The effect of L-arginine and citrulline on endothelial function in patients in heart failure with preserved ejection fraction

Background: To evaluate the effect of the amino acids L-arginine and citrulline on endothelial function in patients in stable diastolic and right heart failure using photoplethysmography. Methods: Thirty patients from the Heart Failure Clinic of the Instituto Nacional de Ciencias Médicas y Nutrición "Salvador Zubirán" underwent photoplethysmography using the hyperemia technique. Index finger flow was assessed at baseline and after ischemia every 30 s by maximum amplitude time (MAT), total time of the curve (TT) and the index of the two (MAT/TT < 30 = normal) before and after the administration of L-arginine (8 g/day in two doses, n = 15) or citrulline (3 g/day in one dose, n = 15) for 60 days in addition to optimal pharmacological treatment. Results: There were no statistically significant differences between the two groups at baseline. After the intervention, the MAT/TT index of all patients normalized in each evaluation period with statistically significant differences. Basal L-arginine group = 38.75 &#177; 11.52, final 23.32 &#177; 6.08, p = 0.007 and basal citrulline group = 41.4 &#177; 13.47, final 23.65 &#177; 6.74, p = 0.007 at 60&#8211;90 s. Post-ischemia: basal L-arginine 36.60 &#177; 11.51, final 18.81 &#177; 15.13, p = 0.004 and basal citrulline = 49.51 &#177; 15.17, final 27.13 &#177; 7.87, p = 0.003. Conclusions: The administration of L-arginine and citrulline has a beneficial effect on endothelial function as shown by the normalized MAT/TT index. It probably improves systemic and pulmonary hemodynamics, which could help in the treatment of diastolic heart failure. (Cardiol J 2010; 17, 5: 464-470

Improvement of ventricular function in systolic heart failure patients with oral L-citrulline supplementation

Background: The utility of L-arginine and L-citrulline in treatment of arterial hypertension by increasing vascular oxide nitric availability has been demonstrated. Photoplethysmography, a simple and low-cost optical technique, makes it possible to assess vascular function and to detect changes in blood flow, pulse and swelling of the microvascular tissular space. The aim of the study was to evaluate the effect of L-citrulline supplementation on functional class, ejection fraction and peripheral blood flow in patients with systolic heart failure. Methods: Thirty-five stable outpatients attending the Heart Failure Clinic at the INCMNSZ underwent clinical evaluation, radioisotopic ventriculography and photoplethysmography before and at the end of 4 months. They were randomized into two groups: experimental group, with oral L-citrulline supplementation (3 g/day, n = 20) and control group, without supplementation (n = 15). Results: In the experimental group the left ventricular ejection fraction (LVEF) increased 20.3% at rest and 12.7% with stress, as well as the right ventricular ejection fraction at rest of 15.10% and 14.88% with stress. In addition, functional class improved in 35%, and the maximum amplitude time/total time (MAT/TT) index decreased 23.1%. These changes were statistically significant compared with the control group. Conclusions: Citrulline supplementation significantly improved the LVEF, the endothelial function (MAT/TT index) and functional class. Citrulline can be an important co-adjuvant in the treatment of stable and stable systolic heart failure patients

Treatment with tocilizumab or corticosteroids for COVID-19 patients with hyperinflammatory state: a multicentre cohort study (SAM-COVID-19)

