COVID-19 outcomes in patients with rheumatoid arthritis with biologic or targeted synthetic DMARDs.

OBJECTIVES: We aimed to investigate the role of rheumatoid arthritis (RA) with biologic or targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARD) exposure in COVID-19 outcomes. METHODS: Our study retrieved data from the US Collaborative Network in TriNetX between 1 January 2018 and 31 December 2022. We investigated b/tsDMARD use for RA: interleukin 6 inhibitor (IL-6i), Janus-associated kinase inhibitors (JAKi) or tumour necrosis factor-alpha inhibitors (TNFi, reference group). The outcomes of COVID-19 were the incidence of infection and adverse outcomes (hospitalisation, critical care services, mechanical ventilation and mortality). The HR and 95% CI of the outcomes were calculated between propensity score-matched (PSM) patients with different b/tsDMARDs. RESULTS: After PSM, 2676 JAKi vs 2676 TNFi users and 967 IL-6i vs 967 TNFi users were identified. As for COVID-19 incidence, JAKi users did not reach statistical significance (HR: 1.058, 95% CI: 0.895 to 1.250) than TNFi users. RA with JAKi users had a significant risk for hospitalisation (HR: 1.194, 95% CI: 1.003 to 1.423), mortality (HR: 1.440, 95% CI: 1.049 to 1.976) and composite adverse outcomes (HR: 1.242, 95% CI: 1.051 to 1.468) compared with TNFi users. Mortality risk tended to be significantly higher in the JAKi group without COVID-19 vaccination (HR: 1.511, 95% CI: 1.077 to 2.121). IL-6i users compared with TNFi users did not have the above findings. CONCLUSIONS: RA with JAKi users had a significant risk for hospitalisation, mortality or composite adverse outcomes, especially higher mortality among those without COVID-19 vaccination. COVID-19 vaccination should be encouraged in these target cohorts. When using JAKi for patients with RA, clinicians should be vigilant about these adverse outcomes to prevent their occurrence or detect them early for early intervention.

Spondyloarthritis and nonbacterial thrombotic endocarditis as paraneoplastic manifestations in treatment-naive Burkitt lymphoma.

Non-radiographic axial spondyloarthropathy (nr-axSpA) is a clinical diagnosis of symptoms matching inflammatory back pain criteria without radiological lesions at the sacroiliac joint. The frequency of an early nr-axSpA-like presentation in lymphoma patients has not been clarified. Here we report a woman in her 20s with a fever and musculoskeletal discomfort. Detailed investigations revealed that she was suffering from Burkitt lymphoma in which nr-axSpA-like symptoms were a musculoskeletal manifestation of the disease, irrelevant to the anti-neoplastic treatment.

Mobilization of Hematopoietic Stem and Progenitor Cells during Dengue Virus Infection.

Hematopoietic stem and progenitor cells (HSPCs) mobilization is the movement of HSPCs from the bone marrow to the peripheral blood or tissue induced by stress. HSPC mobilization is a well-known response to protect the host during infection through urgent differentiation of HSPCs to immune cells. Dengue virus (DENV) infection is known to cause stress in infected humans and the mobilizing capacity of HSPCs during DENV infection in affected patients has not been fully investigated. Here, we investigated whether DENV infection can induce HSPC mobilization and if the mobilized HSPCs are permissive to DENV infection. White blood cells (WBCs) were collected from dengue patients (DENV+) and healthy donors and analyzed by flow cytometry and plaque assay. Elevated HSPCs levels were found in the WBCs of the DENV+ group when compared to the healthy group. Mobilization of HSPCs and homing markers (skin and gut) expression decreased as the patients proceeded from dengue without symptoms (DWoWS) to severe dengue (SD). Mobilizing HSPCs were not only permissive to DENV infection, but infectious DENV could be recovered after coculture. Our results highlight the need for further investigation into HSPC mobilization or alterations of hematopoiesis during viral infections such as DENV in order to develop appropriate countermeasures.

