Proteomics and machine learning in the prediction and explanation of low pectoralis muscle area.

Low muscle mass is associated with numerous adverse outcomes independent of other associated comorbid diseases. We aimed to predict and understand an individual's risk for developing low muscle mass using proteomics and machine learning. We identified eight biomarkers associated with low pectoralis muscle area (PMA).

Proteomics and Machine Learning in the Prediction and Explanation of Low Pectoralis Muscle Area.

Low muscle mass is associated with numerous adverse outcomes independent of other associated comorbid diseases. We aimed to predict and understand an individual's risk for developing low muscle mass using proteomics and machine learning. We identified 8 biomarkers associated with low pectoralis muscle area (PMA).

Practical Considerations for Delandistrogene Moxeparvovec Gene Therapy in Patients With Duchenne Muscular Dystrophy.

Background: Delandistrogene moxeparvovec is a gene transfer therapy approved in the United States, United Arab Emirates, and Qatar for the treatment of ambulatory patients aged four through five years with a confirmed Duchenne muscular dystrophy (DMD)-causing mutation in the DMD gene. This therapy was developed to address the underlying cause of DMD through targeted skeletal, respiratory, and cardiac muscle expression of delandistrogene moxeparvovec micro-dystrophin, an engineered, functional dystrophin protein.

Methods: Drawing on clinical trial experience from Study 101 (NCT03375164), Study 102 (NCT03769116), and ENDEAVOR (Study 103; NCT04626674), we outline practical considerations for delandistrogene moxeparvovec treatment.

Long-term safety and functional outcomes of delandistrogene moxeparvovec gene therapy in patients with Duchenne muscular dystrophy: A phase 1/2a nonrandomized trial.

Introduction/aims: Delandistrogene moxeparvovec is indicated in the United States for the treatment of ambulatory pediatric patients aged 4 through 5 years with Duchenne muscular dystrophy (DMD) with a confirmed mutation in the DMD gene. Long-term delandistrogene moxeparvovec microdystrophin protein (a shortened dystrophin that retains key functional domains of the wild-type protein) expression may positively alter disease progression in patients with DMD. We evaluated long-term safety and functional outcomes of delandistrogene moxeparvovec in patients with DMD.

Delandistrogene Moxeparvovec Gene Therapy in Ambulatory Patients (Aged ≥4 to <8 Years) with Duchenne Muscular Dystrophy: 1-Year Interim Results from Study SRP-9001-103 (ENDEAVOR).

Objective: Delandistrogene moxeparvovec is approved in the USA for the treatment of ambulatory patients (4-5 years) with Duchenne muscular dystrophy. ENDEAVOR (SRP-9001-103; NCT04626674) is a single-arm, open-label study to evaluate delandistrogene moxeparvovec micro-dystrophin expression, safety, and functional outcomes following administration of commercial process delandistrogene moxeparvovec.

Methods: In cohort 1 of ENDEAVOR (N = 20), eligible ambulatory males, aged ≥4 to <8 years, received a single intravenous infusion of delandistrogene moxeparvovec (1.

Associations Between Muscle Weakness and Clinical Outcomes in Current and Former Smokers.

Introduction: Smokers with chronic obstructive pulmonary disease (COPD) are at increased risk of muscle weakness. There are limited data describing weakness in smokers with normal spirometry and preserved ratio-impaired spirometry (PRISm), 2 subgroups at risk of respiratory symptom burden and activity limitations. In this study, we evaluated the associations of 2 weakness measures, sit-to-stand (STS) and handgrip strength (HGS), with clinical outcomes in smokers with COPD, normal spirometry, and PRISm.

Quantitative Interstitial Abnormality Progression and Outcomes in the Genetic Epidemiology of COPD and Pittsburgh Lung Screening Study Cohorts.

Background: The risk factors and clinical outcomes of quantitative interstitial abnormality progression over time have not been characterized.

Research Questions: What are the associations of quantitative interstitial abnormality progression with lung function, exercise capacity, and mortality? What are the demographic and genetic risk factors for quantitative interstitial abnormality progression?

Study Design And Methods: Quantitative interstitial abnormality progression between visits 1 and 2 was assessed from 4,635 participants in the Genetic Epidemiology of COPD (COPDGene) cohort and 1,307 participants in the Pittsburgh Lung Screening Study (PLuSS) cohort. We used multivariable linear regression to determine the risk factors for progression and the longitudinal associations between progression and FVC and 6-min walk distance, and Cox regression models for the association with mortality.

Longitudinal Association Between Muscle Loss and Mortality in Ever Smokers.

Background: Body composition measures, specifically low weight or reduced muscle mass, are associated with mortality in COPD, but the effect of longitudinal body composition changes is undefined.

Research Question: Is the longitudinal loss of fat-free mass (FFM) associated with increased mortality, including in those with initially normal or elevated body composition metrics?

Study Design And Methods: Participants with complete data for at least one visit in the COPDGene study (n = 9,268) and the ECLIPSE study (n = 1,760) were included and monitored for 12 and 8 years, respectively. Pectoralis muscle area (PMA) was derived from thoracic CT scans and used as a proxy for FFM.

Significant Spirometric Transitions and Preserved Ratio Impaired Spirometry Among Ever Smokers.

Background: Emerging data from longitudinal studies suggest that preserved ratio impaired spirometry (PRISm), defined by proportionate reductions in FEV and FVC, is a heterogeneous population with frequent transitions to other lung function categories relative to individuals with normal and obstructive spirometry. Controversy regarding the clinical significance of these transitions exists (eg, whether transitions merely reflect measurement variability or noise).

Research Question: Are individuals with PRISm enriched for transitions associated with substantial changes in lung function?

