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Background: Treatment with direct acting antiviral agents (DAAs) has provided sustained virological response rates in >95% of patients with chronic hepatitis C virus (HCV) infection. However treatment is costly and market access, reimbursement and governmental restrictions differ among countries. We aimed to analyze these differences among European and Eurasian countries., Methods: A survey including 20-item questionnaire was sent to experts in viral hepatitis. Countries were evaluated according to their income categories by the World Bank stratification., Results: Experts from 26 countries responded to the survey. As of May 2016, HCV prevalence was reported as low (≤1%) in Croatia, Czech Republic, Denmark, France, Germany, Hungary, the Netherlands, Portugal, Slovenia, Spain, Sweden, UK; intermediate (1-4%) in Azerbaijan, Bosnia and Herzegovina, Italy, Kosovo, Greece, Kazakhstan, Romania, Russia, Serbia and high in Georgia (6.7%). All countries had national guidelines except Albania, Kosovo, Serbia, Tunisia, and UK. Transient elastography was available in all countries, but reimbursed in 61%. HCV-RNA was reimbursed in 81%. PegIFN/RBV was reimbursed in 54% of the countries. No DAAs were available in four countries: Kazakhstan, Kosovo, Serbia, and Tunisia. In others, at least one DAA combination with either PegIFN/RBV or another DAA was available. In Germany and the Netherlands all DAAs were reimbursed without restrictions: Sofosbuvir and sofosbuvir/ledipasvir were free of charge in Georgia., Conclusion: Prevalence of HCV is relatively higher in lower-middle and upper-middle income countries. DAAs are not available or reimbursed in many Eurasia and European countries. Effective screening and access to care are essential for reducing liver-related morbidity and mortality., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Aim: To examine the variables associated with mortality in patients with Acinetobacter baumannii-related central nervous system infections treated with intrathecal colistin., Materials and Methods: This multi-centre retrospective case control study included patients from 11 centres in Turkey, as well as cases found during a literature review. Only patients with CNS infections caused by multidrug-resistant or extensively drug-resistant Acinetobacter baumannii treated with intrathecal colistin were included in this study. The variables associated with mortality were determined by dividing the patients into groups who died or survived during hospitalisation, and who died or survived from Acinetobacter meningitis., Results: Among the 77 cases enrolled in the study, 35 were found through a literature review and 42 were cases from our centres. Forty-four cases (57.1%) were male and the median age was 48 years (range: 20-78 years). Thirty-seven patients (48%) died during hospitalisation. The variables associated with increased all-cause mortality during hospitalisation included old age (odds ratio, 1.035; 95% confidence interval (CI), 1.004-1.067; p=0.026) and failure to provide cerebrospinal fluid sterilisation (odds ratio, 0.264; 95% confidence interval, 0.097-0.724; p=0.01). There is a trend (P=0.062) towards higher mortality with using of meropenem during meningitis treatment. Fifteen cases (19%) died from meningitis. There were no significant predictors of meningitis-related mortality., Conclusions: The mortality rate for central nervous system infections caused by multidrug-resistant or extensively drug-resistant Acinetobacter baumannii is high. Old age and failure to provide CSF sterilisation are associated with increased mortality during hospitalisation., (Copyright © 2016. Published by Elsevier B.V.)

