Background The absence of specific antivirals to treat COVID-19 leads to the repositioning of candidates’ drugs. Nitazoxanide (NTZ) has a broad antiviral effect. Methods This was a randomized, double-blind pilot clinical trial comparing NTZ 600 mg BID versus Placebo for seven days among 50 individuals (25 each arm) with SARS-COV-2 RT-PCR+ (PCR) that were hospitalized with mild respiratory insufficiency from May 20 th , 2020, to September 21 st , 2020 (ClinicalTrials.gov NCT04348409). Clinical and virologic endpoints and inflammatory biomarkers were evaluated. A five-point scale for disease severity (SSD) was used. Findings Two patients died in the NTZ arm compared to 6 in the placebo arm ( p = 0.564). NTZ was superior to placebo when considering SSD ( p < 0001), the mean time for hospital discharge (6.6 vs. 14 days, p = 0.021), and negative PCR at day 21 ( p = 0.035), whereas the placebo group presented more adverse events ( p = 0.04). Among adverse events likely related to the study drug, 14 were detected in the NTZ group and 22 in placebo ( p = 0.24). Among the 30 adverse events unlikely related, 21 occurred in the placebo group ( p = 0.04). A decrease from baseline was higher in the NTZ group for d -Dimer ( p = 0.001), US-RCP ( p < 0.002), TNF ( p < 0.038), IL-6 ( p < 0.001), IL-8 ( p = 0.014), HLA DR. on CD4 + T lymphocytes ( p < 0.05), CD38 in CD4 + and CD8 + T (both p < 0.05), and CD38 and HLA-DR. on CD4+ ( p < 0.01) Interpretation Compared to placebo in clinical and virologic outcomes and improvement of inflammatory outcomes, the superiority of NTZ warrants further investigation of this drug for moderate COVID-19 in larger clinical trials. A higher incidence of adverse events in the placebo arm might be attributed to COVID-19 related symptoms.
Background: Predictors of the outcome of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-Cov-2) infection remain to be fully determined. We evaluated selected viral characteristics and immunological responses that might predict and/or correlate to the clinical outcome of COVID-19. Methods: The magnitude and breadth of T cell-mediated responses were measured within 36 hours of symptom onset for individuals developing divergent clinical outcomes. Peripheral Blood Mononuclear Cells (PBMCs) were subjected to in vitro stimulation with SARS-CoV-2-based peptides. In addition, SARS-CoV-2 sequences were generated by metagenome, and HLA typing was performed using Luminex technology. Findings: CD4+ T cell activation was found to be negatively correlated with SARS-CoV-2 basal viral load in patients with severe COVID-19 (p = 0·043). The overall cellular immune response, as inferred by IFN-γ signal, was higher at baseline for patients that progressed to mild disease compared to patients that progressed to severe disease (p = 0·0044). Subjects with milder disease developed higher T cell responses for MHC class I and II-restricted peptides (p = 0·033). Interpretation: Mounting specific cellular immune responses in the first days after symptom onset, as inferred by IFN-γ magnitude in the ELISPOT assay, may efficiently favor a positive outcome. In contrast, progression to severe COVID-19 was accompanied by stronger cellular immune responses, higher CD4+ T cell activation, and a higher number of in silico predicted high-affinity class I HLA alleles. Funding: Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) - Grant 2020/10396-2, and Conselho Nacional de Desenvolvimento Científico e Tecnológico - Grant 441817/2018-1.
Os autores estudaram aproximadamente 4.000 pacientes submetidos a gastrectomia por câncer gástrico no período de 1973 a 1999. Foram considerados somente os casos cuja cirurgia foi curativa (sem margens cirúrgicas comprometidas, sem doença residual e sem metástases em outros órgãos). Foram excluídos do estudo todos os pacientes que receberam quimio e/ou radioterapia pré ou pós-operatória. Trata-se de estudo multicêntrico realizado em pacientes de 14 centros de oncologia dos Estados Unidos, englobando um total de 65.560 doentes diagnosticados com câncer de estômago. Foi analisada a sobrevida após a cirurgia, correlacionada com o número de linfonodos ressecados em quatro subgrupos de acordo com a classificação TNM: T1/2N0, T1/2N1, T3N0 e T3N1.Os resultados mostraram que quanto maior o número de linfonodos ressecados, maior era o índice de sobrevida em todos os subgrupos estudados. A sobrevida de 5 anos se somente um linfonodo houvesse sido ressecado por paciente alcançaria: 56% no grupo T1/2N0, 35% no T1/ 2N1, 29% no T3N0 e 13% no T3N1. Para cada 10 linfonodos extras retirados por paciente, havia um aumento de 7,6% no subgrupo T1/2N0, 5,7% no T1/2N1, 11% no T3N0 e 7% no T3N1; e esse aumento da sobrevida continuou acontecendo mesmo acima dos 40 linfonodos extirpados. Na média, houve um aumento de 0,8% na sobrevida a cada linfonodo dissecado a mais, considerando o cut point de um linfonodo extirpado por paciente.
Objective: Clinical trial carried out to evaluate the superiority of efficacy of a treatment regimen with an oral probiotic associated with a fixed combination of 0.1% adapalene and 2.5% benzoyl peroxide compared to an oral placebo with the same topical treatment in patients with mild to moderate acne. Patients and Methods: This was a randomized, double-blind, placebo-controlled study conducted with 212 patients aged from 12 to 35 years; 107 in the test treatment arm and 105 in the comparator arm. The study was divided into two phases of 90 days each, totaling 180 days. In the first phase, patients received treatment with 2.5% benzoyl peroxide and 0.1% adapalene associated with a probiotic (IT), or 2.5% benzoyl peroxide and 0.1% adapalene associated with placebo (CT). In the second phase (90 days), patients received only oral treatment with a probiotic or placebo. Efficacy criteria were: reduction of the Investigator Global Assessment (IGA) scale to 0 or 1, and reduced lesion count. Results: There was a significant difference in the proportion of participants with IGA 0 or 1 – the arm receiving the test treatment was superior to the comparator group at all study time points (30, 60, 90, 120, 150 and 180 days) (p<0.05). Regarding lesion counts, the test arm was superior, although this difference was not statistically significant. Both treatments were safe and well tolerated. Conclusion: In light of the evidence on efficacy and safety, treatment with probiotics should be considered as an adjuvant therapy for acne control.
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