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

Post-intervention Status in Patients With Refractory Myasthenia Gravis Treated With Eculizumab During REGAIN and Its Open-Label Extension

OBJECTIVE: To evaluate whether eculizumab helps patients with anti-acetylcholine receptor-positive (AChR+) refractory generalized myasthenia gravis (gMG) achieve the Myasthenia Gravis Foundation of America (MGFA) post-intervention status of minimal manifestations (MM), we assessed patients' status throughout REGAIN (Safety and Efficacy of Eculizumab in AChR+ Refractory Generalized Myasthenia Gravis) and its open-label extension. METHODS: Patients who completed the REGAIN randomized controlled trial and continued into the open-label extension were included in this tertiary endpoint analysis. Patients were assessed for the MGFA post-intervention status of improved, unchanged, worse, MM, and pharmacologic remission at defined time points during REGAIN and through week 130 of the open-label study. RESULTS: A total of 117 patients completed REGAIN and continued into the open-label study (eculizumab/eculizumab: 56; placebo/eculizumab: 61). At week 26 of REGAIN, more eculizumab-treated patients than placebo-treated patients achieved a status of improved (60.7% vs 41.7%) or MM (25.0% vs 13.3%; common OR: 2.3; 95% CI: 1.1-4.5). After 130 weeks of eculizumab treatment, 88.0% of patients achieved improved status and 57.3% of patients achieved MM status. The safety profile of eculizumab was consistent with its known profile and no new safety signals were detected. CONCLUSION: Eculizumab led to rapid and sustained achievement of MM in patients with AChR+ refractory gMG. These findings support the use of eculizumab in this previously difficult-to-treat patient population. CLINICALTRIALSGOV IDENTIFIER: REGAIN, NCT01997229; REGAIN open-label extension, NCT02301624. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that, after 26 weeks of eculizumab treatment, 25.0% of adults with AChR+ refractory gMG achieved MM, compared with 13.3% who received placebo

Minimal Symptom Expression' in Patients With Acetylcholine Receptor Antibody-Positive Refractory Generalized Myasthenia Gravis Treated With Eculizumab

The efficacy and tolerability of eculizumab were assessed in REGAIN, a 26-week, phase 3, randomized, double-blind, placebo-controlled study in anti-acetylcholine receptor antibody-positive (AChR+) refractory generalized myasthenia gravis (gMG), and its open-label extension

SARS-CoV-2 susceptibility and COVID-19 disease severity are associated with genetic variants affecting gene expression in a variety of tissues

Variability in SARS-CoV-2 susceptibility and COVID-19 disease severity between individuals is partly due to genetic factors. Here, we identify 4 genomic loci with suggestive associations for SARS-CoV-2 susceptibility and 19 for COVID-19 disease severity. Four of these 23 loci likely have an ethnicity-specific component. Genome-wide association study (GWAS) signals in 11 loci colocalize with expression quantitative trait loci (eQTLs) associated with the expression of 20 genes in 62 tissues/cell types (range: 1:43 tissues/gene), including lung, brain, heart, muscle, and skin as well as the digestive system and immune system. We perform genetic fine mapping to compute 99% credible SNP sets, which identify 10 GWAS loci that have eight or fewer SNPs in the credible set, including three loci with one single likely causal SNP. Our study suggests that the diverse symptoms and disease severity of COVID-19 observed between individuals is associated with variants across the genome, affecting gene expression levels in a wide variety of tissue types

A first update on mapping the human genetic architecture of COVID-19

peer reviewe

Impact of protein content on the antioxidants, anti-inflammatory properties and glycemic index of wheat and wheat bran

