were positive correlations between MAP reduction and BK concentration at 3 (BK3; r = 0.58, p < 0.01) and 6 (BK6; r = 0.67, p < 0.001) min with PAN but not with PS. A greater reduction in MAP was seen in patients who were not receiving inotropic support (Mann-Whitney test, p < 0.01). BK3 and BK6 values for the PAN and PS groups were not significantly different. However, BK concentrations greater than 1,000 pg/ml were only seen with PAN (6 patients, MAP reduction 27 [17-31] mm Hg). There were positive (albumin) and negative (age; acute physiology, age, and chronic health evaluation score; C-reactive protein [CRP]; calcium) correlations with BK3/BK6 in the PAN and PS groups, some of which (albumin, CRP) reached statistical significance. In summary, MAP reduction at the start of CRRT correlates with BK concentration. The similarity of response with PAN and PS suggests an importance for other clinical factors. In this study, hemodynamic instability was more likely in patients with evidence of a less severe inflammatory or septic illness. |
| 2001 | A potential role for immune activation in hemodialysis hypotension. | Ren Fail | The necessary exposure of blood to biomembranes during hemodialysis has been viewed by many as an immunogenic challenge leading to an acute phase response. In this study we examined the relationship between hemodialysis-induced immune activation and intradialytic hypotension, using the acute phase reactant serum C-reactive protein (CRP) as a surrogate for immunogenic activation. The maximum percent change in mean arterial pressure (MAP) was found to correlate significantly with CRP (r = 0.67, p < 0.05) in nine consecutive patients with a history of symptomatic hypotension during hemodialysis. In contrast, no correlation was found between CRP and maximum percent change in MAP in eight consecutive hemodialysis patients without intradialytic hypotension. Since interleukin-6 (IL-6) is a major regulator of CRP, the relationship between these two proteins was examined. Plasma IL-6 levels were found to correlate both with CRP (r = 0.67, p < 0.05) and with mean maximum percent change in MAP (r = 0.70, p < 0.05) in hemodialysis patients with a prior history of hypotension. IL-6 levels did not correlate with CRP or blood pressure in the hemodynamically stable patients. The results suggest that immune activation working through IL-6, CRP and other cytokines may play a role in the pathogenesis of hemodialysis hypotension in some patients. |
| 2001 | Prospective, multicenter evaluation of risk factors associated with invasive bacterial infection in children with cancer, neutropenia, and fever. | J Clin Oncol | To identify clinical and laboratory parameters present at the time of a first evaluation that could help predict which children with cancer, fever, and neutropenia were at high risk or low risk for an invasive bacterial infection.Over a 17-month period, all children with cancer, fever, and neutropenia admitted to five hospitals in Santiago, Chile, were enrolled onto a prospective protocol. Associations between admission parameters and risk for invasive bacterial infection were assessed by univariate and logistic regression analyses.A total of 447 febrile neutropenic episodes occurred in 257 children. Five parameters were statistically independent risk factors for an invasive bacterial infection. Ranked by order of significance, they were as follows: C-reactive protein levels of 90 mg/L or higher (relative risk [RR], 4.2; 95% confidence interval [CI], 3.6 to 4.8); presence of hypotension (RR, 2.7; 95% CI, 2.3 to 3.2); relapse of leukemia as cancer type (RR, 1.8, 95% CI, 1.7 to 2.3); platelet count less than or equal to 50,000/mm(3) (RR, 1.7; 95% CI, 1.4 to 2.2); and recent (< or = 7 days) chemotherapy (RR, 1.3; 95% CI, 1.1 to 1.6). Other previously postulated risk factors (magnitude of fever, monocyte count) were not independent risk factors in this study population.In a large population of children, common clinical and laboratory admission parameters were identified that can help predict the risk for an invasive bacterial infection. These results encourage the possibility of a more selective management strategy for these children. |
| 2001 | [Rare complication of a heparin-induced thrombocytopenia type II]. | Dtsch Med Wochenschr | A 63-year-old man was admitted to a surgery department with fracture of the acetabulum and luxation of the hip joint. Eight days after intracondylar nail-extension during subcutaneous heparin prophylaxis he developed a dramatic deterioration of his condition with severe abdominal pain and fever and was admitted to our hospital.White cell count was 12,000/microliter, C-reactive protein 7.90 mg/dl. CT-scan, abdominal ultrasound, mesenteric angiography and exploratory laparotomy revealed no pathological findings. At day 13 abdominal ultrasound showed adrenal haemorrhages on the right. Together with a drop in platelet count below 50,000/microliter, adrenal haemorrhage caused by heparin-induced thrombocytopenia (type II; immunological [HIT II]) was suggested.After discontinuation of heparin and starting therapy with recombinant hirudin and hydrocortisone, a dramatic clinical recovery followed within 24 hours. One year after the initial diagnosis the patient is in a good condition.When abdominal pain, hypotension and fever occurs with a drop in platelet count during heparin therapy HIT II should be considered. An early diagnosis is essential for treatment of this life-threatening complication at an early stage. |
