Cell free DNA as a new prognostic biomarker for COVID-19, A prospective cohort study.

Predicting the need of hospitalization and intensive care in COVID-19 patients has been challenging with current diagnostic tests since the beginning of the pandemic. We aimed to test cell free DNA (cfDNA) as a novel biomarker for COVID-19 disease severity and mortality. cfDNA concentration was quantified by RT-PCR based test. One hundred and sixty-eight patients(85 outpatients, 61 inpatients,22 ICU) included the study. Mean initial plasma cfDNA levels were significantly different (p < 0.01) in outpatients (1.190,66 ng/ml), inpatients (8.258,10 ng/ml) and ICU patients (84.806,87 ng/ml). ROC analysis showed with 95 % specificity that patients with initial cfDNA concentrations ≥6.389 ng/ml need to be hospitalized and those ≥26.104 ng/ml require ICU referral. cfDNA concentration was correlated with neutrophil/lymphocyte ratio, lymphocyte level, CRP, AST, LDH, CK, fibrinogen, ferritin and D-dimer. Plasma cfDNA levels on admission, well correlating with disease severity and mortality in COVID-19 that found as a useful biomarker.

Bone Metabolism in Men who Live with HIV Aged 50 years and Over: Impact of Infection Duration.

BACKGROUND: Early diagnosis and effective antiretroviral therapy (ART) lead to similar life expectancy in people living with HIV (PLWH) compared to the general population. This population faces problems such as decreased bone mineral density (BMD) and increased fracture risk. The aim of this study was to determine the prevalence of osteoporosis in men aged 50 years and over who were PLWH and to determine risk factors and changes in bone metabolism with bone turnover markers. METHODS: 79 male PLWH aged 50 years and over were followed up in our outpatient clinic between May 2021 and October 2021. The patients' demographic, clinical, laboratory, and DEXA data were analyzed. Serum levels of bone turnover markers were measured. RESULTS: The prevalence of osteopenia, osteoporosis, and normal BMD was found to be 55.7%, 13.9%, and 30.4%, respectively. A correlation was found between low BMD and low body mass index, elapsed time since diagnosis of HIV infection, high rate of use of ART, and long usage time of tenofovir disoproxil fumarate + protease inhibitor. A one-year increase in HIV infection duration was associated with an increased risk of low BMD by 1.246. CONCLUSION: Compared to studies conducted on the general population, the prevalence of osteoporosis in male PLWH aged 50 years and older was two times higher. The limited effect of the duration of ART use on low BMD may be due to the patients' histories of replacement therapy. Therefore, to eliminate the negative effects of ART on BMD, it may be beneficial to start replacement therapy when necessary.

Modeling the Health Economic Burden of Hepatitis C Virus Infection in Turkey: Cost-Effectiveness of Targeted Screening.

BACKGROUND/AIMS: In 2016, World Health Organization introduced global goals to eliminate hepatitis C virus by 2030. The aim of this study is to analyze the epidemiologic and economic burden of hepatitis C virus in Turkey and compare current practice (regular care) with a hypothetical active screening and treatment approach (active scenario). MATERIALS AND METHODS: A Markov model was used to analyze and compare regular care with a scenario developed by experts including the screening and treatment of all acute and chronic hepatitis C virus infections between 2020 and 2050. General and targeted populations were focused. The model reflected the natural history of the disease, and the inputs were based on a literature review and expert opinions. Costs were provided by previous studies and national regulations. RESULTS: The active scenario resulted in higher spending for all groups compared with regular care in the first year. Cumulative costs were equalized in the 8th, 12th, 13th, and 16th year and followed by cost-savings of 49.7 million, 1.1 billion, 288.6 million, and 883.4 million Turkish liras in 20 years for prisoners, refugees, people who inject drugs (PWID), and all population, respectively. In all groups, the mortality was found to be lower with the active scenario. In total, 62.8% and 50.6% of expected deaths with regular care in 5 and 20 years, respectively, were prevented with the active scenario. CONCLUSIONS: An active screening and treatment approach for hepatitis C virus infection could be cost-effective for PWID, prisoners, and refugees. Almost two-thirds of deaths in regular care could be prevented in 5 years' time with this approach.

Dermatological lesions among people living with HIV in Turkey.

