Citations

Background/Objective: Although most melanocytic lesions are diagnosed as benign or malignant by histopathologic evaluation, with or without the aid of immunohistochemistry, diagnosis may remain uncertain in a minority of cases. Assessment of copy number abnormalities (CNAs) may provide sufficient additional evidence to favor either a benign or malignant diagnosis in both pediatric and adult cases and in melanocytic lesions of various subtypes, including Spitzoid, mucosal, and acral. CNAs are common in melanomas, while they are rare, with few exceptions, in benign lesions. Detection of CNAs by fluorescence in situ hybridization (FISH) and chromosomal microarray (CMA) has been well established for melanocytic lesions, with advantages and disadvantages for each. The objective of this meta-analysis was to evaluate the utility of CNA testing for the diagnosis of melanoma, across subtypes, when a lesion remains ambiguous after histopathologic and immunohistochemical assessment. In addition, the utility of CNAs to determine prognosis in established diagnoses of melanoma was also evaluated. Methods: The Cancer Genomics Consortium Working Group for Melanocytic Lesions reviewed published data from January 1998 through September 2022 of CNAs in melanocytic lesions detected by either FISH or CMA and conducted a meta-analysis of the findings. Results: Specific abnormalities common in primary cutaneous melanomas of various subtypes and uveal melanomas were enumerated. Differences in CNAs found in primary versus metastatic lesions were also determined, and published evidence for prognosis was summarized. Conclusions: The working group established evidence-based recommendations for the use of CNA testing for evaluation of ambiguous melanocytic lesions.

ABSTRACT Glucagon‐like peptide‐1 (GLP‐1) receptor agonists (GLP‐1 RAs) improve glycaemia and reduce body weight, yet their organ‐level actions on skeletal muscle remain incompletely defined. Framing skeletal muscle as an integrated unit of vasculature and muscle cells, we synthesize evidence with emphasis on glucose and protein metabolism. GLP‐1 and GLP‐1 RAs recruit microvasculature in muscle, expanding capillary surface area and increasing delivery of insulin, glucose, and amino acids. Microvascular recruitment increases interstitial insulin availability and potentiates insulin‐stimulated glucose uptake and glycogen synthesis, whereas direct effects of GLP‐1 on muscle cells remain under investigation. For protein metabolism, microvascular recruitment can enhance muscle protein synthesis when plasma amino acid availability is elevated, whereas effects under basal (fasted) conditions remain unclear. Elucidating the uncertainty regarding GLP‐1 receptor localization in human muscle cells will clarify whether direct signaling occurs within muscle cells, thereby improving our understanding of the relative contribution of direct versus perfusion‐mediated actions of GLP‐1 RAs. Clinically, GLP‐1 RAs reduce lean body mass, likely reflecting energy‐deficit–mediated effects, but studies directly assessing muscle mass are still limited. Overall, current evidence indicates that GLP‐1 RAs exert beneficial effects on muscle vasculature and muscle glucose metabolism. However, their influence on muscle protein turnover remains unclear—primarily due to observed reductions in muscle mass—despite preclinical data suggesting potential favorable effects on muscle protein metabolism that remain to be confirmed in humans.

Background and Aims: Upadacitinib, a selective janus kinase 1 (JAK1) inhibitor, and ustekinumab, an interleukin-12/23 inhibitor, are approved for the treatment of moderate-to-severe ulcerative colitis (UC). However, real-world data in patients with anti-tumor necrosis factor (TNF)-exposure are limited. Methods: We performed a retrospective cohort study in TriNetX US Collaborative Network. Adult patients with UC and prior anti-TNF exposure were identified. Patients who received upadacitinib or ustekinumab between April 2022 and August 2024 were stratified into two cohorts. Patients with Crohn’s disease, rheumatoid arthritis, psoriasis and ankylosing spondylitis were excluded. Propensity-score matching was performed to balance comorbidities, medications, and labs between the two cohorts. Study outcomes included rates of corticosteroid use, colectomies, change of therapy, hospital admissions or emergency department visit, and all-cause mortality. Results: A total of 724 patients in the upadacitinib cohort and 909 in the ustekinumab cohort met the inclusion criteria. After matching, 633 patients remained in each cohort, with balanced baseline characteristics. At 1-year follow-up, the rates of corticosteroid use were 40.1% in the upadacitinib group and 48.5% in the ustekinumab group (aOR= 0.71, 95% CI: 0.69-0.89), mainly driven by differences in oral corticosteroid use (aOR= 0.73, 95% CI: 0.58-0.91). All other outcomes were comparable between the two study groups. Conclusion: In patients with ulcerative colitis and prior anti-TNF exposure, upadacitinib was associated with lower oral corticosteroid use than ustekinumab over 1 year, with no significant differences in rates of colectomy, ED visits or hospitalizations. These findings suggest a potanial higher effectiveness of upadacitinib compared with ustekinumab and may help inform treatment selection in this population.

