Citations

BACKGROUND: Percutaneous microaxial ventricular assist devices (pVADs) have the potential to reduce mortality of patients with cardiogenic shock (CS). However, the association between the distribution of pVAD-performing centers and outcomes of CS has not been explored. METHODS: This observational study included Medicare fee-for-service beneficiaries aged 65 to 99 years treated with pVAD for CS from 2016 to 2020. It examined the associations between patient outcomes and 2 exposure variables: hospitals’ procedure volumes of pVAD and patient-hospital distances (in quintiles [Qn]). We developed Cox proportional hazards regression for 180-day mortality and heart failure readmission rates, and multivariable logistic regression for in-hospital outcomes, adjusting for patient demographics, comorbidities, concomitant treatments, and hospital characteristics, including CS volume, teaching status, and the ability to perform extracorporeal membrane oxygenation. RESULTS: A total of 6637 patients with CS underwent pVAD at 1041 hospitals, with the annualized hospital volume ranging widely from 0.3 to 55.6 cases/year. Patients treated at higher-volume centers experienced lower 180-day mortality compared with those treated at lower-volume centers (Qn1=reference; Qn2: adjusted hazard ratio [aHR], 0.88 [95% CI, 0.79–0.97]; Qn3: aHR, 0.88 [95% CI, 0.79–0.98]; Qn4: aHR, 0.88 [95% CI, 0.78–0.99]; Qn5: aHR, 0.84 [95% CI, 0.74–0.95]; P for trend, 0.026), while we found no evidence that patient-hospital distances were associated with mortality (Qn1=reference; Qn2: aHR, 0.99 [95% CI, 0.89–1.09]; Qn3: aHR, 0.94 [95% CI, 0.85–1.04]; Qn4: aHR, 1.01 [95% CI, 0.92–1.11]; Qn5: aHR, 0.91 [95% CI, 0.82–1.01]; P for trend, 0.160). We found no evidence that the hospital volume and patient-hospital distances were associated with in-hospital bleeding, intracranial hemorrhage, or renal replacement therapy initiation. CONCLUSIONS: Hospital volume was more strongly associated with mortality than patient-hospital distances, suggesting that rational distribution of pVAD-performing centers while ensuring adequate procedure volumes may optimize patient mortality.

Objective Drug-induced long QT syndrome (diLQTS) is an adverse reaction from over 150 FDA-approved medications, posing the risk of triggering torsades de pointes and sudden death. While common genetic variants may modestly impact QT interval individually, their collective effect can significantly amplify risk of diLQTS. Consequently, this study aimed to validate a polygenic risk score (PRS) for diLQTS previously proposed by Strauss et al. Methods A retrospective cohort study was conducted utilizing patients from the Michigan Genomics Initiative prescribed 27 high-risk QT-prolonging drugs and an ECG during the prescription. The primary outcome was marked prolongation of the QTc interval (either >60 ms change from baseline or >500 ms absolute value) during treatment with a high-risk QT-prolonging drug. Results The primary outcome occurred in 12.0% of n = 6070 self-reported White, 12.4% of 558 African American, and 8.2% of 110 Asian patients. The PRS significantly associated with diLQTS in White patients [adjusted odds ratio = 1.44 (95% CI: 1.09–1.89); P = 0.009]. However the study lacked sufficient statistical power to confirm the PRS as a risk factor in African Americans [adjusted odds ratio = 2.18 (95% CI: 0.98–5.49); P = 0.073] and Asians [adjusted odds ratio = 3.21 (95% CI: 0.69–16.87); P = 0.139] due to smaller sample sizes in these groups. Conclusion The previously published PRS for diLQTS was validated in a large, real-world cohort, demonstrating its potential as a tool for identifying high-risk patients. Incorporating this PRS into routine clinical practice could enable proactive measures to prevent life-threatening diLQTS.

