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

Transjugular intrahepatic portosystemic shunt for the management of acute variceal hemorrhage.

International audienceAcute variceal hemorrhage, a life-threatening condition that requires a multidisciplinary approach for effective therapy, is defined as visible bleeding from an esophageal or gastric varix at the time of endoscopy, the presence of large esophageal varices with recent stigmata of bleeding, or fresh blood visible in the stomach with no other source of bleeding identified. Transfusion of blood products, pharmacological treatments and early endoscopic therapy are often effective; however, if primary hemostasis cannot be obtained or if uncontrollable early rebleeding occurs, transjugular intrahepatic portosystemic shunt (TIPS) is recommended as rescue treatment. The TIPS represents a major advance in the treatment of complications of portal hypertension. Acute variceal hemorrhage that is poorly controlled with endoscopic therapy is generally well controlled with TIPS, which has a 90% to 100% success rate. However, TIPS is associated with a mortality of 30% to 50% in such a setting. Emergency TIPS should be considered early in patients with refractory variceal bleeding once medical treatment and endoscopic sclerotherapy failure, before the clinical condition worsens. Furthermore, admission to specialized centers is mandatory in such a setting and regional protocols are essential to be organized effectively. This review article discusses initial management and then focuses on the specific role of TIPS as a primary therapy to control acute variceal hemorrhage, particularly as a rescue therapy following failure of endoscopic approaches

Optimal Duration of MRI Follow-up to Safely Identify Middle Ear Residual Cholesteatoma

International audienceBackground and purpose: Previous studies have demonstrated the usefulness of non-EPI DWI for detection of residual cholesteatoma. However, limited data are available to determine the suitable duration of imaging follow-up after a first MR imaging with normal findings has been obtained. The present study aimed to determine the optimal duration of non-EPI DWI follow-up for residual cholesteatoma.Materials and methods: A retrospective, monocentric study was performed between 2013 and 2019 and included all participants followed up after canal wall up tympanoplasty with at least 2 non-EPI DWI examinations performed on the same 1.5T MR imaging scanner. MR images were reviewed independently by 2 radiologists. Sensitivity and specificity values were calculated as a function of time after the operation. Receiver operating characteristic curves were analyzed to determine the optimal follow-up duration.Results: We analyzed 47 MRIs from 17 participants. At the end of the individual follow-up period, a residual cholesteatoma had been found in 41.1% of cases. The follow-up duration ranged from 20 to 198 months (mean, 65.9 [SD, 43.9] months). Participants underwent between 2 and 5 non-EPI DWI examinations. Analyses of the receiver operating characteristic curves revealed that the optimal diagnostic value of non-EPI DWI occurred 56 months after the operation when the first MR imaging performed a mean of 17.3 (SD, 6.8) months after the operation had normal findings (sensitivity = 0.71; specificity = 0.7, Youden index = 0.43).Conclusions: Repeat non-EPI DWI is required to detect slow-growing middle ear residual cholesteatomas. We, therefore, recommend performing non-EPI DWI for at least the first 5 years after the initial operation

Macroscopic heterogeneity of liver fat: an MR-based study in type-2 diabetic patients.

