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Figen Sarıgül Yıldırım,1 Aslıhan Candevir,2 Sıla Akhan,3 Selçuk Kaya,4 Mehmet Çabalak,5 Gülden Ersöz,6 Dilara İnan,7 Nurgül Ceren,8 İlkay Karaoğlan,9 Tuba Damar Çakırca,10 Şafak Özer Balin,11 Sevil Alkan,12 Özlem Kandemir,6 Ülkü Üser,13 Oğuz Karabay,14 Mustafa Kemal Çelen15 1Antalya Life Hospital, Department of Infectious Diseases and Clinical Microbiology, Antalya, Turkey; 2Cukurova University, Medical Faculty, Department of Infectious Diseases and Clinical Microbiology, Adana, Turkey; 3Kocaeli Üniversity, Medical Faculty, Department of Infectious Diseases and Clinical Microbiology, Kocaeli, Turkey; 4Karadeniz Teknik University, Medical Faculty, Department of Infectious Diseases and Clinical Microbiology, Trabzon, Turkey; 5Mustafa Kemal University Medical Faculty, Department of Infectious Diseases and Clinical Microbiology, Hatay, Turkey; 6Mersin University, Medical Faculty, Department of Infectious Diseases and Clinical Microbiology, Mersin, Turkey; 7Akdeniz University Medical Faculty, Department of Infectious Diseases and Clinical Microbiology, Antalya, Turkey; 8Health Science University, Haydarpaşa Numune Education and Research Hospital, Department of Infectious Diseases and Clinical Microbiology, İstanbul, Turkey; 9Gaziantep University, Medical Faculty, Department of Infectious Diseases and Clinical Microbiology, Gaziantep, Turkey; 10Health Science University, Şanlıurfa Numune Education and Research Hospital, Department of Infectious Diseases and Clinical Microbiology, Şanlıurfa, Turkey; 11Fırat University Medical Faculty, Department of Infectious Diseases and Clinical Microbiology, Elazığ, Turkey; 12Çanakkale 18 Mart University, Medical Faculty, Department of Infectious Diseases and Clinical Microbiology, Çanakkale, Turkey; 13Health Science University, Antalya Education and Research Hospital, Department of Infectious Diseases and Clinical Microbiology, Antalya, Turkey; 14Sakarya University Medical Faculty, Department of Infectious Diseases and Clinical Microbiology, Hatay, Turkey; 15Dicle University, Medical Faculty, Department of Infectious Diseases and Clinical Microbiology, Diyarbakır, TurkeyCorrespondence: Figen Sarıgül Yıldırım, Antalya Life Hospital, Department of Infectious Diseases and Clinical Microbiology, Antalya, Turkey, Tel +90 532 473 44 46, Email drfigensarigul@yahoo.com.trBackground: Rapid initiation of antiretroviral therapy (ART) reduces the transmission of HIV infection in the community. This study aimed to determine whether rapid ART initiation is effective compared to standard ART treatment in our country.Methods: Patients were grouped based on time to treatment initiation. HIV RNA levels, CD+4 T cell count, CD4/CD8 ratio, and ART regimens were recorded at baseline and follow-up visits for 12 months.Results: There were 368-ART naive adults (treatment initiated at the time of HIV diagnosis; 143 on the first day, 48 on the second-seventh day, and 177 after the seventh day). Although virological suppression rates at 12th months were higher in all groups, over 90% on average, there were no statistically significant differences in HIV-1 RNA suppression rates, CD+4 T cell count, and CD4/CD8 ratio normalization in the studied months but in multivariate logistic regression analysis; showed a significant correlation between both virological and immunological response and those with CD4+ T < 350 cells/mL at 12th month in total patients.Conclusion: Our findings support the broader application of recommendations for rapid ART initiation in HIV patients.Keywords: HIV, ART, antiretroviral, rapid start

Background and Aim: This study aimed to define the relapse frequency and risk determinants in chronic hepatitis B (CHB) patients who discontinued nucleoside analog (NA) treatment, were HBeAg-negative, and had achieved both a virological and biochemical response., Materials and Methods: This retrospective cohort study reviewed patients with HBeAg-negative CHB who received antiviral therapy for at least 65 months between January 1, 2013, and December 31, 2020. These patients discontinued treatment after demonstrating a biochemical and virological response and were evaluated at 6, 12, and 24 months post-treatment discontinuation., Results: Sixty-seven patients with CHB who received NA therapy for at least 65 months, discontinued treatment, and had undetectable HBV DNA and normal ALT values were evaluated. After cessation of NA therapy, a relapse was observed in 38 patients (56.7%). The relapse rate was 71.0% in patients treated with tenofovir disoproxil fumarate (TDF) as the last NA type and 37.9% in patients treated with entecavir (ETV) (p=0.017). The cutoff value for the best estimate of age for predicting relapse was 42 years. The relapse rate was 69.2% in patients aged ≥42 years and 39.2% in patients aged <42 years (p=0.007). The relapse rate was 51.3% in patients with a pre-treatment fibrosis score of 2, 56.0% in those with a fibrosis score of 3, and 100% in those with a fibrosis score of 4 (p=0.089)., Conclusion: Among HBeAg-negative CHB patients who achieved a virological and biochemical response to long-term antiviral therapy, those aged 42 years and older, those with high fibrosis scores before treatment, and those who used TDF before treatment cessation should be closely monitored for relapse, especially in the first 12 months after stopping NA treatment., Competing Interests: The authors have no conflict of interest to declare.

