Citations

Summary Achalasia is a motility condition defined by failure of relaxation of the lower esophageal sphincter and loss of peristalsis in the distal esophagus. Per-oral endoscopic myotomy (POEM) is a technique to reduce lower esophageal sphincter pressure. We performed a systematic review and meta-analysis to assess the association between POEM and the clinical outcomes. We performed a systematic review and a meta-analysis (CRD420251052240). Literature search was done on PubMed and Embase (up to 8 June 2025). Original studies involving achalasia patients who underwent esophageal POEM with impedance planimetry using 8-cm balloon at 30 or 40 mL filling volumes with 325 catheter only (not the 322-N catheter) were included. The outcomes of interest were the clinical response groups (responders’ Eckardt score [ES] < 3 and non-responders’ ES > 3), reflux esophagitis, cross-sectional area (CSA), distensibility index (DI), and diameter. Nineteen studies with 1215 patients were included. The responders (ES < 3) showed a statistically significantly greater increase in DI due to POEM (post-op minus pre-op) (mean difference [MD] = 1.92 mm2/mmHg [0.32, 3.53], P = 0.02) as well as a higher postoperative DI (MD = 1.87 mm2/mmHg [0.04, 3.70], P = 0.05) (40 mL). Reflux esophagitis group had statistically significantly higher CSA and diameter values (CSA MD = 15.68 mm2 [6.91, 24.24], P = 0.0005) (diameter MD = 0.96 mm [0.58, 1.33], P < 0.00001) but no statistically significant difference for DI as compared to the non-reflux esophagitis group (DI MD = 0.19 mm2/mmHg [−0.51, 0.89], P = 0.59). In achalasia patients undergoing esophageal POEM, a greater interval increase in the DI as well as a higher post-procedural DI absolute value predicts a favorable clinical response. Higher postoperative CSA and diameter were linked to reflux esophagitis.

Abstract Inflammatory bowel diseases (IBD), principally Crohn’s disease (CD) and ulcerative colitis (UC), are common chronic disorders involving inflammation and often progressive tissue damage. Genome-wide association studies have mapped many risk signals, but the causal variants, effector genes and relevant cellular contexts remain difficult to resolve, limiting mechanistic interpretation and therapeutic translation. Here we performed a multi-ancestry GWAS meta-analysis of 125,992 individuals with IBD and more than 1.2 million controls, identifying 619 independent association signals (374 novel) at 420 IBD regions that account for 77–80% of SNP-based heritability. Fine-mapping resolved 81 high-confidence variants, 41 not previously reported. Although most signals were shared between CD and UC, 39% showed IBD subtype specificity, with UC signals showing stronger enrichment in functional annotations from intestinal epithelial, secretory and enteroendocrine cells, and CD showing stronger genetic correlations with circulating inflammatory biomarkers, including C-reactive protein and glycoprotein acetylation. Latent causal modelling supported a causal effect of decreased high-density lipoprotein on CD risk. By integrating bulk and single-cell eQTL and pQTL resources using colocalisation and Mendelian randomisation, together with coding-variant evidence from exome sequencing, we prioritised 664 candidate effector genes across 341 signals, including 390 newly implicated IBD genes, revealing new biological mechanisms and candidate therapeutic targets supported by human genetics.

