Aims Fibromuscular dysplasia (FMD) is a poorly understood disease that predominantly affects women during middle-life, with features that include stenosis, aneurysm, and dissection of medium-large arteries. Recently, plasma proteomics has emerged as an important means to understand cardiovascular diseases. Our objectives were: (i) to characterize plasma proteins and determine if any exhibit differential abundance in FMD subjects vs. matched healthy controls and (ii) to leverage these protein data to conduct systems analyses to provide biologic insights on FMD, and explore if this could be developed into a blood-based FMD test. Methods and results Females with ‘multifocal’ FMD and matched healthy controls underwent clinical phenotyping, dermal biopsy, and blood draw. Using dual-capture proximity extension assay and nuclear magnetic resonance-spectroscopy, we evaluated plasma levels of 981 proteins and 31 lipid sub-classes, respectively. In a discovery cohort (Ncases = 90, Ncontrols = 100), we identified 105 proteins and 16 lipid sub-classes (predominantly triglycerides and fatty acids) with differential plasma abundance in FMD cases vs. controls. In an independent cohort (Ncases = 23, Ncontrols = 28), we successfully validated 37 plasma proteins and 10 lipid sub-classes with differential abundance. Among these, 5/37 proteins exhibited genetic control and Bayesian analyses identified 3 of these as potential upstream drivers of FMD. In a 3rd cohort (Ncases = 506, Ncontrols = 876) the genetic locus of one of these upstream disease drivers, CD2-associated protein (CD2AP), was independently validated as being associated with risk of having FMD (odds ratios = 1.36; P = 0.0003). Immune-fluorescence staining identified that CD2AP is expressed by the endothelium of medium-large arteries. Finally, machine learning trained on the discovery cohort was used to develop a test for FMD. When independently applied to the validation cohort, the test showed a c-statistic of 0.73 and sensitivity of 78.3%. Conclusion FMD exhibits a plasma proteogenomic and lipid signature that includes potential causative disease drivers, and which holds promise for developing a blood-based test for this disease.
IntroductionMitral valve repair has been established as the preferred treatment option in the management of degenerative mitral valve disease. Compared with other surgical treatment options, mitral valve repair is associated with increased survival and decreased rates of both complications and reoperations. However, among patients undergoing mitral valve repair, little is known about the predictors of postoperative outcomes. The purpose of this study is to identify preoperative patient risk factors associated with postoperative morbidity and mortality within 30 days of mitral valve repair.MethodsData was derived from the American College of Surgeons National Surgical Quality Improvement Program database to assess patients who underwent mitral valve repair from 2011 through 2017. Preoperative risk factors were analyzed to determine their association with a variety of postoperative 30-day outcome measures.ResultsOne thousand three hundred and sixty-six patients underwent mitral valve repair; 849 (62.2%) males and 517 (37.8%) females. Ages ranged from 18 to 90 years, with a mean age of 64 years. The overall 30-day mortality was 3.1% (43 patients). Among the 12 identified risk factors associated with increased mortality on univariate analysis, pre-operative hematocrit level was the only variable significantly correlated with mortality after undergoing multivariate analysis. 259 patients (19.1%) were discharged to a location other than home, an outcome associated with 22 identified risk factors. Among these risk factors, female gender, age, dialysis, pre-operative serum sodium, pre-operative serum albumin, and partial or full living dependency remained statistically significant following multivariate analysis. 126 patients (9.2%) experienced unplanned readmission. This outcome was associated with five risk factors, of which only dyspnea upon mild exertion was significant on multivariate analysis. Reoperation occurred in 105 patients (7.7%). Of the seven identified variables associated with reoperation, patient age, pre-operative platelet count, dyspnea upon mild exertion were independent predictors on multivariate analysis. 53 patients (3.9%) underwent reintubation, which was associated with 11 identified risk factors. Among them, patient age and pre-operative INR value were predictive of reintubation on multivariate analysis. 26 patients (1.9%) experienced stroke, of whom age was the only associated risk factor on both univariate and multivariate analysis. 31 patients (2.3%) experienced acute renal failure, which correlated with 11 risk factors on univariate analysis. Of these, only patient age and pre-operative hematocrit were identified as independent predictors on multivariate analysis.ConclusionsOutcomes are good following mitral valve repair. Although a substantial number of risk factors were found to be associated with adverse outcomes, only a small subset remained statistically significant following multivariate analysis. Identification of these risk factors may help guide clinical decision making with respect ...
The spring semester ended up with reopen of schools in September.The group of students we tutored online (n = 94) have started their new semester in the outpatient and inpatient departments. We had a survey on them and get a feedback that 73 of them (about 78%) considered the online clerkship helpful for their consequent clinical studies. Seventy-eight students (about 83%) chose the answer that the online clerkship in our department was helpful to them. Although it is obvious that real-world clinical clerkship is more attractive, some of these students (n = 38, about 40%) even preferred online tutorial because they felt relaxed when having class at home. Seventy students (about 75%) believe that it would be a great loss if they could not have any clerkship when studying at medical school.
Objective: The present investigation aims to identify characteristics associated with heroin use among those reporting prescription opioid misuse from a nationally representative sample, and how these characteristics vary by urbanicity. Design: A cross-sectional analysis.Setting: Pooled 2015-2018 data from the National Survey on Drug Use and Health (NSDUH), the leading source for nationally representative substance use, mental health, and other health-related data and trends in the United States.Patients and participants: 23,719 participants (12,109 male and 11,610 female) reporting previous prescription opioid misuse in the 2015-2018 NSDUH data. Interventions: None.Main outcome measures: Univariable and multivariable logistic regressions were used to assess the association of characteristics with heroin use, stratified by urbanicity.Results: After multivariable adjustment, factors associated with heroin use among prescription opioid misusers were male sex, non-Hispanic White race, low educational attainment, recent nonopioid illicit drug use, and recent nonopioid prescription drug misuse. Commercial health insurance was associated with lower odds of heroin use among both rural and urban prescription opioid misusers, but an observed association between Medicaid and greater odds of heroin use was stronger among urban versus rural participants. In contrast, observed associations between illicit drug use other than marijuana in the past year and greater odds of heroin use were stronger among rural vs urban participants.Conclusion: Important differences exist between factors associated with heroin use among urban and rural prescription opioid misusers, and there is a need to consider broader polysubstance use trends and barriers to mental healthcare access to adequately address heroin use.
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