| 2000 | A lipid A analog, E5531, blocks the endotoxin response in human volunteers with experimental endotoxemia. | Crit Care Med | Endotoxin (lipopolysaccharide [LPS]) has been associated with sepsis and the high mortality rate seen in septic shock. The administration of a small amount of LPS to healthy subjects produces a mild syndrome qualitatively similar to that seen in clinical sepsis. We used this model to test the efficacy of an endotoxin antagonist, E5531, in blocking this LPS-induced syndrome.In a placebo-controlled, double-blind study, we randomly assigned 32 healthy volunteers to four sequential groups (100, 250, 500, or 1000 microg of E5531). Each group of eight subjects (six assigned to E5531, two assigned to placebo) received a 30-min intravenous infusion of study drug. LPS (4 ng/kg) was administered to all subjects as an intravenous bolus in the contralateral arm at the midpoint of the infusion. Symptoms, signs, laboratory values, and hemodynamics (by echocardiogram) were evaluated at prospectively defined times.In subjects receiving placebo, LPS caused headache, nausea, chills, and myalgias. E5531 led to a dose-dependent decrease in these symptoms that was statistically significant (p < .05) except for myalgias. The signs of endotoxemia (fever, tachycardia, and hypotension) were consistently inhibited at the three higher doses (250, 500, and 1000 microg, p < .05). Tumor necrosis factor-alpha and interleukin-6 blood levels were both lower in those who received E5531 (p < .0001). The C-reactive protein level and white blood cell count response were decreased at all doses (p < .0001). The hyperdynamic cardiovascular state (high cardiac index and low systemic vascular resistance) associated with endotoxin challenge was significantly inhibited at the higher doses of E5531.E5531 blocks the symptoms and signs and cytokine, white blood cell count, C-reactive protein, and cardiovascular response seen in experimental endotoxemia. This agent is a potent inhibitor of endotoxin challenge in humans and may be of benefit in the prevention or treatment of sepsis and septic shock. |
| 2000 | 'Sepsis' and multi-organ failure: predictors of poor outcome after hematopoietic stem cell transplantation in children. | Bone Marrow Transplant | Prognostic scores, such as the PRISM and APACHE II, have been established, predicting with reasonable accuracy the outcome of patients admitted to intensive care units (ICU). In keeping with previous reports, we found, however, that these scores failed to perform in a series of 28 recipients of hematopoietic auto- or allografts (BMT) who required ICU admission for reasons including respiratory (82%) and multi-organ (36%) failure. We therefore retrospectively analyzed the charts of these patients, evaluating predisposing factors and prognostic variables which might confound the validity of these ICU tools which in other clinical scenarios have proven so valuable. Of all the parameters tested, logistic analysis established the following as predictors for poor outcome: increased C-reactive protein (CRP) to > 10 mg/dl (P = 0.04), macroscopic hemorrhage (P = 0.04), hypotension (mean arterial pressure < normal) (P = 0.04) and GVHD > or = III (P = 0.002). Most of these factors are not accounted for by the standard prognostic questionnaires. The development of an 'oncological' or 'post-BMT' risk of mortality score, taking into account these patients' specific clinical problems, might improve the risk assessment for this patient group, and might thus facilitate the timely recognition of those patients most in need of more intensive therapeutic measures. |
| 2000 | Acute acalculous cholecystitis in patients with surgical acute renal failure. | Acta Med Croatica | Acute acalculous cholecystitis (AAC) developed in 11 (7.7%) of 143 patients with surgical acute renal failure (ARF) who had no prior biliary tract disease. The cause of this potentially fatal complication is multifactorial and include trauma, previous surgery, sepsis, intermittent positive pressure ventilation, total parenteral nutrition, multiple transfusions, hypotension, and opiate sedation. The diagnosis of AAC was based on clinical suspicion, ultrasound scanning, and laboratory tests (leukocyte count, liver enzymes, bilirubin and C-reactive protein). All our ARF patients with AAC were receiving antibiotics at the time of diagnosis. Five patients were treated conservatively and six underwent cholecystectomy. The mortality rate in our ARF patients with AAC was 45.5%, and was not significantly different from than in ARF patients without AAC. The diagnosis of AAC should be made early, and judicious management (conservative or surgical) decreases its role as a contributory factor to the mortality in ARF patients. |
