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Background Critically ill COVID-19 patients are prone to bloodstream infections (BSIs). Aim To evaluate the incidence, risk factors, and prognosis of BSIs developing in COVID-19 patients in the intensive care unit (ICU). Methods Patients staying at least 48 h in ICU from 22 March 2020 to 25 May 2021 were included. Demographic, clinical, and laboratory data were analyzed. Results The median age of the sample (n = 470) was 66 years (IQR 56.0-76.0), and 64% were male. The three most common comorbidities were hypertension (49.8%), diabetes mellitus (32.8%), and coronary artery disease (25.7%). Further, 252 BSI episodes developed in 179 patients, and the BSI incidence rate was 50.2 (95% CI 44.3-56.7) per 1000 patient-days. The source of BSI is central venous catheter in 42.5% and lower respiratory tract in 38.9% of the episodes. Acinetobacter baumannii (40%) and carbapenem-resistant Klebsiella pneumoniae (21%) were the most common pathogens. CRP levels were lower in patients receiving tocilizumab. Multivariable analysis revealed that continuous renal replacement therapy, extracorporeal membrane oxygenation, and treatment with a combination of methylprednisolone and tocilizumab were independent risk factors for BSI. The estimated cumulative risk of developing first BSI episode was 50% after 6 days and 100% after 25 days. Of the 179 patients, 149 (83.2%) died, and a statistically significant difference ( p Conclusion BSI is a common complication in COVID-19 patients followed in the ICU, and it can lead to mortality. Failure in infection control measures, intensive immunosuppressive treatments, and invasive interventions are among the main factors leading to BSIs.

Introduction: We aimed to determine the indicators for poor long-term outcome in older adults with community-acquired pneumonia (CAP). Methodology: Patients with CAP requiring hospitalization were included in this retrospective study. The long-term mortality was defined as all-cause 1-year mortality following hospital admission. Results: A total of 145 patients with CAP were recorded. The median age was 70 (18-103), of whom 94 (65%) were ≥ 65 years old and 86 (59.5%) were male. Long-term mortality rates following CAP requiring hospitalization were substantially high in both the younger (n = 16, 31.4%) and older adults (n=43, 45.7%). In univariate analysis, the Pneumonia Severity Index (PSI) (p = 0.007), mechanical ventilation (p > 0.001), mental status changes (p = 0.018) as well as the modified Charlson Comorbidity Index (p=0.001), presence of malignancy (p < 0.001) and hospital readmission (p < 0.001) were associated with long-term mortality in the older group. Our results revealed that the need for mechanical ventilation (OR = 47.61 CI = 5.38-500.0, p = 0.001) and hospital readmission (OR = 15.87 CI = 5.26-47.61, p < 0.001) were major independent predictors of 1-year mortality. Conclusions: Clinicians should consider the lethal possibilities of CAP even after hospital discharge. The need for mechanical ventilation and hospital readmission may predict long-term mortality. Therefore, the patients who have these predictors should be closely monitored.

Introduction: We aimed to evaluate clinical and laboratory findings of hospitalized asthma and chronic obstructive pulmonary disease (COPD) patients with COVID-19 and demonstrate that they have different symptoms and/or laboratory results and outcomes than COVID-19 patients with comorbidity (CoV-com) and without comorbidity (CoV-alone). Methodology: The data of the demographic, clinical, laboratory findings of hospitalized CoV-alone, asthma, COPD patients with COVID-19 (CoV-asthma, CoV-COPD, respectively), and CoV-com were analyzed. Results: Out of 1082 patients hospitalized for COVID-19, 585 (54.1%) had CoV-alone, 40 (3.7%) had CoV-asthma, 46 (4.3%) had CoV-COPD and 411 (38%) had CoV-com. Cough, shortness of breath, fever and weakness were the most common four symptoms seen in all COVID-19 patients. Shortness of breath, myalgia, headache symptoms were more common in CoV-asthma than the other groups (p < 0.001, p < 0.01, p < 0.05 respectively). Sputum was more common in CoV-COPD than other groups (p < 0.01). COPD group most frequently had increased values, different from the other groups with CRP>5ng/mL in 91.3%, D-dimer > 0.05mg/dL in 89.1%, troponin > 0.014micg/L in %63.9, INR>1.15 in 52.2%, CK-MB>25U/L in 48.5%, PT>14s in 40.9% of patients (p < 0.05, p < 0.001, p < 0.001, p < 0.001, p < 0.05, p < 0.001, respectively). NT-ProBNP was found to have the highest AUC value and the best differentiating parameter for CoV-asthma from CoV-alone. Typical CT findings were present in 44.4% of CoV-alone, 57.5% of CoV-asthma, 28.3% of CoV-COPD and 38.9% of CoV-com groups. CoV-COPD and CoV-com patients died more frequently than other groups (17.8%, 18.5%). Conclusions: CoV-asthma and CoV-COPD patients might have different symptoms and laboratory parameters than other COVID-19 patients which can guide the physicians.

Objectives Vaccination against COVID-19 emerges as an effective strategy for combating the pandemic. While many of our patients with rheumatic diseases (RD) wonder whether it is safe to get the vaccine, vaccine hesitancy is rising among the general population. We assessed the willingness to get vaccination and its probable predictors among patients with RD compared to healthcare workers and a sample from the general population. Methods We conducted a web-based questionnaire survey in a cross-sectional design in 3 groups of participants just before the mass vaccination program in Istanbul, Turkey. The questionnaire sought socio-demographic variables, COVID-19 related risk factors, willingness to get vaccination, and concerns and thoughts about vaccine. COVID-19 anxiety scale (CAS) was also evaluated. Results We studied in total 732 patients with RD (Group 1), 763 individuals representing general population (Group 2) and 320 hospital workers (Group 3). Dysfunctional anxiety related to COVID-19 was found in 4.9%, 3.8% and 4.1%, in Group 1, 2 and 3, respectively. Of the patients with RD, 29.2% were willing to be vaccinated, 19.0% were unwilling and 51.8% were undecided. These were somewhat similar among the general population (yes: 34.6%, no: 23.3% and unsure: 42.1%), with significantly less undecided individuals (p

Candidemia is a nosocomial infection mostly found in critically ill patients. Our objectives were to evaluate the change in distribution and resistance profile of Candida spp. isolated from candidemic patients in our intensive care unit over two 5-year periods spanning 15 years and to evaluate the risk factors. Records from the microbiology laboratory were obtained, from January 2004 to December 2008 and from January 2013 to December 2017, retrospectively. Antifungal susceptibility was performed by E-test and evaluated according to EUCAST breakpoints. A total of 210 candidemia cases occurred; 238 Candida spp. were isolated in 197 patients (58.8% male; mean age, 59.2 ± 19.6 years). The most predominant risk factor was central venous catheter use. Species distribution rates were 32%, 28%, 17%, and 11% for C. albicans (n = 76), C. parapsilosis (n = 67), C. glabrata (n = 40), and C. tropicalis (n = 27), respectively. Resistance rate to anidulafungin was high in C. parapsilosis over both periods and increased to 73% in the second period. Fluconazole showed a remarkable decrease for susceptibility in C. parapsilosis (94 to 49%). The prevalence of MDR C. parapsilosis (6%/33%) and C. glabrata (0%/44%) increased in the second period. We observed a predominance of non-albicans Candida spp., with C. parapsilosis being the most frequent and C. glabrata infections presenting with the highest mortality. High level of echinocandin resistance in C. parapsilosis and increasing prevalences of MDR C. parapsilosis and C. glabrata seem emerging challenges in our institution.

Hepatitis delta virus (HDV) infection causes the most severe form of viral hepatitis. PEG-interferon alpha-2a (PEG-IFN alpha-2a) is the only effective treatment but its long-term clinical impact is unclear. the aim of this study was to investigate the long-term outcome after 48 weeks of pegylated interferon alpha-2a therapy. We performed a retrospective follow-up study of the Hep-Net-International-Delta-Hepatitis-Intervention-Study 1 (HIDIT-I trial). Patients had received 48 weeks of treatment with either PEG-IFN alpha-2a plus adefovir dipivoxil (ADV) (Group I), PEG-IFN alpha-2a alone (Group II) or adefovir dipivoxil alone (Group III). Liver-related complications were defined as liver-related death, liver transplantation, liver cancer and hepatic decompensation defined as development of Child-Pugh scores B or C or an increase in Model for End-stage Liver Disease (MELD) scores of five or more points in relation to baseline values. Patients were considered for further analysis when they were retreated with PEG-IFN alpha-2a. Follow-up data (at least 1 visit beyond post-treatment week 24) were available for 60 patients [Group I, (n = 19), Group II (n = 20), Group III (n = 21)]. Mean time of follow-up was 8.9 (1.6 - 13.4) years. 19 patients were retreated with IFN-based therapy: 42% (n = 8) in PEG-IFN alpha-2a arms and 58% (n = 11) in the adefovir only arm. Clinical complications on long-term follow-up occurred in 17 patients and were associated with nonresponse to therapy and baseline cirrhosis. the annual event-free survival rate in patients with cirrhosis vs noncirrhotic patients at year 5 and 10 was 70% vs 91% and 35% vs 76%. Long-term follow-up of a large randomized clinical trial suggests that off-treatment HDV RNA response to PEG-IFN alpha-2a treatment leads to improved clinical long-term outcome., German Centre for Infection Research (DZIF), partner site Hannover-Braunschweig; German Liver Foundation; EASL registry grant, This study was funded by the German Centre for Infection Research (DZIF), partner site Hannover-Braunschweig with a grand to the HepNet Study-House, the German Liver Foundation and an EASL registry grant.