International audienceOBJECTIVE: To assess the heterogeneity of liver fat deposition with MR of the liver in type-2 diabetic (T2D) patients. METHODS: We enrolled 121 consecutive T2D patients. The reference standard was 3.0-T (1)H-MR spectroscopy. Hepatic steatosis was defined as liver fat content (LFC) ≥5.56 %. A triple-echo gradient-echo sequence corrected for T1 recovery and T2* decay was used to calculate LFC in left and right livers and hepatic segments. Analyses were performed using a linear mixed model. RESULTS: Fifty-nine (48.8 %) patients had liver steatosis, whereas 62 (51.2 %) did not. Steatosis was greater in the right than in the left liver (P < 0.0001) [mean difference: 1.32 % (range: 0.01-8.75 %)]. In seven patients (5.8 %), LFC was <5.56 % in one side of the liver, whereas it was ≥5.56 % in the other. Steatosis of the left and right liver was heterogeneous at the segmental level in both non-steatotic (P < 0.001 and P < 0.0001 respectively) and steatotic (P < 0.0001 and P = 0.0002 respectively) patients [mean maximum difference: 3.98 % (range: 0.74-19.32 %)]. In 23 patients (19 %), LFC was <5.56 % in one segment, whereas it was ≥5.56 % in at least one other. CONCLUSION: Overall, the mean segmental/lobar variability of steatosis is low. However, segmental variability can sometimes lead to a misdiagnosis. KEY POINTS: There is a need for methods quantifying steatosis over a large region. Steatosis is usually greater in the right than left lobe of the liver. Steatosis within both left and right hepatic lobes is segmentally heterogeneous. Segmental variability of steatosis can result in misdiagnosis

A symptomatic atherosclerotic persistent pharyngo-hyo-stapedial artery: Treatment management and embryological considerations

International audienceThe stapedial artery (SA) is an embryonic vessel connecting the internal carotid artery (ICA) to the branches of the future external carotid artery (ECA). It passes through the primordium of the stapes that progressively develops around the SA. Normally, SA disappears during the tenth week in utero. Approximately 0.4% of the population can have a persistent SA. It can persist as four types of embryological variations, of which the pharyngo-hyo-stapedial variant has been rarely described before. We reported a case of a 61-year-old woman presented with transient ischemic attacks (TIAs). Computed tomography angiography showed an unusual “duplicated” aspect of the left ICA. Digital subtraction angiography depicted a persistent pharyngo-hyo-stapedial artery with an atherosclerotic wall and was considered the cause of the TIAs. After failure of the antiplatelet therapy in preventing recurrent TIAs, stenting of the artery was planned and successfully performed. Patient was asymptomatic during 12-month follow-up. The pharyngo-hyo-stapedial artery is a very rare variation in which the SA is supplied by the inferior tympanic (rising from the ascending pharyngeal artery) and the hyoid artery (rising from the ICA). To our knowledge, this is a unique case of a pharyngo-hyo-stapedial artery in a patient presenting associated ischemic symptoms. Radiological and embryological findings are discussed

Bronchopulmonary dysplasia in neonates born to mothers with preeclampsia: Impact of small for gestational age.

BACKGROUND AND OBJECTIVES:Small for gestational age and preeclampsia have both been described as risk factors for bronchopulmonary dysplasia in preterm neonates, but their respective role in the occurrence of bronchopulmonary dysplasia is debated. We evaluated the relation between small for gestational age and bronchopulmonary dysplasia in neonates born to mothers with preeclampsia. We hypothesized that low birth weight is still associated with bronchopulmonary dysplasia in this homogeneous population. METHODS:Retrospective single-center cohort study including 141 neonates born between 24 and 30 weeks' gestation to mothers with preeclampsia. The main outcome measure was moderate to severe bronchopulmonary dysplasia at 36 weeks' postmenstrual age. Neonates born small for gestational age (birthweight < 10th percentile on the AUDIPOG curves) were compared to those with appropriate birthweight for gestational age by bivariable analyses and logistic regression models, estimating odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS:Bronchopulmonary dysplasia rates were 61.5% (32/52) and 27.4% (20/73) for small for gestational age and appropriate birthweight for gestational age neonates (p < .001). On adjustment for gestational age and other confounding factors, the risk of moderate to severe bronchopulmonary dysplasia was greater for small for gestational age than appropriate birthweight for gestational age neonates (adjusted OR = 5.9, 95% CI [2.2-15.4]), as was the composite outcome death or moderate to severe bronchopulmonary dysplasia (adjusted OR = 4.7, 95% CI [1.9-11.3]). CONCLUSIONS:Small for gestational age was associated with bronchopulmonary dysplasia in very preterm neonates born to mothers with preeclampsia. REGISTRATION NUMBER:CNIL no. 1747084