Objectives: The objective of this study was to estimate the association between tocilizumab or corticosteroids and the risk of intubation or death in patients with coronavirus disease 19 (COVID-19) with a hyperinflammatory state according to clinical and laboratory parameters. Methods: A cohort study was performed in 60 Spanish hospitals including 778 patients with COVID-19 and clinical and laboratory data indicative of a hyperinflammatory state. Treatment was mainly with tocilizumab, an intermediate-high dose of corticosteroids (IHDC), a pulse dose of corticosteroids (PDC), combination therapy, or no treatment. Primary outcome was intubation or death; follow-up was 21 days. Propensity score-adjusted estimations using Cox regression (logistic regression if needed) were calculated. Propensity scores were used as confounders, matching variables and for the inverse probability of treatment weights (IPTWs). Results: In all, 88, 117, 78 and 151 patients treated with tocilizumab, IHDC, PDC, and combination therapy, respectively, were compared with 344 untreated patients. The primary endpoint occurred in 10 (11.4%), 27 (23.1%), 12 (15.4%), 40 (25.6%) and 69 (21.1%), respectively. The IPTW-based hazard ratios (odds ratio for combination therapy) for the primary endpoint were 0.32 (95%CI 0.22-0.47; p < 0.001) for tocilizumab, 0.82 (0.71-1.30; p 0.82) for IHDC, 0.61 (0.43-0.86; p 0.006) for PDC, and 1.17 (0.86-1.58; p 0.30) for combination therapy. Other applications of the propensity score provided similar results, but were not significant for PDC. Tocilizumab was also associated with lower hazard of death alone in IPTW analysis (0.07; 0.02-0.17; p < 0.001). Conclusions: Tocilizumab might be useful in COVID-19 patients with a hyperinflammatory state and should be prioritized for randomized trials in this situatio

Distribution of PM2.5 Air Pollution in Mexico City: Spatial Analysis with Land-Use Regression Model

In this study, the spatial distribution of PM2.5 air pollution in Mexico City from 37 personal exposures was modeled. Meteorological, demographic, geographic, and social data were also included. Geographic information systems (GIS), spatial analysis, and Land-Use Regression (LUR) were used to generate the final predictive model and the spatial distribution map which revealed two areas with very high concentrations (up to 109.3 µg/m3) and two more with lower concentrations (between 72 to 86.5 µg/m3) (p < 0.05). These results illustrate an overview trend of PM2.5 in relation to human activity during the studied periods in Mexico City and show a general approach to understanding the spatial variability of PM2.5

Prediction of Metabolic Syndrome in a Mexican Population Applying Machine Learning Algorithms

Metabolic syndrome is a health condition that increases the risk of heart diseases, diabetes, and stroke. The prognostic variables that identify this syndrome have already been defined by the World Health Organization (WHO), the National Cholesterol Education Program Third Adult Treatment Panel (ATP III) as well as by the International Diabetes Federation. According to these guides, there is some symmetry among anthropometric prognostic variables to classify abdominal obesity in people with metabolic syndrome. However, some appear to be more sensitive than others, nevertheless, these proposed definitions have failed to appropriately classify a specific population or ethnic group. In this work, we used the ATP III criteria as the framework with the purpose to rank the health parameters (clinical and anthropometric measurements, lifestyle data, and blood tests) from a data set of 2942 participants of Mexico City Tlalpan 2020 cohort, applying machine learning algorithms. We aimed to find the most appropriate prognostic variables to classify Mexicans with metabolic syndrome. The criteria of sensitivity, specificity, and balanced accuracy were used for validation. The ATP III using Waist-to-Height-Ratio (WHtR) as an anthropometric index for the diagnosis of abdominal obesity achieved better performance in classification than waist or body mass index. Further work is needed to assess its precision as a classification tool for Metabolic Syndrome in a Mexican population

Effect of Ivabradine on Endothelial Function in Diastolic and Right Heart Failure Patients

Background. Ivabradine is an If ion current inhibitor that has proved to reduce mortality in patients with systolic heart failure by slowing heart rate without decreasing myocardial contractility. Photoplethysmography is a simple, low-cost optical technique that can evaluate vascular function and detect changes in blood flow, pulse, and swelling of tissular microvascular space. Objective. To evaluate the effect of ivabradine on endothelial function by photoplethysmography in diastolic and right heart failure patients. Methodology. 15 patients were included (mean age of 78.1 ± 9.2 years) with optimally treated diastolic and right heart failure. They underwent photoplethysmography before and after induced ischemia to evaluate the wave blood flow on the finger, using the maximum amplitude time/total time (MAT/TT) index. Two measurements were made before and after oral Ivabradine (mean 12.5 mg a day during 6 months of followup). Results. In the study group, the MAT/TT index was 29.1 ± 2.2 versus 24.3 ± 3.2 () in basal recording and 30.4 ± 2.1 versus 23.3 ± 2.9 (), before versus after ischemia and before versus after Ivabradine intervention, respectively. Conclusions. Ivabradine administration improves endothelial function (shear stress) in diastolic and right heart failure patients

