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Abstract Background Immune dysregulation, immunosuppressive therapy and active inflammatory bowel disease (IBD) increase susceptibility to respiratory syncytial virus (RSV) infection. We evaluated the risk of RSV infection in patients with active and nonactive IBD. Methods Using the TriNetX Analytics Network from October 2024 through March 2025, we identified adult patients (aged ≥18 years) with IBD. Patients were classified as having active IBD if they had recent IBD complications, IBD-related surgery, or elevated inflammatory markers (within preceding 6 months); those without recent complications,surgeries, or elevated inflammatory markers were classified as having nonactive IBD within the same period. Outcomes were assessed within 180 days after the index date and included RSV infection, bacterial pneumonia, intensive care unit (ICU) admission, and mechanical ventilation. Results Among 141 763 patients (47 883 patients with active IBD, 93 880 patients with nonactive IBD), 2879 patients with active IBD and 3583 with nonactive IBD received the RSV vaccination. After matching, each cohort included 46 308 patients. Active IBD was associated with higher odds of RSV infection (adjusted odds ratio [aOR], 1.55; 95% CI, 1.18-2.04), bacterial pneumonia (aOR, 2.58; 95% CI, 2.08-3.19), ICU admissions (aOR, 2.07; 95% CI, 1.88-2.28), and mechanical ventilation (aOR, 2.41; 95% CI, 2.01-2.88). RSV risk remained higher among patients with active IBD both with and without systemic corticosteroid exposure. Among RSV-vaccinated patients, RSV infection rates were not significantly different between active and nonactive IBD (aOR, 1.26; 95% CI, 0.78-1.79). Conclusion Patients with active IBD had higher risk of RSV infection. Increased RSV risk was observed both among patients with active IBD with and without systemic corticosteroid exposure. Among RSV-vaccinated patients, RSV infection rates were not significantly different between active and nonactive IBD. Further prospective studies are needed to validate these findings.

Importance Gastroparesis is a condition of delayed gastric emptying in the absence of gastric outlet obstruction. Based on a 2018 US administrative health insurance claims database study, prevalence of definite gastroparesis (with documented delayed gastric emptying) was 21.5 per 100 000 persons. Observations Gastroparesis, which is caused by reduced contractions of the distal stomach or abnormal pyloric relaxation, is more common among females than males (ratio, 2:1-4:1) and typically causes nausea, vomiting, early satiety, bloating, and abdominal pain or discomfort. In a large US epidemiological study involving 82.6 million patients, the most common causes of gastroparesis were type 2 diabetes (51.7%), postsurgical effects (15%), medication-induced (11.8%), idiopathic (11.3%), type 1 diabetes (5.7%), and other (4.5%). Other risk factors include neurological disorders (eg, Parkinson disease), hypothyroidism, amyloidosis, connective tissue disorders (eg, scleroderma), and viral infections (eg, norovirus, cytomegalovirus, Epstein-Barr virus, SARS-CoV-2). The 2022 American College of Gastroenterology and the 2025 American Gastroenterological Association (AGA) guidelines define the criterion standard diagnostic test for gastroparesis as gastric emptying scintigraphy with more than 10% gastric retention at 4 hours in patients with symptoms of gastroparesis without mechanical obstruction based on upper endoscopy or abdominal imaging such as computed tomographic (CT) scan. The carbon 13 spirulina stable isotope breath test is also approved for diagnosing gastroparesis by the US Food and Drug Administration. Based on the percentage of gastric retention at 4 hours, gastroparesis is categorized in the 2022 AGA clinical practice update as mild (10%-15%), moderate (16%-35%), or severe (>35%). Treatment includes discontinuation of medications that delay gastric emptying such as opioids, cannabis, anticholinergics, and glucagon-like peptide-1 receptor agonists and for patients with diabetes, optimizing glycemic control. First-line therapies according to the AGA 2022 clinical practice update are a small particle diet (food that is blended or chopped into small pieces) that is low in fat and nondigestible fiber and antiemetics (eg, serotonin 5-hydroxytryptamine 3 [5-HT 3 ] receptor antagonists, histamine H 1 receptor antagonists) for mild gastroparesis; antiemetics and prokinetics (metoclopramide, erythromycin) for moderate gastroparesis, and liquid diet or jejunal enteral feeding for severe gastroparesis. Severe refractory gastroparesis may be treated with gastric peroral endoscopic myotomy (G-POEM), which involves endoscopic-guided incision of the pylorus sphincter muscle, or gastric electrical simulation, in which an implanted neurostimulator sends electrical pulses to the stomach muscle. Conclusions and Relevance Gastroparesis is a condition of delayed gastric emptying without gastric outlet obstruction that is diagnosed based on a gastric emptying study. First-line treatments include a small particle diet and antiemetics and prokinetics. Severe refractory gastroparesis may be treated with procedures such as G-POEM or gastric electrical simulation.

