Risk factors for thromboembolic events in patients hospitalized for COVID-19 pneumonia in a general ward and requiring treatment with oxygen.

PURPOSE: To assess risk factors for arterial and venous thromboses (AVT) in patients hospitalized in general wards for COVID-19 pneumonia and requiring oxygen therapy. METHODS: Our study was based on three randomized studies conducted as part of the CORIMUNO-19 platform in France between 27 March and 26 April 2020. Adult inpatients with COVID-19 pneumonia requiring at least 3 l/min of oxygen but not ventilation were randomized to receive standard care alone or standard care plus biologics. Patients were followed up for 3 months, and adverse events were documented. Risk factor for AVT and bleeding was identified by analyzing clinical, laboratory, and treatment data at baseline among the 315 patients with complete datasets. A Fine and Gray model was used to take account of competing events. RESULTS: During the 3-month follow-up period, 39 AVT occurred in 38 (10%) of the 388 patients: 26 deep vein thromboses and/or pulmonary embolisms in 25 (6%) patients, and 14 arterial thrombotic events in 13 (3%) patients. A history of diabetes at inclusion [sHR (95% CI) = 2.65 (1.19-5.91), P = .017] and the C-reactive protein (CRP) level (sHR = 1 [1-1.01], P = .049) were significantly associated with an elevated risk of thrombosis. Obesity was not associated with a higher risk of thrombosis (sHR = 1.01 [0.4-2.57], P = .98). The CRP level and diabetes were not risk factors for hemorrhage. CONCLUSION: Among patients hospitalized in general wards for COVID-19 pneumonia during the first wave of the epidemic, diabetes (but not obesity) and a high CRP level were risk factors for AVT. The use of higher doses of anticoagulant in these high-risk patients could be considered.

Clinician-Reported Physical and Cognitive Impairments After Convulsive Status Epilepticus: Post Hoc Study of a Randomized Controlled Trial.

BACKGROUND: Clinician-reported outcome (ClinRO) measures are emerging as useful contributors to assessments of treatment benefits. The objective of this study was to collect ClinRO measures of physical and cognitive impairments after convulsive status epilepticus (CSE) requiring intensive care unit admission. METHODS: We conducted a post hoc analysis of the data from HYBERNATUS, a multicenter open-label controlled trial that randomized 270 critically ill patients with CSE requiring mechanical ventilation in 11 French intensive care units to therapeutic hypothermia (32-34 °C for 24 h) plus standard care or standard care alone. We included all patients who attended a day 90 in-person neurologist visit with measurement of the functional independence measure (FIM) score (range from 18 [total assistance] to 126 [total independence]), Mini-Mental State Examination (MMSE) score (range 0-30), and Glasgow outcome scale (GOS) score (1, death; 2, vegetative state; 3, severe disability; 4, moderate disability; and 5, mild or no disability). These three scores were compared across groups defined by several patient and CSE characteristics. RESULTS: Of 229 patients with GOS scores ≥ 3 on day 90 (male sex, 58.2%; median age, 56 years [47-67]), 67 (29%) attended an in-person neurologist visit. Twenty-nine (43%) patients had a previous history of epilepsy, and 16 (24%) patients had a primary brain insult. CSE was refractory in 22 (33%) patients. On day 90 after CSE onset, median FIM and MMSE scores were 121 (112-125) and 26.0 (24.0-28.8), respectively. The GOS score was 3 in 16 (33.8%) patients, 4 in 9 (13.4%) patients, and 5 in 42 (62.7%) patients. Worse GOS score values were significantly associated with worse FIM and MMSE scores. CONCLUSIONS: In patients attending the in-person neurologist visit on day 90 after CSE onset, ClinRO measures indicated that the main impairments were cognitive. FIM and MMSE scores were associated with GOS scores. Further studies are needed to evaluate the possible impact of neuroprotective and rehabilitation strategies on disability and cognitive impairments in survivors of CSE. Clinical trial registration NCT01359332.

