14 research outputs found
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
Infiltrating and peripheral immune cell analysis in advanced gastric cancer according to the Lauren classification and its prognostic significance
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Diagnosis and treatment of blunt thoracic aortic injuries: changing perspectives
The diagnosis and management of blunt thoracic aortic injuries has undergone many significant changes over the last decade. The present study compares clinical practices and results between an earlier prospective multicenter study by the American Association for the Surgery of Trauma completed in 1997 (AAST1) and a new similar study completed in 2007 (AAST2).
The AAST1 study included 274 patients from 50 participating centers over a period of 30 months. The AAST2 study included 193 patients from 18 centers, over a period of 26 months. The comparisons between the two studies included the method of definitive diagnosis of the aortic injury [computed tomography (CT) scan, aortography, transesophageal echocardiogram (TEE) or magnetic resonance imaging], the method of definitive aortic repair (open repair vs. endovascular repair, clamp and sew vs. bypass techniques), the time from injury to procedure (early vs. delayed repair), and outcomes (survival, procedure-related paraplegia, other complications).
There was a major shift of the method of definitive diagnosis of the aortic injury, from aortography in the AAST1 to CT scan in AAST2, and a nearly complete elimination of aortography and TEE in the AAST2 study. In the AAST2 study the diagnosis was made by CT scan in 93.3%, aortography in 8.3%, and TEE in 1.0% of patients when compared with 34.8%, 87.0%, and 11.9%, respectively, in the AAST1 study (p < 0.001). The mean time from injury to aortic repair increased from 16.5 hours in the AAST1 study to 54.6 hours in the AAST2 study (p < 0.001). In the AAST1 study, all patients were managed with open repair, whereas in the AAST2 study only 35.2% were managed with open repair and the remaining 64.8% were managed with endovascular stent-grafts. In the patients managed with open repair, the use of bypass techniques increased from 64.7% to 83.8%. The overall mortality, excluding patients in extremis, decreased significantly from 22.0% to 13.0% (p = 0.02). Also, the incidence of procedure-related paraplegia in patients with planned operation, decreased from 8.7% to 1.6% (p = 0.001). However, the incidence of early graft-related complications increased from 0.5% in the AAST1 to 18.4% in the AAST2 study.
Comparison between the two AAST studies in 1997 and 2007 showed a major shift in the diagnosis of the aortic injury, with the widespread use of CT scan and the almost complete elimination of aortography and TEE. The concept of delayed definitive repair has gained wide acceptance. Endovascular repair has replaced open repair to a great extent. These changes have resulted in a major reduction of mortality and procedure-related paraplegia but also a significant increase of early graft-related complications
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Operative repair or endovascular stent graft in blunt traumatic thoracic aortic injuries: results of an American Association for the Surgery of Trauma Multicenter Study
The purpose of this American Association for the Surgery of Trauma multicenter study is to assess the early efficacy and safety of endovascular stent grafts (SGs) in traumatic thoracic aortic injuries and compare outcomes with the standard operative repair (OR).
Prospective, multicenter study. Data for the following were collected: age, blood pressure, and Glasgow Coma Scale (GCS) at admission, type of aortic injury, injury severity score, abbreviate injury scale (AIS), transfusions, survival, ventilator days, complications, and intensive care unit and hospital days. The outcomes between the two groups (open repair or SG) were compared, adjusting for presence of critical extrathoracic trauma (head, abdomen, or extremity AIS >3), GCS score 55 years. Separate multivariable analysis was performed, one for patients without and one for patients with associated critical extrathoracic injuries (head, abdomen, or extremity AIS >3), to compare the outcomes of the two therapeutic modalities adjusting for hypotension, GCS score 55 years.
One hundred ninety-three patients met the criteria for inclusion. Overall, 125 patients (64.9%) were selected for SG and 68 (35.2%) for OR. SG was selected in 71.6% of the 74 patients with major extrathoracic injuries and in 60.0% of the 115 patients with no major extrathoracic injuries. SG patients were significantly older than OR patients. Overall, 25 patients in the SG group (20.0%) developed 32 device-related complications. There were 18 endoleaks (14.4%), 6 of which needed open repair. Procedure-related paraplegia developed in 2.9% in the OR and 0.8% in the SG groups (p = 0.28). Multivariable analysis adjusting for severe extrathoracic injuries, hypotension, GCS, and age, showed that the SG group had a significantly lower mortality (adjusted odds ratio: 8.42; 95% CI: [2.76-25.69]; adjusted p value <0.001), and fewer blood transfusions (adjusted mean difference: 4.98; 95% CI: [0.14-9.82]; adjusted p value = 0.046) than the OR group. Among the 115 patients without major extrathoracic injuries, higher mortality and higher transfusion requirements were also found in the OR group (adjusted odds ratio for mortality: 13.08; 95% CI [2.53-67.53], adjusted p value = 0.002 and adjusted mean difference in transfusion units: 4.45; 95% CI [1.39-7.51]; adjusted p value = 0.004). Among the 74 patients with major extrathoracic injuries, significantly higher mortality and pneumonia rate were found in the OR group (adjusted p values 0.04 and 0.03, respectively). Multivariate analysis showed that centers with high volume of endovascular procedures had significantly fewer systemic complications (adjusted p value 0.001), fewer local complications (adjusted p value p = 0.033), and shorter hospital lengths of stay (adjusted p value 0.005) than low-volume centers.
Most surgeons select SG for traumatic thoracic aortic ruptures, irrespective of associated injuries, injury severity, and age. SG is associated with significantly lower mortality and fewer blood transfusions, but there is a considerable risk of serious device-related complications. There is a major and urgent need for improvement of the available endovascular devices