Early Treatment with Pegylated Interferon Lambda for Covid-19.

BACKGROUND: The efficacy of a single dose of pegylated interferon lambda in preventing clinical events among outpatients with acute symptomatic coronavirus disease 2019 (Covid-19) is unclear. METHODS: We conducted a randomized, controlled, adaptive platform trial involving predominantly vaccinated adults with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in Brazil and Canada. Outpatients who presented with an acute clinical condition consistent with Covid-19 within 7 days after the onset of symptoms received either pegylated interferon lambda (single subcutaneous injection, 180 µg) or placebo (single injection or oral). The primary composite outcome was hospitalization (or transfer to a tertiary hospital) or an emergency department visit (observation for >6 hours) due to Covid-19 within 28 days after randomization. RESULTS: A total of 933 patients were assigned to receive pegylated interferon lambda (2 were subsequently excluded owing to protocol deviations) and 1018 were assigned to receive placebo. Overall, 83% of the patients had been vaccinated, and during the trial, multiple SARS-CoV-2 variants had emerged. A total of 25 of 931 patients (2.7%) in the interferon group had a primary-outcome event, as compared with 57 of 1018 (5.6%) in the placebo group, a difference of 51% (relative risk, 0.49; 95% Bayesian credible interval, 0.30 to 0.76; posterior probability of superiority to placebo, >99.9%). Results were generally consistent in analyses of secondary outcomes, including time to hospitalization for Covid-19 (hazard ratio, 0.57; 95% Bayesian credible interval, 0.33 to 0.95) and Covid-19-related hospitalization or death (hazard ratio, 0.59; 95% Bayesian credible interval, 0.35 to 0.97). The effects were consistent across dominant variants and independent of vaccination status. Among patients with a high viral load at baseline, those who received pegylated interferon lambda had lower viral loads by day 7 than those who received placebo. The incidence of adverse events was similar in the two groups. CONCLUSIONS: Among predominantly vaccinated outpatients with Covid-19, the incidence of hospitalization or an emergency department visit (observation for >6 hours) was significantly lower among those who received a single dose of pegylated interferon lambda than among those who received placebo. (Funded by FastGrants and others; TOGETHER ClinicalTrials.gov number, NCT04727424.).

Effect of Early Treatment with Ivermectin among Patients with Covid-19.

BACKGROUND: The efficacy of ivermectin in preventing hospitalization or extended observation in an emergency setting among outpatients with acutely symptomatic coronavirus disease 2019 (Covid-19), the disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is unclear. METHODS: We conducted a double-blind, randomized, placebo-controlled, adaptive platform trial involving symptomatic SARS-CoV-2-positive adults recruited from 12 public health clinics in Brazil. Patients who had had symptoms of Covid-19 for up to 7 days and had at least one risk factor for disease progression were randomly assigned to receive ivermectin (400 µg per kilogram of body weight) once daily for 3 days or placebo. (The trial also involved other interventions that are not reported here.) The primary composite outcome was hospitalization due to Covid-19 within 28 days after randomization or an emergency department visit due to clinical worsening of Covid-19 (defined as the participant remaining under observation for >6 hours) within 28 days after randomization. RESULTS: A total of 3515 patients were randomly assigned to receive ivermectin (679 patients), placebo (679), or another intervention (2157). Overall, 100 patients (14.7%) in the ivermectin group had a primary-outcome event, as compared with 111 (16.3%) in the placebo group (relative risk, 0.90; 95% Bayesian credible interval, 0.70 to 1.16). Of the 211 primary-outcome events, 171 (81.0%) were hospital admissions. Findings were similar to the primary analysis in a modified intention-to-treat analysis that included only patients who received at least one dose of ivermectin or placebo (relative risk, 0.89; 95% Bayesian credible interval, 0.69 to 1.15) and in a per-protocol analysis that included only patients who reported 100% adherence to the assigned regimen (relative risk, 0.94; 95% Bayesian credible interval, 0.67 to 1.35). There were no significant effects of ivermectin use on secondary outcomes or adverse events. CONCLUSIONS: Treatment with ivermectin did not result in a lower incidence of medical admission to a hospital due to progression of Covid-19 or of prolonged emergency department observation among outpatients with an early diagnosis of Covid-19. (Funded by FastGrants and the Rainwater Charitable Foundation; TOGETHER ClinicalTrials.gov number, NCT04727424.).