This study aimed to document the dermatoses and their relationships with CD4+ T lymphocyte counts and clinical stages of disease among people living with HIV followed by our Clinical Department, to investigate the effect of antiretroviral therapy (ART) on findings and to compare with real-world data. Medical records of people living with HIV were analyzed retrospectively in our outpatient clinic from January 2005 to June 2017. A total of 500 patient files were examined. 179 patients with dermatoses were included in the study. Demographic data, clinical and laboratory findings, dermatological findings, type and distribution of lesions, serological and histopathological examinations, diagnosis, treatment, and follow-up of patients were transferred to data forms. 84.4% of the patients were male and the mean age was 38.65 ± 11.6 years. The median CD4+ T lymphocyte count was 253/mm3 (range:0-1067). At least one dermatosis was present in 69.3% of the patients. Compared with their median CD4+ T lymphocyte counts, the ratio of CD4+ T lymphocytes was significantly lower in the group with three or more dermatoses (p = 0.019). Condyloma acuminatum (15.1%), drug eruption (13.4%), seborrheic dermatitis (11.7%), oral candidiasis (11.2%), dermatophytoses (11.2%), syphilis (8.4%), Kaposi's sarcoma (8.4%), and telogen effluvium (8.4%) were the most common dermatoses. Kaposi sarcoma (KS), oral candidiasis, onychomycosis, and molluscum contagiosum were significantly higher in the CD4+ T lymphocyte <200/mm³ group when CD4+ T lymphocyte threshold value was determined as 200/mm³. Compared with other TDF/FTC-containing regimens, a significantly higher proportion of alopecia was reported in patients receiving TDF/FTC/EVG/c (p = 0.007). Dermatoses may be a good clinical marker for detecting clinical stage and diagnosing HIV infection; also, there may be a significant increase in the number of dermatoses in advanced stages. Although there are only a few studies in the literature, it should be kept in mind that ART-associated alopecia rates may increase nowadays when ART is targeted at everyone.

Detection of SARS-CoV-2 RNA in Upper Respiratory Swap Samples by Pooling Method

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.

Efficacy and safety of an inactivated whole-virion SARS-CoV-2 vaccine (CoronaVac): interim results of a double-blind, randomised, placebo-controlled, phase 3 trial in Turkey.

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 µg 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<0·0001). The frequencies of any adverse events were 1259 (18·9%) in the vaccine group and 603 (16·9%) in the placebo group (p=0·0108) with no fatalities or grade 4 adverse events. The most common systemic adverse event was fatigue (546 [8·2%] participants in the vaccine group and 248 [7·0%] the placebo group, p=0·0228). Injection-site pain was the most frequent local adverse event (157 [2·4%] in the vaccine group and 40 [1·1%] in the placebo group, p<0·0001). INTERPRETATION: CoronaVac has high efficacy against PCR-confirmed symptomatic COVID-19 with a good safety and tolerability profile. FUNDING: Turkish Health Institutes Association.

Clinical and microbiological characteristics of Aeromonas bacteremia in Turkey.

We investigated the cases with Aeromonas bacteremia in terms of clinical and microbiological characteristics, underlying disease and mortality rates. Patients with positive blood cultures were included in this research. Aeromonas bacteremia was diagnosed as at least one positive blood culture for Aeromonas species. The bacteremia was defined as community origin if the onset was in the community or within 72 hours of hospital admission. The others were considered as nosocomial. All bacteria were defined as Aeromonas with conventional method. Species identification was verified by VITEK system. Antibiotic susceptibility tests were analyzed with the disc diffusion, E-test method or VITEK system. Thirty-three patients were diagnosed with bacteremia due to Aeromonas spp. Hematologic and solid tumors were the leading underlying conditions, followed by cirrhosis. Two patients (6%) had community-acquired infections. Aeromonas hydrophila was the most common isolated bacterium. The crude mortality rate was 36%. 12 patients died and 6 deaths and 4 deaths were detected in patients with bacteremia caused by A. hydrophila and Aeromonas sobria respectively. All strains were resistant to ampicillin and more than 90% of the strains were susceptible to trimethoprim-sulfamethoxazole, fluoroquinolone, third generation cephalosporins, and carbapenems. Aeromonas sp. is not a frequent cause of bacteremia however, it may lead to high mortality rates, especially in the immunocompromised hosts and patients with liver cirrhosis. Nosocomial Aeromonas bacteremia is not uncommon in these populations. Broad-spectrum cephalosporins, piperacillin-tazobactam, fluoroquinolones, and carbapenems remain as effective antimicrobial agents for therapy of Aeromonas bacteremia.

The role of quantitative HBsAg in patients with HBV DNA between 2000-20,000 IU/ml.

AIMS: We aimed to determine the contribution of quantitative HBsAg in differentiating chronic infections from chronic hepatitis in HBeAg negative patients with HBV DNA 2000-20,000 IU/ml. MATERIAL AND METHODS: A total of 79 untreated HBeAg negative patients were included. Patients were divided into 3 groups based on HBV DNA levels: group 1 (HBV DNA ≤ 2000 IU/ml), group 2 (HBV DNA: 2000-20,000 IU/ml) and group 3 (HBV DNA > 20,000 IU/ml). We collected serum from all patients for quantitative HBsAg analysis. We compared serum quantitative HBsAg levels with biochemical parameters, HBV DNA and liver biopsy results. RESULTS: In this study 46 patients were female and the mean age was 42 years. Serum quantitative HBsAg levels were found to be significantly lower in chronic infections compared with chronic hepatitis. There was a positive correlation between quantitative HBsAg and HBV DNA, ALT (alanine aminotransferase), HAI score (histological activity index), fibrosis score and disease stage. The cut-off level of quantitative HBsAg was determined as 4425 IU/ml to differentiate chronic infection from chronic hepatitis. With the test specificity of 95%, we found quantitative HBsAg cut-off values 1026 IU/ml and 20,346 IU/ml for the diagnosis of chronic infection and chronic hepatitis, respectively. CONCLUSION: Our study suggests that the quantitative HBsAg ≤ 1000 IU/ml limit value might be used for the diagnosis of chronic infection not only in HBV DNA ≤ 2000 IU/ml but also in patients with HBV DNA between 2000-20,000 IU/ml. In addition, antiviral treatment could be considered in patients with quantitative HBsAg > 20,000 IU/ml and HBV DNA > 2000 IU/ml without further examinations such as liver biopsy.

