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

Carotid endarterectomy: Results and long-term follow-up of a single institution

Objectives : To document our experiences, technical procedure and outcomes of carotid endarterectomy (CEA) in patients with symptomatic carotid stenosis. Material and Methods : A total of 49 consecutive patients underwent 53 CEAs (three bilateral, one redo) for severe carotid artery stenosis. There were 39 males and 10 females, with mean age of 63 years. All patients underwent neck Doppler, computed tomography/magnetic resonance angiography/digital substraction angiography and a detailed cardiological evaluation. Antiplatelet drugs were continued perioperatively. Surgery was performed under general anesthesia with propofol cerebral protection, mild hypothermia and continuous electroencephalogram monitoring. The procedure was done under microscope and closure was done using 6-0 prolene. Clinical and radiological follow-up was done. Results : Our mean follow-up was 4.69 years. All patients underwent primary suturing except one redo CEA done with venous patch graft. Three patients required intraoperative shunting. One patient died secondary to myocardial infarction peroperatively prior to carotid manipulation. One patient had stroke within 6 h, secondary to operative site intraluminal thrombus and was re-explored. Two patients had transient postoperative hemiparesis and aphasia while two patients had altered sensorium, all self-limiting, with normal imaging. One patient developed temporary twelfth-nerve paresis. One patient had persistent transient ischemic attack on the follow-up. Thus, the perioperative mortality rate was 1.89% and stroke rate was 1.89%. Conclusions : CEA for severe carotid stenosis is a safe procedure with good protection from ischemic events. Detailed preoperative cardiac evaluation and appropriate patient selection is essential

Synthesis of R(+)-α-lipoic acid

An efficient enantiospecific synthesis of R(+)-α-lipoic acid (1) a prosthetic group and a vital cofactor in -α-keto acids decarboxylation is described

Discovery of a Highly Selective JAK2 Inhibitor, BMS-911543, for the Treatment of Myeloproliferative Neoplasms

JAK2 kinase inhibitors are a promising new class of agents for the treatment of myeloproliferative neoplasms and have potential for the treatment of other diseases possessing a deregulated JAK2-STAT pathway. X-ray structure and ADME guided refinement of C-4 heterocycles to address metabolic liability present in dialkylthiazole <b>1</b> led to the discovery of a clinical candidate, BMS-911543 (<b>11</b>), with excellent kinome selectivity, <i>in vivo</i> PD activity, and safety profile

Effect of Antiplatelet Therapy on Survival and Organ Support–Free Days in Critically Ill Patients With COVID-19

International audienc