Research on (Rifapentine)-C-reactive protein-chills


TARGET-SYDROM RELATIONSHIP DRUG-TARGET-SYDROM RELATIONSHIP

Year Title Journal Abstract
2021Appendicitis Mimicking Urinoma: A Challenging Emergency Presentation Secondary to Ureteric Stone.CureusThis article describes the case of a 38-year-old male who presented to the ED with three days history of gradually progressing right-sided lower abdominal pain, which had increased in severity two hours prior to his ED visit. The patient was anorexic but denied experiencing any fever, urinary malfunctions, or chills. Blood tests showed an elevated serum creatinine level of 123 umol/L and a high C-reactive protein level of 62 mg/L. Bedside point-of-care ultrasound (POCUS) imaging showed right-sided mild hydroureteronephrosis with surrounding perinephric fluid. Initially, based on the patient's presentation and clinical findings, appendicitis or ureteric colic was strongly suspected. CT of the abdomen with contrast revealed urinoma measuring 16 cm, and there was a 3.2 mm calculus in the distal part of the right ureter, with perinephric and periureteric fat stranding. This rare phenomenon requires prompt care. Delayed medical treatment may result in complications like hydronephrosis, abscess, distorted electrolyte levels, and gradual loss of renal function. Small urinomas are usually treated conservatively, while large-sized urinomas often require aggressive medical treatment. A drainage catheter under CT or ultrasound guidance may be done, and additional decompression and drainage may be needed with percutaneous nephrostomy tubes. The fluid and urine culture guide antibiotic treatment.
2021Chills, fatigue, chest distress, and an abnormal increase in WBC, neutrophil, CRP, and PCT induced by terconazole: A case report.Int J Clin Pharmacol TherThe vaginal routes of administration of terconazole, a synthetic triazole derivative, is widely used by patients with uncomplicated vulvovaginal candidiasis (VVC). A 32-year-old woman suffered from chills, fatigue, and chest distress after receiving one 80-mg terconazole vaginal suppository for the treatment of uncomplicated VVC. Then, the symptom persisted for 10 hours until the residue of terconazole was removed, and the vagina was repeatedly washed with iodophor. In addition, white blood cell (WBC), neutrophil, C-reactive protein (CRP), and procalcitonin (PCT) were tested and showed marked increase when the patient visited our hospital again on the next day after the treatment with terconazole. Intriguingly, these parameters gradually decreased after a single dose of intravenous fluids (0.9% sodium chloride injection 500 mL and 10% glucose injection 500 mL) instead of the antibiotic therapy. On the third day, WBC and neutrophils returned to normal levels. Thus, according to the Naranjo adverse drug reaction probability scale, terconazole was the probable cause of the symptoms and the elevated WBC, neutrophil, CRP, and PCT. To date, this is the first report that chest distress, and at the same time, elevation of WBC, neutrophil, CRP, and PCT were caused by terconazole. This would be beneficial to avoid the overuse of antibiotics. Resolving the adverse drug reaction with drug removal and intravenous fluids would be beneficial to avoid the overuse of antibiotics. Resolving the adverse drug reaction with drug removal and intravenous fluids would be beneficial to avoid the overuse of antibiotics.
Infected hepatic cyst complicating urinary sepsis.Acta Gastroenterol BelgCongenital hepatic cysts are a common disorder. Usually they are asymptomatic and do not have to be treated. However, some serious complications can occur. We report here the case of an 86-year old patient who has been treated by a percutaneous drainage for an infected solitary hepatic cyst due to urinary sepsis. She was admitted to the Department of Internal Medicine for epigastric pain with fever and chills. The patient was treated for a urinary tract infection 3 weeks ago by her General Practitioner. On admission, blood tests showed 21 620 neutrophils per microliter with a C-reactive protein level at 443.7 mg/L, procalcitonin > 200 ng/mL, total bilirubin at 1.43 mg/dL, lactate dehydrogenase at 666 U/L and alanine aminotransferase at 227 U/L. Urinalysis and hemocultures highlighted the presence of Escherichia coli and Streptococcus constellatus. The abdominal tomodensitometry indicated the presence of a left hepatic biliary cyst with banal appearance. She was first treated with intravenous amoxicillin clavulanic acid. After a few days, another abdominal tomodensitometry with contrast pinpointed a large abscess of 11 centimeters in diameter extending to liver segments II and IV with a similar small lesion in segments IV and V. clindamycin per os was added to the treatment because of its good diffusion in tissues. Percutaneous drain was inserted under tomodensitometric control and stayed in place until the follow-up at three weeks. Bacteriologic culture on the fluid sample demonstrated the presence of Escherichia coli and Streptococcus constellatus. The abscess completely regressed after 6 weeks of treatment and the biologic abnormalities resolved at the same time.
2021Risk Factors and Patient Profile of Infective Endocarditis due toAm J Med Case RepThe diagnosis of infective endocarditis is difficult, especially when it involves atypical organisms. Therefore, our study identified risk factors of infective endocarditis caused by rare pathogen, .A systematic review was conducted to investigate characteristics of endocarditis patients infected with using the search term "" and "endocarditis." Case reports were gathered by searching Medline/Pubmed, Google Scholar, CINAHL, Cochrane CENTRAL, and Web of Science databases. 83 articles were selected for review.Five species of were identified. Typical patients were males between 31 and 45 years of age. On admission, patients had fever, tachycardia, and normal blood pressure. Common clinical manifestation other than fever included fatigue and weakness, chills and sweating, and nausea, vomiting, diarrhea, and weight changes. One in four reported a history of congenital heart disease, and a recent oral cavity infection. Laboratory tests reveal anemia, leukocytosis, and elevated erythrocyte sedimentation in all age groups, elevated C-reactive protein is observed among adult and geriatric populations only. Mitral and aortic valves were most commonly infected by . The most common -susceptible antibiotics were penicillin, vancomycin, cephalosporin, macrolide, and aminoglycosides. However, antibiotic resistance was observed against penicillin, aminoglycoside, and fluoroquinolone. Antibiotic course of at least six weeks resulted in superior clinical improvements than durations under six weeks. Finally, one in two patients underwent valve replacement or repair, with common complications affecting the cardiovascular, neurological, and renal systems. Finally, death occurred in 1 in 8 patients, half of which occurred post-surgical procedure, and the majority occurring equal to or greater than 1 week from admission.Our systematic review highlights the importance of considering rare pathogens, particularly in the presence of predisposing risk factors.
2021Clinical and laboratory characteristics in outpatient diagnosis of COVID-19 in healthcare professionals in Rio de Janeiro, Brazil.J Clin PatholThis study aimed to identify the symptoms associated with early stage SARS-CoV-2 (COVID-19) infections in healthcare professionals (HCPs) using both clinical and laboratory data.A total of 1297 patients, admitted between 18 March and 8 April 2020, were stratified according to their risk of developing COVID-19 using their responses to a questionnaire designed to evaluate symptoms and risk conditions.Anosmia/hyposmia (p<0.0001), fever (p<0.0001), body pain (p<0.0001) and chills (p=0.001) were all independent predictors for COVID-19, with a 72% estimated probability for detecting COVID-19 in nasopharyngeal swab samples. Leucopenia, relative monocytosis, decreased eosinophil values, C reactive protein (CRP) and platelets were also shown to be significant independent predictors for COVID-19.The significant clinical features for COVID-19 were identified as anosmia, fever, chills and body pain. Elevated CRP, leucocytes under 5400×10/L and relative monocytosis (>9%) were common among patients with a confirmed COVID-19 diagnosis. These variables may help, in the absence of reverse transcriptase PCR tests, to identify possible COVID-19 infections during pandemic outbreaks.From 19 March to 8 April 2020, 1297 patients attended the Polyclinic Piquet Carneiro for COVID-19 detection. HCP data were analysed, and significant clinical features were anosmia, fever, chills and body pain. Elevated CRP, leucopenia and monocytosis were common in COVID-19.
2020E-Cigarette or Vaping Product Use-Associated Lung Injury (EVALI) Mimicking COVID-19 Disease.Case Rep PulmonolCoronavirus 2 (SARS-CoV-2) is the virus associated with the coronavirus disease (COVID-19) causing a pandemic worldwide in 2020. There are other noninfectious diseases that can present exactly as COVID-19, and the management and approach are completely different, hence the importance of understanding and having a wide differential in patients presenting with similar characteristics. . A 23-year-old male, with a history of childhood asthma, presented to the Emergency Department in a hospital in south Florida in the USA with complaints of a 2-day duration of subjective fever, chills, dry cough, dyspnea, and myalgia. His vital signs were blood pressure 135/65 mmHg, temperature 39°C, pulse 134 bpm, respiratory rate 22 breaths per minute, and saturation of oxygen 96% in room air. Laboratory analysis was significant for white blood cells 15.3 × 10/L, ALT 69 U/L, AST 66 U/L, ferritin 375.6 ng/mL, C-reactive protein 27.70 mg/dL, and procalcitonin 1.43 ng/mL. A respiratory pathogen panel (RPP) and a SARS-CoV-2 test were both negative. The patient was given empiric antibiotic treatment and hydroxychloroquine. Two more tests for SARS-CoV-2 were negative, and the patient reported that he smoked marijuana through an e-cigarette. The patient was started on high-dose steroids, and symptoms improved.COVID-19 is an emergent lung disease that is affecting the population worldwide; many other noninfectious diseases can mimic its presentations and laboratory characteristics; the importance of having a broad differential diagnosis especially in causing confusion during pandemic times is valuable in the management of patients with such presentations, such as EVALI, and glucocorticoids will be indicated in this circumstances.
2020Is C-reactive protein associated with influenza A or B in primary care patients with influenza-like illness? A cross-sectional study.Scand J Prim Health CareIdentifying influenza A or B as cause of influenza-like illness (ILI) is a challenge due to non-specific symptoms. An accurate, cheap and easy to use biomarker might enhance targeting influenza-specific management in primary care. The aim of this study was to investigate if C-reactive protein (CRP) is associated with influenza A or B, confirmed with PCR testing, in patients presenting with ILI.Cross-sectional study.Primary care in Lithuania, Norway and Sweden.A total of 277 patients at least 1 year of age consulting primary care with ILI during seasonal influenza epidemics.Capillary blood CRP analysed as a point-of-care test and detection of influenza A or B on nasopharyngeal swabs in adults, and nasal and pharyngeal swabs in children using PCR.The prevalence of positive tests for influenza A among patients was 44% (121/277) and the prevalence of influenza B was 21% (58/277). Patients with influenza A infection could not be identified based on CRP concentration. However, increasing CRP concentration in steps of 10 mg/L was associated with a significantly lower risk for influenza B with an adjusted odds ratio of 0.42 (0.25-0.70; <.001). Signs of more severe symptoms like shortness of breath, sweats or chills and dizziness were associated with higher CRP.There was no association between CRP and influenza A. Increased concentration of CRP was associated with a lower risk for having influenza B, a finding that lacks clinical usefulness. Hence, CRP testing should be avoided in ILI, unless bacterial pneumonia is suspected. Key points Identifying influenza A or B as cause of influenza-like illness (ILI) is a challenge due to non-specific symptoms. There was no association between concentration of CRP and influenza A. Increased concentration of CRP was associated with a lower risk for having influenza B, a finding that lacks clinical usefulness. A consequence is that CRP testing should be avoided in ILI, unless bacterial pneumonia or similar is suspected.
2020Jejunal Diverticulosis Probably Leading to Pylephlebitis of the Superior Mesenteric Vein.Case Rep SurgThrombophlebitis 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.
2020Case 282: Fishbone Pylephlebitis.RadiologyHistoryA 63-year-old woman with a history of left mastectomy for breast cancer and partial gastrectomy with Roux-en-Y reconstruction for nonhealing peptic ulcer presented to the emergency department and reported a 1-month history of abdominal distention, fevers, chills, and flu-like symptoms. She was initially suspected of having flu, and she completed a course of oseltamivir; however, she had continued to experience fatigue, fever, chills, abdominal bloating, and loss of appetite. She reported no contact with a sick person or recent travel. At admission, laboratory studies revealed leukocytosis, with a white blood cell count of 15.1 × 103/μL (15.1 × 109/L) (normal range, 4.0-10.0 × 103/μL [4.0-10.0 × 109/L]), an elevated sedimentation rate of 100 mm per hour (normal range, 0-30 mm per hour), and a C-reactive protein level of 203.8 mg/L (1940.9 nmol/L) (normal range, ≤10 mg/L [≤95.2 nmol/L]). Liver enzyme levels were elevated, with an alanine aminotransferase level of 48 U/L (0.80 µkat/L) (normal range, 0-29 U/L [0-0.48 µkat/L]), an aspartate aminotransferase level of 98 U/L (1.6 µkat/L) (normal range, 10-37 U/L [0.16-0.62 µkat/L]), an alkaline phosphatase level of 682 U/L (11.4 μkat/L) (normal range, 65-195 U/L [1.1-3.3 μkat/L]), and a total bilirubin level of 1.5 mg/dL (25.7 µmol/L) (normal range, 0.3-1.0 mg/dL [5.1-17.1 μmol/L]). Abdominopelvic CT was performed.
2020Prognostic factors in Spanish COVID-19 patients: A case series from Barcelona.PLoS OneIn addition to the lack of COVID-19 diagnostic tests for the whole Spanish population, the current strategy is to identify the disease early to limit contagion in the community.To determine clinical factors of a poor prognosis in patients with COVID-19 infection.Descriptive, observational, retrospective study in three primary healthcare centres with an assigned population of 100,000.Examination of the medical records of patients with COVID-19 infections confirmed by polymerase chain reaction. Logistic multivariate regression models adjusted for age and sex were constructed to analyse independent predictive factors associated with death, ICU admission and hospitalization.We included 322 patients (mean age 56.7 years, 50% female, 115 (35.7%) aged ≥ 65 years): 123 (38.2) were health workers (doctors, nurses, auxiliaries). Predictors of ICU admission or death were greater age (OR = 1.05; 95%CI = 1.03 to 1.07), male sex (OR = 2.94; 95%CI = 1.55 to 5.82), autoimmune disease (OR = 2.82; 95%CI = 1.00 to 7.84), bilateral pulmonary infiltrates (OR = 2.86; 95%CI = 1.41 to 6.13), elevated lactate-dehydrogenase (OR = 2.85; 95%CI = 1.28 to 6.90), elevated D-dimer (OR = 2.85; 95%CI = 1.22 to 6.98) and elevated C-reactive protein (OR = 2.38; 95%CI = 1.22 to 4.68). Myalgia or arthralgia (OR = 0.31; 95%CI = 0.12 to 0.70) was protective factor against ICU admission and death. Predictors of hospitalization were chills (OR = 5.66; 95%CI = 1.68 to 23.49), fever (OR = 3.33; 95%CI = 1.89 to 5.96), dyspnoea (OR = 2.92; 95%CI = 1.62 to 5.42), depression (OR = 6.06; 95%CI = 1.54 to 40.42), lymphopenia (OR = 3.48; 95%CI = 1.67 to 7.40) and elevated C-reactive protein (OR = 3.27; 95%CI = 1.59 to 7.18). Anosmia (OR = 0.42; 95%CI = 0.19 to 0.90) was the only significant protective factor for hospitalization after adjusting for age and sex.Determining the clinical, biological and radiological characteristics of patients with suspected COVID-19 infection will be key to early treatment and isolation and the tracing of contacts.
2021Successful treatment of 28 patients with coronavirus disease 2019 at a medical center in Taiwan.J Formos Med AssocCoronavirus disease-2019 (COVID-19) is a worldwide pandemic. We present the clinical characteristics and outcomes of 28 COVID-19 patients treated in our hospital in Taiwan.Patients with COVID-19, confirmed by positive real-time reverse-transcriptase polymerase chain reaction results for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral nucleic acids from oropharyngeal swab specimens between February 4, 2020 and July 6, 2020, were enrolled. Their clinical characteristics and outcomes were reviewed.Seventeen of the 28 patients (60.7%) had pneumonia. The most frequent symptoms were cough (n = 23, 82.1%) and fever (n = 17, 60.7%). The development of pneumonia was associated with age ≥40 years (p < 0.024), body mass index (BMI) ≥25 kg/m (p = 0.014), fever (p = 0.007), shortness of breath (p = 0.036), chills ((p = 0.047), and lower platelet counts (<200,000/μL) (p = 0.007). Increased quarantine duration was associated with age ≥40 years (p = 0.026), Charlson index ≥1 (p = 0.037), lower lymphocyte (<1500/uL; p = 0.028) or platelet counts (<200,000/μL) (p = 0.016), lower serum sodium (<140 mEq/L; p = 0.006), and higher C-reactive protein (CRP) level (≥1 mg/dl; p = 0.04). Treatment with hydroxychloroquine or in combination with other medicines did not reduce the quarantine duration. All 28 patients recovered with a median quarantine duration of 27.2 days.COVID-19 patients with older age, higher BMI, fever, chills or shortness of breath, lower serum sodium level, lower platelet or lymphocyte count, and higher CRP level may be associated with developing pneumonia or longer quarantine duration.
2020Clinical characteristics and outcomes of 2019-nCoV-infected patients admitted at different time periods.Eur Rev Med Pharmacol SciThe outbreak of the 2019 Novel Coronavirus Disease (COVID-19) is seriously threatening the health of people all over China and the world. This study aims to investigate the clinical characteristics and outcomes of COVID-19 patients admitted at different time periods.A total of 132 discharged cases and 10 deaths of laboratory or clinically confirmed cases were retrospectively collected from The First People's Hospital of Jingzhou, Hubei. All cases were divided into two groups according to different admission times (group 1 from 2020-1-23 to 2020-2-3 and group 2 from 2020-2-4 to 2020-2-15). Individual data, clinical data, laboratory indices and prognosis were collected for the two groups, and statistical analysis was performed using the t-test or chi-square test to assess differences between the groups.Among the 142 cases, there were 67 in the first group and 75 in the second group. According to the individual data and clinical manifestations of the two groups, the hospital stay in the first group was significantly longer than that of the second group (26 [9-39] compared with 20 [6-30], p=0.000). There were more clinical symptoms upon admission in group 1 than in group 2; although 66.2% of all patients had fever, the proportion of patients with fever on admission in the first group was significantly higher than that in the second group (79.1% compared with 54.7%, p=0.002). The proportion of patients with chills in the first group was higher than that in the second group (16.4% compared with 5.3%, p=0.032), and the proportion of patients with dyspnea was also higher than that in the second group (17.9% compared with 4%, p=0.007). Four of the 67 patients in the first group had symptoms of ocular discomfort, but none in the second group had this symptom (6.0% compared with 0, p=0.032). Based on laboratory examination, the inflammatory index of patients in the first group was higher than that in the second group, and the proportion of patients with a C-reactive protein (CRP) increase was also significantly higher (60% compared with 38.7%, p=0.020). The main difference in routine blood tests involved white blood cell and lymphocyte counts and the lymphocyte percentage. The proportion of patients with reduced white blood cell counts in the first group was higher than that in the second group (23.9% compared with 10.7% p=0.036). Moreover, more patients in the first group had a reduced lymphocyte count and percentage (71.6% compared with 30.7% p=0.000; 49.3% compared with 29.7% p=0.015, respectively), and the former was significantly lower than that in the second group (0.94 [0.24-2.42] compared with 1.365 [0.22-3.62], p=0.000). Regarding prognosis, the proportion of severe cases and mortality in the first group were slightly higher than in the second group (p>0.05).The clinical manifestations, blood changes and outcomes differed in patients admitted at different time periods. In the second group of patients, clinical symptoms were less common than in the first group, routine blood changes and inflammatory indices were milder, and the clinical prognosis was better.
2020Pneumonic versus Nonpneumonic Exacerbations of Chronic Obstructive Pulmonary Disease.Semin Respir Crit Care MedPatients with chronic obstructive pulmonary disease (COPD) often suffer acute exacerbations (AECOPD) and community-acquired pneumonia (CAP), named nonpneumonic and pneumonic exacerbations of COPD, respectively. Abnormal host defense mechanisms may play a role in the specificity of the systemic inflammatory response. Given the association of this aspect to some biomarkers at admission (e.g., C-reactive protein), it can be used to help to discriminate AECOPD and CAP, especially in cases with doubtful infiltrates and advanced lung impairment. Fever, sputum purulence, chills, and pleuritic pain are typical clinical features of CAP in a patient with COPD, whereas isolated dyspnea at admission has been reported to predict AECOPD. Although CAP may have a worse outcome in terms of mortality (in hospital and short term), length of hospitalization, and early readmission rates, this has only been confirmed in a few prospective studies. There is a lack of methodologically sound research confirming the impact of severe AECOPD and COPD + CAP. Here, we review studies reporting head-to-head comparisons between AECOPD and CAP + COPD in hospitalized patients. We focus on the epidemiology, risk factors, systemic inflammatory response, clinical and microbiological characteristics, outcomes, and treatment approaches. Finally, we briefly discuss some proposals on how we should orient research in the future.
2020Case Report: COVID-19 with Bilateral Adrenal Hemorrhage.Am J Trop Med HygA 70-year-old Dominican Republic man presented with lower back pain for 10 days. Fifteen days before pain onset, he had low-grade fever, chills, and asthenia, and 4 days before admission, he had constipation, malaise, generalized weakness, anorexia, nausea, and vomiting. On admission, the patient was afebrile and hypotensive, with a heart rate of 105 and an oxyhemoglobin saturation on room air of 95%. Hyponatremia, lymphopenia, elevated C-reactive protein, and ferritin were observed in complementary tests. Computed tomography (CT) scan showed findings consistent with COVID-19 bilateral bronchopneumonia, and an increase in size and blurring (loss of the Y shape) of both adrenals indicative of acute bilateral adrenal hemorrhage. The patient tested negative by reverse transcription polymerase chain reaction (RT-PCR) of nasopharyngeal swab, yet positive for IgG and IgM by ELISA, suggesting COVID-19 diagnosis.
2021Clinical characteristics and predictors of mortality in African-Americans with COVID-19 from an inner-city community teaching hospital in New York.J Med VirolThere is limited data on the clinical presentation and predictors of mortality in the African-American (AA) patients hospitalized with coronavirus disease 2019 (COVID-19) despite the disproportionately higher burden and mortality. The aim of this study is to report on the clinical characteristics and the predictors of mortality in hospitalized AA patients with COVID-19 infection. In this retrospective cohort review, we included all AA patients with confirmed COVID-19 infection admitted to an inner-city teaching community hospital in New York city. Demographics, clinical presentation, baseline co-morbidities, and laboratory data were compared between survivors and non-survivors. The predictors of mortality were assessed using multivariate logistic regression analysis. Of the 408 (median age, 67 years) patients included, 276 (66.65%, median age 63 years) survived while 132 (33.35%, median age 71 years) died. The most common presenting symptoms were cough, myalgia, fever/chills, shortness of breath, and gastrointestinal symptoms (nausea, vomiting, diarrhea, and abdominal pain), with a prevalence of 62.50%, 43.87%, 53.68%, and 27.21%, respectively. Age (odds ratio [OR], 1.06; confidence interval [CI], 1.04-1.08; P < .001), body mass index (OR, 1.07; CI, 1.04-1.11; P < .001), elevated serum ferritin (OR, 1.99; CI, 1.08-3.66; P < .02), C-reactive protein (OR, 2.42; CI, 1.36-4.33; P < .01), and D-dimers (OR, 3.79; CI, 2.21-6.50; P < .001) at the time of presentation were identified as the independent predictors of mortality. Cough, shortness of breath, fever/chills, gastrointestinal symptoms, and myalgia were the predominant presentation among AAs hospitalized with COVID-19 infection. Advanced age, higher body mass index, elevated serum ferritin, C-reactive protein, and D-dimers are independent predictors of mortality among hospitalized AAs with COVID-19 infection.
2020Correlations of Clinical and Laboratory Characteristics of COVID-19: A Systematic Review and Meta-Analysis.Int J Environ Res Public Health(1) Background: The global threat of Coronavirus disease 2019 (COVID-19) continues. The diversity of clinical characteristics and progress are reported in many countries as the duration of the pandemic is prolonged. We aimed to perform a novel systematic review and meta-analysis focusing on findings about correlations between clinical characteristics and laboratory features of patients with COVID-19. (2) Methods: We analyzed cases of COVID-19 in different countries by searching PubMed, Embase, Web of Science databases and Google Scholar, from the early stage of the outbreak to late March. Clinical characteristics, laboratory findings, and treatment strategies were retrospectively reviewed for the analysis. (3) Results: Thirty-seven ( = 5196 participants) COVID-19-related studies were eligible for this systematic review and meta-analysis. Fever, cough and fatigue/myalgia were the most common symptoms of COVID-19, followed by some gastrointestinal symptoms which are also reported frequently. Laboratory markers of inflammation and infection including C-reactive protein (CRP) (65% (95% confidence interval (CI) 56-81%)) were elevated, while lymphocyte counts were decreased (63% (95% CI 47-78%)). Meta-analysis of treatment approaches indicated that three modalities of treatment were predominantly used in the majority of patients with a similar prevalence, including antiviral agents (79%), antibiotics (78%), and oxygen therapy (77%). Age was negatively correlated with number of lymphocytes, but positively correlated with dyspnea, number of white blood cells, neutrophils, and D-dimer. Chills had been proved to be positively correlated with chest tightness, lung abnormalities on computed tomography (CT) scans, neutrophil/lymphocyte/platelets count, D-dimer and CRP, cough was positively correlated with sputum production, and pulmonary abnormalities were positively correlated with CRP. White blood cell (WBC) count was also positively correlated with platelet counts, dyspnea, and neutrophil counts with the respective correlations of 0.668, 0.728, and 0.696. (4) Conclusions: This paper is the first systematic review and meta-analysis to reveal the relationship between various variables of clinical characteristics, symptoms and laboratory results with the largest number of papers and patients until now. In elderly patients, laboratory and clinical characteristics indicate a more severe disease course. Moreover, treatments such as antiviral agents, antibiotics, and oxygen therapy which are used in over three quarters of patients are also analyzed. The results will provide "evidence-based hope" on how to manage this unanticipated and overwhelming pandemic.