HIV/AIDS-related stigma remains a crucial public health problem in the world. Unfortunately, health provider staffs such as nurses and physicians are the major source of stigmatization and discrimination against peoples living with HIV (PLHIVs) including in Turkey. The aim of this study was to assess HIV-related stigma towards to PLHIV by nurses and physicians and to examine related factors. Descriptive Assessment Form and the HIV-Related Stigma Scale used for data collection. The study consisted of 405 health workers including 251 nurses and 154 physicians. Over 86% of physicians and 69.3% of nurses had no specific education about HIV. More than 11% of the nurses and 8.4% of the physicians expressed that HIV can be transmitted with handshaking or breathing in a shared environment. Fear-driven stigma was significantly different by age, education, occupation, and work experience. Over 14% of the discrimination (Adjusted

Initial case series of small number of patients at the beginning of the pandemic reported a rather guarded prognosis for Behçet’s syndrome (BS) patients infected with SARS-CoV-2. In this prospective study, we describe the incidence, clinical characteristics, disease course, management, and outcome in a large cohort of BS patients with laboratory-confirmed infection of SARS-CoV-2. We defined a cohort of 1047 registered BS patients who were aged between 16 and 60 years and seen routinely before the pandemic at the multidisciplinary outpatient clinic. We followed prospectively this cohort from beginning of April 2020 until the end of April 2021. During 13 months of follow-up, of the 1047 (599 M/448 F) patients, 592 (56.5%) were tested for SARS-CoV-2 PCR at least once and 215 (20.5%; 95% CI 0.18–0.23) were tested positive. We observed 2 peaks which took place in December 2020 and April 2021. Of the 215 PCR positive patients, complete information was available in 214. Of these 214, 14 (6.5%) were asymptomatic for COVID-19. In the remaining, the most common symptoms were anosmia, fatigue, fever, arthralgia, and headache. A total of 40 (18.7%) had lung involvement, 25 (11.7%) were hospitalized, 1 was admitted to the intensive care unit while none died. Favipiravir was the most prescribed drug (74.3%), followed by colchicine (40.2%), and hydroxychloroquine (20.1%) in the treatment of COVID-19. After COVID-19, 5 patients (2.3%) were given supplemental O2 and 31 (14.5%) antiaggregant or anticoagulants. During COVID-19, of the 214 PCR positive patients, 116 (54.2%) decreased the dose of their immunosuppressives or stopped taking completely; 36 (16.8%) experienced a BS flare which was mostly oral ulcers (10.3%). None of the patients reported a thrombotic event. A total of 93 (43.5%) patients reported BS flares after a median 45 days of COVID-19 infection and this was found to be significantly associated with immunosuppressive drug discontinuation. Multiple regression analysis adjusted for age and gender indicated that smoking and using interferon-alpha decreased the likelihood of getting COVID-19. The incidence and severity of COVID-19 did not differ between those who were using colchicine or not. The cumulative incidence of COVID-19 in this prospectively followed cohort of BS patients was almost two folds of that estimated for the general population living in Istanbul, Turkey, however, the clinical outcome of COVID-19 was not severe and there was no mortality. The protective effect of smoking and interferon deserves further investigation. On the other hand, colchicine did not have any positive or negative effect against COVID-19. Significant number of patients flared after COVID-19, however, this was significantly associated with immunosuppressive discontinuation during the infection. Contrary to our previous observations, COVID-19 did not seem to exacerbate thrombotic events during or after the infection. Supplementary Information The online version contains supplementary material available at 10.1007/s00296-021-05056-2.

Aims In this study, we aimed to reveal mortality rates and factors affecting survival in geriatric patients infected with COVID-19. Methods This is a retrospective study of 873 geriatric patients with COVID-19 who were hospitalized between March 11, 2020 and March 11, 2021. Demographic, clinical, laboratory data, and treatment options were obtained from electronic medical records. Multivariate logistic regression was used to explore the risk factors for in-hospital death. Results During the specified period, 643 patients were discharged, and 230 patients died in the hospital. The mean age was 75.08 ± 7.39 years (mean ± SD) and 51.8% were males. We found that older age (≥ 85), polypharmacy, dyspnea, abnormal thorax computed tomography (CT), lower doses of anticoagulation, and high values of white blood cell, aspartate aminotransferase, C-reactive protein, lactate dehydrogenase, ferritin were associated with a significant increase in mortality (P

Limited data exists to date on the predictors for the development of pneumonia in patients with mild and moderate coronavirus (COVID-19). In this study, it was aimed to evaluate the demographic characteristics and clinical findings of mild and moderate COVID-19 and to determine the risk factors for the development of COVID-19 pneumonia in patients admitted to the pandemic outpatient clinic of a university hospital. A total of 414 patients with laboratory confirmed COVID-19 were included. Of these, 220 (53.1%) were male, the mean age was 38.3 ± 12.7. Median duration of hospital admission from the onset of symptoms was three days (0-11). Of the confirmed COVID-19 cases, 154 (37.2%) had a history of family contact and the most common symptoms were weakness (68.4%), myalgia (61.8%), headache (56.5%), loss of smell (45.2%), loss of taste (43.2%) and anorexia (42.8%). Among females, weakness (p= 0.016), headache (p= 0.008), sore throat (p= 0.032), nausea (p= 0.003), anorexia (p= 0.045), loss of taste (p= 0.005) and loss of smell (p0.001) were more common. Loss of taste (47.6% vs. 25%, p0.001) and loss of smell (50% vs. 26.3%, p0.001) were more common in patients with under the age of 50 and cough (43.4% vs. 29.3%, p= 0.003) was more common in patients with above the age of 40. Among 46 (11.1%) patients with asymptomatic COVID-19, there was no significant difference (p= 0.500) between the genders. Pneumonia was detected in 150 (43.8%) of 339 patients who underwent thorax computed tomography. In the univariate analysis; advanced age (p0.001, odds ratio (OR)= 1.44), obesity (p0.001 OR= 2.5), not being actively smoking (p0.001, OR= 6.19), fever at first admission (p= 0.002, OR= 2.02), cough (p0.001, OR= 3.26), shortness of breath (p0.001, OR= 23.37), weakness (p= 0.042, OR= 1.63), anorexia (p= 0.009, OR= 1.79) and elevation of D-dimer (p= 0.014, OR= 1.92) were associated with the development of pneumonia. In multivariate analysis, obesity (p= 0.005, OR= 2.69), not being actively smoking (p0.001, OR= 5.43), cough at first admission p= 0.017, OR= 2.16) and shortness of breath (p= 0.008, OR= 16.22) was determined as an independent risk factor for the development of pneumonia. CRP (p0.001), D-dimer (p0.001), ferritin (p0.001) values among 108 (26.1%) patients with a body-mass index(BMI)30 were high, and 60.9% of the patients had pneumonia (p0.001) . CRP (p0.001), D-dimer (p= 0.010) values were low, lymphocyte count (p= 0.001) was high among 106 (25.6%) active smokers, and 15.6% of the patients had pneumonia (p0.001). Of the patients reported with persistent symptoms, 25.9% had loss of smell, 25% had weakness, and 23.1% had loss of taste on the seventh day; 21.1% had loss of smell, 21.1% had myalgia, and 19.7% had loss of taste on the 14th day. During their follow-up, the COVID-19 polymerase chain reaction (PCR) test was studied in 286 patients for control purposes. The median time of being negative for COVID-19 PCR test was eight days (3-56). In conclusion, symptoms may last longer than 14 days in 20- 30% of patients presenting with mild-moderate clinical findings. In addition, obesity should be considered as an important risk factor for COVID-19 pneumonia.

Brouwer, Willem Pieter/0000-0001-8713-1481; van Campenhout, Margo J.H./0000-0003-0460-4920 WOS:000478827400001 PubMed ID: 31135084 Serum Hepatitis B core-related antigen (HBcrAg) level moderately correlates with cccDNA. We examined whether HBcrAg can add value in monitoring the effect of peginterferon (PEG-IFN) therapy for HBeAg-negative chronic hepatitis B (CHB) infection. Thus, serum HBcrAg level was measured in 133 HBeAg-negative, mainly Caucasian CHB patients, treated with 48 weeks of PEG-IFN alfa-2a. We assessed its association with response (ALT normalization & HBV DNA < 2000 IU/mL) at week 72. HBcrAg level strongly correlated with HBV DNA level (r = 0.8, P < 0.001) and weakly with qHBsAg and ALT (both r = 0.2, P = 0.01). At week 48, mean HBcrAg decline was -3.3 log U/mL. Baseline levels were comparable for patients with and without response at week 72 (5.0 vs 4.9 log U/mL, P = 0.59). HBcrAg decline at week 72 differed between patients with and without response (-2.4 vs -1.0 log U/mL, P = 0.001), but no cut-off could be determined. The pattern of decline in responders resembled that of HBV DNA, but HBcrAg decline was weaker (HBcrAg -2.5 log U/mL; HBV DNA: -4.0 log IU/mL, P < 0.001). For early identification of nonresponse, diagnostic accuracy of HBV DNA and qHBsAg decline at week 12 (AUC 0.742, CI-95% [0.0.629-0.855], P < 0.001) did not improve by adding HBcrAg decline (AUC 0.747, CI-95% [0.629-0.855] P < 0.001), nor by replacing HBV DNA decline by HBcrAg decline (AUC 0.754, CI-95% [0.641-0.867], P < 0.001). In conclusion, in Caucasian patients with HBeAg-negative CHB, decline of HBcrAg during PEG-IFN treatment was stronger in patients with treatment response. However, HBcrAg was not superior to HBV DNA and qHBsAg in predicting response during PEG-IFN treatment. Foundation for Liver and Gastrointestinal Research, Rotterdam, the NetherlandsNetherlands Government; Fujirebio Europe, Ghent, Belgium; Dutch government (Health Holland- TKI-LSH) [LSHM15032]; Dutch government [FES0908]; F. HoffmannLa Roche Ltd., Basel, SwitzerlandHoffmann-La Roche This work was supported, initiated and sponsored by the Foundation for Liver and Gastrointestinal Research, Rotterdam, the Netherlands. Financial support was provided by Fujirebio Europe, Ghent, Belgium and the Dutch government (Health Holland- TKI-LSH, [project number LSHM15032]). The studies are part of the Virgo consortium, funded by the Dutch government [project number FES0908]. For the original study, financial support, study medication and drug supply were provided by F. HoffmannLa Roche Ltd., Basel, Switzerland. The funding sources did not have any influence on study design, data collection, analysis and interpretation of the data, writing of the report nor the decision to submit for publication.

van Campenhout, Margo J.H./0000-0003-0460-4920; Brouwer, Willem Pieter/0000-0001-8713-1481; Liem, Seng/0000-0002-3585-2778 WOS:000457008300010 PubMed ID: 30689258 Background Various treatment combinations of peginterferon (PEG-IFN) and nucleos(t)ide analogues have been evaluated for chronic hepatitis B (CHB), but the optimal regimen remains unclear. Aims To study whether PEG-IFN add-on increases response compared to entecavir (ETV) monotherapy, and whether the duration of ETV pretreatment influences response. Methods Response was evaluated in HBeAg positive patients previously treated in two randomized controlled trials. Patients received ETV pretreatment for at least 24 weeks and were then allocated to 24-48 weeks of ETV+PEG-IFN add-on, or continued ETV monotherapy. Response was defined as HBeAg loss combined with HBV DNA Results Of 234 patients, 118 were assigned PEG-IFN add-on and 116 continued ETV monotherapy. Response was observed in 38/118 (33%) patients treated with add-on therapy and in 23/116 (20%) with monotherapy (P = 0.03). The highest response to add-on therapy compared to monotherapy was observed in PEG-IFN naive patients with HBsAg levels below 4000 IU/mL and HBV DNA levels below 50 IU/mL at randomization (70% vs 34%; P = 0.01). Above the cut-off levels, response was low and not significantly different between treatment groups. Duration of ETV pretreatment was associated with HBsAg and HBV DNA levels (both P < 0.005), but not with response (P = 0.82). Conclusions PEG-IFN add-on to ETV therapy was associated with higher response compared to ETV monotherapy in patients with HBeAg positive CHB. Response doubled in PEG-IFN naive patients with HBsAg below 4000 IU/mL and HBV DNA below 50 IU/mL, and therefore identifies them as the best candidates for PEG-IFN add-on (Identifiers: NCT00877760, NCT01532843). Foundation for Liver Research (Rotterdam, The Netherlands) The study was organised and sponsored by the Foundation for Liver Research (Rotterdam, The Netherlands).

