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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.

Introduction This study aims to evaluate the cost-effectiveness of remdesivir compared to other existing therapies (SoC) in Turkey to treat COVID-19 patients hospitalized with < 94% saturation and low-flow oxygen therapy (LFOT) requirement. Methods We compared remdesivir as the treatment for COVID-19 with the treatments in the Turkish treatment guidelines. Analyses were performed using data from 78 hospitalized COVID-19 patients with SpO(2) < 94% who received LFOT in a tertiary healthcare facility. COVID-19 episode costs were calculated for 78 patients considering the cost of modeled remdesivir treatment in the same group from the payer's perspective. The incremental cost-effectiveness ratio (ICER) per quality-adjusted life-year (QALY) was calculated for remdesivir versus the SoC for the population identified. For Turkey, a reimbursement threshold value between USD 8599 (1 x per capita gross domestic product-GDP) and USD 25.797 (3 x GDP) per QALY was used. Results In the remdesivir arm, the length of hospital stay (LOS) was 3 days shorter than the SOC. The low ventilator requirement in the remdesivir arm was one factor that decreased the QALY disutility value. In patients who were transferred to intensive care unit (ICU) from the ward, the mean LOS was 17.3 days (SD 13.6), and the mean cost of stay was USD 155.3/day (SD 168.0), while in patients who were admitted to ICU at baseline, the mean LOS was 13.1 days (SD 13.7), and the mean cost of stay was USD 207.9/day (SD 133.6). The mean cost of episode per patient was USD 3461.1 (SD 2259.8) in the remdesivir arm and USD 3538.9 (SD 3296.0) in the SOC arm. Incremental QALYs were estimated at 0.174. Remdesivir treatment was determined to be cost saving vs. SoC. Conclusions Remdesivir, which results in shorter LOS and lower rates of intubation requirements in ICU patients than existing therapies, is associated with higher QALYs and lower costs, dominating SoC in patients with SpO(2) < 94% who require oxygen support. SIMER Arastirma Gelistirme Saglik Ekonomi ve Tek Egt Dan Ith Ihr San Tic AS Gilead has provided financial support for the completion the full analysis and write up of the scientific data for publication. All authors had full access to the full data and the content of the publication reflects their views. Gilead has not been involved in any way in the drafting and/or review of the publication. The journal's Rapid Service Fee was funded by SIMER Arastirma Gelistirme Saglik Ekonomi ve Tek Egt Dan Ith Ihr San Tic AS.

Background CoronaVac, an inactivated whole-virion SARS-CoV-2 vaccine, has been shown to be well tolerated with a good safety profile in individuals aged 18 years and older in phase 1/2 trials, and provided a good humoral response against SARS-CoV-2. We present the interim efficacy and safety results of a phase 3 clinical trial of CoronaVac in Turkey. Methods This was a double-blind, randomised, placebo-controlled phase 3 trial. Volunteers aged 18-59 years with no history of COVID-19 and with negative PCR and antibody test results for SARS-CoV-2 were enrolled at 24 centres in Turkey. Exclusion criteria included (but were not limited to) immunosuppressive therapy (including steroids) within the past 6 months, bleeding disorders, asplenia, and receipt of any blood products or immunoglobulins within the past 3 months. The K1 cohort consisted of health-care workers (randomised in a 1:1 ratio), and individuals other than health-care workers were also recruited into the K2 cohort (randomised in a 2:1 ratio) using an interactive web response system. The study vaccine was 3 mu g inactivated SARS-CoV-2 virion adsorbed to aluminium hydroxide in a 0.5 mL aqueous suspension. Participants received either vaccine or placebo (consisting of all vaccine components except inactivated virus) intramuscularly on days 0 and 14. The primary efficacy outcome was the prevention of PCR-confirmed symptomatic COVID-19 at least 14 days after the second dose in the per protocol population. Safety analyses were done in the intention-to-treat population. This study is registered with ClinicalTrials.gov (NCT04582344) and is active but no longer recruiting. Findings Among 11 303 volunteers screened between Sept 14, 2020, and Jan 5, 2021, 10 218 were randomly allocated. After exclusion of four participants from the vaccine group because of protocol deviations, the intention-to-treat group consisted of 10 214 participants (6646 [65.1%] in the vaccine group and 3568 [34.9%] in the placebo group) and the per protocol group consisted of 10 029 participants (6559 [65.4%] and 3470 [34.6%]) who received two doses of vaccine or placebo. During a median follow-up period of 43 days (IQR 36-48), nine cases of PCR-confirmed symptomatic COVID-19 were reported in the vaccine group (31.7 cases [14.6-59.3] per 1000 person-years) and 32 cases were reported in the placebo group (192.3 cases [135.7-261.1] per 1000 person-years) 14 days or more after the second dose, yielding a vaccine efficacy of 83.5% (95% CI 65.4-92.1; p, TUSEB, We are grateful to all participants who volunteered to be part of this study and to all members of the clinical research teams of the participating sites. We thank TUSEB for funding the study and Omega-CRO for the statistical analyses and production of figures, and providing the study protocol. We also thank the members of the data and safety monitoring board for their contributions in the safe execution of this study.