BACKGROUND Despite an overall poor prognosis, about 15% of patients with advanced-stage tubo-ovarian high-grade serous carcinoma (HGSC) survive 10 or more years after standard treatment. METHODS We evaluated the tumor microenvironment of this exceptional, understudied group using a large international cohort enriched for long-term survivors (LTS; 10+ years; n = 374) compared with mid-term (MTS; 5–7.99 years; n = 433) and short-term survivors (STS; 2–4.99 years; n = 416). Primary tumor samples were immunostained and scored for intraepithelial and intrastromal densities of 10 immune-cell subsets (including T cells, B cells, plasma cells, myeloid cells, PD-1 + cells, and PD-L1 + cells) and epithelial content. RESULTS Positive associations with LTS compared with STS were seen for 9 of 10 immune-cell subsets. In particular, the combination of intraepithelial CD8 + T cells and intrastromal B cells showed near 5-fold increased odds of LTS compared with STS. All of these associations were stronger in tumors with high epithelial content and/or the C4/Differentiated molecular subtype, despite immune-cell densities generally being higher in tumors with low epithelial content and/or the C2/Immunoreactive molecular subtype. CONCLUSION The tumor microenvironment of HGSC LTS is distinguished by the intersection of T and B cell coinfiltration, high epithelial content, and C4/differentiated molecular subtype, features which may inspire new approaches to immunotherapy. FUNDING Ovarian Cancer Research Program (OCRP) of the Congressionally Directed Medical Research Program (CDMRP), U.S. Department of Defense (DOD); American Cancer Society; BC Cancer Foundation; Canada’s Networks of Centres of Excellence; Canadian Cancer Society; Canadian Institutes of Health Research; Cancer Councils of New South Wales, Victoria, Queensland, South Australia, and Tasmania, Cancer Foundation of Western Australia; Cancer Institute NSW; Cancer Research UK; Deutsche Forschungsgesellschaft; ELAN Funds of the University of Erlangen-Nuremberg; Fred C. and Katherine B. Andersen Foundation; Genome BC; German Cancer Research Center; German Federal Ministry of Education and Research, Programme of Clinical Biomedical Research; Instituto de Salud Carlos III; Mayo Foundation; Minnesota Ovarian Cancer Alliance; Ministerio de Economía y Competitividad; Medical Research Council (MRC); National Center for Advancing Translational Sciences; National Health and Medical Research Council of Australia (NHMRC); Ovarian Cancer Australia; Peter MacCallum Foundation; Sydney West Translational Cancer Research Centre; Terry Fox Research Institute; The Eve Appeal (The Oak Foundation); UK National Institute for Health Research Biomedical Research Centres at the University of Cambridge; University of Pittsburgh School of Medicine; U.S. National Cancer Institute of the National Institutes of Health; VGH & UBC Hospital Foundation; Victorian Cancer Agency.

Importance The optimal inhaled reliever therapy for asthma remains unclear. Objective To compare short-acting β agonists (SABA) alone with SABA combined with inhaled corticosteroids (ICS) and with the fast-onset, long-acting β agonist formoterol combined with ICS for asthma. Data Sources The MEDLINE, Embase, and CENTRAL databases were searched from January 1, 2020, to September 27, 2024, without language restrictions. Study Selection Pairs of reviewers independently selected randomized clinical trials evaluating (1) SABA alone, (2) ICS with formoterol, and (3) ICS with SABA (combined or separate inhalers). Data Extraction and Synthesis Two reviewers independently extracted data and assessed risk of bias. Random-effects meta-analyses synthesized outcomes. GRADE (Grading of Recommendations Assessment, Development, and Evaluation) was used to evaluate the certainty of evidence. Main Outcomes and Measures Asthma symptom control (5-item Asthma Control Questionnaire; range, 0-6, lower scores indicate better asthma control; minimum important difference [MID], 0.5 points), asthma-related quality of life (Asthma Quality of Life Questionnaire; range, 1-7, higher scores indicate better quality of life; MID, 0.5 points), risk of severe exacerbations, and risk of serious adverse events. Results A total of 27 randomized clinical trials (N = 50 496 adult and pediatric patients; mean age, 41.0 years; 20 288 male [40%]) were included. Compared with SABA alone, both ICS-containing relievers were associated with fewer severe exacerbations (ICS-formoterol risk ratio [RR], 0.65 [95% CI, 0.60-0.72]; risk difference [RD], −10.3% [95% CI, −11.8% to −8.3%]; ICS-SABA RR, 0.84 [95% CI, 0.73-0.95]; RD, −4.7% [95% CI, −8.0% to −1.5%]) with high certainty. Compared with SABA alone, both ICS-containing relievers were associated with improved asthma control (ICS-formoterol RR improvement [MID] in total score, 1.07 [95% CI, 1.04-1.10]; RD, 4.1% [95% CI, 2.3%-5.9%]; ICS-SABA RR, 1.09 [95% CI, 1.03-1.15]; RD, 5.4% [95% CI, 1.8%-8.5%]) with high certainty. In an indirect comparison with ICS-SABA, ICS-formoterol was associated with fewer severe exacerbations (RR, 0.78 [95% CI, 0.66-0.92]; RD, −5.5% [95% CI, −8.4% to −2.0%]) with moderate certainty. Compared with SABA alone, ICS-formoterol (RD, −0.6% [95% CI, −1.3% to 0%]) was not associated with increased risk of serious adverse events (high certainty) and ICS-SABA (RD, 0% [95% CI, −1.1% to 1.2%]) was not associated with increased risk of serious adverse events (moderate certainty). Conclusions and Relevance In this network meta-analysis of patients with asthma, ICS combined with formoterol and ICS combined with SABA were each associated with reduced asthma exacerbations and improved asthma control compared with SABA alone.

