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    New Biomarkers and Immunotherapy Decision
    (Bentham Science Publishers, 2022) Yigit, Abdurrahman; Kuscu, Berkay; Kirik, Ali; Ozcaglayan, Ruhsen; Afsar, Cigdem Usul
    As immune checkpoint blockade and other immune-based therapy approaches lead to broad treatment advances among patients with advanced cancer, an important consideration is how to best select patients whose tumors will respond to these therapies. As a consequence predictive and prognostic markers are needed. There are genomic features, such as tumour mutation burden (TMB), microsatellite instability (MSI), and immune phenotype features, such as programmed death-ligand 1 (PD-L1), CTLA-4 and tumour infiltrating lymphocytes (TILs), to predict response to immunotherapies (ITs). Several studies show the correlation between TMB and predicted neoantigen load across multiple cancer types. Response to immune checkpoint inhibitors is higher in tumours with high TMB. The candidate biomarker that has been studied mostly other than TMB is PD-L1 expression in trials utilizing programmed cell death-1 (PD-1) blockade. PD-L1 and PD-1 expression are dynamic markers that change in relation to local cytokines and other factors, and the thresholds that separate “positive” and “negative” PD-L1 expressions remain under debate. PD-L1 expression is now a routine diagnostic marker for patients with newly diagnosed NSCLC. The potential applicability of PD-L1 in other disease settings is still uncertain. Microsatellite instability is characterised by high rates of alterations to repetitive DNA sequences caused by impaired mismatch repair (MMR); MSI was the biomarker was approved according to tumor's initial location. Combining TMB with specific genomic alterations is crucial. Moreover, new biomarkers are being investigated. © 2022, Bentham Books imprint.
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    Prevalence of MASLD and Fibrosis Risk in Turkish Adults with Cardiometabolic Risk Factors: A Nationwide Multicenter Study (DAHUDER MASLD Study)
    (Mdpi, 2025) Kirik, Ali; Sumbul, Hilmi Erdem; Koca, Nizameddin; Kilit, Turkan Pasali; Sezer, Sibel Demiral; Binnetoglu, Emine; Arac, Esref
    Introduction: Metabolic dysfunction-associated steatotic liver disease (MASLD) prevalence data in Turkiye is limited. We aimed to determine the nationwide prevalence of MASLD and advanced hepatic fibrosis risk in subjects with cardiometabolic risk factors (CMRF). Despite recent international consensus redefining fatty liver disease terminology, no nationwide MASLD study has been reported in Turkiye. Methods: This cross-sectional study included 14,371 adults with >= 1 CMRF from 44 centers across 31 cities. MASLD was diagnosed using liver ultrasonography plus cardiometabolic criteria. Advanced fibrosis risk was assessed by fibrosis-4 (FIB-4) score (>= 1.3 for <= 65 years; >= 2.0 for >65 years). Logistic regression was used to identify independent predictors of high FIB-4. Results: A total of 61.4% of participants were women, the mean age was 51.3 +/- 14.4 years, and the mean BMI was 31.4 +/- 6.0 kg/m(2). MASLD prevalence was 75.7% (n = 10,873), rising with the number of CMRFs (56.5% with one factor vs. 83.4% with all). The prevalence of high FIB-4 scores was 12.0% overall, being lower in MASLD patients than non-MASLD patients (11.2% vs. 14.4%, p < 0.001). FIB-4 scores decreased with increasing BMI (28.1% underweight vs. 8.7% class III obesity). Male sex, T2DM, and hypertension independently predicted high FIB-4 scores, while smoking, higher BMI, and MASLD were inversely associated. Conclusions: Three-quarters of Turkish adults with CMRF have MASLD. Standard FIB-4 thresholds may underestimate fibrosis risk in obese and smoking populations, underscoring the need for adjusted cut-offs or alternative tools. This study is the first to provide nationwide MASLD prevalence data in Turkiye.