Citations

ABSTRACT Background Chronic megacolon is an uncommon neurogastrointestinal disorder typically characterized by a persistent increase in colonic diameter. Methods Our aim was to identify adults with medical treatment‐refractory constipation without radiographic criteria for megacolon but with increased colonic compliance (refractory constipation with colonic hypercompliance (RCCH)), and to compare the colonic compliance in 7 identified patients with “RCCH” to colonic compliance in 10 patients with chronic megacolon by radiographic criteria (i.e., megacolon) and 40 healthy volunteers. After endoscopic placement, compliance of left or transverse colon was measured using a 10‐cm‐long infinitely compliant balloon connected to an electronically controlled rigid piston barostat. The barostat inflated the balloon from 0 to 44 mmHg in 4‐mmHg steps at 30‐s intervals to measure colonic compliance (pressure‐volume relationship). Eligibility criteria for inclusion were increased colonic compliance based on a functional assessment without meeting radiographic criteria for megacolon (i.e., RCCH). In the three groups, we compared colonic volumes at intra‐balloon pressure of 8, 16, 20, 32, and 44 mmHg, the pressure at half maximum volume, and the slope of the colonic compliance curve using ANOVA on ranks and Dunn's pairwise comparison test. Other features of colonic motility were documented. Results Colonic volumes at all pressures (8‐44 mmHg) and the pressure at half maximum volume were significantly greater in patients with megacolon and RCCH than in healthy controls ( p < 0.001 for both), but compliance was not significantly different between RCCH and megacolon. Conclusion A subset of patients with medically‐refractory chronic constipation has colonic compliance similar to that of patients with megacolon.

ABSTRACT Background Chronic obstructive pulmonary disease (COPD) is associated with musculoskeletal comorbidities, including cachexia. Weight loss (WL) is the major criterion for cachexia and increases risk for mortality in COPD. Risk factors for WL in COPD are incompletely understood. We performed this whole genome sequencing (WGS) analysis to identify genetic risk variants for WL in COPD. Methods We studied 16 972 participants from the Trans‐Omics for Precision Medicine (TOPMed) Initiative and All of Us Research Program. COPD was diagnosed using spirometry in TOPMed, while diagnosis codes were used in All of Us. WL was defined as WL ≥ 5% or a final body mass index (BMI) < 20 kg/m 2 . WGS data came from white blood cells in all cohorts. Single‐variant testing was conducted on both race‐ and study‐stratified cohorts and in a cosmopolitan, ancestry‐independent manner using GENESIS in TOPMed and SAIGE in All of Us. SAIGE‐GENE+ gene‐based analyses were performed on race‐stratified and cosmopolitan cohorts. Single variant meta‐analyses were conducted using METAL within (B/AA and NHW analyses of Black/African–American and non‐Hispanic white participants, respectively) and across racial groups (COSMO). Rare variant gene‐based results were combined using Fisher's method. Transcriptomic effects were predicted using MetaXcan. We used the GWAS Catalogue to analyse for colocalization with other related traits. Results Two single variants were associated with WL in COPD among All of Us participants: one intronic variant in HCN1 in Black/African–American participants (chr5:45271359:TACACAC:T, odds ratio with 95% confidence interval (OR (CI 95 )) = 2.43(1.78–3.31), p = 1.95 × 10 −8 ) and one intergenic variant between PPP4R2 and PDZRN3 in the cosmopolitan and NHW cohorts (chr3:73345901:A:G, OR (CI 95 ) = 0.21(0.12–0.35), p = 8.84 × 10 −9 in cosmopolitan and OR (CI 95 ) = 0.18(0.10–0.33), p = 9.44 × 10 −9 in NHW). Single‐variant meta‐analysis identified two loci associated with WL in COPD: five variants within DRAIC in the B/AA meta‐analysis (lead variant chr15:69571341:A:G, OR (CI 95 ) = 1.37(1.23–1.51), p = 1.29 × 10 −9 ) and two intronic variants within RFX3 in the cosmopolitan meta‐analysis (lead variant chr9:3390983:T:C, OR (CI 95 ) = 1.50(1.31–1.73), p = 1.06 × 10 −8 ). Rare variants within RNU6‐565P (NHW analysis in All of Us; p = 2.83 × 10 −7 ) and LOC339298 (B/AA analysis in All of Us, p = 1.85 × 10 −6 ) were associated with WL in COPD. The RNU‐565P signal remained significant after combination with TOPMed results (p combined = 1.23 × 10 −6 ). MetaXcan predicted differential expression of LNC00959 in visceral adipose tissue ( p = 1.16 × 10 −6 in COSMO analysis). Colocalization analyses identified genomic associations between BMI and variants in or near DRAIC , RFX3 , PDZRN3 , and LINC00959 . Conclusions In the first WGS analysis of WL in COPD, we have identified seven novel loci. Further characterization of these loci will validate our findings and improve our understanding of the molecular pathophysiology of this condition.

