Citations

Establishing vascular access early in out-of-hospital cardiac arrest (OHCA) is a crucial factor for improving prognosis. Clinical guidelines recommend both intravascular (IV) and intraosseous (IO) access, but the superiority of one technique over the other has yet to be determined. Our review aimed to compare the efficacy and safety of IV versus IO access in OHCA. A comprehensive search was conducted on PubMed/MEDLINE, Embase, and Cochrane Library from inception till January 2025 for randomized controlled trials or their subgroup analyses comparing IV versus IO access in adult OHCA patients. The data for clinical outcomes were extracted, and forest plots were generated using the random-effects model in the Review Manager 5.4. We included 6 studies reporting data for 19,811 patients. The pooled analysis demonstrated that IO access had significantly higher odds of successful vascular access on first attempt [odds ratio (OR), 1.25; 95% confidence interval (CI), 0.19–0.34], but this did not translate to improved survival to hospital discharge (OR, 1.23; 95% CI, 0.90–1.67), survival to hospital discharge with a favorable neurological outcome (OR, 1.28; 95% CI, 0.93–1.76), and return of spontaneous circulation (OR, 1.13; 95% CI, 0.67–1.93). Intravenous and intraosseous vascular access have similar effects on clinical outcomes in patients with OHCA. The preferred method for vascular access should depend on the responder’s feasibility and expertise.

Definitive endoderm (DE) differentiation leads to the development of the major internal organs including the liver, intestines, pancreas, gall bladder, prostate, bladder, thyroid, and lungs. The two primary methods utilized for in vitro differentiation of induced pluripotent stem cells (iPSCs) into DE cells are the growth factor (GF) and the small molecule (SM) approaches. The GSK-3 inhibitor (CHIR99021) is a key factor for the SM approach. Activin A and Wnt3a are utilized in the GF approach. In this study, both the GF and SM protocols were compared to each other. The results show that both the GF and SM protocol produce DE with a similar morphological phenotype, gene and protein expression, and a similar level of homogeneity and functionality. However, on both the gene expression and proteomic level, there is a divergence between the two protocols during hepatic specification. Proteomic analysis shows that hepatoblasts from the GF protocol have significantly differentially expressed proteins (DEPs) involved in liver metabolic pathways compared to the SM protocol. Well-validated DE differentiation protocols are needed to fully unlock the clinical potential of iPSCs. In the first step of generating DE-derived tissue, either protocol can be utilized. However, for hepatic specification, the GF protocol is more effective.

Key Points Preexisting CKD, elevated serum creatinine, and severe interstitial fibrosis and tubular atrophy were linked to poor renal prognosis in renal sarcoidosis. Steroid therapy was strongly associated with renal recovery and improved long-term outcomes in renal sarcoidosis. Early detection and management of renal involvement in sarcoidosis are critical to preventing irreversible kidney damage. Background Renal sarcoidosis (RS) is a rare but potentially severe manifestation of sarcoidosis, primarily affecting the kidneys through granulomatous interstitial nephritis and calcium metabolic disturbances. This study evaluates the clinicopathologic features and renal outcomes of biopsy-proven RS, focusing on identifying predictors of renal recovery and disease progression. Methods This retrospective study included 43 biopsy-proven RS at Mayo Clinic (2012–2024). Demographic, clinical, laboratory, and histopathologic data were analyzed. Renal recovery within 6 months was classified as complete, partial, or no recovery based on serum creatinine (sCr) changes. Long-term adverse composite outcomes included the CKD onset, CKD progression, ESKD, dialysis initiation, or death. Logistic regression and Cox proportional hazards regression were used to assess predictors of renal outcomes. Results Among the cohort, 84% exhibited interstitial nephritis, with granulomatous interstitial nephritis in 33%. Calcium phosphate deposits were found in 58% of cases. Hypercalciuria (90%) was more common than hypercalcemia (74%). Within 6 months, 86% achieved recovery (74% complete, 12% partial), while 40% experienced long-term adverse composite outcomes. Higher sCr at biopsy (≥2.4 mg/dl) and moderate-to-severe interstitial fibrosis and tubular atrophy were associated with reduced complete recovery and worse long-term outcomes, while preexisting CKD significantly increased the risk of adverse long-term outcomes. Steroid therapy significantly increased the likelihood of complete recovery and reduced the risk of adverse long-term outcomes. Conclusions Preexisting CKD, elevated sCr at biopsy, interstitial fibrosis and tubular atrophy, and steroid therapy are key predictors of renal outcomes in RS. Early diagnosis and intervention are crucial to preventing irreversible kidney damage.

