tbuckley/cabot-search huggingface dataset:
Early vs. Delayed Switching from Controlled to Assisted Ventilation: A Target Trial Emulation
Authors: Carmen A. T. Reep, Evert-Jan Wils, Lucas M. Fleuren, Alexander Breskin, Giacomo Bellani, John G. Laffey, Laurent J. Brochard, Tài Pham, Leo Heunks
Journal: American Journal of Respiratory and Critical Care Medicine (2025)

In critically ill patients receiving invasive mechanical ventilation, switching from controlled to assisted ventilation is a crucial milestone towards ventilator liberation. The optimal timing for switching to assisted ventilation has not been studied. Our objective was to determine whether a strategy of early as compared to delayed switching affects the duration of invasive mechanical ventilation, ICU length of stay, and mortality. We conducted a target trial emulation using the prospective, global WEAN SAFE dataset. Patients were eligible for switching if still on controlled mechanical ventilation, not receiving neuromuscular blockers, and PaO2/FiO2 ratio >150 mmHg. We compared an "early switching" strategy (switch within one day after reaching switching eligibility criteria) to a "delayed switching" strategy (switch one or more days after reaching the switching eligibility criteria). Primary outcome was the 28-day cumulative incidence of successful extubation. Secondary outcomes included 28-day and 90-day ICU discharge and ICU mortality. 1489 patients met the switching eligibility criteria. The early switch group had, on average, 4 additional days of being successfully extubated over the 28-day period (95% CI: 3, 6; P<0.001) compared to the delayed group, with a higher difference in cumulative incidence of successful extubation at day 28 (7%; 95% CI: 0, 13; P=0.04). Early switching was associated with an 11% higher cumulative incidence of ICU discharge at day 28 (95% CI: 7, 18; P<0.001) and an average of 7 additional days discharged from the ICU over the 90-day period (95% CI: 4, 12; P<0.001) compared to delayed switching. ICU mortality rates did not differ between the strategies. Early switching from controlled to assisted ventilation is associated with shorter duration of invasive mechanical ventilation and ICU stay compared to delayed switching.
Effectiveness of Empagliflozin vs Dapagliflozin for Kidney Outcomes in Type 2 Diabetes
Authors: Kasper Bonnesen, Uffe Heide-Jørgensen, Diana H. Christensen, Christian F. Christiansen, Timothy L. Lash, Sean Hennessy, Anthony A. Matthews, Lars Pedersen, Reimar W. Thomsen, Morten Schmidt
Journal: JAMA Internal Medicine (2025)

Importance No large randomized clinical trial has directly compared empagliflozin with dapagliflozin, leaving their comparative effectiveness regarding kidney outcomes unknown. Objective To compare kidney outcomes between initiation of empagliflozin vs dapagliflozin in adults with type 2 diabetes who were receiving antihyperglycemic treatment. Design, Setting, and Participants This target trial emulation used nationwide, population-based routinely collected Danish health care data to compare initiation of empagliflozin vs dapagliflozin in adults with type 2 diabetes who received antihyperglycemic treatment between June 1, 2014, and October 31, 2020. Data were analyzed from October 2023 to August 2024. Persons were followed up until an outcome, emigration, death, 6 years, or December 31, 2021, whichever occurred first. Exposure Initiation of empagliflozin vs dapagliflozin. Main Outcomes and Measures Outcomes included acute kidney injury, incident chronic kidney disease (stages G3 to G5 or stage A2 or A3), and progression of chronic kidney disease (≥40% decrease in estimated glomerular filtration rate from baseline). Risks of kidney outcomes were estimated in intention-to-treat and per-protocol analyses using an Aalen-Johansen estimator that adjusted for 56 potential confounders and considered death as a competing event. Results A total of 32 819 individuals who initiated treatment with empagliflozin and 17 464 with dapagliflozin were included (median [IQR] age, 63 [54-71] years; 18 872 female individuals [37.5%]; median [IQR] estimated glomerular filtration rate, 88 [73-104] mL/min/1.73 m 2 ). After weighting, all measured covariates were well balanced between the groups. In intention-to-treat analyses, people who initiated treatment with empagliflozin and dapagliflozin exhibited comparable 6-year risks of acute kidney injury (18.2% vs 18.5%; risk ratio, 0.98; 95% CI, 0.91-1.06), chronic kidney disease stages G3 to G5 (11.8% vs 12.1%; risk ratio, 0.97; 95% CI, 0.89-1.05), chronic kidney disease stage A2 or A3 (14.8% vs 14.3%; risk ratio, 1.04; 95% CI, 0.93-1.15), and progression of chronic kidney disease (5.3% vs 5.7%; risk ratio, 0.94; 95% CI, 0.56-1.58). The primary analyses were supported by corresponding per-protocol analyses. Conclusions and Relevance The results of this cohort study suggest that people with type 2 diabetes who initiated treatment with empagliflozin and dapagliflozin had comparable long-term kidney outcomes.