Introduction: The information of discharge criteria in patients with Crimean-Congo Hemorrhagic Fever (CCHF) is limited. In this study, we aimed to determine the clinical and laboratory parameters used in discharging the patients by the experienced centers., Materials and Methods: The study was done in 9 reference centers of CCHF from May 1, 2015 to December 1, 2015 and included laboratory-confirmed patients with CCHF. The study was prospective, observational and non-interventional., Results: The study included 260 patients. Mean age was 51.3 ± 16.3 years; 158 (60.8%) were male. Mean hospital stay was 7 ± 2.6 days. The decision of discharging was taken considering clinical and laboratory findings. On discharge, no patients had fever or hemorrhage. The patients were followed-up clinically and a repeat CCHF PCR was not studied. All centers considered the following criteria for discharge: no fever and hemorrhage, improvement in clinical findings and laboratory studies. For all patients except one, platelet count was >50,000/mm(3) and had a tendency to increase. Prothrombin time and international normalized ratio (INR) were normal in 258 (99.6%) and 254 (98.1%) patients respectively. Alanine aminotransferase (ALT) was either normal or not higher than 10-fold and had a tendency to decrease in 259 (99.6%) patients. ALT and aspartate aminotransferase (AST) levels were not taken as discharge criteria with priority. During 30 days following the discharge, complication, relapse, or secondary transmission were not reported., Conclusions: The discharging practice of the centers based on clinical and laboratory parameters seems safe considering no complications, relapses, or secondary infection thereafter. Current discharge practice of the centers composed of no fever and hemorrhage, improvement in clinical findings, platelet count of either >100,000/mm(3) or >50,000/mm(3) with a tendency to increase, and normal bleeding tests can be used as the criteria of discharge., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Crimean-Congo hemorrhagic fever (CCHF) is a geographically widespread tick-borne zoonosis. The clinical spectrum of the illness varies from mild infection to severe disease and death. In severe cases, hemorrhagic manifestations develop, with fatality rates of 4-20%, depending on the geographic region and quality of the health care. Although vast majority of the CCHF cases were reported from Turkey, mortality rate is lower than the other regions, which is 5% on average. Prediction of the clinical course of the disease enables appropriate management planning by the physician and prompt transportation, if needed, of the patient to a tertiary care hospital for an intensive therapy. Thus, predicting the outcome of the disease may avert potential mortality. There are numerous studies investigating the prognostic factors of CCHF in the literature. Majority of them were reported from Turkey and included investigations on clinical and biochemical parameters, severity scoring systems and some novel biomarkers. Somnolence, bleeding, thrombocytopenia, elevated liver enzymes and prolonged bleeding times are the most frequently reported prognostic factors to predict the clinical course of the disease earlier. High viral load seems to be the strongest predictor to make a clinical decision about the patient outcome. The severity scoring systems based on clinically important mortality-related parameters are especially useful for clinicians working in the field to predict the course of the disease and to decide which patient should be referred to a tertiary care hospital for intensive care. In the light of the pathophysiological characteristics of CCHF, some new biomarkers of prognosis including cytokines, soluble adhesion molecules, genetic polymorphisms and coagulopathy parameters were also investigated. However most of these tests are not available to clinicians and they were obtained mostly for research purposes. In spite of the various studies about prognostic factors, they have several inherent limitations, including large variability in the results and confusing data that are not useful for clinicians in routine practice. In this paper, the results of diverse studies of the prediction of the prognosis in CCHF based on epidemiological, clinical and laboratory findings of the disease were summarized and suggestions for future studies are provided., (Copyright © 2016 Elsevier B.V. All rights reserved.)

There have been many studies pertaining to the management of herpetic meningoencephalitis (HME), but the majority of them have focussed on virologically unconfirmed cases or included only small sample sizes. We have conducted a multicentre study aimed at providing management strategies for HME. Overall, 501 adult patients with PCR-proven HME were included retrospectively from 35 referral centres in 10 countries; 496 patients were found to be eligible for the analysis. Cerebrospinal fluid (CSF) analysis using a PCR assay yielded herpes simplex virus (HSV)-1 DNA in 351 patients (70.8%), HSV-2 DNA in 83 patients (16.7%) and undefined HSV DNA type in 62 patients (12.5%). A total of 379 patients (76.4%) had at least one of the specified characteristics of encephalitis, and we placed these patients into the encephalitis presentation group. The remaining 117 patients (23.6%) had none of these findings, and these patients were placed in the nonencephalitis presentation group. Abnormalities suggestive of encephalitis were detected in magnetic resonance imaging (MRI) in 83.9% of the patients and in electroencephalography (EEG) in 91.0% of patients in the encephalitis presentation group. In the nonencephalitis presentation group, MRI and EEG data were suggestive of encephalitis in 33.3 and 61.9% of patients, respectively. However, the