| 2000 | Systemic toxicity and cytokine/acute phase protein levels in patients after isolated limb perfusion with tumor necrosis factor-alpha complicated by high leakage. | Ann Surg Oncol | Since the introduction of high-dose tumor necrosis factor-alpha (TNFalpha) in the setting of isolated limb perfusion (ILP) in the clinic, prevention of leakage to the body of the patient is monitored with great precision for fear of TNF-mediated toxicity. That we observed remarkably little toxicity in patients with and without leakage prompted us to determine patterns of cytokines and acute phase proteins in patients with high leakage and in patients without any leakage.TNFalpha, interleukin (IL)-6, IL-8, C-reactive protein, and secretory (s)-phospholipase A2 were measured at several time points during and after (until 7 days) ILP in 10 patients with a leakage to the systemic circulation varying in percentage from 12% to 65%. As a control, the same measurements, both in peripheral blood and in perfusate, were performed in nine patients without systemic leakage.In patients with systemic leakage, levels of TNFalpha increased during ILP, reaching values to 277 ng/ml. IL-6 and IL-8 peaked 3 hours after ILP with values significantly higher compared with patients without systemic leakage. C-reactive protein and s-phospholipase A2 peaked at day 1 in both patient groups, s-phospholipase A2 with significant higher levels and C-reactive protein, in contrast, with lower levels in the leakage patients.High leakage of TNFalpha to the systemic circulation, caused by a complicated ILP, led to 10-fold to more than 100-fold increased levels of TNFalpha, IL-6, and IL-8 in comparison with patients without leakage. The increase of the acute phase proteins was limited. Even when high leakage occurs, this procedure should not lead to fatal complications. The most prominent clinical toxicity was hypotension (grade III in four patients), which was easily corrected. No pulmonary or renal toxicity was observed in any patient. It is our experience that, even in the rare event of significant leakage during a TNFa-based ILP, postoperative toxicity is usually mild and can be easily managed by the use of fluid and, in some cases, vasopressors. |
| 2000 | Acute phase response to nitroprusside-induced controlled hypotension in patients undergoing radical prostatectomy. | Anaesthesia | This study evaluated the effects of sodium nitroprusside-induced controlled hypotension on the acute phase response in patients undergoing radical prostatectomy. Thirty patients were randomly allocated to two groups, a hypotension group (mean arterial blood pressure was adjusted to 50 mmHg) and a control group (mean arterial blood pressure > 70 mmHg). C-reactive protein increased significantly in the hypotension group from 0.13 (0.23) to 9.85 (2.84) microg x ml-1 and in the control group from 0.15 (0.27) to 7.38 (3.02) microg x ml-1. In both groups, serum amyloid A increased significantly, but levels were higher in the hypotension group [585 (125) microg x l-1] than in the control group [460 (187) microg x l-1]. Interleukin-6 increased significantly in both groups, but was higher in the hypotension group [139 (124) pg x ml-1] than the control group [56 (27) pg x ml-1]. Elastase showed no significant changes in the control group but in the hypotension group there was a significant increase from 65 (51) to 122 (75) ng x ml-1. Sodium nitroprusside-induced hypotension was associated with a more pronounced acute phase reaction. |
| 1998 | A two-part phase I trial of high-dose interleukin 2 in combination with soluble (Chinese hamster ovary) interleukin 1 receptor. | Clin Cancer Res | Our purpose was to determine the maximum tolerated dose and toxicity associated with soluble Chinese hamster ovary [s(CHO)] recombinant human interleukin (IL) 1 receptor (IL-1R; Immunex, Seattle, WA) administration in humans and to determine the effective biological dose and/or maximum tolerated dose of the s(CHO) IL-1R in combination with high-dose IL-2 as determined by reduction in IL-2 toxicity and modulation of its biological effects. Twenty-seven patients with metastatic cancer were treated with escalating doses of s(CHO) IL-1R at 1, 1, 5, 10, 20, 40, and 55 mg/m2 i.v. on days -6 (except cohort 2), 1, and 15 and IL-2 at doses of 300,000 IU/kg (cohort 1) and 600,000 IU/kg (cohorts 2-7) i.v. every 8 h on days 1-5 and 15-19. No toxicity directly attributable to s(CHO) IL-1R was observed. The median number of IL-2 doses was 23. Hypotension and neurotoxicity were the major dose-limiting toxicities for the IL-2/s(CHO) IL-1R combination. Of the 24 patients treated with full-dose IL-2, there were six responses, three complete and three partial (response rate, 25%). Three patients developed thyroid dysfunction, and all 3 responding melanoma patients exhibited vitiligo. The t1/2 of s(CHO) IL-1R alone was 24-30 h and was not significantly altered by coadministration with IL-2. Whole-blood functional assays indicated that sufficient s(CHO) IL-1R was present in the circulation at top dose levels to inhibit the in vitro effects of IL-1beta on IL-8 induction; however, no effect on IL-2-induced IL-8 induction, or on the IL-1beta- or IL-2-induced tumor necrosis factor production, was observed. Suppression of IL-2-mediated tumor necrosis factor alpha and IL-6 induction in vivo during the first 24 h after IL-2 administration was observed, and the neutrophil chemotactic defect normally seen with IL-2 was not observed. IL-1R antagonist induction far exceeded that seen previously with IL-2 alone. No inhibition of either serum C-reactive protein induction or enhanced urinary nitrate excretion and no consistent effect on IL-2-related changes in peripheral blood mononuclear cell phenotype or endothelial adhesion molecule expression were seen. The coadministration of s(CHO) IL-1R produced no apparent reduction in IL-2 clinical toxicity manifested by either the ability to administer more IL-2 than anticipated or a reduction in the toxicity associated with a given amount of IL-2. Therefore, no effective biological dose could be identified for the s(CHO) IL-1R. |