Novel Meningoencephalomyelitis Associated With Vimentin IgG Autoantibodies
Authors: Dongshan Wan, Shufang Zhao, Chen Zhang, Fang Xu, Huizi Wang, Shaoxin Tao, Zhandong Qiu, Hao Jiang, Dawei Li, Fei Wang, Dong Li, Jiahao Chen, Yan Wang, Yao Yan, Yan Zhao, Xiaohan Gao, Bingxue Jin, Di Liu, Mengyao Zhang, Jingjing Feng, Shiyue Hou, Mingyang Wang, Teng Chen, Ming Lin, Jinming Han, Xinmei Wen, Wei Jiang, Liang Liu, Youming Long, Yinan Zhao, Jun-Ichi Kira, Zheng Liu, Guoliang Chai, Junwei Hao
Journal: JAMA Neurology (2025)

Importance Autoantibodies targeting astrocytes, such as those against glial fibrillary acidic protein (GFAP) or aquaporin protein 4, are crucial diagnostic markers for autoimmune astrocytopathy among central nervous system (CNS) autoimmune disorders. However, diagnosis remains challenging for patients lacking specific autoantibodies. Objective To characterize a syndrome of unknown meningoencephalomyelitis associated with an astrocytic autoantibody. Design, Setting, and Participants This retrospective case series study included samples collected from April 2021 to May 2024 at a tertiary referral hospital among patients with uncharacterized CNS autoimmune disorders and similar clinical and radiological features. Single-cell RNA sequencing (scRNA-seq) was performed on cerebrospinal fluid (CSF) cells of 2 index patients to identify the putative target antigen of the clonally expanded B cells. A comprehensive screening for additional patients was conducted using blinded cell-based and tissue-based assay. Candidate patients were followed up for a median (range) duration of 23 (5-31) months. Exposures scRNA-seq, autoantibody characterization, and testing. Main Outcomes and Measures Detection of the autoantibody and characterization of the associated autoimmune meningoencephalomyelitis. Results Fourteen candidate patients (10 [71%] female; median [IQR] age, 33 [23-41] years) were identified. Initially, CSF from 2 female patients with unknown encephalomyelitis showed astrocytic reactivity on rat tissue but was negative for GFAP IgG. A total of 17 of 37 clonally expanded B cell clonotypes (46%) in their CSF expressed IgG autoantibodies targeting the astrocytic intermediate filament protein vimentin. Subsequent screening identified 12 additional patients. These 14 patients shared a unique clinical profile characterized by relapsing courses and symptoms prominently involving the cerebellum, brainstem, and corticospinal tract (CST). All patients also exhibited elevated CSF protein and cells, intrathecal immunoglobulin synthesis, and magnetic resonance imaging (MRI) showing bilateral lesions on CST. Notably, 8 of 12 patients (67%) who received first-line immunotherapy at their first episode responded well. At the last follow-up, 11 patients (79%) experienced significant disability (modified Rankin Scale ≥3). Conclusions and Relevance In this case series, autoantibodies targeting the astrocytic intermediate filament protein vimentin were identified in patients with previously undifferentiated meningoencephalomyelitis and common radiographic features.