2020Epidemiological and clinical characteristics of bacteremic brucellosis.J Int Med ResTo retrospectively investigate the epidemiological features, clinical manifestations and laboratory characteristics of bacteremic brucellosis.Brucellosis patients admitted to our clinic from January 2015 to December 2017 were included in the study. Patient electronic medical records were reviewed for epidemiological features, clinical manifestations, and laboratory findings.A total of 132 brucellosis patients were analyzed (64 cases with bacteremic brucellosis and 68 cases with nonbacteremic brucellosis). The median duration from exposure to onset of symptoms was 6.9 weeks (range: 1 day to 32 weeks) and 21.9 weeks (range: 1-76 weeks) in patients with bacteremic and nonbacteremic brucellosis, respectively. More bacteremic than nonbacteremic patients presented with fever and chills. Arthritis was observed in 34 (25.8%) patients, and was more commonly observed in nonbacteremic patients. Using C-reactive protein (CRP) and procalcitonin (PCT) as serological markers, the areas under the receiving operating characteristic curves were 0.64 [95% confidence interval (CI): 0.54-0.73] and 0.61 (95% CI: 0.51-0.70), respectively, for distinguishing bacteremic from non-bacteremic brucellosis.Fever and chills were frequently observed in bacteremic brucellosis patients, whereas arthritis was more common in nonbacteremic brucellosis patients. Serum CRP and PCT can be used as potential serological markers for diagnosing bacteremic brucellosis.
2020Identification of Enterococcus faecalis in a patient with urinary-tract infection based on metagenomic next-generation sequencing: a case report.BMC Infect DisUrinary tract infection (UTI) caused by various pathogenic microorganisms is ubiquitous in the parts of the urinary system such as kidney, ureter, bladder, and urethra. Currently, clinical detection of UTI is mainly focused on urine culture; however, the diagnostic value of urine culture remains limited due to the time-consuming procedure and low detection rate, especially in patients who have used antibiotics. Generally, treatment for UTI relies on empirical medication rather than pathogen diagnosis, which leads to the inappropriate use of antimicrobial agents and a significant increase in resistant strains. Comparatively, metagenomic next-generation sequencing (mNGS) is capable of overcoming the disadvantages of clinical culture, and identifying pathogens for further treatment.A 33-year-old male patient was admitted to hospital with a high fever and chills. None of his autoimmune disease or thyroid function related indicators were positive, and he had no risk of endocarditis. His white blood cell count, C-reactive protein, procalcitonin, interleukin 6, and neutrophil proportion were markedly elevated. He was initially diagnosed as having an infection of unknown etiology. Since empirical treatment of Sulperazon and Metronidazole did not relieve his symptoms, both the blood and urine specimens were examined using traditional culture, serological testing, and mNGS assay. Traditional culture and serological testing produced negative results, while the mNGS assay revealed the presence of a potential pathogen, Enterococcus faecalis, in the urine specimen, which was further confirmed by both Sanger sequencing and qPCR analysis. A CT scan of the patient's whole abdomen showed stones in the right kidney. Once targeted antibiotic therapy was administered, the patient recovered quickly.Our case illustrated that mNGS, as a novel culture-independent approach, demonstrated the capability of rapid, sensitive, and accurate pathogen identification. Furthermore, this technology provides strong support for guiding clinicians to determine appropriate treatment.
2020Epidemiological and clinical characteristics of COVID-19 patients in Hengyang, Hunan Province, China.World J Clin CasesIn December 2019, an ongoing outbreak of coronavirus disease 2019 (COVID-19) was first identified in Wuhan, China. The characteristics of COVID-19 patients treated in local hospitals in Wuhan are not fully representative of patients outside Wuhan. Therefore, it is highly essential to analyze the epidemiological and clinical characteristics of COVID-19 in areas outside Wuhan or Hubei Province. To date, a limited number of studies have concentrated on the epidemiological and clinical characteristics of COVID-19 patients with different genders, clinical classification, and with or without basic diseases.To study the epidemiological and clinical characteristics of COVID-19 patients in Hengyang (China) and provide a reliable reference for the prevention and control of COVID-19.From January 16 to March 2, 2020, a total of 48 confirmed cases of COVID-19 were reported in Hengyang, and those cases were included in this study. The diagnostic criteria, clinical classification, and discharge standard related to COVID-19 were in line with the Diagnosis and Treatment Protocol for Novel Coronavirus Pneumonia (Trial Version 7) released by National Health Commission and National Administration of Traditional Chinese Medicine. The presence of SARS-CoV-2 in pharyngeal swab specimens was detected by quantitative reverse transcription polymerase chain reaction. All the data were imported into the excel worksheet and statistically analyzed by using SPSS 25.0 software.A total of 48 cases of COVID-19 were collected, of which 1 was mild, 38 were moderate, and 9 were severe. It was unveiled that there were 31 (64.6%) male patients and 17 (35.4%) female patients, with a female-to-male ratio of 1.82:1. The range of age of patients with COVID-19 was dominantly 30-49 years old [25 (52.1%) of 48], followed by those aged over 60 years old [11 (22.9%)]. Besides, 29.2% (14 of 48) of patients had basic diseases, and 57.2% (8 of 14) of patients with basic diseases were aged over 60 years old. The occupations of 48 COVID-19 patients were mainly farmers working in agricultural production [15 (31.5%) of 48], rural migrant workers from Hengyang to Wuhan [15 (31.5%)], and service workers operating in the service sector [8 (16.7%)]. The mean latent period was 6.86 ± 3.57 d, and the median was 7 [interquartile range (IQR): 4-9] d. The mean time from onset of symptoms to the first physician visit was 3.38 ± 2.98 (95%CI: 2.58-9.18) d, with a median of 2 (IQR: 1-5) d, and the mean time from hospital admission to confirmed diagnosis was 2.29 ± 2.11 (95%CI: 1.18-6.42) d, with a median of 2 (IQR: 1-3) d. The main symptoms were fever [43 (89.6%) of 48], cough and expectoration [41 (85.4%)], fatigue [22 (45.8%)], and chills [22 (45.8%)]. Other symptoms included poor appetite [13 (27.1%)], sore throat [9 (18.8%)], dyspnea [9 (18.8%)], diarrhea [7 (14.6%)], dizziness [5 (10.4%)], headache [5 (10.4%)], muscle pain [5 (10.4%)], nausea and vomiting [4 (8.3%)], hemoptysis [4 (8.3%)], and runny nose [1 (2.1%)]. The numbers of peripheral blood leukocytes, lymphocytes, and eosinophils were significantly reduced in the majority of the patients. The levels of C-reactive protein, fibrinogen, blood glucose, lactate dehydrogenase, D-dimer, alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (γ-GT), myoglobin (MB), and creatine kinase (CK) were increased in 64.6%, 44.7%, 43.2%, 37.0%, 29.5%, 22.9%,20.8%, 21.6%, 13.6%, and 12.8% of patients, respectively. The incidence of ALT elevation in male patients was remarkably higher than that in females ( < 0.01), while the incidences of AST, CK, and blood glucose elevations in severe patients were remarkably higher than those in moderate patients ( < 0.05, respectively). Except for the mild patients, chest computed tomography showed characteristic pulmonary lesions. All the patients received antiviral drugs, 38 (79.2%) accepted traditional Chinese medicine, and 2 (4.2%) received treatment of human umbilical-cord mesenchymal stem cells. On March 2, 2020, 48 patients with COVID-19 were all cured and discharged.Based on our results, patients with COVID-19 often have multiple organ dysfunction or damage. The incidences of ALT elevation in males, and AST, CK, and blood glucose elevations in severe patients are remarkably higher.
2020Multisystem Inflammatory Syndrome in Children in New York State.N Engl J MedA multisystem inflammatory syndrome in children (MIS-C) is associated with coronavirus disease 2019. The New York State Department of Health (NYSDOH) established active, statewide surveillance to describe hospitalized patients with the syndrome.Hospitals in New York State reported cases of Kawasaki's disease, toxic shock syndrome, myocarditis, and potential MIS-C in hospitalized patients younger than 21 years of age and sent medical records to the NYSDOH. We carried out descriptive analyses that summarized the clinical presentation, complications, and outcomes of patients who met the NYSDOH case definition for MIS-C between March 1 and May 10, 2020.As of May 10, 2020, a total of 191 potential cases were reported to the NYSDOH. Of 95 patients with confirmed MIS-C (laboratory-confirmed acute or recent severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2] infection) and 4 with suspected MIS-C (met clinical and epidemiologic criteria), 53 (54%) were male; 31 of 78 (40%) were black, and 31 of 85 (36%) were Hispanic. A total of 31 patients (31%) were 0 to 5 years of age, 42 (42%) were 6 to 12 years of age, and 26 (26%) were 13 to 20 years of age. All presented with subjective fever or chills; 97% had tachycardia, 80% had gastrointestinal symptoms, 60% had rash, 56% had conjunctival injection, and 27% had mucosal changes. Elevated levels of C-reactive protein, d-dimer, and troponin were found in 100%, 91%, and 71% of the patients, respectively; 62% received vasopressor support, 53% had evidence of myocarditis, 80% were admitted to an intensive care unit, and 2 died. The median length of hospital stay was 6 days.The emergence of multisystem inflammatory syndrome in children in New York State coincided with widespread SARS-CoV-2 transmission; this hyperinflammatory syndrome with dermatologic, mucocutaneous, and gastrointestinal manifestations was associated with cardiac dysfunction.
2020[Clinical characteristics and CT imaging features of patients with different clinical types of coronavirus disease 2019].Zhonghua Wei Zhong Bing Ji Jiu Yi XueTo investigate the clinical characteristics and CT imaging features of patients with different clinical types of coronavirus disease 2019 (COVID-19), so as to provide a reference for the treatment and evaluation of COVID-19.The clinical data of 278 patients with COVID-19 admitted to Guangzhou Eighth People's Hospital from January 20th to February 10th in 2020 were collected. The patients were divided into mild, ordinary, severe and critical types. The differences of clinical symptoms and signs, laboratory examination indexes and CT image features of lung in different clinical types were analyzed and compared, and the relationship between clinical and imaging features and clinical types of diseases were analyzed.Among the 278 patients with COVID-19, 130 were male (46.8%) and 148 were female (53.2%), of whom 88.8% (247/278) were 20 to 69 years old. 238 (85.6%) patients combined one or more basic diseases. The source of cases was mainly imported cases (n = 201, 72.3%), of whom 89 cases were imported from Wuhan, accounting for 44.3% of all imported cases. With the aggravation of the disease, the male composition ratio, age and the number of basic diseases of patients gradually increased, and the incidences of fever, dry cough, chilly or chills, and fatigue in severe and critical patients were significantly higher than those in the mild and ordinary ones. The white blood cell count (WBC), neutrophil counts (NEU) and proportions (NEU%) of the severe and critical patients were higher than those of the mild and ordinary patients [WBC (×10/L): 5.7±3.1, 6.5±2.4 vs. 5.4±1.7, 4.9±1.6; NEU (×10/L): 4.4±3.1, 4.9±2.5 vs. 2.8±1.2, 2.9±1.3; NEU%: 0.72±0.13, 0.73±0.14 vs. 0.51±0.12, 0.59±0.11; all P < 0.01], while the lymphocyte count (LYM) and ratio (LYM%), platelet count (PLT) were lower than those in the mild and ordinary patients [LYM (×10/L): 1.0±0.4, 1.2±0.8 vs. 2.1±0.9, 1.5±0.6; LYM%: 0.21±0.11, 0.20±0.12 vs. 0.40±0.11, 0.32±0.11; PLT (×10/L): 177.1±47.8, 157.7±51.6 vs. 215.3±59.7, 191.8±64.3; all P < 0.05]. The level of albumin (Alb) was the lowest in the critical patients and the level of total bilirubin (TBil) was the highest, which was statistically significant as compared with the mild, ordinary and severe patients [Alb (g/L): 33.0±5.8 vs. 42.8±4.4, 39.6±5.1, 34.4±4.2; TBil (μmol/L): 20.1±12.8 vs. 12.0±8.7, 10.9±6.3, 12.2±8.3; both P < 0.01]. Lactate dehydration (LDH) and cardiac troponin I (cTnI) in the severe and critical patients were significantly higher than those in the mild and ordinary patients [LDH (μmol×s×L): 5.6±2.2, 5.0±2.9 vs. 2.8±0.9, 3.3±1.2; cTnI (μg/L): 0.010 (0.006, 0.012), 0.010 (0.006, 0.012) vs. 0.005 (0.003, 0.006), 0.005 (0.001, 0.008); both P < 0.05]. C-reactive protein (CRP) level of severe patients were higher than that in the mild, ordinary and critical patients [mg/L: 43.3 (33.2, 72.1) vs. 22.1 (16.2, 25.7), 29.7 (19.8, 43.1), 25.8 (23.0, 36.7), P < 0.01]. The level of procalcitonin (PCT) in the severe and critical patients was higher than that in the mild and ordinary patients [μg/L: 0.17 (0.12, 0.26), 0.13 (0.09, 0.24) vs. 0.06 (0.05, 0.08), 0.05 (0.04, 0.09), P < 0.01]. The typical CT imaging features were as follows: the ordinary type mainly showed the single or multiple ground glass shadows on the chest image; the severe type mainly showed the multiple ground glass shadows, infiltration shadows or solid transformation shadows. Compared with the ordinary patients, the lesions increase, and the scope of the lesion expanded to show double lungs. Critical type was mainly manifested as diffuse consolidation of both lungs with multiple patchy density increase shadows, multiple leafy patchy density increase shadows were seen on each leaf, most of them were ground glass-like density, and some were shown separately lung consolidation.Men, advanced aged, and combining multiple underlying diseases are high-risk populations of COVID-19, and they should pay close attention to the risk of progressing to severe or critical type. CT imaging features could be used as an important supplement when diagnosing severe and critical COVID-19.
2020Clinical Features, Diagnosis, and Treatment of COVID-19 in Hospitalized Patients: A Systematic Review of Case Reports and Case Series.Front Med (Lausanne)The 2019 novel coronavirus (COVID-19) has been declared a public health emergency worldwide. The objective of this systematic review was to characterize the clinical, diagnostic, and treatment characteristics of hospitalized patients presenting with COVID-19. We conducted a structured search using PubMed/Medline, Embase, and Web of Science to collect both case reports and case series on COVID-19 published up to April 24, 2020. There were no restrictions regarding publication language. Eighty articles were included analyzing a total of 417 patients with a mean age of 48 years. The most common presenting symptom in patients who tested positive for COVID-19 was fever, reported in up to 62% of patients from 82% of the analyzed studies. Other symptoms including rhinorrhea, dizziness, and chills were less frequently reported. Additionally, in studies that reported C-reactive protein (CRP) measurements, a large majority of patients displayed an elevated CRP (60%). Progression to acute respiratory distress syndrome (ARDS) was the most common complication of patients testing positive for COVID-19 (21%). CT images displayed ground-glass opacification (GGO) patterns (80%) as well as bilateral lung involvement (69%). The most commonly used antiviral treatment modalities included, lopinavir (HIV protease inhibitor), arbidiol hydrochloride (influenza fusion inhibitor), and oseltamivir (neuraminidase inhibitor). Development of ARDS may play a role in estimating disease progression and mortality risk. Early detection of elevations in serum CRP, combined with a clinical COVID-19 symptom presentation may be used as a surrogate marker for the presence and severity of the disease. There is a paucity of data surrounding the efficacy of treatments. There is currently not a well-established gold standard therapy for the treatment of diagnosed COVID-19. Further prospective investigations are necessary.
2020Case 282.RadiologyHistoryA 63-year-old woman with a history of left mastectomy for breast cancer and partial gastrectomy with Roux-en-Y reconstruction for nonhealing peptic ulcer presented to the emergency department and reported a 1-month history of abdominal distention, fevers, chills, and flu-like symptoms. She was initially suspected of having flu, and she completed a course of oseltamivir; however, she had continued fatigue, fever, chills, abdominal bloating, and loss of appetite. She reported no contact with a sick person or recent travel. At admission, laboratory studies revealed leukocytosis, with a white blood cell count of 15.1 × 10/µL (15.1 × 10/L) (normal range, 4.0-10.0 × 10/µL [4.0-10.0 × 10/L]), an elevated sedimentation rate of 100 mm per hour (normal range, 0-30 mm per hour), and a C-reactive protein level of 203.8 mg/L (1940.9 nmol/L) (normal range, ≤10 mg/L [≤95.2 nmol/L]). Liver enzyme levels were elevated, with an alanine aminotransferase level of 48 U/L (0.80 µkat/L) (normal range, 0-29 U/L [0-0.48 µkat/L]), an aspartate aminotransferase level of 98 U/L (1.6 µkat/L) (normal range, 10-37 U/L [0.16-0.62 µkat/L]), an alkaline phosphatase level of 682 U/L (11.4 µkat/L) (normal range, 65-195 U/L [1.1-3.3 µkat/L]), and a total bilirubin level of 1.5 mg/dL (25.7 µmol/L) (normal range, 0.3-1.0 mg/dL [5.1-17.1 µmol/L]). Abdominopelvic CT was performed (Figs 1-3).
2020Metagenomic next-generation sequencing in the diagnosis of severe pneumonias caused by Chlamydia psittaci.InfectionChlamydia psittaci infection in humans can lead to serious clinical manifestations, including severe pneumonia, adult respiratory distress syndrome, and, rarely, death. Implementation of metagenomic next-generation sequencing (mNGS) gives a promising new tool for diagnosis. The clinical spectrum of severe psittacosis pneumonia is described to provide physicians with a better understanding and to highlight the rarity and severity of severe psittacosis pneumonia.Nine cases of severe psittacosis pneumonia were diagnosed using mNGS. Retrospective analysis of the data on disease progression, new diagnosis tool, treatments, and outcomes, and the findings were summarised.Frequent symptoms included chills and remittent fever (100%), cough and hypodynamia (100%), and headache and myalgia (77.8%). All patients were severe psittacosis pneumonia developed respiratory failure, accompanied by sepsis in 6/9 patients. mNGS takes 48-72 h to provide the results, and help to identify diagnosis of psittacosis. Laboratory data showed normal or slightly increased leucocytes, neutrophils, and procalcitonin but high C-reactive protein levels. Computed tomography revealed air-space consolidation and ground-glass opacity, which began in the upper lobe of one lung, and spread to both lungs, along with miliary, nodular, or consolidated shadows. One patient died because of secondary infection with Klebsiella pneumoniae, while the other eight patients experienced complete recoveries.The use of mNGS can improve accuracy and reduce the delay in diagnosis of psittacosis. Severe psittacosis pneumonia responds well to the timely use of appropriate antibiotics.
2020Acute Pyelonephritis Associated with Ruptured Abdominal Aortic Aneurysm: An Unusual Presentation.Eur J Case Rep Intern MedWe describe a rare presentation of acute pyelonephritis associated with a ruptured abdominal aortic aneurysm. A 68-year-old female presented to the emergency department with a 3 day history of cystitis. General examination revealed the acute onset of pain in the left flank accompanied by fever and chills. Blood tests revealed leucocytosis 25,400×10/L and C-reactive protein 495 mg/L (<6.1), while urinary sediment analysis revealed many leucocytes and gram-negative bacteria. The patient was admitted with acute pyelonephritis. On the third day of admission, the urine culture isolated sensitive to the antibiotic prescribed; however, the patient clinically deteriorated. A computed tomography scan revealed a ruptured abdominal aortic aneurysm involving the left renal artery. The patient underwent an exploratory laparotomy but uncontrollable haemorrhage led to a fatal outcome. This case highlights a rare case of acute pyelonephritis associated with a ruptured abdominal aortic aneurysm. A computed tomography scan or abdominal ultrasound should be considered whenever a patient has acute pyelonephritis with a C-reactive protein >400 mg/L in order to exclude complications and other potentially fatal pathologies.Acute pyelonephritis can lead to a ruptured abdominal aortic aneurysm.There should be a high index of suspicion for other concomitant acute pathologies in patients with pyelonephritis and a C-reactive protein >400 mg/L.A low threshold for abdominal imaging, either a computed tomography scan or abdominal ultrasound, may allow for the diagnosis of pathologies with a high mortality rate, such as a ruptured abdominal aortic aneurysm, at an early stage and thus result in better prognosis.
2020Molecular diagnosis of autochthonous human anaplasmosis in Austria - an infectious diseases case report.BMC Infect DisThe diagnosis of human anaplasmosis remains elusive and is probably often missed. This case report highlights the efficacy of molecular diagnostic techniques.We would like to report the case of a 74-year-old man who was admitted to hospital because of a high fever, marked chills, transient diplopic images and vertigo, 6 weeks after multiple tick bites. The laboratory results showed mild anemia, marked thrombocytopenia and leukopenia and a moderately elevated C-reactive protein. The initial serology seemed to indicate an active infection with Borrelia spp., and Anaplasma phagocytophilum was detected in peripheral blood by polymerase chain reaction (PCR) and subsequent sequencing. The patient received intravenous ceftriaxone for 14 days and oral doxycycline for 4 weeks and made a fast and complete recovery.While human anaplasmosis has been reported very rarely in Austria, it should be considered as a differential diagnosis in febrile patients with low leukocyte and platelet counts with elevated levels of C-reactive protein after exposure to tick bites. Molecular detection of A. phagocytophilum is the technique of choice allowing rapid and reliable diagnosis.
2020Asymptomatic cardiac and gallbladder involvement at initial presentation of Legionnaires' disease.Pol Merkur LekarskiExtrapulmonary manifestations of Legionnaires' disease (LD) include, inter alia cardiac, brain, abdominal, joints and skin involvement.The authors describe a case of a 41-year-old immunocompetent female admitted due to a high fever, chills and fatigue. She negated cough and chest or abdominal pain. Initial chest X-ray was normal. Among laboratory abnormalities were: elevation of C-reactive protein, procalcitonin, transaminases and creatinine, hyponatremia, low white blood cell and platelet count and a moderate proteinuria. ECG showed subtle ST elevation. Echocardiography revealed normal left ventricular (LV) contractility and near normal longitudinal strain, mild myocardial thickening, and a small pericardial effusion; additionally, in subcostal view, gallbladder wall thickening (GBWT) was found. Positive L. pneumophila urinary antigen test confirmed LD diagnosis. Control Xray and CT showed development of pleural effusion and bilateral pulmonary infiltrations. Clinical and radiologic improvement of the disease was achieved with ciprofloxacin therapy started from admission. ECG abnormalities persisted for only 5 days, GBWT resolved after 9 days, pericardial effusion disappeared after 10 days; normalization of LV thickness and an increase in longitudinal strain was found within 2 weeks. However, cardiac magnetic resonance (CMR) performed after a month revealed focal midmyocardial and linear subepicardial late gadolinium enhancement (LGE).The authors underline the fact that being aware of extrapulmonary LD, also silent, may allow to diagnose the disease, especially when pulmonary involvement is initially absent.
2020[Comparison of the clinical characteristics between RNA positive and negative patients clinically diagnosed with coronavirus disease 2019].Zhonghua Jie He He Hu Xi Za ZhiTo raise awareness about 2019 novel coronavirus pneumonia (NCP) and reduce missed diagnosis rate and misdiagnosis rate by comparing the clinical characteristics between RNA positive and negative patients clinically diagnosed with NCP. From January 2020 to February 2020, 54 patients who were newly diagnosed with NCP in Wuhan Fourth Hospital were included in this study. RT-PCR method was used to measure the level of 2019-nCov RNA in pharyngeal swab samples of these patients. The patients were divided into RNA positive and negative group, and the differences of clinical, laboratory, and radiological characteristics were compared. There were 31 RNA of 2019-nCov positive cases, and 23 negative cases. Common clinical symptoms of two groups were fever (80.64% vs. 86.96%) , chills (61.29% vs. 52.17%) , cough (80.64% vs. 95.65%) , fatigue (61.30% vs. 56.52%) , chest distress (77.42% vs.73.91%) . Some other symptoms were headache, myalgia, dyspnea, diarrhea, nausea and vomiting. The laboratory and radiological characteristics of two groups mainly were lymphopenia, increased erythrocyte sedimentation rate, increased C-reactive protein, increased lactate dehydrogenase, decreased oxygenation index, normal white blood cell count and bilateral chest CT involvement. There was no statistically significant difference in other clinical characteristics except for dyspnea between two groups. RNA positive and negative NCP patients shared similar clinical symptoms, while RNA positive NCP patients tended to have dyspnea. Therefore, we should improve the understanding of NCP to prevent missed diagnosis and misdiagnosis; In addition, more rapid and accurate NCP diagnostic approaches should be further developed.