Identification of Anti-Premembrane Antibody as a Serocomplex-Specific Marker To Discriminate Zika, Dengue, and West Nile Virus Infections.

Although transmission of Zika virus (ZIKV) in the Americas has greatly declined since late 2017, recent reports of reduced risks of symptomatic Zika by prior dengue virus (DENV) infection and increased risks of severe dengue disease by previous ZIKV or DENV infection underscore a critical need for serological tests that can discriminate past ZIKV, DENV, and/or other flavivirus infections and improve our understanding of the immune interactions between these viruses and vaccine strategy in endemic regions. As serological tests for ZIKV primarily focus on envelope (E) and nonstructural protein 1 (NS1), antibodies to other ZIKV proteins have not been explored. Here, we employed Western blot analysis using antigens of 6 flaviviruses from 3 serocomplexes to investigate antibody responses following reverse transcription-PCR (RT-PCR)-confirmed ZIKV infection. Panels of 20 primary ZIKV and 20 ZIKV with previous DENV infection recognized E proteins of all 6 flaviviruses and the NS1 protein of ZIKV with some cross-reactivity to DENV. While the primary ZIKV panel recognized only the premembrane (prM) protein of ZIKV, the ZIKV with previous DENV panel recognized both ZIKV and DENV prM proteins. Analysis of antibody responses following 42 DENV and 18 West Nile virus infections revealed similar patterns of recognition by anti-E and anti-NS1 antibodies, whereas both panels recognized the prM protein of the homologous serocomplex but not others. The specificity was further supported by analysis of sequential samples. Together, these findings suggest that anti-prM antibody is a flavivirus serocomplex-specific marker and can be used to delineate current and past flavivirus infections in endemic areas. IMPORTANCE Despite a decline in Zika virus (ZIKV) transmission since late 2017, questions regarding its surveillance, potential reemergence, and interactions with other flaviviruses in regions where it is endemic remain unanswered. Recent studies have reported reduced risks of symptomatic Zika by prior dengue virus (DENV) infection and increased risks of severe dengue disease by previous ZIKV or DENV infection, highlighting a need for better serological tests to discriminate past ZIKV, DENV, and/or other flavivirus infections and improved understanding of the immune interactions and vaccine strategy for these viruses. As most serological tests for ZIKV focused on envelope and nonstructural protein 1, antibodies to other ZIKV proteins, including potentially specific antibodies, remain understudied. We employed Western blot analysis using antigens of 6 flaviviruses to study antibody responses following well-documented ZIKV, DENV, and West Nile virus infections and identified anti-premembrane antibody as a flavivirus serocomplex-specific marker to delineate current and past flavivirus infections in areas where flaviviruses are endemic.

Optimal initial antibiotic regimen for the treatment of acute appendicitis: a systematic review and network meta-analysis with surgical intervention as the common comparator.

BACKGROUND: The optimal antibiotic regimen for the medical management of acute appendicitis remains unknown due to a lack of head-to-head comparisons between different antibiotic regimens. METHODS: We systematically searched the PubMed, EMBASE, Scopus and Cochrane Central Register of Controlled Trials databases from their inception through to August 2020. We selected randomized controlled trials (RCTs) or observational studies comparing antibiotic therapy and appendectomy as the initial treatment for adult or paediatric patients with acute appendicitis. We performed a Bayesian network meta-analysis (NMA) to obtain the indirect comparison results between different antibiotic regimens by employing the group managed by surgery as a common comparator. Antibiotic regimens were classified into three categories: those including a carbapenem; those including a cephalosporin; and those including a ß-lactam/ß-lactamase inhibitor combination. RESULTS: A total of 9 RCTs (adults, n = 8; paediatrics, n = 1) and 12 observational studies (adults, n = 3; paediatrics, n = 9) were included in the NMA, with a total of 4551 patients. The most commonly administered regimen was a ß-lactam/ß-lactamase inhibitor combination (9/21; 43%), followed by a cephalosporin (7/21; 33%) or a carbapenem (5/21; 24%). The NMA indicated that surgery significantly increased 1 year treatment success, compared with cephalosporins [OR: 16.79; 95% credible interval: 3.8-127.64] or ß-lactam/ß-lactamase inhibitor combinations (OR: 19.99; 95% credible interval: 4.87-187.57), but not carbapenems (OR: 3.50, 95% credible interval: 0.55-38.63). In contrast, carbapenems were associated with fewer treatment-related complications compared with surgery (OR: 0.12; 95% credible interval: 0.01-0.85). CONCLUSIONS: Carbapenems might be recommended as the initial antibiotic regimen for the non-operative management of adult patients with acute appendicitis. Nevertheless, due to the imprecise estimates in our NMA, additional RCTs are needed to corroborate these findings, especially for paediatric patients.