| 1997 | Unstable angina: are we able to recognize high-risk patients? | Chest | It is difficult to identify characteristics of patients with unstable angina that are predictive of a high likelihood of developing clinical events. However, several features have been recognized. Patients with a clinical history of previous stable exertional angina symptoms who began to experience rest pain appear to be at risk and tend to have more extensively underlying coronary disease. When the ischemic episodes are accompanied by rates, a new or worsening mitral regurgitation murmur, or hypotension, there is a high likelihood of significant coronary artery disease and one should triage these patients to early cardiac catheterization and prompt revascularization. An angiographic feature that carries a high risk is a lesion in the proximal left anterior descending or in the left main coronary artery. Certain typical ECG patterns are very suggestive for a critical narrowing in these coronary arteries. If chest pain and ST-segment changes recur on vigorous medical management, early invasive evaluation should be strongly considered. Even so, the left ventricular function is very important prognostically. According to serologic tests, the level of C-reactive protein and serum amyloid A protein suggesting that there may be active inflammation predicts an early poor outcome. However, these serologic abnormalities do not have much clinical value. An increased platelet activation and a reduced fibrinolytic capacity play a role in the pathogenesis of unstable angina, but thrombolytic therapy does not improve the prognosis in patients with unstable angina. |
| 1997 | Concurrent phase I trials of intravenous interleukin 6 in solid tumor patients: reversible dose-limiting neurological toxicity. | Clin Cancer Res | Interleukin 6 (IL-6) has antitumor activity comparable to IL-2 in murine models with less toxicity. Because the biological effects of intermittent and continuous infusions may differ, we conducted two concurrent Phase I trials of daily x5, 1-h, and continuous 120-h i.v. infusions to determine the toxicity, biological effects, and maximum tolerated dose of i.v. IL-6. Cohorts of six patients with advanced cancer received escalating doses (1, 3, 10, 30, 100, and 150 microgram/kg/day) of recombinant human IL-6 on days 1-5 and 8-12 of each 28-day course (1-h trial) or on days 1-5 of each 21-day course (120-h trial). Treatment was administered in regular inpatient wards and in outpatient clinics and was withheld in the event of grade 3 toxicity. Sixty-nine patients (1-h trial, n = 40; 120-h trial, n = 29) were enrolled, including 27 with renal cancer and 16 with melanoma. All were ambulatory, and 40 were asymptomatic. Fever (97%), anemia (78%), fatigue (56%), nausea or vomiting (49%), and elevated serum transaminase levels (42%) were the most frequent toxicities. Transient hypotension developed in 23 patients (33%). There were three deaths during the study due to progressive disease and/or infection. There were no objective responses. Dose-related increases in platelet counts and C-reactive protein levels were detected in most patients. Principal dose-limiting toxicities included atrial fibrillation (1 episode in the 1-h trial and 4 episodes in the 120-h trial) and neurological toxicities (3 episodes in the 1-h trial and 4 episodes in the 120-h trial). The neurological toxicities included confusion, slurred speech, blurred vision, proximal leg weakness, paraparesis, and ataxia. These effects were transient and reversed when IL-6 was discontinued. IL-6 can be given by i.v. infusion at biologically active doses with acceptable toxicity. Dose-limiting toxicities consisted mainly of a spectrum of severe but transient neurological toxicities and occasional episodes of atrial fibrillation. The maximum tolerated doses recommended for use with these i.v. schedules in Phase II trials are 100 microgram/kg/day by daily x5 1-h infusion and 30 microgram/kg/day by 120-h infusion. Phase II trials will be performed to determine the antitumor activity of IL-6 and better define its toxicity. Patients in these and other IL-6 studies should be monitored closely for neurological and cardiac effects. |
| 1996 | Phase Ia/Ib trial of anti-GD2 chimeric monoclonal antibody 14.18 (ch14.18) and recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) in metastatic melanoma. | J Immunother Emphasis Tumor Immunol | We performed a phase Ia/Ib trial of chimeric anti-GD2 monoclonal antibody 14.18 (ch14.18) in combination with recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) to determine the maximum tolerated dose as well as immunologic and biologic responses to the regimen. Sixteen patients with metastatic malignant melanoma received escalating doses of ch14.18 (15-60 mg/m2) administered intravenously for 4 h on day 1. Twenty-four hours later, subcutaneous injections of rhGM-CSF were administered daily for a total of 14 days. Significant side effects were related to ch14.18 infusion and consisted of moderate to severe abdominal and/or extremity pain, blood pressure changes, headache, nausea, diarrhea, peripheral nerve dysesthesias, myalgias, and weakness. Dose-limiting toxicity was observed at 60 mg/m2 and consisted of severe hypertension, hypotension, and atrial fibrillation in one patient each, respectively. Significant increases in white blood cell count, granulocyte count, eosinophil count, and monocyte count occurred after rhGM-CSF treatment. Significant enhancement of in vitro and in vivo monocyte and neutrophil tumoricidal activity and antibody-dependent cellular cytotoxicity along with significant elevations in C-reactive protein and neopterin were observed. Despite these immunological and biological changes, no antitumor activity was seen. In short, the combination of ch14.18 and rhGM-CSF resulted in toxicity similar to that observed with ch14.18 alone without improvement in tumor response. |
