Mahmoud Balata

Aims: Transcatheter aortic valve implantation (TAVI) is associated with procedure‐related stroke. Cerebral embolic protection devices (CEPDs) are designed to reduce the risk of embolic debris reaching the brain; however, the evidence supporting their efficacy remains controversial. We aim to evaluate the efficacy and safety of CEPDs in patients undergoing TAVI. Methods: Major databases were systematically searched up to April 2025. Only randomized controlled trials (RCTs) were included and critically appraised using the Cochrane Risk of Bias (ROB‐2) tool. We calculated risk ratios (RRs) with the 95% confidence intervals for the outcomes, and trial sequential analysis (TSA) was conducted to reduce the risk of false‐positive results due to random errors. Results: Eight RCTs (11,589 patients) were analyzed. No significant difference was observed in overall stroke incidence between CEPD and control groups (0.92 (95% CI: 0.75–1.14; p = 0.40, I ² = 0%), including disabling and non‐disabling strokes. Device‐specific analyses showed a non‐significant reduction in disabling stroke with the Sentinel device. All‐cause mortality, transient ischemic attacks, bleeding, acute kidney injury, delirium, and pacemaker implantation rates were similar between groups. CEPD use was linked to a transient improvement in cognitive function (MoCA scores) at 2–5 days post‐TAVI, but this effect was not sustained at later follow‐ups. TSA indicated that current evidence is insufficient to definitively refute CEPD efficacy. Conclusion: CEPDs show no significant reduction in overall, disabling, or non‐disabling stroke, nor in all‐cause mortality post‐TAVI. Trial Registration: This meta‐analysis was registered on PROSPERO. No.: CRD420251026208.

Background: Patients with type 2 diabetes mellitus (T2DM) undergoing percutaneous coronary intervention (PCI) are at high risk of adverse cardiovascular and renal outcomes. While both sodium–glucose cotransporter-2 inhibitors (SGLT-2i) and dipeptidyl peptidase-4 inhibitors (DPP-4i) are widely used in this population, direct evidence comparing their long-term efficacy and safety after PCI remains scarce. This meta-analysis aimed to compare cardiovascular and renal outcomes between SGLT-2i and DPP-4i in patients with T2DM post-PCI. Methods: PubMed, Web of Science, Scopus, and Cochrane CENTRAL were searched through June 2025. Primary outcomes were all-cause mortality, worsening renal function, and heart failure. We included primary studies and assessed the quality of studies using Newcastle Ottawa Scale. RevMan software was used to calculate hazard ratios (HR) estimates and 95% confidence intervals (CI) using the random-effects model. Results: We analyzed the outcomes between SGLT-2i ( n = 7,025 patients) and DPP-4i ( n = 7,459 patients). The mean age was 62.7 years, and 77.4% were males. SGLT-2i significantly reduced all-cause mortality (HR = 0.65; 95% CI: 0.54–0.79; P < 0.001) and the risk of worsening renal function (HR = 0.15; 95% CI: 0.09–0.26; P < 0.001). They also demonstrated a significant reduction in heart failure events (HR = 0.59; 95% CI: 0.48–0.74; P < 0.001). For myocardial infarction, a non-significant trend toward risk reduction with SGLT-2i was observed (HR = 0.85; 95% CI: 0.72–1.02; P = 0.08). For cerebrovascular accidents and the need for repeat revascularization (PCI/CABG), no significant difference was observed. Conclusion: SGLT-2i demonstrates more clinical benefits, and current evidence supports its initiation over DPP-4i in T2DM patients after PCI.