Introduction: The results from 2 phase 3 studies, through 2 years, in chronic hepatitis B infection showed tenofovir alafenamide (TAF) had similar efficacy to tenofovir disoproxil fumarate (TDF) with superior renal and bone safety. We report updated results through 5 years., Methods: Patients with HBeAg-negative or HBeAg-positive chronic hepatitis B infection with or without compensated cirrhosis were randomized (2:1) to TAF 25 mg or TDF 300 mg once daily in double-blind (DB) fashion for up to 3 years, followed by open-label (OL) TAF up to 8 years. Efficacy (antiviral, biochemical, and serologic), resistance (deep sequencing of polymerase/reverse transcriptase and phenotyping), and safety, including renal and bone parameters, were evaluated by pooled analyses., Results: Of 1,298 randomized and treated patients, 866 receiving TAF (DB and OL) and 432 receiving TDF with rollover to OL TAF at year 2 (n = 180; TDF→TAF3y) or year 3 (n = 202; TDF→TAF2y) were included. Fifty (4%) TDF patients who discontinued during DB were excluded. At year 5, 85%, 83%, and 90% achieved HBV DNA <29 IU/mL (missing = failure) in the TAF, TDF→TAF3y, and TDF→TAF2y groups, respectively; no patient developed TAF or TDF resistance. Median estimated glomerular filtration rate (by using Cockcroft-Gault) declined <2.5 mL/min, and mean declines of <1% in hip and spine bone mineral density were seen at year 5 in the TAF group; patients in the TDF→TAF groups had improvements in these parameters at year 5 after switching to OL TAF., Discussion: Long-term TAF treatment resulted in high rates of viral suppression, no resistance, and favorable renal and bone safety., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.)

Background & Aims: Until recently, pegylated interferon-alfa-2a (PEG-IFNa) therapy was the only treatment option for patients infected with hepatitis D virus (HDV). Treatment with PEG-IFNa with or without tenofovir disoproxil fumarate (TDF) for 96 weeks resulted in HDV RNA suppression in 44% of patients at the end of therapy but did not prevent short-term relapses within 24 weeks. The virological and clinical long-term effects after prolonged PEG-IFNa-based treatment of hepatitis D are unknown., Methods: In the HIDIT-II study patients (including 40% with liver cirrhosis) received 180 μg PEG-IFNa weekly plus 300 mg TDF once daily (n = 59) or 180 μg PEG-IFNa weekly plus placebo (n = 61) for 96 weeks. Patients were followed until week 356 (5 years after end of therapy)., Results: Until the end of follow-up, 16 (13%) patients developed liver-related complications (PEG-IFNa + TDF, n = 5 vs PEG-IFNa + placebo, n = 11; p = .179). Achieving HDV suppression at week 96 was associated with decreased long-term risk for the development of hepatocellular carcinoma (p = .04) and hepatic decompensation (p = .009). Including complications irrespective of PEG-IFNa retreatment status, the number of patients developing serious complications was similar with (3/18) and without retreatment with PEG-IFNa (16/102, p > .999) but was associated with a higher chance of HDV-RNA suppression (p = .024, odds ratio 3.9 [1.3-12])., Conclusions: Liver-related clinical events were infrequent and occurred less frequently in patients with virological responses to PEG-IFNa treatment. PEG-IFNa treatment should be recommended to HDV-infected patients until alternative therapies become available. Retreatment with PEG-IFNa should be considered for patients with inadequate response to the first course of treatment., Clinical Trial Registration: NCT00932971., (© 2023 The Authors. Liver International published by John Wiley & Sons Ltd.)

Background & Aims: Infection with the hepatitis D virus (HDV) causes the most severe form of viral hepatitis with a high risk to develop clinical complications of liver disease. In addition, hepatitis delta has been shown to be associated with worse patient-reported outcomes. Until recently, only pegylated interferon alfa could be used to treat hepatitis delta., Methods: Here, we investigated quality of life (QOL) as assessed by the Short Form 36 Health Survey (SF-36) in patients undergoing antiviral therapy with pegylated interferon alfa (PEG-IFNa-2a)-based treatment in the HIDIT-II trial. HIDIT-II was a randomized prospective trial exploring PEG-IFNa-2a with tenofovir disoproxil (TDF) or placebo for 96 weeks in patients with compensated hepatitis delta. Surveys completed by 83 study participants before, during, and after treatments were available., Results: Overall, we observed a reduced QOL of HDV patients compared with a reference population, both in physical as well as mental scores. Interestingly, PEG-IFNa-2a treatment showed only minor impairment of the QOL during therapy. Moreover, HDV-RNA clearance was not associated with relevant changes in physical or social SF-36 scores, whereas an improvement of fibrosis during treatment was associated with increased QOL. Overall, slight improvements of the QOL scores were observed 24 weeks after the end of treatment as compared with baseline. TDF co-treatment had no influence on QOL., Conclusions: Overall, our findings suggest that PEG-IFNa-2a was reasonably tolerated even over a period of 96 weeks by hepatitis D patients reporting SF-36 questionnaires. Of note, several patients may benefit from PEG-IFNa-2a-based therapies with off-treatment improvements in quality of life., (© 2023 The Authors. Liver International published by John Wiley & Sons Ltd.)

Background and Aim: In chronic hepatitis B infection, antiviral therapy significantly reduces the incidence of complications. This study aimed to present real-life 12-month effectiveness and safety data for TAF., Materials and Methods: This Pythagoras Retrospective Cohort Study included patients from 14 centers in Turkiye. The study presents 12-month results of 480 patients treated with TAF as initial therapy or after switching from another antiviral drug., Results: The study shows treatment of about 78.1% patients with at least one antiviral agent (90.6% tenofovir disoproxil [TDF]). The rate of undetectable HBV DNA increased in both treatment-experienced and naive patients. In TDF-experienced patients, the rate of alanine transaminase (ALT) normalization increased slightly (1.6%) within 12 months, but the change was not statistically significant (p=0.766). Younger age, low albumin, and high body mass index and cholesterol were identified as risk factors for abnormal ALT after 12 months, but no linear relationship was detected. In TDF-experienced patients, renal and bone function indicators showed significant improvement three months after the transition to TAF and remained stable for 12 months., Conclusion: Real-life data demonstrated effective virological and biochemical responses with TAF therapy. After switching to TAF treatment, gains in kidney and bone functions were achieved in the early period., Competing Interests: The authors have no conflict of interest to declare., (© Copyright 2023 by Hepatology Forum.)