This JAMA Clinical Guidelines Synopsis summarizes the American College of Gastroenterology’s (ACG) 2025 clinical guideline update on management of ulcerative colitis in adults.

Temozolomide (TMZ) remains the cornerstone of chemotherapeutic agent for glioblastoma (GBM), yet intrinsic and acquired resistance severely limits its clinical benefit. While O6-methylguanine-DNA methyltransferase (MGMT)–mediated repair of TMZ-induced O6-methylguanine (O6-meG) lesions has been extensively studied, the DNA mismatch repair (MMR) pathway is increasingly recognized as a key determinant of TMZ cytotoxicity. Canonical MMR, mediated by MutSα (MSH2–MSH6) and MutLα (MLH1–PMS2) complexes, recognizes O6-meG: thymine mispairs generated during replication and initiates futile repair cycles that culminate in replication stress, replication fork collapse, and apoptotic signaling; intact canonical MMR is, therefore, required for TMZ-induced cell death. Disruption of canonical MMR, frequently via acquired MSH6 mutations, confers TMZ tolerance and drives hypermutated recurrent GBM. Beyond mismatch correction, MMR proteins perform non-canonical functions in DNA damage signaling, replication stress responses, transcriptional regulation, chromatin dynamics, and immune modulation. These activities may shift the outcome from cytotoxic futile repair toward replication stress adaptation, Translesion synthesis (TLS)-mediated lesion tolerance, immune remodeling, and therapeutic resistance. Notably, partial attenuation or functional diversion of MMR may decouple lesion recognition from cytotoxic signaling, enabling TLS-mediated lesion tolerance without complete loss of MMR activity. This review integrates current insights into canonical and non-canonical MMR functions in GBM, defines their distinct contributions to TMZ sensitivity and resistance, and highlights therapeutic opportunities to exploit MMR-associated dependencies, including synthetic lethal strategies and immunotherapeutic vulnerabilities linked to MMR deficiency-driven hypermutation.

Acanthosis nigricans (AN) is a common dermatologic condition characterized by hyperpigmented, velvety plaques that most frequently affect intertriginous areas. Although often associated with insulin resistance and obesity, AN may also serve as a cutaneous marker of underlying endocrinologic disorders, medication effects, genetic syndromes, or internal malignancy. Recognition of AN provides an important opportunity for early identification of systemic disease and implementation of targeted management strategies. This review summarizes the pathogenesis and etiologic subtypes of AN, highlights key clinical features and differential diagnoses, and outlines an evidence-based diagnostic approach. Management strategies are discussed with emphasis on lifestyle modification, pharmacologic therapies, topical treatments, procedural interventions, and the strength of supporting evidence. Practical considerations relevant to physician assistants are emphasized throughout, including interdisciplinary care and patient education. Early recognition and appropriate management of AN can improve both dermatologic outcomes and overall patient health.

Introduction: Limited research explores dermoscopy use among physician associates (PAs), outside of one prior study examining dermoscopy in PA student education. This study sought to investigate dermoscopy use among practicing PAs and its impact on their overall diagnostic confidence, including in darker skin tones, when differentiating between benign and malignant skin lesions. Methods: An anonymous survey was developed in 2023 with input from experts in dermoscopy and survey creation to assess PA confidence in skin lesion evaluation as well as PA dermoscopy knowledge and use, perceptions, barriers to use, and prior education. The dermoscopy survey was included as an optional module in the 2024 American Academy of Physician Associates (AAPA) Salary Survey. Results: Of 3,174 invited PAs, 995 (31.4%) responded. Most had never used dermoscopy in practice (81%) but knew or recognized the term (71%). A majority (53%) believed PAs should be trained in dermoscopy during PA school, and 26% reported no interest in future dermoscopy use. Dermatology PAs reported more frequent dermoscopy use and generally greater confidence in evaluating skin lesions, both overall and in darker skin tones, than PAs in other specialties. PAs in surgical (OR=0.2, 95% CI 0.1-0.6) and medical (OR=0.3, 95% CI 0.2-0.5) subspecialties were less likely to use dermoscopy at least annually compared with PAs in primary care. PAs in rural areas were more likely to feel confident in differentiating skin lesions than those in urban areas (OR 2.9, 95% CI 1.7-5.0). Conclusion: Dermoscopy use is associated with higher overall skin lesion assessment confidence. Wider adoption, especially outside dermatology, requires training, increased advocacy, and expanded education.

