The IGF-1R Inhibitor NVP-AEW541 Causes Insulin-Independent and Reversible Cardiac Contractile Dysfunction

The antitumor treatment NVP-AEW541 blocks IGF-1R. IGF-1R signaling is crucial for cardiac function, but the cardiac effects of NVP-AEW541 are ill defined. We assessed NVP-AEW541′s effects on cardiac function and insulin response in vivo and in isolated working hearts. We performed a dose–response analysis of NVP-AEW541 in male, 3-week-old rats and assessed the chronic effects of the clinically relevant dose in adult rats. We performed glucose tolerance tests and echocardiography; assessed the expression and phosphorylation of InsR/IGF-1R and Akt in vivo; and measured substrate oxidation, contractile function, and insulin response in the isolated working hearts. NVP-AEW541 caused dose-dependent growth retardation and impaired glucose tolerance in the juvenile rats. In the adults, NVP-AEW541 caused a continuously worsening depression of cardiac contractility, which recovered within 2 weeks after cessation. Cardiac Akt protein and phosphorylation were unchanged and associated with InsR upregulation. An acute application of NVP-AEW541 in the working hearts did not affect cardiac power but eliminated insulin’s effects on glucose and fatty acid oxidation. The systemic administration of NVP-AEW541 caused dose- and time-dependent impairment of glucose tolerance, growth, and cardiac function. Because cardiac insulin signaling was maintained in vivo but absent in vitro and because contractile function was not affected in vitro, a direct link between insulin resistance and contractile dysfunction appears unlikely

Early Career Support for Biomedical Exchange Students with an International Mentor-to-Mentor Concept - The Biomedical Education Program (BMEP)

In medicine, many international exchange opportunities exist, yet often only towards the end of the course of study. Opportunities for students to gain high-level international research experience early during the studies are rare. A good student-mentor relationship during a research stay abroad is a key factor for scientific success. The aims of this paper are to report on an international exchange and education program that has funded more than 700 students and has been carefully developed and advanced over more than 40 years, its mentor-to-mentor concept and potential success factors for building and maintain such programs. A summary of the history, the concept and the experiences of students is provided, along with a discussion of evaluation results and success factors. The Biomedical Education Program (BMEP) team has - within the last seven years of leadership by the authors - selected and funded 83 German students from different biomedical studies who went abroad for research projects. Preliminary evaluation results show a high degree of satisfaction with the program and its mentor-to-mentor concept, which we deem to be the key to success. Further factors include continued funding, determination, self-organization and assertiveness, an excellent alumni network and a meticulous selection process for both, students and hosts. Further, more detailed evaluation of survey results has to follow. Our results may support the build-up of similar exchange programs

Coronary-Artery Bypass Surgery in Patients with Ischemic Cardiomyopathy

BACKGROUND: The survival benefit of a strategy of coronary-artery bypass grafting (CABG) added to guideline-directed medical therapy, as compared with medical therapy alone, in patients with coronary artery disease, heart failure, and severe left ventricular systolic dysfunction remains unclear. METHODS: From July 2002 to May 2007, a total of 1212 patients with an ejection fraction of 35% or less and coronary artery disease amenable to CABG were randomly assigned to undergo CABG plus medical therapy (CABG group, 610 patients) or medical therapy alone (medical-therapy group, 602 patients). The primary outcome was death from any cause. Major secondary outcomes included death from cardiovascular causes and death from any cause or hospitalization for cardiovascular causes. The median duration of follow-up, including the current extended-follow-up study, was 9.8 years. RESULTS: A primary outcome event occurred in 359 patients (58.9%) in the CABG group and in 398 patients (66.1%) in the medical-therapy group (hazard ratio with CABG vs. medical therapy, 0.84; 95% confidence interval [CI], 0.73 to 0.97; P=0.02 by log-rank test). A total of 247 patients (40.5%) in the CABG group and 297 patients (49.3%) in the medical-therapy group died from cardiovascular causes (hazard ratio, 0.79; 95% CI, 0.66 to 0.93; P=0.006 by log-rank test). Death from any cause or hospitalization for cardiovascular causes occurred in 467 patients (76.6%) in the CABG group and in 524 patients (87.0%) in the medical-therapy group (hazard ratio, 0.72; 95% CI, 0.64 to 0.82; P CONCLUSIONS: In a cohort of patients with ischemic cardiomyopathy, the rates of death from any cause, death from cardiovascular causes, and death from any cause or hospitalization for cardiovascular causes were significantly lower over 10 years among patients who underwent CABG in addition to receiving medical therapy than among those who received medical therapy alone. (Funded by the National Institutes of Health; STICH [and STICHES] ClinicalTrials.gov number, NCT00023595.)