Abstract Background Breast cancer (BC) diagnosed during pregnancy or postpartum often presents with aggressive features, potentially influenced by hormonal, immunological, and tissue remodeling changes. Studies have suggested that postpartum BC may be associated with worse outcomes, though most evidence is retrospective and constrained by methodological limitations. This study evaluated associations between pregnancy history, recency of childbirth, and long-term outcomes in a prospective cohort of young patients with early-stage BC. Patients and Methods Patients aged ≤40 years with stage I–III BC enrolled in the Young Women’s Breast Cancer Study were categorized at diagnosis as nulligravid, nulliparous, pregnant, or parous (≤5 vs 5 to 10 years postpartum). Analyses were stratified by BC subtype (estrogen receptor-positive [ER+]/HER2−, HER2+, and triple-negative [TNBC]), with distant recurrence-free survival (DRFS) as the primary endpoint. Results Among 859 patients, 257 (29.9%) were nulligravid, 50 (5.8%) nulliparous, 37 (4.3%) pregnant, and 515 (60.0%) parous. Pregnant patients had proportionally more TNBC, nodal involvement, T3/T4, and grade 3 tumors. After 11.1 years median follow-up, pregnancy or postpartum status was not independently associated with DRFS in multivariable models adjusted for age, tumor characteristics, and treatment, with consistent findings across ER+/HER2−, HER2+, and TNBC subtypes. Sensitivity analyses, including further categorization of postpartum diagnoses (<2 vs 2 to 5 years), yielded consistent results. Conclusions Pregnancy history and recency of childbirth were not independently associated with long-term DRFS. Despite more aggressive features at diagnosis, patients diagnosed during or after pregnancy had comparable outcomes after adjustment, suggesting no adverse prognostic impact. Clinical trial registration NCT01468246 (https://clinicaltrials.gov/study/NCT01468246? term=NCT01468246&rank=1).

PURPOSE The Lynch syndrome (LS) genes, MLH1 , MSH2 , MSH6 , and PMS2 , are considered to be some of the highest-priority genes to be tested for population genomic screening, with the aim to prevent and detect cancers early in those with a higher risk for such diagnoses. The objective of this study was to determine the risk of cancer associated with pathogenic variants in MLH1 , MSH2 , MSH6 , or PMS2 in the general population to build evidence-based guidelines for population genomic screening METHODS This retrospective case-control study uses Helix Research Network data from 230,159 participants across nine US health systems. Variant interpretation was performed following the American College of Medical Genetics and Association for Molecular Pathology guidelines. Clinical diagnoses were identified from electronic health records and claims data for 11 cancer types associated with LS, including colorectal and endometrial cancers. RESULTS Individuals with pathogenic variants in MLH1 , MSH2 , and MSH6 showed substantial risk for LS-related cancers compared with those without pathogenic variants. Conversely, individuals with pathogenic variants in PMS2 had no increase in risk for all 11 LS-associated cancers with hazard ratio (HR) of 1.0 (95% CI, 0.6 to 1.8) compared with those without a pathogenic variant. There was a small increase in risk when restricting the analysis to colorectal cancer with an HR of 3.5 (1.7-7.4). This increase in colorectal cancer risk was predominantly observed after age 60 years, 10 years after US Preventive Services Task Force guidelines recommend starting colonoscopies for the average population. Up to age 60 years, 2.6% of individuals with PMS2 pathogenic variants were diagnosed with colorectal cancer, closer to the general population (0.7%) than those with MLH1 (37.3%), MSH2 (28.9%), or MSH6 (6.7%) pathogenic variants. For 100,000 individuals screened for PMS2 , 854 additional colonoscopies would be performed, which would prevent or detect early 3.2 colorectal cancers. CONCLUSION This analysis across nine health systems highlights the clinical phenotypes of PMS2 pathogenic germline variants in the entire population.

Abstract Inflammatory bowel disease (IBD) is a chronic immune-mediated disorder of the gastrointestinal tract whose genetic basis is only partly resolved because most risk variants identified by genome-wide association studies (GWAS) lie in non-coding regions, limiting direct gene assignment and biological interpretation 1,2 . Here we analysed whole-exome and whole-genome sequencing data from 86,213 IBD cases and 478,363 controls of European ancestry. We identified 68 IBD genes directly implicated by conditionally independent protein-coding associations across the allele frequency spectrum. Many newly implicated IBD genes are supported by orthogonal genomic or pleiotropic evidence, pointing to disease-related pathways and nominating targets with therapeutic relevance. We further identified allelic series and non-additive effects at key loci such as NOD2 and TYK2. These results show that large-scale sequencing can resolve disease genes and pathways that remain ambiguous from non-coding association alone, providing a more direct route from human genetics to biological insight and therapeutic hypotheses.