| 1994 | Correlation of serum cytokine and acute phase reactant levels with alterations in weight and serum albumin in patients receiving immunotherapy with recombinant IL-2. | Clin Exp Immunol | Recombinant IL-2 (rIL-2) has been used alone or in combination with other chemotherapeutic agents to enhance host defences against cancer. Prolonged administration of high doses, required for clinical efficacy, may precipitate serious dose-limiting toxicity. rIL-2-induced 'vascular leak syndrome' leads to hypotension, renal insufficiency, respiratory disturbances and other organ dysfunctions. Serial measurements of serum cytokines and the acute phase protein C-reactive protein (CRP) were performed on nine patients who received high-dose i.v. continuous therapy with rIL-2. The influence of these immunological parameters upon alterations in patients' weight and serum albumin, as indicators of toxicity, was assessed. All patients experienced weight increases during the cycle (3-11% of total body weight). The serum levels of tumour necrosis factor (TNF-alpha) and CRP were highly predictive of alterations in patients' weight (both P < 0.001), while no correlation was found with IL-6 and weight change. Serum albumin fell linearly throughout the infusion cycle, but this showed no correlation with variations in serum levels of IL-6, TNF-alpha, or CRP. The complement components C3 and C4 were significantly reduced at the end of the infusion, suggesting a possible role for this cascade system in mediating these clinical changes. The strong association between serum TNF-alpha and weight change, not previously documented, further supports the hypothesis that TNF-alpha is a key mediator in the pathogenesis of the 'vascular leak syndrome'. |
| 1992 | Phase I evaluation of thrice-daily intravenous bolus interleukin-4 in patients with refractory malignancy. | J Clin Oncol | A phase I dose-escalation trial of recombinant human interleukin-4 (IL-4) was performed to determine its toxicity, biologic activity, and potential antineoplastic effects.Ten patients with refractory malignancies received IL-4 by bolus intravenous injection every 8 hours on days 1 to 5 and 15 to 19 (maximum, 28 doses) of a 31-day study period. Three patients received 10 micrograms/kg per dose and seven received 15 micrograms/kg per dose of IL-4.Toxic symptoms noted at the second dose level included nasal congestion, diarrhea, nausea and vomiting, fatigue, anorexia, headache, dyspnea, and capillary leak syndrome (median weight gain, 6.1%; range, 3.4% to 11.7%). Fever or sustained hypotension sufficient to require pressors did not occur. Decreases in lymphocyte count and serum bicarbonate, sodium, albumin, fibrinogen and immunoglobulin (Ig) levels, and increases in hematocrit, prothrombin time/partial thromboplastin time (PT/PTT), soluble CD23, and, occasionally, serum creatinine and transaminases occurred. All side effects resolved by day 31. Phenotypic analysis of peripheral-blood mononuclear cells (PBMC) showed a decrease in the percentage of circulating CD16 and CD14(+) cells. Plasma tumor necrosis factor (TNF) and IL-1 beta levels were unaffected, whereas serum C-reactive protein (CRP) concentrations increased slightly and plasma IL-1 receptor antagonist (IL-1RA) levels increased markedly. No tumor responses were observed.We conclude that 10 micrograms/kg per dose of IL-4 is the maximum-tolerated dose for this schedule, although 15 micrograms/kg per dose can be tolerated if more intensive, but still non-intensive care unit level care is provided. The results of this study should aid in the design of future phase II trials that involve IL-4 alone or phase I studies that combine IL-4 with other cytokines such as IL-2. |
| 1992 | The toxic and hematologic effects of interleukin-1 alpha administered in a phase I trial to patients with advanced malignancies. | J Clin Oncol | A phase I trial was undertaken because interleukin-1 alpha (IL-1 alpha) possesses antiproliferative, immunostimulatory, antiinfection, myeloprotective, and myelorestorative properties that could be beneficial in cancer treatment.In this phase I trial, IL-1 alpha was administered intravenously (IV) during a 15-minute period daily for 7 days to patients with advanced solid malignancies.The maximum-tolerated dose (MTD) of IL-1 alpha alone was 0.3 microgram/kg. A second group of patients received indomethacin plus IL-1 alpha based on preclinical studies, which indicated that indomethacin could abrogate IL-1 alpha-induced hypotension; however, the MTD of IL-1 alpha plus indomethacin was 0.1 microgram/kg lower than IL-1 alpha alone. Fever, chills, headache, nausea, vomiting, and myalgia were common but were not dose-limiting. Hypotension resulted from a marked decrease in systemic vascular resistance and required pressors at 0.3 and 1.0 micrograms/kg IL-1 alpha. Dose-limiting toxicities included hypotension, myocardial infarction, confusion, severe abdominal pain, and renal