Citations

Objective To comprehensively examine hypertension- and heart failure–related mortality rates in the United States to develop a targeted approach to health policy development. Methods We analyzed death certificates from the Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research database, focusing on mortality caused by hypertensive heart failure in adults aged ≥25 years from 2006 to 2020. Age-adjusted mortality rates per 1,000,000 and annual percent changes were calculated and categorized by year, sex, race, urban status, age group, and census region. Results A total of 268,545 deaths occurred due to hypertensive heart failure between 2006 and 2020. The overall age-adjusted mortality rates increased from 60.5 in 2006 to 134.9 in 2020. Males had higher age-adjusted mortality rates than women (76.6 vs. 73.8). Older-aged people exhibited significantly higher age-adjusted mortality rates than young and middle-aged adults. Age-adjusted mortality rates were highest in non-Hispanic Blacks/African Americans and lowest in non-Hispanic Asians/Pacific Islanders (126.8–43.6). Furthermore, age-adjusted mortality rates were highest in individuals from nonmetropolitan areas and the Western region. Conclusion Following a period of decline, the age-adjusted mortality rates increased until 2020. The highest age-adjusted mortality rates were observed in non-Hispanic Blacks and nonmetropolitan areas. An urgent restructuring of healthcare policy is needed to reduce heart failure-associated mortality.

Abstract Background Anti‐M antibodies were described as rarely eliciting hemolytic disease of the fetus and newborn (HDFN) in pregnancy. More recent literature, primarily from Asia, reports severe HDFN attributed to maternal anti‐M. The objective of this study is to determine if there is a difference in the frequency and/or severity of anti‐M HDFN among subjects who self‐report as Asian compared to non‐Asian. Methods Retrospective data were collected from 18 sites. Fetuses/neonates affected by HDFN were categorized as unaffected, mild, moderate, or severe based on clinical management and outcomes. Results Anti‐M was identified in 557 obstetric patients. Among 332 neonates with complete data for analysis, anti‐M was detected in isolation during the pregnancies of 210 (63.3%) neonates; 198 (94.3%) were unaffected by HDFN. The overall frequency of HDFN was 6.5% (2/31) in Asian patients and 5.6% (10/179) in non‐Asian patients. The frequency of severe HDFN was 6.5% (2/31) among Asian patients and 0.6% (1/179) among non‐Asian patients. Among non‐Asian patients, eight (4.5%) were mild and one (0.6%) was moderate. Of 63 pregnancies with anti‐M and ABO incompatibility, 6 (9.5%) were associated with mild HDFN and 57 (90.5%) were unaffected. Of 49 pregnancies with anti‐M and non‐ABO antibody(s), 6 (12.2%) were associated with mild HDFN and 43 (87.8%) were unaffected. One case (10.0%) of HDFN (mild) occurred in the presence of anti‐M, additional antibody(s), and ABO incompatibility. Conclusion In this study, severe anti‐M HDFN was rare in non‐Asian subjects. There is a signal that Asian patients are at greater risk for severe anti‐M HDFN.

Abstract We aim to compare the benefits, harms, and costs of multiple plastic stents (MPS) versus covered self-expandable metallic stents (CSEMS) in the treatment of benign biliary strictures (BBS). A comprehensive database search through June 6, 2024 identified randomized controlled trials (RCT) involving adult patients with BBS comparing MPS to CSEMS in terms of stricture resolution, recurrence, technical success, number of required procedures and stents, treatment duration, all-cause mortality, adverse events, and stent migration. We utilized the Cochrane Risk of Bias (RoB) tool2 for study quality assessment. Meta-analysis following the random effects model was performed. After screening 365 references, we included 7 RCTs (high RoB) involving 594 patients. Most reported stricture etiology is chronic pancreatitis (52.4%), followed by orthotopic liver transplant (40.5%). Compared with MPS, CSEMS achieved similar efficacy and safety. However, CSEMS required fewer procedures (mean difference [MD]: −1.84 [−2.56 to −1.11]; I2 = 76%) and stents (MD: −6.04 [−9.55 to −2.52]; I2 = 93%), amounting for shorter duration of treatment (MD: −119.02 days [−137.41 to −100.62]; I2 = 96%) and savings in costs between 41 and 57% with absolute savings of 4,019$ to 9,192$ favoring CSEMS. All outcomes had a low to very low certainty of evidence (CoE), except for technical success and stricture resolution (moderate CoE). Our analysis suggests that CSEMSs are comparable to MPSs in terms of efficacy and safety. However, it shows that CSEMSs are more cost-effective. Sample size calculations from our analyses can guide the design of future studies to validate the safety profiles and determine the feasibility of the two modalities.

