Edakkanambeth Varayil, Jithinraj

Purpose of review This review aims to synthesize current evidence on the expanding role of glucagon-like peptide-1 (GLP-1) receptor agonists (RAs) beyond glycemic control, particularly in the context of critical illness. With growing recognition of their anti-inflammatory, immunomodulatory, and organ-protective properties, GLP-1RAs show promise in managing complications such as sepsis, acute respiratory distress syndrome (ARDS), acute kidney injury, and multiorgan dysfunction. This review explores their mechanisms across vital systems – including cardiovascular, pulmonary, renal, hepatic, neuropsychiatric, and gut-lung-microbiome axes – highlighting preclinical and clinical data. By consolidating emerging findings, this review aims to inform future translational research and support the integration of GLP-1RAs into critical care strategies. Recent findings Recent evidence highlights GLP-1RAs as promising adjuncts in critical illness due to their multiorgan protective effects. In cardiovascular systems, GLP-1RAs improve endothelial function, reduce ischemia-reperfusion injury, and modulate autonomic tone. In the CNS, they provide neuroprotection by reducing neuroinflammation and pyroptosis. In the lungs, they attenuate ARDS by decreasing cytokine production, enhancing surfactant secretion, and restoring alveolar-capillary integrity. Renally, they reduce acute injury and preserve filtration function. In the gut, GLP-1RAs modulate the microbiome, enhance barrier integrity, and lower systemic inflammation via the gut-lung axis. Additionally, they reduce hepatic inflammation and support pancreatic beta-cell survival, improving insulin sensitivity and metabolic stability in critical care. Summary GLP-1 receptor agonists hold promise as multiorgan protective agents in critical illness, offering benefits beyond glucose control. Their anti-inflammatory, metabolic, and vaso-protective properties may be harnessed to prevent or attenuate organ failure, support recovery, and improve long-term outcomes in critically ill patients. Further clinical trials are warranted to define their safety, efficacy, and optimal application across ICU populations.

Background: Artificial intelligence (AI) platforms can potentially enhance clinical decision-making (CDM) in primary care settings. OpenEvidence (OE), an AI tool, draws from trusted sources to generate evidence-based medicine (EBM) recommendations to address clinical questions. However, its effectiveness in real-world primary care cases remains unknown. Objective: To evaluate the performance of OE in providing EBM recommendations for five common chronic conditions in primary care: hypertension, hyperlipidemia, diabetes mellitus type 2, depression, and obesity. Methods: Five patient cases were retrospectively analyzed. Physicians posed specific clinical questions, and OE responses were evaluated on clarity, relevance, evidence support, impact on CDM, and overall satisfaction. Four independent physicians provided ratings using a 0 to 4 scale. Results: OE provided accurate, evidence-based recommendations in all cases, aligning with physician plans. OE was scored on a scale of zero to four, where zero was very unclear, and four was very clear. Mean scores across cases were clarity (3.55 ± 0.60), relevance (3.75 ± 0.44), support (3.35 ± 0.49), and satisfaction (3.60 ± 0.60). However, the impact on CDM was limited (1.95 ± 1.05), as OE primarily reinforced rather than modified plans. Conclusion: OE was rated high in clarity, relevance, and evidence-based support, reinforcing physician decisions in common chronic conditions. While the impact on CDM was minimal due to the study’s retrospective nature, OE shows promise in augmenting the primary care physician. Prospective trials are needed to evaluate its utility in complex cases and multidisciplinary settings.

AbstractBackgroundAvascular necrosis (AVN) is a known adverse event associated with corticosteroid (CS) usage. Inflammatory bowel disease (IBD) is often treated with a CS for induction of remission. We sought to describe clinical features and outcomes of IBD patients with AVN.MethodsIn this retrospective, single-center, case-control study, patients with IBD who had a diagnosis of osteonecrosis, aseptic necrosis, or AVN from 1976 to 2009 were included, and each was matched with up to 2 controls (IBD but no AVN) on age, sex, IBD subtype, geographic area of residence, and date of IBD diagnosis. We abstracted risk factor data from the medical records. Conditional logistic regression was performed accounting for minor differences in age and date of first IBD visit to assess the relationship between putative risk factors and AVN, expressed as odds ratio and 95% confidence interval.ResultsEighty-five patients were diagnosed with IBD-AVN and were matched with 163 controls. The mean age at AVN diagnosis was 47.5 years. AVN was diagnosed a median of 12.2 years after IBD diagnosis, and the control group was followed for a median of 15 years after IBD diagnosis to ensure that they did not have AVN. Ten percent of patients with AVN did not have any CS exposure. History of arthropathy or estrogen use in Crohn’s disease and use of CS, osteoporosis, and history of arthropathy in ulcerative colitis were significantly associated with AVN.ConclusionsMost patients with IBD-AVN had multifocal involvement. Most had received CS, but many patients had other risk factors including arthropathy.

Background and objectives ESRD requiring dialysis is associated with increased morbidity and mortality rates, including increased rates of cognitive impairment, compared with the general population. About one quarter of patients receiving dialysis choose to discontinue dialysis at the end of life. Advance directives are intended to give providers and surrogates instruction on managing medical decision making, including end of life situations. The prevalence of advance directives is low among patients receiving dialysis. Little is known about the contents of advance directives among these patients with advance directives. Design, setting, participants, & measurements We retrospectively reviewed the medical records of all patients receiving maintenance in–center hemodialysis at a tertiary academic medical center between January 1, 2007 and January 1, 2012. We collected demographic data, the prevalence of advance directives, and a content analysis of these advance directives. We specifically examined the advance directives for instructions on management of interventions at end of life, including dialysis. Results Among 808 patients (mean age of 68.6 years old; men =61.2%), 49% had advance directives, of which only 10.6% mentioned dialysis and only 3% specifically addressed dialysis management at end of life. Patients who had advance directives were more likely to be older (74.5 versus 65.4 years old; P <0.001) and have died during the study period (64.4% versus 46.6%; P <0.001) than patients who did not have advance directives. Notably, for patients receiving dialysis who had advance directives, more of the advance directives addressed cardiopulmonary resuscitation (44.2%), mechanical ventilation (37.1%), artificial nutrition and hydration (34.3%), and pain management (43.4%) than dialysis (10.6%). Conclusions Although one-half of the patients receiving dialysis in our study had advance directives, end of life management of dialysis was rarely addressed. Future research should focus on improving discernment and documentation of end of life values, goals, and preferences, such as dialysis–specific advance directives, among these patients.