insufficiency. IL-1 alpha treatment caused a significant, dose-related increase in the total WBC count (mainly segmented neutrophils and neutrophilic bands). Bone marrow cellularity increased because of enhanced numbers of relatively mature myeloid cells and megakaryocytes. Platelet counts decreased during therapy but were significantly elevated above baseline values 1 to 2 weeks posttreatment; this may have been an effect of IL-6 that was shown to be induced by IL-1 alpha treatment. Significant increases in triglycerides, cortisol, C-reactive protein, thyroid-stimulating hormone and decreases in cholesterol, testosterone, and protein-C were observed with treatment.We conclude that at doses of IL-1 alpha that can be given safely to cancer patients, significant, potentially beneficial hematopoietic effects occur. |
| 1991 | A phase I trial of recombinant human interleukin-1 beta alone and in combination with myelosuppressive doses of 5-fluorouracil in patients with gastrointestinal cancer. | Blood | We studied escalating doses of recombinant human interleukin-1 beta (IL-1 beta) alone and after a myelosuppressive dose of 5-fluorouracil (5-FU) in patients with gastrointestinal cancer. Transient neutropenia, monocytopenia, and lymphocytopenia were observed followed by a 1.3- to 6.0-fold (mean, 3.46-fold) dose-dependent neutrophil leukocytosis (P less than .00001) on the days of IL-1 beta administration. Increases in platelet counts were observed at a median of 14 days (range, 6 to 23) after IL-1 beta administration. Transient hypoglycemia, rebound hyperglycemia, elevations in serum cortisol, and C-reactive protein were observed. Side effects included fever, rigors, and headache in the majority of patients. Hypotension was observed in three of five patients at the highest dose level (0.1 micrograms/kg) and was dose-limiting. Fewer days of neutropenia were noted after 5-FU plus IL-1 beta than after 5-FU alone; however, this difference did not reach statistical significance. These data show that IL-1 beta has stimulatory effects in human hematopoiesis. |
| 1991 | The role of medical treatment of distal type aortic dissection. | Int J Cardiol | We analyzed the short-term and long-term outcome of 42 patients with distal type aortic dissection. Twenty-eight patients underwent intensive medical therapy within two weeks after the onset of pain (acute dissection). The remaining 14 patients had chronic dissection. The goals of medical treatment were to control blood pressure and to attain a negative C-reactive protein test result. Hospital survival rate in the patients with acute dissection was 96% (27/28). In-hospital complications included changes in mental status, renal dysfunction, bradycardia, orthostatic hypotension, and liver dysfunction, all of which were managed medically. Three of these patients underwent surgical therapy in the chronic phase and were discharged uneventfully. Fifteen (62.5%) of the 24 medically treated patients were discharged with negative C-reactive protein tests. Spontaneous resolution of a dissection was demonstrated by radiological examinations in 8 cases. Five-year survival rates in 24 medically treated patients was 93%. Hospital survival rate in the patients with chronic dissection was 100% (14/14). The rigorous control of blood pressure in the acute phase, and subsequent meticulous evaluation of the dissection by radiological tests and C-reactive protein test provides acceptable short-term and long-term outcomes of patients with acute distal dissection without the need for emergency surgical intervention. |
| 1991 | Recombinant tumour necrosis factor alpha administered subcutaneously or intramuscularly for treatment of advanced malignant disease: a phase I trial. | Eur J Cancer | The pharmacokinetics, toxicity and biological effects of subcutaneous and intramuscular treatment of cancer patients with recombinant tumour necrosis factor alpha (rTNF-alpha) was investigated. 17 patients suffering from refractory malignant disease were treated with either 1.0 micrograms/m2, 10 micrograms/m2 or 100 micrograms/m2 rTNF-alpha. Vital signs, peripheral blood cell counts, TNF and interferon (IFN) gamma serum levels, neopterin, beta 2-microglobulin, C reactive protein (CRP) and cortisol levels were measured immediately before and 2, 12, 24, 48 and 168 h after the first administration of rTNF-alpha. Tumour response was evaluated after 4 and 12 weeks of treatment. The pharmacokinetics followed the same characteristics as those reported for other cytokines. Major toxicities were dose dependent and comprised fever, constitutional symptoms and hypotension. TNF dependent changes were observed in serum levels of IFN-alpha, CRP, neopterin, beta 2-microglobulin, cortisol and white blood cell counts. No objective tumour response was observed. This study indicated that rTNF-alpha administered subcutaneously or intramuscularly results in measurable TNF serum levels, significant toxicity and biological response in absence of clinical efficacy in patients with advanced cancer. |