Severe hypoglycaemia among patients with type 2 diabetes requiring emergency hospital admission: The Hypoglycaemia In Portugal Observational Study-Emergency Room (HIPOS-ER).

AIMS: To analyse the prevalence of severe hypoglycaemia in patients with type 2 diabetes (T2DM) treated with antihyperglycaemic agents (AHA) and requiring emergency room (ER) assistance, and to analyse the prevalence according to type of AHA therapy. METHODS: The present study, the Hypoglycaemia In Portugal Observational Study-Emergency Room (HIPOS-ER), was a cross-sectional, observational, multicentre, nationwide study, with specific hypoglycaemia source data collection. RESULTS: Within the study period, a total of 425 706 admissions were recorded in the ERs of participating hospitals. The prevalence of severe hypoglycaemic episodes in patients with T2DM was 0.074%. In all, 238 patients were included, more than half of whom were on insulin-based therapy (55.0%) and a third of whom (31.5%) were on oral secretagogue-based therapy. In 61.2% of patients primary care was the main diabetes care setting. The median patient age was 77.5 years and the mean duration of diabetes was 19 years. Missing a meal or low carbohydrate meal content was the most frequent cause of hypoglycaemia (55.9%) and the most frequent triggers for seeking emergency assistance were pre-syncope (19.2%) and transient loss of consciousness (17.4%). A total of 44.1% of patients were hospitalized for a median of 5.1 days. Patients in the secretagogue group were admitted to hospital more often than patients in the insulin group (70.7% vs 29.0%; P < .001). Nine patients died. CONCLUSIONS: These findings confirm that severe hypoglycaemia in patients with T2DM requiring ER assistance occurs mainly in those on insulin- and secretagogue-based therapies and is associated with a significant medical burden. Antidiabetic therapy should be individualized to minimize the risk of severe iatrogenic hypoglycaemia, and any intervention to this end should always involve primary care stakeholders.

Late positive slow waves as markers of chunking during encoding.

Electrophysiological markers of chunking of words during encoding have mostly been shown in studies that present pairs of related stimuli. In these cases it is difficult to disentangle cognitive processes that reflect distinctiveness (i.e., conspicuous items because they are related), perceived association between related items and unified representations of various items, or chunking. Here, we propose a paradigm that enables the determination of a separate Event-related Potential (ERP) marker of these cognitive processes using sequentially related word triads. Twenty-three young healthy individuals viewed 80 15-word lists composed of unrelated items except for the three words in the middle serial positions (triads), which could be either unrelated (control list), related perceptually, phonetically or semantically. ERP amplitudes were measured at encoding of each one of the words in the triads. We analyzed two latency intervals (350-400 and 400-800 ms) at midline locations. Behaviorally, we observed a progressive facilitation in the immediate free recall of the words in the triads depending on the relations between their items (control < perceptual < phonetic < semantic), but only semantically related items were recalled as chunks. P300-like deflections were observed for perceptually deviant stimuli. A reduction of amplitude of a component akin to the N400 was found for words that were phonetically and semantically associated with prior items and therefore were not associated to chunking. Positive slow wave (PSW) amplitudes increased as successive phonetically and semantically related items were presented, but they were observed earlier and were more prominent at Fz for semantic associates. PSWs at Fz and Cz also correlated with recall of semantic word chunks. This confirms prior claims that PSWs at Fz are potential markers of chunking which, in the proposed paradigm, were modulated differently from the detection of deviant stimuli and of relations between stimuli.

Serological and direct diagnosis of Helicobacter pylori in gastric carcinoma: a case-control study.

