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"Bilgul, Mete"
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Inactive SARS-CoV-2 vaccine generates high antibody responses in healthcare workers with and without prior infection
2022
Healthcare workers (HCWs) were among the first groups to be vaccinated in Turkey. The data to be obtained by the vaccination of HCWs would guide wide spread vaccination programs.
The study included 330 HCWs working at Istanbul University-Cerrahpaşa, Cerrahpaşa Medical Faculty Hospital and vaccinated with inactive CoronaVac (Sinovac Life Sciences, China) SARS-CoV-2 vaccine in two doses (28 days apart). Anti-Spike /RBD IgG levels were measured 14 days after the first dose and 28 days after the second dose. Chemiluminescent microparticle immunoassay (CMIA) (ARCHITECT IgG II Quant test, Abbott, USA), which is 100% compatible with plaque reduction neutralization test (PRNT), was used.
Of the participants, 211 (63.9%) were female, 119 (36.1%) were male, and mean age was 39.6 ± 7.7 years. In those without prior COVID-19 history; (n = 255) antibody positivity was detected as 48.2% (95% CI: 42.1–54.3) 14 days after the first dose of vaccine, and 99.2% (95% CI: 98.1–100) at day 28 after the second dose. Antibody titers were significantly lower in patients with hypertension (p = 0.011). In those with prior history of COVID-19 (n = 75); both the antibody positivity rates after the first vaccine (48.2% vs 100%, p = 0.000) and the anti-spike/RBD antibody levels after the second vaccine (with a ≥ 1050 AU/mL titer equivalent to PRNT 1/80 dilution) was significant than infection-naive group (25.9% vs. 54.7%, p = 0.000). Antibody positivity after two doses of vaccination for all study group was 99.4% (95% CI: 98.6–100).
Two doses CoronaVac produce effective humoral immunity in HCWs. Antibody response is significantly higher in those with prior history of COVID-19 than infection-naive group. Given no significant benefit of the second dose, a single shot of vaccination may be sufficient for those with prior history of COVID-19. Monitoring humoral and cellular immune responses, considering new variants, is required to validate this approach.
Journal Article
Next-generation sequencing of CCR5, CXCR4, and IFNAR1 variants in relation to HIV-1 disease progression and ART response
by
Tabak, Fehmi
,
Mete, Bilgul
,
Mercan, Sevcan
in
3' Untranslated regions
,
5' Untranslated regions
,
631/208
2025
HIV, which causes acquired immune deficiency syndrome (AIDS), invades the host cell via the CD4 receptor and CCR5 or CXCR4 co-receptors. Interferons induced early in HIV infection induce an antiviral defense mechanism through IFNAR signaling. Our study aimed to examine the relationship between
CCR5
,
CXCR4
, and
IFNAR1
gene variations as a risk factor in HIV + patients and their response to their clinical parameters. Targeted next-generation sequencing (tNGS) was used to perform molecular genotyping analysis of the
CCR5
,
CXCR4,
and
IFNAR1
genes in genomic DNA from 22 HIV + patients and 25 healthy individuals as controls. We detected 13 rare mutations in the study, including 3 missense, 1 synonymous, 2 5′UTR, 4 3′UTR, and 1 frameshift variation. We also analyzed 6 common variants in the
IFNAR1
and
CXCR4
genes. HIV + patients carrying the homozygous TT genotype of the
IFNAR1
intronic rs2856973:T > A variant had higher CD4 + T cell counts compared with patients carrying the TA + AA genotypes of the rs2856973 variant in the naive and first month of the ART (
p
= 0.001 and
p
= 0.001, respectively). Similarly, participants receiving ART with a TT genotype of rs2856973:T > A showed a significantly higher CD4 + T cell count in the third month (
p
= 0.001). Patients carrying the homozygous wild-type genotype of the
CXCR4
intronic rs2680880:A > T SNP had lower CD4 + T cell count compared with subjects carrying the AT + TT mutant genotypes of rs2680880:A > T in the naive and first-month period (
p
= 0.015 and
p
= 0.025, respectively). Our results demonstrate that intronic variations in the
IFNAR1
rs2856973:T > A and
CXCR4
rs2680880:A > T genes can contribute to modifications in HIV progression and CD4 + T recovery under ART.
