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Soluble epoxide hydrolase in the liver orchestrates abdominal aortic aneurysm formation in mice
Kim, David S; Horimatsu, Tetsuo; Ogbi, Mourad; Goo, Brandee; Shi, Hong; Veerapaneni, Praneet; Chouhaita, Ronnie; Cyriac, Nicole; Moses, Mary; Prasad, Rosaria; Cave, Stephen; Benson, Tyler W; Harb, Ragheb; Aboud, Ghaith; Sellers, Hunter G; Shivers, Mitchell; Haigh, Stephen; Fulton, David J; Csányi, Gábor; Huo, Yuqing; Long, Xiaochun; Coffey, Philip; Lee, Richard; Guha, Avirup; Zhi, Wenbo; Young, Lufei; Zeldin, Darryl C; Hwang, Sung Hee; Hammock, Bruce D; Weintraub, Neal L; Kim, Ha Won
The liver plays an important role in cardiovascular disease by amplifying systemic inflammation, while the underlying mechanisms remain to be defined. Soluble epoxide hydrolase (sEH) is a pro-inflammatory enzyme, and pharmacological inhibition of sEH was shown to protect against various inflammatory diseases. In this study, we have identified a novel role of the liver, through expression of sEH, in the pathogenesis of abdominal aortic aneurysm (AAA). sEH expression and activity were markedly higher in mouse liver compared with aorta and further increased in the context of AAA. Pharmacological inhibition or hepatocyte-specific disruption of sEH prevented AAA formation in two animal models of AAA (angiotensin II infusion and aortic calcium chloride application in male mice), concomitant with reduced expression of complement C3 and serum amyloid A, liver-derived inflammatory factors causally linked to AAA formation. Interestingly, data from co-incubation of liver ex vivo with aorta identified galectin-3 secreted from the aneurysm-prone aorta that activates sEH in the liver. We also determined 12,13-dihydroxyoctadecenoic acid (DiHOME) and various circulating pro-inflammatory cytokines as a downstream mechanism potentially associated with hepatic sEH in the context of AAA. These novel findings provide direct evidence that bidirectional crosstalk between aorta and liver contributes to AAA via hepatic sEH.
PMCID:13065950
PMID: 41772184
ISSN: 2399-3642
CID: 6073697
Barium Where It Does Not Belong: Retrograde Filling of the Biliary Tree
Walradt, Trent; Senter-Zapata, Michael J; Cohen, Jonah
PMCID:13395485
PMID: 42495168
ISSN: 2326-3253
CID: 6073674
Endoscopic tunneled stricturotomy versus surgical conversion to Roux-en-Y gastric bypass for the management of stenosis after sleeve gastrectomy
Walradt, Trent; Szvarca, Daniel; Thompson, Christopher C
BACKGROUND AND AIMS:Stenosis after laparoscopic sleeve gastrectomy (LSG) is common. Endoscopic balloon dilation is first-line therapy but often requires multiple sessions and may fail. Surgical conversion to Roux-en-Y gastric bypass is effective but invasive. Endoscopic tunneled stricturotomy offers a less-invasive alternative. We compared clinical success, adverse events, and length of stay between endoscopic and surgical treatments for post-LSG stenosis. METHODS:This retrospective, matched cohort study included patients treated with endoscopic stricturotomy (ENDO) group or Roux-en-Y gastric bypass conversion (SURG) group, matched 1:1 by age, sex, body mass index, time from LSG, and previous treatments. The Fisher exact and t tests were used. RESULTS:In 24 patients (12/group), the rate of adverse events was lower in ENDO (0% vs 41.7%, P = .04). Length of stay was shorter in ENDO (1.21 vs 2.57 days, P = .03). Clinical success was 83.3% (ENDO) versus 100% (SURG) (P = .48). CONCLUSIONS:Endoscopic stricturotomy is a safe, effective alternative for refractory post-LSG stenosis.
PMID: 40819677
ISSN: 1097-6779
CID: 6073667
Percutaneous needle decompression for endoscopic iatrogenic pneumoperitoneum: assessment of safety and efficacy in real world practice
Walradt, Trent; Szvarca, Daniel; Melendez Torres, Jonathan; Thompson, Christopher C
PMID: 41986133
ISSN: 1468-3288
CID: 6073672
Hypothalamic representation of aggressiveness across mouse strains
Dai, Xiuzhi; Wang, Yifan; Yamaguchi, Takashi; Genecin, Michael; Rozenfeld, Eyal; Dua, Prakhar; Dai, Bing; Cai, Jing; Lin, Dayu
Aggression is an innate behavior conserved across species, serving as a critical means to compete for food, mating opportunities, and other essential resources. A central question in aggression research is the extent to which inter-individual variability in aggression is shaped by genetic factors. Here, we examine aggressive behaviors in naïve male mice across seven genetically defined strains and find large cross-strain differences. We find a tight correlation between aggressiveness and anxiety levels across strains, but not within the same strain, suggesting strong genetic control of both traits. Pharmacologically elevating anxiety in high-aggression strains reduces aggression, revealing a causal relationship between these behaviors. We further demonstrate that differences in the synaptic and cellular properties of neurons in the ventrolateral ventromedial hypothalamus (VMHvl) largely account for cross-strain variability in male aggression, and that chemogenetically increasing VMHvl excitability enhances attack behavior in a low-aggression strain. Together, these findings reveal the neuronal implementation of the genetic control of innate aggression level.