Background Chronic graft versus host disease (cGVHD) is a complex post-transplant complication resulting in varying degrees of musculoskeletal (MSK) manifestations, including sclerosis-type skin conditions, fasciitis, and osteopenia, avascular necrosis affecting the shoulder, elbow and hands apart from other joints of the body. A large proportion of these can often miss out on the expertise of upper limb therapists. Study Objectives This paper aims to outline upper limb cGVHD manifestations to raise awareness among upper limb physiotherapists and rehabilitation specialists, so that patients can receive more focused, optimal care. Methods An electronic search was conducted across a wide database covering the period from 1990 to 2025. Further manual search used Google Scholar to help identify relevant articles. Boolean operators ‘AND’ and ‘OR’ combined keywords such as chronic graft versus host disease, acute graft versus host disease, allogenic hematopoietic stem cell transplantation, hematopoietic cell transplantation, stem cell transplant, bone marrow transplant, physiotherapy, upper limb specialist, musculoskeletal, fasciitis, and scleroderma. Results A total of 4,393 titles were screened against the pre-set inclusion and exclusion criteria, and only 3 articles were found to be suitable for this narrative review. All 3 articles were case studies of upper limb cGVHD and rehabilitation reporting positive outcomes on patients’ upper and lower limb range of motion, function, and quality of life (QoL). Conclusion cGVHD can cause various MSK issues, especially in the upper limbs. It is important to collaborate with upper limb physiotherapy and occupational therapy experts to improve awareness and patient outcomes.

T cell fitness has emerged as a critical determinant of the efficacy and persistence of Chimeric Antigen Receptor (CAR)-T cell therapy. Defined by the capacity of T cells to proliferate, resist exhaustion, persist in vivo , and exert sustained effector functions, T cell fitness reflects the integration of a dynamic network of intrinsic and extrinsic regulatory mechanisms. In this review, we present a comprehensive synthesis of the molecular and cellular foundations underlying T cell fitness, emphasizing the influence of differentiation trajectories, signaling pathways, metabolic reprogramming, and epigenetic modifications. We further discuss the impact of patient-specific conditions such as age as well as disease biology, prior therapeutic exposures, and timing and quality of T cell collection, on the phenotypic and functional efficacy of CAR-T cell products. Beyond delineating these determinants, we highlight emerging strategies aimed at enhancing T cell fitness. Importantly, we propose T cell fitness as an integrated, multi-layered systems property emerging from the interaction between differentiation state, signaling architecture, metabolic–mitochondrial competence, epigenetic stability, and host-specific inflammatory and treatment-related pressures. We introduce a mechanistic framework that links these layers across the CAR-T therapeutic timeline from leukapheresis to post-infusion tumor engagement and outline how this framework can be operationalized into measurable parameters to guide patient stratification, manufacturing decisions, and rational therapeutic interventions.

Abstract Background The ability of large language models (LLMs) to work collaboratively and screen studies in a systematic review (SR) is under-explored. Hence, we aimed to evaluate the effectiveness of LLMs in automating the process of screening in systematic reviews. Methods This is an observational study which included labeled data (title and abstracts) for five SRs. Originally, two reviewers screened the citations independently for eligibility. A third reviewer cross-checked each citation for quality assurance. GPT-4, Claude-3-Sonnet, and Gemini-Pro-1.0 were used using zero-shot chain-of-thought prompting. Collaborative approaches included (i): conflict resolution using benefit of the doubt, (ii) majority voting using an independent third LLM and (iii) conflict resolution using an informed third LLM. Performance was assessed using accuracy, precision for exclusion, and recall for inclusion. Work saved over samples (WSS) was computed to estimate the reduction in manual human effort. Results A total of 11300 articles were included in this study. The individual models, GPT-4, Claude-3-Sonnet, and Gemini-Pro-1.0 exhibited a high precision for exclusion, achieving 99.7%, 99.7%, and 99.2% and high recall for inclusion achieving 95.5%, 96.6% and 85.7%, respectively. However, the collaborative approach utilizing the two best-performing models (GPT-4 and Claude-3S) achieved an average precision of 99.9% and a recall of 98.5% (across all collaborative approaches). Furthermore, the proposed collaborative approach resulted in an average WSS of 63.5%, compared to the average WSS of 45.2% for individual models. Conversational LLM interactions showed a consistent pattern of results. Limitations This study was limited due to reliance on proprietary models, and evaluation on oncology datasets. Conclusion Evidence shows that collaborative LLMs enable efficient, high-performing screening in systematic reviews, supporting continuous evidence updates. Primary funding source NIH (U24CA265879-01-1) and Carolyn-Ann-Kennedy-Bacon Fund.

