Citations

BACKGROUND Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have expanded from metabolic therapeutics to agents with broad effects on inflammation, tissue repair, cutaneous and adipose biology, and aging-related pathways. Clinicians increasingly encounter cutaneous manifestations and aesthetic sequelae with important implications for dermatologic counseling and multidisciplinary care. OBJECTIVE To review current evidence regarding GLP-1RA effects on skin biology, inflammatory dermatoses, wound healing, cutaneous adverse events, and aesthetic aging. MATERIALS AND METHODS A narrative review of clinical, translational, and mechanistic literature was performed, emphasizing psoriasis, hidradenitis suppurativa, wound repair, skin hypersensitivity reactions, autoimmune blistering disease, and facial volume loss associated with pharmacologic weight reduction. RESULTS GLP-1RAs are hypothesized to improve inflammatory skin conditions and wound repair through anti-inflammatory, immunometabolic, and proreparative pathways. Yet, their use may also be associated with injection-site reactions, hypersensitivity eruptions, rare autoimmune blistering disorders, and clinically significant facial deflation and skin laxity. Current evidence is strongest for mechanistic plausibility and observational clinical signals, whereas dermatology-specific randomized trials remain limited. CONCLUSION GLP-1RAs exert bidirectional effects on cutaneous biology. Recognition of both therapeutic opportunities and potential aesthetic or adverse sequelae is important, with patient counseling ideally occurring within a multidisciplinary framework that integrates metabolic benefits with skin health and appearance.

BACKGROUND Glucagon-like peptide-1 receptor agonists (GLP-1RAs) exert systemic metabolic and anti-inflammatory effects that may be relevant to cellular senescence, a key driver of skin aging. However, human cutaneous data are lacking. OBJECTIVE To explore whether systemic GLP-1RA therapy translates to a detectable reduction in cutaneous senescence, quantified by epidermal p21 expression and supported by AI-driven facial imaging. MATERIALS AND METHODS In this controlled observational pilot study, 3 male adults (GLP-1RA n = 2; GLP-1RA–naïve control n = 1) underwent 3-mm punch biopsies from a standardized, sun-protected gluteal site to isolate intrinsic aging. Senescence was quantified through blinded whole-epidermis digital annotation of p21-positive nuclei. Clinical phenotypes were assessed using noninvasive cheek measurements and AI-based facial age estimation. RESULTS The cohort demonstrated divergence in senescence-associated biomarkers correlating with GLP-1RA exposure. The GLP-1RA–naïve control exhibited 8.0% ( n = 2,062 nuclei) epidermal senescence. By contrast, participants with 163 and 62 days of GLP-1RA exposure showed reduced senescence burdens of 2.4% ( n = 2,045) and 0.6% ( n = 1,636), respectively. Automated facial age estimation remained concordant with chronological age across subjects. CONCLUSION Systemic GLP-1RA exposure is associated with a substantial reduction in epidermal p21 expression in some subjects, suggesting a senomorphic effect and supporting further mechanistic studies at the interface of metabolic regulation and skin aging.

Over 37% of pregnant women report excessive daytime sleepiness or hypersomnia during the first trimester, and commonly throughout the remaining trimesters of pregnancy and the postpartum period. The clinical presentation and symptoms of central disorders of hypersomnolence (CDH) such as narcolepsy, idiopathic hypersomnia, or excessive daytime sleepiness secondary to shift work or obstructive sleep apnea may be confounded by physiological changes in sleep architecture and hormonal fluctuations occurring during pregnancy. These overlapping features may cause delays in diagnosis and treatment, impacting quality of life, maternal functioning, and overall health. Management of CDH during pregnancy and lactation requires careful consideration of maternal benefits, potential side effects of medications and fetal and neonatal safety. Here, we present a case of idiopathic hypersomnia and detail management and outcomes during pregnancy and lactation. We briefly review the existing literature on prevalence, pathophysiological mechanisms, diagnostic challenges, objective findings, and risks posed by CDH in pregnancy and lactation. In this narrative review for primary care clinicians, we also summarize currently available evidence regarding the efficacy, teratogenic and other risks of pharmacologic agents used in the treatment of CDH in pregnancy and lactation. Lastly, we provide a clinical algorithm for management of CDH during pregnancy and lactation.

ABSTRACT HLA‐DPA1*03:25 is characterised by a single nucleotide substitution in codon 96 in exon 3.