Potent Neutralizing Human Monoclonal Antibodies Preferentially Target Mature Dengue Virus Particles: Implication for Novel Strategy for Dengue Vaccine.

The four serotypes of dengue virus (DENV) cause the most important mosquito-borne viral disease in humans. The envelope (E) protein is the major target of neutralizing antibodies and contains 3 domains (domain I [DI], DII, and DIII). Recent studies reported that human monoclonal antibodies (MAbs) recognizing DIII, the D1/DII hinge, the E-dimer epitope, or a quaternary epitope involving DI/DII/DIII are more potently neutralizing than those recognizing the fusion loop (FL) of DII. Due to inefficient cleavage of the premembrane protein, DENV suspensions consist of a mixture of mature, immature, and partially immature particles. We investigated the neutralization and binding of 22 human MAbs to DENV serotype 1 (DENV1) virions with differential maturation status. Compared with FL MAbs, DIII, DI/DII hinge, and E-dimer epitope MAbs showed higher maximum binding and avidity to mature particles relative to immature particles; this feature may contribute to the strong neutralizing potency of such MAbs. FL-specific MAbs required 57 to 87% occupancy on mature particles to achieve half-maximal neutralization (NT50), whereas the potently neutralizing MAbs achieved NT50 states at 20 to 38% occupancy. Analysis of the MAb repertoire and polyclonal sera from patients with primary DENV1 infection supports the immunodominance of cross-reactive anti-E antibodies over type-specific antibodies. After depletion with viral particles from a heterologous DENV serotype, the type-specific neutralizing antibodies remained and showed binding features shared by potent neutralizing MAbs. Taken together, these findings suggest that the use of homogeneous mature DENV particles as an immunogen may induce more potent neutralizing antibodies against DENV than the use of immature or mixed particles.IMPORTANCE With an estimated 390 million infections per year, the four serotypes of dengue virus (DENV) cause the most important mosquito-borne viral disease in humans. The dengue vaccine Dengvaxia was licensed; however, its low efficacy among dengue-naive individuals and increased risk of causing severe dengue in children highlight the need for a better understanding of the role of human antibodies in immunity against DENV. DENV suspensions contain mature, immature, and partially immature particles. We investigated the binding of 22 human monoclonal antibodies (MAbs) to the DENV envelope protein on particles with different maturation states. Potently neutralizing MAbs had higher relative maximum binding and avidity to mature particles than weakly neutralizing MAbs. This was supported by analysis of MAb repertoires and polyclonal sera from patients with primary DENV infection. Together, these findings suggest that mature particles may be the optimal form of presentation of the envelope protein to induce more potent neutralizing antibodies against DENV.

AIDS-related opportunistic illnesses and early initiation of HIV care remain critical in the contemporary HAART era: a retrospective cohort study in Taiwan.

