Preparation of benzolactams by Pd(II)-catalyzed carbonylation of N-unprotected arylethylamines

An unprecedented NH2-directed Pd(II)-catalytic carbonylation of quaternary aromatic α -amino esters to yield 6-membered 10 benzolactams has been developed. The reaction shows a strong bias to 6-membered lactams over 5-membered ones. The steric hindrance around the amino group seems to be pivotal for the success of the process

Ethical considerations in elderly patients with acute coronary syndrome

Acute coronary syndrome (ACS) is one of the main causes of mortality and morbidity in the elderly. The prevalence of ACS increases with age and patients with advanced age have some co-morbidities that require an individualized approach, which includes a comprehensive geriatric assessment. Ageism is a matter of great concern. In this scenario, some ethical conflicts may arise which should be anticipated, considered, and solved. Clinicians will need to prioritize and allocate resources, to avoid futility/proportionality, which is not always easy to assess in these patients. This review aims to summarize the evidence regarding ethical conflicts that may arise in the management of patients with ACS and advanced age. We will discuss how to choose the best option (which frequently is not the only one) with the lowest risk for harm, considering and respecting the patients' decision. The four basic principles of bioethics (beneficence, non-maleficence, autonomy, and justice) are thoroughly reviewed, and discussed, regarding their role in the decision making process

Increasing the length of the time series from altimetry satellites by means of extrapolation: the case of the Mediterranean coast of the Iberian Peninsula

Las series temporales de los satélites altimétricos son, con las de los mareógrafos, una de las dos fuentes principales de información sobre la evolución del nivel del mar. Sus principales ventajas sobre las series de los mareógrafos estriban en que permiten acceder a información espacialmente continua, en registrar cambios absolutos, y en una contrastada precisión. Algunos problemas anteriormente existentes en áreas costeras, como el problema del píxel mixto o aparentes errores en la calibración, han sido superados, o filtrados por la principal fuente de información de este tipo de registros, el Sea Level Research Group de la Universidad de Colorado. Sin embargo, el problema de la escasa duración de las series temporales (empezaron a funcionar en julio de 1992) no ha sido aún resuelto. En este trabajo se propone una metodología que permite alargar la serie hacia el pasado basándose en un análisis de correlación múltiple con datos procedentes de los registros de los mareógrafos, existentes desde décadas antes del lanzamiento de los satélites. Los resultados obtenidos indican que con cierto margen de error es posible interpretar la evolución del nivel del mar en cada celdilla de los satélites altimétricos desde los años 40 en el caso del litoral mediterráneo peninsular.The time series of the altimetric satellites are of the two main sources of information on the evolution of the level of the sea. Its main advantages over the series of tide gauges are that they allow access to information spatially continuous, recording absolute changes. Some problems previously encountered in coastal areas, such as the mixed pixel problem or apparent calibration errors, have been overcome or filtered by the University of Colorado's Sea Level Research Group's main source of information. However, the problem of the short duration of the time series (which began to operate in July 1992) has not yet been solved. This paper proposes a methodology that allows extending the series to the past based on a multiple correlation analysis with data from the records of the gauges, which had existed for decades before the launch of the satellites. The obtained results indicate that it is possible to interpret the evolution of sea level in each cell of the altimetric satellites since the 1940s in the case of the peninsular Mediterranean littoral

Preparation of substituted tetrahydroisoquinolines by Pd(II)-catalyzed NH2-directed insertion of Michael acceptors into C-H bonds followed by NH2-conjugated additions

3,3-Disubstituted tetrahydroisoquinolines are prepared in one step from Michael acceptors and 2-phenylethylamines under Pd catalysis and Ag2CO3 as an oxidant. Presumably, activation of an ortho C-H bond of the aromatic ring with Pd(II) is directed by the primary amine to form a palladacycle. Insertion of the olefin, subsequent conjugated addition of the amine, and reductive elimination of Pd(0) affords the expected products. Silver carbonate is not necessary when 2-phenylethylamines are converted previously to N-benzoyloxy-2-phenylethylamines

Beneficial effect of corticosteroids in preventing mortality in patients receiving tocilizumab to treat severe COVID-19 illness

Objectives: To assess the characteristics and risk factors for mortality in patients with severe coronavirus disease-2019 (COVID-19) treated with tocilizumab (TCZ), alone or in combination with corticosteroids (CS). Methods: From March 17 to April 7, 2020, a real-world observational retrospective analysis of consecutive hospitalized adult patients receiving TCZ to treat severe COVID-19 was conducted at our 750-bed university hospital. The main outcome was all-cause in-hospital mortality. Results: A total of 1,092 patients with COVID-19 were admitted during the study period. Of them, 186 (17%) were treated with TCZ, of which 129 (87.8%) in combination with CS. Of the total 186 patients, 155 (83.3 %) patients were receiving noninvasive ventilation when TCZ was initiated. Mean time from symptoms onset and hospital admission to TCZ use was 12 (±4.3) and 4.3 days (±3.4), respectively. Overall, 147 (79%) survived and 39 (21%) died. By multivariate analysis, mortality was associated with older age (HR = 1.09, p < 0.001), chronic heart failure (HR = 4.4, p = 0.003), and chronic liver disease (HR = 4.69, p = 0.004). The use of CS, in combination with TCZ, was identified as a protective factor against mortality (HR = 0.26, p < 0.001) in such severe COVID-19 patients receiving TCZ. No serious superinfections were observed after a 30-day follow-up. Conclusions: In patients with severe COVID-19 receiving TCZ due to systemic host-immune inflammatory response syndrome, the use of CS in addition to TCZ therapy, showed a beneficial effect in preventing in-hospital mortality

Acute Coronary Syndrome in the Older Patient

Coronary artery disease is one of the leading causes of morbidity and mortality, and its prevalence increases with age. The growing number of older patients and their differential characteristics make its management a challenge in clinical practice. The aim of this review is to summarize the state-of-the-art in diagnosis and treatment of acute coronary syndromes in this subgroup of patients. This comprises peculiarities of ST-segment elevation myocardial infarction (STEMI) management, updated evidence of non-STEMI therapeutic strategies, individualization of antiplatelet treatment (weighting ischemic and hemorrhagic risks), as well as assessment of geriatric conditions and ethical issues in decision making

Coronary Artery Disease and Prognosis of Heart Failure with Reduced Ejection Fraction.