BACKGROUND: Obstructed defecation syndrome and posterior compartment (rectal) prolapse significantly impact patients’ quality of life. Pelvic floor physical therapy is a critical part of multidisciplinary management for these conditions, yet there is little guidance or standardization to guide providers’ referral practices, diagnostic approaches, or treatment. OBJECTIVE: To develop multidisciplinary consensus-based recommendations for incorporating pelvic floor physical therapy into the treatment of obstructed defecation syndrome and posterior compartment prolapse. DATA SOURCES: MEDLINE, PubMed, Embase, and the Cochrane Database of Systematic Reviews were searched for English-language studies on pelvic floor physical therapy, obstructed defecation, diagnostic criteria, imaging, and pelvic organ prolapse. STUDY SELECTION: Studies identified in the literature search were reviewed by multidisciplinary expert subgroups, who formulated draft statements based on the available evidence. INTERVENTION: Consensus meetings were conducted and included experts from colorectal surgery, urogynecology, physical therapy, gastroenterology, radiology, and urology. Statements were evaluated via structured discussions and voting processes. Those reaching more than 70% consensus were adopted for inclusion. Statements underwent final review and editing by the leadership of the American Society of Colon and Rectal Surgeons and the International Urogynecological Association. MAIN OUTCOME MEASURES: Consensus statements addressed referral criteria, diagnostic evaluations, therapy protocols, timing, coordination with surgery, and management of anatomical abnormalities. RESULTS: Fifteen statements reached consensus. Key recommendations included prompt referral to pelvic floor physical therapy for patients without contraindications, individualized therapy based on appropriate diagnostic evaluation and patient goals, timing of pelvic floor physical therapy relative to surgery, and trauma-informed patient care. LIMITATIONS: Recommendations primarily reflect expert consensus due to limited high-quality evidence. Variability in practitioner expertise and geographic access to trained therapists are barriers to consistent implementation. CONCLUSIONS: These recommendations provide structured guidance for integrating pelvic floor physical therapy into the management of obstructed defecation syndrome and rectal prolapse. Additional research and standardized training are essential to optimize patient outcomes.

Limited information on the business practices of liver transplant (LT) centers worldwide has been published. Characterizing this data could help identify best practices as well as opportunities for improvement. As such, the International Liver Transplant Society (ILTS) Business Practice Committee conducted a global online survey of LT centers, which was sent to the ILTS membership. Questions focused on 5 main domains: transplant practice and volumes, workforce, finances, quality assessment and performance improvement, and overall program function. Data was compared across program geographic regions and transplant volume. A total of 89 discrete centers were represented, of which 76.4% were academic/university-affiliated, and about one-third each were from Europe (36.0%) and North America (31.5%). The top 3 problems programs reported were finances/funding (60.7%), adequate program support/guidance (48.3%), and transplant volumes (43.8%). In all, 59.6% of respondents felt their salary was undercompensated, consistent across geographic regions. In addition, 69.7% felt their center was not adequately funded to meet program goals, with programs in Europe (N=28/32, 87.5%) and Oceania (N=2/3, 66.7%) most impacted. Transplant surgeon retainment was noted as more difficult for lower volume programs (<50 liver transplants/year, N=13/31). Nearly half (42.7%) of all programs felt under-resourced to provide high-quality care, and the majority (80.9%) felt there was room for growth and improvement under their current model. While international concerns varied widely among LT centers, inadequate salary and center funding, low transplant and referral volumes, and staff retainment were persistent themes. Focusing on adopting region-specific best practices and developing transplant systems of care that focus on these elements is critical to provide optimal care to LT patients worldwide.