Background: Candidemia is a serious complication after gastrointestinal (GI) perforation and/or ischemia, yet most evidence pools candidemia with intra-abdominal candidiasis (IAC). We sought candidemia-specific risk factors after GI perforation and/or ischemia and evaluated associated outcomes. Methods: We conducted a single-center, retrospective matched case–control study of adults undergoing emergency surgical procedure for GI perforation and/or ischemia and admitted to a surgical intensive care unit. Cases with candidemia during index admission were matched 4:1 to controls by age, Charlson Comorbidity Index, and surgical procedure year. Conditional logistic regression assessed pre-specified risk factors, and exploratory outcomes included mortality, length of stay, and days on invasive ventilation. Results: Twenty-four cases were matched to 99 controls. Factors identified to be independently associated with candidemia include the presence of IAC (adjusted OR [aOR]: 5.51, 95% CI: 1.61, 18.89; p = 0.007), upper GI injury (aOR: 4.28, 95% CI: 1.52–12.08; p = 0.006), and diffuse intra-abdominal contamination, compared with contained/none (aOR: 3.21, 95% CI: 1.06–9.74; p = 0.040). Among candidemia cases, species distribution was Candida albicans 41.7%, C. glabrata 33.3%, C. parapsilosis 12.5%, with single cases of C. tropicalis, C. krusei , and C. dubliniensis . Candidemia was associated with a longer hospital length of stay (+13.97 d; 95% CI: 0.90–27.04; p = 0.036), without significant differences in ICU stay, duration of invasive ventilation, or mortality. Conclusions: After GI perforation and/or ischemia, the risk of candidemia is highest in patients with upper GI injury and diffuse contamination, independent of IAC. These readily identifiable operative features may guide targeted surveillance and selective early antifungal strategies. Prospective validation is warranted.

ABSTRACT BACKGROUND Point-of-care (POC) high-sensitivity cardiac troponin (hs-cTn) testing has the potential to expedite decision-making and reduce emergency department (ED) length of stay for patients presenting with possible myocardial infarction (MI) by ensuring that results are consistently available when looked for by clinicians. We assessed the real-life effectiveness and safety of implementing POC hs-cTn testing in the ED. METHODS We conducted a pragmatic, stepped-wedge cluster randomized trial. The control arm was usual care with an accelerated diagnostic pathway utilizing a single-sample rule-out step with a central laboratory hs-cTn assay. The intervention arm used the same pathway with a POC hs-cTnI. The primary effectiveness outcome was ED length of stay assessed using a generalized linear mixed model, and the safety outcome was 30-day MI or cardiac death. RESULTS Six sites participated with 59,980 ED presentations (44,747 individuals, 61±19 years, 49.5% female) from February 2023 to January 2025, in which 31,392 presentations were during the intervention arm. After adjustment for co-variates associated with length of stay, the intervention reduced length of stay by 13% (95% confidence intervals [CI], 9 to 16%. P<0.001), corresponding to a reduction of 47 minutes (95%CI, 33 to 61 minutes) from a mean length of stay in the control arm of 376 minutes. The 30-day MI or cardiac death rate was similar in the control and intervention arms (0.39% and 0.39% respectively, P=0.54). CONCLUSIONS Implementation of whole-blood hs-cTnI testing at the POC into an accelerated diagnostic pathway was safe and reduced length of stay in the ED compared with laboratory testing. (Australia New Zealand Clinical Trials Registry ACTRN12619001189112) Clinical Perspective What is new? Point-of-care troponin assays with good precision have become available and received regulatory approval as high-sensitivity assays. A pragmatic stepped-wedge cluster randomized trial implementing the validated Siemens VTLi high-sensitivity point-of-care assay into 6 emergency departments investigating ∼60,000 patients, was conducted to ascertain if the rapid turnaround time reduced lengths of stay. Introduction of the VTLi high-sensitivity point-of-care assay into clinical pathways reduced emergency department lengths of stay by an average 13% (47 minutes) without compromising safety. What are the clinical implications? Early decision-making using a point-of-care high-sensitivity troponin assay within a structured clinical pathway was safe. Faster turnaround means troponin results are consistently available when clinicians first seek them. This can facilitate earlier decisions and reduce patient length of stay.