2019Endoscopic Ultrasound-Guided Hepaticogastrostomy With Lumen-Apposing Metal Stent for Management of Pyogenic Liver Abscess.ACG Case Rep JA 45-year-old man presented with abdominal pain, fever with chills, nonproductive cough, mild pleurisy, and anorexia. Computed tomography scan showed a heterogeneously enhancing mass in the left hepatic lobe with leukocytosis and elevated C-reactive protein. Interval growth of the lesion was noted on magnetic resonance imaging obtained several days after admission. Given the clinical suspicion for pyogenic liver abscess and favorable location in the left hepatic lobe, endoscopic ultrasound-guided drainage was pursued. The patient underwent endoscopic ultrasound-guided hepaticogastrostomy with a lumen-apposing metal stent. His symptoms gradually abated after procedure. Radiographic resolution of the abscess was noted 1 week after stent placement, and the stent was subsequently removed. He had no clinical or radiographic evidence of recurrence at 1-month follow-up.
2019Psoas abscess associated with aortic endograft infection caused by bacteremia of Listeria monocytogenes: A case report and literature review (CARE Complaint).Medicine (Baltimore)Endograft infection following endovascular stent for aortic aneurysm is rare (0.6%-3%), but it results in high mortality rate of 25% to 88%.A 66-year-old hypertensive man underwent an endovascular stent graft for abdominal aortic aneurysm 18 months ago. Recurrent episodes of fever, chills, and abdominal fullness occurred 6 months ago before this admission. Laboratory data showed 20 mg/dL of C-reactive protein and abdominal computed tomography (CT) revealed an aortic endoleak at an urban hospital, so 4-day course of intravenous (IV) amoxicillin/clavulanic acid was given and he was discharged after fever subsided. He was admitted to our hospital due to fever, chills, and watery diarrhea for 1 day. Abdominal CT showed left psoas abscess associated with endograft infection. Blood culture grew Listeria monocytogenes.Left psoas abscess associated with endograft infection caused by bacteremia of Listeria monocytogenes.IV ampicillin with 8 days of synergistic gentamicin was prescribed and it created satisfactory response. Ampicillin was continued for 30 days and then shifted to IV co-trimoxazole for 12 days.He remained asymptomatic with a decline of CRP to 0.36 mg/dL and ESR to 39 mm/h. He was discharged on the 44th hospital day. Orally SMX/TMP was prescribed for 13.5 months.Only few cases of aortic endograft infection caused by Listeria monocytogenes had been reported. In selected cases, particularly with smoldering presentations and high operative risk, endograft retention with a prolonged antimicrobial therapy seem plausible as an initial therapeutic option, complemented with percutaneous drainage or surgical debridement if necessary.
2019Nitrofurantoin-associated Acute Pulmonary Toxicity Mimicking Severe Sepsis with Significantly Elevated Procalcitonin.CureusNitrofurantoin is a commonly used treatment for urinary tract infections with a risk for pulmonary toxicity. We report a case of a 48-year-old woman on a prophylactic regimen of nitrofurantoin who exhibited classic signs of bacterial sepsis including elevated procalcitonin (PCL) and C-reactive protein (CRP) levels two days post-nephrolithotripsy. The microbial analysis did not reveal an infectious cause for the initial symptoms and, subsequently, the patient developed a dry cough, fever, chills, and transient hypoxemia requiring supplemental oxygen. Pulmonary imaging revealed significant abnormal features inconsistent with the patient's symptoms which indicated an inflammatory/immune reaction to nitrofurantoin. Treatment discontinuation improved the patient's symptoms and reduced PCL and CRP levels to within normal limits. A high index of suspicion for nitrofurantoin-associated pulmonary toxicity is warranted for patients on a regimen of nitrofurantoin who exhibit severe pulmonary symptoms and elevated PCL and CRP levels with no corresponding infection.
2019Intravascular Large B-Cell Lymphoma Presenting with Hypoxemia without any Abnormalities on Standard Imaging Studies.Am J Case RepBACKGROUND Intravascular large B-cell lymphoma (IVLBCL) is characteristically diagnosed by histological examination of biopsies of bone marrow or randomly harvested skin specimens in the absence of any diagnostic abnormalities on imaging studies, including computed tomography (CT). In particular, diagnosis of IVLBCL with pulmonary manifestations is challenging, because even in patients with severe respiratory failure, there are rarely abnormalities on standard imaging studies. CASE REPORT A 75-year-old female presented with fatigue, weight loss, and high fever with chills for 3 months. Blood examinations on her initial visit to her primary physician showed high concentrations of C-reactive protein, lactate dehydrogenase, and soluble interleukin-2 receptor. There were no abnormalities on imaging studies. She was subsequently admitted to our hospital because of development of dyspnea over time (4 months after symptom onset). Although she was suspected of having IVLBCL, repeated biopsies from bone marrow, skin, liver, and lung did not result in a diagnosis. Finally, a lung biopsy obtained by video-associated thoracic surgery (VATS) from the right lung base, where fluorine-18 fluorodeoxyglucose positron emission tomography had shown high uptake, resulted in a definite diagnosis of IVLBCL. CONCLUSIONS Highly invasive procedures such as thoracoscopic lung resection may be required to diagnose IVLBCL with pulmonary manifestations which can cause severe respiratory failure in the absence of any abnormalities on standard imaging studies.
2019Isolated neutropenia as a rare but serious adverse event secondary to immune checkpoint inhibition.J Immunother CancerCompared to conventional chemotherapy, Immune checkpoint inhibitors (ICI) are known to have a distinct toxicity profile commonly identified as immune-related adverse events (irAEs). These irAEs that are believed to be related to immune dysregulations triggered by ICI can be serious and lead to treatment interruptions and in severe cases, precipitate permanent discontinuation. Isolated neutropenia secondary to ICI has been rarely documented in the literature and needs further description. We report a case of pembrolizumab related severe isolated neutropenia in a patient with metastatic non-small cell lung cancer. We were also able to obtain serial blood and plasma-based biomarkers for this patient during treatment and during neutropenia to understand trends that may correlate with the irAE. In addition we summarize important findings from other studies reporting on ICI related neutropenia.A 74 years old Caucasian male treated with single-agent pembrolizumab for metastatic non-small cell lung cancer presented with fevers, chills, and an isolated neutrophil count (ANC) of 0 2 weeks after the fourth dose. In addition to antibiotics, due to the strong suspicion of this neutropenia being immune-mediated, he was started on 1 mg/kg of steroids and also received filgrastim to accelerate neutrophil recovery. Serial trends in C-reactive protein and certain other inflammatory cytokines demonstrated a corresponding rise at the time of neutropenia. Post recovery, his pembrolizumab was kept on hold. Eight weeks later he had a second episode of neutropenia which was again managed similar to the first episode. Despite permanent discontinuation of ICI after the first neutropenia, his disease showed an ongoing complete metabolic response on imaging. Our literature review reveals that hematological toxicities constitute < 1% irAEs with isolated neutropenia roughly accounting for one-fourth of the hematological irAEs. Based on the handful of ICI related neutropenia cases reported to date, we identified nivolumab to be the most common offender. The median number of ICI cycles administered before presenting with neutropenia was three, and the median time to recovery was approximately two weeks. All of these neutropenic episodes were ≥ grade 3 and led to permanent ICI discontinuation. Using immunosuppressive therapies in conjunction with granulocyte-colony stimulating factor was the most common strategy described to have favorable results.Neutropenia as an isolated irAE secondary to ICI is rare but represents a severe toxicity that needs early recognition and can often result in treatment discontinuations. Careful monitoring of these patients with the prompt initiation of immunosuppressive and supportive measures to promote rapid recovery as well as prevent and treat infectious complications should be part of the management algorithms. Serial monitoring of blood and plasma-based biomarkers from more extensive studies may help in identifying patients at risk for irAEs and thus guide patient selection for ICI.
2019Case 265: Lemmel Syndrome or Biliary Obstruction Due to a Periampullary Duodenal Diverticulum.RadiologyHistory A 70-year-old man presented to the emergency department with fever, chills, rigors, and upper abdominal discomfort. Physical examination revealed jaundice and mild right upper quadrant tenderness. Laboratory tests revealed an increased C-reactive protein level of 133 mg/L (normal range, 0.2-0.9 mg/L), a white blood cell count of 11.69 ×10/L (normal range, 4-10 ×10/L), and an obstructive pattern on liver function tests, with a total bilirubin level of 3.5 mg/dL (59.9 µmol/L) (normal range, 0.4-1.9 mg/dL [6.8-32.5 µmol/L]), an alkaline phosphatase level of 716 U/L (11.9 µkat/L) (normal range, 39-99 U/L [0.65-1.65 µkat/L]), and an aspartate aminotransferase level of 88 U/L (1.47 µkat/L) (normal range, 12-42 U/L [0.20-0.70 µkat/L]). Serum amylase level was within normal limits at 84 U/L (1.40 µkat/L) (normal range, 38-149 U/L [0.63-2.48 µkat/L]). A clinical diagnosis of hepatobiliary sepsis due to ascending cholangitis was made. Relevant medical history included gastric carcinoma treated with a Billroth II surgical procedure 17 years earlier that was performed in conjunction with cholecystectomy. In addition, there were episodes of ascending cholangitis 6-12 months prior to the current admission that were managed conservatively with antibiotics at another institution. Blood cultures were positive for . Administration of intravenous antibiotics was started, and CT examination of the abdomen was performed. Because a previous Billroth II procedure had been performed, the patient underwent percutaneous transhepatic cholangiography.
2019A rare cause of abdominal pain with fever.BMJ Case RepAn 89-year-old man presented to the emergency department with a 1-month history of upper right quadrant pain, worsened in the last 3 days and accompanied by fever and chills. On physical examination, he had scleral icterus and right upper quadrant tenderness. Laboratory findings showed hyperbilirubinemia, elevated liver enzymes and C reactive protein. The patient was admitted, suspecting of an acute cholangitis and started on antibiotics. An upper gastrointestinal endoscopy revealed the presence of a juxtapapillary diverticulum in the second portion of the duodenum, which was confirmed by a magnetic resonance cholangiopancreatography, along with upstream biliary tract ectasia. The imaging findings allowed us to diagnose a Lemmel's syndrome. Due to potential surgical risk, we decided for a conservative approach. The patient had a favourable course and was discharged home.
2019Procalcitonin, mid-regional proadrenomedullin and C-reactive protein in predicting treatment outcome in community-acquired febrile urinary tract infection.BMC Infect DisA reduction in duration of antibiotic therapy is crucial in minimizing the development of antimicrobial resistance, drug-related side effects and health care costs. The minimal effective duration of antimicrobial therapy for febrile urinary tract infections (fUTI) remains a topic of uncertainty, especially in male patients, those of older age or with comorbidities. Biomarkers have the potential to objectively identify the optimal moment for cessation of therapy.A secondary analysis of a randomized placebo-controlled trial among 35 primary care centers and 7 emergency departments of regional hospitals in the Netherlands. Women and men aged ≥18 years with a diagnosis of fUTI were randomly assigned to receive antibiotic treatment for 7 or 14 days. Patients indicated to receive antimicrobial treatment for more than 14 days were excluded from randomization. The biomarkers procalcitonin (PCT), mid-regional proadrenomedullin (MR-proADM), and C-reactive protein (CRP) were compared in their ability to predict clinical cure or failure through the 10-18 day post-treatment visit.Biomarker concentrations were measured in 249 patients, with a clinical cure rate of 94% in the 165 randomized and 88% in the 84 non-randomized patients. PCT, MR-proADM and CRP concentrations did not differ between patients with clinical cure and treatment failure, and did not predict treatment outcome, irrespective of 7 or 14 day treatment duration (ROC 0.521; 0.515; 0.512, respectively). PCT concentrations at presentation were positively correlated with bacteraemia (τ = 0.33, p < 0.001) and presence of shaking chills (τ = 0.25, p < 0.001), and MR-proADM levels with length of hospital stay (τ = 0.40, p < 0.001), bacteraemia (τ = 0.33, p < 0.001), initial intravenous treatment (τ = 0.22, p < 0.001) and time to defervescence (τ = 0.21, p < 0.001). CRP did not display any correlation to relevant clinical parameters.Although the biomarkers PCT and MR-proADM were correlated to clinical parameters indicating disease severity, they did not predict treatment outcome in patients with community acquired febrile urinary tract infection who were treated for either 7 or 14 days. CRP had no added value in the management of patients with fUTI.The study was registered at ClinicalTrials.gov [ NCT00809913 ; December 16, 2008] and trialregister.nl [ NTR1583 ; December 19, 2008].
2019Polyarteritis nodosa presenting atypically as appendicitis and pyelonephritis in a single patient.BMJ Case RepA 17-year-old man presented to the emergency department 10 days postlaparoscopic appendicectomy with ongoing lower abdominal pain. The pain was associated with fevers, chills, sweating and constipation. There were no other associated symptoms. On examination, there was suprapubic and right lower quadrant tenderness and an elevated blood pressure (140/90 mm Hg). The patient later developed severe bilateral flank pain. Investigations revealed elevated C reactive protein, leukocyturia and microscopic haematuria. Blood and urine cultures were negative. CT angiogram demonstrated bilateral wedge-shaped peripheral renal hypodensities suggestive of several peripheral infarcts with intrarenal microaneurysms. Treatment with steroids and cyclophosphamide was initiated, leading to significant clinical improvement. Review of the histological appendix specimen revealed features consistent with small-medium vessel vasculitis.
2019Rare Simultaneous Left and Right-Sided Native Valve Infective Endocarditis Caused by Rare Bacterium.Int Heart JSimultaneous left and right-sided native valve infective endocarditis (IE) is rare. Staphylococcus aureus was the predominant organism for bilateral IE. Shunt diseases are common risk factors of both-sided IE. Streptococcus anginosus (S. anginosus) is usually associated with pyogenic infections, but rarely a cause of IE. Here we present an extremely rare case of simultaneous left and right-sided native valve IE affecting the mitral and tricuspid valves caused by S. anginosus in an adult patient that has not been reported in the literature previously, particularly without the most frequent predisposing factors of IE. A 66-year-old man was admitted due to generalized fatigue, chills, malaise, and intermittent fevers for 1 year. A grade III-IV/VI systolic murmur at the mitral area and a III/VI systolic murmur at the tricuspid area were noted on physical examination. Laboratory evaluation revealed an elevated erythrocyte sedimentation rate and C-reactive protein level, and high fasting blood glucose. Blood culture was positive for S. anginosus. Echocardiography revealed vegetations in both sides of the heart: a large mitral valve vegetation with severe mitral regurgitation, as well as another vegetation on the tricuspid valve with moderate regurgitation. The case highlights a rare pathogen of both-sided IE, a rare presentation of S. anginosus infection, and several points worthy of note in echocardiography of IE.
2019Case 265.RadiologyHistory A 70-year-old man presented to the emergency department with fever, chills, rigors, and upper abdominal discomfort. Physical examination revealed jaundice and mild right upper quadrant tenderness. Laboratory tests revealed an increased C-reactive protein level of 133 mg/L (normal range, 0.2-0.9 mg/L), a white blood cell count of 11.69 ×10/L (normal range, 4-10 ×10/L), and an obstructive pattern on liver function tests, with a total bilirubin level of 3.5 mg/dL (59.9 µmol/L) (normal range, 0.4-1.9 mg/dL [6.8-32.5 µmol/L]), an alkaline phosphatase level of 716 U/L (11.9 µkat/L) (normal range, 39-99 U/L [0.65-1.65 µkat/L]), and an aspartate aminotransferase level of 88 U/L (1.47 µkat/L) (normal range, 12-42 U/L [0.20-0.70 µkat/L]). Serum amylase level was within normal limits at 84 U/L (1.40 µkat/L) (normal range, 38-149 U/L [0.63-2.48 µkat/L]). A clinical diagnosis of hepatobiliary sepsis due to ascending cholangitis was made. Relevant medical history included gastric carcinoma treated with a Billroth II surgical procedure 17 years earlier that was performed in conjunction with cholecystectomy. In addition, there were episodes of ascending cholangitis 6-12 months prior to the current admission that were managed conservatively with antibiotics at another institution. Blood cultures were positive for Klebsiella oxytoca. Administration of intravenous antibiotics was started, and CT examination of the abdomen was performed ( Fig 1 ). Because a previous Billroth II procedure had been performed, the patient underwent percutaneous transhepatic cholangiography ( Fig 2 ). Figure 1a: (a) Arterial phase axial CT image at the level of the pancreatic head. (b) Portal venous phase coronal reformatted CT image shows the upper abdomen. Figure 1b: (a) Arterial phase axial CT image at the level of the pancreatic head. (b) Portal venous phase coronal reformatted CT image shows the upper abdomen. Figure 2: Fluoroscopic image obtained with percutaneous transhepatic cholangiography during the most recent admission.
2018Drug Hypersensitivity due to Azathioprine with Elevated Procalcitonin.Case Rep Dermatol MedWe present a case of azathioprine hypersensitivity presenting as sepsis with elevated procalcitonin in a 68-year-old man with myasthenia gravis. The patient presented with fever, chills, nausea, vomiting, and headache. He developed numerous 1 cm erythematous papules over his upper torso. Infectious workup including bacteriological tests and microbial cultures was negative and a skin biopsy was performed which revealed suppurative folliculitis with eosinophils, consistent with drug hypersensitivity. Notably, acute phase reactants including C-reactive protein and procalcitonin were elevated upon presentation, likely secondary to drug hypersensitivity.
2018Enterococcus gallinarum meningitis: a case report and literature review.BMC Infect DisAs an opportunistic pathogen, E. gallinarum mainly leads to nosocomial infections, and it's multi-drug resistance has gained more and more attention. Central nervous system infections caused by E. gallinarum are rare, but have been reported more often in recent years. The previous cases were generally secondary to neurosurgery, especially ventriculoperitoneal shunts. In recent years, the cases largely occurred in patients with impaired immune function. The patient in our report may have had dual risk factors (immune impairment and an invasive surgical procedure).The patient, a 35-year-old female, was admitted to our hospital for headaches of 3 days duration accompanied by nausea and vomiting for 2 days. The patient had fevers and chills for 3 days before admission; the peak body temperature was 38.5 °C. The patient had a splenectomy in our hospital 2 years earlier for thrombocytopenia and was thought to be immunocompromised. The abnormal findings on physical examination and laboratory testing were as follows: neck stiffness, present; lumbar puncture: pressure, 300 mmHO; Pandy's test, positive; white blood cell (WBC) count, 1536 × 10/L; monocyte count, 602 × 10/L; monocyte percentage, 39.2%; multinucleate cell count, 934 × 10/L; multinucleate cell percentage, 60.8%; protein, 1.08 g/L; WBC count, 21.1 × 10/ L; neutrophil percentage, 85.3%; neutrophil count, 20.55 × 10/L; C reactive protein (CRP): 136.4 mg/L; procalcitonin, 6.70 ng/mL. The patient was given meropenem (2.0 g, intravenous infusion, every 8 h) for anti-infection supplemented with other symptomatic support treatments. The patient's fever and headache had no significant relief.Central nervous system infections caused by E. gallinarum are rare, but should be suspected, particularly inpatients with impaired immune function or ineffective treatment. Avoiding long-term invasive treatment and improving immunity are helpful to reduce the occurrence of E. gallinarum infections. Early detection and diagnosis, as well as rational antibiotic use, are the keys to achieve satisfactory efficacy.
2018Human babesiosis in Southeast China: A case report.Int J Infect DisA 60-year-old female patient living in Southeast China presented with persistent fever, chills, night sweats, fatigue, and dizziness of 12-day duration. Blood tests showed neutropenia, thrombocytopenia, and active hemolytic anemia, with elevated C-reactive protein. Broad-spectrum antibiotics were administered for a possible diagnosis of sepsis, without any response. Malaria was initially diagnosed after visualizing intraerythrocytic ring-shaped parasites in bone marrow and blood smears. The patient resided in an area of unstable endemicity for Plasmodium falciparum. Blood samples were sent to the Centers for Disease Control and Prevention and a definitive diagnosis of human babesiosis was made using Babesia microti-specific PCR. Chloroquine phosphate and clindamycin were started and the patient became normothermic. However, due to the intolerable adverse effects of the antibiotics, intravenous azithromycin was given as an alternative. The patient recovered from fever and hemolysis, and repeated peripheral blood smears showed hemoparasite clearance. Cases of human babesiosis are rarely reported and probably under-diagnosed in China; therefore, improving our understanding of this disease as a newly emerging public health threat is imperative.
2017Fever, rash, and leukopenia in a 32-year-old man · Dx?J Fam PractA 32-year-old man was admitted to our hospital with fever, chills, malaise, leukopenia, and a rash. About 3 weeks earlier, he'd had oral maxillofacial surgery and started a 10-day course of prophylactic amoxicillin/clavulanic acid. Fifteen days after the surgery, he developed a fever (temperature, 103° F), chills, arthralgia, myalgia, cough, diarrhea, and malaise. He was seen by his physician, who obtained a chest x-ray showing a lingular infiltrate. The physician diagnosed influenza and pneumonia in this patient, and prescribed oseltamivir, azithromycin, and an additional course of amoxicillin/clavulanic acid. Upon admission to the hospital, laboratory tests revealed a white blood cell count (WBC) of 3.1 k/mcL (normal: 3.2-10.8 k/mcL). The patient's physical examination was notable for lip edema, white mucous membrane plaques, submandibular and inguinal lymphadenopathy, and a morbilliform rash across his chest. Broad-spectrum antibiotics were initiated for presumed sepsis. On hospital day (HD) 1, tests revealed a WBC count of 1.8 k/mcL, an erythrocyte sedimentation rate of 53 mm/hr (normal: 20-30 mm/hr for women, 15-20 mm/hr for men), and a C-reactive protein level of 6.7 mg/dL (normal: <0.5 mg/dL). A repeat chest x-ray and orofacial computerized tomography scan were normal. By HD 3, all bacterial cultures were negative, but the patient was positive for human herpesvirus-6 on viral cultures. His leukopenia persisted and he had elevated levels of alanine transaminase ranging from 40 to 73 U/L (normal: 6-43 U/L) and aspartate aminotransferase ranging from 66 to 108 U/L (normal range: 10-40 U/L), both downtrending during his hospitalization. He also had elevated levels of antinuclear antibodies and anti-Smith antibody titers. A posterior-auricular biopsy was consistent with lymphocytic perivasculitis. The rash continued to progress, involving his chest, abdomen, and face. Bacterial and viral cultures remained negative and on HD 4, broad-spectrum antibiotics were discontinued.
2019Characteristics of scrub typhus, murine typhus, and Q fever among elderly patients: Prolonged prothrombin time as a predictor for severity.J Microbiol Immunol InfectThe clinical manifestations of scrub typhus, murine typhus and acute Q fever in the elderly are not clear.We conducted a retrospective study to identify the characteristics of the elderly aged ≥65 years with a comparison group aged 18-64 years among patients with scrub typhus, murine typhus, or acute Q fever who were serologically confirmed at three hospitals in Taiwan during 2002-2011.Among 441 cases, including 187 cases of scrub typhus, 166 acute Q fever, and 88 murine typhus, 68 (15.4%) cases were elderly patients. The elderly had a higher severe complication rate (10.3% vs. 3.5%, p = 0.022), but did not have a significantly higher mortality rate (1.47% vs. 0.54%, p = 0.396). Compared with those without severe complications, we found the elderly (p = 0.022), dyspnea (p = 0.006), less relative bradycardia (p = 0.004), less febrile illness (p = 0.004), prolonged prothrombin time (PT) (p = 0.002), higher levels of initial C-reactive protein (p = 0.039), blood leukocyte counts (p = 0.01), and lower platelet counts (p = 0.012) are significantly associated with severe complications. Only prolonged prothrombin time was associated with severe complications in multivariate analysis (p = 0.018, CI 95% 0.01-0.66). Among clinical symptoms and laboratory data, multivariate analysis revealed chills was less frequently occurred in the elderly (p = 0.012, 95% confidence interval [CI]: 1.33-9.99).The elderly cases with scrub typhus, murine typhus, or acute Q fever would be more likely to have severe complications, for which prothrombin time prolongation is an important predictor for severe complications.
2017A Unique Presentation of an Intracranial Abscess Secondary to Retained Projectile after Debridement with Dural Closure.CureusPatients with penetrating head trauma with retained projectiles develop intracranial abscesses as a common complication. The most common presentation is a suddenly worsening headache. The most common pathogen identified is staphylococcus. Outcomes are related to adherence of Matson's tenets. This case study details the presentation of a 19-year-old patient that presented to the neurological surgery clinic without neurologic deficits. Further questioning revealed complaints of intermittent diffuse headaches with bilateral upper extremity shock-like sensation for two weeks. Eight weeks prior he had undergone right craniotomy, after a gunshot wound, for debridement and watertight dural closure. The patient denied symptoms of fever, chills, nausea, vomiting, diarrhea, or seizure. The patient presented with a noncontrast head computed tomography (CT) which revealed retained projectile fragments without clear evidence of abscess. On physical exam, the patient was without any neurological deficit. Laboratory investigation revealed normal white blood cell count, erythrocyte sedimentation rate, C-reactive protein, and negative blood cultures. Head CT with contrast revealed a large intracerebral abscess adjacent to the thalamus. The patient was taken to the operating room for repeat craniotomy with resection of the abscess and removal of the intracranial projectile fragments. Post-operatively, the patient remained neurology intact. Intraoperative cultures were not significant for the growth of any bacteria. In eight weeks time, the patient returned to his employment and his baseline level of activity. This case underscores the importance of thorough assessment in patients with retained intracranial projectiles as well as the need to routine follow-up. The unique presentation of this patient prompted further investigation which elucidated a lesion which correlated to his symptoms although laboratory assessment was without abnormality.