PMID: 42764303
ISSN: 2041-1723
CID: 6073494
CT Fibrosis Extent and BAL Lymphocytosis Reveal Distinct Prognostic Transcriptomic Signatures in Fibrotic ILD
Fernández Pérez, Evans R; Pryor, Joseph B; Kam, Michelle Li Wei; Koslow, Matthew; Solomon, Joshua J; Swigris, Jeffrey J; Koelsch, Tilman L; Vestal, Brian
PMID: 42765486
ISSN: 1535-4989
CID: 6073495
Lung Utilization and Transplant Outcomes after Donor Management at an In-Hospital Donor Care Unit versus the Donor Hospital
Stewart, Darren E; Sommer, Philip M; Victoria Davis, N P; Chang, Stephanie H; Natalini, Jake G; Piper, Greta L; Mehta, Sapna A; McBride, Jennifer P; Boulton, Gabriella C; Lesko, Melissa B; Massie, Allan B; Segev, Dorry L; Montgomery, Robert A; Angel, Luis F
BACKGROUND:Fewer than 20% of donated lungs are transplanted. We examined the impacts of donor management and recovery at an in-hospital donor care unit (DCU) established in 2021 versus the donor hospital (DH). METHODS:(P/F ratio) were examined as a hypothesized effect modifier. We projected the national impact of improved utilization on lung transplant volume. RESULTS:After adjusting for donor differences, lung utilization was 88% higher (aRR: 1.88; 95% CI: 1.40, 2.53) in the DCU versus DH setting. Median P/F ratio increased from 275 to 348 mmHg (p<0.0001) in the DCU and explained approximately 38% of the improvement in lung utilization. Non-lung organ utilization was either improved or non-inferior in the DCU. Lung graft survival and pulmonary function were similar for recipients of DCU versus DH-managed donors. Nationally, an 88% improvement in lung utilization among donors not currently transferred to a DCU could theoretically result in ≥300 more lung transplants per year. CONCLUSIONS:Lung transplantation can be nearly doubled through lung-centric donor management in a DCU, without sacrificing recipient outcomes nor the utilization of other organs. Donor management practices to optimize lung utilization should be proliferated by establishing more DCUs and, where feasible, applying lung-centric protocols in donor hospitals.
PMID: 42764097
ISSN: 1557-3117
CID: 6073493
Preventing pancreatic fistula following pancreatectomy: meta-analysis of randomized clinical trials
Montorsi, Roberto M; Marchetti, Alessio; Hendriks, Tessa E; Daams, Freek; Busch, Olivier R; Groot Koerkamp, Bas; De Pastena, Matteo; van Santvoort, Hjalmar C; Bonsing, Bert A; Paiella, Salvatore; Malleo, Giuseppe; Besselink, Marc G; Salvia, Roberto
BACKGROUND:The majority of postoperative morbidity and mortality after partial pancreatectomy is attributable to postoperative pancreatic fistula. Several interventions to prevent postoperative pancreatic fistula have been assessed in randomized clinical trials but consensus on their efficacy is lacking. This is the first systematic review and meta-analysis of randomized trials focusing on strategies to prevent postoperative pancreatic fistula after all types of partial pancreatectomy. METHODS:Eligible randomized clinical trials assessing postoperative pancreatic fistula following partial pancreatectomy were included from the Evidence Map of Pancreatic Surgery database (2005-2025). As primary endpoint, both the 2005 and 2016 International Study Group for Pancreatic Surgery definitions of grade B/C postoperative pancreatic fistula were accepted. Interventions shown to reduce postoperative pancreatic fistula in at least one randomized trial were identified, and meta-analysis undertaken for those with at least three available trials, irrespective of their outcome. RESULTS:Overall, 193 RCTs were included with 29 408 patients from 24 countries. The pooled rate of postoperative pancreatic fistula grade B/C was 15.1%: 14.2% after pancreatoduodenectomy and 19.1% after left pancreatectomy. Overall, 24 trials identified 18 interventions as effective in reducing the rate of postoperative pancreatic fistula: 11 intraoperative and 7 postoperative. Eight interventions were eligible for meta-analysis, involving 46 trials. Following meta-analysis, three interventions remained effective: drain omission in left pancreatectomy, perioperative use of somatostatin analogues, and administration of perioperative corticosteroids. The certainty of evidence was high for drain omission, moderate for somatostatin analogues, and low for corticosteroids. Eleven trials focused specifically on high-risk patients and four on ongoing postoperative pancreatic fistula. No trial combined interventions. CONCLUSION/CONCLUSIONS:Omission of drains in left pancreatectomy, perioperative use of somatostatin analogues, and administration of perioperative corticosteroids are effective strategies to prevent postoperative pancreatic fistula after partial pancreatectomy. However, current evidence remains immature and further RCTs evaluating these interventions are warranted, as they are likely to change the conclusions of subsequent meta-analyses. Such trials could potentially focus on high-risk patient cohorts and/or assess combinations of interventions.