Risk factors for development of vancomycin-resistant enterococcal bacteremia among VRE colonizers : A retrospective case control study.

AIMS: We aimed to determine the proportion of vancomycin-resistant enterococci (VRE) colonized patients among all inpatients who later developed VRE bacteremia during hospital stay and to identify the risk factors for VRE bacteremia at a tertiary hospital. MATERIAL AND METHODS: Patients with positive rectal screening or any clinically significant positive culture results for VRE were included in 1­year follow-up. Colonization with VRE was defined as a positive culture (rectal, stool, urinary) for VRE without infection and VRE bacteremia was defined as positive blood culture if the signs and symptoms were compatible with infection. To determine the risk factors for VRE bacteremia among VRE colonized patients, a retrospective case control study was performed. The two groups were compared in terms of variables previously defined as risk factors in the literature. RESULTS: Of 947 positive samples, 17 VRE bacteremia were included in the analysis. Cephalosporin use for more than 3 days within 3 months was a significant risk factor for bacteremia (p = 0.008). Prior use of carbapenems was found to be statistically significant for bacteremia (p = 0.007). In multivariate analyses the use of carbapenems and cephalosporins was an independent risk factor for developing bacteremia among VRE colonizers (odds ratio, OR, 6.67; 95% confidence interval, CI, 1.30-34; p = 0.022 and OR 4.32, 95% CI 1.23-15; p = 0.022, respectively). CONCLUSION: A VRE colonization in patients receiving broad-spectrum beta-lactam antibiotics including carbapenems and cephalosporins may result in bacteremia. It is possible to keep mortality at very low levels in VRE bacteremia with effective infection control measures, rapid infectious diseases consultation and rational antimicrobial treatment based on current epidemiological data.

Human immunodeficiency virus and tuberculosis coinfection: clinical features and predictors of mortality

Background/aim: This study was undertaken to identify subjects with human immunodeficiency virus and tuberculosis (HIV/TB) coinfection in a group of HIV-positive patients followed at five different healthcare centers, and to determine the demographic and clinical characteristics of these subjects as well as the predictors of mortality. Materials and methods: A database search for subjects with TB coinfection was performed among 1475 HIV-positive adult patients and a total of 66 individuals were identified with HIV/TB coinfection. Results: There were 66 patients (4.5%) with TB coinfection. Twenty-one percent (n = 14) of the patients with TB coinfection died during the study period and these patients had significantly lower baseline CD4 counts at the time of TB diagnosis (P = 0.005). None of the patients with CD4 count of ≥200 cells/mm3 died during follow-up and a low CD4 count at the time of TB diagnosis (<200 cells/ mm3) was associated with poor survival (P = 0.012). However, none of the parameters emerged as significant independent predictors of survival in multivariate analysis. Conclusion: Coexistence of TB and HIV infection is associated with many clinical challenges and a better understanding of patient characteristics as well as the parameters impacting the outcome will improve the quality of care provided for this group of patients.

N-acetyl cysteine therapy in acute viral hepatitis.

AIM: To investigate the effect of N-acetyl cysteine (NAC) on acute viral hepatitis (AVH). METHODS: We administered 200 mg oral NAC three times daily (600 mg/day) to the study group and placebo capsules to the control group. All patients were hospitalized and diagnosed as AVH. Blood total and direct bilirubin, ALT, AST, alkaline phosphatase, albumin and globulin levels of each patient were measured twice weekly until total bilirubin level dropped under 2 mg/dl, ALT level under 100 U/L, follow up was continued and then the patients were discharged. RESULTS: A total of 41(13 female and 28 male) AVH patients were included in our study. The period for normalization of ALT and total bilirubin in the study group was 19.7+/-6.9 days and 13.7 +/- 8.5 days respectively. In the control group it was 20.4 +/- 6.5 days and 16.9 +/- 7.8 days respectively (P>0.05). CONCLUSION: NAC administration effected neither the time necessary for normalization of ALT and total bilirubin values nor duration of hospitalization, so we could not suggest NAC for the treatment of icteric AVH cases. However, our results have shown that this drug is not harmful to patients with AVH.