Early-onset gout and rare deficient variants of the lactate dehydrogenase D gene.

OBJECTIVES: To investigate whether the lactate dehydrogenase D (LDHD) gene deficiency causes juvenile-onset gout. METHODS: We used whole-exome sequencing for two families and a targeted gene-sequencing panel for an isolated patient. d-lactate dosages were analysed using ELISA. RESULTS: We demonstrated linkage of juvenile-onset gout to homozygous carriage of three rare distinct LDHD variants in three different ethnicities. In a Melanesian family, the variant was (NM_153486.3: c.206C>T; rs1035398551) and, as compared with non-homozygotes, homozygotes had higher hyperuricaemia (P = 0.02), lower fractional clearance of urate (P = 0.002), and higher levels of d-lactate in blood (P = 0.04) and urine (P = 0.06). In a second, Vietnamese, family, very severe juvenile-onset gout was linked to homozygote carriage of an undescribed LDHD variant (NM_153486.3: c.1363dupG) leading to a frameshift followed by a stop codon, p.(AlaGly432fsTer58). Finally, a Moroccan man, with early-onset and high d-lactaturia, whose family was unavailable for testing, was homozygous for another rare LDHD variant [NM_153486.3: c.752C>T, p.(Thr251Met)]. CONCLUSION: Rare, damaging LDHD variants can cause autosomal recessive early-onset gout, the diagnosis of which can be suspected by measuring high d-lactate levels in the blood and/or urine.

Cluster Analysis to Explore Clinical Subphenotypes of Eosinophilic Granulomatosis With Polyangiitis.

OBJECTIVE: Previous studies suggested that distinct phenotypes of eosinophilic granulomatosis with polyangiitis (EGPA; formerly known as Churg-Strauss syndrome) could be determined by the presence or absence of antineutrophil cytoplasmic antibodies (ANCA), reflecting predominant vasculitic or eosinophilic processes, respectively. This study explored whether ANCA-based clusters or other clusters can be identified in EGPA. METHODS: This study used standardized data of 15 European centers for patients with EGPA fulfilling widely accepted classification criteria. We used multiple correspondence analysis, hierarchical cluster analysis, and a decision tree model. The main model included 10 clinical variables (musculoskeletal [MSK], mucocutaneous, ophthalmological, ENT, cardiovascular, pulmonary, gastrointestinal, renal, central, or peripheral neurological involvement); a second model also included ANCA results. RESULTS: The analyses included 489 patients diagnosed between 1984 and 2015. ANCA were detected in 37.2% of patients, mostly perinuclear ANCA (85.4%) and/or antimyeloperoxidase (87%). Compared with ANCA-negative patients, those with ANCA had more renal (P < 0.001) and peripheral neurological involvement (P = 0.04), fewer cardiovascular signs (P < 0.001), and fewer biopsies with eosinophilic tissue infiltrates (P = 0.001). The cluster analyses generated 4 (model without ANCA) and 5 clusters (model with ANCA). Both models identified 3 identical clusters of 34, 39, and 40 patients according to the presence or absence of ENT, central nervous system, and ophthalmological involvement. Peripheral neurological and cardiovascular involvement were not predictive characteristics. CONCLUSION: Although reinforcing the known association of ANCA status with clinical manifestations, cluster analysis does not support a complete separation of EGPA in ANCA-positive and -negative subsets. Collectively, these data indicate that EGPA should be regarded as a phenotypic spectrum rather than a dichotomous disease.

Machine-learning derived algorithms for prediction of radiographic progression in early axial spondyloarthritis.