Abstract Objective We evaluated the quality and adoption of a large language model (LLM)-based summarization tool for ongoing hospital care. Materials and methods An AI summarization tool was created to provide a “Patient Story”, specialty-specific “Recent Notes”, and “Recent Events” over the previous 24 or 72 hours. We conducted a pragmatic mixed-methods quality assessment at three tertiary-care academic hospitals utilizing (1) Provider Documentation Summarization Quality Instrument (PDSQI-9), (2) utilization analytics, and (3) qualitative end user feedback. The PDSQI-9 included whether summaries were accurate, cited, comprehensible, organized, succinct, non-stigmatizing, synthesized, thorough, and useful. 512 users were given access, from whom 52 participants submitted 205 surveys (10.2% response rate). Results 52 respondents submitted an average of 4.3 surveys (range 1–8). Users rated the tool favorably across all PDSQI-9 domains, with a combined average score of 4.68 (range 4.56–4.78, S.D. 0.67) across the eight domains scored on a 5-point modified Likert scale. Utilization metrics demonstrated strong uptake with frequent views. Positive qualitative feedback revealed cognitive offloading for complex patients and effective summarization of medical problems. Critical feedback showed a need to cross-reference narrative notes to current-state data and lack of detailed specialty-specific summarization. Discussion Generative artificial intelligence has emerged as a potentially transformative technology for generating succinct, verifiable summaries of ongoing care. In this pragmatic implementation, end-users indicated high perceived quality across PDSQI-9 domains. Conclusions An LLM-based summarization tool for ongoing hospitalization care was rated of high quality by diverse clinicians in real-world settings, demonstrated a favorable safety profile, and showed sustained utilization.

Purpose: Significant variation is observed in diagnostic assessments for individuals with acquired apraxia of speech (AOS). The lack of consistency across research related to AOS impacts the comparison of intervention outcomes. This extends to diagnostic criteria, assessment, and the inclusion of patient demographics. This viewpoint examines outcomes related to the consistency in diagnostic tool use and collection of demographic information and introduces a template to support researchers and clinicians conducting diagnostic evaluations. Materials include guidelines for a thorough case history, current diagnostic characteristics, and diagnostic assessment tools available for describing AOS. The template illustrates how such materials can be structured and applied in research and clinical practice. Method: The recommendations provided in this viewpoint are part of a recent systematic review about AOS treatment outcomes. Trained raters extracted data from a comprehensive literature search from 1951 to April 2024 using a consensus protocol. Results: Of the 92 studies included in data extraction, demographic information such as age, gender, etiology, and months post-onset was commonly reported, and information about race and ethnicity (described in 15% of studies), socioeconomic status (0%), current/previous occupation (8%), language history (10%), and education (59%) was described less frequently. Reported diagnostic characteristics varied across studies, reflecting differences in using discriminatory versus nondiscriminatory features. Concomitant diagnoses, such as aphasia severity (37%) and presence of dysarthria (32%), were not consistently reported or described. Conclusion: A template with specific criteria and assessments can support research replication, raise awareness of diagnostic strategies, and offer a structured framework for investigators and clinicians. Supplemental Material: https://doi.org/10.23641/asha.32012346

Abstract Purpose To report historical patterns of pharmaceutical expenditures, to identify factors that may influence future spending, and to predict growth in drug spending in 2026 in the United States, with a focus on the nonfederal hospital and clinic sectors. Methods Historical patterns were assessed by examining data on drug purchases from manufacturers using the IQVIA National Sales Perspectives database. Factors that may influence drug spending in hospitals and clinics in 2026 were reviewed—including new drug approvals, patent expirations, and potential new policies or legislation. Focused analyses were conducted for biosimilars, cancer drugs, endocrine drugs, generics, specialty drugs, and vaccines. For nonfederal hospitals, clinics, and overall (all sectors), estimates for growth of pharmaceutical expenditures in 2026 were made based on a combination of quantitative analyses and expert opinion. Results In 2025, overall pharmaceutical expenditures in the US grew 12.7% compared to 2024, for a total of $915.2 billion. Utilization (a 9.3% increase) drove this increase, while growth due to new drugs (0.9%) and price increases (1.2%) had a modest impact. Tirzepatide was the new top drug in 2025, followed by semaglutide and apixiban. Drug expenditures were $42.9 billion (a 9.6% increase) and $190.5 billion (a 19.0% increase) in nonfederal hospitals and in clinics, respectively. In clinics, volume drove drug expense growth, contributing with a 13.6% increase, while price and new drugs each contributed with a 2.7% increase. In nonfederal hospitals, expenditure growth was driven by increases in volume (4.6%), new products (3.7%), and prices (1.5%). Several new drugs that will influence spending are expected to be approved in 2026. Specialty, endocrine, and cancer drugs will continue to drive expenditures. Conclusion For 2026, we expect overall prescription drug spending to rise by 10.0% to 12.0%, whereas in clinics and hospitals we anticipate increases of 14.0%-16.0% and 4.0%-6.0%, respectively, compared to 2025. These national estimates of future pharmaceutical expenditure growth may not be representative of any health system because of the myriad of local factors that influence actual spending

