Importance:One in 3 US women of reproductive age live in states that restrict abortion. Total or near-total abortion bans exempt cases where the health or life of the pregnant person is threatened. However, exemptions are ambiguously defined, and abortion practitioners risk criminal prosecution if they are judged after the fact to have performed a prohibited abortion. Objective:To describe hospital policies and practices for exempted abortions. Design, Setting, and Participants:Qualitative study conducted between June and December 2025. The top 5 hospitals by birth volume in abortion-restrictive states (hospitals in states with total or 6-week abortion bans as of June 2025) were identified and participants from 1 hospital per state who were responsible for making or implementing hospital abortion policies were sequentially enrolled. Main Outcomes and Measures:Two coders conducted content analysis of semistructured interviews investigating how hospitals remained apprised of current state laws, supported evidence-based exempted abortion care and reproductive care, and protected clinicians. Results:Thirty-four participants from 9 hospitals (mean [SD] annual live births, 5257 [3289]) across 9 states were most commonly physicians (16 participants [47.0%]) or hospital administrators (10 participants [29.4%]). Participants identified the following hospital policies or practices as supporting evidence-based reproductive care within legal constraints: (1) providing criminal defense resources for physicians; (2) implementing additional employee protections, such as online threat monitoring, contractual indemnity clauses, and coverage for out-of-state abortions for employees; (3) explicitly aligning institutional definitions of abortion with the fullest extent of care permitted under state law to avoid unnecessarily restrictive care; (4) formalizing decision-making support for exempted abortions (eg, multidisciplinary committees); (5) building intrastate hospital alliances to standardize interpretation of state laws banning abortion; and (6) engaging in legislative advocacy and strategic litigation to maximize reproductive care. Participants reported multiple policy effects, including greater employee retention and recruitment and more timely and expansive reproductive care. Conclusions and Relevance:In this qualitative study of 9 high birth-volume hospitals in 9 abortion-restrictive states, institutions implemented policies to protect their employees and support the fullest extent of legally permissible, evidence-based reproductive care. Identified policies may be instructive to other hospitals that provide legally contested medical care.

A greater understanding of chronic lung allograft dysfunction (CLAD) pathobiology, the primary cause of death after lung transplantation (LTx), is needed to improve outcomes. The complement system links innate to adaptive immune responses and is activated early after lung transplantation to form C3 convertase, a critical enzyme that cleaves the central complement component C3. We hypothesized that LTx recipients with a genetic predisposition to enhanced complement activation have worse CLAD-free survival mediated through increased adaptive alloimmunity. We interrogated a known functional C3 polymorphism (C3 R102G) that increases complement activation through impaired C3 convertase inactivation in 2 independent LTx recipient cohorts. C3 R102G, identified in at least 1 of 3 LTx recipients, was associated with worse CLAD-free survival, particularly in the subset of recipients who developed donor-specific antibodies (DSAs). In a mouse orthotopic LTx model, impaired recipient complement regulation led to B cell-dependent CLAD pathology despite moderate differences in graft-infiltrating effector T cells. Dysfunctional complement regulation promoted intragraft accumulation of memory B cells and Ab-secreting cells, leading to increased local and circulating DSA levels in mice. In summary, genetic predisposition to complement activation is associated with an increased humoral response and worse CLAD-free survival.

BACKGROUND:Approximately one-half of patients with cardiogenic shock (CS) require invasive mechanical ventilation (IMV). Much of the data regarding IMV management is extrapolated from other populations, and little is known regarding management and outcomes of patients with CS who require IMV. OBJECTIVES:This study aims to provide data on IMV management in a CS-specific cohort. METHODS:Retrospective study of 104 patients treated for CS requiring IMV at an academic safety net hospital from 2017 to 2023. Indications for IMV, ventilator settings, and medications were obtained. Outcomes included in-hospital mortality, survival to extubation, and reintubation. RESULTS:Reasons for intubation included ongoing cardiac arrest (37%) and hypoxic respiratory failure (32%). Most were on low-level ventilator support 24 hours after intubation (median fraction of inspired oxygen 40% [IQR: 30%-50%], positive end-expiratory pressure 5 cm H2O [IQR: 5-8]). Spontaneous breathing trials were delayed in 78%, primarily due to hemodynamic instability (82%). Nonpalliative extubation occurred in 62% after a median of 4.8 days (IQR: 2.3-8.0). Among patients who received temporary mechanical circulatory support (tMCS) (49%) and survived, tMCS was removed before extubation in 98%. Reintubation occurred in 14% within 48 hours, and in-hospital mortality was 41%. CONCLUSIONS:In this cohort, patients were frequently on minimal ventilator support within 24 hours of intubation, yet spontaneous breathing trials and extubation were delayed due to hemodynamic instability. Rates of failed extubation were comparable to other forms of critical illness. Further research is necessary to determine optimal approaches to ventilator liberation in patients with CS, particularly when hemodynamic derangements or tMCS persist in patients who are otherwise candidates for extubation.