concomitant use of MRI and EEG indicated encephalitis in 96.3 and 87.5% of the cases with and without encephalitic clinical presentation, respectively. Considering the subtle nature of HME, CSF HSV PCR, EEG and MRI data should be collected for all patients with a central nervous system infection., (Copyright © 2016 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Healthcare-related transmission of Crimean-Congo haemorrhagic fever (CCHF) is a well-recognized hazard. We report a multicentre retrospective cross-sectional study undertaken in Turkey in 2014 in nine hospitals, regional reference centres for CCHF, covering the years 2002 to 2014 inclusive. Data were systematically extracted from charts of all personnel with a reported health care injury/accident related to CCHF. Blood samples were tested for CCHF IgM/IgG by enzyme-linked immunosorbent assay and/or viral nucleic acid detection by PCR after the injury. Fifty-one healthcare-related exposures were identified. Twenty-five (49%) of 51 resulted in laboratory-confirmed infection, with a 16% (4/25) overall mortality. The main route of exposure was needlestick injury in 32/51 (62.7%). A potential benefit of post-exposure prophylaxis with ribavirin was identified., (Copyright © 2016 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Objective: Patients with preeclampsia (PE) have endothelial dysfunction and an increased future risk of cardiovascular (CV) mortality. The number of circulating endothelial cells (CECs) is markedly increased in conditions associated with a high degree of endothelial cell activation/injury including PE. We hypothesized that the number of CECs continues to be increased in women with a history of PE, reflecting ongoing endothelial cell activation/injury., Study Design: CECs, flow-mediated vasodilation, levels of adhesion molecules and soluble vascular endothelial growth factor receptor-1 (sVEGFR1), and urine albumin/creatinine ratio were determined in 21 healthy women with ongoing normal pregnancy, 24 healthy currently nonpregnant women with a history of normal pregnancy, a total of 17 women with currently active mild (n = 11) or severe (n = 6) PE without hemolysis, elevated liver enzymes, and low platelet count (HELLP) syndrome, and 16 currently nonpregnant women with a history of mild (n = 10) or severe (n = 6) PE., Results: Blood samples from women with active preeclampsia had higher CECs (9.9 ± 7.9 cells/mL) than healthy pregnant women (3.0 ± 4.1 cells/mL; P < .001), healthy nonpregnant women with a history of normal pregnancy (3.4 ± 4.0 cells/mL; P < .001), or women with a history of preeclampsia (2.4 ± 2.0 cells/mL; P < .001). The number of CECs were similar between women with a history of preeclampsia and healthy nonpregnant women with a history of normal pregnancy. Patients with active preeclampsia had significantly higher soluble vascular cell adhesion molecule-1, soluble E-selectin, sVEGFR1, and urinary albumin/creatinine ratio than healthy pregnant women. However, soluble vascular cell adhesion molecule-1, soluble E-selectin, urinary albumin/creatinine ratio were similar in women with a history of preeclampsia and healthy nonpregnant women with a history of normal pregnancy. However, women with a history of preeclampsia had higher sVEGFR1 levels than women with a history of normal pregnancy (P < .05)., Conclusion: Markers of endothelial activation, dysfunction, and damage were increased in patients with PE. After the delivery, this activation status is similar to the age-matched nonpregnant women with a history of normal pregnancy. However, sVEGFR-1 levels remain higher in women with a history of preeclampsia compared with women without a history of preeclampsia., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Babesiosis is a zoonotic disease that may be asymptomatic or result in severe clinical conditions, with severe hemolysis, hepatic, and renal failure, in humans. Clinical symptoms depend on the species and immune status of the host. The disease is especially severe in those of advanced age, those with an immune deficiency, and the splenectomized. A severe case of babesiosis that developed in a splenectomy patient is presented here; the patient was admitted from a rural region with severe anemia and a deterioration in her general condition, with an initial diagnosis of malaria. In such situations, an exchange transfusion (ET), in addition to antimicrobial treatment, could be lifesaving., (Copyright © 2015. Published by Elsevier Ltd.)

Crimean-Congo hemorrhagic fever (CCHF) is endemic in Eurasian countries such as, Turkey, Pakistan, Afghanistan and Iran. CCHF virus is spread by the Hyalomma tick, which is found mainly on cattle and sheep. Muslim countries, in which these animals are sacrificed during Eid-Al-Adha, are among the countries where CCHF is endemic, and it has been observed that CCHF is associated with practices surrounding the Eid-ad-Adha festival. The dates for Eid-Al-Adha drift 10 days earlier in each year according to Georgian calendar. In previous years Eid-al-Adha occurred in autumn-winter months however in the next 10-15 years it will be take place in the summer months when CCHF is more prevalent. This may lead to a rise in the number of cases due to increased dissemination of CCHF virus with uncontrolled animal movements in and between countries. This consensus report focuses on the variable practices regarding animal handling in different regions and possible preventative measures to reduce the incidence of CCHF. Environmental hygiene and personal protection are essential parts of prevention. There is a need for international collaborative preparedness and response plans for prevention and management of CCHF during Eid-Al-Adha in countries where the disease is prevalent., (Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: Non-alcoholic fatty liver disease (NAFLD) is associated with atherosclerosis and reduced vascular compliance. The purpose of this study was to examine the relationships between arterial stiffness measures, the histological severity of NAFLD, and epicardial fat thickness (EFT)., Methods: A total of 100 patients with biopsy-proven NAFLD and 50 age- and sex-matched controls were enrolled. The histological severity was assessed in all NAFLD patients. Measurements of arterial stiffness [pulse-wave velocity (PWV) and augmentation index (AIx)] were carried out using a Mobil-O-Graph arteriograph system. EFT was assessed by means of echocardiography., Results: Compared with controls, NAFLD patients had significantly higher PWV and AIx values. Stepwise linear regression analysis demonstrated that the liver fibrosis score and EFT were independent predictors of both PWV and AIx values in NAFLD patients., Conclusions: Patients with NAFLD have an increased arterial stiffness, which reflects both the severity of liver fibrosis and increased EFT values., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

We aimed to provide data on the diagnosis of tuberculous meningitis (TBM) in this largest case series ever reported. The Haydarpasa-1 study involved patients with microbiologically confirmed TBM in Albania, Croatia, Denmark, Egypt, France, Hungary, Iraq, Italy, Macedonia, Romania, Serbia, Slovenia, Syria and Turkey between 2000 and 2012. A positive culture, PCR or Ehrlich-Ziehl-Neelsen staining (EZNs) from the cerebrospinal fluid (CSF) was mandatory for inclusion of meningitis patients. A total of 506 TBM patients were included. The sensitivities of the tests were as follows: interferon-γ release assay (Quantiferon TB gold in tube) 90.2%, automated culture systems (ACS) 81.8%, Löwenstein Jensen medium (L-J) 72.7%, adenosine deaminase (ADA) 29.9% and EZNs 27.3%. CSF-ACS was superior to CSF L-J culture and CSF-PCR (p <0.05 for both). Accordingly, CSF L-J culture was superior to CSF-PCR (p <0.05). Combination of L-J and ACS was superior to using these tests alone (p <0.05). There were poor and inverse agreements between EZNs and L-J culture (κ = -0.189); ACS and L-J culture (κ = -0.172) (p <0.05 for both). Fair and inverse agreement was detected for CSF-ADA and CSF-PCR (κ = -0.299, p <0.05). Diagnostic accuracy of TBM was increased when both ACS and L-J cultures were used together. Non-culture tests contributed to TBM diagnosis to a degree. However, due to the delays in the diagnosis with any of the cultures, combined use of non-culture tests appears to contribute early diagnosis. Hence, the diagnostic approach to TBM should be individualized according to the technical capacities of medical institutions particularly in those with poor resources., (© 2013 The Authors Clinical Microbiology and Infection © 2013 European Society of Clinical Microbiology and Infectious Diseases.)

We report a high-throughput phage selection method to identify mutants of Sfp phosphopantetheinyl transferase with altered substrate specificities from a large library of the Sfp enzyme. In this method, Sfp and its peptide substrates are co-displayed on the M13 phage surface as fusions to the phage capsid protein pIII. Phage-displayed Sfp mutants that are active with biotin-conjugated coenzyme A (CoA) analogues would covalently transfer biotin to the peptide substrates anchored on the same phage particle. Affinity selection for biotin-labeled phages would enrich Sfp mutants that recognize CoA analogues for carrier protein modification. We used this method to successfully change the substrate specificity of Sfp and identified mutant enzymes with more than 300-fold increase in catalytic efficiency with 3'-dephospho CoA as the substrate. The method we developed in this study provides a useful platform to display enzymes and their peptide substrates on the phage surface and directly couples phage selection with enzyme catalysis. We envision this method to be applied to engineering the catalytic activities of other protein posttranslational modification enzymes.

Informed consultation between physicians is an important part of medical practice. The aim of the study was to evaluate the nature and frequency of such consultations in infectious diseases and clinical microbiology practice. This study was done in five university hospitals. Twenty-one infectious diseases and clinical microbiology specialists participated in informal ('curbside') consultations. In a written questionnaire, physicians were asked to report the number and nature of the informal consultations (ICs) they were asked to provide. A total three hundred and sixty-two such consultations were carried out during a three-month period. The ICs occurred most frequently in the hospital (82.3%). Most of the ICs from outside the hospital were by telephone. Most of the ICs (54.4%) were requested by fellows of specialists. 78.7% of the ICs were requested during working hours. 58.8% of consultations took less than 5 min, 18.8% took 6-10 min, 15.2% took 11-20 min, and 7.2% took over 20 min. The four most common reasons for obtaining ICs were to: help to select an appropriate treatment plan (41.4%), help to select an appropriate prophylaxis (19.3%), interpret laboratory data (10.2%), and provide information about antibiotics (10.2%). 30.1% of ICs resulted in subsequent formal consultation and only four patients (1.1%) were transferred to the consultants' clinics. Informal consultations are a frequent occurrence in the practice of infectious diseases and clinical microbiology (ID&CM). Physicians use this sort of consultation to select an appropriate treatment plan and obtain medical information. This study confirms the importance of the ID&CM specialists as a resource for medical personnel.