ABSTRACT Background Infection enteritis is associated with the development of irritable bowel syndrome (IBS) and functional dyspepsia. Aim This study aimed to examine the long‐term risk of IBS and functional dyspepsia, and associated health care utilisation following infection enteritis. Methods We conducted a retrospective cohort study using TriNetX U.S. Network. Adults with infection enteritis were identified and matched to controls, balancing demographics and comorbidities. Primary outcomes were the risk of incident IBS and functional dyspepsia diagnoses at 1, 5, and 10 years. Secondary outcomes were rates of IBS‐ and functional dyspepsia‐related medications, endoscopy, abdominal imaging, and hospitalizations. Pathogen‐specific and multivariate analyses were performed to assess variations in IBS risk. Results After matching, 202,244 patients were identified in each study cohort. At 1 year of follow‐up, the infection enteritis cohort had higher rates of IBS (RR = 2.35; 95% CI: 2.14–2.59), functional dyspepsia (RR = 2.02; 95% CI: 1.84–2.22), use of IBS‐related medications (RR = 1.29; 95% CI: 1.26–1.31), functional dyspepsia‐related medications (RR = 1.56; 95% CI: 1.55–1.59), abdominal imaging (RR = 2.42; 95% CI: 2.29–2.54), and Oesophagogastroduodenoscopy/colonoscopy (RR = 1.57; 95% CI: 1.50–1.65). These risks remained significantly higher in the IE cohort at 5 and 10 years. Salmonella/Shigella (RR = 6.48), and Giardia lamblia (RR = 5.05) had the highest risk of developing incident IBS. Conclusion Infection enteritis was associated with increased risk of IBS and functional dyspepsia, rates of related medication use, and greater healthcare utilisation.

Abstract The purpose of the current study was to identify the influence of individual characteristics on differences in body fat percentage between air displacement plethysmography and dual-energy X-ray absorptiometry (change in body fat percentage) in 360 collegiate student-athletes. Body fat percentage was obtained from air displacement plethysmography and dual-energy X-ray absorptiometry. A 2 (sex)×3 (Brozek body fat percentage, Siri body fat percentage, and dual-energy x-ray absorptiometry body fat percentage) analysis of variance was used to evaluate the difference between the body fat percentages obtained from air displacement plethysmography and dual-energy x-ray absorptiometry in men and women. The agreement between air displacement plethysmography and dual-energy X-ray absorptiometry was evaluated via Bland–Altman plot and linear regression. Multiple linear regression was used to identify the influence of sex, race, height, and body mass on the change in body fat percentages. Dual-energy X-ray absorptiometry yielded greater body fat percentages in both men (4.8±2.8; p < 0.001) and women (2.2±2.9; p < 0.001) compared to air displacement plethysmography measurements. Proportional and systematic biases were observed between air displacement plethysmography and dual-energy X-ray absorptiometry. Race, height, and mass were significant predictors of the body fat percentage difference between air displacement plethysmography and dual-energy X-ray absorptiometry (R 2=0.445, p<0.001, and standard error of the estimate=2.527). The present study suggests that air displacement plethysmography underestimates body fat percentages when compared to dual-energy X-ray absorptiometry and this underestimation may not be the same for every athlete due to their individual characteristics.

Aging is a major risk factor for increased morbidity and mortality following acute respiratory virus infections. To elucidate the immune determinants underlying viral pathogenesis and delayed lung repair in the aged lung, a comprehensive time-course study was conducted. Single-cell RNA sequencing (scRNAseq) and high-dimensional flow cytometry were utilized to compare lungs from young and aged mice infected with influenza A virus (IAV). Aged hosts displayed diminished alveolar macrophage (AM) and dendritic cell (DC) but elevated monocyte-derived macrophage (MoM) and interstitial macrophage (IM) presence following infection. Additionally, enhanced accumulation of adaptive immune cells, including CD4+ tissue-resident helper (TRH) cells, CD8+ tissue-resident memory (TRM) cells, and a B cell subset resembling age-associated B cells, was observed in the memory phase. Pathway analysis revealed that elevated type I and II interferon (IFNα/γ) signaling, especially in MoM/IM subsets, distinguished the aged hosts from the young. Inhibition of IFNα/γ signaling after viral clearance improved long-term respiratory outcomes and reduced both IM and TRH populations in aged mice. These findings highlight the pivotal role of IFNα/γ signaling, likely within MoM/IM subsets, in driving the exuberant persistence of adaptive immune cells and chronic immunopathology in the aged lung following acute viral infection.

