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r a more comprehensive assessment of axSpA in busy clinical settings. To investigate the association between Raynaud phenomenon (RP) and coronary microvascular dysfunction, we measured myocardial flow reserve (MFR) using positron emission tomography/computed tomography (PET/CT) in patients with primary and secondary RP and controls. Patients with RP, patient controls, and healthy participants who underwent dynamic rest-stress 82-rubidium PET/CT were studied. Differences in heart rate-blood pressure product-corrected MFR and clinical predictors of reduced MFR (< 2.0) were determined. Forty-nine patients with RP (80% female; aged 65 ± 11 yrs; 11 with primary RP, 18 with systemic sclerosis [SSc], and 20 with other autoimmune rheumatic diseases [AIRDs] including 6 with systemic lupus erythematosus, 6 with rheumatoid arthritis, 4 with overlap syndrome, 2 with Sjögren syndrome, and 2 with inflammatory arthritis), 49 matched patients without RP or AIRD (78% female; 64 ± 13 yrs), and 14 healthy participants (50% female; 35 ± 5 yrs) were studied. Patients with primary RP, matchy elucidate the prognostic value of MFR in patients with secondary RP. To identify clinical factors, including esophageal dilation on chest high-resolution computed tomography (HRCT), that are associated with pulmonary function decline in patients with systemic sclerosis (SSc). Patients fulfilled 2013 SSc criteria and had ≥1 HRCT and ≥2 pulmonary function tests (PFTs). According to published methods, widest esophageal diameter (WED) and radiographic interstitial lung disease (ILD) were assessed, and WED was dichotomized as dilated (≥19mm) vs. not dilated (<19mm). Clinically meaningful PFT decline was defined as %-predicted change in forced vital capacity (FVC) ≥5 and/or diffusion capacity for carbon monoxide (DLCO) ≥15. Linear mixed effect models were used to model PFT change over time. 138 SSc patients met study criteria 100 (72%) had radiographic ILD; 49 (35%) demonstrated FVC decline (median follow-up 2.9y). Patients with Scl-70 autoantibodies had 5- year %-predicted FVC decline (-6.3; 95% CI -9.9, -2.8), while patients without Scl-70 autoantibodies demonstrated 5-yeSSc-ILD patients with esophageal dilation.Malignant pleural diseases, comprising metastatic lung and breast cancers and malignant pleural mesothelioma (MPM), are aggressive solid tumors with poor therapeutic response. We developed and conducted a first-in-human, phase I study of regionally delivered, autologous, mesothelin-targeted chimeric antigen receptor (CAR) T-cell therapy. Intrapleural administration of 0.3M-60M CAR T cells/kg in 27 patients (25 with MPM) was safe and well tolerated. CAR T-cells were detected in peripheral blood for >100 days in 39% of patients. Following our demonstration that PD-1 blockade enhances CAR T-cell function in mice, 18 patients with MPM also received pembrolizumab safely. Among those patients, median overall survival from CAR T-cell infusion was 23.9 months (1-year overall survival, 83%). Stable disease was sustained for greater than or equal to6 months in 8 patients; 2 exhibited complete metabolic response on PET scan. Combination immunotherapy with CAR T cells and PD-1 blockade agents should be further evaluated in patients with solid tumors. Obesity has rapidly become a major problem for children that has adverse effects on respiratory health. We sought to assess the impact of obesity on health-related quality of life (HRQOL) and hospital outcomes for children hospitalized with asthma or pneumonia. In this multicenter prospective cohort study, we evaluated children (aged 2-16 years) hospitalized with an acute asthma exacerbation or pneumonia between July 1, 2014, and June 30, 2016. Subjects or their family completed surveys for child HRQOL (PedsQL Physical Functioning and Psychosocial Functioning Scales, with scores ranging from 0 to 100) on hospital presentation and 2-6 weeks after discharge. BMI categories were defined as normal weight, overweight, and obesity on the basis of BMI percentiles for age and sex per national guidelines. Multivariable regression models were used to examine associations between BMI category and HRQOL, length of stay, and 30-day reuse. Among 716 children, 82 (11.4%) were classified as having overweight and 138 (19.3%) as having obesity. For children hospitalized with asthma or pneumonia, obesity was not associated with worse HRQOL at presentation or 2-6 weeks after discharge, hospital length of stay, or 30-day reuse. Nearly 1 in 3 children seen in the hospital for an acute asthma exacerbation or pneumonia had overweight or obesity; however, among the population of children in our study, obesity alone does not appear to be associated with worse HRQOL or hospital outcomes. Nearly 1 in 3 children seen in the hospital for an acute asthma exacerbation or pneumonia had overweight or obesity; however, among the population of children in our study, obesity alone does not appear to be associated with worse HRQOL or hospital outcomes. Although patients with kidney disease may be particularly susceptible to the adverse health effects associated with lead exposure, whether levels of lead found commonly in drinking water are associated with adverse outcomes in patients with ESKD is not known. To investigate associations of lead in community water systems with hemoglobin concentrations and erythropoietin stimulating agent (ESA) use among incident patients with ESKD, we merged data from the Environmental Protection Agency (EPA) Safe Drinking Water Information System (documenting average 90 percentile lead concentrations in community water systems during 5 years before dialysis initiation, according to city of residence) with patient-level data from the United States Renal Data System. Among 597,968 patients initiating dialysis in the United States in 2005 through 2017, those in cities with detectable lead levels in community water had significantly lower pre-ESKD hemoglobin concentrations and more ESA use per 0.01 mg/L increase in 90 vels and higher ESA use among patients with advanced kidney disease.Ongoing SARS-CoV-2 vaccine development is focused on identifying stable, cost-effective, and accessible candidates for global use, specifically in low and middle-income countries. Here, we report the efficacy of a rapidly scalable, novel yeast expressed SARS-CoV-2 specific receptor-binding domain (RBD) based vaccine in rhesus macaques. We formulated the RBD immunogen in alum, a licensed and an emerging alum adsorbed TLR-7/8 targeted, 3M-052-alum adjuvants. https://www.selleckchem.com/products/gsk3787.html The RBD+3M-052-alum adjuvanted vaccine promoted better RBD binding and effector antibodies, higher CoV-2 neutralizing antibodies, improved Th1 biased CD4+T cell reactions, and increased CD8+ T cell responses when compared to the alum-alone adjuvanted vaccine. RBD+3M-052-alum induced a significant reduction of SARS-CoV-2 virus in respiratory tract upon challenge, accompanied by reduced lung inflammation when compared with unvaccinated controls. Anti-RBD antibody responses in vaccinated animals inversely correlated with viral load in nasal secretions and BAL.
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