is the seventh member of the family of coronaviruses that infect humans (1) and induces coronavirus disease 2019 (COVID-19). Human coronaviruses have neuroinvasive capacities and may be neurovirulent by two main mechanisms (2-4): viral replication into glial or neuronal cells of the brain or autoimmune reaction with a misdirected host immune response (5). Thus, a few cases of acute encephalitislike syndromes with human coronaviruses were reported in the past 2 decades (5-8). In regard to COVID-19, current data on central nervous system involvement are uncommon but growing (9-17), demonstrating the high frequency of neurologic symptoms. However, the delineation of a large cohort of confirmed brain MRI parenchymal signal abnormalities (excluding ischemic infarcts) related to COVID-19 has never been performed, and the underlying pathophysiologic mechanisms remain unknown. The purpose of the current study was to describe the neuroimaging findings (excluding ischemic infarcts) in patients with severe COVID-19 and report the clinicobiologic profile of these patients. Materials and Methods This retrospective observational national multicenter study was initiated by the French Society of Neuroradiology in collaboration with neurologists, intensivists, and infectious disease specialists and brought together 16 hospitals. The study was approved by the ethical committee of Strasbourg University Hospital (CE-2020-37) and was in accordance with the 1964 Helsinki Declaration and its later amendments. Because of the emergency in the context of the COVID-19 pandemic responsible for

ObjectiveTo describe neuroimaging findings and to report the epidemiological and clinical characteristics of COVID-19 patients with neurological manifestations.MethodsIn this retrospective multicenter study (10 Hospitals), we included 64 confirmed COVID-19 patients with neurologic manifestations who underwent a brain MRI.ResultsThe cohort included 43 men (67%), 21 women (33%), and the median age was 66 years (range: 20-92). 36 (56%) brain MRIs were considered abnormal, possibly related to SARS-CoV-2. Ischemic strokes (27%), leptomeningeal enhancement (17%), and encephalitis (13%) were the most frequent neuroimaging findings. Confusion (53%) was the most common neurological manifestation, following by impaired consciousness (39%), presence of clinical signs of corticospinal tract involvement (31%), agitation (31%), and headache (16%). The profile of patients experiencing ischemic stroke was different from the other patients with abnormal brain imaging since the former had less frequently acute respiratory distress syndrome (p=0·006) and more frequently corticospinal tract signs (p=0·02). Patients with encephalitis were younger (p=0·007), whereas agitation was more frequent for patients with leptomeningeal enhancement (p=0·009).ConclusionsCOVID-19 patients may develop a wide range of neurological symptoms, which can be associated with severe and fatal complications, such as ischemic stroke or encephalitis. Concerning the meningoencephalitis involvement, even if a direct effect of the virus cannot be excluded, the pathophysiology rather seems to involve an immune and/or inflammatory process given the presence of signs of inflammation in both cerebrospinal fluid and neuroimaging but the lack of virus in cerebrospinal fluid.

High-flow nasal oxygen may prevent postextubation respiratory failure in the intensive care unit (ICU). The combination of high-flow nasal oxygen with noninvasive ventilation (NIV) may be an optimal strategy of ventilation to avoid reintubation. OBJECTIVE To determine whether high-flow nasal oxygen with prophylactic NIV applied immediately after extubation could reduce the rate of reintubation, compared with high-flow nasal oxygen alone, in patients at high risk of extubation failure in the ICU. DESIGN, SETTING, AND PARTICIPANTS Multicenter randomized clinical trial conducted from April 2017 to January 2018 among 641 patients at high risk of extubation failure (ie, older than 65 years or with an underlying cardiac or respiratory disease) at 30 ICUs in France; follow-up was until April 2018. INTERVENTIONS Patients were randomly assigned to high-flow nasal oxygen alone (n = 306) or high-flow nasal oxygen alternating with NIV (n = 342) immediately after extubation. MAIN OUTCOMES AND MEASURESThe primary outcome was the proportion of patients reintubated at day 7; secondary outcomes included postextubation respiratory failure at day 7, reintubation rates up until ICU discharge, and ICU mortality. RESULTS Among 648 patients who were randomized (mean [SD] age, 70 [10] years; 219 women [34%]), 641 patients completed the trial. The reintubation rate at day 7 was 11.8% (95% CI, 8.4%-15.2%) (40/339) with high-flow nasal oxygen and NIV and 18.2% (95% CI, 13.9%-22.6%) (55/302) with high-flow nasal oxygen alone (difference, −6.4% [95% CI, −12.0% to −0.9%]; P = .02). Among the 11 prespecified secondary outcomes, 6 showed no significant difference. The proportion of patients with postextubation respiratory failure at day 7 (21% vs 29%; difference, −8.7% [95% CI, −15.2% to −1.8%]; P = .01) and reintubation rates up until ICU discharge (12% vs 20%, difference −7.4% [95% CI, −13.2% to −1.8%]; P = .009) were significantly lower with high-flow nasal oxygen and NIV than with high-flow nasal oxygen alone. ICU mortality rates were not significantly different: 6% with high-flow nasal oxygen and NIV and 9% with high-flow nasal oxygen alone (difference, −2.4% [95% CI, −6.7% to 1.7%]; P = .25). CONCLUSIONS AND RELEVANCEIn mechanically ventilated patients at high risk of extubation failure, the use of high-flow nasal oxygen with NIV immediately after extubation significantly decreased the risk of reintubation compared with high-flow nasal oxygen alone.