2017[Marcato aumento delle concentrazioni di procalcitonina dopo idroclorotiazide-edema polmonare indotta.]Recenti Prog MedIn the Medline database there are approximately 60 cases reporting toxic pulmonary edema, a life-threatening event, induced after consumption of hydrochlorothiazide, one of the most common antihypertensive drugs. Moreover, increased procalcitonin concentrations have been reported after cardiogenic pulmonary edema. We report the rare case of a hydrochlorothiazide-induced pulmonary edema, which was followed by a marked increase of the procalcitonin concentrations.A middle-aged woman was admitted to the Emergency Department for severe dyspnea and chills. Such symptoms began 30 minutes after consumption of hydrochlorothiazide. Her physical examination and chest-X-ray were compatible with pulmonary edema, however her brain natriuretic peptide levels and echocardiogram were almost normal. Interestingly she had extremely elevated procalcitonin concentrations with normal white blood cells count and C-reactive protein levels only mildly increased. We hypothesized toxic pulmonary edema and started treatment with non-invasive mechanical ventilation, with the patient presenting rapid clinical improvement.Even if extremely rare, hydrochlorothiazide may induce pulmonary edema; significant increase of procalcitonin concentrations may occur in this condition and perhaps in other cases of toxic pulmonary edema. Practitioners should be aware of this condition in order to spare expensive and useless, in this case, investigations such as blood cultures and treatments (antibiotics) if other signs of infection are absent.
The typical presentation of an atypical pathogen during an outbreak of Legionnaires' disease in Vila Franca de Xira, Portugal, 2014.Rev Port Pneumol (2006)An outbreak of Legionella pneumophila serogroup 1, with 403 cases was identified on the 7th November 2014 in Vila Franca de Xira, Portugal. Outbreak source was the wet cooling system of a local factory. Hospital Pulido Valente was one of the hospitals receiving patients with Legionnaires' disease (LD).We describe the clinical findings and diagnostic methods used among the 43 confirmed or probable cases admitted to our department.60.5% were male, mean age was 56.1±13.5 years and tobacco smoking was the most frequent risk factor (76.7%). All patients had fever, 62.8% ≥39.5°C, 72.1% had chills and myalgia/arthralgia and 62.8% had dry cough. Extra pulmonary symptoms were frequent: confusion and headache occurred in 34.9% and gastrointestinal symptoms in 20.9%. High C-Reactive Protein (55.8% ≥30mg/dL) and hyponatremia (62.8%) were the laboratorial abnormalities most commonly found. Hypoxemia occurred in 55.8% and hypocapnia in 93%. Urinary Antigen Test (UAT) was positive in 83.7% of the cases.Although not specific, a combination of risk factors, symptoms and laboratory findings can be highly suggestive of LD, even in an outbreak. This should prompt diagnosis confirmation. Routine use of UAT in less severe cases of community acquired pneumonia might contribute to earlier diagnosis.
2016A rare case of abdominal infection: Emphysematous pyelonephritis without diabetes.Interv Med Appl SciEmphysematous pyelonephritis (EP) is a rare form of necrotizing pyelonephritis. It is a life-threatening condition that usually affects patients with diabetes, and a small percentage may be due to urinary tract obstruction. Here, we present the case of an EP caused by urinary tract obstruction without diabetes. A 45-year-old woman presented to the emergency department with fever, chills, and abdominal pain. There was no significant past history. Physical examination depicted bilateral lower abdominal and right flank knocking tenderness. Laboratory exams revealed leukocytosis, neutrophilia, a high C-reactive protein level, and pyuria. Abdominal computerized tomography (CT) showed diffuse gas in the right renal collecting system and dilatation of the right renal pelvis compared to the right side, in addition to multiple millimetric stones located in the right kidney and right ureter. After emergent placement of a percutaneous nephrostomy, she was admitted. Control abdominal CT without contrast revealed the absence of gas, hydronephrosis of the right renal pelvis, and the presence of nephrolithiasis. The patient was discharged 10 days of post-procedure with instructions for follow-up. Emergency physicians need to remain alert about this life-threatening disease and the typical CT findings of this disease to make a timely diagnosis and navigate management.
2017Cocktail treatment with EGFR-specific and CD133-specific chimeric antigen receptor-modified T cells in a patient with advanced cholangiocarcinoma.J Hematol OncolCholangiocarcinoma (CCA) is one of the most fatal malignant tumors with increasing incidence, mortality, and insensitivity to traditional chemo-radiotherapy and targeted therapy. Chimeric antigen receptor-modified T cell (CART) immunotherapy represents a novel strategy for the management of many malignancies. However, the potential of CART therapy in treating advanced unresectable/metastatic CCA is uncharted so far.In this case, a 52-year-old female who was diagnosed as advanced unresectable/metastatic CCA and resistant to the following chemotherapy and radiotherapy was treated with CART cocktail immunotherapy, which was composed of successive infusions of CART cells targeting epidermal growth factor receptor (EGFR) and CD133, respectively. The patient finally achieved an 8.5-month partial response (PR) from the CART-EGFR therapy and a 4.5-month-lasting PR from the CART133 treatment. The CART-EGFR cells induced acute infusion-related toxicities such as mild chills, fever, fatigue, vomiting and muscle soreness, and a 9-day duration of delayed lower fever, accompanied by escalation of IL-6 and C reactive protein (CRP), acute increase of glutamic-pyruvic transaminase and glutamic-oxalacetic transaminase, and grade 2 lichen striatus-like skin pathological changes. The CART133 cells induced an intermittent upper abdominal dull pain, chills, fever, and rapidly deteriorative grade 3 systemic subcutaneous hemorrhages and congestive rashes together with serum cytokine release, which needed emergent medical intervention including intravenous methylprednisolone.This case suggests that CART cocktail immunotherapy may be feasible for the treatment of CCA as well as other solid malignancies; however, the toxicities, especially the epidermal/endothelial damages, require a further investigation.ClinicalTrials.gov NCT01869166 and NCT02541370 .
2017Septic Arthritis of an Atlantoaxial Facet Joint with Normal Inflammatory Markers: Case Report and Literature Review.World NeurosurgSeptic arthritis of the atlantoaxial facet joint is extremely rare. Contiguous spread to the median atlantoaxial joints with subsequent dens erosion can lead to atlantoaxial instability. Misleading normal inflammatory markers can result in delayed diagnosis and catastrophic consequences.A 56-year-old man presented with right-sided neck pain that had lasted for 2 days. He did not have fever or chills, and his serum C-reactive protein and erythrocyte sedimentation rate were normal. The patient was diagnosed with acute neck strain and treated conservatively. The pain continued for the next 3 weeks; cervical spine radiographs demonstrated normal findings with the exception of degenerative changes. The patient was treated with physical rehabilitation for the presumed neck strain and degenerative changes of the cervical vertebrae. Worsening neck pain and stiffness prompted a magnetic resonance imaging study obtained 5 weeks after the initial presentation, which showed an epidural collection with septic arthritis of the right facet and median atlantoaxial joints. Computed tomography demonstrated severe dens erosion. Surgical evacuation of the abscess and occipitocervical fusion were performed. Pathologic evaluation of tissue obtained during surgery demonstrated the presence of an infection, and Streptococcus anginosus grew from cultures.Infection must be considered in the differential diagnosis for neck pain when imaging findings are suggestive of an infectious process, even in an afebrile patient with normal C-reactive protein and erythrocyte sedimentation rate levels. Magnetic resonance imaging and computed tomography can play a critical role in such cases, potentially leading to a more timely diagnosis.
2017Development and validation of a parsimonious and pragmatic CHARM score to predict mortality in patients with suspected sepsis.Am J Emerg MedWe aimed to derive and validate a parsimonious and pragmatic clinical prediction rule using the concepts of Predisposition, Infection, Response, and Organ Dysfunction to predict in-hospital mortality; and to compare it with other prediction rules, as well as with conventional biomarkers for evaluating the mortality risk of patients with suspected sepsis in the emergency department (ED).We conducted a pragmatic cohort study with consecutive ED patients aged 18 or older with documented diagnostic codes of infection and two sets of blood culture ordered by physicians between 2010 and 2012 in a tertiary teaching hospital.7011 and 12,110 patients were included in the derivation cohort and the validation cohort for the final analysis. There were 479 deaths (7%) in the derivation cohort and 1145 deaths (9%) in the validation cohort. Independent predictors of death were absence of Chills (odds ratio: 2.28, 95% confidence interval: 1.75-2.97), Hypothermia (2.12, 1.57-2.85), Anemia (2.45, 1.97-3.04), wide Red cell Distribution Width (RDW) (3.27, 2.63-4.05) and history of Malignancy (2.00, 1.63-2.46). This novel clinical prediction rule (CHARM) performed well for stratifying patients into mortality risk groups (sensitivity: 99.4%, negative predictive value 99.7%, receiver operating characteristic area 0.77). The CHARM score also outperformed the other scores or biomarkers such as PIRO, SIRS, MEDS, CURB-65, C-reactive protein, procalcitonin and lactate (all p<.05).In patients with suspected sepsis, this parsimonious and pragmatic model could be utilized to stratify the mortality risk of patients in the early stage of sepsis.
2016Differential Adverse Event Profiles Associated with BCG as a Preventive Tuberculosis Vaccine or Therapeutic Bladder Cancer Vaccine Identified by Comparative Ontology-Based VAERS and Literature Meta-Analysis.PLoS OneM. bovis strain Bacillus Calmette-Guérin (BCG) has been the only licensed live attenuated vaccine against tuberculosis (TB) for nearly one century and has also been approved as a therapeutic vaccine for bladder cancer treatment since 1990. During its long time usage, different adverse events (AEs) have been reported. However, the AEs associated with the BCG preventive TB vaccine and therapeutic cancer vaccine have not been systematically compared. In this study, we systematically collected various BCG AE data mined from the US VAERS database and PubMed literature reports, identified statistically significant BCG-associated AEs, and ontologically classified and compared these AEs related to these two types of BCG vaccine. From 397 VAERS BCG AE case reports, we identified 64 AEs statistically significantly associated with the BCG TB vaccine and 14 AEs with the BCG cancer vaccine. Our meta-analysis of 41 peer-reviewed journal reports identified 48 AEs associated with the BCG TB vaccine and 43 AEs associated with the BCG cancer vaccine. Among all identified AEs from VAERS and literature reports, 25 AEs belong to serious AEs. The Ontology of Adverse Events (OAE)-based ontological hierarchical analysis indicated that the AEs associated with the BCG TB vaccine were enriched in immune system (e.g., lymphadenopathy and lymphadenitis), skin (e.g., skin ulceration and cyanosis), and respiratory system (e.g., cough and pneumonia); in contrast, the AEs associated with the BCG cancer vaccine mainly occurred in the urinary system (e.g., dysuria, pollakiuria, and hematuria). With these distinct AE profiles detected, this study also discovered three AEs (i.e., chills, pneumonia, and C-reactive protein increased) shared by the BCG TB vaccine and bladder cancer vaccine. Furthermore, our deep investigation of 24 BCG-associated death cases from VAERS identified the important effects of age, vaccine co-administration, and immunosuppressive status on the final BCG-associated death outcome.
2016Anti-thymocyte globulin-induced hyperbilirubinemia in patients with myelofibrosis undergoing allogeneic hematopoietic cell transplantation.Ann HematolAllogeneic hematopoietic cell transplantation (allo-HCT) remains the only curative treatment option for myelofibrosis (MF) despite the emergence of novel targeted therapies. To reduce graft rejection and graft-versus-host disease (GvHD), current allo-HCT protocols often include in vivo T lymphocyte depletion using polyclonal anti-thymocyte globulin (ATG). Shortly after ATG administration, an immediate inflammatory response with fever, chills, and laboratory alterations such as cytopenias, elevation of serum C-reactive protein, bilirubin, and transaminases can develop. Here, we explore whether MF patients, who commonly exhibit extramedullary hematopoiesis in the liver, might be particularly susceptible to ATG-induced liver toxicity. To test this hypothesis, we analyzed 130 control and 94 MF patients from three transplant centers treated with or without ATG during the allo-HCT conditioning regimen. Indeed, hyperbilirubinemia was found in nearly every MF patient treated with ATG (MF-ATG 54/60 = 90 %) as compared to non-ATG treated MF (MF-noATG 15/34 = 44.1 %, p < 0.001) and respectively ATG-treated non-MF patients of the control group (control-ATG, 43/77 = 56 %, p < 0.001). In contrast, transaminases were only inconsistently elevated. Hyperbilirubinemia was in most cases self-limiting and not predictive of increased incidence of non-relapse mortality, hepatic sinusoidal obstruction syndrome (SOS) or liver GvHD. In sum, awareness of this stereotypic bilirubin elevation in MF patients treated with ATG provides a relatively benign explanation for hyperbilirubinemia occurring in these patients during the early transplant. However, attention to drug levels of biliary excreted drugs is warranted, since altered bile flow may influence their clearance and enhance toxicity (e.g., busulfan, antifungal agents).
2016Alendronate- and risedronate-induced acute polyarthritis.Osteoporos IntBisphosphonates are the mainstay treatment for postmenopausal osteoporosis. Although bisphosphonates are safety drugs, they have numerous side-effects such as arthralgia, elevated erythrocyte sedimentation rate and C-reactive protein, gastrointestinal disturbances, and flu-like illness with symptoms of fatigue, fever, chills, malaise, and myalgia. We present a case of acute polyarthritis after administration of alendronate and risedronate in a 52-year-old woman. To the best of the author's knowledge, this is the first case of acute polyarthritis induced by per os administration of both alendronate and risedronate during weekly usage. This is a report of a 52-year-old woman admitted to our hospital every week in a month, within 48 h, after receiving three times alendronate and one time risedronate with diffuse arthralgias, miyalgias, and swelling with effusions in both wrists, both ankles, interphalangeal joints in both hands and feet, and in both knees. When we discontinued alendronate and risedronate, oral raloxifene (60 mg/day) with oral calcium (1 g/day), and vitamin D3 (800 IU/day) was initiated. The symptoms regressed in 1 week. During the 1 year follow-up period, no myalgia, arthritis, or synovitis was detected. The side-effects of bisphosphonates are rarely reported in the literature. We believe that the prevalance of these side-effects would increase by closer follow-up of patients receiving these medications. To our knowledge, this patient is the first reported case of acute polyarthritis induced by per os administration of both alendronate and risedronate during weekly usage.
2016Case 229: Burn-related Global Ankylosis of Interphalangeal Joints with Associated Acroosteolysis.RadiologyHistory A 50-year-old woman presented with a 6-month history of polyarthralgia involving the left and right hands, wrists, elbows, ankles, and knees. Her pain was not associated with morning stiffness but did worsen over the course of the day. She denied experiencing fevers, chills, or mouth ulcers. She did not report paresthesias or blue discoloration of her fingers when they were exposed to cold. Her family history was remarkable for an aunt who died of systemic lupus erythematosus and for a brother with arthritis. Her medical history was remarkable for vitamin D deficiency, hypertension, and rehabilitation for burns. At clinical examination, she had mild tenderness to palpation of her joints, without associated erythema, swelling, or crepitus. Healed skin grafts were also noted. Blood chemistry tests revealed a rheumatoid factor of 8.5 IU/mL (normal range, 0-13.9 IU/mL), an erythrocyte sedimentation rate of 2 mm/hr (normal range, 0-40 mm/hr), and a C-reactive protein value of 0.4 mg/L (3.8 nmol/L) (normal range, 0-4.9 mg/L [0-46.7 nmol/L]). Antinuclear antibodies test results were negative. Radiography of the right and left hands was performed.
2016Identifying Patients with Bacteremia in Community-Hospital Emergency Rooms: A Retrospective Cohort Study.PLoS One(1) To develop a clinical prediction rule to identify patients with bacteremia, using only information that is readily available in the emergency room (ER) of community hospitals, and (2) to test the validity of that rule with a separate, independent set of data.Multicenter retrospective cohort study.To derive the clinical prediction rule we used data from 3 community hospitals in Japan (derivation). We tested the rule using data from one other community hospital (validation), which was not among the three "derivation" hospitals.Adults (age ≥ 16 years old) who had undergone blood-culture testing while in the ER between April 2011 and March 2012. For the derivation data, n = 1515 (randomly sampled from 7026 patients), and for the validation data n = 467 (from 823 patients).We analyzed 28 candidate predictors of bacteremia, including demographic data, signs and symptoms, comorbid conditions, and basic laboratory data. Chi-square tests and multiple logistic regression were used to derive an integer risk score (the "ID-BactER" score). Sensitivity, specificity, likelihood ratios, and the area under the receiver operating characteristic curve (i.e., the AUC) were computed.There were 241 cases of bacteremia in the derivation data. Eleven candidate predictors were used in the ID-BactER score: age, chills, vomiting, mental status, temperature, systolic blood pressure, abdominal sign, white blood-cell count, platelets, blood urea nitrogen, and C-reactive protein. The AUCs was 0.80 (derivation) and 0.74 (validation). For ID-BactER scores ≥ 2, the sensitivities for derivation and validation data were 98% and 97%, and specificities were 20% and 14%, respectively.The ID-BactER score can be computed from information that is readily available in the ERs of community hospitals. Future studies should focus on developing a score with a higher specificity while maintaining the desired sensitivity.
2016[Experience of integrated traditional Chinese and Western medicine in first case of imported Zika virus disease in China].Zhonghua Wei Zhong Bing Ji Jiu Yi XueZika virus disease is an acute infectious disease caused by Zika virus transmitted through Aedes mosquitoes. To explore the therapeutic effect of integrated traditional Chinese and Western Medicine for Zika virus disease, the treatment process of the first imported case in China was reviewed.The first imported Zika virus disease in China was admitted to Ganxian People's Hospital in Jiangxi Province on February 6th, 2016, and the patient received isolation treatment for 9 days and cured later. The effect of antiviral treatments including Xiyanping injection was evaluated based on clinical diagnosis and treatment process of the patient.A 34-year old male patient was admitted with chief complaint of fever for 9 days, orbital pain and itching rash for 4 days on February 6th, 2016. (1) Epidemiological characteristics: the patient was bitted by mosquitoes during his business trip in Venezuela since January 1st, where Zika virus disease was spreading. On January 20th he had dizziness without fever, and the symptom disappeared after taking medicines without details. Paroxysmal dizziness, chills and mild fever without myalgia was experienced on January 28th. On February 3rd small red rash appeared in the neck, spreading to anterior part of chest, limbs and trunk, and the fever, fatigue, nausea was continued, and a new symptom of paroxysmal pain in back of ears and orbits appeared, during which he had not go to hospital. The symptoms relieved on February 4th. He returned to Ganxian County on February 5th, he had yellow stool 3 times with normal temperature, without abdominal pain, and red rash still appeared in the neck. He went to Ganxian People's Hospital on February 6th, 2016. (2) Clinical manifestation: the vital signs showed a temperature of 36.8?centigrade, a pulse rate of 80 bpm, a respiratory rate of 20 bpm, and a blood pressure of 110/70 mmHg (1 mmHg = 0.133 kPa). It was showed by physical examination that red rash appeared in the neck, and no superficial enlarged lymph nodes were found. Bilateral conjunctival congestion was obvious, physiological reflex existed and pathological reflex was not found. (3) Auxiliary lab test and examination: no abnormal finding were revealed throughout examination and laboratory tests, including routine blood test, liver function, renal function, serum myocardial enzyme, electrolyte, blood sugar, C-reactive protein (CRP), troponin I (TnI), and procalcitonin (PCT), except slight prolongation in activated partial thromboplastin time (APTT, 38.6 s) on February 6th; and slightly dense shadow in left lung in lung CT scan, considering inflammatory changes and slight emphysema (especially in the left lower lung) as well as bilateral renal calculus on February 8th. No significant abnormalities were found in electrocardiogram and B ultrasound test of liver, spleen, and pancreas. (4) Virus confirmation: Zika virus nucleic acid was positive reported by Jiangxi Province Center for Disease Control and Prevention (CDC) on February 7th and Chinese CDC on February 9th, respectively, though Dengue virus were negative reported by Ganzhou CDC on February 6th. Right after the first diagnosis, anyone who had been in close contact with the patient received medical monitoring. (5)Treatment process: on February 6th, symptomatic treatment was prescribed since admitted into the infectious isolation wards and daily intravenous drip of Xiyanping injection 250 mg was prescribed for antiviral therapy. On February 7th, the patient had no fever, with occasional chills, neck rash was disappeared, orbital pain relieved and bilateral conjunctival hyperemia range was paler and narrowed, and his condition improved. Ibuprofen was administered for defervesce 3 times a day when his temperature reached to 37.5?centigrade at 16:00. On February 8th, the patient had no fever, times of chills was significantly reduced, without myalgia and rash, orbital pain and conjunctival hyperemia further recovered. On February 9th, bilateral eyes slightly tingling, mild conjunctival congestion, no fever chills or other discomfort was found. The chloramphenicol eye drops was prescribed for relieving sting pain with conjunctival congestion twice a day as recombinant human interferon alpha eye drops was out of store. The patient was comfortable from February 11th to February 13th. Blood and urine test for Zika were reported negative by the Chinese CDC and Jiangxi Province CDC. Because all the discharge criteria were satisfied, the patient was discharged on February 14th.At present, there is no specific effective drug to prevent and treat Zika virus disease effectually. After receiving symptomatic treatment and antiviral treatments including Xiyanping injection, the patient's symptoms were relieved. Zika virus nucleic acid in blood and urine was negative. The patient was discharged. Combination of traditional Chinese medicine and Western medicine maybe a good method to prevent and treat Zika virus disease.
2016An 82-year-old woman with a cardiac mass.HeartAn 82-year-old woman suspected of a cardiac tumour was referred for evaluation. Patient's medical history included atrial fibrillation, implantation of a VVI (ventricular stimulation) pacemaker 3 years earlier due to advanced atrioventicular (AV) block, arterial hypertension and hypothyroidism. Patient was adequately anticoagulated with warfarin (international normalized ratio (INR) 3.0 at admission). She reported occasional palpitations and a 2 kg weight loss in the last 2 years, but denied shortness of breath, chest pain, malaise, fever, chills or cough. Blood samples were taken for tests and cultures. Red blood cells, haemoglobin, white blood cells, platelets, C- reactive protein (CRP) and erythrocyte sedimentation rate (ESR) were within normal ranges. Blood cultures were negative. Echocardiogram (figure 1A) (see online supplementary videos 1 and 2) and cardiac CT were performed (figure 1B).Which of the following is the most likely diagnosis?Caseous calcification of the mitral annulusCoconut left atriumMitral valve myxomaPeriannular abscess.
2015Suction Drain Tip Culture after Spine Surgery: Can It Predict a Surgical Site Infection?Asian Spine JRetrospective clinical study.To assess the diagnostic value of suction drain tip culture in patients undergoing primary posterior spine surgery.To date, the diagnostic value of suction drain tip culture for predicting surgical site infection (SSI) has not been firmly established in orthopedic or spinal surgery.In total, 133 patients who underwent primary posterior spine surgery from January 2013 to April 2015 were included in this retrospective study. Patients diagnosed with infective disease or condition was excluded. The suction drain tip was cut off approximately 5 cm from its far end. The sample was sent to the microbiological laboratory of the hospital for culture analysis. Any signs of infection, such as wound discharge or dehiscence, fever, chills, or chronic pain, were recorded. The culture outcome, identification of bacteria, and postoperative transition of the serum C-reactive protein level were also recorded in all patients. The wounds were followed up for a minimum of 3 months.A positive drain tip culture was found in 48 patients (36.1%), of whom, 6 developed SSI. The sensitivity of drain tip culture for SSI after primary posterior spine surgery was 60.0%, and the specificity was 65.9%. The association between the incidence of positive suction tip culture and SSI was not statistically significant. Among the 48 positive drain tip cultures, there was no significant association between the occurrence of SSI and virulence of isolated bacteria. There was no significant association between drain tip culture positivity and the duration of drainage, or between the rate of SSI and duration of drainage.Suction drain tip culture analysis is a poor predictor of SSI after primary posterior spine surgery. Routine use of a drain tip culture is not supported by the results of this study.
2015[Distribution of pathogenic microorganisms and its relationship with clinical features in children with community-acquired pneumonia].Zhongguo Dang Dai Er Ke Za ZhiTo study the distribution of pathogenic microorganisms in different genders, age groups and seasons in children with community-acquired pneumonia (CAP) and the relationship between the distribution of pathogenic microorganisms and clinical features.A total of 1,155 children with CAP were enrolled, among whom there were 670 boys and 485 girls, with a mean age of 3.1±2.8 years (range: one month to 14 years). Indirect immunofluorescence assay, particle agglutination test, enzyme-linked immunosorbent assay, colloidal gold method. and bacterial culture were applied to determine common respiratory pathogenic microorganisms in sputum, throat swabs, blood samples, bronchoalveolar lavage fluid, and urine.A total of 758 specimens (65.63%) were tested positive by pathogen detection. The top three dominant pathogens were Mycoplasma pneumoniae (MP, 43.64%), bacteria (15.12%), and respiratory syncytial virus (RSV, 9.26%), and the rate of mixed infection was 16.02%. The rates of MP infection between boys and girls with CAP were different (40.8% vs 47.6%; P<0.05). The MP detection rate was the highest in the age group of 6-14 years (77.4%) and the lowest in children younger than 1 year (11.2%), while the detection rates of bacteria and RSV were the highest in children younger than 1 year (21.2% and 17.2%, respectively). The MP detection rate was significantly higher in summer and autumn than in winter and spring, while the detection rates of bacteria and RSV in summer and autumn were significantly lower than those in winter and spring. Among children who were MP positive, fever, chills, cough, crackles were more likely to appear; children with RSV infection were more likely to have wheezes; children with bacterial infection were less likely to have cough. Serum levels of C-reactive protein and procalcitonin were associated with bacterial infection (OR=1.747 and 1.418, respectively; both P<0.05).MP plays a more and more important role in the pathogenic microorganisms of CAP in children. Prevalence and outbreaks of MP infection among children should be alerted in summer and autumn. There are differences in the detection rate of various pathogenic microorganisms in CAP children with various age groups. The clinical features of children with CAP caused by different pathogenic microorganisms are different.