Introduction: Human immunodeficiency virus is a chronic infection that attacks the immune system of the human body, particularly CD4 T lymphocytes. Combined antiretroviral therapies are highly effective in virological suppression of human immunodeficiency virus infection. It has been shown that some retroviral therapies have a higher nephrotoxicity potential. As a result of renal injury, serum creatinine increases and the estimated glomerular filtration rate is reduced. The aim of our study was to assess changes in kidney function during a 24-month period in HIV-positive patients who were begun on combined antiretroviral therapy., Material and Methods: A total of 127 HIV-positive patients were enrolled. The patients were divided into five groups; patients who received no therapy were designated as group 1; those who received Dolutegravir/Abacavir/Lamivudine combination as group 2; those who received Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide Fumarate combination as group 3; those who received Emtricitabine/Tenofovir Disoproxil Fumarate/Dolutegravir combination as group 4; and those who received Emtricitabine/Tenofovir Disoproxil Fumarate/Raltegravir combination as group 5. We compared the effects of these drugs on estimated glomerular filtration rate during a 24-month follow-up period., Results: At the 24th month of therapy, a significant difference was observed between the estimated glomerular filtration rate (eGFR) levels of the study groups (P < .001). eGFR level was significantly higher in group 4 compared with groups 1, 2 and 3 (P = .009, P < .001, P < .001, respectively), whereas it was significantly lower in group 5 than groups 1, 2 and 3 (P = .005, P < .001, P < .001, respectively). No significant eGFR difference was found between group 4 and group 5 (P > .05). Serum creatinine level was significantly higher in groups 4 and 5 compared with the other groups (P < .001)., Conclusion: The use of TDF-containing regimens causes renal dysfunction. Therefore, we recommend close monitoring of renal function, especially in patients treated with TDF., (© 2021 John Wiley & Sons Ltd.)

Previous studies detected higher Golgi protein 73 levels in the serum of patients with chronic liver disease. The Beta-2 microglobulin levels were also observed to be higher in patients with chronic hepatitis B infection compared to the inactive carriers and the protein plays an important role in the response to viral infections. The aim of the present study was to assess the liver fibrosis through non-invasive methods in chronic hepatitis B patients. Three groups were included in the study. The first group comprised of the patients who were admitted to the Infectious Diseases and Clinical Microbiology clinic to undergo a liver biopsy, while the second group included the patients who were admitted inactive hepatitis B carriers. The third group comprised the healthy controls. The Golgi p-73 and Beta-2 microglobulin levels in the plasma were determined using the ELISA method. Beta-2 microglobulin level was highest in the patients group and the difference was statistically significant. No significant difference was observed between the carriers group and the group of healthy controls. The Golgi P-73 values were significantly higher in the patients group in comparison to both other groups. However, the mean Golgi p-73 value was also significantly higher in the carrier group compared to the control group. In patients who are followed up with the diagnosis of chronic hepatitis B and who have undergone biopsies as candidates for treatment, the Beta-2 microglobulin and Golgi p-73 values may be important markers since they indicate the extent of the liver damage.

Objective: The aim of this study was to analyze the temporal trends of HIV epidemiology in Turkey from 2011 to 2016., Methods: Thirty-four teams from 28 centers at 17 different cities participated in this retrospective study. Participating centers were asked to complete a structured form containing questions about epidemiologic, demographic and clinical characteristics of patients presented with new HIV diagnosis between 2011 and 2016. Demographic data from all centers (complete or partial) were included in the analyses. For the cascade of care analysis, 15 centers that provided full data from 2011 to 2016 were included. Overall and annual distributions of the data were calculated as percentages and the Chi square test was used to determine temporal changes., Results: A total of 2,953 patients between 2011 and 2016 were included. Overall male to female ratio was 5:1 with a significant increase in the number of male cases from 2011 to 2016 (p<0.001). The highest prevalence was among those aged 25-34 years followed by the 35-44 age bracket. The most common reason for HIV testing was illness (35%). While the frequency of sex among men who have sex with men increased from 16% to 30.6% (p<0.001) over the study period, heterosexual intercourse (53%) was found to be the most common transmission route. Overall, 29% of the cases presented with a CD4 count of >500 cells/mm3 while 46.7% presented with a CD4 T cell count of <350 cells/mm3. Among newly diagnosed cases, 79% were retained in care, and all such cases initiated ART with 73% achieving viral suppression after six months of antiretroviral therapy., Conclusion: The epidemiologic profile of HIV infected individuals is changing rapidly in Turkey with an increasing trend in the number of newly diagnosed people disclosing themselves as MSM. New diagnoses were mostly at a young age. The late diagnosis was found to be a challenging issue. Despite the unavailability of data for the first 90, Turkey is close to the last two steps of 90-90-90 targets., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Hepatitis D is the most severe form of chronic viral hepatitis. Treatment guidelines recommend 1 year of peginterferon alfa, which is effective in 25-30% of patients only. Whether prolonged therapy with peginterferon alfa-2a for 96 weeks and combination therapy with tenofovir disoproxil fumarate (TDF) would increase hepatitis D virus (HDV) RNA suppression is unknown. We aimed to explore whether prolonged treatment of HDV with 96 weeks of peginterferon would increase HDV RNA response rates and reduces post-treatment relapses., Methods: We did two parallel, investigator-initiated, multicentre, double-blind randomised, controlled trials at 14 study sites in Germany, Greece, Romania, and Turkey. Patients with chronic HDV infection and compensated liver disease who were aged 18 years or older were eligible for inclusion. All patients were HBsAg positive for at least 7 months, anti-HDV positive for at least 3 months, and HDV-RNA positive at the local laboratory at the screening visit. Patients were ineligible if alanine aminotransferase levels were higher than ten times above the upper limit of normal and if platelet counts were lower than 90 000 per μL, or if they had received interferon therapy or treatment with a nucleoside and nucleotide analogue within the preceding 6 months. Patients were randomly assigned by blinded stratified block randomisation (1:1) to receive 180 μg of peginterferon alfa-2a weekly plus either TDF (300 mg once daily) or placebo for 96 weeks. The primary endpoint was the percentage of patients with undetectable HDV RNA at the end of treatment assessed by intention to treat. The trials are registered as NCT00932971 and NCT01088659., Findings: Between June 24, 2009, and Feb 28, 2011, we randomly assigned 59 HDV RNA-positive patients to receive peginterferon alfa-2a plus TDF and 61 to receive peginterferon alfa-2a plus placebo, including 48 (40%) patients with cirrhosis to the two treatment groups (23 in the peginterferon alfa-2a plus TDF group and 25 in the peginterferon alfa-2a plus placebo group). The primary endpoint was achieved in 28 (48%) of 59 patients in the peginterferon alfa-2a plus TDF group and in 20 (33%) of 61 patients in the peginterferon alfa-2a plus placebo group (odds ratio 1·84, 95% CI 0·86-3·91, p=0·12). We recorded 944 adverse events (459 in the peginterferon alfa-2a plus TDF group and 485 in the peginterferon alfa-2a plus placebo group). The most common adverse events were haematological, behavioural (eg, fatigue), musculoskeletal, influenza-like syndromes, and psychiatric complaints., Interpretation: Addition of TDF resulted in no significant improvement in HDV RNA response rates at the end of treatment. These findings highlight that alternative treatment options are needed for hepatitis D., Funding: The HepNet Study-House (a project of the German Liver Foundation founded by the German Liver Foundation, the German Ministry for Education and Research, and the German Center for Infectious Disease Research), Hoffmann-La Roche, and Gilead Sciences., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Aim: The aim of this study is to examine the role of the mean platelet volume (MPV), platelet distribution width (PDW), platelet/lymphocyte ratio (PLR), and platelet values for predicting mortality in patients with sepsis., Materials and Methods: This is a retrospective study, involving patients 18 years and above who were diagnosed with sepsis. Blood samples were analyzed for platelets characteristics (counts, MPV, PDW, and PLR). The patients were separated into two groups namely the survivors and deceased. The two groups' MPV, PDW, PLR, and platelet counts which were considered to have an effect on mortality, were compared., Results: Three hundred and thirty patients who were diagnosed with sepsis in our emergency department and complying with the study participation criteria were studied retrospectively. Comparison of the MPV, PDW, PLR, and platelet counts of the deceased and survivors showed that the MPV, PDW, and PLR were higher in the deceased while the platelet counts were higher in the survivors., Conclusion: The low number of platelets in patients with sepsis at the moment of application and the high PDW and PLR values are valuable for predicting a high mortality., Competing Interests: There are no conflicts of interest