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Preoxygenation with high-flow therapy by nasal cannulae (HFNC) is now widespread in the intensive care unit (ICU). However, no large randomized study has assessed its relevance in non-severely hypoxemic patients. In a randomized controlled trial (PROTRACH study), we aimed to evaluate preoxygenation with HFNC vs. standard bagvalve mask oxygenation (SMO) in non-severely hypoxemic patients during rapid sequence intubation (RSI) in the ICU. Methods: Randomized controlled trial including non-severely hypoxemic patients requiring intubation in the ICU. Patients received preoxygenation by HFNC or SMO during RSI. HFNC was maintained throughout the intubation procedure whereas SMO was removed to perform laryngoscopy. The primary outcome was the lowest pulse oximetry (SpO 2) throughout the intubation procedure. Secondary outcomes included drop in SpO 2 , adverse events related to intubation, and outcome in the ICU. Results: A total of 192 patients were randomized. In the intent-to-treat analysis, 184 patients (HFNC n = 95; SMO n = 89), the median [IQR] lowest SpO 2 was 100% [97; 100] for HFNC and 99% [95; 100] for the SMO group (P = 0.30). Mild desaturation below 95% was more frequent with SMO (23%) than with HFNC (12%) (RR 0.51, 95% CI 0.26-0.99, P = 0.045). There were fewer adverse events in the HFNC group (6%) than in the SMO group (19%) (RR 0.31, 95% CI 0.13-0.76, P = 0.007), including fewer severe adverse events, respectively 6 (6%) and 14 (16%) with HFNC and SMO (RR 0.38, 95% CI 0.15-0.95, P = 0.03). Conclusions: Compared with SMO, preoxygenation with HFNC in the ICU did not improve the lowest SpO 2 during intubation in the non-severely hypoxemic patients but led to a reduction in intubation-related adverse events. Trial registration: Clinical trial Submission: 7 March 2016. Registry name: Benefits of high-flow nasal cannulae oxygen for preoxygenation during intubation in non-severely hypoxemic patients: the PROTRACH study. Clinicaltrials.gov identifier: NCT02700321. Eudra CT: 2015-A00145-44. CPP: 15/13-975 (Comité de protection des personnes de Rennes). URL registry: https ://clini caltr ials.gov/ct2/show/recor d/NCT02 70032 1.

Background: Improving timeliness of pathogen identification is crucial to allow early adaptation of antibiotic therapy and improve prognosis in patients with pneumonia. We evaluated the relevance of a new syndromic rapid multiplex PCR test (rm-PCR) on respiratory samples to guide empirical antimicrobial therapy in adult patients with communityacquired pneumonia (CAP), hospital-acquired pneumonia (HAP), and ventilator-acquired pneumonia (VAP). Methods: This retrospective multicenter study was conducted in four French university hospitals. Respiratory samples were obtained from patients with clinical and radiological signs of pneumonia and simultaneously tested using conventional microbiological methods and the rm-PCR. A committee composed of an intensivist, a microbiologist, and an infectious diseases specialist retrospectively assessed all medical files and agreed on the most appropriate antimicrobial therapy for each pneumonia episode, according to the results of rm-PCR and blinded to the culture results. The rm-PCR-guided antimicrobial regimen was compared to the empirical treatment routinely administered to the patient in standard care. Results: We included 159 pneumonia episodes. Most patients were hospitalized in intensive care units (n = 129, 81%), and episodes were HAP (n = 68, 43%), CAP (n = 54, 34%), and VAP (n = 37, 23%). Conventional culture isolated ≥ 1 microorganism(s) at significant level in 95 (60%) patients. The syndromic rm-PCR detected at least one bacteria in 132 (83%) episodes. Based on the results of the rm-PCR, the multidisciplinary committee proposed a modification of the empirical therapy in 123 (77%) pneumonia episodes. The modification was a de-escalation in 63 (40%), an escalation in 35 (22%), and undetermined in 25 (16%) patients. In microbiologically documented episodes (n = 95), the rm-PCR increased appropriateness of the empirical therapy to 83 (87%), as compared to 73 (77%) in routine care.

