Reproducible metabolic topographies associated with multiple system atrophy: Network and regional analyses in Chinese and American patient cohorts

© 2020 The Authors Purpose: Multiple system atrophy (MSA) is an atypical parkinsonian syndrome and often difficult to discriminate clinically from progressive supranuclear palsy (PSP) and Parkinson\u27s disease (PD) in early stages. Although a characteristic metabolic brain network has been reported for MSA, it is unknown whether this network can provide a clinically useful biomarker in different centers. This study was aimed to identify and cross-validate MSA-related brain network and assess its ability for differential diagnosis and clinical correlations in Chinese and American patient cohorts. Methods: We included 18F-FDG PET scans retrospectively from 128 clinically diagnosed parkinsonian patients (34 MSA, 34 PSP and 60 PD) and 40 normal subjects in China and in the USA. Using PET images from 20 moderate-stage MSA patients of parkinsonian subtype and 20 normal subjects in both centers, we reproduced MSA-related pattern (MSAPRP) of spatial covariance and estimated its reliability. MSAPRP scores were evaluated in assessing differential diagnosis among moderate- and early-stage MSA, PSP or PD patients and clinical correlations with disease severity. Regional metabolic differences were detected using statistical parameter mapping analysis. MSA-related network and regional topographies of metabolic abnormality were cross-validated between the Chinese and American cohorts. Results: We generated a highly reliable MSAPRP characterized by decreased loading in inferior frontal cortex, striatum and cerebellum, and increased loading in sensorimotor, parietal and occipital cortices. MSAPRP scores discriminated between normal, MSA, PSP and PD subjects and correlated with standardized ratings of clinical stages and motor symptoms in MSA. High similarities in MSAPRPs, network scores and corresponding maps of metabolic abnormality were observed between two different cohorts. Conclusion: We have demonstrated reproducible metabolic topographies associated with MSA at both network and regional levels in two independent patient cohorts. Moreover, MSAPRP scores are sensitive for evaluating disease discrimination and clinical correlates. This study supports differential diagnosis of MSA regardless of different patient populations, PET scanners and imaging protocols

EDA2R mediates podocyte injury in high glucose milieu

© 2020 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM) EDA2R is a member of the large family of tumor necrosis factor receptor (TNFR). Previous studies suggested that EDA2R expression might be increased in the kidneys of diabetic mice. However, its mRNA and protein expression in kidneys were not analyzed; moreover, its role in the development of diabetic kidney disease was not explored. Here we analyzed the mRNA and protein expressions of EDA2R in diabetic kidneys and examined its role in the podocyte injury in high glucose milieu. By analysis with real-time PCR, Western blotting, we found that both the mRNA and protein levels of EDA2R were increased in the kidneys of diabetic mice. Immunohistochemical studies revealed that EDA2R expression was enhanced in both glomerular and tubular cells of diabetic mice and humans. In vitro studies, high glucose increased EDA2R expression in cultured human podocytes. Overexpression of EDA2R in podocytes promoted podocyte apoptosis and decreased nephrin expression. Moreover, ED2AR increased ROS generation in podocytes, while inhibiting ROS generation attenuates EDA2R-mediated podocyte injury. In addition, EDA2R silencing partially suppressed high glucose-induced ROS generation, apoptosis, and nephrin decrease. Our study demonstrated that high glucose increases EDA2R expression in kidney cells and that EDA2R induces podocyte apoptosis and dedifferentiation in high glucose milieu partially through enhanced ROS generation

Role of a Pediatric Cardiologist in the COVID-19 Pandemic

© 2020, Springer Science+Business Media, LLC, part of Springer Nature. Coronavirus disease 2019 (COVID-19) has affected patients across all age groups, with a wide range of illness severity from asymptomatic carriers to severe multi-organ dysfunction and death. Although early reports have shown that younger age groups experience less severe disease than older adults, our understanding of this phenomenon is in continuous evolution. Recently, a severe multisystem inflammatory syndrome in children (MIS-C), with active or recent COVID-19 infection, has been increasingly reported. Children with MIS-C may demonstrate signs and symptoms of Kawasaki disease, but also have some distinct differences. These children have more frequent and severe gastrointestinal symptoms and are more likely to present with a shock-like presentation. Moreover, they often present with cardiovascular involvement including myocardial dysfunction, valvulitis, and coronary artery dilation or aneurysms. Here, we present a review of the literature and summary of our current understanding of cardiovascular involvement in children with COVID-19 or MIS-C and identifying the role of a pediatric cardiologist in caring for these patients

How can we improve antidepressant adherence in the management of depression? A targeted review and 10 clinical recommendations.