A long-term follow-up of a girl with dilated cardiomyopathy after mitral valve replacement and septal anterior ventricular exclusion

We treated a 10 year 11 month old girl with severe mitral valve regurgitation, stenosis and dilated cardiomyopathy, presented with New York Heart Association (NYHA) functional classification IV. She acutely developed cardiogenic shock with a dyskinetic anterior-septal left ventricle and entered a shock state during our consultation about heart transplantation. Septal-anterior ventricular exclusion and mitral valve replacement were performed emergently. She successfully recovered from cardiogenic shock. Left ventricular end-diastolic diameter and fractional shortening improved from 71.5 mm (188.0% of normal) to 62.5 mm (144.2% of normal) and 7.6% to 18.3% respectively. Furthermore, her serum BNP decreased from 2217.5 pg/ml to 112.0 pg/ml. Her cardiac function has remained stable for 7 years since the procedures were performed

Logistic Organ Dysfunction Score (LODS): A reliable postoperative risk management score also in cardiac surgical patients?

<p>Abstract</p> <p>Background</p> <p>The original Logistic Organ Dysfunction Sore (LODS) excluded cardiac surgery<ul/>patients from its target population, and the suitability of this score in cardiac surgery patients has never been tested. We evaluated the accuracy of the LODS and the usefulness of its daily measurement in cardiac surgery patients. The LODS is not a true logistic scoring system, since it does not use β-coefficients.</p> <p>Methods</p> <p>This prospective study included all consecutive adult patients who were admitted to<ul/>the intensive care unit (ICU) after cardiac surgery between January 2007 and December 2008. The LODS was calculated daily from the first until the seventh postoperative day. Performance was assessed with Hosmer-Lemeshow (HL) goodness-of-fit test (calibration) and receiver operating characteristic (ROC) curves (discrimination) from ICU admission day until day 7. The outcome measure was ICU mortality.</p> <p>Results</p> <p>A total of 2801 patients (29.6% female) with a mean age of 66.4 ± 10.7 years were<ul/>included. The ICU mortality rate was 5.2% (n = 147). The mean stay on the ICU was 4.3 ± 6.8 days. Calibration of the LODS was good with no significant difference between expected and observed mortality rates on any day (p ≥ 0.05). The initial LODS had an area under the ROC curve (AUC) of 0.81. The AUC was best on ICU day 3 with a value of 0.93, and declined to 0.85 on ICU day 7.</p> <p>Conclusions</p> <p>Although the LODS has not previously been validated for cardiac surgery<ul/>patients it showed reasonable accuracy in prediction of ICU mortality in patients after cardiac surgery.</p

Diabetes is an independent risk factor for cancer after heart and/or lung transplantation

Background: De novo cancers are feared complications after heart or lung transplantation. Recent data suggest that diabetes mellitus (DM) might also be a risk factor for cancer. We hypothesized that transplanted diabetic patients are at greater risk of developing cancer compared to non-diabetic ones. Methods: We reviewed 353 patients post-heart and/or -lung transplantation from our center between October 1999 and June 2021. Patients with follow-up <180 days ( n = 87) were excluded from the analysis. The remaining 266 patients were divided into patients who had preoperative DM (n = 88) or developed it during follow-up ( n = 40) and patients without DM ( n = 138). Results: The diabetic cohort showed higher rates of malignancies in all patients (30.33 vs. 15.97%, p = 0.005) and in the matched population (31.9 vs. 16.1%, p < 0.001). There were also significantly more solid tumors (17.9 vs. 9.4%, p = 0.042; matched: 16.6 vs. 9.1%, p = 0.09) The presence of diabetes was associated with a 13% increased risk of cancer when compared to non-diabetic patients. New-onset post-transplant diabetes doubled the likelihood of cancer development. Conclusions: Pre-transplant diabetes mellitus increases the risk of cancer after heart and/or lung transplantation. However, new-onset diabetes after transplantation is associated with a much greater cancer risk. This information is relevant for screening during follow-up