Comparative Effectiveness of Individual Sodium-Glucose Cotransporter 2 Inhibitors
Authors: HoJin Shin, Julie M. Paik, Brendan M. Everett, Elyse DiCesare, Caroline Alix, Robert J. Glynn, Deborah J. Wexler, Elisabetta Patorno
Journal: JAMA Internal Medicine (2025)

Importance Evidence on cardiovascular benefits and safety of sodium-glucose cotransporter 2 (SGLT-2) inhibitors is mainly from placebo-controlled trials. Therefore, the comparative effectiveness and safety of individual SGLT-2 inhibitors remain unknown. Objective To compare the use of canagliflozin or dapagliflozin with empagliflozin for a composite outcome (myocardial infarction [MI] or stroke), heart failure hospitalization, MI, stroke, all-cause death, and safety outcomes, including diabetic ketoacidosis (DKA), lower-limb amputation, bone fracture, severe urinary tract infection (UTI), and genital infection and whether effects differed by dosage or cardiovascular disease (CVD) history. Design, Setting, and Participants This comparative effectiveness study using target trial emulation included adults with type 2 diabetes (T2D) using 3 US claims databases using data from August 2014 through June 2020. The study was conducted from August 2023 to July 2024, with a follow-up period of up to 8 years, and the analysis was completed in July 2024. Exposures First dispensing of canagliflozin, dapagliflozin, or empagliflozin without any use of SGLT-2 inhibitors during the prior 365 days. Main outcomes and measures Database-specific models were weighted using propensity score matching-weights to adjust for 129 confounders. Hazard ratios and 95% CIs for outcomes were estimated using weighted Cox proportional hazards models. HRs were pooled across databases using a fixed-effect meta-analysis. Results : Across the databases, 232 890 patients receiving canagliflozin, 129 881 patients receiving dapagliflozin, and 295 043 patients receiving empagliflozin were identified. Compared with empagliflozin initiators, those receiving canagliflozin or dapagliflozin were less likely to have diabetes-related conditions or a history of CVD at baseline. For MI/stroke risk, both canagliflozin (HR, 0.98; 95% CI, 0.91-1.05) and dapagliflozin (HR, 0.95; 95% CI, 0.89-1.03) were comparable to empagliflozin. For heart failure hospitalization, dapagliflozin initiators had a higher risk (HR, 1.19; 95% CI, 1.02-1.39), particularly at the low dose of 5 mg (HR, 1.30; 95% CI, 1.12-1.50). These findings were consistent across subgroups of CVD history. For safety events, compared with empagliflozin, canagliflozin initiators had a lower risk of genital infections (HR, 0.94; 95% CI, 0.91-0.97) but a higher risk of severe UTIs (HR, 1.13; 95% CI, 1.03-1.24), and dapagliflozin initiators had lower risks of genital infections (HR, 0.92; 95% CI, 0.89-0.95) and DKA (HR, 0.78; 95% CI, 0.68-0.90). Conclusions and Relevance This study found that individual SGLT-2 inhibitors demonstrated comparable cardiovascular effectiveness at clinically effective doses, though low-dose dapagliflozin showed a reduced benefit for heart failure hospitalization compared with empagliflozin.
Location of Care Delivery for Pulmonary Arterial Hypertension in the United States
Authors: Peter J Leary, Rachel J Le, Sumeet Panjabi, John Hartney, Amit Goyal, Charlotte Ward, Dwaipayan Mukherjee, Nathan Hatton, Samuel G Rayner, Hayley D. Germack, John J Ryan
Journal: American Journal of Respiratory and Critical Care Medicine (2025)

Guidelines recommend patients with pulmonary arterial hypertension (PAH) be referred to pulmonary hypertension (PH) centers, but little is known about where care is actually delivered in the United States (US). To use prescription patterns to estimate the proportion of PAH care delivered at US PH centers and explore factors associated with location of care. This retrospective study analyzed claims from the Komodo database in adults who received ≥1 PAH prescription between March 2021 and February 2022. A PH center was defined as accredited (Pulmonary Hypertension Association accreditation), high-volume (≥10 patients receiving parenteral prostacyclin), or a composite including either definition. Analyses included 12,137 patients. Only 37.1% of patients received PAH-specific prescriptions from PH centers. A minority of patients on monotherapy (31.8%) received prescriptions from PH centers. A greater fraction of patients on triple therapy (61.8%) received prescriptions from PH centers. Patients on monotherapy were less likely to receive prescriptions from a PH center if they were older, male, had a higher comorbidity burden, had Medicaid, resided in the South or West, or lived in a 3-digit ZIP code without a PH center. Fewer characteristics were associated with PH center-based care for patients on dual or triple therapy; however, ZIP code and insurance status were associated with center-based care for these patients. A minority of US patients received PAH-specific prescription from a PH center. This potential guideline discordance warrants further exploration and may require guidelines to be revisited or the health system to adapt.
