The effect of β-blockers on infarct size when used in conjunction with primary percutaneous coronary intervention is unknown. We hypothesize that metoprolol reduces infarct size when administered ...early (intravenously before reperfusion).
Patients with Killip class II or less anterior ST-segment-elevation myocardial infarction (STEMI) undergoing percutaneous coronary intervention within 6 hours of symptoms onset were randomized to receive intravenous metoprolol (n=131) or not (control, n=139) before reperfusion. All patients without contraindications received oral metoprolol within 24 hours. The predefined primary end point was infarct size on magnetic resonance imaging performed 5 to 7 days after STEMI. Magnetic resonance imaging was performed in 220 patients (81%). Mean ± SD infarct size by magnetic resonance imaging was smaller after intravenous metoprolol compared with control (25.6 ± 15.3 versus 32.0 ± 22.2 g; adjusted difference, -6.52; 95% confidence interval, -11.39 to -1.78; P=0.012). In patients with pre-percutaneous coronary intervention Thrombolysis in Myocardial Infarction grade 0 to 1 flow, the adjusted treatment difference in infarct size was -8.13 (95% confidence interval, -13.10 to -3.16; P=0.0024). Infarct size estimated by peak and area under the curve creatine kinase release was measured in all study populations and was significantly reduced by intravenous metoprolol. Left ventricular ejection fraction was higher in the intravenous metoprolol group (adjusted difference, 2.67%; 95% confidence interval, 0.09-5.21; P=0.045). The composite of death, malignant ventricular arrhythmia, cardiogenic shock, atrioventricular block, and reinfarction at 24 hours in the intravenous metoprolol and control groups was 7.1% and 12.3%, respectively (P=0.21).
In patients with anterior Killip class II or less ST-segment-elevation myocardial infarction undergoing primary percutaneous coronary intervention, early intravenous metoprolol before reperfusion reduced infarct size and increased left ventricular ejection fraction with no excess of adverse events during the first 24 hours after STEMI.
http://www.clinicaltrials.gov. Unique identifier: NCT01311700. EUDRACT number: 2010-019939-35.
Aim
To analyse the incidence, risk factors and clinical outcomes of late graft failure after heart transplantation.
Methods and results
We conducted an observational, single‐centre study based on 547 ...patients who underwent cardiac transplantation from 1991 to 2014 and who survived the in‐hospital postoperative period. Late graft failure was defined as the first hospitalization due to this condition after discharge. Over a mean follow‐up of 8.4 ± 6 years, 178 (32.5%) patients were hospitalized due to late graft failure incidence rate: 3.6 cases per 100 patient‐years, 95% confidence interval (CI) 3.1–4.2. Pre‐transplant diabetes, higher pre‐transplant transpulmonary pressure gradient and lower donor–recipient weight ratio were independently associated with higher risk of graft failure. Cardiac allograft vasculopathy, cellular rejection grade ≥1R, and antibody‐mediated rejection grade ≥1 were detected in 50.6%, 44.9% and 19.2% patients, respectively, admitted due to graft failure. Left ventricular ejection fraction was ≥50% in 60.1% of these patients. Re‐transplant free survival 1, 5, 10 and 15 years after the diagnosis of late graft failure was 72.2%, 38.4%, 18.4%, and 7.5%, respectively; the incidence rate of re‐hospitalization due to decompensated heart failure was 40.9 episodes per 100 patient‐years (95% CI 36.6–46.1). The need for inotropes, the presence of cardiac allograft vasculopathy, higher creatinine serum levels, lower ejection fraction and lower sodium serum levels were independent predictors of worse outcomes.
Conclusions
Late graft failure is frequent after heart transplantation, as it is associated with poor outcomes. Rejection and cardiac allograft vasculopathy are the most frequent underlying causes.
A highly enantioselective biocatalytic dynamic kinetic resolution (DKR) of 2‐(quinoline‐8‐yl) 3‐methylbenzaldehydes and 1‐naphthaldehydes is described. The reaction proceeds by atroposelective ...carbonyl reduction catalyzed by commercial ketoreductases (KREDs), generally reaching high conversions and excellent enantiomeric excesses. Both atropoisomers of the final alcohols can be obtained by a proper selection of the biocatalyst. The DKR strategy relies in the racemization of the stereogenic axis that takes place thanks to a transient Lewis acid‐base interaction (LABI) between the nitrogen in the quinoline and the carbonyl group.
In this study we determined the causes of mortality and disease in a total of 325 lagomorphs (rabbits and hares) in northern Spain between 2000 and 2018. Risk factors such as the species, age, sex, ...time of year and origin were also considered. Clinical signs, gross and histopathological findings and ancillary test results were the basis for the final diagnoses that were reviewed to classify and identify the different disorders. A total of 26 different conditions were identified. A single cause of death or illness was detected in 267 animals. They were grouped into parasitic conditions (
= 65; 24.34%) represented by encephalitozoonosis, hepatic coccidiosis, hepatoperitoneal cysticercosis, intestinal coccidiosis, parasitic gastritis and cutaneous ectoparasitosis; bacterial diseases (
= 56; 20.97%) including pseudotuberculosis, blue breast, skin abscesses, tularemia, pneumonic pasteurellosis and staphylococcal infections; nutritional and metabolic diseases (
= 48; 17.97%) with epizootic rabbit enteropathy, hepatic steatosis and pregnancy toxemia as prominent diseases; viral infections (
= 31; 11.61%) comprising rabbit hemorrhagic disease and myxomatosis and miscellaneous causes (
= 31; 11.61%) where rabbit enteritis complex, renal conditions (nephrosis), heat stroke, and arterial bone metaplasia were included; neoplasms (
= 12; 4.49%) represented by uterine adenocarcinoma, mammary adenocarcinoma, cutaneous fibroma, intestinal lymphoma and hepatic cholangiocarcinoma; toxicoses (
= 11; 4.11%); trauma-related injuries (
= 9; 3.37%) and finally congenital diseases (
= 4; 1.49%). In 58 animals of the study, some of these conditions were presented jointly. We discuss the detection frequency, possible causes or associated factors of the different pathologies as well as the importance of the different variables considered.
Catalysts generated by combinations of Pd(TFA)2 and pyridine‐hydrazone ligands have been applied to 1,2 addition of arylboronic acids to aliphatic N‐carbamoyl (Cbz) hydrazones, affording protected ...α‐aryl monoalkylhydrazines with high enantioselectivities (37‐99% ee). Subsequent removal of the benzyloxy carbonyl protecting group provides a direct entry to free monosubstituted hydrazines, key building blocks for the synthesis of appealing 1,2‐diaza‐heterocycles, aminoacid derived hydrazides and other pharmacophores thereof.
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