BACKGROUND: No study has reported the epidemiology of AIDS-related opportunistic illnesses (AOIs) in patients with newly diagnosed HIV infection in Taiwan in the past decade. Understanding the current trends in AOI-related morbidity/mortality is essential in improving patient care and optimizing current public health strategies to further reduce AOIs in Taiwan in the era of contemporary highly active antiretroviral therapy (HAART). METHODS: Eligible patients were evaluated at two referral centers between 2010 and 2015. The patients were stratified by date of diagnosis into three periods: 2010-2011, 2012-2013, and 2014-2015. The demographics, HIV stage at presentation according to the United States CDC 2014 case definition, laboratory variables, and the occurrence of AOIs and associated outcomes were compared among the patients. Logistic regression and Cox regression were respectively used to identify variables associated with the occurrence of AOIs within 90 days of HIV enrollment and all-cause mortality. RESULTS: Over a mean observation period of 469 days, 1264 patients with newly diagnosed HIV with a mean age of 29 years and mean CD4 count of 275 cells/µL experienced 394 AOI episodes in 290 events. At presentation, 37.7% of the patients had AIDS; the frequency did not significantly differ across groups. The overall proportion of AOIs within the study period was 21.0%, and no decline across groups was observed. The majority of AOIs (91.7%) developed within 90 days of enrollment. All-cause and AOI-related mortality did not significantly differ across groups. Throughout the three study periods, AOIs remained the main cause of death (47/56, 83.9%), especially within 180 days of enrollment (40/42, 95.2%). A CD4 cell count of < 200 cells/µL at presentation was associated with increased adjusted odds of an AOI within 90 days [adjusted odds ratio, 40.84; 95% confidence intervals (CI), 12.59-132.49] and an elevated adjusted hazard of all-cause mortality (adjusted hazard ratio, 11.03; 95% CI, 1.51-80.64). CONCLUSIONS: Despite efforts toward HIV prevention and management, early HIV care in Taiwan continues to be critically affected by AOI-related morbidity and mortality in the era of contemporary HAART. Additional targeted interventions are required for the earlier diagnosis of patients with HIV.

Anti-HIV seropositivity was related to HBsAg seropositivity among injecting drug users in Taiwan.

In Taiwan, the number of new cases of human immunodeficiency virus (HIV) infection via drug injection has been increasing since 2003. Due to HIV and hepatitis B virus (HBV) having similar transmission routes, HBV and HIV infections among injecting drug users (IDUs) has become an important public health issue. The aim of this study was explore the prevalence of HBV infection among IDUs with and without HIV infection, and examine whether HIV infection is associated with HBV infection among IDUs in Southern Taiwan. We enrolled 566 IDUs, including 87 anti-HBV positive IDUs and 479 anti-HBV negative IDUs, and also analyzed the results of liver function tests, HBV DNA, anti-HIV, HIV RNA, and CD4 cell count. The results showed that the prevalence of HBV infection among IDUs was 15.4%. The prevalence of hepatitis B surface antigen (HBsAg) was higher among individuals born before 1985 (15.9% vs. 4.0%), but this was not significant. Anti-HIV seropositivity was related to HBsAg seropositivity [odds ratio (OR) = 2.47, 95% confidence interval = 1.26-4.82, p = 0.008). Anti-HCV and anti-HIV were risk factors for abnormal alanine aminotransferase (ALT; OR = 2.11, 95% confidence interval = 1.005-4.42, p = 0.048 and OR = 1.47, 95% confidence interval = 1.02-2.10, p = 0.04, respectively), and HBsAg was not a factor related to abnormal ALT. In conclusion, the prevalence of HBV infection was similar in the general population and in IDUs, and due to anti-HIV seropositivity being significantly related to HBsAg seropositivity, HBV infection among IDUs is still important. We suggest that for IDUs, HBsAg should be monitored closely.

Incarcerated intravenous heroin users: predictors of post-release utilization of methadone maintenance treatment.