| 1990 | Inhibition of interleukin-2-induced tumor necrosis factor release by dexamethasone: prevention of an acquired neutrophil chemotaxis defect and differential suppression of interleukin-2-associated side effects. | Blood | High concentrations of tumor necrosis factor (TNF) alpha have been detected in the plasma of patients undergoing immunotherapy with interleukin 2 (IL-2), suggesting that this cytokine may play a role in the fever and shocklike state induced by the administration of high-dose IL-2. Dexamethasone has been shown to inhibit the synthesis of TNF by monocytes activated in vitro by endotoxin. To determine if dexamethasone can exert a similar suppressive effect on IL-2-induced TNF synthesis in vivo, the concentration of TNF alpha was measured in plasma samples serially obtained (a) from cancer patients participating in a phase I dose escalation clinical trial with high-dose IL-2 administered in conjunction with dexamethasone (IL-2/Dex) and (b) from patients participating in concurrent studies with IL-2 alone. In contrast to the high plasma levels of TNF alpha detected in patients receiving IL-2 alone, TNF levels in most of the IL-2/Dex patients remained below the threshold of detectability of our TNF radioimmunoassay. The concurrent administration of dexamethasone also prevented the IL-2-induced increase in serum levels of C-reactive protein, a hepatic acute phase reactant whose synthesis is regulated by proinflammatory cytokines such as TNF. The steroid-treated patients also failed to develop the neutrophil chemotactic defect characteristic of IL-2 recipients. The concomitant administration of dexamethasone increased the maximum tolerated dose of IL-2 approximately threefold and markedly reduced the hypotension and organ dysfunction ordinarily observed in these patients. These results demonstrate that dexamethasone inhibits the release of TNF into the circulation of patients undergoing immunotherapy with IL-2. They further suggest that the altered spectrum and reduced severity of IL-2 side effects observed in patients receiving dexamethasone may be attributable in part to the suppressive effect of steroids on IL-2-induced TNF synthesis. |
| 1989 | [A study of rheumatoid arthritis patients associated with biopsy-proven secondary amyloidosis]. | Ryumachi | Reactive systemic amyloidosis associated with rheumatoid arthritis (RA) was studied clinically in 28 patients (2 men and 26 women). The diagnosis of amyloidosis was established by histological examination of biopsy materials. Upper gastrointestinal tract biopsy was performed in 14 patients, and renal and rectal biopsy in 8 and 4 respectively. The mean age and duration of RA at diagnosis of amyloidosis were 58.6 (range 35-72) years and 15.5 (range 4-44) years respectively. Almost all patients had intractable and progressive courses of RA. Serological activities determined by C-reactive protein (CRP) and erythrocyte sedimentation rates were moderate to high in over 80% of the cases. Renal abnormalities were noticed in 19 cases, and gastrointestinal disorders in 10. Eight patients died from 1 to 54 (mean 15.3) months after the diagnosis of amyloidosis; 5 died of renal failure and 2 of gastrointestinal involvements. Renal impairments progressed frequently and serum creatinine elevated over 1.5 mg/dl in another 8 cases. Five patients progressing to renal failure were treated with hemodialysis. Three died within several weeks after the induction of hemodialysis, although 2 were treated for more than 2 years. Intractable hypotension and pulmonary congestion were frequently observed in these cases. A close relationship was found between serum amyloid A protein (SAA) and CRP concentration, so that the measurement of SAA seemed to be valuable in assessing disease activity. Concerning the treatment of amyloidosis, cyclophosphamide and corticosteroids seemed to be effective in several cases, although it had been unsatisfactory in most cases. |
| 1988 | Acute acalculous cholecystitis in acute renal failure. | Intensive Care Med | Acute acalculous cholecystitis developed in 16 of 92 patients with acute renal failure who had no prior or coincidental biliary tract disease. The cause of this complication is considered to be multifactorial. Risk factors include sepsis, previous surgery, trauma, total parential nutrition, intermittent positive pressure ventilation, opiate sedation, multiple transfusions and hypotension. One patient had 5 risk factors, 15 had 6 or more. Diagnosis was based on clinical suspicion, serial ultrasound scanning and serial estimations of white cell count, liver function and C-reactive protein. Four patients were treated conservatively with antibiotics and ultrasound observation, 10 underwent cholecystotomy and 2 patients had cholecystectomy. Eleven patients survived (69% survival). No patient treated by cholecystotomy required further surgery to the biliary tract. Acute acalculous cholecystitis has become a significant complication in our "high risk" acute renal failure population as intensive care has advanced and patients are surviving longer. Prompt and appropriate treatment will prevent it contributing significantly to the already high mortality of acute renal failure. Anticipation is the watchword. |
| 1987 | Tumour necrosis factor in man: clinical and biological observations. | Br J Cancer | Eighteen patients with advanced cancer have been treated intravenously with human recombinant tumour necrosis factor (rhTNF). The drug produced febrile reactions at all doses although these were preventable by steroids and indomethacin. Doses at or above 9 x 10(5) units (400 micrograms)m-2 were associated with hypotension, abnormal liver enzymes, leucopenia and mild renal impairment in a substantial proportion of patients. RhTNF was cleared from plasma with a half life of approximately 20 minutes but non-linear pharmacokinetics lymphoma, improvements in their tumours were recorded. RhTNF was noted to produce rapid increases in serum C-reactive protein concentrations. Endogenous TNF levels were not found to be elevated in 72 cancer patients. TNF deserves further therapeutic evaluation and these observations support its biological importance as an endogenous pyrogen, mediator of acute phase protein responses, and a mediator of endotoxic shock. |