Invasive pulmonary aspergillosis (IPA) in intensive care unit patients is a major concern. Influenza-associated acute respiratory distress syndrome (ARDS) and severe COVID-19 patients are both at risk of developing invasive fungal diseases. We used the new international definitions of influenza-associated pulmonary aspergillosis (IAPA) and COVID-19-associated pulmonary aspergillosis (CAPA) to compare the demographic, clinical, biological, and radiological aspects of IAPA and CAPA in a monocentric retrospective study. A total of 120 patients were included, 71 with influenza and 49 with COVID-19-associated ARDS. Among them, 27 fulfilled the newly published criteria of IPA: 17/71 IAPA (23.9%) and 10/49 CAPA (20.4%). Kaplan–Meier curves showed significantly higher 90-day mortality for IPA patients overall (p = 0.032), whereas mortality did not differ between CAPA and IAPA patients. Radiological findings showed differences between IAPA and CAPA, with a higher proportion of features suggestive of IPA during IAPA. Lastly, a wide proportion of IPA patients had low plasma voriconazole concentrations with a higher delay to reach concentrations > 2 mg/L in CAPA vs. IAPA patients (p = 0.045). Severe COVID-19 and influenza patients appeared very similar in terms of prevalence of IPA and outcome. The dramatic consequences on the patients’ prognosis emphasize the need for a better awareness in these particular populations.

Background While the psychiatric disorders are conditions frequently encountered in hospitalized patients, there are little or no data regarding the characteristics and short- and long-term outcomes in patients with preexisting psychiatric disorders in ICU. Such assessment may provide the opportunity to determine the respective impact on mortality in the ICU and after ICU discharge with reasons for admission, including modalities of self-harm, of underlying psychiatric disorders and prior psychoactive medications.MethodsICU and 1-year survival analysis performed on a retrospective cohort of patients with preexisting psychiatric disorders admitted from 2000 through 2013 in a 21-bed polyvalent ICU in a university hospital.ResultsAmong the 1751 patients of the cohort, 1280 (73%) were admitted after deliberate self-harm. Psychiatric diagnoses were: schizophrenia, n = 97 (6%); non-schizophrenia psychotic disorder, n = 237 (13%); depression disorder, n = 1058 (60%), bipolar disorder, n = 172 (10%), and anxiety disorder, n = 187 (11%). ICU mortality rate was significantly lower in patients admitted after self-harm than in patients admitted for other reasons than self-harm [38/1288 patients (3%) vs. 53/463 patients (11%), respectively, p < 0.0001]. Compared with patients admitted for deliberate self-poisoning with psychoactive medications, patients admitted for self-harm by hanging, drowning, jumping from buildings, or corrosive chemicals ingestion had a significantly higher ICU mortality rate. In the ICU, SAPS II score [adjusted odds ratio (OR) 1.061, 95% CI 1.041–1.079, p < 0.0001], use of vasopressors (adjusted OR 7.40, 95% CI 2.94–18.51, p < 0.001), out-of-hospital cardiac arrest (adjusted OR 14.70, 95% CI 3.86–38.51, p < 0.001), and self-harm by hanging, drowning, jumping from buildings, or corrosive chemicals ingestion (adjusted OR 11.49, 95% CI 3.76–35.71, p < 0.001) were independently associated with mortality. After ICU discharge SAPS II score [adjusted hazard ratio (HR) 1.023, 95% CI 1.010–1.036, p < 0.01], age (adjusted HR 1.030, 95% CI 1.016–1.044, p < 0.0001), admission for respiratory failure (adjusted HR 2.23, 95% CI 1.19–4.57, p = 0.01), and shock (adjusted HR 3.72, 95% CI 1.97–6.62, p < 0.001) were independently associated with long-term mortality. Neither psychiatric diagnoses nor psychoactive medications received before admission to the ICU were independently associated with mortality.ConclusionsThe study provides data on the short- and long-term outcomes of patients with prepsychiatric disorders admitted to the ICU that may guide decisions when considering ICU admission and discharge in these patients.