Incarcerated intravenous heroin users have more problematic patterns of heroin use, but are less likely to access methadone maintenance treatment by their own initiative than heroin users in the community. The present study examined predictors for receiving methadone maintenance treatment post-release among incarcerated intravenous heroin users within a 24-month period. This cohort study recruited 315 incarcerated intravenous heroin users detained in 4 prisons in southern Taiwan and followed up within the 24-month period post-release. Cox proportional hazards regression analysis was applied to determine the predictive effects of sociodemographic and drug-use characteristics, attitude toward methadone maintenance treatment, human immunodeficiency virus serostatus, perceived family support, and depression for access to methadone maintenance treatment after release. There were 295 (93.7%) incarcerated intravenous heroin users released that entered the follow-up phase of the study. During the 24-month follow-up period, 50.8% of them received methadone maintenance treatment. After controlling for the effects of the detainment period before and after recruitment by Cox proportional hazards regression analysis, incarcerated intravenous heroin users who had positive human immunodeficiency virus serostatus (HR = 2.85, 95% CI = 1.80-4.52, p < .001) and had ever received methadone maintenance treatment before committal (HR = 1.94, 95% CI = 1.23-3.05, p < .01) were more likely to enter methadone maintenance treatment within the 24-month follow-up period. Positive human immunodeficiency virus serostatus with fully subsidized treatment and previous methadone maintenance treatment experiences predicted access of methadone maintenance treatment post-release. Strategies for getting familiar with methadone maintenance treatment during detainment, including providing methadone maintenance treatment prior to release and lowering the economic burden of receiving treatment, may facilitate entry of methadone maintenance treatment for incarcerated intravenous heroin users.

Infectious dengue vesicles derived from CD61+ cells in acute patient plasma exhibited a diaphanous appearance.

The levels of neutralizing antibody to a pathogen are an effective indicator to predict efficacy of a vaccine in trial. And yet not all the trial vaccines are in line with the theory. Using dengue virus (DENV) to investigate the viral morphology affecting the predictive value, we evaluated the viral morphology in acute dengue plasma compared to that of Vero cells derived DENV. The virions in plasma were infectious and heterogeneous in shape with a "sunny-side up egg" appearance, viral RNA was enclosed with CD61+ cell-derived membrane interspersed by the viral envelope protein, defined as dengue vesicles. The unique viral features were also observed from ex vivo infected human bone marrow. Dengue vesicles were less efficiently neutralized by convalescent patient serum, compared to virions produced from Vero cells. Our results exhibit a reason why potencies of protective immunity fail in vivo and significantly impact dengue vaccine and drug development.

Water extract of Pueraria lobata Ohwi has anti-viral activity against human respiratory syncytial virus in human respiratory tract cell lines.

Human respiratory syncytial virus (HRSV) infects all age groups and causes bronchiolitis, pneumonia, and acute respiratory distress syndrome with a significant mortality rate. To date, only ribavirin has been used to manage HRSV infection. However, ribavirin is expensive with an only modest effect. Furthermore, ribavirin has several side effects, which means it has limited clinical benefit. Pueraria lobata Ohwi (P. lobata) is a common ingredient of Ge-Gen-Tang (Kakkon-to) and Sheng-Ma-Ge-Gen-Tang (Shoma-kakkon-to), which are prescriptions of Chinese traditional medicine proven to have antiviral activity against HRSV. Therefore, it was hypothesized that P. lobata might be effective against HRSV. To find a cost-effective therapeutic modality, both human upper (HEp-2) and lower (A549) respiratory tract cell lines were used to test the hypothesis that P. lobata could inhibit HRSV-induced plaque formation. Results showed that the water extract of P. lobata was effective (p < 0.0001) against HRSV-induced plaque formation. P. lobata was more effective when given prior to viral inoculation (p < 0.0001) by inhibiting viral attachment (p < 0.0001) and penetration (p < 0.0001). However, supplementation with P. lobata could not stimulate interferon secretion after HRSV infection. In conclusion, P. lobata has antiviral activity against HRSV-induced plaque formation in airway mucosa mainly by inhibiting viral attachment and internalization. Further identification of effective constituents could contribute to the prevention of HRSV infection.

Analysis of epitopes on dengue virus envelope protein recognized by monoclonal antibodies and polyclonal human sera by a high throughput assay.