Addition of peginterferon alpha (PEG-IFN add-on) to entecavir (ETV) treatment after a short lead-in phase results in more response than ETV monotherapy in HBeAg-positive chronic hepatitis B infection (CHB). This study is the first to assess long-term efficacy of this treatment strategy. Patients who received ETV ± 24 weeks of PEG-IFN add-on in a global trial (ARES study) and completed follow-up were eligible to participate in this observational LTFU study if they had at least one combined HBeAg and HBV DNA measurement beyond week 96 of the ARES study. The primary endpoint was combined response (HBeAg loss and HBV DNA

Tenofovir use is associated with lower risk of mother-to-infant transmission of the virus, and discontinuation of the treatment is not safe. However, the safety of the drug during pregnancy and breastfeeding is not clear. In this study, we aimed to determine the tenofovir concentration in plasma of mother-infant pairs along with breast milk in chronic hepatitis B patients during the lactation period. A total of 11 mother-infant pairs were enrolled in the study. All the mothers received tenofovir disoproxil fumarate (TDF) 245mg/day for at least 1 month because of chronic hepatitis B infection. Maternal blood, breast milk, and infant blood samples were obtained concomitantly. Tenofovir concentrations were determined by liquid chromatography-tandem mass spectrometry. The median concentrations of tenofovir in maternal plasma and breast milk samples were 88.44 (interquartile range [IQR], 62.47 to 116.17) ng/ml and 6.69 (IQR, 4.88 to 7.03) ng/ml, respectively. Tenofovir concentrations were undetectable (,4ng/ml) in all of the infant plasma samples. The ratio of tenofovir concentration in breast milk to that in maternal plasma was 0.07. Tenofovir disoproxil fumarate passes through the breast milk in a small amount. Infants had no detectable tenofovir level in their plasma. Our study suggests that tenofovir disoproxil fumarate treatment is safe during the breastfeeding period in chronic hepatitis B patients. Viral Hepatitis Society ; Istanbul University

Objective To assess antibody response to inactivated COVID-19 vaccine in patients with immune-mediated diseases (IMD) among hospital workers and people aged 65 and older. Methods In this cross-sectional study, we studied 82 hospital workers with IMD (mean age: 42.2 +/- 10.0 years) and 300 (mean age: 41.7 +/- 9.9 years) controls. Among + 65 aged population, we studied 22 (mean age: 71.4 +/- 4.5 years) patients and 47 controls (mean age: 70.9 +/- 4.8 years). All study subjects had a negative history for COVID-19. Sera were obtained after at least 21 days following the second vaccination. Anti-spike IgG antibody titers were measured quantitatively using a commercially available immunoassay method. Results Patients with IMD were significantly less likely to have detectable antibodies than healthy controls both among the hospital workers (92.7% vs 99.7%, p < 0.001) and elderly population (77.3% vs 97.9%, p = 0.011). Among patients with IMD, those using immunosuppressive or immune-modulating drugs (64/75, 85.3%) were significantly less likely to have detectable antibodies compared to those off treatment (29/29, 100%) (p = 0.029). Additionally, a negative association between age and the antibody titer categories among patients (r = - 0.352; p < 0.001) and controls (r = - 0.258; p < 0.001) were demonstrated. Conclusions Among hospital workers, the vast majority of patients with IMD and immunocompetent controls developed a significant humoral response following the administration of the second dose of inactivated COVID-19 vaccine. This was also true for the elderly population, albeit with lower antibody titers. Immunosuppressive use, particularly rituximab significantly reduced antibody titers. Antibody titers were significantly lower among those aged >= 60 years both in patient and control populations. Whether these individuals should get a booster dose warrants further studies. Turkish Rheumatology Society [26.03.2021/5] This study was supported by the Turkish Rheumatology Society (26.03.2021/5).

BackgroundOne-fifth of COVID-19 patients are seriously and critically ill cases and have a worse prognosis than non-severe cases. Although there is no specific treatment available for COVID-19, early recognition and supportive treatment may reduce the mortality. The aim of this study is to develop a functional nomogram that can be used by clinicians to estimate the risk of in-hospital mortality in patients hospitalized and treated for COVID-19 disease, and to compare the accuracy of model predictions with previous nomograms.MethodsThis retrospective study enrolled 709 patients who were over 18 years old and received inpatient treatment for COVID-19 disease. Multivariable Logistic Regression analysis was performed to assess the possible predictors of a fatal outcome. A nomogram was developed with the possible predictors and total point were calculated.ResultsOf the 709 patients treated for COVID-19, 75 (11%) died and 634 survived. The elder age, certain comorbidities (cancer, heart failure, chronic renal failure), dyspnea, lower levels of oxygen saturation and hematocrit, higher levels of C-reactive protein, aspartate aminotransferase and ferritin were independent risk factors for mortality. The prediction ability of total points was excellent (Area Under Curve = 0.922).ConclusionsThe nomogram developed in this study can be used by clinicians as a practical and effective tool in mortality risk estimation. So that with early diagnosis and intervention mortality in COVID-19 patients may be reduced.

Mortality due to K. pneumoniae bacteremia is on rise, particularly in regions with high rates of carbapenem and colistin resistance. We aimed to define risk factors for colistin resistance and its impact on mortality. Patients diagnosed with "carbapenem-resistant K. pneumoniae (CRKp)" bacteremia between 2014 and 2018 were divided into two groups as "colistin susceptible (ColS)" and "colistin resistant (ColR)" based on broth microdilution method. Retrospective case-control study was conducted to compare characteristics and outcomes. Multiple logistic regression model was used to define independent risk factors for acquired colistin resistance and Cox proportional hazard model for 28-day mortality. A total of 82 patients (39 ColS and 43 ColR) were included. Mean age was 61.5 years, and 50 (61%) were male. Colistin resistance was significantly increased with duration of hospital stay (p = 0.007) and prior colistin use (p = 0.007). Overall, the 28-day mortality rate was 66%. Age (p = 0.014) and colistin resistance significantly increased 28-day (p = 0.009) mortality. Microbiological response to treatment within 7 days favors survival. PFGE analysis revealed an outbreak with K. pneumoniae ST78 and ST45 clones. Patients treated with combined antimicrobials had significantly lower 28-day mortality (p = 0.045) in comparison to monotherapy. However, types of combinations did not show significant superiority on each other. Colistin resistance increases 28-day mortality in CRKp bacteremia. Although combined regimens are more effective than monotherapy, existing antibacterial combinations have no apparent superiority to each other. New treatment options are pivotal.

Cancer is responsible for elevated human immunodeficiency virus (HIV)-related mortality but there are insufficient data about cancer in HIV-positive patients in Turkey.We aimed to investigate the prevalence and mortality of cancer among people living with HIVand AIDS patients in Istanbul, Turkey.Between January 1998 and December 2016, people living with HIVand AIDS patients were enrolled in this study by the ACTHIV-IST Study Group, which consists of 5 centres to follow-up HIV-positive patients in Istanbul. The cancer diagnoses included AIDS-defining cancers (ADCs) and non AIDS-defining cancers (NADCs).Among 1872 patients, 37 (1.9%) were diagnosed with concurrent cancer. Eleven patients were diagnosed during follow-up; the prevalence of cancer among people living with HIVand AIDS patients was 2.6%. Among 48 cancer patients, 35 patients had ADCs, and 32 of them were diagnosed at their first hospital admission. There were 1007 late presenters and 39 of them had cancer (29 were ADCs). The most prevalent NADCs were gastrointestinal, genitourinary, and pulmonary cancers. NADCs were mostly diagnosed during follow-up of patients. The mortality of this group was significantly higher than that of patients with ADCs (53.9% vs 22.9%).These results indicate the importance of cancer screening at diagnosis and during follow-up of HIV infection. A detailed physical examination contributes to diagnosis of the most prevalent ADCs (Kaposi's sarcoma and non-Hodgkin's lymphoma), especially in late presenters. For NADCs, individual risk factors should be considered.انتشار السرطان بين مرضى فيروس العوز المناعي البشري/الإيدز والوفيات الناجمة عنه: دراسة أترابية في تركيا.أوزليم آيدين، آلبير غندوز، فاطمة سارجن، بلجول ميتي، حياة كاراعثمان أوجلو، ديلك سيفجي، مجاهد يامزن، بولنت دوردو، إلياز دوكميتاش، فهمي تاباك، مجموعة دراسة ACTHIV-IST¹.يُعد السرطان مسؤولاً عن ارتفاع نسبة الوفيات المقترنة بفيروس العوز المناعي البشري، ولكن لا تتوافر معلومات كافية بشأن السرطان في صفوف المرضى المصابين بفيروس العوز المناعي البشري في تركيا.هدفت الدراسة إلى الاستقصاء بشأن انتشار السرطان بين مرضى فيروس العوز المناعي البشري/الإيدز والوفيات الناجمة عنه في إسطنبول، تركيا.في الفترة بين يناير/كانون الثاني 1998 وديسمبر/كانون الأول 2016، سجلت مجموعة دراسة ACTHIV-IST (العمل من أجل مكافحة فيروس العوز المناعي البشري في إسطنبول) المرضى المصابين بفيروس العوز المناعي البشري في هذه الدراسة، التي تشمل 5 مراكز لمتابعة المرضى المصابين بفيروس العوز المناعي البشري في إسطنبول. وتضمن التشخيص أنواع السرطان التي تحدد مرض الإيدز، وأنواع السرطان التي لا تحدد مرض الإيدز.من بين 1872 مريضاً، شُخِّص 37 مريضاً منهم (1.9٪) بالسرطان المُصاحب لفيروس العوز المناعي البشري. وشُخص أحد عشر مريضاً خلال المتابعة؛ وبلغت نسبة انتشار السرطان بين مرضى فيروس العوز المناعي البشري/الإيدز 2.6٪. ومن بين 48 مريضاً بالسرطان، كان لدى 35 مريضاً أنواع السرطان التي تحدد مرض الإيدز، وشُخص 32 مريضاً منهم عند دخولهم المستشفى أول مرة. وتأخر 1007 من مُقدمي البيانات، منهم 39 شخصاً مصاباً بالسرطان (وكان لدى 29 منهم أنواع السرطان التي تحدد مرض الإيدز). ومن بين أنواع السرطان التي لا تحدد مرض الإيدز الأكثر انتشاراً: سرطان المَعِدة والأمعاء، وسرطان الجِهَاز البَوليّ التَّناسُليّ، وسرطان الرئة. وكانت أنواع السرطان التي لا تحدد مرض الإيدز تُشخص أثناء متابعة المرضى. ومعدل الوفيات في هذه الفئة أعلى بكثير عنه في المرضى المصابين بأنواع السرطان التي تحدد مرض الإيدز (53.9٪ مقابل 22.9٪).توضح هذه النتائج أهمية تحري الإصابة بالسرطان عند التشخيص بعدوى فيروس العوز المناعي البشري وأثناء متابعة المرضى المصابين به. ويساعد إجراء فحص بدني مُفصل في تشخيص أكثر الأمراض انتشاراً من أنواع السرطان التي تحدد مرض الإيدز (ساركومة كابوزي ولمْفُومة هودجكين)، خاصة في صفوف مُقدمي البيانات المتأخرين. أما أنواع السرطان التي لا تحدد مرض الإيدز، فينبغي أن تؤخذ بعين الاعتبار عوامل الخطر الفردية.(العمل من أجل مكافحة فيروس العوز المناعي البشري في إسطنبول).¹.Prévalence et mortalité du cancer chez les personnes vivant avec le VIH et les patients atteints de sida : étude de cohorte à grande échelle en Turquie.Le cancer est responsable d’une mortalité élevée liée au virus de l’immunodéficience humaine (VIH), mais les données relatives au cancer chez les personnes séropositives en Turquie sont insuffisantes.Étudier la prévalence et la mortalité du cancer chez les personnes vivant avec le VIH et les patients atteints de sida à Istanbul (Turquie).Entre janvier 1998 et décembre 2016, des personnes séropositives ont été recrutées comme sujets pour la présente étude par le groupe d’étude ACTHIV-IST, qui se compose de cinq centres de suivi des personnes séropositives pour le VIH à Istanbul. Les diagnostics de cancer incluaient les cancers classant sida et les cancers non classant sida.Sur 1 872 malades, 37 (1,9 %) ont reçu un diagnostic de cancer concomitant. Onze patients ont été diagnostiqués en phase de suivi post-thérapeutique. La prévalence du cancer chez les personnes vivant avec le VIH et les patients atteints de sida était de 2,6 %. Sur 48 patients cancéreux, 35 avaient un cancer classant sida, parmi lesquels 32 avaient été diagnostiqués lors de leur première hospitalisation ; 1 007 personnes se présentaient à un stade avancé de l’infection, et 39 d’entre elles avaient un cancer (29 avaient un cancer classant sida). Les cancers non classant sida les plus prévalents étaient les cancers gastro-intestinal, uro-génital et pulmonaire. Ces cancers avaient principalement été diagnostiqués chez les patients en phase de suivi post-thérapeutique. Dans ce groupe, la mortalité était considérablement plus élevée que celle des patients de cancers classant sida (53,9 % contre 22,9 %).Ces résultats soulignent l’importance du dépistage du cancer lors du diagnostic et du suivi post-thérapeutique des infections à VIH. Un examen clinique détaillé contribue au diagnostic des cancers classant sida les plus prévalents (sarcome de Kaposi et lymphome non hodgkinien), en particulier chez les patients se présentant à un stade avancé. Concernant les cancers non classant sida, les facteurs de risque individuels devraient être pris en compte.

