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Background Fever of unknown origin (FUO) remains a significant diagnostic challenge. Changes in patient populations and diagnostic technologies may shift the spectrum of underlying etiologies. This study aimed to examine recent FUO cases at a single tertiary center to identify changes in etiology compared with previous reports and between the pre- and post-COVID-19 pandemic periods, assess the diagnostic value of laboratory and imaging findings, and examine FUO characteristics in underrepresented subpopulations, including people living with HIV (human immunodefficiency virus), those on immunosuppressive therapy, and individuals with recurrent fever, with the goal of informing a center-specific diagnostic approach. Methods A retrospective analysis was performed on 100 patients hospitalized with FUO between 2017 and 2024, classified according to Durack and Street’s criteria. Subgroups included classical ( n  = 85), HIV-associated ( n  = 13), neutropenic ( n  = 1), and nosocomial FUO ( n  = 1). Clinical, laboratory, imaging, and biopsy findings were reviewed, and subgroup-specific analyses were conducted. Results Among 100 FUO patients (mean age 45.1 years; 52 males), recurrent fever was observed in 14 patients within the classical FUO group. The median fever duration at admission was 6 weeks. The average time to diagnosis was 14 days, and the mean hospital stay was 21 days. Final diagnoses were: collagen vascular diseases (CVD, 39%), infections (19%), malignancies (17%), miscellaneous (12%), and undiagnosed (13%). Vasculitis predominated among CVDs (25.6%), extrapulmonary tuberculosis (TB) among infections (36.8%), lymphomas among malignancies (52.9%) and, subacute thyroiditis among “miscellaneous” category (25%). In subgroup analysis, people living with HIV had no CVD, while no infections were found in recurrent fever cases. Among people living with HIV, infections (46%) and malignancies (38%) were most common. Immunosuppressed patients had diverse etiologies, including drug-induced pneumonitis and disease flares. CRP ≥140 mg/L, low hemoglobin, and anti-HIV positivity were independent predictors of malignancy; ferritin ≥875 µg/L was significantly associated ( p  = 0.01). PET-CT (Positron Emission Tomography – Computed Tomography) had the highest diagnostic yield, especially in infections and malignancies ( p  = 0.004). Microbiological studies were diagnostic in > 50% of infectious cases; autoantibodies aided diagnosis in ~50% of CVDs. During follow-up, 11 patients died, including 7 from the malignancy group. Conclusion Our findings indicate a shift toward non-infectious inflammatory causes of FUO, with CVD surpassing infections. PET-CT and targeted biopsies are valuable diagnostic tools, particularly in suspected malignancies or infections. Subgroup-specific approaches are essential, especially in people living with HIV and immunosuppressed patients. Despite advances, a proportion of FUO cases remain undiagnosed, underscoring the need for stepwise, individualized diagnostic strategies. Clinical trial number Not applicable.

Tuberculosis (TB) is one of the most common opportunistic infections in people living with HIV (PLHIV). Mycobacterium tuberculosis may cause more TB in all stages of HIV infection than in the general population, with the incidence of TB and the spread of pulmonary TB to other organs increasing as the CD4 count decreases. In this HIV cohort study, we aimed to evaluate the clinical features, diagnosis, and prognosis of TB among PLHIV in Türkiye. We conducted a retrospective cohort study to analyze clinical outcomes and identify determinants of mortality among people living with HIV (PLHIV) co-infected with tuberculosis. We included 264 patients diagnosed and treated for TB across six centers in Türkiye. We extracted clinical, demographic, laboratory, microbiological, and radiological data from patient medical records. To identify independent predictors of mortality, we performed multivariable logistic regression and reported the results as odds ratios (ORs) with 95% confidence intervals (CIs). Of the 9,687 PLHIV who were followed for 10 years, 2.7% (264 individuals) developed TB. The median age of these individuals was 40 years, and 89% were male. The prevalence of pulmonary TB only, extrapulmonary TB only, and the coexistence of pulmonary and extrapulmonary TB were 42.4%, 48.8%, and 8.7%, respectively. Opportunistic infections and cancers were found in 23% (62 out of 264) of patients with HIV/TB co-infection. Among patients with HIV/TB co-infection, 42% showed lymphadenopathy, with 70% of these cases being generalized. In patients who underwent chest CT scans (n=200), radiological patterns revealed post primary TB in 46%, primary TB in 36%, and miliary TB in 18%. The positivity rates of Ehrlich-Ziehl-Neelsen staining (EZN), polymerase chain reaction (PCR), and TB cultures in clinical samples were found to be 47.5%, 72.5%, and 53%, respectively. Most of our patients (95%) were given the standard TB treatment regimen (HRZE), with a paradoxical reaction observed in 11.6% of cases and hepatotoxicity occurring in 18% of cases. Age, CD4 count (<200 cells/mm3-late presenters), and thrombocytopenia were identified as independent risk factors for mortality in the 58 patients (22%) who died after diagnosis. Even today, more than one fifth of patients with HIV-TB co-infection in our cohort died. Mortality was higher among individuals who presented late with tuberculosis disease, especially those with advanced immunosuppression (CD4 <200 cells/μL). These findings underscore the urgent need for early HIV diagnosis and systematic TB screening to reduce co-infection-related mortality and improve clinical outcomes.