Aim: To make efficacy and safety comparison of telbivudine-raodmap and tenofovir-roadmap in hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (CHB) patients., Methods: This was the first prospective, randomised, two-arm, open-label, non-inferiority study in HBeAg-negative CHB patients that compared telbivudine and tenofovir administered as per roadmap concept. Patients were treated up to 24 wk and, depending on virologic response, continued the same therapy or received add-on therapy up to 104 wk. Eligible patients received an additional 52 wk of treatment in the extension period ( i.e ., up to 156 wk). Patients who developed virologic breakthrough (VB) while on monotherapy also received add-on therapy. The primary efficacy endpoint was the rate of patients achieving hepatitis B virus (HBV) DNA < 300 copies/mL at week 52. Secondary efficacy endpoints included the rates of HBV DNA < 300 and < 169 copies/mL, HBV DNA change from baseline, alanine aminotransferase normalisation, hepatitis B surface antigen (HBsAg) loss, HBsAg seroconversion, VB, and emergence of resistance at various timepoints throughout the study. Safety and estimated glomerular filtration rate (eGFR) were also analysed., Results: A total of 241 patients were randomised. Non-inferiority of telbivudine arm to tenofovir arm was demonstrated at week 52 (± 7 d window), with over 91% of patients in each treatment arm achieving HBV DNA level < 300 copies/mL. Both arms were similar in terms of key secondary efficacy variables at weeks 104 and 156. The percentage of patients achieving HBV DNA < 300 copies/mL remained high and was similar in the telbivudine and tenofovir arms at both weeks 104 and 156. Over 82% of patients in both arms achieved alanine aminotransferase normalisation at week 52, and this percentage remained high at weeks 104 and 156. Telbivudine treatment progressively reduced serum HBsAg levels from baseline while no change was reported in quantitative HBsAg during therapy with tenofovir. Both treaments showed acceptable safety profiles. The telbivudine arm showed eGFR improvement unlike the tenofovir arm., Conclusion: Efficacy was shown for both telbivudine-roadmap and tenofovir-roadmap regimens in HBeAg-negative CHB patients over 156 wk. Telbivudine arm was associated with renal improvement., Competing Interests: Conflict-of-interest statement: Krastev Z received fees for serving as a member of advisory board of Gilead, as well as research funding from Abbvie, Applied Clinical Pharmacology Services, Centocor, Comac Medical, Gilead, GSK, Idenix, Johnson and Johnson, Millennium Pharmaceuticals, MSD, Norgine, Novartis, Roche, Receptos and Schwabe; Petrova D received research funding from Aventis, Centocor, Gilead, GSK, Idenix, Johnson and Johnson, Norgine, Novartis and Roche; Kotzev I received lecture fees from Novartis; Celen MK has nothing to declare; Mendelson M, Chandra R and Hamed K are employees of Novartis Pharmaceuticals Corporation; Pandey P is an employee of Novartis Healthcare Pvt. Ltd.

Objective: Neuroimaging abnormalities in central nervous system (CNS) brucellosis are not well documented. The purpose of this study was to evaluate the prevalence of imaging abnormalities in neurobrucellosis and to identify factors associated with leptomeningeal and basal enhancement, which frequently results in unfavorable outcomes., Methods: Istanbul-3 study evaluated 263 adult patients with CNS brucellosis from 26 referral centers and reviewed their 242 magnetic resonance imaging (MRI) and 226 computerized tomography (CT) scans of the brain., Results: A normal CT or MRI scan was seen in 143 of 263 patients (54.3 %). Abnormal imaging findings were grouped into the following four categories: (a) inflammatory findings: leptomeningeal involvements (44), basal meningeal enhancements (30), cranial nerve involvements (14), spinal nerve roots enhancement (8), brain abscesses (7), granulomas (6), and arachnoiditis (4). (b) White-matter involvement: white-matter involvement (32) with or without demyelinating lesions (7). (c) Vascular involvement: vascular involvement (42) mostly with chronic cerebral ischemic changes (37). (d) Hydrocephalus/cerebral edema: hydrocephalus (20) and brain edema (40). On multivariate logistic regression analysis duration of symptoms since the onset (OR 1.007; 95 % CI 1-28, p = 0.01), polyneuropathy and radiculopathy (OR 5.4; 95 % CI 1.002-1.013, p = 0.044), cerebrospinal fluid (CSF)/serum glucose rate (OR 0.001; 95 % CI 000-0.067, p = 0.001), and CSF protein (OR 2.5; 95 % CI 2.3-2.7, p = 0.0001) were associated with diffuse inflammation., Conclusions: In this study, 45 % of neurobrucellosis patients had abnormal neuroimaging findings. The duration of symptoms, polyneuropathy and radiculopathy, high CSF protein level, and low CSF/serum glucose rate were associated with inflammatory findings on imaging analyses.