Lung transplant survival is limited by the development of chronic lung allograft dysfunction (CLAD), a type of graft rejection that lacks effective treatments. Autophagy plays a crucial role in maintaining cellular homeostasis. In a single-nucleotide polymorphism screen, we found that lung recipients with two copies of a common hypofunctional genetic variant of autophagy-related 16-like 1 rs2241880 ( ATG16L1 T300A/T300A ), known to deplete this protein from macrophages, were more likely to develop early CLAD. To understand this, we used a mouse orthotopic lung transplant model. Recipients encoding myeloid cell-specific deletion of Atg16l1 ( Atg16l1 Δ/Δ ) or who harbor an engineered orthologous mutation ( Atg16l1 T316A/T316A ) showed similar susceptibility to CLAD. Transcript profiling and mitochondrial tracking studies indicated that increased mitochondrial damage and decreased autophagic removal of mitochondria in Atg16l1-deficient macrophages were associated with heightened activation of the hypoxia-inducible factor 1α (Hif1α) pathway and accumulation of glycolytic transcripts. Metabolic analysis revealed reduced oxidative phosphorylation, increased glycolytic activity, and higher IL-1β expression in Atg16l1-deficient macrophages. Notably, the development of CLAD in Atg16l1 Δ/Δ lung recipients could be significantly prevented by additionally deleting Hif1α in myeloid cells or by treating with the glycolysis inhibitor 2-deoxyglucose. Our results show how a common autophagy-related genetic variant disrupts macrophage metabolism and impairs lung transplant tolerance, pointing toward potential therapeutic strategies to combat CLAD.

BACKGROUND:Lack of consensus on the appropriate look-back period for multi-drug resistance (MDR) complicates antimicrobial clinical decision support. We compared the predictive performance of different MDR look-back periods for five common MDR mechanisms (MRSA, VRE, ESBL, AmpC, CRE).METHODS:We mapped microbiological cultures to MDR mechanisms and labeled them at different look-back periods. We compared predictive performance for each look-back period-MDR combination using precision, recall, F1 scores, and odds ratios.RESULTS:Longer look-back periods resulted in lower odds ratios, lower precisions, higher recalls, and lower delta changes in precision and recall compared to shorter periods. We observed higher precision with more information available to clinicians.CONCLUSION:A previously positive MDR culture may have significant enough precision depending on the mechanism of resistance and varying information available. One year is a clinically relevant and statistically sound look-back period for empiric antimicrobial decision-making at varying points of care for the studied population.

A greater understanding of chronic lung allograft dysfunction (CLAD) pathobiology, the primary cause of mortality after lung transplantation, is needed to improve outcomes. The complement system links innate to adaptive immune responses and is activated early post-lung transplantation to form the C3 convertase, a critical enzyme that cleaves the central complement component C3. We hypothesized that LTx recipients with a genetic predisposition to enhanced complement activation have worse CLAD-free survival mediated through increased adaptive alloimmunity. We interrogated a known functional C3 polymorphism (C3R102G) that increases complement activation through impaired C3 convertase inactivation in two independent LTx recipient cohorts. C3R102G, identified in at least one out of three LTx recipients, was associated with worse CLAD-free survival, particularly in the subset of recipients who developed donor-specific antibodies (DSA). In a mouse orthotopic lung transplantation model, impaired recipient complement regulation resulted in more severe obstructive airway lesions when compared to wildtype controls, despite only moderate differences in graft-infiltrating effector T cells. Impaired complement regulation promoted the intragraft accumulation of memory B cells and antibody-secreting cells, resulting in increased DSA levels. In summary, genetic predisposition to complement activation is associated with B cell activation and worse CLAD-free survival.