Abstract Background Pulmonary Hypertension (PH) is a diverse condition associated with elevated mortality. We sought to determine the association of Transthoracic Echocardiography (TTE) parameters with in-hospital mortality in patients with PH admitted to Cardiac Intensive Care Unit (CICU). Methods We included 1 Clinic CICU admissions from 2007 to 2018, with available TTE parameters within the first day of CICU admission who had PH defined as an estimated right ventricular systolic pressure (RVSP) ≥36 mmHg. The primary outcome was in-hospital mortality, evaluated using logistic regression. Results We included 3085 unique CICU patients with PH, predominantly WHO group 2 and 3. Median age was 73.7 (63.8, 82.4) years, and 1343 (43.5%) were females. Heart failure (65.6%) and respiratory failure (34.0%) were the most common admission diagnoses. The median RVSP was 47 (41, 56) mmHg, and 1314 (42.6%) had RVSP ≥50 mmHg. A total of 337 (10.9%) patients died during hospitalization. In-hospital deaths had higher RVSP (51 versus 47 mmHg, p <0.001), reflecting higher right atrial (RA) pressure (14 versus 10 mmHg, p <0.001) (Figure). In-hospital mortality increased with worse TTE parameters reflecting Right Ventricle-Pulmonary Artery (RV-PA) coupling, such as Tricuspid Annular Plane Systolic Excursion/ Right Ventricular Systolic Pressure (RVSP), Tricuspid Annular Systolic Velocity (TASV)/RVSP and TASV/ Tricuspid Regurgitation velocity ratios. Conclusion In CICU patients with PH, we have identified the specific Doppler TTE parameters with strong associations with outcomes. Specifically, RA pressure and parameters of RV-PA coupling had the highest discrimination for in-hospital mortality. Comprehensive Doppler TTE is valuable for identification of high-risk PH patients to facilitate further investigation plans, management, and prognostication. Figure: In-hospital mortality in association with right ventricular (RV) function and right atrial pressure (RAP).In-hospital mortality in association wit

Objective Epilepsy surgery is vital in managing of children with drug-resistant epilepsy. Noninvasive and invasive testing modalities allow for evaluation and treatment of children with drug-resistant epilepsy. Evidence-based algorithms for this process do not exist. This study examines expert response to a vignette of pediatric nonlesional epilepsy to assess associations in evaluation and treatment choices. Methods We analyzed annual report data and an epilepsy practice survey reported in 2020 from 135 pediatric epilepsy center directors in the United States. Characteristics of centers along with noninvasive and invasive testing and surgical treatment strategies were collected. Multivariable logistic regression modeling was performed. Results The response rate was 100% with 135 responses included in the analyses. Most used noninvasive testing modalities included Neuropsychology evaluation (90%), interictal brain fluorodeoxyglucose-positron emission tomography (85%), and functional magnetic resonance imaging (MRI) (72%) with nearly half obtaining genetic testing. Choosing functional MRI was associated with stereo electroencephalography (EEG) ( P = .025) and selecting Wada with subdural grid/strips ( P = .038). Directors from pediatric-only centers were more likely to choose stereo EEG as opposed to combined centers ( P = .042). Laser interstitial thermal therapy was almost 7 times as likely to be chosen as a treatment modality compared with open resection in dedicated pediatric centers (OR 6.96, P = .002). Significance In a vignette of nonlesional childhood drug-resistant epilepsy, epilepsy center directors’ patterns of noninvasive testing, invasive testing, and treatment were examined. Management choices were associated with pediatric versus combined pediatric/adult center characteristics. Expert opinions demonstrated equipoise in evaluation and management of children with drug-resistant epilepsy and the need for evidence-based management strategies.