BACKGROUND: The envelope (E) protein of dengue virus (DENV) is the major target of neutralizing antibodies and vaccine development. While previous studies on domain III or domain I/II alone have reported several epitopes of monoclonal antibodies (mAbs) against DENV E protein, the possibility of interdomain epitopes and the relationship between epitopes and neutralizing potency remain largely unexplored. METHODOLOGY/PRINCIPAL FINDINGS: We developed a dot blot assay by using 67 alanine mutants of predicted surface-exposed E residues as a systematic approach to identify epitopes recognized by mAbs and polyclonal sera, and confirmed our findings using a capture-ELISA assay. Of the 12 mouse mAbs tested, three recognized a novel epitope involving residues (Q211, D215, P217) at the central interface of domain II, and three recognized residues at both domain III and the lateral ridge of domain II, suggesting a more frequent presence of interdomain epitopes than previously appreciated. Compared with mAbs generated by traditional protocols, the potent neutralizing mAbs generated by a new protocol recognized multiple residues in A strand or residues in C strand/CC' loop of DENV2 and DENV1, and multiple residues in BC loop and residues in DE loop, EF loop/F strand or G strand of DENV1. The predominant epitopes of anti-E antibodies in polyclonal sera were found to include both fusion loop and non-fusion residues in the same or adjacent monomer. CONCLUSIONS/SIGNIFICANCE: Our analyses have implications for epitope-specific diagnostics and epitope-based dengue vaccines. This high throughput method has tremendous application for mapping both intra and interdomain epitopes recognized by human mAbs and polyclonal sera, which would further our understanding of humoral immune responses to DENV at the epitope level.

The importance of hematopoietic progenitor cells in dengue.

Scientific investigations designed to better understand and assess the distinguishing clinical characteristics pave the way to a successful treatment for a disease. Since the peripheral blood is obtained easily, the most frequent type of investigation performed on infectious agents focuses on the hematological components of blood drawn from patients. Bone marrow aspirates, although somewhat more difficult to obtain, should be evaluated more frequently because they provide additional information, giving us a glimpse into the development of the disease. Understanding the distinct and unique changes in hematological components of the bone marrow induced by a particular pathogen or corresponding to a specific illness may be a valuable asset for the diagnosis and prognosis of disease. A good example of a pathogen that could be better evaluated with greater knowledge of the bone marrow is dengue, one of the most important public vector-borne human diseases. Owing to the multitude of clinical manifestations and the dynamic alterations of various blood components over time, this disease is one of the most difficult to prevent and treat in humans. Although large amounts of data have been generated in the literature, there remains a large gap between this information and its relevance for the purpose of patient care. While evaluating the cellular components in the circulated blood from ill patients provides us with valuable information about the pathogenesis of various pathogens, there are other players participating in the progression to disease. The goal of this review is to emphasize the importance of bone marrow hematopoietic progenitor cells in disease and to inspire other researchers to incorporate them into their investigations on dengue pathogenesis. It is anticipated that the knowledge derived from these investigations not only elicit original concepts on the pathogenesis of dengue but also foster a new way of thinking in terms of vaccine or therapeutic development to prevent and treat dengue.

Unfavorable attitudes toward receiving methadone maintenance therapy and associated factors among the inmates using intravenous heroin.

The aims of this study were to examine unfavorable attitudes toward receiving methadone maintenance therapy (MMT) and associated factors among inmates using intravenous heroin in Taiwan. A total of 315 inmates using intravenous heroin were recruited. Their unfavorable attitudes toward receiving MMT after discharge from prison were evaluated using the Client Attitudes Toward Methadone Programs Scale. The associations of unfavorable attitudes toward receiving MMT with sociodemographic and drug-using characteristics, human immunodeficiency virus serostatus, perceived family support, and depression were examined using multiple regression analysis. The results of this study showed that the mean score of unfavorable attitudes toward receiving MMT, determined on the Client Attitudes Toward Methadone Programs Scale, was 9.918 (standard deviation=2.277, range=5-20). Heroin-using inmates who were young, started using heroin earlier, perceived many advantages and few disadvantages of heroin use, had never received MMT, and had severe depression, had unfavorable attitudes toward receiving MMT. Based on the results of this study, we suggest that inmates who have the factors associated with unfavorable attitudes toward receiving MMT should receive intervention and motivational interviewing to improve their attitudes toward MMT and to increase their opportunity to receive MMT after discharge from prison.