Introduction Early integration of palliative care (EIPC) has been proposed to improve quality of life in heart failure (HF), but evidence is mixed and potential differences by HF subtype remain unclear. This exploratory secondary analysis of the EPCHF trial examined whether patient-reported outcomes differed between patients with and without reduced EF. Methods A total of 205 patients with symptomatic HF were randomized 1:1 to EIPC or standard care in the EPCHF trial. For this exploratory analysis, patients were stratified by left ventricular ejection fraction (≤ 40% vs > 40%). Patient-reported outcomes were assessed over 12 months using the Kansas City Cardiomyopathy Questionnaire (KCCQ), Functional Assessment of Chronic Illness Therapy–Palliative Care (FACIT-PAL), Hospital Anxiety and Depression Scale (HADS), MIDOS, and FACIT–SP12. Results KCCQ scores, HADS-anxiety, and MIDOS symptom intensity improved significantly over 12 months in both EIPC and control groups, with no significant between-group differences in either EF subgroup. Reductions in HADS-depression occurred only in patients with HFrEF, with similar improvements in both EIPC (–1.37; 95% CI: –2.31 to –0.44; p = 0.004) and control (–1.99; 95% CI: –2.89 to –1.09; p < 0.001). Among patients with LVEF > 40%, EIPC produced a significant improvement in spiritual well-being compared with standard care (mean difference 3.47; 95% CI: 0.32 to 6.62; p = 0.031), whereas the control group showed no improvement. Mortality and hospitalization rates did not differ between groups. Conclusion In this exploratory EF-stratified analysis of EPCHF trial, EIPC did not improve overall HRQOL, mood, or symptom burden compared with standard care. A significant effect was observed only for spiritual well-being in patients with LVEF > 40%, suggesting that this subgroup may have distinct supportive-care needs warranting further investigation. Graphical Abstract

Host genetic factors influencing immune regulation are believed to modulate susceptibility to hepatitis C virus (HCV) and related hepatocellular carcinoma (HCC). This study aimed to investigate the association of Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) genetic variants with HCV-related HCC risk, soluble CTLA-4 (sCTLA-4) levels, and disease severity. 225 age- and sex-matched participants (75 controls, 75 HCV, and 75 HCV-HCC) were enrolled. TaqMan allelic discrimination assays were used for genotyping three CTLA-4 SNPs, and sCTLA-4 was quantified by ELISA. Our results demonstrated that the rs231726 TT genotype and T-allele were significantly associated with HCC. The rs11571317 CC genotype and C-allele, alongside the rs13384548 GG genotype and G-allele, conferred increased risk for both HCV and HCC. Clinically, these high-risk genotypes correlated with worse liver function (Child–Pugh C), higher MELD/Na scores, and larger tumors. Moreover, sCTLA-4 levels showed a stepwise elevation from controls to HCV to HCC patients, peaking in carriers of the rs231726 TT and rs13384548 GG genotypes. In conclusion, this study identifies rs231726, rs11571317, and rs13384548 as robust genetic markers for HCV-related HCC susceptibility and cancer aggressiveness. Our findings provide novel evidence of their role in immune evasion through sCTLA-4 upregulation, offering new perspectives into genotype-based risk stratification and tailored immunotherapeutic strategies.

Background: Sodium‐glucose cotransporter‐2 inhibitors (SGLT2is) reduce cardiovascular mortality and heart failure (HF)‐related hospitalizations in HF patients. However, the mechanisms underlying these benefits remain unclear, and it is uncertain whether empagliflozin and dapagliflozin have differential effects on cardiac structure and function.Aim: This study aims to compare the effects of these two SGLT2is on left ventricular echocardiographic parameters in HF patients over 1 year.Methods: This retrospective study included 558 consecutive HF patients newly prescribed either dapagliflozin or empagliflozin. Key echocardiographic parameters, such as peak E‐wave velocity, E/e' ratio, left atrial volume index (LAVI), LV end‐diastolic and end‐systolic volumes (LV‐EDVI, LV‐ESVI), LV mass index (LV‐MI), relative wall thickness (RWT), LV sphericity index (LV‐SI), and ejection fraction (LVEF), were measured at baseline and after 1 year.Results: At 1‐year, significant reductions were observed only in the empagliflozin group for peak E‐wave velocity (mean difference = −12.76 cm/s, 95% CI: −16.26 to −9.27, p < 0.001), E/e' ratio (mean difference = −3.04, 95% CI: −4.17 to −1.91, p < 0.001), and LV sphericity index (LV‐SI; mean difference = −0.01, 95% CI: −0.02 to −0.0005, p = 0.040). Both SGLT2is significantly improved E‐wave deceleration time, LAVI, LV‐EDVI, LV‐ESVI, LV‐MI, and LVEF. Neither medication produced significant changes in RWT, and no significant differences were noted between groups regarding HF hospitalizations or all‐cause mortality.Conclusion: Empagliflozin demonstrated more pronounced effects on LV remodeling markers, including peak E‐wave velocity, E/e' ratio, and LV‐SI, compared to dapagliflozin. These findings suggest potential efficacy differences between SGLT2is, highlighting the need for future randomized comparative studies.