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

Objectives: Elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) is a recommended and widely used regimen for HIV infection. In this study, we aimed to determine the efficacy and safety of E/C/F/TAF in people living with HIV (PLWH), who are either treatment-naïve or switched from any tenofovir disoproxil fumarate-containing regimen. For switched patients, we aimed to determine the impact of switching from tenofovir disoproxil fumarate (TDF) to TAF on lipid profile and kidney functions. Methods: ACTHIV-IST Study Group produced a database, and five dedicated HIV centres in Istanbul entered data of PLWH who switched from any TDF-containing regimen to E/C/F/TAF and treatment-naïve patients who were initiated with the E/C/F/TAF regimen between January 2017 and December 2019. Clinical findings, viral parameters, lipid studies, renal function tests, adverse events and adherence to the treatment were recorded in this prospective observational study. Results: The study included a total of 614 switched and treatment-naïve patients. Of 430 treatment-experienced patients, 89% (382) were men, and the mean age was 42 ± 12 years. Among them, 47% (181/382) self-identified as men who have sex with men (MSM). The median duration of HIV diagnosis was 54 ± 29 months. The median duration of E/C/F/TAF use was 20 ± 36 months and that of previous treatment was 23 ± 18 months. HIV-RNA was undetectable at baseline and month 12 in 84.1% (360/428) and 86.1% (328/381) of patients, respectively ( p > 0.05). Mean CD4 counts were 708 ± 287 cells/µL and 802 ± 305 cells/µL at baseline and month 12, respectively ( p < 0.001). Serum creatinine levels remained stable during the treatment period. Mean total cholesterol levels at baseline and month 12 were 172 and 211 mg/dL ( p < 0.01), LDL-cholesterol 104 and 138 mg/dL ( p < 0.01), HDL-cholesterol 39 and 49 mg/dL ( p < 0.01) and triglycerides 134 and 174 mg/dL ( p < 0.01), respectively. The treatment was generally well tolerated. Eight patients discontinued the therapy (drug interaction: 3; lost to follow-up: 1; pregnancy: 1; pulmonary tuberculosis: 1; side effect: 1; patient’s decision: 1). Of 184 treatment-naïve patients, 88% (162) were men, and the mean age was 36.5± 12 years. Among them, 50% (81/162) self-identified as MSM. The mean duration of HIV infection was 21.6 ± 17.1 months. The mean duration of E/C/F/TAF use was 16 ± 4 months. HIV-RNA was undetectable at baseline and month 12 in 1% and 89.1% of patients, respectively. Mean CD4 counts at baseline and month 12 were 469 ± 223 cells/µL and 740 ± 298 cells/µL, respectively. During the treatment period, creatinine levels remained stable. Total cholesterol, LDL-cholesterol, triglyceride and also HDL-cholesterol levels increased. Mean total cholesterol levels at baseline and month 12 were 167 and 211 mg/dL ( p < 0.01), LDL-cholesterol 108 and 143 mg/dL ( p < 0.01), HDL-cholesterol 41 and 47 mg/dL ( p < 0.01) and triglycerides 136 and 172 mg/dL, respectively ( p < 0.01). The treatment was generally well tolerated. Three patients discontinued the therapy (drug interaction: 1; non-responder: 1; patient’s decision: 1). Conclusion: Starting with or switching to E/C/F/TAF in PLWH effectively suppresses HIV infection, is associated with an increase in CD4 cell count and is well tolerated in a real-life setting. Renal functions remained stable during the treatment. E/C/F/TAF use was associated with an increase in LDL-cholesterol and triglyceride levels along with an increase in HDL-cholesterol levels.