OBJECTIVES: To compare machine learning (ML) to traditional models to predict radiographic progression in patients with early axial spondyloarthritis (axSpA). METHODS: We carried out a prospective French multicentric DESIR cohort study with 5 years of follow-up that included patients with chronic back pain for <3 years, suggestive of axSpA. Radiographic progression was defined as progression at the spine (increase of at least 1 point of mSASSS scores/2 years) or at the sacroiliac joint (worsening of at least one grade of the mNY score between 2 visits). Statistical analyses were based on patients without any missing data regarding the outcome and variables of interest (295 patients).Traditional modelling: we performed a multivariate logistic regression model (M1); then variable selection with stepwise selection based on Akaike Information Criterion (stepAIC) method (M2), and Least Absolute Shrinkage and Selection Operator (LASSO) method (M3).ML modelling: using "SuperLearner" package on R, we modelled radiographic progression with stepAIC, LASSO, random forest, Discrete Bayesian Additive Regression Trees Samplers (DBARTS), Generalized Additive Models (GAM), multivariate adaptive polynomial spline regression (polymars), Recursive Partitioning And Regression Trees (RPART) and Super Learner. Accuracy of these models was compared based on their 10-fold cross-validated AUC (cv-AUC). RESULTS: 10-fold cv-AUC for traditional models were 0.79 and 0.78 for M2 and M3, respectively. The three best models in the ML algorithms were the GAM, the DBARTS and the Super Learner models, with 10-fold cv-AUC of: 0.77, 0.76 and 0.74, respectively. CONCLUSIONS: Two traditional models predicted radiographic progression as good as the eight ML models tested in this population.

Prevention of cardiac surgery-associated acute kidney injury: a systematic review and meta-analysis of non-pharmacological interventions.

BACKGROUND: Cardiac surgery-associated acute kidney injury (CSA-AKI) is frequent. While two network meta-analyses assessed the impact of pharmacological interventions to prevent CSA-AKI, none focused on non-pharmacological interventions. We aim to assess the effectiveness of non-pharmacological interventions to reduce the incidence of CSA-AKI. METHODS: We searched PubMed, Embase, Central and clinical trial registries from January 1, 2004 (first consensus definition of AKI) to July 1, 2023. Additionally, we conducted manual screening of abstracts of major anesthesia and intensive care conferences over the last 5 years and reference lists of relevant studies. We selected all randomized controlled trials (RCTs) assessing a non-pharmacological intervention to reduce the incidence of CSA-AKI, without language restriction. We excluded RCTs of heart transplantation or involving a pediatric population. The primary outcome variable was CSA-AKI. Two reviewers independently identified trials, extracted data and assessed risk of bias. Random-effects meta-analyses were conducted to calculate risk ratios (RRs) with 95% confidence intervals (CIs). We used the Grading of Recommendations Assessment, Development, and Evaluation to assess the quality of evidence. RESULTS: We included 86 trials (25,855 patients) evaluating 10 non-pharmacological interventions to reduce the incidence of CSA-AKI. No intervention had high-quality evidence to reduce CSA-AKI. Two interventions were associated with a significant reduction in CSA-AKI incidence, with moderate quality of evidence: goal-directed perfusion (RR, 0.55 [95% CI 0.40-0.76], I2 = 0%; Phet = 0.44) and remote ischemic preconditioning (RR, 0.86 [0.78-0.95]; I2 = 23%; Phet = 0.07). Pulsatile flow during cardiopulmonary bypass was associated with a significant reduction in CSA-AKI incidence but with very low quality of evidence (RR = 0.69 [0.48; 0.99]; I2 = 53%; Phet < 0.01). We found high quality of evidence for lack of effect of restrictive transfusion strategy (RR, 1.02 [95% CI 0.92; 1.12; Phet = 0.67; I2 = 3%) and tight glycemic control (RR, 0.86 [95% CI 0.55; 1.35]; Phet = 0.25; I2 = 26%). CONCLUSIONS: Two non-pharmacological interventions are likely to reduce CSA-AKI incidence, with moderate quality of evidence: goal-directed perfusion and remote ischemic preconditioning.

PD-1 blockade with pembrolizumab in classic or endemic Kaposi's sarcoma: a multicentre, single-arm, phase 2 study.