2015Salmonella paratyphi B mycotic aneurysm of the abdominal aorta in an HIV-infected patient: a case report.Infez MedAn HIV-infected 49-year-old man was admitted with polyuria, fever, chills and a dull left lumbar pain. Laboratory tests showed increased C-reactive protein while urine analysis and abdomen ultrasound scan were negative. Blood cultures revealed a Salmonella paratyphi B, identified through MALDI-TOF mass spectrometry. Targeted antibiotic therapy with intravenous piperacillin/tazobactam was started and a multi-phase contrast-enhanced abdomen CT-scan was performed at 24 hours from admission showing a saccular aneurysm of the abdominal aorta with a 1 cm penetrating aortic ulcer on posterior wall. The patient underwent emergency vascular surgery at 34 hours from admission for debridement and homo-graft placement of sub-renal aorta, and surgical samples were sent for microbiological analysis. Unfortunately, the patient died on post-surgical day 7 after haemorrhagic shock due to laceration of his graft. Salmonella paratyphi infection can be responsible for sepsis in severely immunosuppressed patients with poorly controlled HIV, requiring careful work-up for cardiovascular involvement.
2015Febrile reaction associated with the infusion of haploidentical peripheral blood stem cells: incidence, clinical features, and risk factors.TransfusionWe reported febrile reaction after the infusion of haploidentical peripheral blood stem cells (PBSCs). The aim of this study was to better characterize this new clinical entity named by infusion-related febrile reaction (IRFR).A retrospective analysis of 490 patients received allogeneic stem cell transplantation (SCT) between October 2009 and December 2011 at our institution.The distribution of transplant type was 173 patients in HLA-identical siblings, 30 in unrelated, and 287 in haploidentical. IRFR was defined as unexplained fever of more than 38°C within 24 hours after the infusion of allogeneic PBSCs. We did not observe any IRFRs in patients undergoing HLA-identical sibling and unrelated transfusions. After excluding patients with a known source of infection, we classified haploidentical patients into IRFR and non-IRFR groups. Eighty-eight patients (30.7%) of 287 cases after the infusion of haploidentical PBSCs were diagnosed as IRFRs, chills in 3.5% (10/88), diarrhea in 21.6% (19/88), an erythematous skin rash in 0.3% (1/88), hypoxemia in 1.0% (3/88), and no other accompanying symptoms in 62.5% (55/88). Significantly higher elevation of C-reactive protein and complement C3 was seen in the IRFR group compared with the non-IRFR group. Multivariate analysis showed higher CD34+ dose was a significant predictor for IRFR (p = 0.023; hazard ratio = 1.848; 95% confidence interval, 1.087-3.142).As a clinical feature belonging to haploidentical SCT, IRFR was associated with the higher numbers of CD34+ from PBSCs.
2015Diffuse alveolar hemorrhage after use of a fluoropolymer-based waterproofing spray.SpringerplusA 30-year-old man developed chills, cough and dyspnea a few minutes after using a fluoropolymer-based waterproofing spray in a small closed room. He visited our hospital 1 h later. Examination revealed that the patient had incessant cough, tachypnea, fever and decreased peripheral arterial oxygen saturation. Blood tests revealed leukocytosis with elevated serum C-reactive protein levels. Chest radiographs and computed tomography (CT) scan showed bilateral ground glass opacities, mainly in the upper lobes. Bronchoalveolar lavage (BAL) fluid obtained from the right middle lobe showed a bloody appearance. Microscopic examination of a BAL cytospin specimen revealed the presence of numerous red blood cells associated with extreme neutrophilia. Microbiological studies of the BAL fluid were negative. The patient was observed without corticosteroid therapy, and his symptoms and abnormal shadows on the chest radiographs and CT improved. On day 7 after admission, the patient was discharged from the hospital. Accidental inhalation of waterproofing spray may cause diffuse alveolar hemorrhage, a rare manifestation of acute lung injury. Supportive treatment may be effective and sufficient.
2015Predictive value of the usual clinical signs and laboratory tests in the diagnosis of septic arthritis.CJEMTo determine the sensitivity and specificity of clinical and laboratory signs for the diagnosis of septic arthritis (SA). Patients and methods This prospective study included all adult patients with suspected SA seen in the emergency department or rheumatology department at the University Hospital, Clermont-Ferrand, France, over a period of 18 months.In total, 105 patients with suspected SA were included, 38 (36%) presenting with SA (29 [28%] with bacteriologically documented SA). In the univariate analysis, chills (p=0.015), gradual onset (p=0.04), local redness (p=0.01), as well as an entry site for infection (p=0.01) were most often identified in SA. A history of crystal-induced arthritis (p=0.004) was more frequent in non-SA cases. An erythrocyte sedimentation rate (ESR)>50 mm (p=0.005), a C-reactive protein (CRP) level >100 mg/L (p=0.019), and radiological signs suggestive of SA (p=0.001) were more frequent in the SA cases. Synovial fluid appearance: purulent (p50,000/μL (p < 0.001), differentiated between SA and non-SA. In multivariate analysis, only chills (odds ration [OR]=4.7, 95% confidence interval [CI] 1.3-17.1), a history of crystal-induced arthritis (OR=0.09, 95% CI 0.01-0.9), purulent appearance of the joint fluid (OR=8.4, 95% CI 2.4-28.5), synovial WBC count >50,000/mm3 (OR=6.8, 95% CI 1.3-36), and radiological findings (OR=7.1, 95% CI 13-37.9) remained significant.No clinical sign or laboratory test (excluding bacteriological test), taken alone, is conclusive for the differentiation between SA and non-SA, but the association of several signs, notably chills, history of crystal-induced arthritis, radiological findings, and the appearance and cellularity of joint fluid may be suggestive.
2014Pyogenic hepatic abscess presenting years after a choledochojejunostomy: a rare clinical occurrence.BMJ Case RepA 69-year-old Caucasian man presented with fever, chills/rigors and night sweats since 6 days. Blood cultures (4/4) initially reported Gram negative lactose-fermenting rods. Physical examination was fairly benign which included a normal abdominal examination. Laboratory tests were significant for an elevated white cell count, erythrocyte sedimentation rate and C reactive protein . Empirically, he was treated with piperacillin tazobactam. A chart review showed that he had undergone a choledochojejunostomy for a pancreatic head tumour 7 years before. We found a few reported cases of hepatic abscesses after choledochojejunostomy presenting years after the procedure. An abdominal CT scan confirmed our suspicion. Percutaneous drainage was performed and his antibiotics were switched to ciprofloxacin and metronidazole, based on the sensitivity report. The patient's clinical condition steadily improved.
2013Liver abscesses after peritoneal venous shunt.Case Rep GastroenterolA 70-year-old man was referred to our hospital for high-grade fever with chills. He has visited our hospital for alcoholic liver cirrhosis and diabetes mellitus for over 20 years. Nine months earlier, he had received a peritoneal venous shunt (Denver shunt®) because of refractory ascites. Laboratory examinations revealed elevated C-reactive protein and liver dysfunction. Ultrasonography and abdominal enhanced computed tomography showed multiple small abscesses in the right lobe of the liver. Blood culture test did not detect the pathogenic bacteria of liver abscesses. The patient was treated with antibiotics for more than 2 months and cured from the infection, but 3 months later, he developed high-grade fever again. He had a recurrence of multiple small liver abscesses involving both lobes of the liver. He was treated with antibiotics, and the abscesses disappeared within a month. After the antibiotic treatment, he had selective intestinal decontamination with kanamycin. He has had no recurrence of liver abscess for over a year. To our knowledge, this is the first report of liver abscess in a cirrhotic patient with Denver shunt. Clinicians should bear liver abscess in mind when treating patients with high-grade fever and liver dysfunction following Denver shunt implantation.
2013Pneumonic and nonpneumonic exacerbations of COPD: inflammatory response and clinical characteristics.ChestCommunity-acquired pneumonia (CAP) is a frequent event in patients with COPD, although it is not currently considered an acute exacerbation of COPD (AECOPD). To our knowledge, no studies have compared the inflammatory response of patients with COPD who develop CAP or AECOPD. The aim of our study was to compare clinical and evolutive manifestations and biologic signaling of AECOPD and CAP + COPD.Prospective data were collected from 249 consecutively hospitalized patients with COPD. Comparative analyses were performed in patients with AECOPD (n = 133) and patients with CAP + COPD (n = 116). Measures of clinical characteristics, blood biomarkers, and evolution were recorded on admission, after 3 and 30 days, and in a follow-up period of 30 days, 90 days, and 1 year.Patients with CAP + COPD had higher FEV1 compared with patients with COPD without pneumonia. In-hospital and long-term outcomes (1 year) were similar for both populations. However, patients with AECOPD had more readmissions, and patients with CAP had more prior episodes of pneumonia. At day 1 and day 3, patients with CAP + COPD had significantly (P < .001) higher serum levels of C-reactive protein (CRP), procalcitonin, tumor necrosis factor-α, and IL-6. Repetition of the analyses after stratifying patients based on severity of disease, current inhaled pharmacotherapy, and noninfectious AECOPD cause confirmed higher levels of the same biomarkers in patients with CAP + COPD. Chills, pleuritic pain, sputum purulence, and CRP levels at day 1 were independent clinical predictors of CAP + COPD.Our study confirms that two different clinical and inflammatory profiles exist in hospitalized patients with COPD in response to CAP (stronger response) and AECOPD, although with similar short-term and long-term outcomes.
2013[Recurrent multifocal osteomyelitis in the absence of skin disease].Dtsch Med WochenschrA 64-year-old man complained of pain and a symmetric swelling of the clavicles. There were no fever and chills. 27 years earlier, a resection of the mandible was necessary, due to osteomyelitis. In the past, he complained of recurrent episodes of pain in the sternum and in the thoracic spine. Skin disorders were not reported.The leucocyte count was within the normal range, however, levels of c-reactive protein and the erythrocyte sedimentation rate were increased. Autoantibodies and blood cultures were negative. On X-ray, osteosclerotic and cystic lesions in both clavicles were found, consistent with osteomyelitis. A bone scintigraphy revealed increased radionuclide activity in the clavicles and the sternum. A bone biopsy sample from the clavicle revealed signs of osteitis with fibrosis together with CD 68 und CD 138 positive cells. These findings indicated the diagnosis of a SAPHO syndrome (Synovitis, Acne, Pustulosis, Hyperostosis, Osteitis) without skin disease.NSAIDs, bisphosphonates and azithromycin were administered , thereby sufficient pain relief was rapidly achieved.SAPHO syndrome is a rare disease complex including osteoarticular disorders which are frequently accompanied by skin disease. However, the diagnosis may be difficult due to a variable clinical manifestation and especially - like in our case - if skin disease is absent. Current treatment options are not evidence-based due to the rarity of the syndrome but include NSAIDs, bisphosphonates and glucocorticoids.
2013Scrub typhus cases in a teaching hospital in Penghu, Taiwan, 2006-2010.Vector Borne Zoonotic DisScrub typhus is a mite-borne infectious disease caused by Orientia tsutsugamushi (previously called Rickettsia tsutsugamushi). The severity of this disease varies from only mild symptoms to death, and its manifestations are nonspecific. Therefore, clinicians may not correctly diagnose scrub typhus early enough for successful treatment. Reports of infections in travelers returning from Asia to their home countries are increasingly common. Thus, it is important that even clinicians in nonepidemic regions be alert for this disease. Here we describe the epidemiological aspects and clinical manifestations of scrub typhus encountered at a teaching hospital in Penghu, Taiwan, over the past 5 years. A total of 126 patients were confirmed to be positive for scrub typhus at the hospital from 2006 to 2010. All cases were confirmed by the Centers for Disease Control and Prevention or its contract laboratory through pathogen isolation and an indirect immunofluorescence assay. Medical records of these patients were reviewed, and demographic and clinical characteristics, laboratory data, seasonal data, geographic distribution, complications, and outcome were analyzed. The incidence of scrub typhus peaked in individuals aged 0-10 and 51-60 years, with the highest incidence among those ≤10 years of age. No significant difference was noted between sexes. Fever was the most common symptom (93.6%), followed by chills (23.8%), cough (18.3%), and headache (14.3%). Eschars were observed in 78 (61.9%) patients, with the axilla being the most frequent site (n=17; 21.8%). Most patients were retirees (n=63; 50%), followed by students (n=16; 12.7%). Patients were more likely to live in rural areas than urban areas. Scrub typhus was epidemic in the spring (April to June) and fall (October to December) in a bimodal distribution similar to that observed in Japan. Leukocytosis was not common, but most patients had abnormal C-reactive protein levels, thrombocytopenia, and elevated liver function test results. Residents of Penghu, particularly Makung City and Husi Township, as well as travelers to the region during the spring and fall seasons should be educated about the signs and symptoms of scrub typhus. All physicians who come into contact with individuals residing in or traveling to or from epidemic regions should remain alert about the manifestations of this disease.
2013New paraneoplastic syndrome in chronic basophilic leukemia.Int J HematolChronic basophilic leukemia (CBL) is an extremely rare disorder. A female patient presented with recurrent attacks of chills, fever and abdominal pain was found to have simultaneous cyclic oscillation in leukocyte counts and C-reactive protein values. She was initially diagnosed with familial Mediterranean fever and treated with colchicine. Diagnosis of CBL was established by morphologic studies of peripheral blood and bone marrow. Her febrile attacks recurred with marked elevation in serum interleukin-6 (IL-6) level when basophil counts climbed to peak levels during cyclic oscillation. Molecular studies by real-time PCR showed IL-6 gene expression in neoplastic basophils separated by magnetic-activated cell sorting infiltrating the bone marrow, suggesting that IL-6 is released by neoplastic basophils of an underlying CBL, resulting in a new paraneoplastic syndrome that mimics autoinflammatory disorders.
2013Recurrent Fever of Unknown Origin (FUO) Due to Periodic Fever, Aphthous Stomatititis, Pharyngitis and Adenitis (FAPA) Syndrome in an Adult.J Clin MedFAPA syndrome (periodic fever, aphthous stomatititis, pharyngitis and adenitis) is a relatively new entity described in pediatric patients. In adults, reports of FAPA are limited to rare case reports. The differential diagnosis of FAPA in adults includes Behcet's syndrome, familial Mediterranean fever (FMF), Hyper IgD syndrome and juvenile rheumatoid arthritis (JRA), i.e., adult Still's disease. With FAPA syndrome, between episodes patients are completely asymptomatic and serologic inflammatory markers such as erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and white blood cell (WBC) count are normal. The etiology of FAFA is unknown, but lack of secondary cases or clustering in close contacts, lack of seasonality, and the lack of progression for years argue against an infectious etiology. We describe an extremely rare case of an adult with a recurrent FUO with profuse night sweats and prominent chills due to FAPA syndrome.
2012[Two cases of acute hepatitis associated with Q fever].Mikrobiyol BulQ fever which is caused by Coxiella burnetii, is a worldwide zoonosis. Many species of wild and domestic mammals, birds, and arthropods, are reservoirs of C.burnetii in nature, however farm animals are the most frequent sources of human infection. The most frequent way of transmission is by inhalation of contaminated aerosols. The clinical presentation of Q fever is polymorphic and nonspecific. Q fever may present as acute or chronic disease. In acute cases, the most common clinical syndromes are selflimited febrile illness, granulomatous hepatitis, and pneumonia, but it can also be asymptomatic. Fever with hepatitis associated with Q fever has rarely been described in the literature. Herein we report two cases of C.burnetii hepatitis presented with jaundice. In May 2011, two male cases, who inhabited in Malkara village of Tekirdag province (located at Trace region of Turkey), were admitted to the hospital with the complaints of persistent high grade fever, chills and sweats, icterus, disseminated myalgia and headache. Physical examination revealed fever, icterus and the patient appeared to be mildly ill but had no localizing signs of infection. Radiological findings of the patients were in normal limits. Laboratory findings revealed leukocytosis, increased hepatic and cholestatic enzyme levels, and moderate hyperbilirubinemia- mainly direct bilirubin, whereas serum C-reactive protein and erythrocyte sedimentation rate were found normal. Blood and urine cultures of the patients yielded no bacterial growth. Serological markers for acute viral hepatitis, citomegalovirus and Epstein-Barr virus infections, brucellosis, salmonellosis, toxoplasmosis and leptospirosis were found negative. Acute Q fever diagnosis of the cases were based on the positive results obtained by C.burnetii Phase II IgM and IgG ELISA (Vircell SL, Spain) test, and the serological diagnosis were confirmed by Phase I and II immunofluorescence (Vircell SL, Spain) method. Both cases were treated with doxycycline for 14 days and became afebrile within four days. These cases were presented to emphasize that C.burnetii infection should be considered in the differential diagnosis of patients with fever and elevated serum transaminase levels, irrespective of the presence of abdominal pain and exposure to potentially infected animals.
2012Serial and panel analyses of biomarkers do not improve the prediction of bacteremia compared to one procalcitonin measurement.J InfectWe evaluated the value of a single biomarker, biomarker panels, biomarkers combined with clinical signs of sepsis, and serial determinations of biomarkers in the prediction of bacteremia in patients with sepsis.Adult patients visiting the emergency department because of a suspected infection with at least two of the following symptoms: temperature >38.3°C or <36°C, heart rate >90/min, respiratory rate >20/min, chills, altered mental status, systolic blood pressure <90 mmHg, MAP <65 mmHg, and hyperglycemia in the absence of diabetes mellitus were included. Procalcitonin (PCT), interleukin-6 (IL-6), lipopolysaccharide-binding protein (LBP), C-reactive protein (CRP) were measured, and two blood cultures were taken. The analyses included: (1) determination of the biomarker with the highest predictive value for bacteremia and to examine the predictive value of this biomarker in combination with other biomarkers; (2) analysis of the best biomarker data in combination with clinical signs of sepsis; and (3) analysis of serial determinations of the best biomarker.Of 342 included patients, PCT had the best predictive value for bacteremia with an area under the curve of 0.80, sensitivity 89%, specificity 58%. The predictive value of a combination of PCT plus a panel of other biomarkers, clinical signs, or analysis of serial PCT levels did not lead to a significant improvement of the predictive value of PCT alone.The ability of PCT to predict bacteremia in patients with sepsis does not further improve when combined with IL-6, LBP, CRP, clinical signs, or serial measurements. Naturally, this does not exclude that a panel of other biomarkers may lead to different results.
2012The absence of typical pneumonia symptoms in a patient with rheumatoid arthritis during tocilizumab and steroid treatment.BMJ Case RepA 78-year-old woman with rheumatoid arthritis while being treated with tocilizumab and steroid treatment presented with pharyngeal pain and general malaise. She felt chills and vomited while waiting in the waiting room, in addition to urinary incontinence. An immediate evaluation of her condition indicated that she was in shock and a physical examination revealed moist rales in the right lung field. Her white cell count and C reactive protein level were within normal limits; however, a radiological study indicated pneumonia. Antibiotic treatment resulted in improvement of her condition. Blood culture later revealed bacteraemia due to Streptococcus pneumoniae. The anti-inflammatory effect of tocilizumab and steroid treatment may mask the typical symptoms and signs of infection, so physicians must be aware of the potential for hidden infection when such patients present with an unidentified complaint.
2012Aetiology of community-acquired pneumonia among adults in an H1N1 pandemic year: the role of respiratory viruses.Eur J Clin Microbiol Infect DisThis study aimed to determine the aetiology of community-acquired pneumonia (CAP) by adding polymerase chain reaction (PCR) to conventional methods and to describe the clinical and laboratory features between patients with bacterial pneumonia (BP) and viral pneumonia (VP). Adults with CAP admitted from November 2009 to October 2010 were included. Demographics, comorbidities, severity and clinical features were recorded. Conventional microbiological methods included blood and sputum cultures, acute and convalescent serologic samples, and antigen urinary detection. New methods included multiplex PCR for Mycoplasma pneumoniae, Legionella pneumophila, Chlamydophila pneumoniae, Bordetella pertussis and 15 respiratory viruses. A total of 169 patients were included. Using conventional methods, we identified a pathogen in 51 % of cases. With PCR, up to 70 % of cases had an aetiological diagnosis. Forty-five patients had BP (34 %), 22 had VP (17 %) and 25 (19 %) had co-infection (BP and VP). Pneumococci and respiratory syncytial virus (RSV) were the most frequently identified pathogens. Procalcitonin (PCT) and C-reactive protein (CRP) median values were significantly higher in BP than in VP patients. Shaking chills, higher CURB score and shock were significantly more frequent in BP. A viral infection was identified in more than one-third of patients with CAP. Clinical and laboratory features could help to differentiate between VP and BP and to guide empirical therapy.
2012A pharmacokinetic, pharmacodynamic, and electrocardiographic study of liposomal mifamurtide (L-MTP-PE) in healthy adult volunteers.Eur J Clin PharmacolThis study evaluated the pharmacokinetics (PK), pharmacodynamics (PD), safety/tolerability, and cardiac safety of liposomal muramyl tripeptide phosphatidyl-ethanolamine [mifamurtide (L-MTP-PE)] in healthy adults.L-MTP-PE 4 mg was administered intravenously over 30 min. Study participants were monitored from 24 h preinfusion until 72 h postinfusion. Blood samples were drawn over 0-72 h postdose to determine serum MTP-PE, interleukin (IL)-6, tumor necrosis factor (TNF)-α, and C-reactive protein (CRP) concentrations. Electrocardiograpic (ECG) data were collected via continuous Holter monitoring beginning 24 h predose through 24 h postdose. Changes from time-matched pretreatment baseline QTc and associated two-sided 90 % confidence intervals were calculated.Twenty-one participants received L-MTP-PE. Total serum MTP-PE declined rapidly with a terminal half-life of 2.05 ± 0.40 h. PK variability was low, with <30 % coefficient of variation in systemic exposure. Serum concentrations of IL-6, TNF-α, and CRP increased following L-MTP-PE infusion. Maximum observed increases in IL-6 and TNF-α occurred at 4 and 2 h, respectively, returning toward baseline by 8 h postdose. L-MTP-PE was generally well tolerated, with no adverse events greater than grade 3. Headache, chills, tachycardia, nausea, and pyrexia were the most frequent adverse events. L-MTP-PE infusion resulted in an increased heart rate without readily apparent QTc prolongation.MTP-PE PK following L-MTP-PE administration were characterized by a short serum half-life and low variability. Increases in IL-6, TNF-α, and CRP and the safety profile were consistent with the immunomodulatory mechanism of action. No clinically significant effect of L-MTP-PE on cardiovascular repolarization was observed based on analysis of ECG QTc intervals.
2012Contained ruptured paravisceral aortic aneurysm related to immunoglobulin G4 aortitis.Ann Vasc SurgTo describe a case of autoimmune inflammatory abdominal aortic aneurysm (AAA) associated with rupture.A 63-year-old woman presented with 5 days of abdominal pain, malaise, fever, and chills after 6 months of debilitating back pain with a 3-kg weight loss. On examination, she was shown to have a tender palpable pulsatile abdominal mass. Computed tomographic angiography revealed a multilobulated paravisceral AAA (5.5 cm in maximal diameter) and bilateral popliteal aneurysms. The appearance of the aneurysms was indicative of primary aortic infection. Laboratory examinations demonstrated a white blood cell (WBC) count of 12.3×10(9)/L, erythrocyte sedimentation rate of 131 mm/hr, normal antinuclear antibody level, and C-reactive protein level of 211 mg/L. Nuclear WBC scan showed no uptake of tracer around the aorta. Blood and urine cultures were negative. Because of the AAA size and symptoms, open repair was expedited. The operation was performed through a transabdominal midline incision with a mediovisceral rotation. Extensive retroperitoneal inflammation extending into the paravisceral aorta was encountered. Supraceliac clamping was possible. The aorta was replaced from the level of the superior mesenteric artery to the aortic bifurcation with a 16-mm rifampin-soaked graft with reimplantation of the left renal artery. Cultures and biopsies were done.Histology demonstrated vessel wall rupture, adventitial fibrosis and inflammatory cell infiltration, obliterative phlebitis, lymphoid follicles, perineural inflammation, and immunoglobulin G4 (IgG4) plasma cell infiltration, consistent with a contained ruptured aneurysm associated with IgG4 periaortitis. The patient had a long postoperative course with prolonged intubation and renal failure requiring hemodialysis, which resolved 8 weeks postoperatively. Immunosuppression was paramount for her improvement.IgG4-related inflammatory AAAs are rare; this is the first report of one with a contained rupture. The patient's symptoms, the unusual appearance on computed tomography, the presence of popliteal aneurysms in a woman, and the normal WBC scan were indicative of an inflammatory etiology. Tissue biopsy was critical to obtain histological diagnosis and direct treatment.
