Oxidative stress in diverse clinical conditions of SARS-CoV-2 Cuban hospitalized patients

Context: COVID-19 related to SARS-CoV-2 infection generates inflammation with increased reactive oxygen species production. Drug treatment and others factors could influence systemic oxidative stress during pathogenic insult. Aims: To determine the redox status in COVID-19 patients with different clinical conditions and explore the relationship between redox and hematological hemochemical variables. Methods: In this comparative longitudinal study, blood samples were drawn from 160 individuals divided into four groups: COVID-19 asymptomatic, COVID-19 symptomatic (low and moderate symptoms), COVID-19 convalescent, and presumable healthy subjects. Demographic, redox, hematological, and hemochemical indices were assessed. Statistical analyses compared the median values of each variable and explored individual, simultaneous indices, and multivariate alteration. Results: Relative to the healthy group, acute COVID-19, and convalescent groups had significant differences in global damage indices and antioxidant status (p<0.05). The convalescent group showed significantly higher damage (malondialdehyde, advanced oxidation protein products, nitric oxide) and lower antioxidant enzymatic activities and glutathione concentration compared to other groups (p<0.05). Global modification of redox indices showed that more than 80% of studied individuals in acute conditions had simultaneous detrimental differences compared to a healthy status. The discriminant analysis permitted obtaining two canonical functions (p< 0.05) that reflect 98% of redox variables with 95% of variances with successful case classifications. Conclusions: These results corroborate that oxidative stress occurred in different COVID-19 and post-acute conditions with different molecular alterations of redox indices. Redox diagnosis should be considered in early diagnosis and treatment of infection, which would be worthwhile to conduct a more comprehensive study and management of disease evolution. © 2023 Journal of Pharmacy & Pharmacognosy Research.

Who Benefits More of Durvalumab after Chemoradiotherapy (CRT) in Real-World Patients with Locally Advanced Non-Small-Cell Lung Cancer (NSCLC)?

Introduction: Durvalumab received EMA approval as consolidation therapy (CT) for unresectable stage III NSCLC with PD-L1 ≥1% and who did not have progression after CRT. Our objective was to analyze in real clinical practice the effectiveness of durvalumab and explore the clinical factors that may be associated with the benefit from CT. Methods: Retrospective study was made at Hospital of Leon (Spain), including 37 patients with locally advanced NSCLC treated with durvalumab after CRT treatment between March 2018 and october 2021 (40.5% patients were included in the durvalumab early access program). The neutrophil-to-lymphocyte ratio (NLR) could identified after CRT as a factor that may be benefit from durvalumab. Results: Median age was 67 years (range 46-82 years). 40.5% of patients were ≥70 years old. 78.4% were male and 51.4% smokers. 54% had non-squamous histology. PD-L1 expression was <1% in 5% and not available in 8% patients. 2.7% ROS1 rearrangements, 5.4% KRAS mutations and not available in 43.2% patients. Stage IIIA, IIIB, IIIC disease were 24.3%, 54.1% and 21.6%, respectively. Median time from end of CRT to onset durvalumab was 44 days (range 13-120 days). Overall median CT duration was 214.8 days (range 69-399 days) with a median of 14 infusions (range 6-27 infusions). With a median follow up of 19.7 months (range 1.4-34.9 months);67.6% had stopped CT: 37.8% due to completing treatment, 16.2% disease progression, 10.8% adverse event and 2.7% due to COVID19 infection. Median real-world progression-free survival (rwPFS) was 17 months (95% CI, 11-23). Median real-world overall survival (rwOS) was 29.9 months (95% CI, 23.3-36.6). %rwOS at 6, 18 and 24 months were 100%, 86.9% and 74.5%, respectively. For patients with post-CRT NLR not exceeding the cohort median value of 6, receipt of durvalumab was associated with an improvement in rwOS (median not reached vs 25.7 months;p=0.025). 56.8% patients had any grade of radiation pneumonitis (median time from CRT start: 119 days [range 36-241 days]). Of these, 19% patients developed worsening of radiation pneumonitis with durvalumab. 54,1% developed immune-mediated toxicity, mostly G1-2 (85.1%). Conclusions: Our results demonstrate the effectiveness of durvalumab consolidation in this patients population in a real-life setting. We identified low NLR after CRT as a potentially predictive factor for the benefit of CT in locally advanced NSCLC. Keywords: DURVALUMAB, PACIFIC, REAL WORLD DATA

Non-invasive ventilation in acute respiratory distress syndrome due to COVID-19

Introduction: The use of non-invasive mechanical ventilation has become widespread in the world, with widespread use even in patients with hypoxemic respiratory failure. Objective: To identify what is known about the use of non-invasive ventilation in acute respiratory distress syndrome and to analyze its application in this complication in COVID-19. Development: Non-invasive mechanical ventilation could appear as one more resource to give respiratory support in patients with COVID-19 infection, however, the scant scientific evidence on its effectiveness in acute respiratory distress syndrome and the risk of contagion by the particle scattering, generates controversy over its use. Conclusions: In adults with COVID-19 and acute hypoxemic respiratory failure, the use of noninvasive mechanical ventilation should be contraindicated, only assessing its use in very specific and justified cases. © 2021, Editorial Ciencias Medicas. All rights reserved.

Observance of adverse reactions and analysis of biosafety compliance in the rectal application of ozone therapy in COVID-19 Cuban patients with acute infection or convalescent

Context: Patients with COVID-19 present different biochemical and metabolic alterations from the acute state of infection until months later with variability of symptoms and increased toxicity of drugs related to oxidative stress according to previous studies. There are various alternatives to modulate oxidative stress, including the use of medical ozone, which rectal way requires observing both compliance with biosafety measures and adverse reactions in patients. Aims: To evaluate compliance with biosafety measures and the possible manifestations of adverse events in the rectal application of ozone therapy in patients with acute infection or convalescent of COVID-19. Methods: Descriptive, longitudinal studies in two clinical trials conducted at the Ernesto Guevara Hospital and the Salvador Allende Hospital, from May to July 2020. Rectal ozone therapy was applied to patients in two trials with a cycle of up to 20 applications according to the study. The activities were described and the performance of the professionals in the procedure was evaluated through an observation guide. Patient follow-up and surveillance for potential adverse reactions were performed. Results: 80% (28/36) of the patients reported the feeling of fullness of the intestines, without other reports, in no case treatment was required. The evaluation of the practices showed full compliance with the procedures without transmission of infection during the period. Conclusions: Compliance with good practices and biosafety in the rectal application of ozone results in the adequate performance of the protocols with benefit and safety for patients under treatment.