This study evaluated the sensitivity of serological and direct methods for the diagnosis of Helicobacter pylori infection in 127 patients with gastric carcinoma and in 127 controls without this disease, matched for age and sex. Antral and oxyntic mucosal specimens were obtained from all patients, at operation in patients with gastric carcinoma and at endoscopy from controls. The urease test, microscopy of stained smears and culture for H. pylori were performed on all specimens. Sera from all patients were tested for antibodies to H. pylori by a highly sensitive and specific IgG-ELISA. Culture, urease test, stained smear and ELISA were significantly less sensitive in the patients with gastric carcinoma than in control subjects. However, the combination of several methods improved the diagnosis of H. pylori infection in the gastric carcinoma group. Infection was significantly more frequent in the gastric carcinoma patients than in the controls. H. pylori infection was associated with an increased risk of developing gastric carcinoma.

Gastric epithelial cell proliferation and cagA status in Helicobacter pylori gastritis at different gastric sites.

OBJECTIVE: Helicobacter pylori infection causes hyperproliferation which is believed to predispose to the development of gastric carcinoma. The aim of this study was to analyze epithelial cell proliferation topographically in H. pylori gastritis in relationship to cagA status. MATERIAL AND METHODS: The proliferative index (PI: Ki-67-labeled nuclei/total number of foveolar nuclei) was determined in gastric mucosa biopsies taken at the antrum (lesser and greater curvatures), incisura, and corpus (greater curvature) from 78 patients with H. pylori gastritis and 20 H. pylori-negative patients. H. pylori and cagA status were determined by polymerase chain reaction (PCR) and serology. RESULTS: PIs were significantly higher in H. pylori- and cagA-positive patients, in comparison with H. pylori- and cagA-negative patients, at all sites (p

Apoptosis in Helicobacter pylori gastritis is related to cagA status.

BACKGROUND: Helicobacter pylori infection increases gastric epithelial cell apoptosis; however, the influence of cagA status is still controversial. We aimed to investigate if cagA status is related to apoptosis in H. pylori gastritis at different anatomic sites of the gastric mucosa. MATERIALS AND METHODS: We studied by immunohistochemistry (streptavidin-biotin method) pro-apoptotic (Bax and Bak) and antiapoptotic (Bcl-2 and Bcl-x) proteins expression, scored from 0 to 4, in gastric biopsies, at the antrum (lesser and greater curvatures), incisura, and corpus (greater curvature) from 50 patients with H. pylori gastritis (22 males, 28 females, median age 40 years) and eight non-infected patients (6 males, median age 39.6 years). H. pylori and cagA status were determined by polymerase chain reaction. RESULTS: Apoptotic proteins were expressed in a granular pattern, in the cytoplasm of foveolar cells; Bax and Bak expression was higher than Bcl-2 and Bcl-x in most cases and was significantly higher in patients infected by cagA-positive strains than in those infected by cagA-negative strains (p = .001). Bak expression was higher at the lesser curvature (antrum and incisura) than in the other regions (p = .002) and was correlated with atrophy. Anti-apoptotic proteins were significantly more expressed at the antral lesser curvature than in the other regions of the stomach (Bcl-2: p = .02; Bcl-x: p < .001). CONCLUSIONS: Infection with cagA-positive strains is significantly associated with overexpression of pro-apoptotic proteins in the gastric mucosa, mainly at the antral lesser curvature, which may have a role on atrophy development. Anti-apoptotic proteins were also overexpressed at the lesser curvature, which may occur to keep epithelial cell turnover or might be related to malignant transformation.

Tratamento da leucemia de células cabeludas com interferon alfa / Treatment of hairy cell leukemia with alpha interferon

O presente trabalho descreve cinco casos de pacientes portadores de leucemia de células cabeludas (LCC) ou tricoleucemia, que foram tratados com interferon alfa, um modificador da resposta biológica com grande atividade nesta doença crônica linfoproliferativa. Novos conceitos considerando seu uso como terapêutica de primeira linha säo discutidos, bem como aspectos marcantes de sua etiopatogenia, diagnóstico clínico-laboratorial e histopatológico.