Journal Article
Kidney function on admission predicts in-hospital mortality in COVID-19
by
Tabak, Fehmi
,
Seyahi, Nurhan
,
Karaca, Cebrail
in
Acute Kidney Injury - diagnosis
,
Acute Kidney Injury - epidemiology
,
Adult
2020
Recent data have suggested the presence of a reciprocal relationship between COVID-19 and kidney function. To date, most studies have focused on the effect of COVID-19 on kidney function, whereas data regarding kidney function on the COVID-19 prognosis is scarce. Therefore, in this study, we aimed to investigate the association between eGFR on admission and the mortality rate of COVID-19.
We recruited 336 adult consecutive patients (male: 57.1%, mean age: 55.0±16.0 years) that were hospitalized with the diagnosis of COVID-19 in a tertiary care university hospital. Data were collected from the electronic health records of the hospital. On admission, eGFR was calculated using the CKD-EPI formula. Acute kidney injury was defined according to the KDIGO criteria. Binary logistic regression and Cox regression analyses were used to assess the relationship between eGFR on admission and in-hospital mortality of COVID-19.
Baseline eGFR was under 60 mL/min/1.73m2 in 61 patients (18.2%). Acute kidney injury occurred in 29.2% of the patients. In-hospital mortality rate was calculated as 12.8%. Age-adjusted and multivariate logistic regression analysis (p: 0.005, odds ratio: 0.974, CI: 0.956-0.992) showed that baseline eGFR was independently associated with mortality. Additionally, age-adjusted Cox regression analysis revealed a higher mortality rate in patients with an eGFR under 60 mL/min/1.73m2.
On admission eGFR seems to be a prognostic marker for mortality in patients with COVID-19. We recommend that eGFR be measured in all patients on admission and used as an additional tool for risk stratification. Close follow-up should be warranted in patients with a reduced eGFR.
Journal Article
Integrative bioinformatic and clinical validation reveals dynamic regulation of circulating microRNAs before and after antiretroviral therapy in HIV-positive patients
2025
MicroRNAs (miRNAs) play a crucial role in gene regulation, including HIV, where they influence viral replication and immune response. This study aims to identify key miRNAs involved in HIV pathogenesis, using bioinformatics and cohort validation to explore their potential as biomarkers for early detection, disease monitoring, and therapeutic targets. HIV-host interactomes for HIV-1 and HIV-2 were analyzed using STRING and Cytoscape to construct interaction networks for key HIV receptors. Gene-disease associations, GWAS data, and tissue expression profiles were retrieved to refine miRNA predictions, utilizing multiMiR and enrichment analyses to identify significant regulatory interactions. Blood samples of HIV-positive untreated patients were collected longitudinally over six months (baseline, 1, 3, and 6 months) after antiretroviral therapy initiation to validate bioinformatics predictions using Fluidigm qRT-PCR. We identified key miRNAs involved in HIV regulation by ranking HIV-disease interactors, highlighting miR-590-3p as the most significant, along with other miRNAs associated with critical pathways. Enrichment analysis of miRNA targets revealed their involvement in immune signaling, apoptosis regulation, and disease-related pathways, particularly in rheumatoid arthritis and neoplastic processes. Significant reductions were observed as early as 1 month for miR-590-3p, miR-1-3p, miR-146a-5p, let-7b-5p, miR-155-5p and miR-16-5p (
p
< 0.0001 for all) compared with ART-naive patients, indicating an early therapeutic response. Our study identifies key miRNAs as significant HIV-disease interactors through in silico prediction and cohort validation. Our findings lay the groundwork for future studies exploring the functional roles of these miRNAs and their potential as biomarkers of immune recovery or targets for therapeutic modulation in ART-treated populations.