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

Background: Efficacy of elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil (E/C/F/TDF) in treatment-naïve and experienced patients with HIV infection was demonstrated in phase 3 trials. The primary objective of this study was to evaluate effectiveness and safety of E/C/F/TDF in real world settings. Methods: Retrospective, observational data collected by the Turkish ACTHIV-IST study group between May 2015 and December 2016 were analysed. Results: A total of 387 patients were prescribed E/C/F/TDF; 210 patients with available data at 6th month were eligible; 91.5% were male, and mean age was 35.2 (SD: 10.8) years; 54.0% of males identified themselves as MSM. Sixty-three percent (133) of the study population were treatment-naïve patients, and 37% (77) were treatment experienced. HIV RNA level was below 100 copies/mL in 78.9% of treatment-naïve patients and 89.9% of treatment experienced patients at month 6. Median increase in CD4 T lymphocyte count was 218 copies/mL in treatment-naïve patients and remained stable or increased in treatment experienced patients. Adverse events were observed in 15% of the patients, and the regimen was discontinued in only six patients. Conclusion: Real world data on the effectiveness and safety of E/C/F/TDF is comparable with the phase 3 trial results Adverse events are uncommon and manageable. Keywords: Elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate; HIV; effectiveness; safety.

Most of the published data relate to classical forms of rheumatic diseases (RD) and information on rare inflammatory disorders such as Behçet's syndrome (BS) and familial Mediterranean fever (FMF) is limited. We studied the frequency of side effects and disease flares after COVID-19 vaccination with either Pfizer/BioNTech or Sinovac/CoronaVac in 256 patients with BS, 247 with FMF, and 601 with RD. Telephone interviews were conducted using a questionnaire survey in a cross-sectional design in patients with BS, FMF, and RD followed by a single university hospital. Study participants were vaccinated either with CoronaVac (BS:109, FMF: 90, and RD: 343,) or BioNTech (BS: 147, FMF: 157 and RD: 258). The majority have received double dose (BS: 94.9%, FMF 92.3% and RD: 86.2%). BioNTech ensured a significantly better efficacy than CoronaVac against COVID-19 in all patient groups (BS: 1.4% vs 10.1%; FMF: 3.2% vs 12.2%, RD:2.7% vs 6.4%). Those with at least one adverse event (AE) were significantly more frequent among those vaccinated with BioNTech than those with CoronaVac (BS: 86.4% vs 45%; FMF: 83.4% vs 53.3%; and RD: 83.3% vs 45.5%). The majority of AEs were mild to moderate and transient and this was true for either vaccine. There were also AEs that required medical attention in all study groups following CoronaVac (BS: 5.5%, FMF: 3.3%, and RD:2.9%) or BioNTech (BS: 5.4%, FMF: 1.9%, and RD: 4.7%). The main causes for medical assistance were disease flare and cardiovascular events. Patients with BS (16.0%) and FMF (17.4%) were found to flare significantly more frequently when compared to those with RD (6.0%) (p 0.001). This was true for either vaccine. BS patients reported mainly skin-mucosa lesions; there were however, 11 (4.3%) who developed major organ attack such as uveitis, thrombosis or stroke. Flare in FMF patients were associated mainly with acute serositis with or without fever. Arthralgia/arthritis or inflammatory back pain were observed mainly in the RD group. Our study demonstrates that BS and FMF patients vaccinated with either CoronaVac or BioNTech demonstrated similar AE profile and frequency compared to RD patients. AEs that required physician consultation or hospitalization occurred in all study groups after either CoronaVac or BioNTech. Increased frequency of flares in BS and FMF compared to that seen in RD might reflect defects in innate immunity and deserves further investigation. Caution should be required when monitoring these patients after vaccination.