Antimicrobial stewardship is of major importance in patients with febrile neutropenia (FN). In this study, we aimed to investigate the trends in resistance and the relationship with mortality rates in patients with FN. The single-center surveillance data of inpatients with FN and diagnosed as microbiologically confirmed bloodstream infections (BSIs) between 2006 and 2016 were reviewed retrospectively. A total of 950 episodes in 552 patients with BSIs were analyzed. Of whom, 55.9% were male, the median age was 43 years, and 35.6% had acute myeloid leukemia. In total, 1016 microorganisms were isolated from blood cultures. Gram-negatives accounted for 42.4% (n = 403) of the episodes. Among Gram-negatives, Enterobacteriaceae accounted for 346 (86%) (E. coli, n = 197; 34% extended-spectrum β-lactamases (ESBL) producers, and Klebsiella spp., n = 120; 48.3% ESBL producers). Also, 24 (20.0%) of Klebsiella spp. had carbapenemase activity. There were 6 (5.0%) colistin-resistant Klebsiella spp. Thirteen (26.5%) of Pseudomonas spp. and 17 (60.7%) of Acinetobacter spp. had carbapenemase activity. There were 2 (5.6%) colistin-resistant Acinetobacter spp. The 30-day mortality rates were 12.0%, 21.5%, 34.6%, and 29.0% in BSIs due to Gram-positive, Gram-negative bacterial, fungal, and polymicrobial etiology respectively (p = 0.001). BSIs with ESBL-producing (p = 0.001) isolates, carbapenem (p

Maintaining optimal adherence to antiretroviral therapy (ART) is essential for optimizing the management of HIV infection. The aim of this study is to explore ART adherence rates in Turkey. Included in this study were a total of 263 HIV-infected patients followed up by the ACTHIV-IST (ACTion against HIV in Istanbul) Study Group affiliated with four tertiary hospitals. The study population included patients 18 years of age or older who were on ART for over 12 months. Adherence was assessed by the medication possession ratio (MPR) calculated for each patient using data (a list of all drugs dispensed within the previous year for that patient) obtained from pharmacy medication records. In addition, patients completed a self-report questionnaire addressing missed doses and the AIDS Clinical Trials Group (ACTG) adherence questionnaire. The study was reviewed and approved by the Ethics Committee of Cerrahpasa Medical Faculty. Patient ages ranged from 19 to 71 years. Two hundred and thirty-one patients were male (88%). Two hundred and twenty-four patients (85%) had optimal adherence (MPR ≥95%). During the course of ART, 236 patients (90%) reported no missed doses in the past 4 days of their treatment, whereas 206 patients (78%) reported no missed doses in the past month. Simply forgetting was the most common reason for nonadherence. MPR was associated with virologic rebound. Major factors affecting adherence were being female, taking antituberculosis drugs, having an opportunistic infection, being able to take all or most of the medication as directed, and being aware of the need to take medication exactly as instructed to prevent the development of drug resistance. Adherence to ART measured by MPR and self-report surveys is relatively high in Turkey when compared with other countries, which probably led to high ART success rates.

The prevalence of human immunodeficiency virus (HIV) infection is low but it is steadily increasing in Turkey. In the current study, we aimed to assess the status of HIV infection management with the proposed 90–90–90 targets in a large HIV cohort in Istanbul, Turkey. The cohort included 2382 patients (2082 male, 300 female, mean age was 36.3 ± 11.3 years). Mean CD4 cell count was 399 cells/mm3and HIV-RNA level was 576,235 copies/ml. According to the modeling by the Modeling tool of European Center for Diseases Control Software, 72 and 74% of all HIV patients had been diagnosed in 2016 and 2017, respectively (the first target). Among 2382 patients, 2191 (92%) were on antiretroviral therapy (the second target). The third target of virally suppressing those on treatment was achieved among 70.2% of the patients. The current study suggests that both the fraction of those living with undiagnosed HIV and the proportion of those on treatment who are virally suppressed should be targeted to sustain optimal HIV care. Efforts should continue to surpass the targets of 90–90–90.

balkan, ilker inanc/0000-0002-8977-5931; Mete, Bilgul/0000-0001-9091-6087 WOS:000487585400009 PubMed ID: 32065823 Introduction: The frequency, causality, severity, preventability and risk factors of ADRs (adverse drug reactions) in infectious disease units are not well defined in the literature. Thus, the aim of this study was to determine the characteristics of the ADRs encountered in an infectious disease unit of a tertiary teaching hospital. Methodology: The patients who were admitted to the infectious disease unit of a tertiary teaching hospital longer than 24 hours between January and December of 2016 were followed prospectively. Patients were observed and questioned for any sign of ADRs. The proportion of ADRs and patient characteristics were investigated. Causality was evaluated by the Naranjo algorithm, severity was determined using the Hartwig classification, and preventability was assessed using the Schumock and Thornton scale. Results: 210 patients were admitted to the unit during the study period, of whom 44 patients (20.9%) experienced 51 ADRs. 5.9% of ADRs were found to be serious according to the Hartwig severity classification. In addition, 88.1% of ADRs were not preventable. The most frequently detected ADR was skin and subcutaneous tissue reactions (33.3%), and systemic antimicrobials were the most common type of drugs that caused an ADR. Prolonged hospitalization (p < 0.001) and usage of an increased number of drugs (p < 0.001) were found to be significant risk factors for ADR development. Conclusions: Prolonged hospital stay and polypharmacy are significant risk factors that increase the incidence of ADRs in infectious disease units. The likelihood of unavoidable ADRs should arouse the attention of clinicians when prescribing antimicrobials.

Mete, Bilgul/0000-0001-9091-6087 WOS:000471741500006 PubMed ID: 30700656 We aimed to assess the 24-week virological and immunological success of the treatment of treatment-naive and treatment-experienced patients included in the Action against HIV in Istanbul (ACTHIV-IST) database. The ACTHIV-IST database was screened retrospectively from January 2012 to January 2014. The data for these patients such as age, sex, treatment-naive or treatment-experienced status, date of diagnosis, date of commencing antiretroviral therapy, antiretroviral therapy regimen, CD4+ cell count, and viral load before and after therapy were analyzed. In the 24th week of antiretroviral therapy, there were 40 (17.9%) and 29 (14.1%) virological and immunological failures, respectively. Virological failure (VF) was associated with a baseline viral load > 100,000 copies (p = 0.004). A CD4+ cell count lower than 200 cells/mu l was not found to be associated with VF (p = 0.843). Immunological failure was substantially rare in patients with a baseline CD4+ cell count > 200 cells/mu l (p = 0.005). Although an HIV-RNA 100,000 copies/ml, VF was 3.2 times more likely to occur. Baseline VF was the most predictive parameter to estimate 24th week virological success and VF. VF is an important prognostic parameter resulting in CD4+ cell depletion, AIDS-related events, and increased mortality.

WOS: 000392282500007 PubMed ID: 26377840 Objective: The significance of mannose-binding lectin (MBL) and H-ficolin deficiency in febrile neutropenic (FN) patients and the correlation of these markers along with consecutive C-reactive protein (CRP) and procalcitonin (PCT) levels during the infectious process are investigated. Materials and Methods: Patients with any hematological malignancies who were defined to have "microbiologically confirmed infection", "clinically documented infection", or "fever of unknown origin" were included in this single-center prospective observational study. Serum levels of CRP, PCT, MBL, and H-ficolin were determined on 3 separate occasions: at baseline (between hospital admission and chemotherapy), at the onset of fever, and at the 72nd hour of fever. Results: Forty-six patients (54% male, mean age 41.7 years) with 61 separate episodes of FN were evaluated. Eleven patients (23.9%) had "microbiologically confirmed infection", 17 (37%) had "clinically documented infection", and 18 (39.1%) had "fever of unknown origin". Fourteen (30.4%) patients had low (