BACKGROUND:The maternal mortality rate in the United States is unacceptably high. However, the relative contribution of pregnancy to these outcomes is unknown. Studies comparing outcomes among pregnant vs nonpregnant critically ill patients show mixed results and are limited by small sample sizes. RESEARCH QUESTION:What is the association of pregnancy with critical illness outcomes? STUDY DESIGN AND METHODS:We performed a retrospective cohort study of women 18 to 55 years of age who received invasive mechanical ventilation (MV) on hospital day 0 or 1 or who demonstrated sepsis on admission (infection with organ failure) discharged from Premier Healthcare Database hospitals from 2008 through 2021. The exposure was pregnancy. The primary outcome was in-hospital mortality. We created propensity scores for pregnancy (using patient and hospital characteristics) and performed 1:1 propensity score matching without replacement within age strata (to ensure exact age matching). We performed multilevel multivariable mixed-effects logistic regression for propensity-matched pairs with pair as a random effect. RESULTS:Three thousand ninety-three pairs were included in the matched MV cohort, and 13,002 pairs were included in the sepsis cohort. The characteristics of both cohorts were well balanced (all standard mean differences, < 0.1). Among matched pairs, unadjusted mortality was 8.0% vs 13.8% for MV and 1.4% vs 2.3% for sepsis among pregnant and nonpregnant patients, respectively. In adjusted regression, pregnancy was associated with lower odds of in-hospital mortality (MV: OR, 0.50; 95% CI, 0.41-0.60; P < .001; sepsis: OR, 0.52; 95% CI, 0.40-0.67; P < .001). INTERPRETATION:In this large US cohort, critically ill pregnant women receiving MV or with sepsis showed better survival than propensity score-matched nonpregnant women. These findings must be interpreted in the context of likely residual confounding.

OBJECTIVES: Describe the clinical characteristics and outcomes of 32 critically ill patients who underwent central venous cannulation of the internal jugular vein while in prone position. DESIGN: Retrospective cohort analysis. SETTING: Single tertiary-care urban academic safety-net hospital. PATIENTS/SUBJECTS: Patients requiring mechanical ventilation and prone positioning for severe acute respiratory distress syndrome from March 1, 2020, through March 31, 2021. INTERVENTIONS: Internal jugular vein cannulation while in the prone position. MEASUREMENTS AND MAIN RESULTS: The technique used for venous access, procedural complications, patient demographics, and clinical outcomes are described. Thirty-six prone internal jugular vein cannulations for 32 hemodialysis catheters and four central venous catheters were successfully performed in 32 patients. One immediate and one delayed pneumothorax occurred. Inhospital mortality was 88%. CONCLUSIONS: In the largest series to date, cannulation of the internal jugular vein with the patient in prone position is feasible but associated with a 6% risk of pneumothorax. Severity of illness in patients intolerant of supine positioning results in high inhospital mortality.

The extent to which policies are genuinely responsive to public opinion is a key indicator of democratic performance. The media plays an agenda-setting role between the public and the legislators, serving as a mechanism through which policies can be responsive to the public. Existing literature has explored policy responsiveness, the media's agenda-setting power, and how the media's effect on the political agenda is contingent on socio-political contextual factors. However, the literature has yet to provide rigorous empirical evidence with chronological precision that policies do respond to media attention. This study examines the driving forces behind the responsiveness of energy development policies to media discourse with a novel methodological approach. Using a machine-learning approach, the author analyses thousands of state-level media reports and legislation featuring hydraulic fracturing ('fracking') issues in 15 US states from 2007 to 2017. To model legislation's responsiveness to media reports, the author identifies topic models for prevalent topics in news articles published in the period leading up to the proposal of a bill. Logistic regression models are estimated with political and socio-economic factors as the predictor variables and whether the bill targets prevalent topics in the news as the dependent variable. The findings suggest that state government ideology, legislators' partisan affiliations, and unemployment rates predict state-level policy responsiveness to media attention on fracking issues. This study advances our understanding of policymaking's democratic implications for unconventional energy development and highlights how policymakers can respond strategically to media attention.