Introduction: People who inject drugs (PWID) should be treated in order to eliminate hepatitis C virus (HCV) in the world. Aims: The aim of this study was to compare direct acting antivirals (DAAs) treatment of HCV for PWID and non-PWID in real life setting. Materials and methods: We performed a prospective, non-randomized, observational multi-center cohort study in 37 centers. All patients treated with DAAs therapy between April 1, 2017 to February 28, 2019 were included. In total, 2,713 patients were included in the study among which 250 were PWID and 2,463 were non-PWID. Besides patient characteristics, treatment response, follow-up and side effects of treatment were also analyzed. Results: Genotype 1a and 3 were more prevalent in PWID infected patients (20.4% vs 9.9% and 46.8% vs 5.3%). The number of naïve patients was higher in PWID (90.7% vs 60.0%), while the number of patients with cirrhosis was higher in non-PWID (14.1% vs 3.7%). The loss of follow up was higher in PWID (29.6% vs 13.6%). There was no difference in the sustained virologic response at 12 weeks after treatment (98.3% vs 98.4%), but the end of treatment response was lower in PWID (96.2% vs 99.0%). In addition, the rate of treatment completion was lower in PWID (74% vs 94.4%). Conclusion: DAAs were safe and effective in PWID. Primary measures should be taken to prevent the loss of follow-up and poor adherence in PWID patients in order to achieve World Health Organization’s objective of eliminating viral hepatitis.

Background: Widespread and effective use of molecular diagnostic tests is indispensable for protecting public health and containing the severe respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. More than 1 year into the pandemic, as resources have reached a point of depletion, grouping samples in pools of certain sizes appears to be a reasonable method to reduce both the costs and the processing time without necessitating additional training, equipment, or materials. Aims: To assess whether the pooling strategy that was used in past outbreaks and is used in blood tests prior to transfusion for screening large populations can also be used in SARS CoV-2 tests. Study Design: Diagnostic accuracy study. Methods: This prospective study was conducted with 2815 samples, sent to the coronavirus disease 2019 (COVID-19) Laboratory of our hospital between February 12 and 21, 2021, to be tested for the presence of SARS-CoV-2. The samples were examined individually and in pools of five 100 µl taken from each sequential sample, using 3 different SARS-CoV-2 reverse transcription-polymerase chain reaction (RT-PCR) kits, the Allplex™ 2019-nCoV Assay kit (Seegene, Republic of Korea), the GeneMAP™ 2019-nCoV detection V.3 kit (GenMark, Türkiye), and the Bio-Speedy™ SARS-CoV-2 Double Gene™ RT-qPCR kit (Bioeksen, Türkiye) on the BioRAD CFX96™ Touch (Bio-Rad Laboratories Inc., Hercules, CA, USA) platform available in our laboratory. Results: Following the extraction of serial dilutions prepared from the SARS-CoV-2 RNA positive (cycle of threshold: 20) sample, the standard curves of RT-PCR were analyzed. By evaluating the efficiency (E) values, all 3 kits showed high sensitivity and similar results; while the highest level was detected with the Allplex™ 2019-nCoV Assay kit in the nucleocapsid (N) gene (E: 124%), the lowest was detected with the Double Gene™ RT-qPCR kit in the N and ORF 1ab genes (E: 90%). Of the samples included in the study, only 1 positive sample with low viral load was found to be negative when studied by pooling. The total number of kits to be used in pooled tests and then to individually retest the 5 samples in positive pools was calculated as 827 and the savings rate as 69.91% (1968/2815). Conclusion: The pooling strategy is an effective approach to extend the impact of limited testing resources and reagents available in certain periods of the COVID-19 pandemic. Testing by pooling samples requires improvement of RNA extraction methods and careful monitoring of RT-PCR test sensitivity to avoid missing low-positive entities. Therefore, based on the prevalence of COVID-19 in their regions, laboratories should conduct their own validation of pooling studies for RNA extraction and amplification methods they use.