MicroRNAs (miRNAs), key regulators of cellular pathways, play crucial roles in the pathogenesis of various diseases, including Human Immunodeficiency Virus (HIV). This study aimed to evaluate the expression and diagnostic potential of -identified miRNAs (miR-124-3p, miR-27a-3p, miR-548ac-3p, miR-3163) before and during antiretroviral treatment (ART), together with their correlations with immunological markers (CD4 count, CD4/CD45 ratio) and virological parameters (HIV RNA load). Blood samples and clinical data of 16 patients were collected at 4 different time points; before the initiation of ART (baseline), 1 , 2 and 6 months following HIV diagnosis. 16 healthy controls were enrolled to this study. RT-qPCR and ELISA techniques were used to analyze miRNA expression levels while immunological markers (CD4 count and ratio) were assessed by flow cytometry. miR-27a-3p expression was significantly increased at 2 and 6 months of ART (p<0.001). miR-548ac-3p was upregulated at 6 month compared to healthy individuals and ART-naive subjects (p<0.05). miR-124-3p expression was significantly elevated in ART-naive subjects in comparison with healthy controls (p<0.001). Conversely, miR-3163 was downregulated in ART-naive, 1-month, and 2-month ART groups (p<0.001), but returned to normal levels by 6 months. miR-548ac-3p and miR-3163 showed moderate-to-strong positive correlations with CD4 counts (R=0.46, R=0.67; p<0.001). ROC analysis identified miR-3163 as a promising prognostic marker, with an AUC of 0.8561, (95% CI: 0.756-0.9265). Our findings highlight the potential of miR-3163 as a robust prognostic biomarker for monitoring HIV progression and optimizing ART strategies. Validation in larger cohorts is warranted to confirm its clinical utility.

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

Objectives: Regulatory T-cells (T-regs) maintain immune tolerance by affecting other cells of the immune system. They play an important role in autoimmune diseases and the prevention of graft rejection. Steroids suppress the immune system, especially inhibiting cytokine secretion of T-lymphocytes, initiation of the cellmediated immune response, and stimulation of T-regs. Interferons (IFN) also have immunomodulatory, antiviral, and anti-proliferative effects. They activate macrophages and cytotoxic T-cells and stimulate the differentiation of T-regs. The aim of this study was to evaluate the effects of IFN and steroids on T-regs in the liver, spleen, and bone marrow in a mouse model, and to determine if they exert their immunosuppresive/immunomodulatory effects through T-regs. Materials and Methods: A total of 24 mice were randomly separated into 3 groups and administered an intraperitoneal injection for five days. The control group received 0.1 mL saline every day, the IFN group received IFN-alpha-2b 20,000 IU on the first, third, and fifth days, and only 0.1 mL saline on the other days, and the steroids group received 5 mg/kg dexamethasone in 0.1 mL saline every day. Two days after the end of therapy, each mouse was anesthetized, the portal vein was explored via laparotomy, and 5 mL bovine serum albumin (BSA) was administered through the portal vein. The inferior vena cava was cut to allow BSA perfusion of the liver, and then the mice were sacrificed. The liver, spleen, and bone marrow were removed for analysis. T-regs were identified and counted using flow cytometry. Results: The flow cytometry count results showed no significant difference between the IFN, steroid, and control groups. Conclusion: IFN and steroid use do not seem to affect the quantity of T-regs.