Background: Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive neoplasm often diagnosed at advanced stages. Immune checkpoint molecules, particularly programmed cell death protein-1 (PD-1) and its ligand PD-L1, are pivotal in tumor immune evasion. Genetic polymorphisms in PD-1/PD-L1 and their soluble isoforms (sPD-1/sPD-L1) may influence individual susceptibility to cancer and disease progression. Therefore, this study was conducted to examine the correlation between PD-1/PD-L1 gene polymorphisms, serum levels of sPD-1/sPD-L1, and their association with PDAC susceptibility, severity, and prognostication. Methods: This case–control study was performed with 150 PDAC patients and 150 controls. Clinical and laboratory data, including tumor markers (CA19-9 and CEA), were recorded. Allele-specific PCR was utilized to genotype PD-1 (rs6749527 and rs7421861) and PD-L1 (rs2297136, and rs4143815). sPD-1/sPD-L1 were quantified with ELISA. Mapping of the Kaplan–Meier survival curve of mutant genes was performed. Results: The rs7421861 AG and GG and rs4143815 GG genotypes, together with their G-alleles, were linked to increased PDAC risk and greater tumor burden. In contrast, the rs2297136 GG genotype and G-allele conferred protection against PDAC development. Serum sPD-L1 levels, rather than sPD-1, were markedly elevated in PDAC patients, progressively increased with tumor grade, and correlated with tumor markers. Also, higher PD-L1 gene expression was associated with lower overall survival. Conclusions: PD-1/PD-L1 genetic variants, particularly rs7421861 and rs4143815, along with sPD-L1 levels, correlate with PDAC susceptibility and disease severity. These findings endorse the prospects of integrating immune checkpoint genetic variants and soluble biomarkers for early identification, risk stratification, prognostication, and personalized therapeutic strategies in PDAC management.

Background: Mitral regurgitation (MR) presents either as primary or secondary, with options for surgical or transcatheter repair. Thromboembolic risks following surgery are significant despite the use of antithrombotic medications, and guidelines for postoperative anticoagulation therapy lack consistency. This systematic review aims to compare antithrombotic medications after mitral valve repair (MVR). In this study, we intend to compare antithrombotic medications after MVR. Materials and methods: The study followed the Cochrane handbook and PRISMA guidelines. We systematically searched databases (PubMed, Scopus, Ovid, Cochrane, Web of Science) until June 2024 for TMVR studies using specific criteria. Quality assessment utilized the Newcastle-Ottawa scale. Data extraction encompassed study characteristics and outcomes. Primary outcomes included thromboembolic events and bleeding within six months. Statistical analysis employed R software to assess heterogeneity and publication bias. Results: From the 121 articles screened, 12 were included in the study. These cohort studies, involving 20,644 participants, spanned from 2008 to 2022. While most studies were of good to high quality, some exhibited lower quality. Analysis favored oral anticoagulants (OAC) over single antiplatelet therapy (SAPT) for reducing bleeding risk (RR = 0.31, 95% CI: [0.11–0.87], P < 0.05), with moderate heterogeneity. Thromboembolic events did not significantly differ among interventions. Transient ischemic attacks and stroke outcomes were similar between SAPT and vitamin K antagonists (VKA). Six-month mortality rates were comparable between SAPT and VKA, with notable heterogeneity and higher mortality with SAPT in one study. Qualitative synthesis highlighted procedural success rates and bleeding complications across different interventions in transcatheter mitral valve repair studies. Conclusion: OACs showed a lower risk of bleeding compared to antiplatelet therapies, while VKAs and OAC + SAPT may reduce thromboembolic events. No significant differences were found in stroke, TIA, or short-term mortality. These findings support individualized therapy and highlight the need for further randomized trials.