Citations

Background Caffeine plays a dual role in headache disorders, acting as an analgesic adjuvant while potentially contributing to headache chronification. Its relationship with medication-overuse headache (MOH) and the severity of analgesic dependence remains insufficiently characterized. The study aimed to compare MOH and non-MOH patients in terms of headache burden, psychological characteristics, and caffeine use, and secondarily to assess whether caffeine use disorder is associated with severity of dependence on analgesics in MOH. Methods This is a cross-sectional study conducted on adults with primary headache disorders. Participants were asked to complete the following validated questionnaires: caffeine food frequency (C-FFQ), caffeine use disorder (CUDQ), headache impact test-6 (HIT-6), Severity of Dependence Scale (SDS). Depression Anxiety Stress Scales–12 (DASS-12), and Substance Use Risk Profile Scale (SURPS). Headache diaries were reviewed to document monthly headache days (MHD) and acute medication days (AMD); subsequently, patients were divided into MOH or non-MOH groups, according to ICHD-3 criteria. Results Among 482 patients with primary headache disorders, 160 (33.2%) fulfilled ICHD-3 criteria for MOH. Patients with MOH had significantly higher MHD, AMD, HIT-6 scores, DASS-12 and SURPS total scores than those with non-MOH (all p < 0.001). Heavy caffeine consumption was more prevalent in MOH patients (23.8% vs. 9.3%), who also demonstrated higher CUDQ scores (median 10 vs. 7, p < 0.001). CUDQ scores correlated positively with MHD, AMD, HIT-6, DASS-12, and SURPS (all p < 0.001). Among patients with MOH, SDS scores correlated with MHD, AMD, HIT-6, DASS-12, SURPS, and CUDQ scores (all p < 0.05). Multivariable regression analysis revealed that AMD, HIT-6 score, and CUDQ score were independently associated with SDS scores ( p -value = 0.002, 0.046, 0.002, respectively). Conclusion Patients with MOH had significantly greater headache burden, psychological distress, and caffeine consumption compared with those without MOH. Caffeine use disorder is significantly associated with greater severity of analgesic dependence in patients with MOH. These findings highlight the importance of assessing caffeine-related behaviors when evaluating patients with MOH and suggest that caffeine use disorder may represent a clinically relevant behavioral factor associated with medication dependence severity.

Variability in novel inflammatory markers (HBP and SAA) post-surgery could indicate ongoing perioperative inflammation. This pilot cohort study collected blood from 99 patients undergoing elective cardiac surgery at baseline, 24 hours, 7 days, and 3 months post-surgery. Inflammatory markers (HBP, SAA, PCT, CRP, IL-6) were measured with a point-of-care device. Demographic and clinical data were extracted from health records. Serum SAA increased significantly in the acute postoperative phase (M e [IQR];SAA baseline =81.1[87] vs SAA 24hr= 232.65[88.02];U[72]=2343,p<0.0001), remained elevated at 7 days (Me 7d =252.6[88.56];U[57]=1484,p<0.0001) and were still more pronounced than baseline at t 3m (Me 3m =118.44[101.52];U[38]=448,p=0.0008). HBP showed a significant rise at seven days (HBP baseline =45[26;89] vs HBP 7d =121[69.75;224.5]; U[56]=805,p<0.0001) then returned to near baseline by t 3m (Me 3m =32.5[15.75;98.5]). Traditional inflammatory markers PCT, CRP, and IL-6 demonstrated a rapid increase at t 24h and plateaued at t 7d . None of the biomarkers showed variability at baseline or postoperatively with preoperative status or postoperative complications. Cluster analysis of the inflammatory markers at 24 hours (t 24h ) identified distinct subgroups. Cluster #1-patients with a modest increase in all markers; Cluster#2 characterized with a robust increase in IL-6; Cluster #3 showed increase in CRP and decline in HBP; Cluster #4 showed a modest increase in IL-6 and decline in HBP; Cluster #5 represented a decline in both CRP and SAA. Patients in these clusters differ with respect to age, pre-existing peripheral artery disease, and borderline differences in perioperative acetaminophen use. SAA and HBP remain elevated longer than IL-6, CRP, and PCT after surgery, suggesting that inflammation may persist beyond 3 months.