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

Aims: The COVID-19 pandemic has substantially changed lives and presented several barriers to health services. HIV care continuum needs a high rate of diagnosis, effective treatment, and sustained suppression of viral replication. The COVID-19 pandemic has affected these three steps of HIV care. This study investigated the characteristics of newly diagnosed patients living with HIV/AIDS (PLWH) during the COVID pandemic and compared them with those before the pandemic. Methods: All newly diagnosed patients in three HIV healthcare centers, in Istanbul, Turkey, were included in the study. The pandemic period included April 1, 2020, to April 1, 2021, and the prepandemic period included March 1, 2019, to March 1, 2020. Results: 756 patients were diagnosed with HIV/AIDS. In the pandemic period, this figure was 58% less: 315. Patients in the pre-pandemic and pandemic period had comparable age and gender distributions. PLWH diagnosed in the pandemic period had higher rates of low CD4 cells: low CD4 ( Conclusion: A low number of newly diagnosed PLWH can be explained by less HIV testing, less admission to health care, or an actual decrease of HIV prevalence during the pandemic. Sexual behaviors may have changed during the COVID-19 pandemic, leading to HIV transmission restriction. Lower CD4 counts among the newly diagnosed PLWH suggest that admittance to health care is late and a significant portion of PLWH remain undiagnosed.

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.

Background Cytokine release syndrome (CRS), characterized by overproduction of proinflammatory cytokines in the course of severe coronavirus disease 2019 (COVID-19), has been suggested as the major cause of mortality. Tocilizumab, a recombinant humanized monoclonal antibody against human IL-6 receptor, poses a therapeutic option for the treatment of CRS leading to severe acute respiratory syndrome in coronavirus-2 (SARS-CoV-2) infection. Methods We performed a single-center retrospective study to reveal the outcome of COVID-19 patients on tocilizumab and proposed “the Cerrahpasa-PREDICT score”, a new clinical scoring system using clinical and laboratory parameters that would help predicting the 28-day mortality of COVID-19 patients receiving tocilizumab. Results Eighty-seven patients (median age: 59 years) were included of whom 75.8% were male. Tocilizumab use significantly improved clinical and laboratory parameters. The 28-day mortality rate on tocilizumab was 16.1%. The Cerrahpasa-PREDICT score, consisting of platelet counts, procalcitonin, D-dimer levels, SO2R and the time from symptom onset to tocilizumab administration had a positive predictive value of 94.5% and negative predictive value of 92.9% for anticipating 28-day mortality. Conclusions Severe COVID-19 should closely be monitored for the signs of hyperinflammation. We showed that administration of tocilizumab early in the course of the disease (prior to ICU admission) resulted in a favorable outcome. Close monitoring usually aids identifying patients who would benefit from tocilizumab. In this regard, the Cerrahpasa-PREDICT score might serve as a practical tool for estimating the 28-day mortality in COVID-19 patients who received tocilizumab and would facilitate timely recognition of fatal cases to be evaluated for other therapeutic options.