This article belongs to the Special Issue Bioactive Compounds, Antioxidants, and Health Benefits.Conventional wheat milling generates important volumes of wheat bran (WB), which is a concentrated source of polyphenols and insoluble fiber. In terms of health benefits and based on epidemiological and experimental evidence, these compounds contribute to reducing the risk of certain chronic pathologies. Protein concentration is the main quality factor conditioning wheat use in the agroindustry. When turning waste into feasible resources, it is essential to evaluate the variability of the raw material. The aim of this study was the evaluation of the impact of protein content in the valorization of WB based on its antioxidants, anti-inflammatory properties and glycemic index (GI). A significantly (p ≤ 0.05) lower content of phenolic compounds was found in the whole grain (WG) fractions, both free (FP) and bound (BP), as compared to the WB phenolic fractions, differences that ranged from 4- to 6-fold (538 to 561 mg GAE 100 g−1 in WG vs. 1027 to 1236 in WB mg GAE 100 g−1 in FP and 2245 to 2378 vs. 6344 to 7232 mg GAE 100 g−1 in BP). A significant (p ≤ 0.05) effect of the protein content on the resulting phenolic content and antioxidant capacity was observed, especially in WG, but also in WB, although in the latter a significant (p ≤ 0.05) negative correlation was observed, and increasing the protein content resulted in decreasing total phenolic content, antioxidants, and ferric-reducing capacities, probably due to their different types of proteins. The highest protein content in WB produced a significant (p ≤ 0.05) reduction in GI value, probably due to the role of protein structure in protecting starch from gelatinization, along with phytic acid, which may bind to proteins closely associated to starch and chelate calcium ions, required for α-amylase activity. A significant (p ≤ 0.05) effect of the protein content on the GI was also found, which may be explained by the structural effect of the proteins associated with starch, reducing the GI (21.64). The results obtained show the importance of segregation of WB in valorization strategies in order to increase the efficiency of the processes.Grant AGL2017-83718-R funded by MCIN/AEI/10.13039/501100011033 and “ERDF A way of making Europe”. I.J.J.-P. thanks for his FPI fellowship (PRE2019-087824) to AEI/Spain and ESF/UE.Peer reviewe

Efecto varietal en el proceso de valorización de salvados de trigo para el desarrollo de ingredientes nutraceúticos

Trabajo presentado al XV Congreso Internacional de la Sociedad Española de Dietetica y Ciencias de la Alimentación (SEDCA), celebrado los días 29, 30 y 31 de marzo de 2022 en Madrid.Peer reviewe

Sprouting and hydrolysis as biotechnological tools for development of nutraceutical ingredients from oat grain and hull

This article belongs to the Special Issue Grain and Pulses: Composition, Characteristics, Application and Health Promising Prospects.Oat consumption has increased during the last decade because of the health benefits associated with its soluble dietary fiber (β-glucan), functional proteins, lipids, and the presence of specific phytochemicals, such as avenanthramides. Oat is consumed mainly as whole grain, and the hull (seed coat), comprising 25–35% of the entire grain, is removed, generating a large amount of waste/by-product from the milling industry. The objective of this study was to evaluate the use of biotechnological strategies, such as sprouting for oat grain (OG) and hydrolysis for oat hull (OH), to enhance antioxidant and anti-inflammatory properties and lower the glycemic index (GI). Sprouting produced significant (p ≤ 0.05) increases in free (32.10 to 76.62 mg GAE (100 g)−1) and bound phenols (60.45 to 124.36 mg GAE (100 g)−1), increasing significantly (p ≤ 0.05) the avenanthramide (2c, 2p and 2f) soluble phenolic alkaloid content and anti-inflammatory properties of OG. On the other hand, the hydrolysis of OH using Viscoferm (EH2-OH) and Ultraflo XL (EH21-OH) increased by 4.5 and 5-fold the release of bound phenols, respectively; meanwhile, the use of Viscoferm increased the 4.55-fold soluble β-glucan content in OH, reaching values close to those of OG (4.04 vs. 4.46 g (100 g)−1). The study shows the potential of both strategies to enhance the nutritional and bioactive properties of OG and OH and describes these processes as feasible for the industry to obtain an ingredient with high antioxidant and anti-inflammatory activities. Single or combined biotechnological tools can be used on oat grains and hulls to provide nutraceutical ingredients.Grant AGL2017-83718-R funded by MCIN/AEI/10.13039/501100011033 and “ERDF A way of making Europe”. I.J.J.-P. thanks AEI/Spain and ESF/UE for his FPI fellowship (PRE2019-087824).Peer reviewe

Germination as green biotechnological process to enhance the nutritional and bioactive profile of oat grains

Resumen del póster presentado a la 36th EFFoST International Conference: "Shaping the Production of Sustainable, Healthy Foods for the Future", celebrada del 7 al 9 de noviembre de 2022 en Dublin (Ireland).Peer reviewe