Abstract Early-phase clinical trials of Bruton’s tyrosine kinase (BTK) degraders have demonstrated efficacy in patients with BTK inhibitor-resistant chronic lymphocytic leukemia (CLL). How clinical resistance to BTK degraders arises is unknown. Here we sequenced serial CLL samples from patients enrolled in the phase I trials of zelebrudomide and bexobrutideg and observed recurrent expansion of preexisting BTK A428D mutations at relapse. Unlike previously studied BTK inhibitor resistance mutations, BTK A428D conferred pan-resistance to BTK inhibitors and degraders. In the absence of BTK-directed therapies, however, cells bearing BTK A428D exhibited a competitive disadvantage. A crystal structure of BTK A428D revealed that the mutant aspartate clashes with the adenine ring of ATP and the adenine-mimetic moiety of BTK inhibitors and degraders. Combining BTK degraders with venetoclax mitigated the expansion of BTK A428D. These results provide the molecular basis for clinical resistance to BTK degraders and will inform the development of next-generation BTK degrader therapies.

Abstract Background Appendectomy has been proposed to influence ulcerative colitis (UC) outcomes, but its effect based on timing before or after diagnosis and long-term UC outcomes remains unclear. Materials and Methods Using TriNetX U.S. Collaborative Network, we identified adults with UC (2010-2024) who underwent appendectomy before or after diagnosis. Two 1:1 propensity score-matched comparisons were performed: appendectomy-before-UC and appendectomy-after-UC versus controls. The primary outcome was a 5-year composite of oral/intravenous (IV) corticosteroid use or colectomy. Secondary outcomes included individual composite outcomes and advanced therapy initiation in biologic-naive patients. Subgroup analyses stratified by age and biologic exposure were also performed. Results After matching, appendectomy after UC diagnosis showed no association with the composite outcome (aHR 0.98, 95% CI, 0.83-1.16), oral steroids (aHR 0.90, 95% CI, 0.75-1.09), IV steroids (aHR 1.11, 95% CI, 0.87-1.43), colectomy (aHR 1.24, 95% CI, 0.77-1.99), or advanced therapy initiation (aHR 0.97, 95% CI, 0.63-1.48). Appendectomy before UC diagnosis also showed no difference in the composite outcome (aHR 0.91, 95% CI, 0.76-1.09), oral steroids (aHR 0.88, 95% CI, 0.72-1.08), colectomy (aHR 0.99, 95% CI, 0.60-1.63), or advanced therapy initiation (aHR 0.77, 95% CI, 0.53-1.13). However, IV steroid use was reduced (aHR 0.68, 95% CI, 0.51-0.90, P = .006). In subgroup analyses, advanced therapy initiation was lower in patients aged 18-40 years following appendectomy after UC diagnosis (aHR 0.56, 95% CI, 0.33-0.96, P = .03). Conclusion Appendectomy was not associated with improved long-term UC outcomes of oral/IV steroid use, colectomy or initiation of advanced therapy regardless of timing.

Whole-body cross-sectional imaging has largely replaced skeletal survey as the standard for evaluating hematologic malignancies and bone marrow disorders, but the practical choice between whole-body low-dose CT (WBCT) and whole-body MRI (WBMRI) remains incompletely resolved. This clinical review provides a practical, scenario-based comparison of WBCT and WBMRI across diagnosis, staging, treatment response, and surveillance. We emphasize real-world practical considerations, including scanner access, expertise, patient tolerance, radiation considerations, and cost. In multiple myeloma, with available comparative evidence, we include a focused research synthesis of 3 studies (152 patients) demonstrating high pooled CT-MRI concordance of 0.895 (95% CI: 0.834-0.935) with no detectable heterogeneity ( I 2 =0%), supporting either modality as a reasonable first-line depending on the clinical question. Across all included disease categories, the broader pooled concordance estimate was 0.797 (95% CI: 0.667-0.885) with substantial heterogeneity reflecting variability in clinical context, reference standard, and protocol. WBMRI dominates in non-neoplastic marrow disorders where marrow characterization is essential. In lymphoma, FDG-PET/CT remains the standard for adult disease, with WBMRI most indicated in pediatrics and adolescents. Emerging CT techniques, including dual-energy CT with virtual noncalcium images and photon-counting detector CT, are extending CT into the marrow imaging space and narrowing the historical gap with MRI. Modality selection should be guided by the specific clinical scenario, available resources, and patient factors rather than by global judgments of modality superiority.