Background/objectives: To develop expert consensus on peripheral venous access devices (PVAD) and associated care practices, and to formulate guidance recommendations aimed at improving peripheral venous access and management, including the integration of vein visualization technology. This is particularly important for patient populations with peripheral venous depletion, who often present with compromised vasculature that complicates successful PVAD access and increases the risk of complications. Preserving vascular integrity in these patients is essential for maintaining treatment pathways and preventing long-term vascular damage. Methods: A multi-phase approach to consensus development was used consisting of the following: (1) a literature review, (2) a survey and consultation with a vascular access expert panel ( n = 9), and (3) a consultation meeting with patient and public representatives ( n = 2). Results: Survey results and consultation findings from the expert panel demonstrated consensus for 14 of 24 statements. Further analysis resulted in a total of four key problem statements on peripheral venous access and care, and 11 recommendations for future development. Following review by patient and public representatives, three additional recommendations were added, and three existing recommendations were refined. The final consensus statement reflects four problem statements with 14 recommendations. Conclusion: This expert consensus presents 14 evidence-informed statements designed to strengthen practice, improve patient safety, and enhance clinician confidence and competence. Central to these recommendations is the adoption of routine structured pre-insertion vessel assessment using vein visualization technology where appropriate to minimize vessel trauma, and promote more consistent, high-quality vascular access care.

Introduction Eczema and food allergy commonly emerge during infancy and are linked to changes in the gut microbiome, yet it remains unclear when microbiome differences associated with allergic disease first appear during development. Methods We analyzed age-stratified shotgun metagenomic data from 97 children aged 4–36 months, including physician-confirmed cases of eczema or food allergy and non-allergic controls, excluding recent antibiotic or probiotic exposure. Microbial taxa, functional pathways, and composite microbiome metrics were evaluated across three developmental stages: early infancy (4–6 months), mid-infancy (6–12 months), and toddlerhood (12–36 months). Results Differences between allergic and non-allergic children were minimal before 6 months of age but became more apparent during mid-infancy and persisted into toddlerhood. Allergic conditions were associated with reduced abundance of fiber-fermenting and butyrate-producing taxa, enrichment of facultative and inflammation-associated microbes, lower microbiome maturation scores, and shifts in metabolic and inflammatory functional capacity. Discussion These findings suggest that gut microbiome divergence associated with allergic disease becomes more apparent during mid-infancy, highlighting a developmentally relevant period for understanding early immune disruption. The results support further longitudinal and interventional studies aimed at clarifying whether earlier microbiome-targeted strategies may help modify progression along the atopic march.

Introduction Recent transcriptome analysis has demonstrated increased expression of Vascular Endothelial Growth Factor receptor-1 (VEGFR-1/FLT1) and in AD brain. Increased expression of VEGFR1 and its ligand VEGFB were associated with a more rapid rate of cognitive decline, providing evidence of a potential link between increased VEGFR-1 expression in AD pathogenesis. In this study, we explored the potential role of VEGFR-1 expression in neurons on AD pathology. Methods To confirm VEGFR1 expression in AD brains, we first performed immunostaining in AD brain sections (AD - Braak stage V-VI, and normal controls - Braak 0-II). And to determine a potential detrimental role of neuronal VEGFR1 expression on AD associated pathologies, we exposed SH-SY5Y human neuroblastoma cells and mouse primary neurons to either hypoxia conditions (1%O 2 ) or 5 μ Aβ1-42 oligomers or fibrils for 24, 28 and 72hrs. Results In this study, we found preferential staining of VEGFR-1 in the neuropil and neuronal cell bodies both in AD and Control hippocampus and increased VEGFR-1 immunoreactivity in dystrophic neuritic processes in the vicinity of Thio-S positive amyloid plaques in AD brains. And treatment of SH-SY5Y human neuroblastoma cell line and mouse primary neurons, with either hypoxia conditions or Aβ1-42 oligomers, resulted in increased VEGFR-1 expression and cleaved caspase 3 activation, leading to neuronal toxicities/cell death. Similarly, treatment with Aβ1-42 fibrils also increased VEGFR-1 and cleaved caspase 3 protein levels in the SH-SY5Y cells whereas treatment with Aβ1-42 monomers had no effect on VEGFR-1 expression. In addition, we show that over-expression of VEGFR-1 intracellular domains in SH-SY5Y cells directly induced neuronal toxicities and importantly, siRNA-mediated knockdown of VEGFR-1 in neurons prevented the hypoxia, Aβ1-42 oligomer and Aβ1-42 fibril-induced toxicities and cell death phenotypes. Treatment with either hypoxia or Aβ1-42 oligomers also reduced expression of cell survival genes including VEGFR-2 and Hippo pathway YAP1 and siRNA-mediated VEGFR-1 knockdown in the neurons normalized expression of both VEGFR-2 and YAP1. Using differential gene expression analysis, we demonstrated upregulation of several inflammatory/interferon-stimulated genes (ISGs) as well as increased expression of genes involved in activation of oxidative stress and cell death pathways in response to Aβ1-42 oligomers treatment in mouse primary neurons. And siRNA-mediated VEGFR-1 knockdown in the mouse primary neurons, reduced gene expression of both the ISGs and oxidative stress/cell death pathways in response to Aβ1-42 oligomer treatment. Discussion In summary, these results show that siRNA-mediated knockdown of VEGFR-1 in neurons significantly prevented hypoxia, Aβ1-42 oligomer and Aβ1-42 fibril-induced cellular toxicities and cell death phenotypes, indicating a potential detrimental role of aberrant VEGFR-1 expression and signaling in response to AD associated pathologies.

