Remarkable resolution of COVID-19-associated cerebral vasculitis with methylprednisolone

International audienc

Vascular Abnormalities in the Neck Associated with Intracranial Aneurysms

ABSTRACT In 102 cases of ruptured intracranial aneurysms, the cervical as well as the cranial areas were explored by angiography. Loops in the course of the cervical vessels were present in 28 patients; features of fibromuscular dysplasia were present in 31 patients; and in 50 patients, no abnormalities were observed. In 7 patients, both cervical anomalies were present. Loops were associated with single aneurysms (95%), located primarily on the anterior communicating artery (76%), predominantly in men (M/F = 1.6). Aneurysms with fibromuscular dysplasia affected women more than men (F/M = 7), were frequently multiple (58%), and were located mainly on the intracranial part of the internal carotid and vertebral arteries (51%). These data suggest new concepts of aneurysm formation from inherited diseases and should permit the detection of some aneurysms before rupture

Effects of antibiotic prophylaxis on ventilator-associated pneumonia in severe traumatic brain injury. A post hoc analysis of two trials

International audiencePurpose To investigate the role of antibiotic prophylaxis (AP) in the incidence of ventilator-associated pneumonia (VAP) in patients suffering from traumatic brain injury (TBI). Materials and methods This post hoc analysis was conducted based on data from 2 multicentre double-blind studies that aimed to prevent VAP using hydrocortisone or povidone iodine. Data from TBI patients were extracted and pooled. Patients were classified into 2 groups those who received an AP (AP group) and those who did not (control group). Results 295 patients were included (AP group, n = 146; control group, n = 149). The incidence of VAP was 145 (49%). VAP incidence was lower in the AP group (39% vs 59%, Relative Risk = 0.33, 95%CI, 0.19–0.56, p = 0.001). Time to VAP occurrence was delayed (Hazard Ratio = 0.50, 95%CI 0.36–0.69, p 2 and ≤ 5 days) was lower in the AP group (10% vs 32%; p 5 days) did not differ (AP group 29% vs control group 28%; p = 0.811). Length of stay and mortality did not differ between the 2 groups. Conclusions Early use of AP delayed and may prevent the occurrence of VAP in severe TBI patients but did not change length of stay or mortality. © 2018 Elsevier Inc

Characteristics and outcome of varicella-zoster virus central nervous system infections in adults

International audienceWe conducted an observational retrospective study of all adults hospitalized for documented varicella-zoster virus (VZV) meningitis or encephalitis during years 2000-2015 in one referral centre. Thirty-six patients (21 males, 15 females) were included, with meningitis (n = 21), or meningoencephalitis (n = 15). Median age was 51 years [interquartile range, 35-76], and 6 patients (17%) were immunocompromised. Aciclovir was started in 32 patients (89%), with a median dose of 11 mg/kg/8 h [10-15]. No patient died, but 12 (33%) had neurological sequelae at discharge. Age was the only variable associated with adverse outcome (OR 1.98 [1.17-3.35] per 10-year increment, P = 0.011)

Molecular networking for drug toxicities studies: The case of hydroxychloroquine in covid-19 patients

International audienceUsing drugs to treat COVID-19 symptoms may induce adverse effects and modify patient outcomes. These adverse events may be further aggravated in obese patients, who often present different illnesses such as metabolic-associated fatty liver disease. In Rennes University Hospital, several drug such as hydroxychloroquine (HCQ) have been used in the clinical trial HARMONICOV to treat COVID-19 patients, including obese patients. The aim of this study is to determine whether HCQ metabolism and hepatotoxicity are worsened in obese patients using an in vivo/in vitro approach. Liquid chromatography high resolution mass spectrometry in combination with untargeted screening and molecular networking were employed to study drug metabolism in vivo (patient’s plasma) and in vitro (HepaRG cells and RPTEC cells). In addition, HepaRG cells model were used to reproduce pathophysiological features of obese patient metabolism, i.e., in the condition of hepatic steatosis. The metabolic signature of HCQ was modified in HepaRG cells cultured under a steatosis condition and a new metabolite was detected (carboxychloroquine). The RPTEC model was found to produce only one metabolite. A higher cytotoxicity of HCQ was observed in HepaRG cells exposed to exogenous fatty acids, while neutral lipid accumulation (steatosis) was further enhanced in these cells. These in vitro data were compared with the biological parameters of 17 COVID-19 patients treated with HCQ included in the HARMONICOV cohort. Overall, our data suggest that steatosis may be a risk factor for altered drug metabolism and possibly toxicity of HCQ. © 2021 by the authors. Licensee MDPI, Basel, Switzerland

Impact des échanges plasmatiques au cours des hémorragies alvéolaires graves associées aux vascularites associées aux ANCA