Abstract Aims Infective endocarditis (IE) is a serious and potentially fatal complication of mitral valve (MV) intervention. There are limited data comparing the incidence of IE after MV repair compared with bioprosthetic MV replacement. The aim of this study was to analyse the incidence and timing of IE after MV repair compared with bioprosthetic valve replacement, in both surgical and transcatheter patient populations. Methods and results A literature search of Medline, Embase, and Cochrane Library (January 2000—September 2025) was conducted. Pooled IE incidence rates were derived using random-effects models. Eighty-two studies (80 939 patients, total follow-up 350 252 patient-years) were included. The overall incidence rate of IE was 0.97 per 100-patient-years (95% confidence interval [CI] 0.71–1.34). IE was more common after surgical MV replacement (SMVR) than surgical MV repair (SMVr): incidence rate 0.93 (95% CI 0.41–1.81) vs 0.39 (95% CI 0.25–0.62) per 100-patient-years, incidence rate ratio (IRR) 2.34 (95% CI 1.06–5.18), P = .035. The incidence of IE after transcatheter MV replacement (TMVR) was comparable to transcatheter MV repair (TMVr) (2.88 [95% CI 1.91–4.33] vs 1.70 [95% CI 0.84–3.43] per 100-patient-years), IRR 1.56 (95% CI 0.73–3.34), P = .250. The cumulative incidence of IE following SMVR was significantly higher than following SMVr at 1- and 2-years post-procedure, but not at 6 months. Conclusions IE is an infrequent complication of mitral valve intervention. The incidence of IE following SMVR is significantly higher than following SMVr, while the incidence of IE following TMVR is numerically but not significantly higher than following TMVr. Reducing IE risk after mitral intervention is a clinical and research priority.

BACKGROUND In patients with drug-resistant epilepsy (DRE) who are not candidates for resective surgery, thalamic neuromodulation targeting structures such as the anterior nucleus of the thalamus (ANT), centromedian nucleus (CM), and pulvinar (PUL) has emerged as a promising therapy. The clinical investigation of these targets’ efficacy and side effect profiles is ongoing, complicating discussions between neurosurgeons, neurologists, and patients. The implementation of single-pulse and continuous stimulation protocols to conduct patient-specific side effect screens and generate prognostic biomarkers could offer guidance for target selection. OBSERVATIONS A 32-year-old male with extensive polymicrogyria and DRE underwent stereo-electroencephalography (SEEG) with multisite thalamic sampling to inform neuromodulation target selection. Single-pulse stimulation was conducted to screen for acute sensorimotor effects, followed by continuous (12- to 24-hour) stimulation using clinically relevant parameters. Intolerable paresthesia occurred during CM single-pulse stimulation, leading to its exclusion as a target. Single-pulse and continuous stimulation of the ANT and PUL were well tolerated. PUL stimulation offered superior suppression of epileptiform discharges during sleep. LESSONS These findings meaningfully informed the selection of the PUL as a neuromodulation target. This case illustrates the safety, feasibility, and utility of patient-specific single-pulse and continuous stimulation assessments during SEEG monitoring to evaluate efficacy and tolerability prior to chronic neuromodulation, particularly for novel thalamic targets. https://thejns.org/doi/10.3171/CASE25947