Cisplatin- or Carboplatin-Based Chemotherapy Plus Pembrolizumab in Advanced Urothelial Cancer: Exploratory Analysis From the Phase 3 KEYNOTE-361 Study.

Introduction: KEYNOTE-361 evaluated first-line pembrolizumab with and without platinum-based chemotherapy versus chemotherapy alone in advanced or metastatic urothelial carcinoma. The primary end points of progression-free survival (PFS) or overall survival (OS) were not met. Exploratory analysis of efficacy by platinum agent (cisplatin or carboplatin) is reported.

Association of Tumor Mutational Burden and PD-L1 with the Efficacy of Pembrolizumab with or without Chemotherapy versus Chemotherapy in Advanced Urothelial Carcinoma.

Purpose: The three-arm, phase III KEYNOTE-361 study did not meet its dual primary endpoints of progression-free survival (PFS) or overall survival (OS) with first-line pembrolizumab plus chemotherapy versus chemotherapy in advanced urothelial carcinoma. This prespecified exploratory analysis assessed the association of tumor mutational burden (TMB) and PD-L1 combined positive score (CPS) with clinical outcomes.

Patients And Methods: TMB and PD-L1 CPS were determined via whole-exome sequencing and PD-L1 IHC 22C3 pharmDx, respectively.

Assessment of Genetic Variants Linked to Susceptibility to Mechanical Prosthetic Valve Thrombosis.

Prosthetic valve thrombosis (PVT) is a critical and life-threatening condition driven by multifactorial etiologies, including genetic predispositions. The study was designed as a single-center retrospective manner. Echocardiographic features and genetic test including factor II/prothrombin (G20210A), factor V Leiden (G1691A), factor V R2 (A4070G), apolipoprotein (Apo) B-100 (G10708A), ApoE (C112R), ApoE (R158C), methylenetetrahydrofolate reductase (MTHFR) C677T, MTHFR A1298C, factor XIII G103T (V34L), β-fibrinogen (455G>A), PAI-1 4G/5G, and HPA-1 GPIIIa (T196C) genotyping variations were assessed.

Affecting Factors Unfavorable Treatment Outcomes of Rifampicin-resistant/Multidrug-resistant Tuberculosis Patients Treated with Long-term Regimen.

Background: Drug-resistant tuberculosis (DR-TB) poses a significant threat to global TB control and remains a major public health issue. This study aims to evaluate treatment outcomes and identify risk factors for unfavorable outcomes in patients with multi-DR-TB (MDR-TB) treated at a major reference hospital in Istanbul.

Methods: We conducted a retrospective analysis of 413 patients with rifampicin-resistant and MDR-TB who received treatment between January 1, 2013, and December 31, 2023, at the University of Health Sciences Süreyyapaşa Chest Diseases Training and Research Hospital.

vNOTES scarless and painless endometrial cancer staging surgery.

Aims: Sentinel lymph node dissection is performed in endometrial cancer surgery instead of staging surgery, particularly when the disease is advanced and confined to the uterus. The aim of this study is to share our sentinel lymph node detection rates via the vaginal natural orifice transluminal endoscopic surgery method with the literature and to demonstrate a safer and more comfortable surgical treatment process.

Methods: The analysis includes the patients who underwent surgery sentinel lymph node dissection for endometrial cancer utilizing indociyanin green in our center between January 2022 and June 2024.

Percutaneous Delivery of Oncogel for Targeted Liver Tumor Ablation and Controlled Release of Therapeutics.

Advanced-stage liver cancers are associated with poor prognosis and have limited treatment options, often leading the patient to hospice care. Percutaneous intratumoral injection of anticancer agents has emerged as a potential alternative to systemic therapy to overcome tumor barriers, increase bioavailability, potentiate immunotherapy, and avoid systemic toxicity, which advanced-stage cancer patients cannot tolerate. Here, an injectable OncoGel (OG) comprising of a nanocomposite hydrogel loaded with an ionic liquid (IL) is developed for achieving a predictable and uniform tumor ablation and long-term slow release of anticancer agents into the ablation zone.

Artificial intelligence based diagnosis of sulcus: assesment of videostroboscopy via deep learning.

Purpose: To develop a convolutional neural network (CNN)-based model for classifying videostroboscopic images of patients with sulcus, benign vocal fold (VF) lesions, and healthy VFs to improve clinicians' accuracy in diagnosis during videostroboscopies when evaluating sulcus.