HIV-1 replication is rapid and highly error-prone. Transmission of a drug-resistant HIV-1 strain is possible and occurs within the HIV-1-infected population. In this study, we aimed to determine the prevalence of transmitted drug resistance mutations (TDRMs) in 1,306 newly diagnosed untreated HIV-1-infected patients from 21 cities across six regions of Turkey between 2010 and 2015. TDRMs were identified according to the criteria provided by the World Health Organization's 2009 list of surveillance drug resistance mutations. The HIV-1 TDRM prevalence was 10.1% (133/1,306) in Turkey. Primary drug resistance mutations (K65R, M184V) and thymidine analogue-associated mutations (TAMs) were evaluated together as nucleos(t)ide reverse transcriptase inhibitor (NRTI) mutations. NRTI TDRMs were found in 8.1% (107/1,306) of patients. However, TAMs were divided into three categories and M41L, L210W, and T215Y mutations were found for TAM1 in 97 (7.4%) patients, D67N, K70R, K219E/Q/N/R, T215F, and T215C/D/S mutations were detected for TAM2 in 52 (3.9%) patients, and M41L + K219N and M41L + T215C/D/S mutations were detected for the TAM1 + TAM2 profile in 22 (1.7%) patients, respectively. Nonnucleoside reverse transcriptase inhibitor-associated TDRMs were detected in 3.3% (44/1,306) of patients (L100I, K101E/P, K103N/S, V179F, Y188H/L/M, Y181I/C, and G190A/E/S) and TDRMs to protease inhibitors were detected in 2.3% (30/1,306) of patients (M46L, I50V, I54V, Q58E, L76V, V82A/C/L/T, N83D, I84V, and L90M). In conclusion, long-term and large-scale monitoring of regional levels of HIV-1 TDRMs informs treatment guidelines and provides feedback on the success of HIV-1 prevention and treatment efforts.

Introduction: The rates of multiresistant bacteria colonization or infection (MRB+) development in intensive care units are very high. The aim of this study was to determine the possible association between the risk of development of nosocomial infections and increased daily nurse workload due to understaffing in intensive care unit., Methods: We included 168 patients. Intensity of workload and applied procedures to patients were scored with the Project de Recherché en Nursing and the Omega scores, respectively. The criteria used for infections were those defined by the Centers for Disease Control., Results: Of the 168 patients, 91 (54.2%) were female and 77 (45.8%) were male patients. The mean age of female and male was 64.9 ± 6.2 years and 63.1 ± 11.9 years, respectively. The mean duration of hospitalization in intensive care unit was 18.4 ± 6.1 days. Multiresistant bacteria were isolated from cultures of 39 (23.2%) patients. The development of MRB+ infection was correlated with length of stay, Omega 1, Omega 2, Omega 3, Total Omega, daily PRN, and Total PRN (p < 0.05). There was no correlation between development of MRB+ infection with gender, age and APACHE-II scores (p > 0.05)., Conclusion: The risk of nosocomial infection development in an intensive care unit is directly correlated with increased nurse workload, applied intervention, and length of stay. Understaffing in the intensive care unit is an important health problem that especially affects care-needing patients. Nosocomial infection development has laid a heavy burden on the economy of many countries. To control nosocomial infection development in the intensive care unit, nurse workload, staffing level, and working conditions must be arranged., (Copyright © 2014 Sociedade Brasileira de Anestesiologia. Published by Elsevier Editora Ltda. All rights reserved.)

Brucellosis is a zoonotic disease that primarily affects the reticuloendothelial system. But, the extent of liver damage in due course of the disease is unclear. This study included 325 brucellosis patients with significant hepatobiliary involvement identified with microbiological analyses from 30 centers between 2000 and 2013. The patients with ≥5 times of the upper limit of normal for aminotransferases, total bilirubin level ≥2 mg/dl or local liver lesions were enrolled. Clinical hepatitis was detected in 284 patients (87.3 %) and cholestasis was detected in 215 (66.1 %) patients. Fatigue (91 %), fever (86 %), sweating (83 %), arthralgia (79 %), and lack of appetite (79 %) were the major symptoms. Laboratory tests showed anemia in 169 (52 %), thrombocytopenia in 117 (36 %), leukopenia in 81 (25 %), pancytopenia in 42 (13 %), and leukocytosis in 20 (6 %) patients. The most commonly used antibiotic combinations were doxycycline plus an aminoglycoside (n = 73), doxycycline plus rifampicin (n = 71), doxycycline plus rifampicin and an aminoglycoside (n = 27). The duration of ALT normalization differed significantly in three treatment groups (p < 0.001). The use of doxycycline and an aminoglycoside in clinical hepatitis showed better results compared to doxycycline and rifampicin or rifampicin, aminoglycoside, doxycycline regimens (p < 0.05). However, the length of hospital stay did not differ significantly between these three combinations (p > 0.05). During the follow-up, treatment failure occurred in four patients (1 %) and relapse was seen in three patients (0.9 %). Mortality was not observed. Hepatobiliary involvement in brucellosis has a benign course with suitable antibiotics and the use of doxycycline and an aminoglycoside regimen seems a better strategy in select patients.