Outcomes of a Population-Based Congenital Cytomegalovirus Screening Program
Authors: Jessica K. E. Dunn, Pranesh Chakraborty, Emily Reuvers, Lauren Gallagher, Kristin D. Kernohan, Melanie Lacaria, Michelle Barton, Kirk Leifso, Jeffrey M. Pernica, Emeril Santander, Marie Pigeon, Sharon L. Cushing, Johnna MacCormick, Soren Gantt, Stacey Weber, Ari Bitnun, Jason Brophy
Journal: JAMA Pediatrics (2025)

Importance Detection of congenital cytomegalovirus (cCMV) infection has previously relied on targeted screening programs or clinical recognition; however, these approaches miss most cCMV-infected newborns and fail to identify those infants who are asymptomatic at birth but at risk for late-onset sensorineural hearing loss. Objective To determine the feasibility of using routinely collected newborn dried blood spots (DBS) in a population-based cCMV screen to identify infants at risk for hearing loss and describe outcomes of infants screened. Design, Setting, and Participants This diagnostic study of a population-based screening program in Ontario, Canada, took place from July 29, 2019, to July 31, 2023. All newborns with a DBS sample collected as part of routine care were screened using polymerase chain reaction (PCR) analysis for cCMV as a risk factor for hearing loss. Infants with positive DBS PCR results for cCMV were referred for confirmation of infection by urine PCR (the gold standard), as well as complete medical and audiologic assessments for sequelae of cCMV infection. Infants with possible or confirmed symptomatic cCMV were referred to pediatric infectious disease specialists for evaluation for potential treatment with valganciclovir. Exposure Detection of cCMV by polymerase chain reaction assay on a newborn DBS. Main Outcomes and Measures Number of infants with positive screening results successfully retrieved and confirmed to have cCMV and the timeliness of retrieval and symptomatic evaluation. Results Of 565 987 infants born in the screening period, 551 034 (97.4%) received cCMV screening on the DBS (45.7% female, 54.3% male). Of these infants, 689 (0.13%) screened positive for cCMV; 601 (87.2%) had cCMV infection confirmed and a complete assessment of sequelae of their congenital infection. Ninety-six infants with completed assessments (16.0%) were deemed to have cCMV symptoms, and 63 of these (65.6%) began valganciclovir treatment. Sensorineural hearing loss was confirmed in 34 of 96 infants (35.4%). Conclusions and Relevance This program found acceptable and feasible implementation of a population-based screening program using routinely collected DBS samples, suggesting that it may serve as a template for jurisdictions considering universal cCMV screening. The program had a much lower than expected prevalence of cCMV-positive screens but still identified many children who would otherwise not have been diagnosed and who would benefit from ongoing audiologic surveillance.
Genomic Drivers of Coronary Artery Disease and Risk of Future Outcomes After Coronary Angiography
Authors: Kelvin Supriami, Sarah M. Urbut, José R. Tello-Ayala, Ozan Unlu, Samuel F. Friedman, Roukoz Abou-Karam, Satoshi Koyama, Md Mesbah Uddin, Eugene Pomerantsev, Michael T. Lu, Michael C. Honigberg, Krishna G. Aragam, Finale Doshi-Velez, Aniruddh P. Patel, Pradeep Natarajan, Patrick T. Ellinor, Akl C. Fahed
Journal: JAMA Network Open (2025)

Importance Disease characteristics of genetically mediated coronary artery disease (CAD) on coronary angiography and the association of genomic risk with outcomes after coronary angiography are not well understood. Objective To assess the angiographic characteristics and risk of post–coronary angiography outcomes of patients with genomic drivers of CAD: familial hypercholesterolemia (FH), high polygenic risk score (PRS), and clonal hematopoiesis of indeterminate potential (CHIP). Design, Setting, and Participants A retrospective cohort study of 3518 Mass General Brigham Biobank participants with genomic information who underwent coronary angiography was conducted between July 18, 2000, and August 1, 2023. Exposures The presence of a genomic risk factor of CAD, defined as FH variant, high CAD PRS, or CHIP driver variation. Main Outcomes and Measures Coronary artery disease presentation (stable or acute), angiographic CAD characteristics (severity and burden), angiographic outcomes (repeat angiogram, revascularization, and in-stent restenosis), and clinical outcomes (heart failure and all-cause mortality). Results Among 3518 participants (2467 [70.1%] male; median age, 64.0 [IQR, 55.0-72.0] years), 1509 (42.9%) had at least 1 genomic driver of CAD (26 FH, 1191 high CAD PRS, and 466 CHIP) that was associated with the presentation of acute coronary syndromes (adjusted odds ratio, 2.67; 95% CI, 2.19-3.26) and with the presence, burden, and severity of angiographic CAD. This association was driven by FH and CAD PRS. One SD of CAD PRS was associated with a 12.51-point higher Gensini score. During 9 years of follow-up, there was an increased risk among FH carriers for a repeat angiogram (adjusted hazard ratio [AHR], 1.70; 95% CI, 1.02-2.83), and revascularization (AHR, 1.97; 95% CI, 1.02-3.80), and among people with high CAD PRS (repeat angiogram: AHR, 1.79; 95% CI, 1.45-2.22; revascularization: AHR, 1.85; 95% CI, 1.37-2.50; and in-stent restenosis: AHR, 3.89; 95% CI, 2.16-7.01). CHIP carriers had no significant increase in angiographic outcomes but were at higher risk of heart failure (AHR, 1.58; 95% CI, 1.04-2.40) and all-cause mortality (AHR, 1.78; 95% CI, 1.47-2.16). Conclusions and Relevance The findings of this study suggest that germline monogenic and polygenic risk are associated with acute coronary syndromes presentation, severity and burden of atherosclerosis, and risk of repeat angiogram, revascularization, and in-stent restenosis. CHIP variant status is associated with incident heart failure and mortality after coronary angiography.