Materials And Methods: Videostroboscopies of 433 individuals who were diagnosed with sulcus (91), who were diagnosed with benign VF diseases (i.e.

Effects of captan, mancozeb and azoxystrobin fungicides on motility, oxidative stress and fatty acid profiles in rainbow trout (Oncorhynchus mykiss) spermatozoa.

An in vitro study using rainbow trout spermatozoa was designed to evaluate the toxic effects of different concentrations of captan (CPT), mancozeb (MCZ), and azoxystrobin (AZX) fungicides on motility parameters, lipid peroxidation, SOD activity, total antioxidant capacity (TAC), and DPPH inhibition. Moreover, changes in fatty acids profiles caused by the fungicides were determined for the first time. The results revealed that motility parameters, SOD activities, TAC values, and DPPH inhibitions decreased significantly while lipid peroxidation increased after ≥2 µg/L of CPT, ≥1 µg/L of MCZ, and ≥5 µg/L of AZX incubations for 2 h at 4 °C.

Prostate tissue ablation and drug delivery by an image-guided injectable ionic liquid in ex vivo and in vivo models.

Benign prostatic hyperplasia and prostate cancer are often associated with lower urinary tract symptoms, which can severely affect patient quality of life. To address this challenge, we developed and optimized an injectable compound, prostate ablation and drug delivery agent (PADA), for percutaneous prostate tissue ablation and concurrently delivered therapeutic agents. PADA is an ionic liquid composed of choline and geranic acid mixed with anticancer therapeutics and a contrast agent.

Pembrolizumab for advanced urothelial carcinoma: exploratory ctDNA biomarker analyses of the KEYNOTE-361 phase 3 trial.

Circulating tumor DNA (ctDNA) is emerging as a potential biomarker in early-stage urothelial cancer, but its utility in metastatic disease remains unknown. In the phase 3 KEYNOTE-361 study, pembrolizumab with and without chemotherapy was compared with chemotherapy alone in patients with metastatic urothelial cancer. The study did not meet prespecified efficacy thresholds for statistical significance.

Medical reasons for permanent and temporary disqualification of Turkish civil aviation pilots.

The aim of this study was to identify diseases that result in permanent and temporary medical disqualification for civil aviation pilots and their changes over the years. A retrospective analysis was conducted on the medical examination records performed in Turkey from 2018 to 2022, in accordance with ICAO and EASA standards. The permanent disqualification rate was 1.

Catheter-Directed Ionic Liquid Embolic Agent for Rapid Portal Vein Embolization, Segmentectomy, and Bile Duct Ablation.

Embolic materials currently in use for portal vein embolization (PVE) do not treat the tumor, which poses a risk for tumor progression during the interval between PVE and surgical resection. Here, is developed an ionic-liquid-based embolic material (LEAD) for portal vein embolization, liver ablation, and drug delivery. LEAD is optimized and characterized for diffusivity, X-ray visibility, and cytotoxicity.

Combination anticoagulation strategy in pregnancy with mechanical valves: The KYBELE study.

Background: Optimal first-trimester anticoagulation is still challenging in pregnant women with mechanical heart valves (MHVs) requiring high-dose warfarin. This multicenter prospective study aims to determine the optimal anticoagulation regimens for pregnant patients with MHVs.

Methods: All women were allocated to one of three treatment options during first trimester including lone low-molecular-weight heparin (LMWH), combination of LMWH + 2.

Management of prosthetic valve thrombosis with unfractionated heparin.

Background: Prosthetic valve thrombosis (PVT) is a severe and life-threatening complication. Surgery and thrombolytic therapy (TT) carry a high risk, and in several circumstances, optimal anticoagulation with unfractionated heparin (UFH) infusion may be an alternative treatment. This study aimed to assess the results of UFH in patients diagnosed with both obstructive and non-obstructive PVT.

Bioengineered Ionic Liquid for Catheter-Directed Tissue Ablation, Drug Delivery, and Embolization.

Delivery of therapeutics to solid tumors with high bioavailability remains a challenge and is likely the main contributor to the ineffectiveness of immunotherapy and chemotherapy. Here, a catheter-directed ionic liquid embolic (ILE) is bioengineered to achieve durable vascular embolization, uniform tissue ablation, and drug delivery in non-survival and survival porcine models of embolization, outperforming the clinically used embolic agents. To simulate the clinical scenario, rabbit VX2 orthotopic liver tumors are treated showing successful trans-arterial delivery of Nivolumab and effective tumor ablation.

