Assessment of Magnetic Resonance Imaging Changes and Functional Outcomes Among Adults With Severe Herpes Simplex Encephalitis.

Importance: Current guidelines recommend brain magnetic resonance imaging (MRI) for clinical management of patients with severe herpes simplex encephalitis (HSE). However, the prognostic value of brain imaging has not been demonstrated in this setting. Objective: To investigate the association between early brain MRI data and functional outcomes of patients with HSE at 90 days after intensive care unit (ICU) admission. Design, Setting, and Participants: This multicenter cohort study was conducted in 34 ICUs in France from 2007 to 2019 and recruited all patients who received a clinical diagnosis of encephalitis and exhibited cerebrospinal fluid positivity for herpes simplex virus DNA in the polymerase chain reaction analysis. Data analysis was performed from January to April 2020. Exposures: All patients underwent a standard brain MRI during the first 30 days after ICU admission. Main Outcomes and Measures: MRI acquisitions were analyzed by radiologists blinded to patients' outcomes, using a predefined score. Multivariable logistic regression and supervised hierarchical classifiers methods were used to identify factors associated with poor outcome at 90 days, defined by a score of 3 to 6 (indicating moderate-to-severe disability or death) on the Modified Rankin Scale. Results: Overall, 138 patients (median [interquartile range {IQR}] age, 62.6 [54.0-72.0] years; 75 men [54.3%]) with an admission median (IQR) Glasgow Coma Scale score of 9 (6-12) were studied. The median (IQR) delay between ICU admission and MRI was 1 (1-7) days. At 90 days, 95 patients (68.8%) had a poor outcome, including 16 deaths (11.6%). The presence of fluid-attenuated inversion recovery MRI signal abnormalities in more than 3 brain lobes (odds ratio [OR], 25.71; 95% CI, 1.21-554.42), age older than 60 years (OR, 7.62; 95% CI, 2.02-28.91), and the presence of diffusion-weighted MRI signal abnormalities in the left thalamus (OR, 6.90; 95% CI, 1.12-43.00) were independently associated with poor outcome. Machine learning models identified bilateral diffusion abnormalities as an additional factor associated with poor outcome (34 of 39 patients [87.2%] with bilateral abnormalities had poor outcomes) and confirmed the functional burden of left thalamic lesions, particularly in older patients (all 11 patients aged >60 years had left thalamic lesions). Conclusions and Relevance: These findings suggest that in adult patients with HSE requiring ICU admission, extensive MRI changes in the brain are independently associated with poor functional outcome at 90 days. Thalamic diffusion signal changes were frequently observed and were associated with poor prognosis, mainly in older patients.

High flow nasal cannula oxygenation in COVID-19 related acute respiratory distress syndrome: a safe way to avoid endotracheal intubation?

BACKGROUNDS: High flow nasal cannula (HFNC) is an alternative therapy for acute respiratory distress syndrome (ARDS) due to coronavirus disease 2019 (COVID-19). This study aimed first to describe outcomes of patients suffering from COVID-19-related ARDS treated with HFNC; secondly to evaluate safety of HFNC (patients and healthcare workers) and compare patients according to respiratory outcome. METHODS: A retrospective cohort was conducted in French general hospital intensive care unit (ICU). Patients were included if receiving HFNC for hypoxemia (saturation pulse oxygen (SpO2) <92% under oxygen ⩾6 L/min) associated with ARDS and positive SARS-CoV-2 polymerase chain reaction (PCR). Main clinical characteristics and outcomes are described in patients: (a) with do not intubate order (HFNC-DNIO); (b) who did not need intubation (HFNC-only); and (c) eventually intubated (HFNC-intubation). Medians are presented with (1st-3rd) interquartile range. RESULTS: From 26 February to 30 June 2020, 46 patients of median age 75 (70-79) years were included. In the HFNC-DNIO group (n = 11), partial arterial oxygen pressure (PaO2)/inhaled fraction of oxygen (FiO2) ratio median worst PaO2/FiO2 ratio was 109 (102-172) and hospital mortality was 54.5%. Except the HFNC-DNIO patients (n = 35), 20 patients (57%) were eventually intubated (HFNC-intubation group) and 15 were only treated by HFNC (HFNC-only). HFNC-intubation patients presented higher worst respiratory rates per minute in ICU [37 (34-41) versus 33 (24-34) min, p < 0.05] and worsened ICU admission PaO2/FiO2 ratios [121 (103-169) versus 191 (162-219), p < 0.001] compared with HFNC-only patients. Hospital mortality was 35% (n = 7/20) in HFNC-intubation group, 0% in HFNC-only group with a global mortality of these two groups of 20% (n = 7/35). Among tests performed in healthcare workers, 1/12 PCR in symptomatic healthcare workers and 1.8% serologies in asymptomatic healthcare workers were positive. After review of each case, COVID-19 was likely to be acquired outside hospital. CONCLUSIONS: HFNC seems to be useful for COVID-19-related ARDS and safe for healthcare workers. ARDS severity with PaO2/FiO2 <150 associated with respiratory rate >35/min could be regarded as a predictor of intubation.The reviews of this paper are available via the supplemental material section.

Cellulose binding domains of a Phytophthora cell wall protein are novel pathogen-associated molecular patterns.

The cellulose binding elicitor lectin (CBEL) from Phytophthora parasitica nicotianae contains two cellulose binding domains (CBDs) belonging to the Carbohydrate Binding Module1 family, which is found almost exclusively in fungi. The mechanism by which CBEL is perceived by the host plant remains unknown. The role of CBDs in eliciting activity was investigated using modified versions of the protein produced in Escherichia coli or synthesized in planta through the potato virus X expression system. Recombinant CBEL produced by E. coli elicited necrotic lesions and defense gene expression when injected into tobacco (Nicotiana tabacum) leaves. CBEL production in planta induced necrosis. Site-directed mutagenesis on aromatic amino acid residues located within the CBDs as well as leaf infiltration assays using mutated and truncated recombinant proteins confirmed the importance of intact CBDs to induce defense responses. Tobacco and Arabidopsis thaliana leaf infiltration assays using synthetic peptides showed that the CBDs of CBEL are essential and sufficient to stimulate defense responses. Moreover, CBEL elicits a transient variation of cytosolic calcium levels in tobacco cells but not in protoplasts. These results define CBDs as a novel class of molecular patterns in oomycetes that are targeted by the innate immune system of plants and might act through interaction with the cell wall.