Journal Article
Molecular epidemiology of JC polyomavirus genotypes in PLWH from Turkey
by
Aydoğan, Okan
,
İnkaya, Ahmet Çağkan
,
Mete, Bilgül
in
Adult
,
Amino acids
,
Biomedical and Life Sciences
2025
Background
JC polyomavirus (JCPyV) is a globally prevalent human polyomavirus that establishes lifelong latency, primarily in renal tissue. Despite its global importance, molecular epidemiological data on JCPyV still remain limited.
Objectives
This study aimed to investigate the prevalence, genotype distribution, and genetic variations of JCPyV in urine and plasma samples from people living with HIV (PLWH) in Turkey. Additionally, we explored the correlation between JCPyV presence, immunological parameters, and demographic factors, providing the first molecular epidemiological report of JCPyV in this population. A prospective, multicentre, cross-sectional study was conducted on 107 PLWH and 77 healthy controls. JCPyV DNA was detected and quantified using qPCR, and VP1 gene sequencing was performed to determine viral genotypes. Phylogenetic analysis was conducted using Clustal Omega and the Neighbour-Joining method with a bootstrap value of 1000.
Results
JCPyV viruria was detected in 46% of PLWH and 18.18% of healthy individuals, with no significant association between viruria frequency and immunodeficiency severity (
p
> 0.05). Genotype IV was the most prevalent (37.5%), followed by Genotype I (31.25%) and Genotype II (31.25%), aligning with European epidemiological data. No Genotype III was detected. No VP1 mutations associated with PML or immune evasion were identified. However, amino acid substitutions were observed at positions 74, 92, 116, 127, and 133, warranting further investigation.
Conclusion
This study provides the first molecular epidemiological analysis of JCPyV in PLWH from Turkey, demonstrating a genotype distribution consistent with European data. While no significant PML-associated VP1 mutations were detected, the identification of substitutions underscores the need for continued molecular surveillance. Understanding JCPyV genotype dynamics and immune evasion strategies is crucial for developing targeted therapeutics, including VP1-based vaccines and monoclonal antibody treatments for high-risk populations.
Journal Article
Characteristics of small airway disease in patients with HIV infection: insights from spirometry and impulse oscillometry
by
Culpan, Hazal Cansu
,
Tabak, Fehmi
,
Caliskaner Ozturk, Buket
in
Adult
,
Airway management
,
Antiretroviral drugs
2026
BackgroundAirway diseases that are independent of smoking behaviour are frequent in people living with HIV (PLWH). Spirometry, the gold standard for diagnosing airway diseases, may not detect small airway disease (SAD) when forced expiratory volume in 1 s/forced vital capacity is normal. However, impulse oscillometry (IOS) can detect SAD even when the spirometry is normal. This study aims to evaluate characteristics of SAD in PLWH by using IOS and exploring the diagnostic performance of IOS measurements to detect SAD.MethodsThis cross-sectional study included 127 PLWH on antiretroviral therapy without known airway disease. IOS was done first, followed by spirometry. Patients whose maximal mid-expiratory flow (MMEF) value was below 65% were defined as having spirometric SAD. Clinical characteristics and IOS measures were compared between those who had and those who did not have SAD. A receiver operating characteristic analysis was done to determine the diagnostic performance of IOS measures to diagnose spirometric SAD.ResultsMean age was 43.5±12.5 years and 60 patients were non-smokers. Spirometric SAD was observed in 34% of all patients. R5, R5–R20, AX and Fres were significantly higher in the patients who had spirometric SAD. Smoking history, duration of antiretroviral therapy and history of pneumonia were significantly associated with SAD. The optimal cut-off value for R5–R20 was 0.08 for SAD (sensitivity of 71.8% and specificity of 58.1%) and the optimal cut-off value for AX was 0.55 (sensitivity of 51.2% specificity of 91.7%).ConclusionSAD is common in PLWH and IOS may serve as a supportive tool for the clinical assessment of small airway involvement.