Entecavir is a guanosine analogue with activity against hepatitis B virus. The aim of this 4-year trial was to evaluate entecavir treatment in nucleos(t)ide-naïve HBeAg-positive chronic hepatitis B patients. Forty-nine patients received entecavir and nine of them withdrew from the trial at the end of week 96. The initial mean value of alanine aminotransferase was 79.4 +/- 41.5 IU/L, and at the end of the 4-year study period, 90% of patients had alanine aminotransferase values within the normal range. At week 96, 91.7% of patients had HBV DNA < 300 copies; at month 48, 90% of patients had HBV DNA < 50 IU/mL. HBeAg loss was recorded in 7.1% of patients at week 96 and in 12.5% at month 48. The rate of HBeAg seroconversion was 4.8% at week 96 and 7.5% at month 48. The rate of HBsAg seroconversion was 2.1% at week 96 and 2.5% at month 48. Entecavir as a potent and safe agent leading to continuous viral suppression proved to be safe and well tolerated therapy.

Aim: To evaluate the effects of tenofovir disoproxil fumarate (TDF) use during late pregnancy to reduce hepatitis B virus (HBV) transmission in highly viremic mothers., Methods: This retrospective study included 45 pregnant patients with hepatitis B e antigen (+) chronic hepatitis B and HBV DNA levels > 10⁷ copies/mL who received TDF 300 mg/d from week 18 to 27 of gestation (n = 21). Untreated pregnant patients served as controls (n = 24). All infants received 200 IU of hepatitis B immune globulin (HBIG) within 24 h postpartum and 20 μg of recombinant HBV vaccine at 4, 8, and 24 wk. Perinatal transmission rate was determined by hepatitis B surface antigen and HBV DNA results in infants at week 28., Results: At week 28, none of the infants of TDF-treated mothers had immunoprophylaxis failure, whereas 2 (8.3 %) of the infants of control mothers had immunoprophylaxis failure (P = 0.022). There were no differences between the groups in terms of adverse events in mothers or congenital deformities, gestational age, height, or weight in infants. At postpartum week 28, significantly more TDF-treated mothers had levels of HBV DNA < 250 copies/mL and normalized alanine aminotransferase compared with controls (62% vs none, P < 0.001; 82% vs 61%, P = 0.012, respectively)., Conclusion: TDF therapy during the second or third trimester reduced perinatal transmission rates of HBV and no adverse events were observed in mothers or infants.

Introduction: H1N1 Influenza made a great impact a worldwide, as well as in Turkey, in 2009. Clinical experiences have shown that it had a more serious prognosis in pregnant women. In this report, we summarize the cases of 16 pregnant women with H1N1 Influenza., Methodology: The study included 16 pregnant women hospitalized in Dicle University Hospital with complaints of fever, sore throat, cough and myalgia between October and December 2009. The diagnosis of pandemic H1N1 Influenza was confirmed on nasopharyngeal specimens using real-time reverse-transcriptase polymerase chain reaction (RT-PCR) in all patients. Patients who had the same complaints but were not diagnosed as H1N1 Influenza were excluded. The epidemiological, clinical, diagnostic, and outcome features of the patients were recorded., Results: The median age of the patients was 27 years (range 18-41 years). The mean gestational age was 25.4 weeks (range 5-38 weeks). Two cases were twin pregnancy. Two cases had co-morbid diseases including asthma and anemia. The most frequent admission symptoms were fever in 13 cases (81%), cough in 12 cases (75%) and dyspnea in 6 cases (37,5%). Antiviral treatment (oseltamivir 75 mg p.o. bid) was applied in 15 cases. Four cases needed intensive care monitoring and two of them died (12.5%) because of severe respiratory insufficiency., Conclusion: Patients with late gestational age, the presence of co-morbid disease, and multiple pregnancy have poor prognosis. Immediate intervention with antiviral treatment is associated with reduced severity of the disease and duration of hospital stay.

No data on whether brucellar meningitis or meningoencephalitis can be treated with oral antibiotics or whether an intravenous extended-spectrum cephalosporin, namely, ceftriaxone, which does not accumulate in phagocytes, should be added to the regimen exist in the literature. The aim of a study conducted in Istanbul, Turkey, was to compare the efficacy and tolerability of ceftriaxone-based antibiotic treatment regimens with those of an oral treatment protocol in patients with these conditions. This retrospective study enrolled 215 adult patients in 28 health care institutions from four different countries. The first protocol (P1) comprised ceftriaxone, rifampin, and doxycycline. The second protocol (P2) consisted of trimethoprim-sulfamethoxazole, rifampin, and doxycycline. In the third protocol (P3), the patients started with P1 and transferred to P2 when ceftriaxone was stopped. The treatment period was shorter with the regimens which included ceftriaxone (4.40 ± 2.47 months in P1, 6.52 ± 4.15 months in P2, and 5.18 ± 2.27 months in P3) (P = 0.002). In seven patients, therapy was modified due to antibiotic side effects. When these cases were excluded, therapeutic failure did not differ significantly between ceftriaxone-based regimens (n = 5/166, 3.0%) and the oral therapy (n = 4/42, 9.5%) (P = 0.084). The efficacy of the ceftriaxone-based regimens was found to be better (n = 6/166 [3.6%] versus n = 6/42 [14.3%]; P = 0.017) when a composite negative outcome (CNO; relapse plus therapeutic failure) was considered. Accordingly, CNO was greatest in P2 (14.3%, n = 6/42) compared to P1 (2.6%, n = 3/117) and P3 (6.1%, n = 3/49) (P = 0.020). Seemingly, ceftriaxone-based regimens are more successful and require shorter therapy than the oral treatment protocol.

Osteomyelitis in adolescents is a serious disease with the potential for lifelong disability. The key to successful management is early diagnosis, including bone sampling for microbiological and pathological examination to allow targeted and long-lasting antibiotic therapy. Staphylococcus aureus is the most frequently isolated microorganism in these patients. Methicillin-resistant S. aureus (MRSA) is usually considered a nosocomial pathogen, but increasingly it is acquired in the community. We present a case of acute osteomyelitis caused by community-associated MRSA (CA-MRSA) who had never been hospitalized and had no other known risk factors for MRSA. The changing epidemiology of MRSA became evident when infections occurred in previously healthy patients without established risk factors. MRSA infections have been increasingly reported in pediatric patients, but they are uncommon in adults. Skin and soft tissue infections remain the most common manifestations of CA-MRSA infections. Glycopeptides can be used as initial therapy and oral trimetoprim-sulfamethoxazole as sequential therapy for these patients.

