Obesity and its associated complications such as insulin resistance and non-alcoholic fatty liver disease are reaching epidemic proportions. In mice, the TGF-β superfamily is implicated in the regulation of white and brown adipose tissue differentiation. The kielin/chordin-like protein (KCP) is a secreted regulator of the TGF-β superfamily pathways that can inhibit both TGF-β and activin signals while enhancing bone morphogenetic protein (BMP) signaling. However, KCP's effects on metabolism and obesity have not been studied in animal models. Therefore, we examined the effects of KCP loss or gain of function in mice that were maintained on either a regular or a high-fat diet. KCP loss sensitized the mice to obesity and associated complications such as glucose intolerance and adipose tissue inflammation and fibrosis. In contrast, transgenic mice that expressed KCP in the kidney, liver, and adipose tissues were resistant to developing high-fat diet-induced obesity and had significantly reduced white adipose tissue. Moreover, KCP overexpression shifted the pattern of SMAD signaling , increasing the levels of phospho (P)-SMAD1 and decreasing P-SMAD3. Adipocytes in culture showed a cell-autonomous effect in response to added TGF-β1 or BMP7. Metabolic profiling indicated increased energy expenditure in KCP-overexpressing mice and reduced expenditure in the KCP mutants with no effect on food intake or activity. These findings demonstrate that shifting the TGF-β superfamily signaling with a secreted protein can alter the physiology and thermogenic properties of adipose tissue to reduce obesity even when mice are fed a high-fat diet.
We describe the case of a patient who had suspected myocardial ischemia, showed normal findings on multiple perfusion scans, and showed isolated cardiac sarcoidosis on 18 F-FDG-PET. Also discussed are the diagnosis and the monitoring of disease response using imaging follow-up.
Iatrogenic pulmonary vein stenosis (PVS) is a known, yet rare, complication of atrial radiofrequency ablation. Alterations in pulmonary perfusion may mimic massive pulmonary embolism on a ventilation/perfusion (V/Q) scintigraphy. This is particularly important due to the overlap in presenting clinical symptoms. The present case illustrates the functional significance of PVS and the changes in perfusion in response to angioplasty.
Introduction: With a 30-day all cause readmission rate around 23%, individuals with heart failure (HF) are a medically high risk and costly patient population. Though predictive models have been developed for readmission based on descriptive variables, many of these tools are cumbersome and limited in prognosticative capacity. A few studies have examined the role of the six-minute walk test (6MWT) and found good predictive ability for both 30-day and 1-3-year readmission rates. The goal of this study was to further elucidate the prognostic ability of the 6MWT in stage C/D HF patients with NYHA class IIIb-VI symptoms. Methods: We prospectively enrolled 97 patients who from our step-down units with a primary diagnosis of heart failure between October 2016 and March 2017. Every patient who was enrolled had a standardized 6MWT prior to discharge. Multivariate logistic regression analysis was constructed to determine relationships between 6MW distance and 30-day survival free of readmission. Results: Baseline characteristics were compared between the 6minute walk test distance groups using Wilcoxon rank-sum tests for continuous variables and Fisher's exact tests for categorical variables, and no significant differences were found between the patients. The 135-meter cut-point was selected as the threshold which maximizes the sum of sensitivity and specificity of a logistic regression model for 30-day readmission with 6-minute walk test distance as a continuous predictor. Approximately 25.7% of the patients walked less than 135 meters. Out of these about 32% were admitted within 30 days [p= .026]. Among the patients who walked > 135 meters, 11.1% were admitted within 30 days [p= 0.026]. Furthermore, patients who walked <135m, also had higher frequency of annual re-admissions (36% vs. 12.5%) compared to patients who walked more than 135 meters. Conclusions: 6MWT distance less than 135m was associated with not only increased risk of 30 day readmission but also correlated with increased frequency of admissions in patients admitted with stage C/D heart failure. Figure 1. Probability of all-cause death.
The patient is a 70-year-old male with no other atherogenic risk factors who presented with an acute coronary syndrome (ACS) of unstable angina subsequently complicated by a non-ST elevation myocardial infarction (NSTEMI). The patient’s presentation posed 3 unique features: (1) cardiac catheterization demonstrated nonobstructive 3-vessel multi-aneurysmal coronary artery disease with sluggish antegrade coronary flow; (2) a nonobstructive aneurysmal dissection flap based on contrast staining of the mid left anterior descending artery, which may have led to in situ nonocclusive thrombosis and distal microvascular embolization; and (3) successful conservative medical therapy of coronary artery aneurysmal disease (CAAD) complicated with ACS. CAAD has an incidence of 1.5% to 4.9% in adults. The most common etiology of CAAD is atherosclerotic coronary artery disease. There are no guidelines for the management of CAAD complicated by ACS, and controversies exist as to whether conservative, catheter-based, or surgical management should be pursued.
Background: Heart failure with recovered ejection fraction (HFrecEF) is an emerging clinical subgroup of patients with previous heart failure with reduced ejection fraction (HFrEF) that have recovered their EF. It is important to identify predictors of recovery and the impact of contributing comorbidities to define the optimal medical management. The aim of this study was to identify clinical phenotypes of patients with HFrecEF in a large inner city teaching hospital. Methods: We conducted a retrospective chart review of patients admitted to the University of Florida Jacksonville hospital with a diagnosis of heart failure with reduced ejection fraction (HFrEF) from January 1, 2009 December 31, 2015. Patients 18 years or older had to have at least 2 echocardiograms within the study period with the initial EF <40%. The diagnosis of HFrecEF was defined as the most recent LVEF ≥40% and a previously documented LVEF <40%. Results of echocardiograms and etiology of HF as well as documentation of age, gender, race, body mass index, hypertension (HTN), hyperlipidemia, coronary artery disease (CAD), diabetes mellitus (DM) were analyzed. The diagnosis of ischemic cardiomyopathy was defined as a decrease in ejection fraction that can be explained by the presence of significant CAD diagnosed by catheterization or non invasive testing (functional or anatomic). Results: A total of 6459 patients were included in the study. Of these 921(14.2%) met criteria for HFrecEF. Twenty-one patients had missing data and were excluded from the analysis. The median age of patients with HFrecEF was 67.5 years, 58% (522 of 900) were male, 50.5% (545 of 900) were White and 45.5% (410 of 900) were Black, 36% (327 of 900) were diagnosed with ischemic cardiomyopathy. 36.3% had DM, 41.9% had CAD, 70.7% had HTN, with highest prevelence in Blacks (87%). 23.8% (214 of 900) received an implantable cardioverter defibrillator (ICD) for primary prevention. 3% (27 of 900) received cardiac resynchronization therapy (CRT). Conclusions: HFrecEF in urban, inner city teaching hospital is a diverse, heterogeneous group with different comorbidity profiles and etiologies of cardiomyopathy across different racial groups. Non ischemic etiology and hypertensive disease are most common in blacks whereas ischemic etiology is predominant in whites. Further investigations to determine the natural history, risk stratification and predictors of EF recovery are necessary to establish optimal medical management of this subgroup of patients.
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