The genetic causes for most cases of Alzheimer’s disease (AD) and the underlying biology of pathogenesis remain unknown. Recent large scale proteomics studies on AD patient brains have identified novel protein networks and targets that are highly correlated with AD diagnosis and neuropathology. The most significantly AD-correlated protein network identified contains the cytoskeletal protein Plectin (PLEC) as a network hub. PLEC functions to crosslink different cytoskeletal components and plays a role in axonal transport of synaptic proteins. Considering that microtubule associated protein-Tau (MAPT) dysfunction is an AD hallmark, we hypothesize that PLEC dysfunction increases AD susceptibility by disrupting cytoskeletal homeostasis and synaptic function. Utilizing a combination of genetic and proteomic analyses, we validate Plectin as a potential AD risk factor. We assessed the role of PLEC in Tau-induced neurotoxicity in the animal model Drosophila melanogaster and human neuronal cell culture. Furthermore, we have also elucidated PLEC mutant neurodegenerative phenotypes independent of Tau overexpression in the fly. Immunoprecipitation-mass spectrometry (IP-MS) analysis was performed to define a Drosophila Plectin protein-protein interaction network in adult brains. This network will serve as the basis for cross-species analysis of protein networks. The Drosophila homolog of Plectin (dPLEC) is ubiquitously expressed within the adult brain with strong enrichment in neuronal rich tissues. Using Drosophila models of human tauopathy, dPLEC regulates age dependent Tau-induced neurotoxicity and locomotor dysfunction. Plus, altering levels dPLEC regulates Tau-phosphorylation in both adult Drosophila brains and human neurons. In the absence of Tau overexpression, dPLEC functions in light-induced neuronal transmission confirming its role in normal neuronal function. Continued mechanistic analysis in both Drosophila and human neuronal cultures will determine PLEC’s role in AD neuropathogenesis and elucidate the underlying role of the cytoskeleton in AD susceptibility. To that end, we generated an endogenous GFP-tagged dPLEC (dPLEC-GFP) and performed immunoprecipitation-mass spectrometry (IP-MS) analysis to identify dPLEC protein interactors. Several cytoskeletal and synaptic proteins were identified and are currently being tested for their role in Tau-induced neurodegeneration and synaptic dysfunction. We functionally validate the AD target PLEC as a regulator of Tau-induced neurodegeneration and identify PLEC as a regulator of Tau dynamics and neuronal function.

Introduction: There is a wide range in the reported incidence of pneumothorax (PTX) and pneumomediastinum (PMN) in patients with coronavirus disease 2019 (COVID-19). PTX alone and PTX/PMN combined has also been associated with higher mortality in patients with COVID-19 related acute respiratory distress syndrome (ARDS), however, current data regarding outcomes or predictors of PTX and PMN in COVID-19 ARDS is limited. The purpose of this study was to determine if the incidence of PTX/PMN in a large cohort with COVID-19 related respiratory failure was associated with mortality. Further, we looked to determine which clinical factors or ventilator management strategies may have impacted mortality in underserved patient population with PTX. Methods: We conducted a retrospective analysis of data from a single center COVID-19 intensive care unit of an urban tertiary safety net hospital including all adult patients admitted with COVID-19 associated ARDS requiring mechanical ventilation between March 2020 and January 2021. Following identification of a cohort with radiographic evidence of PTX and/or PMN, demographics, ventilator data, radiographic data, position, information regarding chest tube and sedation management and outcome data were obtained from the electronic medical record. Results: Among 502 patients admitted to the ICU with COVID-19 related ARDS, PTX was identified in 103/ 502 (20.5%), predominantly affecting Hispanic (88%) and male (66%) patients. Thirty-four patients had PMN (18.7%) alone. Of patients with documented PTX, 60 (50.8%) had preceding or co-morbid PMN. PTX with/without PMN was associated with increased mortality (OR 2.19, p=0.0027) even after adjustment for ventilator days. There was no significant association between PMN alone and mortality (OR 0.82, p=0.60). Conservative management without tube thoracostomy was rarely possible (18.4% of PTX). Time to development of PTX was not associated with mortality, but PTX was associated with longer survival times (HR 2.10; p< 0.001). Conclusions: There is a high incidence of PTX/PMN in critically ill patients with COVID-19. PTX, but not PMN alone, is associated with higher mortality in ICU patients.

"The Epidemiology of Maternal Critical Illness Between 2008-2021." Annals of the American Thoracic Society, 0(ja), pp.