Infectious Mononucleosis (IM), a benign lymphoproliferative disease, is the best known clinical syndrome caused by Epstein-Barr Virus (EBV). It usually resolves over a period of weeks or months without sequelae but may occasionally be complicated by a wide variety of neurologic, hematologic, hepatic, respiratory, and psychological complications. In this report we describe a patient with acute hepatitis following EBV-IM in a previously healthy woman. A 26-year-old woman who presented with fever, generalized weakness, nausea, sore throat, yellowing of skin, and a generalized skin rash was admitted to our clinic. Tonsillar enlargement, pharyngeal erythema, palatal petechiae, lymphadenopathy, and jaundice were noted. Significant atypical lymphocytes ( > 10%) were seen on the peripheral blood smear. Liver function tests such as ALT: 303 U/L, AST: 172 U/L, ALP: 193 U/L and total bilirubin: 7.3 mg/dl were elevated. Serological tests for EBV infection were consistent with acute infection (EBV virus capsid antigen was reactive with IgM and IgG antibodies). The Monospot test was also positive. On the seventh day, liver function tests and bilirubin had risen to peak level and platelets were decreased. The patient was managed supportively and her critical condition improved and was finally stabilized. Although the prognosis for IM is very favorable, a variety of acute complications may occur.

Objective: Treatment of perianal abscesses requires prompt surgical drainage and antimicrobial therapy. However, we should encourage the selective use of antimicrobial agents on a case-by-case basis, especially because there is no evidence that uncomplicated perianal abscesses can be safely treated only with drainage. For this reason, it is important to identify the causative organisms; therefore, we accessed the microbiological analysis of these patients., Patients and Methods: In this study, 81 consecutive adult patients with perianal abscesses, who presented at a university hospital in Diyarbakir from January 2004 to December 2006, were included. Clinical and laboratory data, and results of microbiological analysis were recorded., Results: All specimens, except seven, yielded bacterial growth. Escherichia coli, Bacteriodes spp., coagulase-negative Staphylococci, and Staphylococcus aureus were the most common isolated organisms., Conclusion: In contrast to other investigators, this study demonstrated that aerobic organisms are the predominant isolates in these infections.

Objective: the different clinical and laboratory features and response to treatment of patients with acute brucellar epididymo-orchitis (BEO) reporting to the reference hospital in Southeastern Anatolia of Turkey., Material and Methods: in this study, 27 male patients with brucellosis, who presented with epididymitis or epididymo-orchitis (EO) at the university hospital in Diyarbakir from 1998 to 2006, were included. They were compared with the other male patients. Positive blood culture or high agglutination titers of > 1/160 and positive clinical manifestations of brucellosis were the main criteria for diagnosing brucellosis., Results: fourteen patients had unilateral EO. Leukocytosis was present in 10 patients; all of them had initial agglutination titers of > 1/160 and 10 patients had a positive blood culture. All patients received combined therapy with streptomycin for the first 21 days (or oral rifampicin for 6-8 weeks) with doxycycline or tetracycline for 6-8 weeks. All showed improvement, fever subsided in 3-7 days, and the scrotal enlargement and tenderness regressed. Only one patient had a relapse within one year., Conclusion: in brucellosis-endemic areas, clinicians encountering EO should consider the likelihood of brucellosis. In this study, young age was the most common risk factor, and leukocytosis and high CRP level were the most common laboratory findings. Most cases were unilateral. All patients responded to medical management very well. Conservative management with combination antibiotic therapy was adequate for managing BEO. Conclusively, brucellosis must be considered as a cause of orchitis, especially in endemic regions like Turkey.

Purpose: The infection of bone that contains bone marrow called osteomyelitis, and is caused by different microorganisms. In this study, we aimed to determine the diagnostic value and accuracy of cultures of material from a sinus track compared with those of cultures of bone specimens that have been controversial., Materials and Method: Prospective study was conducted at Hospital University of Dicle, a 1,090-bed university-based hospital located in Diyarbakir, Turkey. Between May 2005 and September 2006, sinus-track cultures were compared with those of bone cultures from 43 patients with chronic osteomyelitis., Results: The patients' mean age was 30.6 +/- 3.6 years, and 29 (67%) male and 14 (33%) female. Organisms isolated from bone cultures were Staphylococcus 69% (29/42), Escherichia coli 9.5% (4/42), Pseudomonas aeruginosa 9.5% (4/42), Proteus mirabilis 7% (3/42), respectively. Cultures of sinus track and bone specimens gave identical results in 38% of patients., Conclusion: The value of bone culture in the therapy of osteomyelitis must be emphasized; it is the only reliable means of determining the responsible agent, up on which the antibiotic therapy is based. The correlation between sinus track and bone cultures was 38%, i.e., failure in the treatment for 6 patients out of 10.

Objectives: The objectives of this study were to identify the causative microorganisms and factors associated with survival in patients with Fournier's gangrene and to determine the accuracy of the Fournier's gangrene severity index., Materials and Methods: We retrospectively evaluated 27 patients with Fournier's gangrene who were treated and followed up at our hospital between January 2005 and December 2006. Biochemical, hematologic, and bacteriologic study results at admission and at the final evaluation, etiologic and predisposing factors at admission, physical examination findings, the timing and extent of surgical debridement, and antibiotic therapy used were all recorded., Results: The admission laboratory parameters that were significantly correlated with outcome included urea, creatinine, sodium, and potassium; at the final evaluation, in addition to these parameters, hematocrit, albumin, and bicarbonate levels were also significantly associated with outcome. The mean Fournier's gangrene severity index score (FGSIS) at admission for survivors was 5.04+/-2.49 compared with 13.6+/-4.61 for non-survivors. There was a strong correlation between the FGSIS and mortality (p<0.0001). Escherichia coli and Pseudomonas aeruginosa were the most commonly isolated microorganisms., Conclusions: Patient metabolic status and predisposing factors are important in the prognosis of Fournier's gangrene. Hence, we believe that the FGSIS should be used clinically to evaluate therapeutic options and assess results.