Journal Article
Change in species distribution and antifungal susceptibility of candidemias in an intensive care unit of a university hospital (10-year experience)
2021
Candidemia is a nosocomial infection mostly found in critically ill patients. Our objectives were to evaluate the change in distribution and resistance profile of Candida spp. isolated from candidemic patients in our intensive care unit over two 5-year periods spanning 15 years and to evaluate the risk factors. Records from the microbiology laboratory were obtained, from January 2004 to December 2008 and from January 2013 to December 2017, retrospectively. Antifungal susceptibility was performed by E-test and evaluated according to EUCAST breakpoints. A total of 210 candidemia cases occurred; 238 Candida spp. were isolated in 197 patients (58.8% male; mean age, 59.2 ± 19.6 years). The most predominant risk factor was central venous catheter use. Species distribution rates were 32%, 28%, 17%, and 11% for C. albicans (n = 76), C. parapsilosis (n = 67), C. glabrata (n = 40), and C. tropicalis (n = 27), respectively. Resistance rate to anidulafungin was high in C. parapsilosis over both periods and increased to 73% in the second period. Fluconazole showed a remarkable decrease for susceptibility in C. parapsilosis (94 to 49%). The prevalence of MDR C. parapsilosis (6%/33%) and C. glabrata (0%/44%) increased in the second period. We observed a predominance of non-albicans Candida spp., with C. parapsilosis being the most frequent and C. glabrata infections presenting with the highest mortality. High level of echinocandin resistance in C. parapsilosis and increasing prevalences of MDR C. parapsilosis and C. glabrata seem emerging challenges in our institution.
Journal Article
An eleven-year cohort of bloodstream infections in 552 febrile neutropenic patients: resistance profiles of Gram-negative bacteria as a predictor of mortality
2020
Antimicrobial stewardship is of major importance in patients with febrile neutropenia (FN). In this study, we aimed to investigate the trends in resistance and the relationship with mortality rates in patients with FN. The single-center surveillance data of inpatients with FN and diagnosed as microbiologically confirmed bloodstream infections (BSIs) between 2006 and 2016 were reviewed retrospectively. A total of 950 episodes in 552 patients with BSIs were analyzed. Of whom, 55.9% were male, the median age was 43 years, and 35.6% had acute myeloid leukemia. In total, 1016 microorganisms were isolated from blood cultures. Gram-negatives accounted for 42.4% (n = 403) of the episodes. Among Gram-negatives, Enterobacteriaceae accounted for 346 (86%) (E. coli, n = 197; 34% extended-spectrum β-lactamases (ESBL) producers, and Klebsiella spp., n = 120; 48.3% ESBL producers). Also, 24 (20.0%) of Klebsiella spp. had carbapenemase activity. There were 6 (5.0%) colistin-resistant Klebsiella spp. Thirteen (26.5%) of Pseudomonas spp. and 17 (60.7%) of Acinetobacter spp. had carbapenemase activity. There were 2 (5.6%) colistin-resistant Acinetobacter spp. The 30-day mortality rates were 12.0%, 21.5%, 34.6%, and 29.0% in BSIs due to Gram-positive, Gram-negative bacterial, fungal, and polymicrobial etiology respectively (p = 0.001). BSIs with ESBL-producing (p = 0.001) isolates, carbapenem (p < 0.001), and colistin-resistant isolates (p < 0.001) were associated with increased mortality risk. The tremendous rise in resistance rates among Gram-negatives is dreadfully related to increasing mortality and leads to sharp shifts toward extreme restrictions of unnecessary antibiotic uses. Antimicrobial stewardship in patients with FN requires vigilance and tailoring of treatment upon local surveillance data.