Donation after circulatory death (DCD) livers increasingly use machine perfusion (MP). This study evaluates MP’s impact on older DCD livers based on data from the United Network for Data Sharing, covering all first adult DCD liver transplants (2016–2025). The cohort, divided into pre-MP and MP eras (separated by the FDA approval of the first normothermic MP platform in 2021), showed accelerated growth in DCD liver transplants during the MP era. Donors ≥60 rose 7.8-fold, including donors ≥70 (a USA first). By 2025, DCD livers accounted for 43.2%, with 61.35% from donors ≥50. Normothermic regional perfusion (NRP) (3.0%–21.7%), NMP (2.3%–35.6%), and sequential NRP-NMP (0.1%–19.2%) increased significantly (p < 0.001). The MP era was associated with a decrease in median waitlist time from 112 to 62 days (p < 0.001). Early graft survival was similar across ages. For ages 50–59, 1- and 3-year survivals were 87.9%/78.4% pre-MP and 90.1%/78.8% in the MP era. For 60–69, survival was 85.0%/80.6% pre-MP and 90.0%/71.3% in the MP era. DCD LTs for ≥70 were limited to the MP era with 87.8% 1-year survival. Multivariable Cox regression showed that static cold storage (HR = 1.19), donor age 50–69 versus 18–49, and recipient age (HR = 1.04) increased the risk of graft loss after adjustment. MP is associated with an increased number of older DCD liver transplants and acceptable early graft survival.

Background Intermittent fasting (IF) represents a dietary strategy with known metabolic benefits, however its safety and applicability in patients with chronic kidney disease (CKD) remains poorly understood. AI chatbots’ reliability for clinical and dietary guidance in clinically complex areas remains underexplored. No study has examined AI performance on IF in patients with CKD. This study evaluated the accuracy, consistency, readability, and quality of responses generated by ChatGPT-5 and Claude 4.5 Sonnet regarding IF in CKD. Methods Twenty-five patient-centered questions spanning seven clinical domains were developed by two board-certified nephrologists and submitted independently to ChatGPT-5 and Claude 4.5 Sonnet twice per model. Prompts were submitted under standard and unmodified user conditions without customized system instructions to represent a zero-shot evaluation that is illustrative of typical patient use. Responses were evaluated for accuracy, consistency (comparatively between responses), and appropriateness by the evaluators. Response readability and quality were assessed using the Flesch-Kincaid Grade Level (FKGL) formula and the DISCERN instrument respectively. Results Both ChatGPT-5 and Claude 4.5 Sonnet demonstrated identical accuracy scores during the first question prompts with notable improvement upon re-prompting after 24-hours. Both models demonstrated an identical internal consistency at 90%. ChatGPT-5 produced responses at the middle school level, better aligned with the US adult health literacy benchmark, while Claude 4.5 Sonnet generated responses at the high school level. DISCERN scoring was comparable between chatbots indicative of good response quality. Both chatbots had similar performance regarding individual subdomains. Conclusions Both chatbots illustrated clinically accurate and cautious responses to questions regarding IF in CKD. ChatGPT-5 responses were better suited to the average health literacy of the general United States adult population. Despite our findings, we do not recommend either chatbot be used as the primary source for clinical counseling regarding IF in CKD. It is important for clinicians to help to guide patients toward evidence-based clinical information.