Aims Despite high vaccination rates, increasing case numbers continue to be reported with the identification of new variants of concern, and the issue of durability of the vaccine-induced immune response remains hot topic. Real-life data regarding time-dependent immunogenicity of inactivated COVID-19 vaccines are scarce. We aimed to investigate the changes in the antibody at the different times after the second dose of the CoronaVac vaccine. Methods The study included 175 HCWs vaccinated with inactive CoronaVac (Sinovac Life Sciences, China) SARS-CoV-2 vaccine in two doses. Anti-spike/RBD IgG levels were measured first, third, and sixth months after the second dose. Chemiluminescent microparticle immunoassay (IgG II Quant test, Abbott, USA), which is 100% compatible with plaque reduction neutralization test, was used. Results Mean age of the participants was 38 ± 11.23 years (range between 22 and 66) of whom 119 (63.9%) were female, and 56 (32%) were male. Dramatic reductions were demonstrated in median antibody levels particularly in the infection-naïve group, comprising 138 HCWs compared to those with prior history of COVID-19 infection ( n  = 37) ( p  < 0.001). There was no difference between the two groups in terms of age, gender, blood groups, BMI, and comorbid diseases. Conclusions While antibody positivity remained above 90% in the 6th month after two doses of inactivated vaccine in HCWs, the median titers of neutralizing antibodies decreased rapidly. The decrease was more rapid and significant in those with no history of prior COVID-19 infection. In this critical phase of the pandemic, where we are facing the dominance of the Omicron variant after Delta, booster doses have become vital.

Objective: Late presentation of the patients with human immunodeficiency virus (HIV) infection is associated with less favourable treatment responses, more accelerated clinical progression, and a higher mortality risk. Although HIV prevalence is low in Turkey, it is steadily increasing and the information about late presentation among HIV-positives is limited. We aimed to analyze the status of late presentation among HIV-positive patients in Turkey. Methods: All newly diagnosed HIV/AIDS patients from 2003 to 2016 were enrolled in this study by five dedicated centres in Istanbul, Turkey. Demographic data, CD4+ counts, and HIV RNA were collected from medical records and were transferred to a HIV database system. Late presentation was defined as presentation for care with a CD4 count < 350 cells/mm3 or presentation with an AIDS-defining event, regardless of the CD4 cell count. A medical literature search was done for the analysis of late presentation in Turkey. Results: The cohort included 1,673 patients (1,440 males, median age 35 years). Among them, 847 (50.6%) had an early diagnosis, with a CD count of more than 350 cells/mm3. The remaining 826 were late presenters. Among late presenters, 427 (25.5% of all, 51.7% of late presenters) presented with advanced HIV disease. Late presenters were more elderly and less educated. The gender seemed comparable between groups. Late presentation was more likely among married patients. Early presenters were more likely among homosexuals, those diagnosed in screening studies, and in lower HIV-RNA viral load category. There has been a decreasing trend among late presenters in 2011-2016 when compared to 2003-2011 period. Conclusion: Current data suggest that half of HIV-infected patients present late in Turkey. In our cohort, those presented late were more elderly, less educated, married and had heterosexual intercourse. On admission, late presenters had more HIV-related diseases and were more likely in higher HIV-RNA category. In the cohort, men having sex with men were less likely late presenters. Efforts to reduce the proportion of late presentation are essential for almost every country. The countries should identify the risk factors of late presentation and should improve early diagnosis and presentation for HIV care.

Objectives: We aimed to evaluate the etiological, epidemiological and laboratory characteristics of adult patients admitted to our hospital with acute hepatitis. Materials and Methods: The patients with alanine aminotransferase (ALT) levels exceeding 10-fold and appropriately examined for etiology were included in the study. The markers for hepatothropic viruses and the others, autoimmune markers and hepatobiliary ultrasound were evaluated. Results: In this study, 111 patients were included, 46 (41%) were female and 41.4% of the patients had AH-A, 17.1% had AH-B, 2.7% had AH-C and 6.3% were not found any cause. The mean age was 22.11±6.05 years in AH-A. The majority of AH-A cases were male with 65%. The mean age was 33.5±14.78 in AH-B. There was a statistically significant difference between ages of patients with AH-A and AH-B (p=0.004). Conclusion: Since no specific treatment is available for acute viral hepatitis, preventive measures are more significant. The prevalence of AH-A and AH-B have declined in the recent years. It is clear that extensive vaccine policies and improved sanitation help eliminate these diseases. In order to ensure complete elimination of viral hepatitis, it is essential to give due importance to the vaccination in childhood as well as in adults.