Knochenmorphogenesefaktor 7 (BMP-7) in Plattenepithelkarzinomen der Lunge

46 Plattenepithelkarzinome der Lunge (NSCLC) und die entsprechenden Normalgewebeproben wurden auf mRNA-Ebene mittels RT-PCR und auf Proteinebene mittels Immunhistologie auf Faktoren der TGFß-Familie untersucht. In allen untersuchten Tumorproben konnte BMP-7-mRNA nachgewiesen werden, wobei sich die mRNA-Expression in den meisten Fällen stärker zeigte als die des korrespondierenden Normalgewebes. Es zeigten sich eine signifikante Korrelationen mit histopathologischen und klinischen Parametern: Je höher die mRNA-Expression im Tumor im Vergleich mit dem Normalgewebe zu messen war, desto eher galt der Tumor als höher differenziert im histologischen Befund. Plattenepithelkarzinome, die histologisch als verhornend eingestuft worden waren, wiesen signifikant mehr BMP-7-mRNA-Expression auf als nicht-verhornende Karzinome. Auch bei dem pN-Status zeigte sich die Tendenz, daß niedrigere Stadien mit höheren BMP-7-mRNA-Expressionsleveln einhergingen. Immunhistologisch konnte in allen untersuchten Paraffinschnitten in den tumorösen Anteilen BMP-7-Proteine nachgewiesen werden, wobei sich die Normalgewebe als durchweg negativ erwiesen. In den soliden Arealen von Plattenepithelkarzinomen der Lunge kommt es im Zuge der tumorösen Regression zur vermehrten Expression von BMP-7-mRNA und zu einem erhöhten BMP-7-Protein-Gehalt. BMP-7 ist auf mRNA-Ebene mit dem Differenzierungszustand des Tumors assoziiert. Die BMP-7-mRNA-Expression ist mit den günstigen Markern Differenzierungsgrad (p<0,001) und Verhornung (p<0,01) signifikant positiv korreliert

Omecamtiv mecarbil in chronic heart failure with reduced ejection fraction, GALACTIC‐HF: baseline characteristics and comparison with contemporary clinical trials

Aims: The safety and efficacy of the novel selective cardiac myosin activator, omecamtiv mecarbil, in patients with heart failure with reduced ejection fraction (HFrEF) is tested in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure (GALACTIC‐HF) trial. Here we describe the baseline characteristics of participants in GALACTIC‐HF and how these compare with other contemporary trials. Methods and Results: Adults with established HFrEF, New York Heart Association functional class (NYHA) ≥ II, EF ≤35%, elevated natriuretic peptides and either current hospitalization for HF or history of hospitalization/ emergency department visit for HF within a year were randomized to either placebo or omecamtiv mecarbil (pharmacokinetic‐guided dosing: 25, 37.5 or 50 mg bid). 8256 patients [male (79%), non‐white (22%), mean age 65 years] were enrolled with a mean EF 27%, ischemic etiology in 54%, NYHA II 53% and III/IV 47%, and median NT‐proBNP 1971 pg/mL. HF therapies at baseline were among the most effectively employed in contemporary HF trials. GALACTIC‐HF randomized patients representative of recent HF registries and trials with substantial numbers of patients also having characteristics understudied in previous trials including more from North America (n = 1386), enrolled as inpatients (n = 2084), systolic blood pressure &lt; 100 mmHg (n = 1127), estimated glomerular filtration rate &lt; 30 mL/min/1.73 m2 (n = 528), and treated with sacubitril‐valsartan at baseline (n = 1594). Conclusions: GALACTIC‐HF enrolled a well‐treated, high‐risk population from both inpatient and outpatient settings, which will provide a definitive evaluation of the efficacy and safety of this novel therapy, as well as informing its potential future implementation

Low rate of access site complications after transradial coronary catheterization: A prospective ultrasound study