2011Inflammatory responses predict long-term mortality risk in community-acquired pneumonia.Eur Respir JLong-term outcomes in patients surviving community-acquired pneumonia (CAP) are still incompletely understood. This study investigates the association of clinical parameters and blood markers with long-term mortality. We prospectively followed 877 CAP patients from a previous multicentre trial for 18 months follow-up and investigated all-cause mortality following hospital discharge. Overall mortality was 17.3% (95% CI 14.8-19.8%) with a 12.8% (95% CI 10.9-15.0%) mortality incidence rate per year. Initial risk assignment using the Pneumonia Severity Index was accurate during the 18 month follow-up. Multivariable regression models (hazard ratio, 95% CI) designated the following as independent risk factors for long-term mortality: male sex (1.7, 1.2-2.5); chronic obstructive pulmonary disease (1.5, 1.1-2.1); neoplastic disease (2.5, 1.7-3.7); and highest quartile of peak pro-adrenomedullin level (3.3, 1.7-6.2). Initial presentation with temperature>38.7°C (0.4, 0.2-0.6), chills (0.6, 0.4-0.99) and highest quartile of the inflammatory marker C-reactive-protein (0.3, 0.2-0.5) were independent protective factors. A weighted risk score based on these variables showed good discrimination (area under receiver operating characteristic curve 0.78, 95% CI 0.74-0.82). Pronounced clinical and laboratory signs of systemic inflammatory host response upon initial hospital stay were associated with favourable long-term prognosis. Further studies should address whether closer monitoring of high-risk CAP patients after hospital discharge favourably impacts long-term mortality.
2010[An adult case of visceral leishmaniasis in a province of Black-Sea region, Turkey].Mikrobiyol BulVisceral leishmaniasis (VL) which is a chronic disease caused by the protozoon, Leishmania, occurs widely worldwide and it is widespread in most of the countries in the Mediterranean basin. The infection which is transmitted by a sandfly (Phlebotomus) vector, has a prolonged incubation period and insidious onset. VL generally affects children and may be fatal if not treated. In this report, a 31 years old male patient, who was the first adult VL case from Zonguldak (a province located at western Black-Sea region of Turkey) was presented. He was admitted to the hospital with two-months history of fever, chills, sweating and weight loss. There was no history of travel outside the city nor insect bites, however, he indicated that there would be unnoticed sandfly bites since sandflies were very common in the coal mines he worked. His physical examination revealed body temperatue of 39.2°C and hepatosplenomegaly, while laboratory findings yielded anemia, leucopenia, hypoalbuminemia and hypergamaglobulinemia. Erythrocyte sedimentation rate was 62 mm/h, C-reactive protein was 113 mg/L and liver transaminases were 2 to 5 folds higher than the reference values. The only pathological finding was hepatosplenomegaly in the abdominal ultrasound and computerized tomography. He was further examined to rule out infections with similar signs and symptoms, connective tissue diseases and malignancies and all were found negative. Hypercellular bone marrow were detected in the aspiration material. Bone marrow smears, bone marrow samples inoculated in NNN medium and serum samples of the patient were sent to the reference parasitology laboratory of Refik Saydam National Public Health Agency for evaluation in terms of VL. The diagnosis was confirmed by the detection of Leishmania IgG titer as 1/512 with in-house indirect immunofluorescence antibody test, by positivite rK39 Dipstick (InBios, USA) test and by the observation of Leishmania amastigote forms in the bone marrow smears. Bone marrow culture in NNN medium also revealed positive result by the determination of Leishmania promastigote forms on the 7th day. The treatment was initiated by pentavalent antimony [glucantime 1 x 10 mg/kg/day intramuscular (IM)] however, due to severe adverse effects it has switched to liposomal amphotericin B (3 mg/kg/day). The patient completely recovered without complication. In conclusion VL should be considered in the differential diagnosis of patients, even adults, with persistent fever, hepatosplenomegaly and pancytopenia, in endemic countries such as Turkey.
2010[The clinical manifestations of three cases with melioidosis].Zhonghua Jie He He Hu Xi Za ZhiTo investigate the clinical features of 3 cases of Burkholderia pseudomallei septicemia in Guangxi Province, and therefore to improve its diagnosis and treatment.The clinical features, treatment and prognosis of 3 cases of acute septicemic melioidosis admitted to this hospital from October 2006 to December 2008 were retrospectively analyzed.The 3 male patients were local farmers, with an average age of (42 ± 2) years. Two of them had a history of frequent trauma and contact with polluted water, and another had a history of exposure to the dust and soil. All patients had an acute onset, manifested as septicemia with chills, high-grade fever, anemia and weight loss. At the same time, the disease was often complicated with multiple organ abscesses. The pus was characterized by smelling like mud. One case was manifestated with lung abscess, with right calf skin pyogenic infection, and the another case was with liver, spleen, pancreas and mediastinal abscess, and the third presented with right facial and ankle soft tissue abscess. The leukocyte counts [(11.6 ± 0.5) × 10(9)/L] and neutrophils [(8.3 ± 0.4) × 10(9)/L] in 2 patients were slightly increased, but decreased in the other patient. There were significant increase of erythrocyte sedimentation rate (63.5 ± 2.7) mm/1 h and c-reactive protein (155 ± 4) mg/L, and liver dysfunction and elevated blood glucose occurred in 3 patients. Chest radiology and CT showed a number of patchy infiltrates, consolidation, and nodules with varying sizes in the upper lung lobes. Abscess in other organs mainly occurred in liver, spleen, and skin. The final diagnosis was confirmed as infection with Burkholderia pseudomallei by repeated blood or pus culture. The isolated Burkholderia pseudomallei was sensitive to carbapenem, and β-lactam + β-lactamase inhibitors. One patient was treated effectively with Imipenem, and other 2 patients with β-lactam + β-lactamase inhibitors. After 3 - 4 days of treatment with antibiotics, the body temperature of these patients gradually decreased, and the intravenous drug was used as long as 4 to 8 weeks, and a total course of antibiotic therapy would continue for 4 to 6 months.Human melioidosis exists in the south and southwest of Guangxi. Repeated blood or pus culture can confirm the diagnosis. A relatively long course of antibiotic treatment with β-lactam/β-lactamase inhibitors or carbapenem is recommended.
2011Serum procalcitonin does not differentiate between infection and disease flare in patients with systemic lupus erythematosus.LupusSystemic erythematosus lupus (SLE) is a common autoimmune disease. Disease flares may mimic infection with fever, inflammatory syndrome and chills, sometimes resulting in a difficult differential diagnosis. Elevated serum procalcitonin (PCT) levels have been reported to be predictive of bacterial infections, but with conflicting results. The value of serum procalcitonin has not been assessed in large series of SLE. We aimed to describe the distribution of PCT levels in SLE patients with and without flares, to assess the factors associated with increased PCT levels, and to determine the positive and negative predictive values of increased PCT for bacterial infection in SLE patients. Hospitalized SLE patients were included in a retrospective study. Serum PCT had been assayed, or a serum sample had been frozen on admission, before treatment modification. Serum PCT, measured by an automated immunofluorometric assay, and SLEDAI were assessed at the same time. Some 53 women (median age: 33.7 years, range 16-76) and seven men (median age: 52.5 years ± 19) were included. The median SLEDAI for patients with flare (n = 16, 28%) was 2 (range: 0-29). Five patients (8%) had systemic infection. Only one patient had increased PCT levels. Men had significantly higher PCT levels than women (0.196 ± 0.23 versus 0.066 ± 0.03, p < 0.01) and a significant correlation was observed between PCT, age, erythrocyte sedimentation rate, and C-reactive protein. We conclude that PCT levels were within the normal range in infected and non-infected SLE patients and there was no ability to differentiate SLE patients with or without bacterial infection.
2009Clinical features and prognostic factors of emphysematous urinary tract infection.J Microbiol Immunol InfectEmphysematous urinary tract infection (EUTI) is a rare and potentially life-threatening condition that requires prompt evaluation and management. This study was conducted to ascertain the clinical features and prognostic factors of EUTI.Patients diagnosed with EUTI radiologically and treated at the Kaohsiung Medical University Hospital, Kaohsiung, Taiwan, from March 2001 to February 2007 were evaluated. The patients' demographic and clinical characteristics, laboratory data, treatment, and outcomes were analyzed retrospectively.Of 31 patients enrolled, 16 had emphysematous pyelonephritis (EP) and 15 had emphysematous cystitis (EC) classified according to the imaging findings. The symptoms and signs of fever, chills, flank pain, and percussion tenderness at the costovertebral angle were significantly greater among patients in the EP group than in the EC group (p = 0.029, p = 0.009, p < 0.001, and p < 0.001, respectively). There were no statistically significant differences in the initial laboratory data except for C-reactive protein between the 2 groups (220.4 microg/mL vs 91.4 microg/mL; p = 0.001). Escherichia coli was the most commonly isolated organism. The overall mortality rate was similar in both groups. Significant differences in renal function and hematuria were seen between the patients who died and the survivors in the EP group (p = 0.004 and p = 0.027, respectively), but these were not noted in the EC group.There was no significant clinical feature suggesting the presence of EC. The clinical features of EP were similar to uncomplicated pyelonephritis. Impaired renal function and hematuria were poor prognostic factors for patients with EP, but not for patients with EC.
2010Additional value of procalcitonin for diagnosis of infection in patients with fever at the emergency department.Crit Care MedFirst, to determine whether procalcitonin (PCT) significantly adds diagnostic value in terms of sensitivity and specificity to a common set of markers of infection, including C-reactive protein (CRP), at the Emergency Department. Second, to create a simple scoring rule implementing PCT values. Third, to determine and compare associations of CRP and PCT with clinical outcomes.The additional diagnostic value of PCT was determined using multiple logistic regression analysis. A score was developed to help distinguish patients with a culture-proven bacterial infection from patients not needing antibiotic treatment using 16 potential clinical and laboratory variables. The prognostic value of CRP and PCT was determined using Spearman's correlation and logistic regression.Emergency Department of a 310-bed teaching hospital.Patients between 18 and 85 years old presenting with fever to the Emergency Department.None.A total of 211 patients were studied (infection confirmed, n = 73; infection likely, n = 58; infection not excluded, n = 46; no infection, n = 34). CRP and chills were the strongest predictors for the diagnosis of bacterial infection. After addition of PCT to these parameters, model fit significantly improved (p = .003). The resulting scoring rule (score = 0.01 * CRP + 2 * chills + 1 * PCT) was characterized by an AUC value of 0.83 (sensitivity 79%; specificity of 71%), which was more accurate than physician judgment or SIRS (systemic inflammatory response syndrome). PCT levels were significantly associated with admission to a special care unit, duration of intravenous antibiotic use, total duration of antibiotic treatment, and length of hospital stay, whereas CRP was related only to the latter two variables.These data suggest that PCT may be a valuable addition to currently used markers of infection for diagnosis of infection and prognosis in patients with fever at the Emergency Department.
Risk index score for bacteremia in febrile neutropenic episodes in children with malignancies.J BUONTo prospectively determine risk factors for bacteremia in febrile neutropenic children with malignancies.We studied 199 episodes of febrile neutropenia in 80 children with malignancies, treated by conventional chemotherapy for a 4-year period (2000 - 2004). A standardized computer database with a set of variables for each febrile neutropenic episode was used. C-reactive protein (CRP) was measured at the first febrile episode and on the 3rd and 5th day from the beginning of antibiotic therapy by immunoturbidimetric method. Blood cultures were taken at the onset of fever and before initiation of antibiotic therapy.Multivariate logistic regression analysis determined 5 variables as independent risk factors for bacteremia: the underlying malignant disease (leukemia, non - Hodgkin's lymphoma / NHL, stage IV), chills, perianal cellulitis, presence of central venous catheter and CRP rise >or=34.5 mg/L between the onset of fever and the 3rd day of empiric antibiotic therapy. Thus we identified a low-risk group for bacteremia of 19.1%.Serial measurement of CRP allows for definite risk stratification of febrile neutropenic episodes on the 3rd day from the onset of fever. The low-risk group could be eligible for sequential empiric antibiotic therapy.
2009[Prolonged course of tick-borne ulceroglandular tularemia in a 20-year-old patient in Germany--case report and review of the literature].Dtsch Med WochenschrA 20-year-old female patient presented with painful axillary lymphadenopathy. She reported a tick bite five months ago in her right hand followed by fever, chills and regional lymphadenopathy. Empiric antibiotic treatment with doxycyclin and ciprofloxacin had led to defervescence but no change in painful lymph node swellings. Surgical removal of a cubital lymph node had already been performed three months after the tick bite.Laboratory findings were normal except for moderate elevation of C-reactive protein. Serology confirmed the suspected clinical diagnosis of ulceroglandular tularemia. Retrospective real-time PCR (markers fopA and tul4) for Francisella tularensis from the previously removed lymph node (paraffin tissue blocks) was negative.Clinical presentation and serological test results were consistent with a prolonged course of tick-borne ulceroglandular tularemia associated with reactive lymph node swelling. The patient requested surgical removal of the painful axillary lymph node. Histology showed reticulocytic, abscess forming lymphadenitis with pseudotuberculosis type of granulomatosis and negative acid-fast staining. Blood culture, capture ELISA and real-time PCR for Francisella tularensis performed on material from the lymph node preparations were negative. A complete recovery was achieved without renewed antibiotic treatment.According to recent seroprevalence studies, the emergence of tularemia as a rare zoonosis in Germany is clinically underestimated. This case report illustrates possible appearance of the disease in other than known risk groups (e.g. hunters, lumbermen). Ectoparasites like infected ticks have to be considered as vectors, even in non-endemic regions.
2009Bacteremia coexisting with tophaceous gout of the spine mimicking spondylodiscitis: a case report.Spine (Phila Pa 1976)A case report and review of the literature.To report a rare case of bacteremia coexisting with spinal gout initially suspected as pyogenic spondylodiscitis.Gouty spine is a rare disease. It is even rare when coexisting with bacteremia. The presentation as pain, fever, and positive blood culture will make it more difficult to distinguish from spinal infection.A 64-year-old woman with type II diabetes mellitus and chronic renal insufficiency was admitted to the emergency department with a fever of 39 degrees C, chills, and back pain. Laboratory studies revealed an elevated white count and neutrophils; her serum glucose level was 279 mg/dL. The C-reactive protein level was 25.55 mg/dL and serum uric acid was in the upper range of normal. Blood cultures revealed Escherichia coli, Klebsiella pneumoniae, and Enterococcus faecalis. Urine culture revealed 3 separate gram-negative bacilli. Magnetic resonance imaging of the spine revealed contrast enhancement in the L4-L5 and T5-T9 vertebral bodies. Infective spondylodiscitis of the lumbar and thoracic spine was suspected.Because antibiotic treatment had failed, surgical debridement with diskectomy, partial corpectomy, and allogenous strut graft reconstruction (T8-T9) was performed. During the operation, 600 cc of pleural effusion was drained. Chalky white material was noted at the T8-T9 disc and the adjacent vertebral bodies. Cultures for bacteria, tuberculosis, and fungus were all negative. Histologic examination revealed deposition of eosinophilic crystal-like material, and a diagnosis of tophaceous gout of the spine was established.This is, to our knowledge, the first case of bacteremia coexisting with multiple areas of tophaceous gout of the spine. Although uncommon, gouty spine should be added into the differential diagnosis of patients with back pain and bacteremia.
Infective endocarditis due to Haemophilus aphrophilus: a case report.J Pediatr (Rio J)To report the case of a child with infective endocarditis caused by Haemophilus aphrophilus.Boy with 20 days of fever and chills. On admission, he was febrile, pale and with no signs of hemodynamic instability; on cardiac auscultation, a mitral-related holosystolic murmur was observed. Laboratory examination identified anemia (hemoglobin = 9.14 g/dL), total leukocytes of 11,920 mm3, platelets of 250,000 mm3, elevated sedimentation velocity of red cells and elevated C-reactive protein. The echocardiogram revealed image on mitral valve, resembling vegetation. Considering endocarditis, antibiotic therapy was started with crystalline penicillin (200,000 UI/kg/day) in association with gentamicin (4 mg/kg/day). On the third day of treatment, Haemophilus aphrophilus was identified in the blood cultures and the antibiotic scheme was replaced with ceftriaxone (100 mg/kg/day). On the 20th day of evolution, the patient was pale but with no fever or other complaints. Examinations showed hemoglobin = 7.0 g/dL, leukocytes = 2,190 mm3, platelets = 98,000 mm3, international normalized ratio = 1.95 and R = 1.89. Considering the hypothesis of adverse reaction to ceftriaxone, a 6-week replacement treatment with ciprofloxacin (20 mg/kg/day) was started. Examination results normalized after 72 hours of the replacement therapy. During ambulatory follow-up, patient presented with severe mitral regurgitation, undergoing a valve replacement with a metallic prosthetic valve 9 months after acute event. Patient has done well throughout the 3-year ambulatory follow-up.Identification of agents of the HACEK group (Haemophilus ssp, Actinobacillus actinomycetemcomitans, Cardiobacterium hominis, Eikenella corrodens and Kingella kingae) in children with infective endocarditis is rare. This case report, with no HACEK agent-related risk factors, reinforces the need for identification of the etiological agent of endocarditis to ensure adequate treatment.
2007[An elderly woman with duodenal perforation difficulty diagnose].Nihon Ronen Igakkai ZasshiAn 86-year-old woman was referred with acute epigastric pain. She had tenderness, but no muscular guarding of the epigastric lesion. Abdominal ultrasound showed a gallstone with a normal gallbladder wall and no ascites. The white blood cell count was 11,600/mm(3), but she was negative for C-reactive protein (CRP). An upper gastrointestinal tract endoscopic examination revealed only edema of the duodenal mucosa. Although H2-receptor antagonists were given, she had to be admitted due to chills and high fever. While the abdominal symptoms did not change, the CRP concentration became 14.79mg/dl. While plain abdominal X-ray did not show an abnormal gas pattern, subsequent abdominal CT examination showed air and fluid collection around the second portion of the duodenum. We diagnosed duodenal perforation and prepared for emergency operation. However, her general condition had markedly deteriorated during the hours. Laparotomy revealed a free purulent fluid around second portion of the duodenum caused by perforation of a duodenal diverticulum. The patient gradually recovered and was discharged after 58 days. Since a duodenal perforation in an elderly patient is difficult to diagnose early in spite of serious illness, abdominal CT should be encouraged.
2006[Cat-scratch disease. Review of eight adult patients hospitalized for fever or adenopathy].Rev Med ChilCat-scratch disease is common among children. Among adults the disease is less often considered in the differential diagnosis of enlarged lymph nodes and fever.To report the clinical and laboratory features of eight patients with cat-scratch disease.Review of the medical records of eight patients (aged 22 to 57 years, six males) with a serological diagnosis of cat-scratch disease (an IgG titer over 1:256, by immunofluorescence).Only five patients recalled having had contact with cats. Seven had fever and weight loss. Six had excessive sweating and five had chills. Seven had painfully enlarged lymph nodes mainly in submandibular and axillary regions. All had an increased C reactive protein and six had elevated erythrocyte sedimentation rate. Five had leukocytosis and four an elevated serum lactate dehydrogenase. The disease subsided in all, even in one patient that did not receive antimicrobials.Cat-scratch disease should be considered in the differential diagnosis of adult patients with lymph adenitis and fever.
2006New-onset rheumatoid arthritis after anthrax vaccination.Ann Allergy Asthma ImmunolAnthrax vaccine was licensed in 1970 and is used to protect individuals exposed to biological warfare and those who may come in contact with Bacillus anthracis in infected animals or in laboratory settings. The current adsorbed anthrax vaccine is regarded as effective and safe. Adverse effects reported include fever, chills, myalgia, arthralgia, and nausea. Four cases of rheumatoid arthritis (RA) temporally related to anthrax vaccine have been reported. As the number of administered doses increases, a better understanding of its adverse events profile will be forthcoming.To describe another patient with RA temporally related to anthrax vaccination.A 42-year-old man developed bilateral knee stiffness and pain in all the proximal interphalangeal joints 5 days after receiving the first dose of anthrax vaccine. He reported chills, fever, and joint and neck pain, with a tender nodule at the injection site after dose 2. Hours after receiving dose 3 he experienced fever, chills, nausea, vomiting, and neck, hand, and shoulder pain. The vaccination series was terminated after the third dose.Physical examination revealed moderate swelling and tenderness of his bilateral proximal interphalangeal joints. His complete blood cell count was normal; rheumatoid factor level, 198 IU/mL; erythrocyte sedimentation rate, 53 mm/h; antinuclear antibodies, negative; C-reactive protein level, 2.7 mg/L; and anti-cyclic citrullinated peptide antibody level, 168 EU. Radiographs revealed mild degenerative changes in his hands and knees bilaterally.This case represents a fifth patient with RA temporally related to anthrax vaccine.
2006[Leptospirosis after a stay in Thailand].Dtsch Med WochenschrA 35-year-old man was admitted to our hospital with chills, headache, pain in the calves for five days and a bloody sputum. The day before he had returned from a 4-week trip to the north of Thailand. There he had participated in hiking trips and walked sometimes over wet fields with small skin injuries on his feet. The admission examination was uneventful except fever as high as 39 Celsius, particularly no rash, no conjunctivitis, no spleno- or hepatomegaly and no palpable lymph nodes could be noted.An x-ray of the chest showed confluent opacities, a bronchoscopy revealed diffuse alveolar hemorrhagy. Blood chemistry showed elevated liver enzymes, elevated kidney retention parameters and an increased C-reactive protein. An extended microbiological diagnostic procedure showed elevated antibody titers for leptospira and a PCR detected leptospira-DNA, representing acute leptospirosis.After initiation of an antibiotic regimen including ceftriaxone and erythromycine the fever resolved immediately and the general condition improved. The patient could be discharged after two weeks in a good physical condition.The constellation of flu-like symptoms, hepatitis and nephritis, eventually escorted by bloody sputum, may suggest leptospirosis.
2006Initial symptoms in pulmonary embolism differ from those in pneumonia: a retrospective study during seven years.Eur J Emerg MedTo compare initial symptoms in pulmonary embolism with community-acquired pneumonia and relate to C-reactive protein and pulmonary infiltrates in order to improve the clinical assessment at the emergency department.A retrospective review of patients with pulmonary embolism diagnosed in the clinic for infectious diseases (CID), (n=25), and a randomized sample of patients with pulmonary embolism diagnosed in the department of medicine (n=64), and a randomized sample of patients with community-acquired pneumonia (n=54) diagnosed in the clinic for infectious diseases.Initial symptoms in pulmonary embolism, dominated by dyspnoea and/or pleuritic chest pain were significantly different from those in community-acquired pneumonia, dominated by fever, chills and/or cough (P<0.001). On admission, C-reactive protein and body temperature were significantly higher and pulmonary infiltrates were more common in pneumonia compared with randomized pulmonary embolism patients. Twenty-five patients with a final diagnosis of pulmonary embolism were erroneously suspected of having lung infection, owing to increased C-reactive protein, presence of pulmonary infiltrates and/or high fever. However, they had classical symptoms of pulmonary embolism.Pulmonary infiltrates, high fever and a high level of C-reactive protein can deceive the physician to suspect pneumonia instead of pulmonary embolism. Classical initial symptoms ought to direct the physician in diagnosing pulmonary embolism. We emphasize a detailed patient history of initial symptoms.
2006Does open reduction increase the chance of infection during intramedullary nailing of closed tibial shaft fractures?J Orthop TraumaTo evaluate whether an open technique used to obtain reduction during intramedullary nailing of closed tibial shaft fractures increases the risk of infection, compared to closed reduction and nailing.University level 1 trauma center.Retrospective database analysis.One hundred seventeen patients with 119 fractures from our trauma database who had sufficient follow-up and met study criteria. The patients were grouped by open versus closed reduction. Only OTA fracture types 42 A to C were included in this study.Locked reamed intramedullary nailing for closed tibial shaft fractures accomplished through either open or closed reduction.The presence or absence of infection as determined by the clinical presentation (erythema, warmth, purulent drainage, fevers, chills, increased pain at the fracture site), indicative laboratory work (complete blood count, erythrocyte sedimentation rate, C-reactive protein), and/or positive culture.There were 85 males and 32 females. The average age was 35.7 years; the average follow-up was 14.3 months. Of the 119 fractures, 79 had closed reduction whereas 40 had open reduction. The open reductions consisted of 13 with a formal incision (>1 cm in length), 22 with percutaneous incisions, and 5 with fasciotomies. There were no infections in the closed reduction group and 2 infections (5%) in the open reduction group. This difference was not statistically significant (P=0.1). The average time to union was 7.0 months in closed reductions and 7.3 months in open reductions. By latest follow-up, 107 fractures had reached union (89.9%), 1 had not (0.8%), and 11 were lost to final follow-up (9.2%).Limited open techniques can greatly facilitate the reduction of closed tibial shaft fractures but raise concern for infection through exposure of the fracture site. This study found that the rate of infection for open versus closed reductions was higher but not statistically different. Judicious use of open reduction techniques during intramedullary nailing of closed tibia fractures seems to have a minimal risk of infection.
2006A dose escalating, placebo controlled, double blind, single dose and multidose, safety and tolerability study of fontolizumab, a humanised anti-interferon gamma antibody, in patients with moderate to severe Crohn's disease.GutThis study was designed to evaluate the safety of fontolizumab, a humanised anti-interferon gamma antibody, in patients with moderate to severe Crohn's disease (CD).Forty five patients with a CD activity index (CDAI) of 250-450 were randomised in a double blind, placebo controlled, dose escalating fashion to receive single doses of fontolizumab (0.1, 1.0, and 4.0 mg/kg) or placebo. By day 29, patients with clinical response were re-randomised to receive three additional doses of one half their initial fontolizumab dose or placebo at four weekly intervals. Primary objectives were safety and tolerability. Secondary outcomes included assessments of immunogenicity, clinical activity, and potential pharmacodynamic surrogates.Treatment was generally well tolerated. There were slightly more reports of chills, flu-like syndrome, asthenia, nausea, and vomiting in the 1.0 mg and 4.0 mg/kg fontolizumab cohorts. Two serious adverse events rated as worsening of CD occurred under fontolizumab. Antibodies to fontolizumab were confirmed in one patient. No differences in clinical activity parameters were noted between any of the active treatment groups and placebo, with the placebo group having a particularly favourable outcome (60% response and 40% remission). By day 29, a more enhanced decrease in median Crohn's disease endoscopic index of severity (p = 0.02) and serum C reactive protein (p<0.001) was observed in the 4.0 mg/kg (n = 14) fontolizumab cohort compared with placebo (n = 10). Pharmacodynamic effects were observed by immunohistochemistry.Fontolizumab was well tolerated with minimal immunogenicity at doses of up to 4.0 mg/kg in patients with CD. A biological activity of fontolizumab is suggested.