Background: Heart transplantation (HT) remains the definitive therapy for end-stage heart failure, yet rejection and cardiac allograft vasculopathy (CAV) continue to limit long-term outcomes. Beyond donor-specific HLA antibodies, non-HLA antibodies, particularly anti-angiotensin II type 1 receptor antibodies (AT1R-Abs), have been implicated in allograft injury, but published findings are heterogeneous. Aim: The aim of this study is to systematically evaluate the evidence linking AT1R gene expression and anti-AT1R antibodies with key post-heart transplant outcomes. Methods: We conducted a systematic review in accordance with PRISMA guidelines. Scopus, PubMed, Web of Science, and the Cochrane Library were searched (December 2025) for cohort and case–control studies evaluating AT1R gene expression and/or AT1R-Ab status in HT recipients and their association with post-transplant outcomes. Two reviewers independently screened studies, extracted data, and assessed risk of bias using the NIH Quality Assessment Tool. Results: Twelve studies encompassing 951 recipients met the inclusion criteria. Five studies evaluated AT1R mRNA expression, reporting variable patterns: several observed reduced AT1R/AT2R transcription after transplantation without clear clinical correlation, whereas others associated higher donor or recipient AT1R expression with transplant coronary artery disease and recurrent rejection. AT1R-Ab prevalence varied widely and appeared to increase after mechanical circulatory support, with substantial seroconversion reported during LVAD support in initially antibody-negative patients. Associations between AT1R-Ab and acute cellular rejection and antibody-mediated rejection were inconsistent across studies, and survival findings were inconclusive; however, some reports linked elevated AT1R-Abs to poorer long-term freedom from adverse events. Evidence regarding CAV was mixed, with signals of increased vasculopathy risk in some cohorts but not others. Conclusions: Current evidence suggests a potential role for AT1R expression and AT1R-Abs in cardiac allograft dysfunction, including rejection phenotypes and vasculopathy. Larger prospective studies with harmonized testing strategies are needed to define clinically meaningful AT1R-Ab cutoffs and clarify their utility in risk stratification and targeted therapeutic trials.

ABSTRACT Background In patients with atrial fibrillation (AF) and heart failure with reduced ejection fraction (HFrEF), atrioventricular node ablation (AVNA) and permanent pacing are often pursued when rhythm control is not pursued. Biventricular pacing (BiVP) has demonstrated benefits over right ventricular pacing, while conduction system pacing (CSP) has emerged as an alternative. However, evidence directly comparing CSP with BiVP in this high‐risk population remains inconsistent. Objective To compare CSP versus BiVP in patients with AF and HFrEF undergoing AVNA, focusing on cardiac function, clinical outcomes, and procedural metrics. Methods Following PRISMA guidelines, we searched PubMed, Scopus, and Web of Science through February 2026 for studies comparing CSP and BiVP in adults with AF and HFrEF undergoing AVNA. Outcomes included all‐cause mortality, heart failure hospitalization (HFH), changes in left ventricular ejection fraction (LVEF), QRS duration, New York Heart Association (NYHA) class, pacing threshold, procedure duration, and fluoroscopy duration. A random‐effects model was used to pool mean differences (MDs) or risk ratios (RRs) with 95% confidence intervals (CIs). Results Six studies (one randomized crossover trial and five observational studies; N = 766 patients: CSP = 356, BiVP = 410) were included. All‐cause mortality was significantly reduced in favor of CSP (RR 0.64 [CI: 0.44 to 0.94], p = 0.02, I 2 = 0%). There was also a trend towards lower HFH, but it marginally missed statistical significance (RR 0.77 [CI: 0.58 to 1.03], p = 0.08; I 2 = 0%). Additionally, CSP decreased NYHA class (MD ‐0.64 [CI: −1.18 to −0.10], p = 0.02; I 2 = 85%) and significantly reduced QRS duration (MD −33.56 ms [CI: −52.36 to −14.76], p = 0.0005; I 2 = 97%). LVEF improvement did not significantly differ between groups (MD 4.51% [95% CI: −1.50 to 10.52], p = 0.14; I 2 = 98%). Procedure duration and fluoroscopy times did not show statistically significant difference between the two groups (MD −11.54 min [CI: −50.05 to 26.97], p = 0.56, I 2 = 96%), and (MD −5.75 min [CI: −13.13 to 1.63], p = 0.13, I 2 = 88%), respectively. Overall pacing thresholds did not significantly differ between CSP and BiVP; however, modality‐specific subgroup analysis showed comparable thresholds between HBP and BiVP, whereas LBBP was associated with significantly lower pacing thresholds than BiVP. Conclusions Among patients with AF and HFrEF undergoing AVNA, CSP may offer symptomatic and electrocardiographic advantages over BiVP, with a possible signal toward improved major clinical outcomes that requires confirmation in larger randomized studies.