Study Design And Methods: Current and former smokers enrolled in the Genetic Epidemiology of COPD (COPDGene) study with spirometry available in phases 1 through 3 (enrollment, 5-year follow-up, and 10-year follow-up) were analyzed.

Loss of Pulmonary Vascular Volume as a Predictor of Right Ventricular Dysfunction and Mortality in Acute Pulmonary Embolism.

Background: In acute pulmonary embolism, chest computed tomography angiography derived metrics, such as the right ventricle (RV): left ventricle ratio are routinely used for risk stratification. Paucity of intraparenchymal blood vessels has previously been described, but their association with clinical biomarkers and outcomes has not been studied. We sought to determine if small vascular volumes measured on computed tomography scans were associated with an abnormal RV on echocardiography and mortality.

Relationship between Emphysema Progression at CT and Mortality in Ever-Smokers: Results from the COPDGene and ECLIPSE Cohorts.

Background The relationship between emphysema progression and long-term outcomes is unclear. Purpose To determine the relationship between emphysema progression at CT and mortality among participants with emphysema. Materials and Methods In a secondary analysis of two prospective observational studies, COPDGene (, NCT00608764) and Evaluation of Chronic Obstructive Pulmonary Disease Longitudinally to Identify Predictive Surrogate End-points (ECLIPSE; , NCT00292552), emphysema was measured at CT at two points by using the volume-adjusted lung density at the 15th percentile of the lung density histogram (hereafter, lung density perc15) method.

Distinguishing Smoking-Related Lung Disease Phenotypes Via Imaging and Molecular Features.

Background: Chronic tobacco smoke exposure results in a broad range of lung pathologies including emphysema, airway disease and parenchymal fibrosis as well as a multitude of extra-pulmonary comorbidities. Prior work using CT imaging has identified several clinically relevant subgroups of smoking related lung disease, but these investigations have generally lacked organ specific molecular correlates.

Research Question: Can CT imaging be used to identify clinical phenotypes of smoking related lung disease that have specific bronchial epithelial gene expression patterns to better understand disease pathogenesis?

Study Design And Methods: Using K-means clustering, we clustered participants from the COPDGene study (n = 5,273) based on CT imaging characteristics and then evaluated their clinical phenotypes.

Cost-effectiveness microsimulation of catheter-directed thrombolysis in submassive pulmonary embolism using a right ventricular function model.

Approximately 30-50% of hemodynamically stable patients presenting with acute pulmonary embolism (PE) have evidence of right ventricular (RV) dysfunction. These patients are classified as submassive PE and the role of reperfusion therapy remains unclear. We sought to identify the circumstances under which catheter-directed thrombolysis (CDT) would represent high-value care for submassive PE.

Semi-quantitative visual assessment of chest radiography is associated with clinical outcomes in critically ill patients.

Background: Respiratory pathology is a major driver of mortality in the intensive care unit (ICU), even in the absence of a primary respiratory diagnosis. Prior work has demonstrated that a visual scoring system applied to chest radiographs (CXR) is associated with adverse outcomes in ICU patients with Acute Respiratory Distress Syndrome (ARDS). We hypothesized that a simple, semi-quantitative CXR score would be associated with clinical outcomes for the general ICU population, regardless of underlying diagnosis.

Seizures as a presenting symptom of acute arterial ischemic stroke in childhood.

Objectives: To define the incidence of seizures as a presenting symptom of acute arterial ischemic stroke (AIS) in children and to determine whether younger age, infarct location, or AIS etiology were risk factors for seizure at AIS presentation.

Study Design: Children aged 2 months to 18 years presenting with AIS between January 2005 and December 2008 were identified from a single center prospective pediatric stroke registry. Clinical data were abstracted, and a neuroradiologist reviewed imaging studies.

Optical measurement of cerebral hemodynamics and oxygen metabolism in neonates with congenital heart defects.

We employ a hybrid diffuse correlation spectroscopy (DCS) and near-infrared spectroscopy (NIRS) monitor for neonates with congenital heart disease (n=33). The NIRS-DCS device measured changes during hypercapnia of oxyhemoglobin, deoxyhemoglobin, and total hemoglobin concentrations; cerebral blood flow (rCBF(DCS)); and oxygen metabolism (rCMRO(2)). Concurrent measurements with arterial spin-labeled magnetic resonance imaging (rCBF(ASL-MRI), n=12) cross-validate rCBF(DCS) against rCBF(ASL-MRI), showing good agreement (R=0.

Preoperative brain injury in transposition of the great arteries is associated with oxygenation and time to surgery, not balloon atrial septostomy.

Background: Preoperative brain injury is an increasingly recognized phenomenon in neonates with complex congenital heart disease. Recently, reports have been published that associate preoperative brain injury in neonates with transposition of the great arteries with the performance of balloon atrial septostomy (BAS), a procedure that improves systemic oxygenation preoperatively. It is unclear whether BAS is the cause of brain injury or is a confounder, because neonates who require BAS are typically more hypoxemic.

Arterial spin labeling perfusion MRI in pediatric arterial ischemic stroke: initial experiences.

Purpose: To investigate the feasibility and utility of arterial spin labeling (ASL) perfusion MRI for characterizing alterations of cerebral blood flow (CBF) in pediatric patients with arterial ischemic stroke (AIS).

Materials And Methods: Ten children with AIS were studied within 4 to 125 hours following symptom onset, using a pulsed ASL (PASL) protocol attached to clinically indicated MR examinations. The interhemisphere perfusion deficit (IHPD) was measured in predetermined vascular territories and infarct regions of restricted diffusion, which were compared with the degree of arterial stenosis and volumes of ischemic infarcts.