Although the commonest manifestation of Salmonella infection is acute gastroenteritis, infection may spread to the blood-stream may and the illness can present with focal lesions in almost any organ with or without septicemia. We describe here a case of Salmonella typhi infection of a sacroiliac joint that was cured with ciprofloxacin therapy for six weeks. The patient was immunologically normal. Salmonella etiology was not suspected in this case, and the diagnosis was made only after bacterial isolation. Physicians should be aware of this rare manifestation of Salmonella infection, especially in endemic areas.

Background: Streptococcus pyogenes is a well-known cause of a variety of clinical infections including local symptoms such as tonsillopharyngitis, cervical lymphadenitis, otitis media, cellulites, erysipelas, as well as more severe diseases such as scarlet fever, osteomyelitis, necrotizing fasciitis, sepsis, and toxic shock syndrome. However, acute bacterial meningitis caused by this pathogen is unusual., Objective: We report a case of group A streptococcus (GAS) meningitis in a previously healthy woman with a dramatically rapid course and fatal outcome., Case: A 41-year-old previously healthy woman presented a history of fever, headache, vomiting, and sore throat of three days' duration. Neurological examination revealed diminished consciousness and neck rigidity. The cerebrospinal fluid (CSF) was turbid with 10,000 leukocytes/mm(3). Direct examination of CSF showed Gram-positive cocci in chains, and cultures yielded S. pyogenes. Blood cultures yielded growth of S. pyogenes. The patient was treated initially with ceftriaxone (4 g/day) and the control CSF examination was not changed on the third day, so vancomycin (2 g/day) was added to the treatment; however, she died on the fourth day of the treatment., Conclusion: S. pyogenes meningitis is uncommon and the incidence seems to be persistently low; nevertheless, clinicians should be aware that sporadic cases may occur and may have a fulminant course with a relevant neurological sequel.

Objective: To assess the epidemiology of healthcare-associated infections (HAIs) in a neurology unit in a university hospital., Methods: The study was carried out prospectively at Dicle University Hospital, Diyarbakir, Turkey (1050-bed) between 1st January 1999 and 31st December 2004. Active surveillance for HAIs was performed by the infection control team, using the criteria proposed by the Centers for Diseases Control and Prevention (CDC) and National Nosocomial Infections Surveillance System (NNIS) methodology., Results: During the 6-year follow up period, 219 HAIs episodes were detected in 203 patients out of 3323 in patients. The mean length of stay of patients with HAI was 28+/-5 days, while that of patients without infections was 11+/-1 days. Eighty-two patients died with HAIs, while 1330 died in the patients without infections. The overall incidence rates (HAI/100) and incidence densities (HAI/1000 days of stay) of HAIs were 6.6% and 4.4/1,000 patients-days. The most common HAIs by primary site were urinary tract infection (44.2%) and decubitus infection (30.4%). The most prevalent microorganisms were Escherichia coli (27%), Klebsiella species (14%), Pseudomonas aeruginosa (13%), Enterobacter species (12%), coagulase-negative Staphylococci (10%) and Staphylococcus aureus (7%)., Conclusion: The results may contribute to observe the magnitude and characteristics of HAIs and to plan and evaluate policies and guidelines of infection control in neurology units.

Objective: To evaluate the efficacy of dexamethasone added to the treatment of adult patients with bacterial meningitis in our region., Methods: One hundred and forty-four patients were randomized prospectively and evaluated to determine the efficacy of dexamethasone treatment in adult patients with acute bacterial meningitis at Dicle University Hospital, Diyarbakir, Turkey between January 2000 and December 2004. While the first group received ceftriaxone 4 gr/day plus dexamethasone, the second group received ceftriaxone 4 gr/day only. Dexamethasone was given 10-15 minutes before the first 8 mg dose of antibiotic treatment. It was continued at 16 mg/day for 3 days., Results: The study included 144 patients with the diagnosis of acute bacterial meningitis. Cerebrospinal fluid (CSF) was analyzed at the time of admission, after 24-48 hours (Table 1), and at the end of treatment. Accordingly, CSF leukocyte level was found to be 1710+/-2140/mm3 in group 1 receiving dexamethasone treatment compared to 1950+/-2244/mm3 in group 2 (p=0.001). The consciousness in the group receiving dexamethasone improved significantly more rapidly than the control group (p=0.001). While mortality was 9.7% in the patient group receiving dexamethasone it was 16.7% in the control group, however, it was not significant (p=0.093)., Conclusion: The use of dexamethasone in adult patients is still under debate, and the administration of dexamethasone 10-15 minutes before antibiotherapy to unconscious patients in a poor state of health, is effective in the clinical improvement of the patient.

Aim: To evaluate the efficacy and safety of pegylated-interferon alpha-2a in hemodialysis patients with chronic hepatitis C., Methods: Thirty-six hemodialysis patients with chronic hepatitis C were enrolled in a controlled and prospective study. All patients were treatment naive, positive tested for anti-HCV antibodies, and positive tested for serum HCV-RNA. Twenty-two patients received 135 microg peglyated-interferon alpha-2a weekly for 48 wk (group A). The remaining patients were left untreated, eleven refused therapy, and three were not candidates for kidney transplantation and were allocated to the control group (group B). At the end of the treatment biochemical and virological response was evaluated, and 24 wk after completion of therapy sustained virological response (SVR) was assessed. Side effects were monitored., Results: Of 22 hemodialysis patients, 12 were male and 10 female, with a mean age of 35.2 +/- 12.1 years. Virological end-of-treatment response was observed in 14 patients (82.4%) in group A and in one patient (7.1%) in group B (P = 0.001). Sustained virological response was observed in 11 patients (64.7%) in group A and in one patient in group B (7.1%). Biochemical response parameters normalized in 10/14 patients (71.4%) at the end of the treatment. ALT levels in group B were initially high in six patients and normalized in one of them (25%) at the end of the 48 wk. In five patients (22.7%) therapy had to be stopped at mo 4 due to complications of weakness, anemia, and bleeding., Conclusion: SVR could be achieved in 64.7% of patients on hemodialysis with chronic hepatitis C by a treatment with peglyated-interferon alpha-2a. Group A had a significantly better efficacy compared to the control group B, but the side effects need to be concerned.