Patients receiving hematopoietic stem cell transplantation (HSCT) are exposed to highly immunosuppressive conditions and bloodstream infections (BSIs) are one of the most common major complications within this period. Our aim, in this study, was to evaluate the epidemiology of BSIs in these patients retrospectively.The epidemiological properties of 312 patients with HSCT were retrospectively evaluated.A total of 312 patients, followed between 2000 and 2011, who underwent autologous (62%) and allogeneic (38%) HSCT were included in the study. The most common underlying malignancies were multiple myeloma (28%) and Hodgkin lymphoma (21.5%). A total of 142 (45%) patients developed at least 1 episode of BSI and 193 separate pathogens were isolated from the blood cultures. There was a trend of increase in the numbers of BSIs in 2005-2008 and a relative increase in the proportion of gram-positive infections in recent years (2009-2011), and central venous catheter-related BSI was found to be most common source. Coagulase-negative staphylococci (49.2%) and Acinetobacter baumannii (8.8%) were the most common pathogens. Extended-spectrum beta-lactamase-producing strains were 23% and 22% among Escherichia coli and Klebsiella spp. isolates, respectively. Quinolone resistance was detected in 10% of Enterobacteriaceae. Resistance to carbapenems was not detected in Enterobacteriaceae, while it was seen at 11.1% and 23.5% in Pseudomonas and Acinetobacter strains, respectively.A shift was detected from gram-negative bacteria to gram-positive in the etiology over the years and central lines were the most common sources of BSIs.Amaç: Hematopoetik kök hücre transplantasyonu (HKHT) yapılan hastaların bağışıklık sistemi ciddi şekilde baskılanmıştır ve kan akımı enfeksiyonları (KAE) bu süre içinde karşılaşılan majör komplikasyonlardan biridir. Bu çalışmada amacımız, geriye dönük olarak bu hastalarda KAE’lerinin epidemiyolojisini değerlendirmektir. Gereç ve Yöntemler: HKHT yapılan 312 hastanın epidemiyolojik özellikleri retrospektif olarak değerlendirildi. Bulgular: 2000 ve 2011 yılları arasında otolog (%62) ve allojeneik (%38) HKHT yapılan 312 hasta, çalışmaya dahil edildi. Çalışmaya dahil edilen hasta grupları en sık multipl miyelom (%28) ve Hodgkin lenfoma (%21,5) tanılı hastalar idi. Yüz kırk iki hastada (%45) en az bir kez KAE gelişmiş ve kan kültürlerinden 193 ayrı patojen elde edilmiştir. KAE’lerde 2005-2008 yılları arası bir artışın yanında, 2009-20011 yılları arasında da gram pozitiflerde göreceli bir artış da saptanmış ve en sık KAE kaynağı santral venöz kataterler olarak tespit edilmiştir. Koagülaz negatif staphylococi (%49,2) ve Acinetobacter baumannii (%8,8), kan kültürlerinden en sık elde edilen patojenlerdir. Genişlemiş spektrumlu beta laktamaz üretimi Escherichia coli ve Klebsiella spp. suşları arasında sırası ile %23 ve %22 idi. Kinolon dirençli Enterobacteriaceae oranı %10 olarak tespit edilmiştir. Pseudomonas ve Acinetobacter suşlarında karbapenem direni sırasıyla, %11,1 ve %23,5 iken, Enterobacteriaceae grubunda karbapenemlere hiç direnç saptanmamıştır. Sonuç: Yıllar içinde, gram negatif bakterilerden gram pozitiflere doğru bir kayma gözlenirken, en sık KAE kaynağı santral kataterler olarak saptanmıştır.

Simultaneous central nervous system (CNS) infection with Cryptococcus and tuberculosis (TB) is very rare. Despite improved therapeutic options, treatment of CNS cryptococcosis is still difficult and needs invasive treatment modalities, such as intrathecal or intraventricular amphotericin B, in refractory cases. We describe a patient with systemic lupus erythematosus diagnosed with simultaneous cryptococcal and TB meningitis who had a poor response to intravenous liposomal amphotericin B and fluconazole, but was successfully treated with intraventricular amphotericin B, in addition to anti-TB therapy.

It is unknown whether peginterferon (PEG-IFN) add-on to entecavir (ETV) leads to more HBsAg decline compared to PEG-IFN monotherapy or combination therapy, and whether ETV therapy may prevent HBsAg increase after PEG-IFN cessation. We performed a post hoc analysis of 396 HBeAg-positive patients treated for 72 weeks with ETV + 24 weeks PEG-IFN add-on from week 24 to 48 (add-on, n = 85), 72 weeks with ETV monotherapy (n = 90), 52 weeks with PEG-IFN monotherapy (n = 111) and 52 weeks PEG-IFN + lamivudine (combination, n = 110) within 2 randomized trials. HBsAg decline was assessed at the end of PEG-IFN (EOP) and 6 months after PEG-IFN (EOF) discontinuation. Differences in baseline characteristics were accounted for using inversed probability of treatment weights. At EOP, a HBsAg reduction of >= 1log(10) IU/mL was more frequently achieved for patients in the add-on or combination therapy arms (both 36%), compared to PEG-IFN mono (20%) or ETV (8%) (add-on vs PEG-IFN mono P = 0.050). At EOF, the HBsAg reduction >= 1log(10) IU/mL was only sustained in patients treated with ETV consolidation (add-on vs combination and PEG-IFN mono: 40% vs 23% and 18%, P = 0.029 and P = 0.003, respectively). For add-on, combination, PEG-IFN mono and ETV, the mean HBsAg-level change at EOF was -0.84, -0.81, -0.68 and -0.33 log(10) IU/mL, respectively (P > 0.05 for PEG-IFN arms). HBeAg loss at EOF was 36%, 31%, 33% and 20%, respectively (P > 0.05). PEG-IFN add-on for 24 weeks results in more on-treatment HBsAg decline than does 52 weeks of PEG-IFN monotherapy. ETV therapy may maintain the HBsAg reduction achieved with PEG-IFN.

Introduction Chronic hepatitis C virus (HCV) infection is a major health problem worldwide. The majority of cases involving HCV infection develop into chronic hepatitis because of a failure to develop an effective immune response. Apoptosis of the hepatocytes plays a significant role in the pathogenesis of HCV infection: the interaction between the Fas antigen on hepatocytes and the Fas ligand on T cells corresponds to the main mechanism for hepatocyte damage. Interferon (IFN)-α has antiviral, immunoregulatory, and antiproliferative properties, and apoptosis seems to be a critical event in the action mechanisms of both IFNs. In this study, we aimed to detect any relationship between apoptotic markers in the liver and the response to the treatment. Materials and methods The study included 180 chronic HCV patients treated with IFN and ribavirin in four centers. Apoptotic markers (Fas, Fas ligand, Fas-associated death domain, caspases 3, 8, and 9, and in-situ apoptosis) were studied in the liver. The age, sex of the patients, response to therapy, ALT level, viral load, and genotype were recorded. Results The results of the study showed that the histological activity index and fibrosis correlated with CD95 staining density, caspase-8 intensiveness, and portal and parenchymal Fas ligand scores. The apoptotic parameters of the responsive cases were not significantly different from those of the unresponsive cases. Conclusion The apoptotic parameters studied in liver tissue are associated with inflammation and fibrosis; however, these parameters may not predict response to treatment.

WOS: 000354124400016 PubMed ID: 25959163 Background: Hepatitis C virus (HCV) status cannot be reliably predicted in anti-HCV positive/HCV-RNA negative individuals who may either have recovered spontaneously or have a false-positive test due to antibody cross-reaction. Investigating T lymphocyte responses in individuals with different HCV status may help understand the cellular immune mechanisms underlying spontaneous recovery, treatment response, and chronicity. Objective: We aimed to determine whether anti-HCV positive, HCV-RNA negative individuals are truly spontaneous recoverers from acute HCV infection. Study design: We used enzyme-linked immunosorbent spot (ELISPOT) assay to compare HCV-specific lymphocyte response among anti-HCV positive/HCV-RNA negative individuals, patients with sustained virological response to interferon-gamma/ribavirin treatment, and patients with chronic HCV infection. Results: We found that 83% of anti-HCV positive/HCV-RNA negative individuals without a past medical history of acute icteric hepatitis had an HCV-specific T lymphocyte response in peripheral blood. Lymphocyte responses in these individuals were similar in magnitude to treatment responders unlike patients with chronic HCV whose virus-directed immunity was significantly suppressed. Conclusions: Detection of HCV-specific T lymphocyte responses using ELISPOT is a feasible method to ascertain past asymptomatic acute HCV infection. Office of Scientific Research Projects, Istanbul University [BYPS-1-26/31012007] This study is funded in part by the Office of Scientific Research Projects, Istanbul University (no: BYPS-1-26/31012007).

Entecavir (ETV) is a potent inhibitor of hepatitis B viral replication, but long-term therapy may be required. We investigated whether adding on pegylated interferon (Peg-IFN) to ETV therapy enhances serological response rates. In this global investigator-initiated, open-label, multicenter, randomized trial, hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) patients with compensated liver disease started on ETV monotherapy (0.5 mg/day) and were randomized in a 1:1 ratio to either Peg-IFN add-on therapy (180 µg/week) from week 24 to 48 (n = 85) or to continue ETV monotherapy (n = 90). Response was defined as HBeAg loss with HBV DNA

Background: Blood stream infections (BSIs) due to carbapenem-resistant Enterobacteriaceae (CRE) are associated with high hospital mortality rates and present a tremendous challenge to clinicians. The optimal treatment remains undefined. We aimed to investigate the risk factors for mortality and the correlation between different treatment modalities and outcomes. Methods: The clinical characteristics and treatment outcomes of a cohort of 36 patients with BSIs due to CRE were investigated and a retrospective nested case–control study of surviving and non-surviving patients was conducted. Results: Fifty percent of the cases were male and the mean patient age was 54.9 ± 15.8 years. Klebsiella pneumoniae was the etiological agent in 26 cases (72.2%), Escherichia coli in eight (22.2%), and Enterobacter aerogenes in two (5.5%). All strains were phenotypically positive for carbapenemase activity and all except two (one E. coli and one K. pneumoniae) yielded both blaOXA-48 carbapenemases and blaCTX-M-type extended-spectrum beta-lactamases (ESBLs) in PCR products. The 14-day, 28-day, and all-cause in-hospital mortality rates were 41.6%, 50%, and 58.3%, respectively. The median time to death was 8 days (range 2–52 days). No significant differences were observed between survivors and non-survivors in terms of baseline characteristics, comorbid conditions, etiologies, or sources of bacteremia, however hematological malignancies (p = 0.015) and prolonged neutropenia (p = 0.044) were more common in non-survivors. Microbiological eradication and clinical response within 7 days were two major determinants of 28-day attributable mortality (p = 0.001 and p = 0.001, adjusted r2 = 0.845). Colistin-based dual combinations, and preferably triple combinations, were associated with significantly better outcomes when compared to non-colistin-based regimens (p

Summary Background Polymorphisms of the HLA-DP gene are associated with the natural clearance of the hepatitis B virus in Asian patients. Aim To investigate the association of HLA-DP polymorphisms with response to peginterferon (PEG-IFN) in Caucasian chronic hepatitis B (CHB) patients. Methods We studied 262 Caucasian chronic hepatitis B patients infected with HBV genotype A or D, treated with PEG-IFN for 1 year in two randomised controlled trials (HBV 99-01 and PARC study). Response was defined as an HBV DNA

Hepatitis B virus (HBV) infection is a health problem worldwide. Current treatment options for chronic hepatitis B (CHB) are nucleoside or nucleotide analogues and pegylated interferons. Tenofovir and entecavir are much more commonly used as they have better efficacy, tolerability, and high genetic barriers to resistance.The aim of this study was to assess the efficacies of tenofovir and entecavir in previously untreated CHB patients in a treatment cohort.We included CHB patients in a cohort including previously untreated HBeAg-positive and HBeAg-negative patients from 10 centers in Istanbul, Turkey. The patients were compared in terms of baseline characteristics, decrease in alanine transaminase (ALT), decrease in HBV-DNA to undetectable levels, HBeAg loss and anti-HBe development (among baseline HBeAg-positive patients), interventions to therapy because of lack of efficacy, side effects, severe side effects, and side effects that required change in treatment.The study included 121 patients who were administered tenofovir and 130 patients who were administered entecavir. The majority of patients were men, with mild to moderate histology in both treatment groups. The mean duration of follow-up was 18 and 20 months for tenofovir and entecavir, respectively. Patients receiving both drugs showed comparable rates of HBeAg loss, rates of undetectable HBV-DNA levels, rates of ALT normalization, ALT decrease, and decrease in HBV-DNA. Both drugs were well tolerated.This study shows that although the baseline characteristics did not match, tenofovir and entecavir sustained comparable virological efficacies. More patients discontinued entecavir during follow-up. Both drugs provided effective viral control, with few side effects.