The traditional combined hematology and oncology fellowship model is increasingly strained by accelerating subspecialization and therapeutic complexity. This commentary focuses on structural reforms within fellowship training to better align education with contemporary clinical practice and evolving workforce demands. We propose standardized, career-aligned tracks, earlier subspecialty focus within fellowship, and redesigned continuity clinic models that preserve foundational breadth while enabling depth of expertise. We further highlight how emerging assessment reforms and educational tools can support these structural changes. By aligning fellowship training with both real-world clinical demands and established educational science, we can ensure a more sustainable and effective pathway for preparing future hematologists and oncologists.

Abstract Background Hyponatremia has long been recognized as a common electrolyte abnormality among skilled nursing facility (SNF) residents. In the literature, hyponatremia is associated with increases in falls, cognitive impairment, hospitalization, and increased mortality. Although many medical conditions and medications contribute to hyponatremia risk, the role of enteral feeding tubes in this population has not been well defined in clinical practice. This study examined the association between enteral feeding tube use and incident hyponatremia and evaluated selected chronic conditions and medication exposures in SNF patients. Methods We conducted a retrospective cohort study using secondary data from a suburban skilled nursing facility. Adults aged ≥ 18 years residing in the SNF with available laboratory data were included (n = 1,256). Exposures included presence of an enteral feeding tube at admission, selected chronic conditions, and high-risk medication exposures. The primary outcome was incident hyponatremia, defined as any corrected serum sodium value < 135 mEq/L occurring after admission. Relative risks were estimated using modified Poisson regression. Results Incident hyponatremia occurred in 34.6% of residents. In adjusted models, enteral feeding tubes (aRR 2.42; 95% CI 1.84–3.19), chronic kidney disease (aRR 1.87; 95% CI 1.43–2.44), and Liver Disease (aRR 1.58; 95% CI 1.20–2.07) remained the significant independent predictors. Congestive Heart Failure, ethnicity, sex, age, and high-risk medication exposure were not significantly associated with risk at the predetermined alpha = 0.01, and no significant interactions were observed between CKD, CHF, and liver disease and enteral feeding tubes on incident hyponatremia. Conclusions Hyponatremia remains a common electrolyte abnormality among SNF residents. Enteral feeding tube use was strongly associated with increased cumulative risk of incident hyponatremia. Both CKD and liver disease also pose risk of incident hyponatremia. SNF residents with enteral feeding tubes may benefit from targeted monitoring and risk stratification in long-term care settings. Clinicians should be aware of these risks while ordering water flushing of enteral tubes and assess these patients regularly for hyponatremia.

Background: Understanding drivers of supply and labor cost variation in orthopaedic surgery is crucial to provide value-based care. Time-driven activity-based costing (TDABC) is a more accurate methodology for capturing costs of care than traditional methods. Anterior cruciate ligament reconstruction (ACLR) is one of the most performed outpatient procedures within orthopaedic surgery. The purpose of this study was to characterize the cost composition of ACLR and identify factors that drive cost variation. Methods: Cost data for supplies and time-based personnel usage were extracted from electronic health records and were used to calculate costs using TDABC. TDABC methodology was applied to calculate the cost of personnel usage by multiplying the duration and associated cost per minute. Descriptive statistics and mixed-effects modeling were used to determine cost drivers. Results: This study included 861 patients who underwent ACLR at 8 hospitals. The mean patient age (and standard deviation) was 31.1 ± 11.6 years. Of the 861 patients, 350 were male and 511 were female; 85.6% of patients were White, 8.1% were Asian, and 3.4% were Black. There was 3.2-fold variation in supply costs ($2,950) and 1.6-fold variation in labor costs ($940) between the 10th and 90th percentiles. Overall, supply costs accounted for 58.2% of total costs, whereas labor costs comprised the remaining 41.8%. The intraoperative phase was the greatest generator of total cost (89.7%). After adjusting for surgeon and hospital variability, variation in total cost was most effectively explained by graft type, primary surgery status, and meniscal repair (conditional R 2 = 0.84; marginal R 2 = 0.27). On subanalysis, patients undergoing allograft ACLR had significantly higher total costs, implant costs, and age compared with those undergoing ACLR with any autograft type (all p < 0.01). Conclusions: The most notable drivers of labor and supply cost variation were graft type, surgeon, surgery center, primary surgery status, and concomitant meniscal repair. Understanding modifiable cost drivers may aid health systems in designing value-based pathways, implant formularies, and surgeon education programs. Future studies may integrate cost with outcome measures for a more holistic view of value. Level of Evidence: Economic and Decision Analysis Level III . See Instructions for Authors for a complete description of levels of evidence.