Advances and Challenges in Interventional Immuno-Oncology Locoregional Therapies.

Interventional immuno-oncology is making strides in locoregional therapies to address complex tumor microenvironments. Long-standing interventional radiology cancer therapies, such as tumor ablation and embolization, are being recharacterized in the context of immunotherapy. Intratumoral injections, such as those of genetically engineered or unaltered viruses, and the delivery of immune cells, antibodies, proteins, or cytokines into targeted tumors, along with advancements in delivery techniques, have produced promising results in preliminary studies, indicating their antitumor effectiveness.

Transcatheter Closure or Surgery for Symptomatic Paravalvular Leaks: The Multicenter KISS Registry.

Background: The optimal treatment of symptomatic paravalvular leak (PVL) remains controversial between transcatheter closure (TC) and surgery. This large-scale study aimed to retrospectively evaluate the long-term outcomes of the patients who underwent reoperation or TC of PVLs.

Methods And Results: A total of 335 (men, 209 [62.

Transcatheter mitral paravalvular closure: a single centre experience with techniques and outcomes.

Background: In patients with symptomatic mitral PVL, successful transcatheter reduction of the PVL to less than mild is associated with significant improvement in short- and midterm survival.

Objectives: In this study, we present our single-centre, same operators' experience on percutaneous paravalvular leak closure with techniques and outcomes.

Methods: In this retrospective observational designed study, we retrieved hospital records of patients with a surgical history of mechanical or biological prosthetic valve replacement and who subsequently underwent transcatheter mitral paravalvular leak closure (TMPLC).

A Comprehensive Evaluation of National Cardiology Congresses Abstracts on the Basis of the 2016 Academic Criteria.

Objective: This study aimed to describe the effects of new academic criteria established in 2016 on the abstracts of the National Congress of the Turkish Society of Cardiology.

Methods: The abstracts presented at 13 consecutive annual congresses were obtained. A literature search was conducted with PubMed, Google Scholar, and Web of Science databases to analyze whether the abstract was published in a scientific journal.

Effect of adenomyosis on prognosis of patients with endometrial cancer.

Objective: Our goal was to contrast the prognoses of patients with endometrial cancer who had adenomyosis against those that did not.

Methods: All patients who had received surgical staging for hysterectomy-based endometrial cancer had their medical data retrospectively examined. The analysis covered 397 patients, who were split into two groups depending on the presence of adenomyosis.

Monitoring of Hypochlorite Level in Fruits, Vegetables, and Dairy Products: A BODIPY-Based Fluorescent Probe for the Rapid and Highly Selective Detection of Hypochlorite.

Hypochlorite/hypochlorous acid (ClO/HOCl), among the diverse reactive oxygen species, plays a vital role in various biological processes. Besides, ClO is widely known as a sanitizer for fruits, vegetables, and fresh-cut produce, killing bacteria and pathogens. However, excessive level of ClO can lead to the oxidation of biomolecules such as DNA, RNA, and proteins, threatening vital organs.

An Anthracene and Indole-based Fluorescent Probe for the Detection of Chromium(III) Ions in Real Water Samples.

A novel fluorescent probe possessing anthracene with an indole unit was designed and synthesized to detect chromium(III) ions (Cr) with high sensitivity and selectivity. The probe was synthesized in one step by mixing two commercially available chemicals, 2-aminoanthracene and Indole-5-carboxaldehyde. The probe molecule (ANT-In) demonstrates distinct properties, for instance, "turn-on" fluorescence response, high sensitivity and selectivity in less than one minute, and low detection limit (0.

The genetic history of the Southern Arc: A bridge between West Asia and Europe.

By sequencing 727 ancient individuals from the Southern Arc (Anatolia and its neighbors in Southeastern Europe and West Asia) over 10,000 years, we contextualize its Chalcolithic period and Bronze Age (about 5000 to 1000 BCE), when extensive gene flow entangled it with the Eurasian steppe. Two streams of migration transmitted Caucasus and Anatolian/Levantine ancestry northward, and the Yamnaya pastoralists, formed on the steppe, then spread southward into the Balkans and across the Caucasus into Armenia, where they left numerous patrilineal descendants. Anatolia was transformed by intra-West Asian gene flow, with negligible impact of the later Yamnaya migrations.