Clinical features and prognostic factors of emphysematous urinary tract infection.

BACKGROUND AND PURPOSE: Emphysematous 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Effect of serotypes on clinical manifestations of dengue fever in adults.

BACKGROUND AND PURPOSE: Dengue fever (DF) is a major public health issue. However, it is unclear whether different dengue virus serotypes (DENV) are associated with different clinical manifestations and outcomes. This study investigated the association between viral serotype and clinical manifestations of DF. METHODS: Adult patients with DENV-2 and DENV-3 who were treated at Kaohsiung Medical University Hospital and Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung, Taiwan, from January 1998 to September 2007 were enrolled. The patients' demographic data, underlying diseases, clinical manifestations, laboratory data, and disease outcomes were retrospectively analyzed. RESULTS: 294 patients had DENV-2 and 91 had DENV-3. The median age was 50 years, and 45.7% of patients were men. Patients with DENV-3 were more likely to have a malignancy (p = 0.011), myalgia (p = 0.03), skin rash (p < 0.001), ascites (p = 0.04), and fever (p = 0.003) than patients with DENV-2. Patients with DENV-3 had their lowest levels of white blood cells and platelets, and peak plasma activated partial thromboplastin time (aPTT) 1 day later than patients with DENV-2. DENV-2 infection was associated with a higher monocyte count and more prolonged aPTT early in the clinical course. Infection by DENV-2 more commonly occurred as a secondary infection, while infection by DENV-3 was more common as a primary infection (p < 0.001). There were no differences between the groups in organ involvement, disease severity, duration of hospital stay, and medical expenditure. CONCLUSION: The symptoms, signs, and laboratory findings appear to be different for patients infected with DENV-2 and DENV-3, but there is no difference in outcomes.

Acute Q fever with hemophagocytic syndrome: case report and literature review.

Hemophagocytic syndrome is a rare complication of acute Q fever. We reported the case of 26-year-old man with fever, chills, severe headache, non-productive cough and progressive thrombocytopenia. Bone marrow aspirate revealed hemophagocytosis. We discussed the differences among the three previous reported cases and the possible mechanisms of hemophagocytic syndrome.

Epidemiologic analysis and antifungal susceptibility of Candida blood isolates in southern Taiwan.

Candidemia is a clinically important disease which has increased in incidence worldwide in recent decades. In order to identify the risk factors for mortality in candidemic patients and to elucidate the role of antifungal susceptibility testing, a retrospective cohort study was performed of 56 episodes of candidemia in 1998 at a medical center in southern Taiwan. The minimal inhibitory concentration (MIC) of these isolates was determined by E-test. Malignancy and alimentary diseases (42.9%) were the most common underlying conditions of these patients. There was no difference of Candida spp. distribution among patients treated in medical or surgical departments, except that all 5 isolates of C. intermedia were found in patients treated in medical departments (p=0.02) and 50% of candidemic infants had C. parapsilosis isolates (p=0.046). Among all Candida isolates, 3 (5.4%) were fluconazole non-susceptible. C. tropicalis had a significantly higher rate of amphotericin B resistance than the other species (p=0.007). Thirty four patients died and 70.6% of these deaths were attributable to candidemia. Thrombocytopenia, septic shock at the date of candidemia onset, C-reactive protein > 100 mg/L, blood urea nitrogen > 20 mg/dL, length of stay < 60 days, and Acute Physiology and Chronic Health Evaluation II score > or = 10 points were significantly associated with the death attributable to candidemia. Thrombocytopenia was the only independent predictor for mortality in the multivariate analysis. When the breakpoint of fluconazole was set at 2 microg/mL, as opposed to 8 microg/mL as in the National Committee for Clinical Laboratory Standards (NCCLS) criteria, the clinical outcome of death was significantly correlated to the MICs of the blood isolates. The correlation between MIC of fluconazole determined by E-test data, which is more easily obtainable than with NCCLS methods, and outcome requires larger scale investigation.