Adherence to antidepressants is crucial for optimal treatment outcomes when treating depressive disorders. However, poor adherence is common among patients prescribed antidepressants. This targeted review summarizes the main factors associated with poor adherence, interventions that promote antidepressant adherence, pharmacological aspects related to antidepressant adherence, and formulates 10 clinical recommendations to optimize antidepressant adherence. Patient-related factors associated with antidepressant non-adherence include younger age, psychiatric and medical comorbidities, cognitive impairment, and substance use disorders. Prescriber behavior-related factors include neglecting medical and family histories, selecting poorly tolerated antidepressants, or complex antidepressant regimens. Multi-disciplinary interventions targeting both patient and prescriber, aimed at improving antidepressant adherence, include psychoeducation and providing the patient with clear behavioral interventions to prevent/minimize poor adherence. Regarding antidepressant choice, agents with individually tailored tolerability profile should be chosen. Ten clinical recommendations include four points focusing on the patient (therapeutic alliance, adequate history taking, measurement of depressive symptoms, and adverse effects improved access to clinical care), three focusing on prescribing practice (psychoeducation, individually tailored antidepressant choice, simplified regimen), two focusing on mental health services (improved access to mental health care, incentivized adherence promotion and monitoring), and one relating to adherence measurement (adherence measurement with scales and/or therapeutic drug monitoring)

Effectiveness of Fluorography Versus Cineangiography at Reducing Radiation Exposure During Diagnostic Coronary Angiography

Coronary angiography is the gold standard for defining obstructive coronary disease. However, radiation exposure remains an unwanted hazard. Patients referred for coronary angiography with abdominal circumference60 ml/min were randomized to the fluorography (n = 25) or cineangiography (n = 25) group. Patients in the fluorography group underwent coronary angiography using retrospectively stored fluorography with repeat injection under cineangiography only when needed for better resolution per operator\u27s discretion. Patients in the cineangiography group underwent coronary angiography using routine cineangiography. The primary end point was patient radiation exposure measured by radiochromic film. Secondary end points included the radiation output measurement of kerma-area product and air kerma at the interventional reference point (Ka,r) and operator radiation exposure measured by a dosimeter. Patient radiation exposure (158.2 mGy [76.5 to 210.2] vs 272.5 mGy [163.3 to 314.0], p = 0.001), kerma-area product (1,323 mu Gy.m(2) 1826 to 1,765] vs 3,451 mu Gy.m(2) [2,464 to 4,818], p \u3c 0.001), and Ka,r (175 mGy [112 to 252] vs 558 mGy [313 to 621], p \u3c 0.001) were significantly lower in the fluorography compared with cineangiography group (42%, 62%, and 69% relative reduction, respectively). Operator radiation exposure trended in the same direction, although statistically nonsignificant (fluorography 2.35 mu Gy [1.24 to 6.30] vs cineangiography 5,03 mu Gy 12.48 to 7.80], p = 0.059). In conclusion, the use of fluorography in a select group of patients during coronary angiography, with repeat injection under cineangiography only when needed, was efficacious at reducing patient radiation exposure. (C) 2014 Elsevier Inc. All rights reserved

How well does the standardized video interview score correlate with traditional interview performance?

© 2019 Chung et al. Introduction: In 2017, all medical students applying for residency in emergency medicine (EM) were required to participate in the Standardized Video Interview (SVI). The SVI is a video-recorded, unidirectional interview consisting of six questions designed to assess interpersonal and communication skills and professionalism. It is unclear whether this simulated interview is an accurate representation of an applicant’s competencies that are often evaluated during the in-person interview. Objective: The goal of this study was to determine whether the SVI score correlates with a traditional in-person interview score. Methods: Six geographically and demographically diverse EM residency programs accredited by the Accreditation Council for Graduate Medical Education participated in this prospective observational study. Common demographic data for each applicant were obtained through an Electronic Residency Application Service export function prior to the start of any scheduled traditional interviews (TI). On each TI day, one interviewer blinded to all applicant data, including SVI score, rated the applicant on a five-point scale. A convenience sample of applicants was enrolled based on random assignment to the blinded interviewer. We studied the correlation between SVI score and TI score. Results: We included 321 unique applicants in the final analysis. Linear regression analysis of the SVI score against the TI score demonstrated a small positive linear correlation with an r coefficient of +0.13 (p=0.02). This correlation remained across all SVI score subgroups (p = 0.03). Conclusion: Our study suggests that there is a small positive linear correlation between the SVI score and performance during the TI