Early allograft failure (EAF) after living donor liver transplantation (LDLT) remains a clinical challenge. Existing prediction models developed for deceased donor transplantation poorly apply to LDLT due to distinct surgical and physiological factors. This study identifies clinical determinants of EAF and develops an LDLT-specific prediction model. We conducted a multicenter retrospective cohort study from 17 high-volume LDLT centers (January 2016–December 2020) with external validation at a tertiary center in Saudi Arabia (January 2015–December 2022). The primary outcome was EAF (graft loss or patient death ≤90 d). Multivariable mixed-effects logistic regression identified preoperative/intraoperative risk factors. The EAGLE-LDLT model was constructed using postoperative laboratory values. Performance was compared against established models (EAD, MEAF, A2ALL) using ROC analysis and decision curve analysis. The development cohort included 2944 adult LDLT recipients (67.7% male; median age 55 y; median MELD 14) with a 5.5% EAF rate. External validation included 1020 recipients (median MELD 21, 6.7% EAF). Independent risk factors for EAF were MELD (OR 1.06, 95% CI 1.04–1.08), donor BMI (OR 1.05, 95% CI 1.00–1.10), portal vein thrombosis (OR 1.73, 95% CI 1.13–2.63), and hepaticojejunostomy (OR 1.58, 95% CI 1.06–2.36). The EAGLE-LDLT model incorporating peak ALT (>468 U/L), peak INR (>1.9), and bilirubin (>3.5 mg/dL) and INR (>1.3) at POD7, demonstrated superior discrimination (AUC=0.81) compared with MEAF (AUC=0.77, p =0.004), EAD (AUC=0.67, p <0.001), and A2ALL (AUC=0.65, p <0.001). EAGLE-LDLT achieved balanced sensitivity (75.0%) and specificity (73.7%), effectively stratifying patients into high-risk (15% of patients; 40.4% EAF incidence) and low-risk groups. Preoperative and intraoperative clinical factors predict EAF in LDLT. The EAGLE-LDLT model accurately identifies LDLT recipients at the highest risk for EAF postoperatively.

399 Background: The standard of care for resectable GEA adenocarcinomas is perioperative chemotherapy with the FLOT (fluorouracil, leucovorin, oxaliplatin, docetaxel) regimen. Recent studies investigating the addition of checkpoint inhibitors (CPIs) to perioperative chemotherapy have shown mixed results. An NMA can leverage both direct and indirect comparisons to evaluate the relative efficacies of available regimens in this setting. Methods: MEDLINE, EMBASE, Scopus, Web of Science and CENTRAL were searched until August 27th, 2025. Eligible studies included phase 3 randomized trials evaluating perioperative or neoadjuvant chemotherapy +/- CPIs ± radiation in resectable GEA. The primary outcomes were disease-free survival (DFS) and overall survival (OS). Hazard ratios and 95% confidence intervals (CIs) were estimated using a frequentist NMA framework. Results: Fifteen trials including 8072 patients were analyzed. For DFS, perioperative durvalumab + FLOT (dFLOT) ranked highest (P-score = 0.99), followed by FLOT (P-score = 0.84) (HR for dFLOT vs. FLOT was 0.71, 95% CI 0.58-0.86). dFLOT also ranked higher than perioperative pembrolizumab + cisplatin and fluorouracil/capecitabine (KN-585), though this comparison was not statistically significant (HR 0.65, 95% CI 0.40-1.04). Compared with CROSS, dFLOT showed superior DFS (HR of 0.48, 95% CI 0.36-0.63). For OS, dFLOT ranked the highest (P-score=0.95) and was superior to CROSS (HR 0.57, 95% CI 0.42-0.77). While dFLOT appeared favorable versus FLOT (HR 0.78, 95% CI 0.62-0.98), this finding was primarily driven by MATTERHORN, which did not meet its prespecified OS significance boundary (P = 0.03 vs threshold P < 0.0001), and the proportional hazards assumption was violated. Similarly, no significant OS difference was observed between dFLOT and the KN-585 arms (HR 0.75, 95% CI 0.45-1.23). Conclusions: In this NMA, perioperative FLOT remained the benchmark regimen for resectable GEA. dFLOT has shown promising early results, ranking the highest for DFS and showing favorable, but not statistically definitive OS trends in comparison to FLOT. Importantly, the network enabled indirect comparisons not tested in head-to-head trials, demonstrating that dFLOT ranked above pembrolizumab+CF/CX (KN-585) without reaching statistical significance, and also outperformed CROSS. However, these findings should be interpreted with caution, as they are primarily driven MATTERHORN data in which OS did not cross the prespecified threshold and proportional hazards assumptions were violated. Perioperative immunotherapy combinations appear promising, but final MATTERHORN results and further confirmatory studies are needed before dFLOT can be considered as a new standard of care.