Objectives Comparing clinical outcomes after cardiopulmonary bypass with hemodsorption (HA) versus cardiopulmonary bypass without HA in patients undergoing cardiac surgery in terms of mortality and major complications. Methods PubMed, Scopus, and Web of Science databases were searched for relevant randomized control trials (RCTs) that compared postoperative clinical outcomes between patients receiving intraoperative HA with cardiopulmonary bypass versus patients receiving cardiopulmonary bypass without intraoperative HA in cardiac surgery. Results Sixteen RCTs with 851 patients (433 in the HA group and 418 in the control group), were included in our meta-analysis. Our meta-analysis found no significant differences between the intraoperative HA group and the control group in patients undergoing cardiac surgery in terms of 30-days/in-hospital mortality, new-onset atrial fibrillation, stroke or cerebrovascular events, postoperative delirium, renal failure/acute kidney injury, need for renal replacement, postoperative liver dysfunction, thrombocytopenia, bleeding, volume of blood loss, pneumonia, sepsis, respiratory insufficiency, duration of postoperative ventilation, distributive/septic shock, pericardial tamponade, need for extracorporeal membrane oxygenation (ECMO) support, sequential organ failure assessment (SOFA) score at ICU admission, plasma-free hemoglobin levels, and fibrinogen levels. However, the pooled analysis showed a significant association between HA and decreased albumin at ICU admission (MD = − 0.28, 95% CI [0.55 to 0.01], p -value = 0.04), decreased length of ICU stay (MD = −0.66, 95% CI [−1.24 to 0.08], p -value = 0.03), and decreased length of hospital stay (MD = −0.99, 95% CI [−1.88 to −0.10], p -value = 0.03). Conclusion Our findings suggest that there is not enough evidence to endorse the role of routine intraoperative HA during cardiopulmonary bypass in improving clinical outcomes after cardiac surgery. Factors such as patient risk profile, procedure complexity, and cost implications should be taken into account when considering this adjunct therapy.

ABSTRACT Background Inflammatory bowel disease (IBD) and myeloproliferative neoplasms (MPNs) share chronic inflammation and immune dysregulation. Aim We evaluated the incidence of MPNs among patients with IBD and clinical outcomes of IBD–MPN coexistence. Methods Two retrospective cohort analyses were conducted using the TriNetX database. First, adults with ulcerative colitis (UC) or Crohn's disease (CD) were compared with matched non‐IBD controls to estimate incident MPN risk. A coexistence second analysis included patients with UC or CD who developed MPNs and then were matched to IBD without MPN controls to assess 5‐year outcomes, including IBD‐related complications, surgical interventions, colorectal cancer (CRC) and primary sclerosing cholangitis (PSC). Medication subgroup analyses were performed to evaluate associations with MPN risk. Results After matching, 3873 patients with UC–MPN and 3474 patients with CD–MPN were included. Compared with matched non‐IBD controls, incident MPN risk was higher in UC (HR 1.60, p = 0.01) and CD (HR 1.56, p < 0.001). In CD, MPN coexistence was associated with higher risks of CRC (HR 1.52, p = 0.012), intestinal fistula (HR 2.84, p < 0.001), obstruction (HR 2.05, p < 0.001), perforation (HR 2.37, p < 0.001), small bowel resection (HR 3.69, p < 0.001) and colectomy (HR 2.10, p < 0.001). In UC, MPN coexistence was associated with higher risks of CRC (HR 1.50, p = 0.001), PSC (HR 1.75, p = 0.03) and pouchitis (HR 1.68, p = 0.003). Exposure to thiopurines (HR 1.28, p < 0.001) was associated with increased MPN risk, whereas TNF, IL‐23 and JAK inhibitors were not. Conclusions IBD is associated with increased MPN risk, and IBD–MPNs coexistence is associated with worse IBD‐related complications and malignancy risk.