Transradial artery (TRA) left heart catheterization is an increasingly used technique for both diagnostic and interventional coronary procedures. This study evaluates the incidence of access site complications in the current interventional era. A total of 507 procedures were performed under standardized conditions. Each procedure was performed using high levels of anticoagulation, hydrophilic sheaths, and short post-procedural compression times. Vascular complications were assessed one day after TRA catheterization using Duplex sonography and classified according to the necessity of additional medical intervention. A simple questionnaire helped identifying upper extremity neurologic or motor complications. Vascular complications were detected in 12 patients (2.36%): radial artery occlusion was detected in 9 patients (1.77%), 1 patient developed an AV-fistula (0.19%), and 2 patients had pseudoaneurysms (0.38%). None of the patients required specialized medical or surgical intervention. Under our procedural conditions, small radial artery diameter was the only significant predictor for the development of post-procedural vascular complications (2.11 ± 0.42 mm vs 2.52 ± 0.39 mm, p = 0.001). None of the previously reported risk factors, namely, advanced renal failure, diabetes, acuteness/complexity of procedure, or sheath and catheter size significantly influenced the rate of vascular complications. No major hematoma or local neurologic or motor complications were identified. Using current techniques and materials, we report a very low rate of local complications associated with TRA catheterization

Low rate of access site complications after transradial coronary catheterization: A prospective ultrasound study

Background: Transradial artery (TRA) left heart catheterization is an increasingly used technique for both diagnostic and interventional coronary procedures. This study evaluates the incidence of access site complications in the current interventional era. Methods and results: A total of 507 procedures were performed under standardized conditions. Each procedure was performed using high levels of anticoagulation, hydrophilic sheaths, and short post-procedural compression times. Vascular complications were assessed one day after TRA catheterization using Duplex sonography and classified according to the necessity of additional medical intervention. A simple questionnaire helped identifying upper extremity neurologic or motor complications. Vascular complications were detected in 12 patients (2.36%): radial artery occlusion was detected in 9 patients (1.77%), 1 patient developed an AV-fistula (0.19%), and 2 patients had pseudoaneurysms (0.38%). None of the patients required specialized medical or surgical intervention. Under our procedural conditions, small radial artery diameter was the only significant predictor for the development of post-procedural vascular complications (2.11 ± 0.42 mm vs 2.52 ± 0.39 mm, p = 0.001). None of the previously reported risk factors, namely, advanced renal failure, diabetes, acuteness/complexity of procedure, or sheath and catheter size significantly influenced the rate of vascular complications. No major hematoma or local neurologic or motor complications were identified. Conclusions: Using current techniques and materials, we report a very low rate of local complications associated with TRA catheterization

Cardiac myosin activation with omecamtiv mecarbil in systolic heart failure

BACKGROUND The selective cardiac myosin activator omecamtiv mecarbil has been shown to improve cardiac function in patients with heart failure with a reduced ejection fraction. Its effect on cardiovascular outcomes is unknown. METHODS We randomly assigned 8256 patients (inpatients and outpatients) with symptomatic chronic heart failure and an ejection fraction of 35% or less to receive omecamtiv mecarbil (using pharmacokinetic-guided doses of 25 mg, 37.5 mg, or 50 mg twice daily) or placebo, in addition to standard heart-failure therapy. The primary outcome was a composite of a first heart-failure event (hospitalization or urgent visit for heart failure) or death from cardiovascular causes. RESULTS During a median of 21.8 months, a primary-outcome event occurred in 1523 of 4120 patients (37.0%) in the omecamtiv mecarbil group and in 1607 of 4112 patients (39.1%) in the placebo group (hazard ratio, 0.92; 95% confidence interval [CI], 0.86 to 0.99; P = 0.03). A total of 808 patients (19.6%) and 798 patients (19.4%), respectively, died from cardiovascular causes (hazard ratio, 1.01; 95% CI, 0.92 to 1.11). There was no significant difference between groups in the change from baseline on the Kansas City Cardiomyopathy Questionnaire total symptom score. At week 24, the change from baseline for the median N-terminal pro-B-type natriuretic peptide level was 10% lower in the omecamtiv mecarbil group than in the placebo group; the median cardiac troponin I level was 4 ng per liter higher. The frequency of cardiac ischemic and ventricular arrhythmia events was similar in the two groups. CONCLUSIONS Among patients with heart failure and a reduced ejection, those who received omecamtiv mecarbil had a lower incidence of a composite of a heart-failure event or death from cardiovascular causes than those who received placebo. (Funded by Amgen and others; GALACTIC-HF ClinicalTrials.gov number, NCT02929329; EudraCT number, 2016 -002299-28.)