Our aim was to determine the prognostic impact of coronary artery disease (CAD) on heart failure with reduced ejection fraction (HFrEF) mortality and readmissions. From a prospective multicenter registry that included 1831 patients hospitalized due to heart failure, 583 had a left ventricular ejection fraction of <40%. In total, 266 patients (45.6%) had coronary artery disease as main etiology and 137 (23.5%) had idiopathic dilated cardiomyopathy (DCM), and they are the focus of this study. Significant differences were found in Charlson index (CAD 4.4 ± 2.8, idiopathic DCM 2.9 ± 2.4, p < 0.001), and in the number of previous hospitalizations (1.1 ± 1, 0.8 ± 1.2, respectively, p = 0.015). One-year mortality was similar in the two groups: idiopathic DCM (hazard ratio [HR] = 1), CAD (HR 1.50; 95% CI 0.83-2.70, p = 0.182). Mortality/readmissions were also comparable: CAD (HR 0.96; 95% CI 0.64-1.41, p = 0.81). Patients with idiopathic DCM had a higher probability of receiving a heart transplant than those with CAD (HR 4.6; 95% CI 1.4-13.4, p = 0.012). The prognosis of HFrEF is similar in patients with CAD etiology and in those with idiopathic DCM. Patients with idiopathic DCM were more prone to receive heart transplant.This research was funded by CIBERCV I and supported by the Instituto de Salud Carlos III. L.V. is funded by the Instituto de Salud Carlos III, Spain (CM20/00104 and ).S

Does anemia affect the predictive ability of bleeding risk scores in patients with acute coronary syndromes?

Introduction and objective: Anemia is a common comorbidity in patients with acute coronary syndromes (ACS), and is associated with higher risk for both bleeding and ischemic complications. We aimed to assess the predictive ability of bleeding risk scores (Can Rapid risk stratification of Unstable angina patients Suppress ADverse outcomes with Early implementation of the ACC/AHA guidelines [CRUSADE], Mehran and Acute Coronary Treatment and Intervention Outcomes Network [ACTION]) in ACS patients with anemia. Methods: All consecutive ACS patients were prospectively included. The primary outcome was in-hospital major bleeding according to the CRUSADE, Mehran and ACTION definitions. Anemia was defined as hemoglobin <130 g/l in men and <120 g/l in women. The predictive ability of the bleeding risk scores was assessed by binary logistic regression, calculating receiver operating characteristic (ROC) curves and their corresponding area under the curve (AUC). Results: We included 2255 patients, mean age 62.4 years. Anemia was present in 550 patients (24.4%). Patients with anemia had a significantly higher prevalence of comorbidities. The three bleeding risk scores adequately predicted major bleeding in the whole cohort. No significant differences were observed regarding the predictive ability of each of the scores in patients with and without anemia (CRUSADE: AUC 0.73 without anemia vs. 0.74 with anemia, p=0.913; ACTION: AUC 0.68 without anemia vs. 0.73 with anemia, p=0.353; Mehran: AUC 0.69 without anemia vs. 0.61 with anemia, p=0.210). Only the Mehran score showed significantly lower predictive ability in patients with hemoglobin <11 g/dl (AUC 0.51, p=0.044). Conclusions: Anemia was a common comorbidity in patients with ACS from our series. Currently available bleeding risk scores showed an adequate predictive ability in patients with mild anemia

Clinical Outcomes of Severe COVID-19 Patients Admitted to an Intermediate Respiratory Care Unit

Introduction: Many severe COVID-19 patients require respiratory support and monitoring. An intermediate respiratory care unit (IMCU) may be a valuable element for optimizing patient care and limited health-care resources management. We aim to assess the clinical outcomes of severe COVID-19 patients admitted to an IMCU. Methods: Observational, retrospective study including patients admitted to the IMCU due to COVID-19 pneumonia during the months of March and April 2020. Patients were stratified based on their requirement of transfer to the intensive care unit (ICU) and on survival status at the end of follow-up. A multivariable Cox proportional hazards method was used to assess risk factors associated with mortality. Results: A total of 253 patients were included. Of them, 68% were male and median age was 65 years (IQR 18 years). Ninety-two patients (36.4%) required ICU transfer. Patients transferred to the ICU had a higher mortality rate (44.6 vs. 24.2%; p < 0.001). Multivariable proportional hazards model showed that age ≥65 years (HR 4.14; 95%CI 2.31-7.42; p < 0.001); chronic respiratory conditions (HR 2.34; 95%CI 1.38-3.99; p = 0.002) and chronic kidney disease (HR 2.96; 95%CI 1.61-5.43; p < 0.001) were independently associated with mortality. High-dose systemic corticosteroids followed by progressive dose tapering showed a lower risk of death (HR 0.15; 95%CI 0.06-0.40; p < 0.001). Conclusions: IMCU may be a useful tool for the multidisciplinary management of severe COVID-19 patients requiring respiratory support and non-invasive monitoring, therefore reducing ICU burden. Older age and chronic respiratory or renal conditions are associated with worse clinical outcomes, while treatment with systemic corticosteroids may have a protective effect on mortality