2006Clinical and laboratory features in the early stage of severe acute respiratory syndrome.J Microbiol Immunol InfectTo characterize the clinical and laboratory features of severe acute respiratory syndrome (SARS) in the early stage and to compare them with those of patients initially suspected of having SARS who were later determined to have other febrile diseases.Between March and June 2003, 122 patients with possible SARS were admitted to the isolation ward of Tri-Service General Hospital. SARS was diagnosed according to the modified World Health Organization case definition (May 1, 2003). Among them, 43 were classified as probable SARS cases and a SARS etiology was excluded in 32 patients.Presenting symptoms on admission included fever (97.7% of probable cases, 84.4% of excluded cases), chills (39.5% vs 18.8%), cough with sputum production (16.3% vs 40.6%), dry cough (23.3% vs 9.4%), dyspnea (18.6% vs 9.4%), diarrhea (14.0% vs none), rhinorrhea (2.3% vs none), and myalgia (7.0% vs 6.6%). Common laboratory features included lymphopenia and elevated aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, C-reactive protein and creatine kinase values. Intubation and mechanical ventilation were required in 12 probable cases and 6 excluded cases. Five patients with probable SARS (11.6%) died. A scoring system which was developed to differentiate SARS patients from other febrile patients in the emergency room could differentiate probable cases from excluded cases with a sensitivity of 36.4% and a specificity of 70.6%.The clinical presentation and laboratory features at the early stage do not allow differentiation of patients with SARS-CoV infection from other febrile patients. Thus, it is mandatory for all healthcare workers to strictly follow standard isolation precautions during an outbreak to minimize disease transmission.
2005Pyogenic liver abscess: a retrospective analysis of 107 patients during a 3-year period.Jpn J Infect DisPyogenic liver abscess (PLA) is a potentially life-threatening disease, and early diagnosis may be difficult. In order to provide diagnostic clues and to enhance the prompt management of such cases, we retrospectively investigated the clinical characteristics of PLA during a 3-year period in a tertiary-care hospital. The crude incidence rate of PLA in our study was 446.1 per 100,000 hospital admissions. Male predominance and a mean age of 57.6 +/- 14.4 years were observed. Diabetes mellitus was the most common concomitant disease, and biliary pathologies were the most common predisposing cause of this type of abscess. The most common clinical features were fever, chills, and abdominal pain. Leukocytosis was found in 67.3% of the patients, and the observed C-reactive protein (CRP) values were high. The most common pathogen was Klebsiella pneumoniae. The mortality rate was 6.5%. A complete history, physical examination, evaluation of the white blood cell count and CRP, and the prompt arrangement of imaging studies may lead to an earlier diagnosis. The aggressive performance of image-guided catheter drainage and the appropriate administration of antibiotics may reduce the mortality rate of PLA.
2005A simple prediction algorithm for bacteraemia in patients with acute febrile illness.QJMExisting prediction models for the risk of bacteraemia are complex and difficult to use. Physicians are likely to use a model only if it is simple and sensitive.To develop a simple classification algorithm predicting the risk of bacteraemia.Hospital-based study.We enrolled 526 adult consecutive patients with acute febrile illness (40 with bacteraemia) presenting to the emergency department at a community hospital in Okinawa, Japan. Recursive partitioning analysis was used to build the classification algorithm with V-fold cross-validation. We used two clinical scenarios: in the first, laboratory tests were not available; in the second, they were.The two prediction algorithms generated three different risk groups for bacteraemia. In the first scenario, the important variables were chills, pulse, and physician diagnosis of a low-risk site. The low-risk group from this first algorithm included 68% of the total patients; sensitivity was 87.5% and the misclassification rate was 1.4% (5/358). In the second scenario, the important variables were chills, C-reactive protein, and physician diagnosis of a low-risk site. The low-risk group for the second algorithm included 62% of the total patients; sensitivity was 92.5% and misclassification rate 0.9% (3/328). The algorithms had negative predictive values of 98.6% (first scenario) and 99.1% (second).This simple and sensitive prediction algorithm may be useful for identifying patients at low risk of bacteraemia. Prospective validation is needed in other settings.
2005Hemorrhagic fever with renal syndrome in the Pomurje region of Slovenia--an 18-year survey.Wien Klin WochenschrTo 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.
2004Comparison of patients fulfilling criteria for confirmed and probable human granulocytic ehrlichiosis.Scand J Infect DisIn order to assess the validity of definitions for human granulocytic ehrlichiosis (HGE), epidemiological, clinical and laboratory findings for 13 patients with confirmed HGE and 21 patients fulfilling criteria for probable HGE were compared. The patients were identified during a prospective study on the aetiology of febrile illness occurring after a tick bite, performed in Slovenia from 1995 to 2002. Significant differences between the 2 groups were found for age of patients, duration of fever before the first examination, and several clinical and laboratory parameters including the occurrence of chills, myalgia, arthralgia, leukopenia, thrombocytopenia, abnormal liver function tests results, and elevated concentration of C-reactive protein. All the abnormalities were established more often in patients with confirmed HGE than in those with probable HGE. Patients with confirmed HGE exhibited higher geometric mean titre values and higher peak antibody titres to Anaplasma phagocytophilum that developed later in the course of their illness. The differences indicate that in some patients fulfilling criteria for probable HGE the signs and symptoms most probably are not the result of a recent infection with A. phagocytophilum.
2005Clinical manifestations of Kikuchi's disease in southern Taiwan.J Microbiol Immunol InfectHistiocytic necrotizing lymphadenitis, or Kikuchi's disease (KD), is a self-limiting cervical lymphadenitis of unknown origin. The diagnosis of KD is problematic due to the lack of specific laboratory tests. This study reviewed the clinical characteristics of 58 patients with KD. Clinical manifestations were of considerable diversity. The mean age of patients was 24.88 +/- 7.44 years and there was a female predominance (1.76:1). The most frequent clinical findings were enlarged tender lymph nodes (50%), fever (43%), sore throat (21%), non-productive cough (12%), headache (10%), chills (9%) and rhinorrhea (9%). The most common initial laboratory abnormalities were leukopenia (29%), elevated erythrocyte sedimentation rate (14%), liver function impairment (14%), elevated C-reactive protein level (12%), and anemia (10%). Most patients had unilateral lymph node involvement (79%), which was usually located in the posterior triangle of the cervical lymph nodes (90%). Most patients had no comorbid disease (93%). No recurrence occurred. KD should be included in the differential diagnosis of fever with cervical lymphadenopathy.
2004Eight-month prospective study of 14 patients with hospital-acquired severe acute respiratory syndrome.Mayo Clin ProcTo define the clinical characteristics and clinical course of hospital-acquired severe acute respiratory syndrome (SARS).This 8-month prospective study of 14 patients with hospital-acquired SARS in Taipei, Taiwan, was conducted from April through December 2003.The most common presenting symptoms in our 14 patients with hospital-acquired SARS were fever, dyspnea, dizziness, malaise, diarrhea, dry cough, muscle pain, and chills. Lymphopenia and elevated serum levels of lactate dehydrogenase (LDH) and C-reactive protein (CRP) were the most common Initial laboratory findings. Initial chest radiographs revealed various pattern abnormalities and normal results. Five of the 14 patients required mechanical ventilation. The need for mechanical ventilation was associated with bilateral lung involvement on the initial chest radiograph and higher peak levels of LDH and CRP. Clinical severity of disease varied from mild to severe. At 8 months after disease onset, patients with mild or moderate SARS had normal findings or only focal fibrosis on chest high-resolution computed tomography. However, bilateral fibrotic changes remained in the 4 patients who had recovered from severe SARS, 1 of whom had mild restrictive ventilatory impairment. One patient with severe SARS died; she was elderly and had other comorbidities. Five additional patients had reduced diffusing capacity.The clinical picture of our patients presenting with hospital-acquired SARS revealed atypical pneumonia associated with lymphopenia, elevated serum levels of LDH, rapid clinical deterioration, and lack of response to empirical antibiotic therapy. Substantially elevated levels of LDH and CRP correlated with severe illness requiring mechanical ventilatory support. In those receiving mechanical ventilation, pulmonary function was only mildly reduced at 6 to 8 months after acute illness, consistent with the natural history of acute respiratory distress syndrome due to other causes.
2004Muckle-Wells syndrome: clinical and histological skin findings compatible with cold air urticaria in a large kindred.Br J DermatolMuckle-Wells syndrome is a rare familial disease with autosomal dominant inheritance, characterized by cold sensitivity and polyarthralgias since childhood, with possible later development of nerve deafness and renal amyloidosis. The nature of the skin manifestations is, however, not well characterized.To clarify the nature of cutaneous cold sensitivity in patients with Muckle-Wells syndrome by studying clinical aspects and histological features.Eighteen members of a family with Muckle-Wells syndrome and the recently identified mutation of the CIAS1 gene at locus 260 of chromosome 1q44 were available for study. Examination included a thorough history, physical examination and a battery of laboratory tests. In two brothers, standard cold contact and cold air provocation tests were performed, as were biopsies from normal and lesional skin.All affected family members reported an increased sensitivity to cold, dampness or changes in temperature, and most had arthritis and conjunctivitis. Eight had developed hearing loss, four renal involvement, and amyloid deposits were found in three of five patients in whom rectal biopsies were performed. Laboratory tests showed leucocytosis and elevated C-reactive protein, but no serum cold agglutinins and cryoglobulins. Skin eruptions, with weals of 0.2-3 cm, lasted from 5 to 24 h and were associated with local itching or pain as well as fever, malaise and chills. On cold provocation of two patients, lesions could be reproduced by cold air, but not by contact with an ice cube or cold water. On histology, there was increased vasodilatation, marked infiltration with neutrophils and monocytes/macrophages, and increased expression of beta 2 integrins in lesional vs. normal skin. Numbers of mast cells as well as expression of interleukin-3 and tumour necrosis factor-alpha were unchanged.Cold-induced skin lesions in Muckle-Wells syndrome represent typical generalized cold air/wind inflammatory reactions, as also observed in familial cold urticaria. Microscopic features are similar to those observed in other types of urticaria.
2004[A case of probable bacterial translocation-associated sepsis in healthy adult].Kansenshogaku ZasshiWe report a patient with bacterial translocation-associated sepsis who was healthy and did not have any related-background. The 57-year-old male had been well until 16 hours before admission, when nausea and vomiting gradually developed and increased in intensity. In the morning of May 22, 2002, he had shaking chills, temperature of 38.6 degrees C and watery diarrhea, and was admitted to Kawasaki Municipal Hospital. On admission, temperature was 40.7 degrees C but otherwise physical examination revealed no particular abnormality. Laboratory data showed total white blood cells of 28,400/microliter, platelet count of 130,000/microliter, creatinine of 2.0 mg/dl and C-reactive protein of 7.5 mg/dl. 1 g of cefmetazole was administered every eight hours. In the early morning of May 23, he suddenly went into shock. At that time, laboratory findings revealed total white blood cells of 33,700/microliter, platelet count of 65,000/microliter, C-reactive protein of 24.9 mg/dl, creatinine of 5.6 mg/dl and serum potassium concentration of 5.7 mEq/l. Gram positive cocci and gram negative rods were isolated from blood culture obtained on admission. Cefmetazole was changed to 1.5 g/day of imipenem/cilastatin sodium and 600 mg/day of clindamycin. In addition, hemodialysis and endotoxin removal with an adsorbent column using polymyxin B were performed. Bacteria detected in the blood on admission were identified as Klebsiela oxytoca and Enterococcus faecium. Imipenem/cilastatin sodium and clindamycin were continued for 13 days. The patient recovered fully and was discharged on June 11. This case suggests that bacterial translocation-associated sepsis might occur even in a hitherto healthy adult.
2004Severe acute respiratory syndrome in Taiwan: analysis of epidemiological characteristics in 29 cases.J InfectTo describe the clinical characteristics and outcomes of patients with severe acute respiratory syndrome (SARS).Between March 28 and June 30 '2003, 29 patients with probable SARS seen at Shin Kong Wu Ho-Su Memorial Hospital, Taipei, were analysed.Presenting symptoms included fever (100%), cough (69.0%), chills or rigor (62.1%), and shortness of breath (41.4%). Mean days to defervescence were 6.8+/-2.9 days, but fever recurred in 15 patients (51.7%) at 10.9+/-3.4 days. Common laboratory features included lymphopenia (72.4%), thrombocytopenia (34.5%) and elevated C-reactive protein (CRP), lactate dehydrogenase (LDH), and aspartate aminotransferase (AST) (93.1, 62.1, 44.8%, respectively). All patients except one had initial abnormal chest radiographs and 20 (69.0%) had radiological worsening at 7.5+/-2.6 days. Nine patients (31.0%) subsequently required mechanical ventilation with four deaths (13.8%). Most patients with clinical deterioration responded to pulse corticosteroid therapy (14 out of 17) but six complicated with nosocomial infections. The risk factors associated with severe disease were presence of diarrhoea, high peak LDH and CRP, high AST and creatine kinase on admission and high peak values.Prudent corticosteroid use, vigilant microbiological surveillance and appropriate antibiotics coverage are the key to successful treatment.
2003Outcomes and prognostic factors in 267 patients with severe acute respiratory syndrome in Hong Kong.Ann Intern MedSevere acute respiratory syndrome (SARS) has become a global public health emergency.To evaluate the characteristics and outcomes of patients with SARS in Hong Kong and to identify predictors of mortality.Retrospective cohort study.Quarantine hospital for patients with SARS in Hong Kong.267 consecutive patients hospitalized from 26 February to 31 March 2003 for probable or confirmed SARS.Clinical, laboratory, and radiographic measures; 3-month mortality rate.According to our case definition, there were 227 cases of confirmed SARS and 40 cases of probable SARS. Common presenting symptoms were fever (99% of patients), chills (74%), malaise (63%), and myalgia (50%). Laboratory findings included lymphopenia (73%), thrombocytopenia (50%), hyponatremia (60%), and elevated levels of lactate dehydrogenase (47%) and C-reactive protein (75%). During hospitalization, incidence of diarrhea (53%), anemia (53%), and acute renal failure (6%) increased. Sixty-nine patients (26%) required intensive care because of respiratory failure. The 3-month mortality rate was 12% (95% CI, 8% to 16%). Factors contributing to mortality were respiratory failure, acute renal failure, and nosocomial sepsis. On multivariate Cox regression, age older than 60 years (relative risk, 5.10 [CI, 2.30 to 11.31]; P < 0.001) and lactate dehydrogenase level greater than 3.8 micro kat/L at presentation (relative risk, 2.20 [CI, 1.03 to 4.71]; P = 0.04) were independent predictors of mortality.Because of the longer follow-up period in our cohort, the mortality rate in these patients is higher than rates reported in previous studies. Advanced age and high lactate dehydrogenase level at presentation predict mortality. *For members of the Princess Margaret Hospital SARS Study Group, see the Appendix.
2003Comparison and evaluation of real-time PCR, real-time nucleic acid sequence-based amplification, conventional PCR, and serology for diagnosis of Mycoplasma pneumoniae.J Clin MicrobiolMycoplasma pneumoniae is a common cause of community-acquired pneumonia and lower-respiratory-tract infections. Diagnosis has traditionally been obtained by serological diagnosis, but increasingly, molecular techniques have been applied. However, the number of studies actually comparing these assays is limited. The development of a novel duplex real-time PCR assay for detection of M. pneumoniae in the presence of an internal control real-time PCR is described. In addition, real-time nucleic acid sequence-based amplification (NASBA) on an iCycler apparatus is evaluated. These assays were compared to serology and a conventional PCR assay for 106 clinical samples from patients with lower-respiratory-tract infection. Of the 106 samples, 12 (11.3%) were positive by all the molecular methods whereas serology with acute sample and convalescent samples detected 6 (5.6%) and 9 (8.5%), respectively. Clinical symptoms of the patients with Mycoplasma-positive results were compared to those of the other patients with lower-respiratory-tract infections, and it was found that the results for mean lower age numbers as well as the presence of chills, increased erythrocyte sedimentation rate, and raised C-reactive protein levels showed significant differences. Molecular methods are superior for diagnosis of M. pneumoniae, providing more timely diagnosis. In addition, using real-time methods involves less hands-on time and affords the ability to monitor the reaction in the same tube.
2003Blocking of responses to endotoxin by E5564 in healthy volunteers with experimental endotoxemia.J Infect DisE5564 is a second-generation synthetic analogue of the lipid A component of endotoxin (lipopolysaccharide [LPS]). The ability of E5564 to block the toxic activity of LPS was assessed in a double-blind, placebo-controlled study. A bolus infusion of endotoxin (4 ng/kg) was administered to healthy subjects to induce a mild transient syndrome similar to clinical sepsis. Single E5564 doses of 50-250 microg ameliorated or blocked all of the effects of LPS in a dose-dependent manner. All E5564 dose groups had statistically significant reductions in elevated temperature, heart rate, C-reactive protein levels, white blood cell count, and cytokine levels (tumor necrosis factor-alpha and interleukin-6), compared with placebo (P<.01). In doses of > or = 100 microg, E5564 acted as an LPS antagonist and completely eliminated these signs. E5564 also blocked or ameliorated LPS-induced fever, chills, headache, myalgia, and tachycardia (P<.01). These results demonstrate that E5564 blocks the effects of LPS in a human model of clinical sepsis and indicate its potential in the treatment and/or prevention of clinical sepsis.
2002Epidemiological, clinical and laboratory distinction between human granulocytic ehrlichiosis and the initial phase of tick-borne encephalitis.Wien Klin WochenschrTo establish epidemiological, clinical and laboratory differences between adult patients with proven acute human granulocytic ehrlichiosis (HGE) and patients with the initial phase of tick-borne encephalitis (TBE).Epidemiological, clinical and laboratory findings were compared in nine patients with acute HGE (established by the presence of specific DNA sequences of Ehrlichia phagocytophila in whole blood by polymerase chain reaction and/or by seroconversion or at least a four-fold change of serum antibody titres to E. phagocytophila by indirect immunofluorescence assay) and 29 patients with the initial phase of TBE (demonstrated in ELISA tests by the presence of serum IgM antibodies to TBE virus).Findings were similar for the majority of the general parameters examined, which included sex, age, incubation period, duration of fever, and frequency of additional tick bites. However, a statistically significant difference was found for the duration of fever before the first visit (median 7 days in patients with acute HGE and 4 days in patients with the initial phase of TBE; p = 0.0169), and for the frequency of hospitalisation, which was higher for patients with the initial phase of TBE (29/29) than for those with acute HGE (5/9; p = 0.0017). Comparison of clinical signs and symptoms and laboratory findings in the two groups revealed significant differences: in patients with acute HGE there was a higher frequency of chills (4/9 versus 3/29, respectively; p = 0.0407), myalgia (8/9 versus 13/29, respectively; p = 0.0263), and arthralgia (7/9 versus 3/29, respectively; p = 0.0003), and elevated values of lactate dehydrogenase (7/9 versus 3/29, respectively; p = 0.0003) and concentration of C-reactive protein (9/9 versus 6/29, respectively; p = 0.0000).In a patient with febrile illness occurring after a tick bite, a clinical report of chills, myalgia and arthralgia, and laboratory findings of elevated values for lactate dehydrogenase and concentration of C-reactive protein direct towards a diagnosis of acute HGE rather than the initial phase of TBE.
2001Successful treatment of a small cohort of patients with adult onset of Still's disease with infliximab: first experiences.Ann Rheum DisTo test the efficacy of infliximab in the treatment of patients with severe and active adult onset Still's syndrome (AOSD) despite conventional immunosuppressive therapy.Six patients with the diagnosis of AOSD according to the Yamagushi criteria of 1992 were treated with infliximab. All patients had severe disease with high clinical and serological activity. Patients were treated initially with high dose steroids or more intensive immunosuppressive therapy. Two patients had a history of multiple disease modifying antirheumatic drug (DMARD) treatments. One patient had a history of three years of AOSD with fever, chills, pleural and pericardial effusions, and hepatosplenomegaly. Despite these treatments, he developed increasing serological signs of inflammation and arthritis of both hips and peripheral joints. Another patient had a history of five years of AOSD with oligoarthritis, myalgias, and recurrent fever despite multiple DMARD treatment, including cyclophosphamide pulse therapy. Our patients with AOSD presented with massive polyarthralgias, polyarthritis, splenomegaly or hepatomegaly, the typical rash, sore throat, weight loss, serositis, continuing fever, leucocytosis, and raised C reactive protein (CRP), erythrocyte sedimentation rate (ESR), and ferritin levels. Four patients with early onset of the disease, fulfilling the diagnostic criteria for AOSD and a clinical and serological high disease activity, were included in our pilot study without any further DMARD treatment apart from the initial steroid treatment. Reduction of established treatment, mainly with steroids, caused a relapse of the disease in all our patients. Patients then received 3-5 mg/kg infliximab on weeks 0, 2, and 6, continuing with intervals of 6-8 weeks depending on the patient's individual disease activity.In all patients, fever, arthralgias, myalgias, hepatosplenomegaly, and the rash resolved after the first courses of treatment with infliximab. All serological variables (CRP, ESR, hyperferritinaemia) returned to normal. After three courses of infliximab infusions, splenomegaly could not be detected in any of our patients. One caused by hip postarthritic osteoarthrosis, requiring hip replacement. After three courses of treatment with infliximab, splenomegaly could not be detected in any of our patients. Up to now, our patients have received infliximab infusion treatment for between five and 28 months. Throughout this period all patients have continued to benefit from this treatment, with improvement in their clinical symptoms, joint counts, and serological disease activity. One of our patients had a moderate infusion reaction during the second treatment. The infusion was discontinued for one hour and then was resumed with no further problems.The disease improved remarkably in all six patients with AOSD after treatment with infliximab, also in the early stage of AOSD. These preliminary data suggest the potential therapeutic benefit of anti-tumour necrosis factor alpha treatment in AOSD.
2001[A case of eosinophilic pneumonia possibly due to ifenprodil].Nihon Kokyuki Gakkai ZasshiA 69-year-old woman with a history of subarachnoid hemorrhage was started on ifenprodil for dizziness. Three weeks later, fever, cough, chills, dyspnea and skin eruption developed. A chest radiograph showed bilateral ground-glass shadows. Blood tests showed a white cell count of 14,400/mm3 with 32% eosinophils and a C reactive protein (CRP) level of 20 mg/dl. The arterial blood gases on room air were as follows: pH 7.45, PaCO2 33 torr, and PaO2 56 torr (Table 1). Ifenprodil was withdrawn and intravenous meropenem and minocycline administration was started on admission. Her fever improved rapidly and the CRP decreased, but hypoxemia and hypereosinophilia persisted. On the third hospital day, she underwent bronchoscopy with bronchoalveolar lavage (BAL). The differential count of BAL cells was 63% eosinophils, 15% lymphocytes, 21% macrophages, and 1% neutrophils. Intravenous methylprednisolone 250 mg/day for 3 days was commenced, leading to a clinical improvement. She received oral prednisolone (30 mg/day) for the next 4 days, and was then discharged without any symptoms. She has had no recurrence since. Both the drug lymphocyte stimulation test and the skin test for ifenprodil were negative.
2001[Weil's syndrome with bone marrow involvement after collecting walnuts].Dtsch Med WochenschrA 65 year-old man was transferred to our department from a neighbouring hospital with anuria and epistaxis. A few days prior to hospitalization, he had experienced severe muscular and joint pain accompanied by chills. A careful history revealed that, in recent weeks, the patient had frequently collected wild walnuts growing, for the most part, on the banks of a small stream, known to have an infestation of rats. The physical examination revealed pronounced jaundice of the skin and sclerae, and petechia on the lower legs.Laboratory results showed marked thrombocytopenia, hyperbilirubinaemia, appreciably elevated urine retention parameters and increased C-reactive protein. During the subsequent course of his illness, serum leptospiral antibody titres were elevated, indicating an acute leptospiral infection manifesting as Weil's syndrome. Silver staining (>>Warthin-Starry<<) revealed rod-shaped bacteria, presumably representing leptospires, in some bone marrow macrophages.Treatment with i. v. penicillin was immediately initiated, and urine output established by intravenous fluid resuscitation in the intensive care unit, so that haemodialysis was not necessary. The platelet count returned to normal and bilirubin began to decrease again. The patient was discharged home after 2 weeks in the hospital.When a patient presents with the triad of renal failure, jaundice and thrombocytpenia in the setting of a possible infection, then the severe form of leptospirosis known as Weil inverted question marks syndrome must be considered, and antibiotic treatment initiated without delay. Of importance for the definitive diagnosis is the repeated determination of the titres of antibodies to leptospires in the serum and urine, which usually become positive only in the second week of the illness. In our case, we detected bacteria directly in some bone marrow macrophages as well.
2000A lipid A analog, E5531, blocks the endotoxin response in human volunteers with experimental endotoxemia.Crit Care MedEndotoxin (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.