International audienceIntroductionLes hémorragies intra-alvéolaires (HIA) sont responsables d’une mortalité élevée au cours des vascularites associées aux ANCA (VAA) [1]. Les échanges plasmatiques (EP) ont été proposés en traitement d’induction des VAA graves en association au traitement standard, en particulier pour les glomérulonéphrites rapidement progressives et les HIA graves. L’essai PEXIVAS n’a pas montré de supériorité des EP sur la mortalité chez les patients présentant une VAA sévère avec insuffisance rénale et/ou HIA [2]. Néanmoins, seuls 27 % des patients inclus avaient une HIA et moins de 9 % d’entre eux avaient une HIA sévère définie par une SpO2 < 85 % en air ambiant ou le recours à la ventilation mécanique. Cette population de patients graves pourrait bénéficier des EP comme l’ont suggéré des résultats ancillaires de l’essai PEXIVAS, avec une mortalité à 90 jours de 16,1 % dans le groupe EP versus 30 % dans le groupe sans EP [3]. L’objectif de cette étude est d’étudier l’effet des EP sur la mortalité des patients hospitalisés pour une VAA avec HIA grave.Patients et méthodesIl s’agit d’une étude rétrospective multicentrique française incluant des patients ayant présenté une HIA grave au cours d’une poussée de granulomatose avec polyangéite (GPA) ou polyangéite microscopique (PM) au cours des 10 dernières années. Le critère de jugement principal était la mortalité à 30 jours (J30). Les analyses univariées ont été réalisées avec un test du χ2 ou de Fisher pour les variables catégorielles, ou un test de Mann-Whitney pour les variables quantitatives. L’analyse du critère de jugement principal a été réalisée par un modèle de Cox pour prendre en compte les données censurées, avec ajustement sur les facteurs de confusion définis a priori.RésultatsNous avons inclus 186 patients issus de 40 centres (88 GPA et 91 PM, âge médian 66 ans [53; 75], 46,7 % d’hommes). Les ANCA étaient positifs chez tous les patients (anti-PR3 46,2 %, anti-MPO 54,3 %). En plus du traitement standard, 144 patients ont reçu des EP (77,4 %) et 42 n’en ont pas reçu (22,6 %). Les patients traités par EP étaient plus sévères que les patients sans EP avec une atteinte rénale significativement plus fréquente dans le groupe EP (94,2 vs. 84,6 %, p < 0,05) et un débit de filtration glomérulaire significativement inférieur chez les patients traités par EP (DFG médian à 25 mL/min/1,73 m2 vs 41 mL/min/1,73 m2, p < 0,05). La ventilation mécanique n’était pas significativement plus utilisée dans le groupe EP (52,1 % vs 41,5 % p = 0,23). Les patients du groupe EP recevaient significativement plus souvent des bolus de méthylprednisolone (97,2 % vs 88,1 %, p < 0,05) et du cyclophosphamide (78,5 % vs 54,8 %, p < 0,01). Le score BVAS était en revanche comparable entre les groupes (23,1 dans le groupe EP vs 21,4 dans le groupe sans EP, p = 0,18).Sans ajustement sur les facteurs associés à l’utilisation des EP, la mortalité à J30 était comparable entre les 2 groupes (14,1 % vs 14,3 %, p = 0,97), avec un hazard ratio pour la mortalité à J30 de l’admission en réanimation à 1,2 [IC95 % 0,4–3,1], p = 0,8), de même que la mortalité à J90, J180 et aux dernières nouvelles. Après ajustement sur les facteurs de confusion (valeur maximale de créatininémie, âge, score de gravité à l’admission et nécessité d’une ventilation invasive), la réalisation d’EP n’était toujours pas associée à la survie dans cette étude (HR 0,9 [IC95 % 0,3–2,4], p = 0,8).ConclusionDans cette large étude, nous observons que les EP restent largement utilisés en France dans les HIA sévères au cours des VAA. Cette première analyse avec ajustement ne retrouve pas d’impact des EP sur la mortalité précoce, mais une analyse avec émulation est en cours pour préciser ces résultats

Personalized Antibodies for Gastroesophageal Adenocarcinoma (PANGEA): A Phase II Study Evaluating an Individualized Treatment Strategy for Metastatic Disease

The one-year and median overall survival (mOS) rates of advanced gastroesophageal adenocarcinomas (GEA) are ∼50% and <12 months, respectively. Baseline spatial and temporal molecular heterogeneity of targetable alterations may be a cause of failure of targeted/immunooncologic therapies. This heterogeneity, coupled with infrequent incidence of some biomarkers, has resulted in stalled therapeutic progress. We hypothesized that a personalized treatment strategy, applied at first diagnosis then serially over up to three treatment lines using monoclonal antibodies combined with optimally sequenced chemotherapy, could contend with these hurdles. This was tested using a novel clinical expansion-platform type II design with a survival primary endpoint. Of 68 patients by intention-to-treat, the one-year survival rate was 66% and mOS was 15.7 months, meeting the primary efficacy endpoint (one-sided P = 0.0024). First-line response rate (74%), disease control rate (99%), and median progression-free survival (8.2 months) were superior to historical controls. The PANGEA strategy led to improved outcomes warranting a larger randomized study. SIGNIFICANCE: This study highlights excellent outcomes achieved by individually optimizing chemotherapy, biomarker profiling, and matching of targeted therapies at baseline and over time for GEA. Testing a predefined treatment strategy resulted in improved outcomes versus historical controls. Therapeutic resistance observed in correlative analyses suggests that dual targeted inhibition may be beneficial.This article is highlighted in the In This Issue feature, p. 211

Comparative immune profiling of acute respiratory distress syndrome patients with or without SARS-CoV2 infection

International audienceAcute respiratory distress syndrome (ARDS) is the main complication of coronavirus disease 2019 (COVID-19), requiring admission to the intensive care unit (ICU). Despite extensive immune profiling of COVID-19 patients, to what extent COVID-19-associated ARDS differs from other causes of ARDS remains unknown. To address this question, here, we build 3 cohorts of patients categorized in COVID-19ARDS, COVID-19ARDS, and COVID-19ARDS, and compare, by high-dimensional mass cytometry, their immune landscape. A cell signature associating S100A9/calprotectin-producing CD169 monocytes, plasmablasts, and Th1 cells is found in COVID-19ARDS, unlike COVID-19ARDS patients. Moreover, this signature is essentially shared with COVID-19ARDS patients, suggesting that severe COVID-19 patients, whether or not they experience ARDS, display similar immune profiles. We show an increase in CD14HLA-DR and CD14CD16 monocytes correlating to the occurrence of adverse events during the ICU stay. We demonstrate that COVID-19-associated ARDS displays a specific immune profile and may benefit from personalized therapy in addition to standard ARDS management