Aging is a major risk factor for increased morbidity and mortality following acute respiratory virus infections. To elucidate the immune determinants underlying viral pathogenesis and delayed lung repair in the aged lung, a comprehensive time-course study was conducted. Single-cell RNA sequencing (scRNAseq) and high-dimensional flow cytometry were utilized to compare lungs from young and aged mice infected with influenza A virus (IAV). Aged hosts displayed diminished alveolar macrophage (AM) and dendritic cell (DC) but elevated monocyte-derived macrophage (MoM) and interstitial macrophage (IM) presence following infection. Additionally, enhanced accumulation of adaptive immune cells, including CD4+ tissue-resident helper (TRH) cells, CD8+ tissue-resident memory (TRM) cells, and a B cell subset resembling age-associated B cells, was observed in the memory phase. Pathway analysis revealed that elevated type I and II interferon (IFNα/γ) signaling, especially in MoM/IM subsets, distinguished the aged hosts from the young. Inhibition of IFNα/γ signaling after viral clearance improved long-term respiratory outcomes and reduced both IM and TRH populations in aged mice. These findings highlight the pivotal role of IFNα/γ signaling, likely within MoM/IM subsets, in driving the exuberant persistence of adaptive immune cells and chronic immunopathology in the aged lung following acute viral infection.

The rapid adoption of telemedicine has transformed healthcare delivery in the US, enhancing access and communication for surgical patients across wide geographic areas. However, a critical challenge persists: the need to define and standardize quality metrics specifically for telemedicine in surgery. Existing studies suggest that telemedicine can yield equivalent or improved outcomes compared with in-person visits. Nevertheless, literature remains limited in evaluating patient satisfaction, cost-effectiveness, and diagnostic accuracy. Through expert consensus within the American College of Surgeons Board of Governors Telehealth Pillar, we propose a structured framework for defining and implementing quality metrics for surgical telemedicine. This is based on the Donabedian model, addressing structure, process, and outcome, while also considering the distinct phases of surgical care: preoperative, intraoperative, and postoperative. This framework identifies unique domains of telemedicine in surgical care, emphasizing hospital and organizational structure, patient and provider readiness, and policy alignment. A comparative analysis with existing AHRQ and WHO frameworks highlights gaps in surgical applicability. Finally, we propose an implementation roadmap prioritizing immediate, feasible metrics while identifying areas for future validation. Collaboration among researchers, clinicians, and policymakers will be essential to establish these metrics and ensure that telemedicine delivers on its potential to improve surgical care delivery while addressing disparities in access and outcomes.

Abstract Advances in biomarker technology, digital cognitive assessments, and amyloid‐targeting therapies have redefined the opportunities for accurate and early diagnosis and care of Alzheimer's disease (AD). These advances also create new possibilities for intervention before the onset of cognitive impairment. This paradigm shift has increased the focus on Stages 1 and 2 of AD, in which individuals are cognitively unimpaired but exhibit biological evidence of disease. While early identification of AD offers an opportunity to intervene early to delay progression and preserve quality of life, it also presents complex challenges related to communicating diagnostic results to patients and their families, contextualizing the cost effectiveness of early diagnosis and treatment, and implementation of and equitable access to treatments. Recent, successfully enrolled, preclinical AD trials highlight the complex strategies required to identify asymptomatic, biomarker‐positive individuals on a large scale, and demonstrate critical knowledge gaps in inclusion, follow‐up, and long‐term outcome measurement. The Spring 2025 Alzheimer's Association Research Roundtable (AARR) meeting brought together academics, clinicians, industry, and regulatory leaders to exchange perspectives on current challenges, key learnings, and potential strategies for identifying and treating individuals in very early stages of AD, effectively and safely. This paper presents key takeaways from the Spring 2025 AARR meeting. Highlights New criteria for Alzheimer's disease (AD) enable early identification of AD pathology. Blood tests and digital cognitive assessment tools may facilitate early and personalized care. Plasma biomarkers may be scalable in clinical settings but need confirmation or follow‐up assessments in those individuals with equivocal results. Early therapy shows best results in people with lower initial amyloid and tau burden.