Introduction: the aim of this was to describe the predictors of mortality related to COVID-19 infection and to evaluate the association between overweight, obesity, and clinical outcomes of COVID-19. Methods: we included the patients >18 years of age, with at least one positive SARS-CoV-2 reverse transcriptase-polymerase chain reaction. Patients were grouped according to body mass index values as normal weight = 35 kg/m(2) (Group D). Mortality, clinical outcomes, laboratory parameters, and comorbidities were compared among 4 groups. Results: there was no significant difference among study groups in terms of mortality. Noninvasive mechanical ventilation requirement was higher in group B and D than group A, while it was higher in Group D than Group C (Group B vs. Group A [p = 0.017], Group D vs. Group A [p = 0.001], and Group D vs. Group C [p = 0.016]). Lung involvement was less common in Group A, and presence of hypoxia was more common in Group D (Group B vs. Group A [p = 0.025], Group D vs. Group A [p < 0.001], Group D vs. Group B [p = 0.006], and Group D vs. Group C [p = 0.014]). The hospitalization rate was lower in Group A than in the other groups; in addition, patients in Group D have the highest rate of hospitalization (Group B vs. Group A [p < 0.001], Group C vs. Group A [p < 0.001], Group D vs. Group A [p < 0.001], Group D vs. Group B [p < 0.001], and Group D vs. Group C [p = 0.010]). Conclusion: COVID-19 patients with overweight and obesity presented with more severe clinical findings. Health-care providers should take into account that people living with overweight and obesity are at higher risk for COVID-19 and its complications., European Association for the Study of Obesity

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.

Candida auris, draws attention as a new emerging antifungal resistant pathogen, leading to healthcare-associated infections and outbreaks. This is the first report of C. auris fungemia in a 81-year-old patient, confirmed by sequential analysis, from Turkey. Although the source of the isolate could not be identified, its spread in the hospital has been taken under control by effective infection control measures.

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

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.

During infection, the human immunodeficiency virus type 1 (HIV-1) manipulates host cell mechanisms to its advantage, thereby controlling its replication or latency, and evading immune responses. Sumoylation is an essential post-translational modification that controls vital cellular activities including proliferation, stemness, or anti-viral immunity. SUMO peptides oppose pathogen replication and mediate interferon-dependent anti-viral activities. In turn, several viruses and bacteria attack sumoylation to disarm host immune responses. Here, we show that HIV-1 impairs cellular sumoylation and targets the host SUMO E1–activating enzyme. HIV-1 expression in cultured HEK293 cells or in CD4+ Jurkat T lymphocytes diminishes sumoylation by both SUMO paralogs, SUMO1 and SUMO2/3. HIV-1 causes a sharp and specific decline in UBA2 protein levels, a subunit of the heterodimeric SUMO E1 enzyme, which likely serves to reduce the efficiency of global protein sumoylation. Furthermore, HIV-1–infected individuals display a significant reduction in total leukocyte sumoylation that is uncoupled from HIV-induced cytopenia. Because sumoylation is vital for immune function, T-cell expansion and activity, loss of sumoylation during HIV disease may contribute to immune system deterioration in patients.

Entecavir (ETV) and tenofovir disoproxil fumarat (TDF) are the two first-line therapies recommended in the treatment of chronic hepatitis B because of having potent antiviral effect and high genetic barriers against resistance. We aimed to compare efficacy of these drugs and to evaluate predictors of viral suppression.This multicenter retrospective study was conducted in nucleos(t)ide analogue-naive chronic hepatitis B (CHB) patients from different 6 centers.Of the 252 patients, 166 received ETV and 86 TDF. The two groups were similar in terms of age, gender, baseline ALT levels and fibrosis scores. ETV had significantly higher baseline HBV DNA, histological activity index and lower hepatitis B early antigen (HBeAg) seropositivity. Treatment duration was longer in ETV group (P0.001). In univariate analysis, undetectable HBV DNA and ALT normalization rates were detected significantly higher in ETV groups (P0.001 and 0.049, respectively). There was no significant difference between groups in terms of HBeAg seroconversion, virological breakthrough, time to virological breakthrough and time to ALT normalization. Entecavir was more effective in reducing HBV DNA levels at the 3rd, 6th and 12th months of the treatment (P=0.06, 0.021 and 0.012, respectively). However, multivariate Cox regression analysis indicated that TDF therapy compared to ETV had an increased probability of achieving complete viral suppression (HR=1, 66; 95% CI 1.21-2.33; P=0.010). Hepatitis B surface antigen (HBsAg) seroconversion was occurred in only one patient in ETV group.ETV leads to an early response on HBV DNA decline in the first year of the treatment. However, TDF is more successful than entecavir in achieving virological suppression.