1998A randomized, double blind, placebo controlled multicenter trial of murine anti-CD4 monoclonal antibody therapy in rheumatoid arthritis.J RheumatolTo assess safety and efficacy of a murine anti-CD4 monoclonal antibody (Mab) in a population of patients with rheumatoid arthritis (RA) compared to treatment with placebo.Fifty-eight patients with defined RA were included in this placebo controlled, randomized, double blind, multicenter study. Of the 48 women and 10 men (mean age 54.5 years), 25 were functional class II and 31 were class III, with 9 years' disease duration; the mean of previous disease modifying antirheumatic drugs was 4; 49 were taking steroids (mean dosage 11 mg/day of prednisone). Eighty percent were rheumatoid factor positive. All were in an active state of the disease with: pain > 4 (mean at inclusion 6.6), tender joints > 4 (mean 12), swollen joint count > 3 (mean 9), morning stiffness > 45 min (mean 185), erythrocyte sedimentation rate > 30 mm (mean 59) or C-reactive protein (CRP) > 30 mg/l (mean 63). Treatment was randomized between murine anti-CD4 Mab (B-F5, Diaclone, 20 mg/day) or placebo intravenously for 10 consecutive days. Efficacy was assessed with a composite index (Paulus), with evaluation of number of patients with 20 or 50% improvement in each group. Changes in measures of single clinical or biological variables were also evaluated.The 2 groups were comparable at inclusion. Treatment was well tolerated. Mild side effects (chills, fever, rash) were seen in both groups. Percentage of patients with global 20 or 50% response did not differ between placebo and Mab groups at Day 10 or at Day 30. Evaluation of single variables showed reduced CRP, swollen joint count, and Ritchie index in some B-F5 patients at Day 10, although in the B-F5 group as a whole only CRP was significant.No significant improvement in RA after murine anti-CD4 Mab was observed.
1998Primary iliopsoas abscess successfully treated by ultrasonographically guided percutaneous drainage.J Orthop SciWe report a case of primary iliopsoas abscess successfully treated by ultrasonographically guided percutaneous drainage. A 56-year-old man presented at our hospital with lumbago, right-sided back pain, fever (temperature 38.5 degrees C) and chills. On physical examination, we found dark red skin, swelling, and tenderness localized at the right side at the back of his waist. Laboratory examination showed leukocytosis (white blood cell count 9700/mm3) with a leftward shift and elevated C-reactive protein (5.2 mg/dl). Ultrasonography (US), computed tomography (CT), and magnetic resonance imaging revealed a hypodense lesion in the right iliopsoas muscle extending to the subcutaneous tissue. About 50 ml of thick yellow pus was obtained by ultrasonographically guided aspiration drainage. A drain catheter was inserted in the abscess cavity. Laboratory findings improved and clinical symptoms abated rapidly after drainage. On the twenty-first day after drainage, US and CT showed that the abscess was no longer present. The patient was discharged after 32 days of hospitalization. As possible primary diseases causing iliopsoas abscess, such as digestive tract disease, tuberculosis, and osteomyelitis, were not found, we diagnosed the disease as primary iliopsoas abscess. Although surgical drainage has been performed in most reported cases of iliopsoas abscess, this case report shows that ultrasonographically guided percutaneous drainage is also effective for treating primary iliopsoas abscess if it is diagnosed early enough.
1996Effects of recombinant soluble type I interleukin-1 receptor on human inflammatory responses to endotoxin.BloodEffects of soluble recombinant human type I interleukin-1 receptor (sIL-1RI) were evaluated in 18 volunteers given intravenous endotoxin and randomized to placebo (n = 6), low-dose (n = 6), or high-dose (n = 6) sIL-1RI. Soluble IL-1RI decreased IL-1 beta (P = .001), but decreased IL-1ra (P = .0001), and resulted in 10-fold and 43-fold dose-related increases in sIL-1RI-IL-1ra complexes compared with placebo (P < or = .001). High-dose sIL-1RI was associated with increased levels of immunoactive tumor necrosis factor-alpha (P = .02), IL-8 (P = .0001), and cell-associated IL-1 beta (P = .047). C-reactive protein levels were higher after sIL-1RI than placebo (P = .035). Soluble IL-1RI decreased the severity of chills (P = .03), but did not alter other symptoms, changes in temperature, systemic hemodynamic responses, or changes in leukocyte and platelet number. Thus, sIL-1RI had no discernable antiinflammatory effect following endotoxin administration due in part to low levels of circulating IL-1 beta and neutralization of IL-1ra inhibitory function. This latter interaction represents an indirect mechanism of agonist activity elicited by sIL-1RI and may contribute to increases in inflammatory mediators, limiting therapy with sIL-1RI during endotoxemia.
1996Infective endocarditis complicated with rapidly progressive glomerulonephritis: a case report.Zhonghua Yi Xue Za Zhi (Taipei)A 26-year-old man who had suffered from intermittent chills and fever over a two month period was quite clear of heart or kidney involved developed acute deterioration of renal function. A new pansystolic murmur over the apex of the heart was heard on auscultation, and echocardiography clearly showed a vegetation about 0.7-0.9 cm in size on the atrial site of the mitral value. Laboratory investigation displayed normochromic anemia with negative Coombs' test. Immunological studies were positive for rheumatoid factor and circulating immune complex. High serum levels of erythrocyte sedimentation rate and C-reactive protein, nephritic sediment of urinalysis and negative blood cultures for bacteria, tuberculosis or fungus were also noted. Abdominal sonography showed normal kidney size, bilaterally. Renal biopsy revealed typical crescentic glomerulonephritis. After intravenous penicillin therapy for two weeks, the serum creatinine level recovered from 6.7 mg/dl to 2.0 mg/dl and circulating immune complex disappeared. In consideration of cardiac insufficiency and the potential risk for complications of the vegetation, the patient underwent mitral valve replacement. Four weeks after operation, all the abnormal data had resolved completely. These data suggested that infective endocarditis with rapidly progressive glomerulonephritis is curable by antibiotic therapy and surgical intervention.
1995Treatment of refractory juvenile chronic arthritis by monoclonal CD4 antibodies: a pilot study in two children.Ann Rheum DisOBJECTIVE--To study the effect of anti-CD4 treatment in patients suffering from refractory systemic onset juvenile chronic arthritis (JCA). METHODS--Two children were treated with the mouse CD4 antibody MAX.16H5. The effects on numbers of circulating CD4 T cells, clinical symptoms and C reactive protein (CRP) level were studied and the appearance of human antimouse immunoglobulin antibodies investigated. RESULTS--In patient one, disappearance of fever and malaise and a reduction of arthritic activity were observed together with a reduction in CRP. When disease activity returned eight weeks later, a second successful course of treatment was administered. It was possible to reduce the corticosteroid dosage permanently. In the other child, a first treatment cycle did not alter disease activity. A marked reduction in clinical and laboratory disease activity markers was observed after the second course. Only transient and mild side effects were observed. One patient exhibited a short lasting febrile reaction with chills, the other an urticarial rash. In both patients, human antibodies to mouse immunoglobulin became detectable. The decrease in the number of CD4 T cells in the peripheral blood was only short lasting and numbers returned to normal values within one to eight weeks, even after the second course of antibody treatment and under concomitant immunosuppressive treatment. No sustained clinical remissions could be achieved. CONCLUSIONS--These preliminary observations support the evidence of positive effects of CD4 antibody treatment in refractory systemic onset JCA. Long term efficacy, however, remains to be established.
1994[Septicemia due to Streptococcus milleri with pulmonary complications].Arch PediatrStreptococcus milleri can occasionally cause serious septicemia, that is often complicated by abscesses, particularly pulmonary.A 12.5 year-old boy was admitted because he had suffered from fever for 6 days. He also had headache, diffuse abdominal pain, chills and a cough. Laboratory investigations showed leukocytes: 9,300/mm3 (PMN: 6,700/mm3; lymphocytes: 1,400/mm3; monocytes: 1,200/mm3); hemoglobin: 12.5 g/dl; platelets: 106,000/mm3; sedimentation rate: 120 mm at 1 hour; blood fibrinogen: 5.6 g/l and C-reactive protein: 193 mg/l. His chest X-rays was normal. Four blood cultures showed Streptococcus milleri. The patient was given amoxicillin (150 mg/kg/d) plus gentamicin (3 mg/kg/d). Two foci of dental infection were found and treated by tooth extraction. Blood cultures remained positive 2, 3 and 6 days after onset of treatment and a second chest X-rays and CT scan showed several bilateral pulmonary abscesses. Cardiac ultrasonographs showed no valvular vegetations. The patient was then given ceftriaxone (100 mg/kg/d) plus rifampicin (20 mg/kg/d) and netilmicin (6 mg/kg/d). Blood culture was negative two days later, but the fever persisted and ceftriaxone was then successfully replaced by vancomycin (40 mg/kg/d) for three weeks.There are several reasons for the apparent resistance to treatment of this potentially severe infection; they are discussed by the authors.
1993Phase I trial of subcutaneous interleukin-6 in patients with advanced malignancies.J Clin OncolBased on preclinical evidence in murine models that interleukin-6 (IL-6) mediates regression of metastatic tumors, we performed a phase I study of recombinant human IL-6 in patients with refractory advanced malignancies to determine its pharmacokinetics, toxicities, and possible immunologic and antitumor effects.Recombinant IL-6 was administered as a single subcutaneous dose daily for 7 days, with 7 days off therapy followed by another 7 days of IL-6. Doses were escalated in cohorts of three patients starting at 3 micrograms/kg/d, provided that toxicity at the preceding dose level was not dose-limiting. Dose-limiting toxicity was defined as grade III or IV major organ toxicity that did not resolve to grade II or less in 24 hours after stopping IL-6, using the National Cancer Institute Common Toxicity Criteria. Patients were treated with 3, 10, and 30 micrograms/kg/d IL-6 subcutaneously.Three patients each were treated at the 3- and 10-micrograms dose levels. Two of five patients treated with 30 micrograms/kg/d IL-6 subcutaneously had grade III major organ toxicity that required IL-6 therapy to be discontinued. All patients experienced fever, chills, and minor fatigue. Significant increases in C-reactive protein (CRP), fibrinogen, platelet counts, and lymphocyte IL-2 receptor levels were seen in patients at the 10- and 30-micrograms/kg dose levels. Decreases in albumin and hemoglobin were observed, particularly at the 30-micrograms/kg dose level. The half-life (T1/2 beta) was 4.2 hours, with a peak IL-6 level at 5 hours. No antitumor responses were seen.A safely tolerated dose of daily subcutaneous IL-6 is 10 micrograms/kg, with hepatotoxicity and cardiac arrhythmia being the dose-limiting toxicities at 30 micrograms/kg. Phase II trials of IL-6 administered subcutaneously daily for at least 7 days for two cycles with an intervening week of rest are recommended for phase II trials. However, patients with extensive replacement of liver by tumor and abnormal liver functions should receive IL-6 therapy with caution.
1992The toxic and hematologic effects of interleukin-1 alpha administered in a phase I trial to patients with advanced malignancies.J Clin OncolA 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.
1991Phase I study of liposomal MTP-PE-activated autologous monocytes administered intraperitoneally to patients with peritoneal carcinomatosis.J Clin OncolWe have conducted a phase I study with autologous monocytes activated ex vivo and administered intraperitoneally in nine patients with peritoneal carcinomatosis. Blood monocytes were collected by leukapheresis and then purified by counterflow elutriation (up to 10(9) cells, with a purity of greater than 90%). Ex vivo activation was obtained by incubating these cells with 1 micrograms liposomal MTP-PE/10(6) monocytes for 18 hours in hydrophobic culture bags at 37 degrees C in 5% carbon dioxide humidified air. The activated monocytes were then infused in the peritoneal cavity once a week for 5 consecutive weeks through an implanted peritoneal infusion system, Port-A-Cath (Pharmacia Deltec, St Paul, MN), on an intrapatient dose-escalating schedule (10(7) to 10(9) monocytes). No severe adverse reactions occurred. Toxicity was mild, the chief acute reactions being fever (27%), chills (13%), and abdominal pain (25%). None of the side effects led to dose reduction. No consistent change in hemostatic function, liver function, or renal function was observed. Significant increases in granulocyte counts, neopterine, and acute phase reactants (fibrinogen, C-reactive protein) occurred in the peripheral blood. In vitro monocyte activation was demonstrated by the relapse of procoagulant activity and monokines (interleukin-1 [IL-1], IL-6, and tumor necrosis factor-alpha [TNF alpha]) in the supernatants of cultured monocytes. Evidence for in vivo monocyte activation was provided by the increase of these monokines in the peritoneal fluids. Kinetic studies with indium-111 (111In)-labeled activated autologous monocytes in five patients suggest that these infused monocytes may remain in the peritoneal cavity for up to 7 days. This locoregional immunotherapeutic approach seems to be encouraging in view of adjuvant therapeutic modality in ovarian cancer patients with minimal residual intraabdominal disease following second-look laparotomy.
1991Treatment of rheumatoid arthritis with an anti-CD4 monoclonal antibody.Arthritis RheumThe effect of treatment with a monoclonal antibody against the CD4 antigen present on T helper cells was studied in 10 patients with severe intractable rheumatoid arthritis. In an open trial, monoclonal antibody 16H5 was infused at a dosage of 0.3 mg/kg of body weight on 7 consecutive days. Studies of the kinetics demonstrated a drastic depletion of CD4+ cells, to as low as 25 cells/microliters, 1 hour after the first infusion. The subsequent recovery of the CD4+ cell numbers 24 hours after infusion did not reach initial levels, and after the full 7-day treatment cycle there was a significant reduction of the number of CD4+ cells (mean +/- SD 51 +/- 28%; P less than 0.02). There was a reduced or even inverse CD4:CD8 ratio, which generally persisted 3-4 weeks. Lymphocyte transformation assays demonstrated significantly reduced reactivity in 5 of the 9 patients who completed the 7-day course, whereas 4 individuals exhibited an unexpected elevation in the T cell response to mitogens and common antigens. Parallel laboratory studies showed a significant decrease in the erythrocyte sedimentation rate (P less than 0.05), rheumatoid factor titer (P less than 0.04), and total immunoglobulin values (P less than 0.01), as well as a reduction in C-reactive protein levels, in 7 of the 9 patients. Clinically, there was a significant reduction in the Ritchie articular index (P less than 0.05) and in the number of swollen joints (P less than 0.04). Adverse effects were urticaria in 2 patients, which led to withdrawal of therapy in 1 of them, and chills with fever, suggestive of a lymphokine release syndrome, in another 2 patients. Only low levels of human anti-mouse immunoglobulin antibodies developed (not exceeding 1.7 mg/liter). It was therefore possible to repeat the treatment cycle, achieving still better efficacy, in 4 of the patients (reductions in the Ritchie index and the number of swollen joints P less than 0.02). Our findings indicate that treatment with monoclonal antibodies against the CD4 antigen leads to immunomodulation which results in clinical benefits, at least during initial observation periods (up to 6 months postinfusion). However, it remains to be determined whether long-term remission can be induced with this therapeutic approach. The use of immunosuppressive therapies or repeated antibody treatments will have to be considered.
1991Treatment of cancer patients with endotoxin induces release of endogenous cytokines.PathobiologyThis study sought to determine whether endogenous tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6) and granulocyte-colony-stimulating factor (G-CSF) were detectable in sera of lipopolysaccharide (LPS)-treated cancer patients. Twenty patients received an intravenous bolus of purified LPS from Salmonella abortus-equi (4.0 ng/kg). Patients were pretreated with ibuprofen (1,600 mg) to prevent constitutional side effects like fever and chills. Serum TNF-alpha levels increased from less than 0.01 ng/ml before treatment up to maximal levels of 21 ng/ml, peaking 1.5 h after LPS injection. Similarly, serum IL-6 concentrations increased from less than 0.01 to 11 ng/ml, but peak levels were obtained 30 min later than TNF-alpha. Circulating G-CSF appeared still later than TNF-alpha and IL-6. It was detectable within 3 h and peaked 6 h after LPS injection. Parallel to the release of the above cytokines a marked increase in granulocyte counts was observed. In all patients administration of LPS led to an acute-phase response as measured by C-reactive protein.
1990[An autopsied case of infective endocarditis with cardiac tamponade due to myocardial rupture].Kansenshogaku ZasshiSince it is very rare that cardiac tamponade due to myocardial rupture caused by infective endocarditis, occurs we are reporting this case. A 62 year old man, who had underlying diseases of pneumoconiosis and hypertensive heart disease, visited Chikuho Rosai Hospital complaining of chest oppression and general fatigue on Feb. 7, 1987. He was diagnosed as having ischemic heart disease by electrocardiogram. Two days later, he suddenly had chills and a fever, and the laboratory data showed leukocytosis and a positive C-reactive protein (CRP). The echo cardiogram showed mitral regurgitation (MR) and aortic regurgitation (AR), but neither vegetation nor pericardial effusion was observed. On Feb. 16, he was admitted with shock, and he died the next day. The blood cultures grew gram-positive cocci, respectively. From the clinical symptoms, chest roentgenogram and electrocardiogram, we suspected a cardiac tamponade. On autopsy findings, though coronary arteries were intact, the aortic valves had severe valvular adhesions, calcifications and hypertrophies. The rupture hole was observed in the left ventricles, which was just under the aortic valve through the pericardiac space. It seemed that he died of a cardiac tamponade due to the outflow of blood from this hole. On histopathologic findings of the cardiac wall, gram-positive cocci and many of neutrophils were observed.
1990Biological response to intravenously administered endotoxin in patients with advanced cancer.J Biol Response ModThe purpose of the study was to evaluate the toxicity and biological activity of highly purified lipopolysaccharide (LPS) administered intravenously to cancer patients in order to establish an optimum dosage scheme. An initial subtoxic dose was increased in weekly increments in accordance with individual regimens that maintained patient reaction at a safe and acceptable level. Purified LPS from Salmonella abortus equi was administered to 11 patients with advanced solid tumors on a weekly schedule with intraindividually escalating dosage as determined by patient response. Biological response was monitored by complete blood count, C-reactive protein, and cytokine measurements at different time points after LPS injection. Tumor necrosis factor-alpha (TNF) and interleukin-1 beta serum levels were measured by enzyme-linked immunosorbent assay and interleukin-6 (IL-6) by bioassay. Dose-limiting toxicities including chills and fever (WHO grade III) were reached at 1.0 ng/kg of body weight (maximal tolerated dose-1, MTD-1). Pretreatment with ibuprofen (1,600 mg) abrogated these side effects, allowing further escalation of LPS doses up to 10 ng/kg of body weight. At dose levels greater than 8.0 ng/kg of body weight (MTD-2), the aforementioned side effects occurred again and, additionally, hepatic toxicity (WHO grade III) was observed. Hematological changes included neutropenia followed by a pronounced neutrophilia contributed to by up to 30% bands, marked monocytopenia for 3 h, and retarded lymphopenia. By 24 h, all hematological parameters returned to pretreatment values. TNF serum levels increased from 10 pg/ml before treatment to 7,000 pg/ml as a function of dosage. Maximum serum levels were reached at 60 to 90 min after LPS injection. Similarly, IL-6 serum concentrations increased from less than 4 to 2,500 U/ml; peak levels were obtained 30 min after TNF peak values. Prior administration of ibuprofen had no effect on the above-mentioned hematological changes nor on cytokine release. LPS can be administered intravenously in weekly intervals at escalating doses from 0.15-10.0 ng/kg of body weight, when patients are protected by pretreatment with ibuprofen at dose levels above 1.0 ng/kg of body weight. Cytokine release as measured by TNF and IL-6 increased in a dose-dependent manner although the constitutional symptoms are completely attenuated.
1990Ultraviolet light induces increased circulating interleukin-6 in humans.J Invest DermatolAlthough the clinical effects of acute exposure to ultraviolet (UV) light--such as cutaneous inflammation, malaise, somnolence, chills and fever--have been appreciated many years, the underlying mechanisms mediating these effects are poorly understood. Interleukin-6 (IL-6) is a potent cytokine with a wide variety of biologic activities, including induction of fever and acute phase response. Because IL-6 is produced by keratinocytes in vivo and in vitro and because the release is enhanced by UV light, the present study was performed to investigate the effect of a single UV dose eliciting moderate to severe sunburn reaction on the production of IL-6 in vivo. Therefore, plasma of UV-treated human subjects was evaluated for IL-6 activity by testing its capacity to induce the proliferation of an IL-6-dependent hybridoma cell line (B9). In contrast to plasma samples obtained before UV exposure, post-UV-specimens contained significant levels of IL-6 peaking at 12 h after UV irradiation. Plasma IL-6 activity was neutralized by an antiserum directed against recombinant human IL-6, and upon HPLC gel filtration exhibited a molecular weight of around 20 kD. Moreover, plasma IL-6 levels correlated remarkably with fever course followed by an increase of acute phase proteins such as C-reactive protein. These data indicate that IL-6, which is released by keratinocytes following UV exposure, may gain access to the circulation and via its pyrogenic as well as acute phase-inducing effect may function as an important mediator of systemic sunburn reaction.
1990Phase I and immunomodulatory study of a muramyl peptide, muramyl tripeptide phosphatidylethanolamine.Cancer ResMuramyl tripeptide phosphatidylethanolamine (MTP-PE; CGP 19835A from Ciba Geigy) is a synthetic muramyl tripeptide structurally related to bacterial cell wall constituents. MTP-PE activates monocytes in vitro to a tumoricidal state and has in vivo antitumor effects in animal models. We studied the toxicity and immunomodulatory effects of once weekly i.v. administration of liposomal-encapsulated MTP-PE for 8 weeks in 27 patients with advanced malignancies. Doses ranged from 0.1 to 2.7 mg/m2. No major tumor responses were seen; 11 patients had stable disease after 8 weeks of therapy and 3 continued on maintenance therapy because of minor tumor regressions and/or clinical improvement. MTP-PE at these doses was well tolerated. Shaking chills and fevers were the most common toxicities and occurred at all dose levels. There was no treatment-induced loss of performance status. Immunomodulatory studies revealed evidence of a biological effect on monocytes. C-reactive protein levels rose in the majority of patients with end-of-treatment values 2 to 10 times higher than baseline. Serum neopterin levels were consistently increased 24 h after MTP-PE administration and significant decreases in expression of two different types of Fc receptors on peripheral blood monocytes were noted 6 h after treatment. Although no major tumor responses were seen in this group of patients with advanced malignancies, MTP-PE was well tolerated and exerted biological effects on monocytes. Serum neopterin levels may be a useful marker for the biological effects of MTP-PE.
1989Phase I trial of liposomal muramyl tripeptide phosphatidylethanolamine in cancer patients.J Clin OncolTwenty-eight evaluable patients with metastatic cancer refractory to standard therapy received escalating doses of muramyl tripeptide phosphatidylethanolamine (MTP-PE) (.05 to 12 mg/m2) in phosphatidylserine (PC):phosphatidylcholine (PS) liposomes (lipid:MTP-PE) ratio 250:1). Liposomal MTP-PE (L-MTP-PE) was infused over 1 hour twice weekly; doses were escalated within individual patients every 3 weeks as tolerated for a total treatment duration of 9 weeks. Routine clinical laboratory parameters, acute phase reactants and various immunologic tests were monitored at various time points during treatment. Toxicity was moderate (less than or equal to grade II) in 24 patients with chief side effects being chills (80% of patients), fever (70%), malaise (60%), and nausea (55%). In four patients L-MTP-PE treatment was deescalated due to severe malaise and recurrent fever higher than 38.8 degrees C. The maximum-tolerated dose (MTD) was 6 mg/m2. Significant (P less than .05) increases in WBC count, absolute granulocyte count, ceruloplasmin, beta 2-microglobulin, c-reactive protein, monocyte tumoricidal activity, and serum IL-1 beta were found. Significant decreases in serum cholesterol were also observed. Clearance of intravenously (iv)-infused technetium-99 (99mTc)-labeled liposomes containing MTP-PE in four patients was biphasic; gamma camera scans revealed uptake of radiolabel in liver, spleen, lung, nasopharynx, thyroid gland, and tumor (two patients). No objective tumor regression was seen. In view of its definite immunobiologic activity and lack of major toxicity, additional phase II and adjuvant trials of L-MTP-PE are warranted.
Osteoarticular complications of brucellosis: a study of 169 cases.Rev Infect DisOf 452 patients with brucellosis, 169 (111 male and 58 female) had osteoarticular complications. Brucella melitensis was isolated from the blood in 7.7% of the cases. Fever, chills, arthralgia, backache, high levels of C-reactive protein, positive rheumatoid factor, and splenomegaly were more frequent in osteoarticular brucellosis than in nonosteoarticular disease. Arthritis occurred in the hip joint in 90 cases (53%), knees in 61 (36%), sacroiliacs in 33 (20%), ankles in 25 (15%), elbows in nine (5.3%), shoulders in eight (5%), wrists in six (3.5%), and sternoclavicular arthritis occurred in three cases (1.8%). Spondylitis occurred in 10 cases (6%), osteomyelitis in four (2.4%), and tendinitis or bursitis in two (1.2%). Treatment with tetracycline or trimethoprim-sulfamethoxazole (TMP-SMZ) alone (four to eight weeks) or in combination with streptomycin (two to four weeks) resulted in a relapse rate of 16.6%. No relapses occurred in seven patients treated with repeated four- to six-weeks courses of rifampin plus tetracycline or TMP-SMZ plus streptomycin.
1986Phase I evaluation of recombinant interleukin-2 in patients with advanced malignant disease.J Clin OncolSeventeen 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.