Author Correction: Intestinal TM6SF2 protects against metabolic dysfunction-associated steatohepatitis through the gut–liver axis
Authors: Xiang Zhang, Harry Cheuk-Hay Lau, Suki Ha, Chuanfa Liu, Cong Liang, Hye Won Lee, Queena Wing-Yin Ng, Yi Zhao, Fenfen Ji, Yunfei Zhou, Yasi Pan, Yang Song, Yating Zhang, Jennie Ching Yin Lo, Alvin Ho Kwan Cheung, Jianfeng Wu, Xiaoxing Li, Hongzhi Xu, Chi Chun Wong, Vincent Wai-Sun Wong, Jun Yu
Journal: Nature Metabolism (2025)
Factors Associated With Semaglutide Initiation Among Adults With Obesity
Authors: Meghan I. Podolsky, Rafeya Raquib, Paul R. Shafer, Katherine Hempstead, Randall P. Ellis, Andrew C. Stokes
Journal: JAMA Network Open (2025)

Importance Semaglutide, a novel glucagon-like peptide-1 (GLP-1) receptor agonist medication, was approved for weight management in individuals with obesity in June 2021. There is limited evidence on factors associated with uptake among individuals in this subgroup without diabetes. Objective To explore factors associated with semaglutide initiation among a population of commercially insured individuals with obesity but no diagnosed diabetes. Design, Setting, and Participants This retrospective observational cohort study used data from the Merative MarketScan Commercial Claims and Encounters Database and included adults in the US aged 18 years or older with a first diagnosis of obesity in an outpatient or inpatient setting between June 5, 2021, and July 1, 2022. Inclusion criteria were no prior antiobesity medication, GLP-1, bariatric surgery, or diabetes-related claim in the 12 months prior to obesity diagnosis, and continuous enrollment in the 12 months preceding and 6 months following obesity diagnosis. Analysis was conducted from February to November 2024. Exposures Medication classes prescribed, clinical diagnoses, and sociodemographic factors. Exposures were identified within the 12 months prior to obesity diagnosis. Main Outcomes and Measures Factors associated with incident semaglutide prescription within 6 months after obesity diagnoses were identified using a 10-fold cross-classified random forest model. The top 20 features of the model feature importance list were ranked in a Shapley Additive Explanations plot and used in a multivariable logistic regression model to quantify associations with semaglutide initiation. Results In this study of 97 456 individuals, 58 124 (59.6%) were female, 26 582 (27.3%) were aged 45 to 54 years, 50 705 (52.0%) resided in the South region, and 49 390 (50.7%) were covered by preferred provider organization plans. Of all participants, 1963 (2.0%) initiated semaglutide within 6 months of their initial obesity diagnosis. The random forest model had an area under the receiver operating characteristic curve of 0.71 (95% CI, 0.69-0.74). The most important exposures identified via Shapley Additive Explanations were sex, use of antidepressants, and employer industry. The top 20 factors were used in the logistic regression model, and significant associations were found with semaglutide initiation, including being female (adjusted odds ratio [aOR], 2.30; 95% CI, 2.05-2.58), use of certain medication classes including antidepressants (aOR,1.62; 95% CI, 1.46-1.78), and being covered by a point-of-service plan (aOR, 1.78; 95% C, 1.42-2.22). Conclusions and Relevance This cohort study found that key sociodemographic, health care, and clinical factors are associated with receipt of semaglutide in those without diabetes. These findings suggest that insurance plan type and structure may be a crucial intervention point for improving equity in obesity treatment access.