| 1987 | Role of circulating complement and polymorphonuclear leukocyte transfusion in treatment and outcome in critically ill neonates with sepsis. | J Pediatr | We examined the effects of early administration of polymorphonuclear leukocyte (PMN) transfusions in neonates with sepsis by prospectively randomizing 35 consecutive critically ill infants with sepsis, 21 of whom received PMN transfusions in addition to supportive care, one transfusion every 12 hours for a total of five transfusions. Each transfusion consisted of 15 mL/kg containing 0.5 to 1.0 X 10(9) PMN with less than 10% lymphocytes, and was subjected to 1500 rads. PMNs were obtained by continuous-flow centrifugation leukopheresis. Pretreatment values that did not significantly affect survival included weight, gestational age, sex, prematurity, C-reactive protein, initial hematocrit, platelet count and absolute granulocyte count (AGC less than or equal to 1500/mm3), IgM, IgG, IgA, neutrophil supply pool depletion, hypoxia, acidosis, and hypotension. Postnatal age was significantly lower in the nontransfused group than in the transfused group; 2.3 +/- 0.6 vs 6.1 +/- 2.2, (P less than 0.001). Positive blood cultures were obtained in 80% of both groups. Low circulating levels of total hemolytic complement were associated with a poor outcome and higher mortality: 56 +/- 4.0 IU in survivors vs 31 +/- 4.4 IU in nonsurvivors (P less than 0.01). Survival was significantly greater in the PMN transfused group than in the nontransfused group: 20 (95%) of 21 vs nine (64%) of 14 (P less than or equal to 0.05). No untoward effects were attributable to PMN transfusions, either during the study or on subsequent follow-up visits. These preliminary data suggest that early treatment with PMN transfusions improves survival in neonates with overwhelming sepsis. In addition, depleted or low circulating levels of complement may influence prognosis and thus future treatment strategies for neonatal sepsis. |
| 1986 | Phase I evaluation of recombinant interleukin-2 in patients with advanced malignant disease. | J Clin Oncol | Seventeen patients with refractory malignant tumors were treated with recombinant human interleukin-2 (IL-2) administered by weekly bolus intravenous (IV) injection in a phase I dose escalation trial. Patients received 10,000 to 1,000,000 U/m2 per injection over a course of 3 to 33 weeks. Toxicity was dose related and consisted primarily of fever, chills, nausea, and vomiting. Hypotension was observed at doses of 500,000 U/m2 or higher and in one instance was sufficiently severe to require pressors. No tumor regression was seen and all patients eventually developed progressive disease. Blood levels of cortisol, ACTH, prolactin, and growth hormone as well as the acute phase reactant C-reactive protein (CRP) increased after the administration of IL-2 in most patients. Serum IL-2 levels in excess of 250 U/mL were detected five minutes after an IV injection of 1,000,000 U/m2, after which the levels declined with a half-life of approximately 25 minutes. No alteration in lymphocyte surface phenotype or enhancement in natural cell-mediated cytotoxicity against natural killer (NK)-sensitive and resistant tumor cell lines was observed when these parameters were measured weekly just before the IL-2 injections. However, a dramatic but transient decline in circulating lymphocytes and NK activity was noted within hours of receiving IL-2. This effect was independent of fever and was not abrogated by pretreatment with ibuprofen or metyrapone. The majority of patients developed serum IgG antibodies of IL-2 detectable with a sensitive enzyme-linked immunosorbent assay (ELISA) and a nitrocellulose dot blot assay. The development of anti-IL-2 antibodies was not associated with symptoms suggestive of serum sickness, reductions in serum complement levels, or deterioration in lymphocyte tumoricidal activity. This investigation provides insight into the in vivo actions of this potent biological response modifier and will assist in the design of future studies with IL-2 administered alone or in conjunction with other treatment modalities. |
| 1984 | Captopril: a new treatment for rheumatoid arthritis? | Lancet | Captopril, an inhibitor of angiotensin converting enzyme, is prescribed for hypertension. Its molecular structure shares features with D-penicillamine, in that both agents contain a thiol group. In addition, captopril has immunosuppressant activity. Captopril was therefore considered a potential slow-acting drug for treating rheumatoid arthritis. In an open study 15 patients with active arthritis were treated with captopril and followed for 48 weeks. Two-thirds of the patients reported improved arthritis symptoms, and significant changes were seen in several clinical and biochemical measurements, notably Ritchie articular index, clinical score, plasma viscosity, and C-reactive protein. Side-effects were generally mild and included transient taste loss, rashes, and hypotension. Only 2 patients withdrew as a result of drug intolerance. |