BACKGROUND: Although the treatment of iatrogenic and HIV-related Kaposi sarcoma is well defined and mostly based on restoring immune function, the treatment of classic and endemic Kaposi sarcoma is less well established. Chemotherapy or interferon α is used for patients with extensive cutaneous or visceral Kaposi sarcoma, but tolerance might be poor and long-term remission is rare. We aimed to evaluate the activity of pembrolizumab in classic and endemic Kaposi sarcoma with cutaneous extension requiring systemic treatment. METHODS: We did a multicentre, single-arm, proof-of-concept, phase 2 trial in adults aged 18 years or older with histologically proven classic or endemic Kaposi's sarcoma with progressive cutaneous extension requiring systemic treatment and an Eastern Cooperative Oncology Group performance status of 0-1 in three hospitals in France. The patients were treated with 200 mg pembrolizumab intravenously every 3 weeks for 6 months (eight cycles) or until severe toxicity. The primary endpoint was the best overall response rate within the 6-month timeframe, defined by the occurrence of a complete response or partial response and assessed by an investigator using the modified AIDS Clinical Trial Group (ACTG) criteria. Three or more responses among a total 17 patients were needed for the primary endpoint to be met, using a Simon's two-stage optimal design assuming a 30% response rate as desirable. For this final study analysis, all patients were included following the intention-to-treat principle. This study is registered with ClinicalTrials.gov, NCT03469804, and is closed to new participants. FINDINGS: 30 patients were screened for eligibility and 17 patients (eight [47%] with classic and nine [53%] with endemic Kaposi's sarcoma) were enrolled between July 2, 2018, and Dec 16, 2019. The median follow-up was 20·4 months (IQR 18·1-24·1). Two (12%) patients had a complete response, ten (59%) had a partial response, and five (29%) had stable disease as the best response within the 6-month treatment timeframe, with a best overall response rate of 71% (95% CI 44-90), meeting the predefined primary outcome (ie, exceeding a response rate of 30%). Treatment-related adverse events occurred in 13 (76%) of 17 patients, including two grade 3 adverse events (one [6%] acute cardiac decompensation and one [6%] granulomatous reaction). Treatment was prematurely discontinued in two (12%) patients due to grade 3 acute reversible cardiac decompensation and grade 2 pancreatitis, and one other patient had a grade 3 granulomatous reaction in mediastinal lymph nodes requiring steroids and methotrexate treatment. There were no serious adverse events or treatment-related deaths. INTERPRETATION: In this prospective trial, which to our knowledge is the first to assess the role of PD-1 blockade in patients with classic and endemic Kaposi's sarcoma, pembrolizumab showed promising anti-tumour activity with an acceptable safety profile. If this result is supported by further studies, treatment with anti-PD-1 could be part of the therapeutic armamentarium for patients with classic and endemic Kaposi's sarcoma. FUNDING: MSD France.

Effect of interleukin-6 receptor antagonists in critically ill adult patients with COVID-19 pneumonia: two randomised controlled trials of the CORIMUNO-19 Collaborative Group.

