Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Les facteurs limitant la gradation du risque de lésions du pied diabétique en médecine générale (étude qualitative à partir de 28 entretiens auprès de médecins généralistes installés dans le Bas-Rhin)

STRASBOURG-Medecine (674822101) / SudocSudocFranceF

Diabètes du nouveau-né et du nourrisson

Le diabète le plus fréquemment rencontré chez les jeunes enfants est le diabète sucré de type 1. Il est la conséquence de la destruction des cellules b du pancréas par un processus auto-immun. Il se traduit par un taux de glucose sanguin supérieur à la normal et un syndrome plolyuro-polydipsique. Les diabètes néonatals et les diabètes MODY peuvent également survenir très tôt dans la vie. Le diabète gestationnel est diagnostiqué pour la 1ère fois au cours de la grossesse et peut avoir des conséquences chez le nouveau-né. La prise en charge du diabète de type 1 nécessite le recours à l'insuline. A cet âge les 2 schémas de traitement principaux sont le schéma à deux injections journalières ou le traitement par pompe à insuline. Le régime alimentaire est au moins aussi important que l'insulinothérapie dans l'équilibre d'un diabète. Cet équilibre est indispensable pour prévenir la survenue de complications à long terme. Les jeunes malades sont dépendants de leurs parents et incapables d'exprimer leur mal-être. L'exemple des nourrissons suivis à l'hôpital de clermont-Ferrand permet d'illustrer les différents aspects de la prise en charge.CLERMONT FD-BCIU-Santé (631132104) / SudocLYON1-BU Santé (693882101) / SudocSudocFranceF

Prognostic scores for colorectal liver metastasis: clinically important or an academic exercise?

AbstractObjectivesOver the last decade, various groups have proposed prognostic scoring systems for patients with colorectal liver metastasis (CLM) treated with hepatic resection. The aims of the current study were to evaluate the differences between and clinical importance of these prognostic scoring systems and to determine their clinical applicability.MethodsRelevant articles were reviewed from the published literature using the MEDLINE database. The search was performed using the keywords ‘colorectal cancer’, ‘metastases’, ‘liver resection’ and ‘hepatectomy’.ResultsTwelve prognostic scoring systems were identified from 1996 to 2009. Six of these originated from European institutions, three from Asian and three from North American centres. The median study sample was 288 patients (range 81–1568 patients) and median follow-up was 35 months (range 16–52 months). All studies were retrospective in nature and the numbers of groups proposed by the various scoring systems ranged from three to six. All the studies used the Cox proportional hazard model for multi-variable analysis.ConclusionsThere is no ‘ideal’ prognostic scoring system for the clinical management of patients with CLM for hepatic resection. These prognostic scoring systems are clinically relevant with respect to survival but have not been used for risk stratification in controversial areas such as the administration of chemotherapy or surveillance programmes

Current opinion on optimal treatment for colorectal cancer

The medical treatment of colorectal cancer (CRC) has evolved greatly in the last 10 years, involving complex combined chemotherapy protocols and, in more recent times, new biologic agents. Advances in adjuvant therapy have been limited to the addition of oxaliplatin and the substitution of oral fluoropyrimidine (e.g., capecitabine) for intravenous 5-fluorouracil with no evidence for improved outcome with biological agents. Clinical benefit from the use of the targeted monoclonal antibodies, bevacizumab, cetuximab and panitumumab, in the treatment of metastatic CRC is now well established, but the optimal timing of their use requires careful consideration to derive the maximal benefit. Evidence to date suggests potentially distinct roles for bevacizumab and EGF receptor-targeted biological agents (cetuximab and panitumumab) in the treatment of metastatic CRC. This article reviews the evidence in support of modern treatments for CRC and the decision-making behind the treatment choices, their benefits and toxicities.Timothy J Price, Eva Segelov, Matthew Burge, Daniel G Haller, Stephen P Ackland, Niall C Tebbutt, Christos S Karapetis, Nick Pavlakis, Alberto F Sobrero, David Cunningham and Jeremy D Shapir