There is a lack of knowledge regarding the effect of peginterferon (PEG-IFN) on the expression of intrahepatic hepatitis B core and surface antigen (HBcAg and HBsAg) in chronic hepatitis B (CHB) and its relation with response to therapy. Fifty-two HBeAg-positive and 67 HBeAg-negative CHB patients with paired liver biopsies taken at baseline and after 1 year of PEG-IFN therapy were studied. After PEG-IFN therapy, HBeAg-negative patients showed a significant reduction in both intrahepatic HBcAg (P = 0.04) and HBsAg expression (P < 0.001). In contrast, a reduction in intrahepatic HBcAg expression was not observed in HBeAg-positive patients, while a trend in reduction of intrahepatic HBsAg staining was found (P = 0.09). Post-treatment, 7 (13%) HBeAg-positive and 9 (14%) HBeAg-negative patients had no expression of intrahepatic HBsAg. Patients without any intrahepatic HBsAg expression post-treatment were more likely to achieve a combined response (HBeAg loss with hepatitis B virus (HBV) DNA

Hepatitis B surface antigen (HBsAg) loss is the ideal clinical endpoint but is achieved rarely during oral antiviral treatment. A current unmet need in CHB management is achievement of HBsAg loss with a finite course of oral antiviral therapy, thereby allowing discontinuation of treatment. Significantly higher rates of HBsAg loss at 72 weeks post-treatment have been demonstrated when tenofovir disoproxil fumarate (TDF) was combined with pegylated interferon (PEG-IFN) for 48 weeks compared with either monotherapy. This analysis provides follow-up data at week 120.In an open-label, active-controlled study, 740 patients with chronic hepatitis B were randomly assigned to receive TDF plus PEG-IFN for 48 weeks (group A), TDF plus PEG-IFN for 16 weeks followed by TDF for 32 weeks (group B), TDF for 120 weeks (group C), or PEG-IFN for 48 weeks (group D). Efficacy and safety at week 120 were assessed.Rates of HBsAg loss at week 120 were significantly higher in group A (10.4%) than in group B (3.5%), group C (0%), and group D (3.5%). Rates of HBsAg loss and HBsAg seroconversion in group A were significantly higher than rates in group C (P 0.001 for both) or group D (HBsAg loss: P = 0.002; HBsAg seroconversion: P 0.001).The results of this analysis confirm the results from earlier time points which demonstrate the increased rate of HBsAg loss in patients treated with a finite course of PEG-IFN plus TDF compared with the rates in patients receiving either monotherapy.

Background: In patients with chronic hepatitis B, tenofovir disoproxil fumarate (TDF) plus pegylated interferon (PEG-IFN) for 48-weeks results in higher rates of hepatitis B surface antigen (HBsAg) loss than either monotherapy. Aim: To identify baseline and on-treatment factors associated with HBsAg loss at Week 72 and provide a model for predicting HBsAg loss in patients receiving combination therapy for 48 weeks. Methods: A secondary analysis of data from an open-label study where patients were randomised to TDF (300 mg/day, oral) plus PEG-IFN (PI, 180 μg/week, subcutaneous) for 48 weeks (TDF/PI-48w); TDF plus PEG-IFN for 16 weeks, TDF for 32 weeks (TDF/PI-16w+TDF-32w); TDF for 120 weeks (TDF-120w) or PEG-IFN for 48 weeks (PI-48w). Logistic regression methods were used to identify models that best predicted HBsAg loss at Week 72. Results: Rates of HBsAg loss at Week 72 were significantly higher in the TDF/PI-48w group (6.5%) than in the TDF/PI-16w+TDF-32w (0.5%), TDF-120w (0%) and PI-48w (2.2%) groups (P = 0.09). The only baseline factor associated with response was genotype A. HBsAg decline at Week 12 or 24 of treatment was associated with HBsAg loss at Week 72 (P < 0.001). HBsAg decline >3.5 log10 IU/mL at Week 24 in the TDF/PI-48w group resulted in a positive predictive value of 85% and a negative predictive value of 99% for HBsAg loss at Week 72. Conclusions: HBsAg decline at Week 24 of TDF plus PEG-IFN combination therapy may identify patients who, after completing 48 weeks of treatment, have a better chance of achieving HBsAg loss at Week 72.

Fascioliasis, which is a zoonotic infestation caused by the trematode Fasciola hepatica (liver fluke), is primarily a disease of herbivorous animals such as sheep and cattle. Humans become accidental hosts through ingesting uncooked aquatic plants such as watercress. It presents a wide spectrum of clinical pictures ranging from fever, eosinophilia and vague gastrointestinal symptoms in the acute phase to cholangitis, cholecystitis, biliary obstruction, extrahepatic infestation, or asymptomatic eosinophilia in the chronic phase. However, it may often be overlooked, especially in the acute phase, because of vague symptoms. As a result of newly introduced serological assays facilitating the diagnosis, there has been an increase in the number of reported cases. Here, we report the clinical and laboratory assessment and therapeutic approach of a series of three cases diagnosed (in order of) one week, three months and one and a half years after presentation of the first symptoms of the disease.

Spontaneous intracranial hypotension (SIH) is recognized with increasing frequency. A throbbing headache occurring or worsening in the upright position and improving after lying down, a so-called 'orthostatic headache', low cerebrospinal fluid (CSF) pressure, and diffuse pachymeningeal enhancement on brain magnetic resonance imaging (MRI) are the major features of the classic syndrome. These patients, who are admitted with fever, headache, and CSF findings revealing lymphocytic pleocytosis, elevated protein concentration, normal glucose levels, and negative culture results, are prone to be misdiagnosed with aseptic meningitis. The aims of this single-centre retrospective study were to determine the epidemiological, clinical, laboratory, and radiological features of patients initially evaluated as having aseptic meningitis but subsequently diagnosed with SIH, and to touch upon the key points of the differential diagnosis in daily infectious diseases practice.Patients referred to Cerrahpasa Medical School with a presumed diagnosis of aseptic meningitis or viral meningitis between 1 January 2006 and 1 January 2011 were reviewed. Epidemiological, clinical, laboratory, radiological, and follow-up data obtained from the hospital database were processed. Patients confirmed to have SIH syndrome were included for evaluation.Eleven cases of SIH syndrome were diagnosed during the study period (8 male and 3 female, median age 30 y, range 21-44 y). All had headache, hearing changes, and nausea. Vomiting (10/11) and posterior neck pain (9/11) were also frequent. Seven had fever and 5 had a stiff neck. Four cases had lymphocytic pleocytosis, 4 cases had elevated CSF protein concentrations (1.5 times the upper limit of normal), and 2 cases had slightly lower CSF glucose levels. Polymerase chain reaction (PCR) analyses of the CSF for Mycobacterium tuberculosis complex, herpes simplex viruses 1 and 2, and enteroviruses were negative in all cases. MRI of the 11 cases revealed signs of spontaneous CSF leaks with diffuse pachymeningeal gadolinium enhancement (11/11), sagging of the brain (9/11), enlargement of the pituitary (6/11), engorgement of the venous structures (5/11), and subdural fluid collections (2/11). CSF leaks were demonstrated by intrathecal magnetic resonance or computed tomography myelography at different levels along the thoracic spine (7/11), cervico-thoracic junction (2/11), and thoraco-lumbar junction (2/11). Autologous blood injection into the spinal epidural space ('blood patch') was performed for treatment. Strict bed rest followed, and all patients recovered fully within a week; no recurrence or complication was observed during the follow-up periods, which ranged from 6 months to 5 y.Findings of fever, headache, and meningeal irritation are generally accepted as the clinical features of meningitis. When CSF findings are not characteristically compatible with bacterial meningitis and particularly when the headache is orthostatic in nature, SIH should also be included in the differential diagnosis. MRI findings are characteristic and clearly contribute to the differential diagnosis between viral meningitis and SIH.

Background: Liver biopsy is an imperfect gold standard for assessing the disease severity in hemodialysis patients with chronic hepatitis C. Our purpose was to compare the accuracy of the FibroTest (FT) and ActiTest (AT) with liver biopsy and the AST-to-platelet ratio index (APRI) in determining hepatic fibrosis and necroinflammatory activity in hemodialysis patients with hepatitis C virus (HCV). Methods: The FT-AT index combining 6 biochemical markers was assessed in 33 hemodialysis patients with HCV. Liver fibrosis and necroinflammatory activity was staged and graded according to the METAVIR scoring system. Results: The accuracy of FT-AT versus biopsy was 0.46 for significant fibrosis and 0.36 for severe necroinflammatory activity. The FT index had a positive predictive value of 20% for scores greater than 0.6 and a negative predictive value of 45% for scores less than 0.2. Eleven of the 33 patients had scores ≤0.2, 6 had significant fibrosis on biopsy. Four out of 5 patients with FT scores >0.6 had mild fibrosis. APRI correlated well with the biopsy. Conclusion: The FT-AT test does not seem to be a reliable noninvasive marker for the prediction of necroinflammatory activity and fibrosis in hemodialysis patients with HCV and cannot be used as an alternative to either liver biopsy or APRI.

Treatment of chronic hepatitis B (CHB) is difficult. The response rate to interferon (IFN) as well as nucleoside analogs is not more than 30% in general. While interferon has many side effects, development of resistance in most of the nucleoside analogs precludes long-term use. Both groups of drugs are most efficacious in patients who already had or develop strong cellular immunity with treatment. A pre-S2-containing vaccine was shown to enhance cellular immunity and suppress hepatitis B virus (HBV)-DNA in subjects with chronic hepatitis B. We aimed to test the efficacy of short-term use of a nucleoside analog in combination with a pre-S2-containing vaccine in patients with CHB. In this open study, 48 consecutive patients (32 males and 16 females, mean age +/- SD: 33 +/- 12 years) with CHB without cirrhosis were treated with 100 mg/day lamivudine and four weekly intramuscular injections of Genhevac B 20 mcg (six doses) for 24 weeks. While 19 patients were hepatitis B e antigen (HBeAg) positive (+ve), 29 patients were Anti-HBe/HBV-DNA +ve at the outset. Response was defined as seroconversion to anti-HBe in HBeAg +ve subjects and normalization of alanine aminotransferase (ALT) with loss of HBV-DNA in anti-HBe/HBV-DNA +ve subjects. HBeAg seroconversion occurred in 5/19 subjects (26%). Eighteen of 29 anti-HBe/HBV-DNA +ves responded. In the follow-up, while relapse was not observed in any of the patients who seroconverted, 11/18 from the anti-HBe/HBV-DNA +ve group relapsed, resulting in a sustained response (SR) rate of 24% in this group. All the relapses happened in the first 48 weeks of follow-up, with no relapse thereafter. Pretreatment high serum HBV-DNA was a strong negative predictor of sustained response (SR) in HBeAg +ve group. Pretreatment serum ALT over 2 x upper limit of normal and HBV-DNA less than 200 pg/ml appeared positive predictors. None of HBeAg +ve previous interferon failures responded. Twenty-four weeks of lamivudine and hepatitis B vaccine treatment induces SR in around 1/4 of the patients with CHB. Most of the responders had high ALT and relatively low DNA.