PMCID:13591280
PMID: 42765565
ISSN: 2474-9842
CID: 6073497
A Scoping Review and Meta-Analysis of Proportions of Central Nervous System Manifestations Reported in Patients with Sjögren's Disease
Varadhachary, Arun; Noaiseh, Ghaith; Frantsve-Hawley, Julie; Vivino, Frederick B; McCombe, Jennifer A; Bhattacharyya, Shamik; Brown, E Sherwood; Carey, Andrew R; Fox, Robert; Grader-Beck, Thomas; Lewis, Janet E; Maitz, Stephen; Mandel, Steven; Rasmussen, Astrid; Sarka, George; Scofield, R Hal; Wallace, Daniel J; Zak, Rochelle; Cox, Kristie; Hammitt, Katherine M; Carsons, Steven; Carteron, Nancy
OBJECTIVE:The objective of this scoping review was to synthesize evidence on the proportion of individuals living with Sjögren's disease who experience central nervous system (CNS) manifestations. METHODS:We searched MEDLINE (via PubMed) and Embase from 1980 through January 29, 2026, and the ECRI Guidelines Trust from 2020 through January 29, 2026. Title and abstract screening, followed by full-text review, were performed in duplicate using prespecified inclusion and exclusion criteria. One reviewer extracted data, with an independent audit completed by one of the project co-leads. Meta-analyses of proportions were conducted. Sensitivity analyses were planned a priori to evaluate the influence of statistical outliers. RESULTS:We identified 22,857 citations, of which 108 met the inclusion criteria. Pooled proportion estimates were generated for 23 CNS manifestations. Several manifestations occurred at frequencies exceeding those reported in the general population, including depression, migraine, insomnia, cognitive dysfunction, psychosis, movement disorders, aseptic meningoencephalitis, neuromyelitis optica spectrum disorder, optic neuritis, multiple sclerosis, cerebral vasculitis, cerebellar syndrome, spinal cord involvement, and non-localizing somatosensory complaints. The degree of increased frequency differed substantially across manifestations, and several estimates were highly influenced by individual studies, as indicated by sensitivity analyses. CONCLUSION/CONCLUSIONS:The spectrum of CNS involvement in Sjögren's disease is broad and heterogeneous. Attributing CNS manifestations to direct SjD involvement or coexisting conditions remains unclear and cannot be assumed to be causally linked. Our findings underscore the complexity of CNS manifestations in Sjögren's disease and highlight the need for evidence-informed guidance to support accurate diagnosis, attribution, and management of neurologic manifestations.
PMID: 42765529
ISSN: 2151-4658
CID: 6073496
A Multi-Site Evaluation of a Psychedelic Medicine Curriculum for Psychiatry Trainees
Yaden, Mary E; O'Donnell, Kelley C; Roberts, Daniel E; Goldway, Noam; Tiwari, Praachi; Ching, Terence H W; Hokanson, Jamila; Gukasyan, Natalie; Appold, Brendan; Glick, Giancarlo; Kelmendi, Benjamin; Ross, Stephen; Pittenger, Christopher
OBJECTIVE:Interest in psychedelic medicine is increasing, yet psychiatry trainees report limited education in this area. The authors developed a standardized curriculum and evaluated its impact on trainee knowledge and attitudes toward psychedelic medicines. METHODS:A 6-h psychedelic medicine course was delivered across four psychiatry residency programs in the Northeast United States in 2025-2026. The curriculum included six modules covering foundational concepts and evidence, as well as clinical considerations. Anonymous pre- and post-course surveys assessed knowledge, interest, and confidence in counseling. Statistical comparisons were used to evaluate pre-post changes. RESULTS:Forty trainees participated across institutions; 34 completed a pre-course survey and 22 completed a post-course survey. Most trainees reported minimal prior didactic exposure to psychedelic medicine. Self-assessed knowledge as well as scores on a knowledge quiz improved significantly following the course. Self-rated understanding of both the rationale for psychedelic treatments and limitations of evidence increased. Most substantially, confidence in counseling patients about clinical research, harm reduction, and treatment risks improved across domains. Baseline interest in psychedelic medicine was high at the start of the course and did not change significantly following its completion. CONCLUSIONS:A multi-site curriculum in psychedelic medicine was associated with increased knowledge and counseling confidence in trainees. The curriculum did not significantly impact interest or plans to pursue opportunities in psychedelic medicine, suggesting the course did not overinflate enthusiasm for the field. Standardized curricula in residency education may help address gaps in psychiatric training as clinicians increasingly encounter questions about these emerging treatments.
PMID: 42778871
ISSN: 1545-7230
CID: 6073487