Which is better to preserve pulmonary function: Short-term or prolonged leukocyte depletion during cardiopulmonary bypass?

ObjectivesNeutrophils are crucial in the development of acute lung injuries during cardiopulmonary bypass. However, the efficacy of leukocyte depletion on pulmonary protection remains controversial, possibly owing to different filtration strategies used in the literature. In this study, we investigated whether short-term leukocyte depletion strategy is more efficacious than prolonged leukocyte depletion in preserving pulmonary function.MethodsEighteen adult dogs were randomized equally into 3 groups. Leukocyte-depleting filters were used for 10 minutes in the LD-S group, throughout cardiopulmonary bypass in the LD-T group, and not used in the control group. Neutrophil counts, elastase, and interleukin-8 concentrations in plasma, myeloperoxidase and interleukin-8 concentrations in pulmonary tissue, and pulmonary vascular resistance and oxygen index were determined to evaluate the inflammatory response and damage to pulmonary function.ResultsAlthough the neutrophil count and pulmonary parenchymal myeloperoxidase contents were significantly lower in both LD-S and LD-T groups than that in the control group, lower pulmonary parenchymal interleukin-8 level, lower pulmonary vascular resistance (113 ± 33 dyne · s/cm5), higher oxygen index (366 ± 82.3 mm Hg), and thinner alveolus wall thickness were seen only in the LD-S group, and the pulmonary parenchymal interleukin-8 levels were also lower in the LD-S group after cardiopulmonary bypass. The plasma elastase and interleukin-8 levels were significantly lower in the LD-S group, but they were significantly higher in the LD-T group compared with the control group after cardiopulmonary bypass.ConclusionsShort-term rather than prolonged leukocyte depletion during cardiopulmonary bypass appears to be more efficacious in protecting pulmonary function via attenuation of the extracorporeal circulation–induced inflammatory response

Federated learning enables big data for rare cancer boundary detection.

Although machine learning (ML) has shown promise across disciplines, out-of-sample generalizability is concerning. This is currently addressed by sharing multi-site data, but such centralization is challenging/infeasible to scale due to various limitations. Federated ML (FL) provides an alternative paradigm for accurate and generalizable ML, by only sharing numerical model updates. Here we present the largest FL study to-date, involving data from 71 sites across 6 continents, to generate an automatic tumor boundary detector for the rare disease of glioblastoma, reporting the largest such dataset in the literature (n = 6, 314). We demonstrate a 33% delineation improvement for the surgically targetable tumor, and 23% for the complete tumor extent, over a publicly trained model. We anticipate our study to: 1) enable more healthcare studies informed by large diverse data, ensuring meaningful results for rare diseases and underrepresented populations, 2) facilitate further analyses for glioblastoma by releasing our consensus model, and 3) demonstrate the FL effectiveness at such scale and task-complexity as a paradigm shift for multi-site collaborations, alleviating the need for data-sharing

Author Correction: Federated learning enables big data for rare cancer boundary detection.

10.1038/s41467-023-36188-7NATURE COMMUNICATIONS14

Federated Learning Enables Big Data for Rare Cancer Boundary Detection

Although machine learning (ML) has shown promise across disciplines, out-of-sample generalizability is concerning. This is currently addressed by sharing multi-site data, but such centralization is challenging/infeasible to scale due to various limitations. Federated ML (FL) provides an alternative paradigm for accurate and generalizable ML, by only sharing numerical model updates. Here we present the largest FL study to-date, involving data from 71 sites across 6 continents, to generate an automatic tumor boundary detector for the rare disease of glioblastoma, reporting the largest such dataset in the literature (n = 6, 314). We demonstrate a 33% delineation improvement for the surgically targetable tumor, and 23% for the complete tumor extent, over a publicly trained model. We anticipate our study to: 1) enable more healthcare studies informed by large diverse data, ensuring meaningful results for rare diseases and underrepresented populations, 2) facilitate further analyses for glioblastoma by releasing our consensus model, and 3) demonstrate the FL effectiveness at such scale and task-complexity as a paradigm shift for multi-site collaborations, alleviating the need for data-sharing

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Perventricular device closure of perimembranous ventricular septal defects in 61 young children: Early and midterm follow-up results

ObjectivesPerventricular device closure of perimembranous ventricular septal defect as a novel technique has recently been described in several small series with initial experience. Further studies with larger cohorts and longer-term follow-up are needed to confirm the validity of this new approach. This report describes our recent experience with perventricular device closure of perimembranous ventricular septal defects on beating hearts in 61 young children with over 1 year of follow-up.MethodsBetween April 2007 and April 2008, 61 patients with perimembranous ventricular septal defects were enrolled for a prospective study of perventricular device closure of their defects. The hospital course and the immediate and midterm complications during follow-up were herein reported.ResultsThe defects were closed successfully with devices in 57 (93.4%) patients without mortality or major morbidity. Four (6.6%) patients were converted to surgical repair when device closure was deemed unsuccessful; the failure of device closure was associated with the subaortic rim (odds ratio = 21.471; P = .038). Residual shunt was observed in 4 (6.6%) patients during the procedure. One of them was converted into surgical repair, and the residual shunt of the other 3 resolved during the 6-month follow-up period. Two (3.3%) patients had complete atrioventricular block develop in the operating room or during follow-up. One was converted into surgical repair and the other patient converted to sinus rhythm after treatment with steroids.ConclusionsPerventricular device closure of ventricular septal defect is a safe and efficacious treatment option with acceptable midterm outcomes. For infants with poor vascular access, it might be the procedure of choice

Differential MicroRNA Expression in Human Macrophages with Mycobacterium tuberculosis Infection of Beijing/W and Non-Beijing/W Strain Types.

The role of microRNAs in association with Mycobacterium tuberculosis (MTB) infection and the immunology regulated by microRNAs upon MTB infection have not been fully unravelled. We examined the microRNA profiles of THP-1 macrophages upon the MTB infection of Beijing/W and non-Beijing/W clinical strains. We also studied the microRNA profiles of the host macrophages by microarray in a small cohort with active MTB disease, latent infection (LTBI), and from healthy controls.The results revealed that 14 microRNAs differentiated infections of Beijing/W from non-Beijing/W strains (P<0.05). A unique signature of 11 microRNAs in human macrophages was identified to differentiate active MTB disease from LTBI and healthy controls. Pathway analyses of these differentially expressed miRNAs suggest that the immune-regulatory interactions involving TGF-β signalling pathway take part in the dysregulation of critical TB processes in the macrophages, resulting in active expression of both cell communication and signalling transduction systems.We showed for the first time that the Beijing/W TB strains repressed a number of miRNAs expressions which may reflect their virulence characteristics in altering the host response. The unique signatures of 11 microRNAs may deserve further evaluation as candidates for biomarkers in the diagnosis of MTB and Beijing/W infections

Clustering analysis of the 11 miRNAs was performed using DataAssist 3.0v based on ΔCt-values of the TLDA results.

<p>Upregulated miRNAs are designated by various shades of red and down-regulated miRNAs by various shades of green. Clinical phenotypes are labelled in different colours: active MTB infection (red), latent infection (blue), and healthy controls (green).</p