Physico-Chemical and Structural Interpretation of Discrete Derivative Indices on N-Tuples Atoms

This report examines the interpretation of the Graph Derivative Indices (GDIs) from three different perspectives (i.e., in structural, steric and electronic terms). It is found that the individual vertex frequencies may be expressed in terms of the geometrical and electronic reactivity of the atoms and bonds, respectively. On the other hand, it is demonstrated that the GDIs are sensitive to progressive structural modifications in terms of: size, ramifications, electronic richness, conjugation effects and molecular symmetry. Moreover, it is observed that the GDIs quantify the interaction capacity among molecules and codify information on the activation entropy. A structure property relationship study reveals that there exists a direct correspondence between the individual frequencies of atoms and Hückel’s Free Valence, as well as between the atomic GDIs and the chemical shift in NMR, which collectively validates the theory that these indices codify steric and electronic information of the atoms in a molecule. Taking in consideration the regularity and coherence found in experiments performed with the GDIs, it is possible to say that GDIs possess plausible interpretation in structural and physicochemical terms. © 2016 by the authors; licensee MDPI, Basel, Switzerland.Pharmaceutical Preparation

Global Impact of the COVID-19 Pandemic on Stroke Volumes and Cerebrovascular Events: One-Year Follow-up.

BACKGROUND AND OBJECTIVES Declines in stroke admission, intravenous thrombolysis, and mechanical thrombectomy volumes were reported during the first wave of the COVID-19 pandemic. There is a paucity of data on the longer-term effect of the pandemic on stroke volumes over the course of a year and through the second wave of the pandemic. We sought to measure the impact of the COVID-19 pandemic on the volumes of stroke admissions, intracranial hemorrhage (ICH), intravenous thrombolysis (IVT), and mechanical thrombectomy over a one-year period at the onset of the pandemic (March 1, 2020, to February 28, 2021) compared with the immediately preceding year (March 1, 2019, to February 29, 2020). METHODS We conducted a longitudinal retrospective study across 6 continents, 56 countries, and 275 stroke centers. We collected volume data for COVID-19 admissions and 4 stroke metrics: ischemic stroke admissions, ICH admissions, intravenous thrombolysis treatments, and mechanical thrombectomy procedures. Diagnoses were identified by their ICD-10 codes or classifications in stroke databases. RESULTS There were 148,895 stroke admissions in the one-year immediately before compared to 138,453 admissions during the one-year pandemic, representing a 7% decline (95% confidence interval [95% CI 7.1, 6.9]; p<0.0001). ICH volumes declined from 29,585 to 28,156 (4.8%, [5.1, 4.6]; p<0.0001) and IVT volume from 24,584 to 23,077 (6.1%, [6.4, 5.8]; p<0.0001). Larger declines were observed at high volume compared to low volume centers (all p<0.0001). There was no significant change in mechanical thrombectomy volumes (0.7%, [0.6,0.9]; p=0.49). Stroke was diagnosed in 1.3% [1.31,1.38] of 406,792 COVID-19 hospitalizations. SARS-CoV-2 infection was present in 2.9% ([2.82,2.97], 5,656/195,539) of all stroke hospitalizations. DISCUSSION There was a global decline and shift to lower volume centers of stroke admission volumes, ICH volumes, and IVT volumes during the 1st year of the COVID-19 pandemic compared to the prior year. Mechanical thrombectomy volumes were preserved. These results suggest preservation in the stroke care of higher severity of disease through the first pandemic year. TRIAL REGISTRATION INFORMATION This study is registered under NCT04934020