Abstract In this study, we quantified differences in iris stiffness between female and male subjects in healthy and postlaser peripheral iridotomy (post-LPI) groups using an image-based inverse modeling approach. We analyzed anterior segment optical coherence tomography (AS-OCT) images from 25 participants across four groups. Finite element models were created using **solidworks, **abaqus, and a custom C program, modeling the iris as a neo-Hookean material. We found that post-LPI females had significantly higher normalized elastic modulus (E′=3.81±1.74) than healthy females (E′=0.92±0.31,p=0.004), while no significant difference was observed in males. Post-LPI females also showed significantly higher stiffness than post-LPI males (p=0.003). Here, p denotes the probability value, with p<0.05 considered statistically significant. Our findings suggest that sex-based differences in iris biomechanics may contribute to the higher susceptibility of females to primary angle-closure disease. Despite the small sample size, this preliminary study highlights the need for larger, sex-stratified investigations into glaucoma pathophysiology.

ImportanceMidlife vascular risk factors are associated with an elevated risk of dementia. However, the total contribution of vascular risk factors in midlife and late life with incident dementia is uncertain.ObjectiveTo quantify the proportion of incident dementia attributable to modifiable vascular risk factors measured in midlife and late life and to examine differences by apolipoprotein ε4 genotype, self-reported race, and sex.Design, Setting, and ParticipantsThis was a prospective cohort analysis of the Atherosclerosis Risk in Communities (ARIC) study using 33 years of follow-up (1987-2020). The setting included ARIC field centers (Jackson, Mississippi; Forsyth County, North Carolina; Minneapolis suburbs, Minnesota; Washington County, Maryland). Study baseline in Black and White participants with complete exposure and covariate data was set by age at risk factor measurement (45-54 years, 55-64 years, and 65-74 years). Data were analyzed from August 2023 to December 2024.ExposuresHypertension (systolic blood pressure [BP] ≥130 mm Hg, diastolic BP ≥80 mm Hg, or use of medication for BP), diabetes (fasting glucose ≥126 mg/dL, nonfasting glucose ≥200 mg/dL, self-reported physician’s diagnosis, or use of any diabetes medication), and current smoking (self-reported).Main Outcomes and MeasuresIncident dementia. Population attributable fractions were estimated by age 80 years, and separately after 80 years, from having at least 1 vascular risk factor by age at risk factor measurement.ResultsA total of 7731 participants were included in analysis of risk factors measured at age 45 to 54 years (4494 female [58%]; 2207 Black [29%]; 5524 White [71%]), 12 274 contributed to analysis of risk factors measured at age 55 to 64 years (6698 female [55%]; 2886 Black [24%]; 9388 White [76%]), and 6787 contributed to analysis of risk factors measured at age 65 to 74 years (3764 female [56%], 1375 Black [20%]; 5412 White [80%]). There were 801, 995, and 422 dementia cases by 80 years, respectively. The fraction of dementia by 80 years attributable to at least 1 vascular factor at age 45 to 54 years was 21.8% (95% CI, 14.3%-29.3%), at 55 to 64 years was 26.4% (95% CI, 19.1%-33.6%), and at 65 to 74 years was 44.0% (95% CI, 30.9%-57.2%). Attributable fractions for these factors were higher in apolipoprotein ε4 noncarriers at age 55 years and older (range, 33.3%-61.4%), Black individuals at age 45 years and older (range, 25.5%-52.9%), and female individuals at age 55 years and older (range, 29.2%-51.3%). Only 2% to 8% of dementia cases after 80 years were attributable to these factors.Conclusions and RelevanceResults of this cohort study suggest that between 22% and 44% of incident dementia cases by 80 years in the ARIC study were attributed to midlife and late-life vascular risk factors. Assuming causal relationships, maintaining optimal vascular health across the life course could mitigate a sizeable proportion of dementia risk by 80 years.

This case series describes a distinctive inspiratory noise observed during sleep in patients with IgLON5-antibody disease.

The prevalence of comorbid metabolic dysfunction–associated steatotic liver disease (MASLD) and obesity has increased exponentially over the last several years, with current estimates demonstrating that up to 40% of adults in the United States have MASLD. Metabolic dysfunction–associated steatohepatitis is now a leading indication for liver transplantation, and rates of obesity and MASLD pre-transplant and post-transplant are on the rise. Our understanding of the physiology of obesity and metabolic disease and the availability of effective obesity treatments have evolved over the same time frame. With the availability of new anti-obesity medications, there has been a debate over the role of pharmacotherapy versus interventional approaches in the treatment of obesity and MASLD in the liver transplantation population. In October 2024, the American Society of Transplantation (AST) Liver and Intestinal Community of Practice held a virtual Controversies Conference on obesity and liver transplantation. Experts in the field presented the available data, and smaller working groups had interactive breakout sessions that identified knowledge gaps and developed recommendations. This perspective prepared on behalf of the participants of the AST Controversies Conference on obesity and liver transplant aims to summarize the available evidence for surgical and pharmaceutical treatment in the liver transplantation population.