Background and aim Viral load is used for the diagnosis and monitoring the treatment of chronic hepatitis B (CHB). These methods are molecular-based and are expensive. Previous studies suggest that quantitative hepatitis B surface antigen (HBsAg) studied by automated chemiluminescent microparticle immunoassay can be a surrogate marker. In this study, we aimed to investigate whether quantitative HBsAg correlates hepatitis B virus (HBV) DNA levels during CHB treatment. Methods The study included 18 patients (13 male, 5 female, mean age: 33 ± 9 years) with CHB. They were given pegylated interferon ± lamivudine for 52 months and serum samples were obtained in weeks 0, 4, 8, 24, 48, 52, and 76. HBV DNA was measured by TaqMan polymerase chain reaction (PCR; Erasmus MC, University Medical Center, Rotterdam, The Netherlands). Quantitative HBsAg was studied by automated chemiluminescent microparticle immunoassay (Architect HBsAg, Abbott, IL). Results HBV DNA levels were measured as follows: 9.66, 7.69, 7.06, 5.93, 5.89, 5.88, and 7.27 logarithmic genome equivalent/ml, respectively. The corresponding HBsAg quantitation results were 42,888, 31,176, 37,882, 27,277, 28,279, 29,471, and 31,535 IU/ml, respectively. They showed a significant correlation (canonical correlation = 0.85). Conclusions HBsAg studied by automated chemiluminescent microparticle immunoassay correlates with HBV DNA and can be a surrogate marker during the monitoring of the efficacy of HBV treatment.

Febrile neutropenic episodes (FNEs) are among major causes of mortality in patients with hematological malignancies. Secondary infections develop either during the empirical antibiotic therapy or one week after cessation of therapy for a FNE. The aim of the study was to investigate the risk factors associated with secondary infections in febrile neutropenic patients.We retrospectively analyzed 750 FNEs in 473 patients between January 2000 and December 2006.Secondary infections were diagnosed in 152 (20%) of 750 FNEs. The median time to develop secondary infection was 10 days (range 2-34 days). The duration of neutropenia over 10 days significantly increased the risk of secondary infections (p0.001). The proportion of patients with microbiologically documented infections was found to be higher in primary infections (271/750, 36%) compared to secondary infections (43/152, 28%) (p=0.038). Age, sex, underlying disease, antibacterial, antifungal or antiviral prophylaxis, blood transfusion or bone marrow transplantation, central venous catheter or severity of neutropenia did not differ significantly between primary and secondary infections (p0.05) While fever of unknown origin (FUO) (p=0.005) and catheter-related bacteremia (p0.001) were less frequently observed in secondary infections, the frequency of microbiologically (p=0.003) and clinically (p0.001) documented infections, fungal pneumonias (p0.001), infections related with gram positive bacteria (p=0.04) and fungi (p0.001) and 30-day mortality rate (p0.001) were significantly higher in secondary infections (p0.001).Secondary infections should be regarded as life-threatening complications of febrile neutropenia. Secondary infections represent a more severe and mortal complication and cannot be regarded just as another febrile neutropenic episode.Amaç: Febril nötropenik atak (FNA) hematolojik hastalığı olan hastalarda ölümlerinin başlıca nedenleri arasında yer almaktadır. İkincil enfeksiyonlar FNA’nın ampirik antibiyotik tedavi ya da bu tedavinin kesilmesinden bir hafta sonrasına kadar gelişebilir. Bu çalışmada amacımız, febril nötropenik hastalarda ikincil enfeksiyonları ile ilişkili risk faktörlerini araştırmaktır. Yöntem: Kliniğimizde Ocak 2000 ile Aralık 2006 tarihleri arasında 73 hastada 750 FNA geriye dönük olarak incelenmiştir. Bulgular: Enfeksiyonlar 750 FNA’nın 152 sinde (% 20) tespit edilmiştir. Sekonder enfeksiyon gelişmesi için geçen medyan süre 10 gün (1-34 gün) idi. Nötropeni süresinin 10 günün üzerinde olması ikincil enfeksiyon riskini anlamlı derecede artırmaktadır (p0.001). Mikrobiyolojik dökümante enfeksiyon oranı primer enfeksiyonu (271/750, % 36) olan hastalarda sekonder enfeksiyonlu hastalara (43/152, % 28) göre daha yüksek olduğu bulunmuştur (p=0.038). Yaş, cinsiyet, altta yatan hastalık, antibakteriyel, antifungal veya antiviral profilaksi, kan transfüzyonu veya kemik iliği nakli, santral venöz kateter ya da nötropeni şiddeti açısından primer ve sekonder enfeksiyonu olan hastalar arasında anlamlı farklılık yoktu (p0.05). Katetere bağlı bakteremi (p0.001) ve nedeni bilinmeyen ateş (p=0.005) ikincil enfeksiyonlu hastalarda daha az sıklıkta gözlenirken, mikrobiyolojik (p=0.003) ve klinik olarak dökümante enfeksiyonlar (p0.001), fungal pnömoniler (p0.001), gram-pozitif bakteriler ile ilgili enfeksiyonlar (p=0.04) ve mantar enfeksiyonları (p0.001) ve 30-günlük mortalite oranı (p0.001) ikincil enfeksiyonlarda (p0.001) anlamlı olarak yüksek bulunmuştur. Sonuç: İkincil enfeksiyonlar febril nötropenik hastada hayatı tehdit eden komplikasyonlar olarak kabul edilmelidir. Enfeksiyonlar daha ağır ve ölümcül şekilde ortaya çıkabilir ve yeni bir febril nötropenik atak olarak kabul edilmemelidir.Amaç: Febril nötropenik atak (FNA) hematolojik hastalığı olan hastalarda ölümlerin başlıca nedenleri arasında yer almaktadır. İkincil enfeksiyonlar FNA’nın ampirik antibiyotik tedavi ya da bu tedavinin kesilmesinden bir hafta sonrasına kadar gelişebilir. Bu çalışmada amacımız, febril nötropenik hastalarda ikincil enfeksiyonları ile ilişkili risk faktörlerini araştırmaktır. Gereç ve Yöntemler: Kliniğimizde Ocak 2000 ile Aralık 2006 tarihleri arasında 73 hastada 750 FNA geriye dönük olarak incelenmiştir. Bulgular: Enfeksiyonlar 750 FNA’nın 152’sinde (%20) tespit edilmiştir. Sekonder enfeksiyon gelişmesi için geçen medyan süre 10 gün (1-34 gün) idi. Nötropeni süresinin 10 günün üzerinde olması ikincil enfeksiyon riskini anlamlı derecede arttırmaktadır (p0,001). Mikrobiyolojik dökümante enfeksiyon oranı, primer enfeksiyonu (271/750, %36) olan hastalarda sekonder enfeksiyonlu hastalara (43/152, %28) göre daha yüksek olduğu bulunmuştur (p=0,038). Yaş, cinsiyet, altta yatan hastalık, antibakteriyel, antifungal veya antiviral profilaksi, kan transfüzyonu veya kemik iliği nakli, santral venöz kateter ya da nötropeni şiddeti açısından primer ve sekonder enfeksiyonu olan hastalar arasında anlamlı farklılık yoktu (p0,05). Katetere bağlı bakteremi (p0,001) ve nedeni bilinmeyen ateş (p=0,005) ikincil enfeksiyonlu hastalarda daha az sıklıkta gözlenirken, mikrobiyolojik (p=0,003) ve klinik olarak dökümante enfeksiyonlar (p0,001), fungal pnömoniler (p0,001), gram-pozitif bakteriler ile ilgili enfeksiyonlar (p=0,04) ve mantar enfeksiyonları (0,001) ve 30-günlük mortalite oranı (p0,001) ikincil enfeksiyonlarda (p0,001) anlamlı olarak yüksek bulunmuştur. Sonuç: İkincil enfeksiyonlar febril nötropenik hastada hayatı tehdit eden komplikasyonlar olarak kabul edilmelidir. Enfeksiyonlar daha ağır ve ölümcül şekilde ortaya çıkabilir ve yeni bir febril nötropenik atak olarak kabul edilmemelidir.

BACKGROUND & AIMS: Interferon is the only effective treatment for chronic hepatitis D virus (HDV) infection. No rules have been set for stopping treatment based on viral kinetics. We analyzed data from an international study of hepatitis D treatment to identify factors associated with outcomes of pegylated interferon treatment, with and without adefovir. METHODS: We analyzed data from the Hep-Net-International Delta Hepatitis Intervention Trial on 50 patients with compensated liver disease who tested positive for anti-HDV and HDV RNA. Subjects received pegylated interferon alpha 2a, with adefovir or placebo, or only adefovir, for 48 weeks. Twenty-four weeks after treatment ended, 41 patients were evaluated for levels of HDV RNA and DNA, liver enzymes, and hepatitis B surface antigen (HBsAg); liver biopsy specimens were analyzed for fibrosis. Response to therapy was defined as end-of-treatment response or post-treatment week 24 virologic response. In both cases virologic response was associated with undetectable HDV RNA levels. Patients with less than a 1 log decrease in HDV RNA at the end of treatment were considered null responders. RESULTS: Based on univariate and multivariate analysis, the level of HDV RNA at week 24 of treatment was associated more strongly with response to therapy than other factors analyzed. The level of HBsAg at week 24 of treatment was associated with a response to therapy only in univariate analysis. Lack of HDV RNA at week 24 of treatment, or end of treatment, identified responders with positive predicted values of 71% and 100%, respectively. At 24 weeks after treatment, a decrease in HDV RNA level of less than 1 log, combined with no decrease in HBsAg level, identified null responders with a positive predictive value of 83%. A decrease in HDV RNA level of more than 2 log at week 24 of treatment identified null responders with a negative predictive value of 95%. CONCLUSIONS: Based on an analysis of data from a large clinical trial, the level of HDV RNA at week 24 of treatment with pegylated interferon, with or without adefovir for 48 weeks, can identify patients who will test negative for HDV RNA 24 weeks after the end of treatment. This information can be used to help physicians manage patients receiving therapy for chronic hepatitis D. Hep-Net Germany (German Ministry for Education and Research, BMBF-Forderkennzeichen) Roche Turkey

Different clinical outcomes of acute HBV infection have been partially explained by individual differences in immune response. In this study we investigated interferon gamma (IFN-γ) secretion of peripheral blood mononuclear cells (PBMC) in vitro against specific (Hepatitis B core antigen; recombinant HB-cAg) and non-specific (CMV, EBV, Influenza peptide pool; CTL CEF peptide pool "plus") antigens using enzyme linked immunospot (ELISPOT) assay in 7 patients with chronic hepatitis B (CHB group), 8 inactive carriers Of HBV (carrier group) and 8 subjects who spontaneously recovered from acute HBV infection as detected by anti-HBs positivity (immune group). Phytohemaglutinin served as the positive test control. Response against recombinant HBcAg was 88±135, 50±110, 105±150 spot forming cell (SFC)/10(5) PBMC, in CHB, carrier and immune groups, respectively. HBcAg-specific T-cell response was slightly higher in the immune group; however, statistically there was no significant difference between the groups. Assessment of cellular immunity by IFN-γ ELISPOT was not sufficient to explain the various outcomes of HBV infection such as resolution, chronicity and carriership.