Effects of pre-operative isolation on postoperative pulmonary complications after elective surgery: an international prospective cohort study an international prospective cohort study

We aimed to determine the impact of pre-operative isolation on postoperative pulmonary complications after elective surgery during the global SARS-CoV-2 pandemic. We performed an international prospective cohort study including patients undergoing elective surgery in October 2020. Isolation was defined as the period before surgery during which patients did not leave their house or receive visitors from outside their household. The primary outcome was postoperative pulmonary complications, adjusted in multivariable models for measured confounders. Pre-defined sub-group analyses were performed for the primary outcome. A total of 96,454 patients from 114 countries were included and overall, 26,948 (27.9%) patients isolated before surgery. Postoperative pulmonary complications were recorded in 1947 (2.0%) patients of which 227 (11.7%) were associated with SARS-CoV-2 infection. Patients who isolated pre-operatively were older, had more respiratory comorbidities and were more commonly from areas of high SARS-CoV-2 incidence and high-income countries. Although the overall rates of postoperative pulmonary complications were similar in those that isolated and those that did not (2.1% vs 2.0%, respectively), isolation was associated with higher rates of postoperative pulmonary complications after adjustment (adjusted OR 1.20, 95%CI 1.05–1.36, p = 0.005). Sensitivity analyses revealed no further differences when patients were categorised by: pre-operative testing; use of COVID-19-free pathways; or community SARS-CoV-2 prevalence. The rate of postoperative pulmonary complications increased with periods of isolation longer than 3 days, with an OR (95%CI) at 4–7 days or ≥ 8 days of 1.25 (1.04–1.48), p = 0.015 and 1.31 (1.11–1.55), p = 0.001, respectively. Isolation before elective surgery might be associated with a small but clinically important increased risk of postoperative pulmonary complications. Longer periods of isolation showed no reduction in the risk of postoperative pulmonary complications. These findings have significant implications for global provision of elective surgical care. We aimed to determine the impact of pre-operative isolation on postoperative pulmonary complications after elective surgery during the global SARS-CoV-2 pandemic. We performed an international prospective cohort study including patients undergoing elective surgery in October 2020. Isolation was defined as the period before surgery during which patients did not leave their house or receive visitors from outside their household. The primary outcome was postoperative pulmonary complications, adjusted in multivariable models for measured confounders. Pre-defined sub-group analyses were performed for the primary outcome. A total of 96,454 patients from 114 countries were included and overall, 26,948 (27.9%) patients isolated before surgery. Postoperative pulmonary complications were recorded in 1947 (2.0%) patients of which 227 (11.7%) were associated with SARS-CoV-2 infection. Patients who isolated pre-operatively were older, had more respiratory comorbidities and were more commonly from areas of high SARS-CoV-2 incidence and high-income countries. Although the overall rates of postoperative pulmonary complications were similar in those that isolated and those that did not (2.1% vs 2.0%, respectively), isolation was associated with higher rates of postoperative pulmonary complications after adjustment (adjusted OR 1.20, 95%CI 1.05–1.36, p = 0.005). Sensitivity analyses revealed no further differences when patients were categorised by: pre-operative testing; use of COVID-19-free pathways; or community SARS-CoV-2 prevalence. The rate of postoperative pulmonary complications increased with periods of isolation longer than 3 days, with an OR (95%CI) at 4–7 days or ≥ 8 days of 1.25 (1.04–1.48), p = 0.015 and 1.31 (1.11–1.55), p = 0.001, respectively. Isolation before elective surgery might be associated with a small but clinically important increased risk of postoperative pulmonary complications. Longer periods of isolation showed no reduction in the risk of postoperative pulmonary complications. These findings have significant implications for global provision of elective surgical care