Background: Supracondylar humerus fractures (SCH) are the most common type of elbow fracture in children, with many cases requiring surgery. Treatment of postoperative pain for SCH has high variability, but can often be treated effectively with minimal or no opioids. Furthermore, there is significant morbidity related to pediatric opioid consumption. The goal of this study was to characterize prescription patterns in the United States following closed reduction and percutaneous pinning (CRPP) of SCH. Methods: All patients aged 10 or younger years who underwent CRPP of SCH from January 2010 to December 2021 were identified in the PearlDiver Mariner Claims Database. The primary outcome was postoperative pain medication prescriptions in the 30 days following SCH CRPP. Patient demographics, prescription duration, and morphine milligram equivalents (MME) were analyzed. Multivariable-log-binomial mixed regression models were constructed to assess factors associated with increased opioid prescription. Results: In total, 43,611 SCH CRPP cases in patients aged 10 or younger were identified from 2010 to 2021. Throughout the study period, 48.6% of patients (21,191/43,611) received and filled a narcotic pain prescription. The percentage of patients receiving opioid medication decreased from 54.7% in 2010 to 27.4% in 2021. Opioid prescriptions totaled a mean of 6.1±2.1 days of narcotics with a mean of 79.2 MME prescribed per patient. Increased patient age, increased Elixhauser comorbidity index, and Medicaid insurance were all associated with increased opioid prescription (P<0.001). Living in the Northeast, increased family income, and commercial insurance were associated with decreased opioid prescriptions (P<0.001). Conclusions: Nearly half of the patients over the past decade treated with CRPP for SCH received a narcotic prescription. However, there has been a steady decline in the proportion of patients being prescribed opioids, with only 27.4% receiving opioids in 2021. Further, patients with increased comorbidities or those insured by Medicaid with lower mean family income may be at risk for increased opioid prescription. While efforts have been made to reduce opioid overprescribing, there continues to be room for further reduction in opioid utilization after CRPP for SCH moving forward.

ABSTRACT Background Kidney disease significantly increases the risk of dementia, including among kidney transplant (KTx) recipients. To date, the cost implications of dementia after KTx are not well described. Methods We performed a retrospective cohort study of US Renal Data System (USRDS) data (2006–2020) to estimate cost of care for ≥65‐year‐old Medicare insured KTx recipients (2006–2020) with newly diagnosed dementia ( n = 3285), compared to propensity‐matched controls without dementia ( n = 6570). KTx recipients age 65+ years with post‐KTx dementia were identified by diagnosis codes, and costs were computed based on payments on Medicare claims. Average costs per month, marginal costs per month, and cumulative costs were compared after dementia diagnosis versus after the equivalent time post‐KTx in controls. Results Dementia was diagnosed at a mean of 5.1 ± 3.4 years post‐KTx. Patients' characteristics were well matched in cases versus controls, including age (mean: 70.1 vs. 69.9 years), sex (38.4% vs. 37.9% women), race (23.7% vs. 22.2% African American), and cause of ESKD (45.4% vs. 43.7% diabetes). Over 4 years post‐KTx, dementia was associated with reduced survival (27% vs. 68%) along with $66 145 (95% CI $51 560‐$78 489) higher Medicare spending. Average monthly costs in dementia patients reached a maximum of $12 713 and exceeded the cost of unaffected patients by up to $9789 per month. Conclusions Post‐KTx dementia dramatically increased resource utilization and reduced post‐KTx surivival. These findings highlight the need for care pathways that better integrate cognitive health assessment and management into the care of KTx candidates and recipients.

(1) Burn injuries demand multidisciplinary, evidence-based care, yet the extensive literature complicates timely decision making. Retrieval-augmented generation (RAG) synthesizes research while addressing inaccuracies in pretrained models. However, citation bias in sourcing for RAG often prioritizes highly cited studies, overlooking less-cited but valuable research. This study examines RAG’s performance in burn management, comparing citation levels to enhance evidence synthesis, reduce selection bias, and guide decisions. (2) Two burn management datasets were assembled: 30 highly cited (mean: 303) and 30 less-cited (mean: 21). The Gemini-1.0-Pro-002 RAG model addressed 30 questions, ranging from foundational principles to advanced surgical approaches. Responses were evaluated for accuracy (5-point scale), readability (Flesch–Kincaid metrics), and response time with Wilcoxon rank sum tests (p < 0.05). (3) RAG achieved comparable accuracy (4.6 vs. 4.2, p = 0.49), readability (Flesch Reading Ease: 42.8 vs. 46.5, p = 0.26; Grade Level: 9.9 vs. 9.5, p = 0.29), and response time (2.8 vs. 2.5 s, p = 0.39) for the highly and less-cited datasets. (4) Less-cited research performed similarly to highly cited sources. This equivalence broadens clinicians’ access to novel, diverse insights without sacrificing quality. As plastic surgery evolves, RAG’s inclusive approach fosters innovation, improves patient care, and reduces cognitive burden by integrating underutilized studies. Embracing RAG could propel the field toward dynamic, forward-thinking care.