SummaryObjective We aimed to compare community-onset healthcare-associated (CO-HCA) and hospital-acquired (HA) urinary tract infections (UTIs) caused by extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli in terms of epidemiology, clinical outcomes and antimicrobial activities. Methods Patients from both groups with ESBL-producing E. coli detected by urine culture between January 2009 and January 2011 were included in this retrospective study. Relevant demographical, microbiologic and clinical data were obtained from case records. Results A total of 173 patients (mean age of 58 years, 74% female) were included, of whom 75 (43.4%) had a CO-HCA UTI and 98 (56.6%) had an HA UTI. Eighty (46.2%) patients had more than one comorbid disease, of whom 57 (32.5%) had urological problems. The most common clinical manifestations were pyelonephritis (43.9%) and urosepsis (16.2%). An age of > 65 years (p = 0.005) in addition to urinary catheterisation (p = 0.001), urosepsis (p = 0.001) and mortality (p = 0.001) were significantly more common in the HA UTI group. Acute cystitis (p = 0.027), complicated cystitis (p = 0.001) and non-urologic neoplasm (p = 0.032) were significantly more common in the CO-HCA UTI group. No isolate was resistant to carbapenems or fosfomycin. Sensitivities to nitrofurantoin, amikacin, trimethoprim sulfamethoxazole-trimoxazole and quinolones were 97.6%, 89%, 29.4% and 17.9% respectively. Both groups showed similar rates of antibiotic resistance. Conclusion ESBL-producing E. coli should be taken into consideration in patients with a CO HCA UTI, not only in hospital settings but also in outpatient settings. We suggest ertapenem as a first-line empirical treatment for patients with an upper UTI and fosfomycin and nitrofurantoin for those with a lower UTI when ESBL-producing E. coli is suspected.

Background and aim Delta hepatitis is characterized by rapidly progressive liver disease with adverse prognosis in most patients. Patients benefit from high doses and prolonged courses of interferon (IFN) therapy; however, lamivudine as a single agent has been disappointing. Data relating to the efficacy of IFN and lamivudine in combination is limited. The aim of this study was to test the efficacy of IFN-alpha 2b and lamivudine combination treatment in comparison to IFN-alpha 2b alone in patients with chronic delta hepatitis. Methods Twenty-six patients with chronic delta hepatitis were randomized into two groups. Twelve patients received IFN-alpha 2b alone (eight men, four women; mean +/- SD age: 43.83 +/- 8.57 years), and 14 patients received IFN-alpha 2b plus lamivudine combination (seven men, seven women; mean +/- SD age: 42.5 +/- 11.02 years). The dose of IFN-alpha 2b was 10 MU t.i.w. and of lamivudine was 100 mg/day. The groups were comparable in reference to serum alanine aminotransferase (ALT), aspartate aminotransferase, bilirubin, albumin levels, histological activity and stage. Four patients (33.3%) in the IFN group and two (14.3%) in the combination group had cirrhosis (P = 0.2). The duration of treatment was 48 weeks with an untreated follow-up period of at least 96 weeks (mean +/- SD, 3.1 +/- 1.9 years). A liver biopsy was performed at the end of treatment. Results Eight patients from the IFN group and 11 from the combination group completed treatment. Serum ALT values became normal in 8/14 patients (57.1%) treated with IFN plus lamivudine and in 5/12 patients (41.7%) treated with IFN alone (P = 0.43). Serum hepatitis delta virus RNA was no longer detectable in nine of 14 (64.3%) patients treated with IFN plus lamivudine as compared to five of 12 (41.6%) patients treated with IFN alone (P = 0.024). In both groups female patients had significantly better virological response rate (P = 0.007). There was a significant improvement in histological activity in the combination group (mean decrease 5.27 +/- 1.08 score, P = 0.001), but not in the IFN group (mean decrease 1.44 +/- 1.59 score, P = 0.39). No significant improvement was observed in regards to fibrosis. Four of the 14 patients (28.6%) treated with combination therapy as compared to two of 12 patients treated with IFN (16.7%) were sustained virological responders (P = 0.47). The 5-year survival rate was 65% in the IFN group and 85% in the combination group (P > 0.05). Conclusion Interferon and lamivudine in combination is an encouraging treatment method and may be superior to IFN alone in chronic delta hepatitis.

We aimed to determine the following things: the frequency of patients with Mediterranean spotted fever (MSF) during the last 10 years among those patients admitted with fever and rash, their clinical features, and the factors predicting the diagnosis of MSF among patients admitted with fever and rash. Between 1993-2002, the files of all patients admitted to our hospital with fever and rash were collected. The clinical features and serologic results of the patients diagnosed with MSF were further investigated. The diagnosis of MSF was established by epidemiological and clinical features and also by the clinical response within 2 days after doxycycline treatment. During the previous 10 years, 140 patients were admitted with fever and rash, and 15 (10%; four females, 11 males; mean age: 41 years; range: 17-70) of them were diagnosed with MSF. Clinical features were as follows: fever (100%), rash (100%), myalgia and/or arthralgia (93%), headache (87%), petechiae (27%), tache noire (13%), leucocytosis (74%), thrombocytopenia (33%), and accelerated erythrocyte sedimentation rate (100%). In nine of these patients, the diagnosis of MSF was established by epidemiological and clinical features and was confirmed by serologic studies. As a complication, one patient developed facial paralysis. Six (40%) were given several antibiotics. In conclusion, MSF should be considered in the differential diagnosis when a patient is admitted with fever, maculopapular rash, headache, myalgia and/or arthralgia, especially in spring, summer, or autumn.

Hepatitis C virus (HCV) is the most common chronic blood-borne infection in the worldwide. This infection is often insidious and one-half of infected patients are asymptomatic. Determination of risk factors for HCV transmission is very important. The aim of this study was to assess the risk factors, transmission to spouses and children for HCV infection in Turkish population. One hundred and fifty-one patients with chronic hepatitis C and 151 control cases were investigated for the probable risk factors of HCV infection. Complete blood count, ALT, AST, albumin, prothrombin time, upper abdomen ultrasonography assessment and percutaneous liver biopsy (not for cirrhotics) were performed in all patients with chronic hepatitis C. Anti-HCV testing was done by using second-generation ELISA in 302 cases. Minor surgical operation (p < 0.001), major surgical operation (p = 0.001), blood transfusion (p < 0.001), multi-partner sex (p < 0.05), frequent dental therapy (p < 0.05), and dental extraction (p < 0.001) in patients with a chronic HCV infection were found to be higher than the control group. No significant difference was found in other risk factors. The rate of hepatitis C virus in index cases was found to be 1.8% in their spouses and 1.2% in their children. Our study showed that surgical operation, frequent dental therapy, dental extraction, multi-partner sex, and blood transmission are the main risk factors for HCV infection in Turkish community.

Early diagnosis of tuberculous meningitis (TBM) is essential for a positive outcome; but present microbiological diagnostic techniques are insensitive, slow, or laborious. We evaluated the standard BDProbeTec ET strand displacement amplification method (the standard ProbeTec method) for the detection of Mycobacterium tuberculosis complex organisms in parallel with the ProbeTec method with a modified pretreatment procedure with 101 prospectively collected cerebrospinal fluid specimens from 94 patients with suspected TBM. By the modified method, the sample-washing step was omitted. A definitive diagnosis was attained by culture. Thirteen specimens from 12 patients were culture positive for M. tuberculosis complex organisms; three specimens (23%) were microscopy positive for acid-fast bacilli. Among the culture-positive specimens, the standard ProbeTec method was positive for 8 (61.5%) and the modified assay was positive for 10 (76.9%). The overall specificity by both procedures was 98.8% compared to the results of culture. After discrepancy analysis, conducted by reviewing the patients' previous laboratory data, the specificity increased to 100%. If the cutoff value for respiratory specimens was adjusted from the recommended value of 3,400 to 1,000, the sensitivity of the modified procedure increased to 84.7%, with unchanged specificity. Results were obtained in 3 to 4 h. The new pretreatment procedure with the ProbeTec assay described here provides a rapid, simple, and sensitive tool for the diagnosis of TBM.

In this study we aimed to investigate the findings in patients with adult-onset Still's disease (AOSD) admitted with fever of unknown origin (FUO) during the last 18 years in our unit, in order to discover the ratio of such patients to all patients with FUO during the same period, and to determine the clinical features of AOSD in FUO. The number and the aetiologies of the patients with FUO diagnosed between 1984 and 2001, and the clinical features of those with AOSD, were taken from the patient files. The diagnosis of AOSD was reanalysed according to the diagnostic criteria of Cush et al. [11]. The presumed diagnoses before a diagnosis of AOSD was established were also noted. The chi(2) and Fisher's exact tests were used for statistical analysis. We studied 130 patients with a diagnosis of FUO, 36 (28%) of whom had collagen vascular diseases. Of these 36 patients, 20 (56%, 12 female, 8 male, mean age 34 years, range 16-65) had AOSD. Clinical and laboratory findings were as follows: fever (100%), arthralgia (90%), rash (85%), sore throat (75%), arthritis (65%), myalgia (60%), splenomegaly (40%), hepatomegaly (25%), lymphadenopathy (15%), anaemia (65%), neutrophilic leukocytosis (90%), increased erythrocyte sedimentation rate (100%), elevated transaminase levels (65%), a negative RF (100%), and a negative FANA (80%). Antibiotics had been prescribed in 18 (90%) of cases. The presumed infectious diagnoses were streptococcal tonsillitis/pharyngitis (50%), infective endocarditis (four patients), sepsis (two patients) and acute bacterial meningitis (two patients). The presumed non-infectious diagnoses were acute rheumatic fever (three patients), seronegative rheumatoid arthritis (two patients) and polymyositis (two patients). Sixteen patients were followed for a mean duration of 30 months (range 2-59). A remission was obtained with indomethacin in three cases (19%), and with prednisolone in the remainder. Relapse was detected in three cases (19%). AOSD is one of the most frequent aetiologies of FUO. During the diagnostic course of a patient with FUO, a maculopapular rash and/or arthralgia and/or sore throat should raise the suspicion of AOSD. Because the disease has heterogeneous clinical findings, certain bacterial infections (e.g. streptococcal pharyngitis and sepsis) are generally considered and the prescribing of antibiotics is common.