The present guideline updates the Turkish recommendations for the screening, diagnosis and management of Hepatitis C virus (HCV) infection prepared by the Turkish Association for the Study of the Liver (TASL) and Viral Hepatitis Society (VHS). The aim of this guidance was to provide updates recommendations to physicians, who are interested in HCV care on the optimal screening, diagnosis and pre-treatment management for patients with HCV infection in Turkey. These recommendations, produced by panel experts, were aimed to addresses the management issues ranging from diagnosis and linkage to care, to the optimal treatment regimen in patients with HCV infection. Recommendations are based on evidence and opinions of more than 70% of the panelists. This guidance is supported by the memberships of two societies and not by pharmaceutical companies. This guidance will be updated frequently as new data become available.

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.

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

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.

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.

The conflict in Syria is a big humanitarian emergency. More than 200,000 Syrians have been killed, with more than half of the population either having been displaced or having immigrated. Healthcare has been interrupted due to the destruction of facilities, a lack of medical staff, and a critical shortage of life-saving medications. It produced suitable conditions leading to the re-emergence of tuberculosis, cutaneous leishmaniasis, polio, and measles. Lebanon and Jordan reported increased rates of tuberculosis among Syrian refugees. Cutaneous leishmaniasis outbreaks were noted not only in Syria but also in Turkey, Jordan, and Lebanon. After a polio-free 15 years, Syria reported a polio outbreak. Ongoing measles outbreaks in the region was accelerated by the conflict. Iraq declared a cholera outbreak among the Syrian refugees. The healthcare facilities of the countries hosting immigrants, mainly Turkey, Lebanon, Jordan, Iraq, and Egypt, are overburdened. The majority of the immigrants live in crowded and unsanitary conditions. Infectious diseases are big challenges for Syria and for the countries hosting immigrants. More structured support from international organizations is needed for the prevention, control, diagnosis, and treatment of infectious diseases.

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.

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.

Mete, Bilgul/0000-0001-9091-6087 WOS:000490537600010 PubMed ID: 31580559 Objective: Late presentation of the patients with human immunodeficiency virus (HIV) infection is associated with less favourable treatment responses, more accelerated clinical progression, and a higher mortality risk. Although HIV prevalence is low in Turkey, it is steadily increasing and the information about late presentation among HIV-positives is limited. We aimed to analyze the status of late presentation among HIV-positive patients in Turkey. Methods: All newly diagnosed HIV/AIDS patients from 2003 to 2016 were enrolled in this study by five dedicated centres in Istanbul, Turkey. Demographic data, CD4+ counts, and HIV RNA were collected from medical records and were transferred to a HIV database system. Late presentation was defined as presentation for care with a CD4 count

This consensus report includes expert opinions and recommendations regarding the screening, and if necessary, the follow-up, prophylaxis, and treatment of hepatitis B before the treatment in patients who will undergo immunosuppressive therapy due to the risk of hepatitis B reactivation emergency. To increase awareness regarding the risk of hepatitis B reactivation in immunosuppressive patients, academicians from several university health research and training centers across Turkey came together and discussed the importance of the subject, current status, and issues in accordance with the current literature data and presented solutions.

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

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