Journal Article
Predictors of Long-term Outcomes in the Older Adults with Community-Acquired Pneumonia
by
Tabak, Fehmi
,
Mete, Bilgul
,
Saltoğlu, Nese
in
Aged
,
Aged, 80 and over
,
Community-Acquired Infections - mortality
2021
Introduction: We aimed to determine the indicators for poor long-term outcome in older adults with community-acquired pneumonia (CAP). Methodology: Patients with CAP requiring hospitalization were included in this retrospective study. The long-term mortality was defined as all-cause 1-year mortality following hospital admission. Results: A total of 145 patients with CAP were recorded. The median age was 70 (18-103), of whom 94 (65%) were ≥ 65 years old and 86 (59.5%) were male. Long-term mortality rates following CAP requiring hospitalization were substantially high in both the younger (n = 16, 31.4%) and older adults (n=43, 45.7%). In univariate analysis, the Pneumonia Severity Index (PSI) (p = 0.007), mechanical ventilation (p > 0.001), mental status changes (p = 0.018) as well as the modified Charlson Comorbidity Index (p=0.001), presence of malignancy (p < 0.001) and hospital readmission (p < 0.001) were associated with long-term mortality in the older group. Our results revealed that the need for mechanical ventilation (OR = 47.61 CI = 5.38-500.0, p = 0.001) and hospital readmission (OR = 15.87 CI = 5.26-47.61, p < 0.001) were major independent predictors of 1-year mortality. Conclusions: Clinicians should consider the lethal possibilities of CAP even after hospital discharge. The need for mechanical ventilation and hospital readmission may predict long-term mortality. Therefore, the patients who have these predictors should be closely monitored.
Journal Article
Resistance Genes and Mortality in Carbapenem-resistant Klebsiella pneumoniae Bacteremias: Effects of the COVID-19 Pandemic
by
Otlu, Barış
,
Tabak, Fehmi
,
Kuşkucu, Mert Ahmet
in
Adult
,
Aged
,
Anti-Bacterial Agents - pharmacology
2024
Emerging carbapenem-resistant
(
) (CRKP) bacteremias are presenting significant public health risks due to limited treatment options and increased mortality.
isolates exhibit carbapenem resistance rates that vary from 25% to 50% throughout the European continent, including our country.
To assess the characteristics of CRKP bacteremia, a condition that has recently demonstrated an increasing prevalence in our center. We sought to ascertain the resistance rates of isolated strains to antibiotics other than carbapenems, identify the responsible carbapenemase genes, evaluate the efficacy of antibiotics, determine mortality rates, explore clonality among strains, and investigate the influence of the COVID-19 pandemic on all these factors.
Retrospective observational study.
This study included patients aged 18 and older who had experienced meropenem-resistant
bacteremia. Meropenem resistance was confirmed by employing the Kirby-Bauer disk diffusion method. Meropenem minimum inhibitory concentration (MIC) levels were determined using the gradient test, while colistin MIC levels were ascertained using the disk elution technique. Carbapenemase genes were evaluated via colony polymerase chain reaction (PCR), and clonality analysis was performed using the arbitrarily primed PCR technique.
The study comprised 230 patients, with a mean age of 63.1 ± 15.9 years, of whom 58.7% were male. Oxacillinase-48 (OXA-48) was detected in 74.8% of the patients, New Delhi metallo-beta-lactamase (NDM) in 12.6%, OXA-48 + NDM in 7.8%, and KPC in 4.8%. The 14-day and 30-day mortality rates were 57% and 69.6%, respectively. Multivariate analysis of the 30-day mortality revealed several crucial factors, including bacteremia development in the intensive care unit, the occurrence of bacteremia during the COVID-19 pandemic, polymicrobial bacteremia, the use of indwelling intravenous catheters, a platelet count of ≤ 140,000/μl, procalcitonin levels of ≥ 6 μg/l, and a Charlson comorbidity score ≥ 3. Notably, the
and
genes were upregulated significantly during the COVID-19 pandemic, while the
gene groups were downregulated. Additionally, both 14-day and 30-day mortality rates increased significantly.
In this study, the most prevalent carbapenemase gene was OXA-48; however, there has been a recent increase in
genes. No dominant epidemic strain was identified through clonality analysis. The clustering rate was 68% before the pandemic, increasing to 85.7% during the pandemic. The significance of infection control measures is underscored by the rise in both clustering and mortality rates during the COVID-19 pandemic.
Journal Article