Background/Objectives: Myelodysplastic syndromes (MDS) carry a highly variable prognosis, stratified by the Revised International Prognostic Scoring System (IPSS-R) and the Molecular IPSS (IPSS-M). CEBPA mutations define a favorable-risk subgroup in acute myeloid leukemia (AML), yet their prognostic significance in MDS has not been characterized. Methods: We analyzed 2442 patients from the International Working Group (IWG) 2022 multi-center MDS registry after pre-specified exclusions. Overall survival (OS) and leukemia-free survival (LFS) were compared between CEBPA-mutated (n = 66; 2.7%) and wild-type patients using Kaplan–Meier estimation and Cox proportional hazards regression, adjusting for age, sex, and IPSS-R score; pre-specified subgroup, sensitivity, competing-risk, and mutation subtype analyses were performed. Results:CEBPA-mutated patients had markedly inferior OS (median 17.2 versus 42.2 months; HR 2.05, 95% CI 1.50–2.79; p < 0.001). After IPSS-R adjustment, the hazard ratio remained adverse (HR 1.39, 95% CI 1.00–1.94; p = 0.053), with uniform directionality across all 13 evaluable subgroups and no significant interaction. Co-mutation adjustment for ASXL1 and STAG2 further attenuated the hazard ratio to HR 1.11 (95% CI 0.79–1.57; p = 0.54), suggesting part of the observed signal reflects co-mutation burden rather than an independent CEBPA effect. Competing-risk analysis suggested that the excess mortality is mediated through AML transformation (CEBPA-mutated versus wild-type subdistribution hazard ratio of 1.89, 95% CI 1.20–2.99; p = 0.006) rather than non-transformative MDS mortality (cause-specific HR 0.97; p = 0.890). Truncating mutations drove the adverse signal (HR 2.21; p = 0.023), while basic leucine zipper (bZIP) domain mutations showed no significant effect (HR 1.25; p = 0.470). Conclusions:CEBPA mutations identify a rare MDS subgroup with markedly inferior survival, driven by truncating loss-of-function mutations and associated with leukemic transformation; the AML-derived bZIP-favorable paradigm does not translate to MDS, and CEBPA mutation status merits a prospective study to assess clinical utility for risk stratification.

Premature ventricular contractions (PVCs) are common arrhythmia encountered in patients with and without structural heart disease. Although often benign and asymptomatic, they may also cause palpitations, exercise intolerance, presyncope, and reduced quality of life, and in some patients can contribute to PVC-induced cardiomyopathy or trigger malignant ventricular arrhythmias. Their clinical significance depends on symptom burden, PVC frequency, ventricular function, and the presence of underlying myocardial disease. Diagnostic evaluation includes electrocardiography, ambulatory rhythm monitoring, echocardiography, exercise testing, and cardiac magnetic resonance imaging for tissue characterization and risk stratification. Management ranges from reassurance and lifestyle modification to pharmacologic therapy and catheter ablation. Beta-blockers and nondihydropyridine calcium channel blockers remain common first-line options, whereas antiarrhythmic drugs may be considered in carefully selected patients. Catheter ablation is an effective treatment for symptomatic PVCs, high PVC burden, and PVC-induced cardiomyopathy, with high procedural success rates and favorable effects on arrhythmic burden and ventricular function. Novel approaches, including electrocardiographic imaging-guided planning, pulsed field ablation, stereotactic radioablation, neuromodulation, and renal denervation, may further expand future therapeutic options. This review summarizes the pathophysiology, clinical implications, diagnostic evaluation, and contemporary management of PVCs, with emphasis on medical therapy, catheter ablation, and emerging treatments.

Abstract Background Large language models (LLMs) offer promise for systematic review data extraction, but performance in complex multidisciplinary domains and utility for clinical statement generation remain insufficiently described. Objectives To evaluate Google NotebookLM for AI-assisted data extraction and RAND/UCLA consensus statement generation in a systematic review of IBD, obesity, and cardiometabolic comorbidities. Methods Studies were organized into domain-specific notebooks; structured prompts generated standardized evidence tables. Two independent reviewers validated outputs against full-text articles using a four-category error classification. Cell-level accuracy and critical accuracy (cells free of major factual errors) were the primary metrics; workflow time was compared against a published conventional extraction benchmark. Concordance between AI-generated and expert-finalized statements was assessed. Results Across 57 articles, 1,710 data cells were extracted; 151 (8.83%) were flagged, yielding 91.17% cell-level accuracy. Major factual errors occurred in only 4 cells (0.23%), for a critical accuracy of 99.77%. Most errors were minor omissions (59.6%) or incomplete extractions (30.5%); domain error rates ranged from 7.08% to 11.33%. The pipeline required 17.7 versus a projected 165.1 person-hours (89.3% reduction). PICO-structured prompting generated 70 candidate statements; 58 of 112 finalized panel statements (51.8%) were AI-derived, and 85.7% were retained in the finalized set. Conclusion Google NotebookLM demonstrates feasibility as a primary extraction and synthesis tool in a multidisciplinary systematic review, with extractive incompleteness as the principal limitation and substantial time savings over conventional approaches. Its novel application to RAND/UCLA consensus statement generation extends AI-assisted evidence synthesis to clinical consensus generation workflow.