BACKGROUND: Our objective was to determine whether anti-interleukin (IL)-6 receptors improve outcomes of critically ill patients with coronavirus disease 2019 (COVID-19) pneumonia. We report on two cohort-embedded, investigator-initiated, multicentre, open-label, Bayesian randomised controlled clinical trials. METHODS: Patients were randomly assigned to receive either usual care (UC) or UC+tocilizumab (TCZ) 8 mg·kg-1 (TOCI-2 trial) or UC or UC+sarilumab (SARI) 200 mg (SARI-2 trial), both intravenously on day 1 and, if clinically indicated, on day 3. RESULTS: Between 31 March and 20 April 2020, 97 patients were randomised in the TOCI-2 trial, to receive UC (n=46) or UC+TCZ (n=51). At day 14, numbers of patients who did not need noninvasive ventilation (NIV) or mechanical ventilation (MV) and were alive with TCZ or UC were similar (47% versus 42%; median posterior hazard ratio (HR) 1.19, 90% credible interval (CrI) 0.71-2.04), with a posterior probability of HR >1 of 71.4%. Between 27 March and 4 April 2020, 91 patients were randomised in the SARI-2 trial, to receive UC (n=41) or UC+SARI (n=50). At day 14, numbers of patients who did not need NIV or MV and were alive with SARI or UC were similar (38% versus 33%; median posterior HR 1.05, 90% CrI 0.55-2.07), with a posterior probability of HR >1 of 54.9%. Overall, the risk of death up to day 90 was: UC+TCZ 24% versus UC 30% (HR 0.67, 95% CI 0.30-1.49) and UC+SARI 29% versus UC 39% (HR 0.74, 95% CI 0.35-1.58). Both TCZ and SARI increased serious infectious events. CONCLUSION: In critically ill patients with COVID-19, anti-IL-6 receptors did not significantly increase the number of patients alive without any NIV or MV by day 14.

Emergency computed tomography evaluation of caustic ingestion.

Computed tomography (CT) is used increasingly for the emergency assessment of caustic injuries and the need for emergency endoscopy has been challenged. The study evaluates outcomes of caustic ingestion in the modern era and the feasibility of abandoning emergency endoscopy. Between 2013 and 2019, 414 patients (197 men, median age 42 years) were admitted for caustic ingestion. Emergency and long-term outcomes of patients managed by CT and endoscopy (n = 120) and by CT alone (n = 294) were compared. Propensity score-based analysis was performed to limit bias of between-group comparison. A standard mortality ratio (SMR) was used to compare the observed mortality with the expected mortality in the general French population. Complications occurred in 97 (23%) patients and 17 (4.1%) patients died within 90 days of ingestion. Among 359 patients who underwent nonoperative management, 51 (14%) experienced complications and 7 (2%) died. Of 55 patients who underwent emergency surgery, 46 (84%) experienced complications and 10 (18%) died. The SMR was 8.4 for whole cohort, 5.5 after nonoperative management, and 19.3 after emergency surgery. On multivariate analysis, intentional ingestion (P < 0.016), age (P < 0.0001) and the CT grade of esophageal injuries (P < 0.0001) were independent predictors of survival. The CT grade of esophageal injuries was the only independent predictor of success (P < 0.0001). Crude and propensity match analysis showed similar survival in patients managed with and without endoscopy. CT evaluation alone can be safely used for the emergency management of caustic ingestion.

Relative survival after meningioma surgery. A French nationwide population-based cohort study.

BACKGROUND: Survival after meningioma surgery is often reported with inadequate allowance for competing causes of death. METHODS: We processed the Système National des Données de Santé, the French administrative medical database to retrieve appropriate patients' case of surgically treated meningiomas. The Pohar Perme relative survival (RS) method was implement. RESULTS: A total of 28,778 patients were identified between 2007 and 2017 of which 75% were female. Median age at surgery 59 years. Cranial convexity was the most common (24.7%) location and, benign meningioma represented 91.5% of all meningioma. Median follow-up was 3.5 years interquartile range [3.4-3.5]. At data collection, 2,232 patients were dead. The five-year survival relative to the expected survival of an age- and gender-matched French standard population was 96.2% 95% confidence interval (CI)[95.7-96.8]. Meningioma absolute excess risk of death was 973/100,000 person-years 95%CI[887-1068] (p< .001). The related standardised mortality ratio was 1.8 95%CI[1.7-1.9] (p< .001). In the adjusted model, male gender (hazard ratio [HR] =1.39, 95%CI[1.27-1.54], p< .001), age at surgery (HR=0.97, 95%CI[0.97-0.97], p < .001), type 2 neurofibromatosis (HR=2.95, 95%CI[1.95-4.46], p < .001), comorbidities HR=1.39, 95%CI[1.36-1.42], p < .001), location (HR=0.8, 95%CI[0.67-0.95], p= .0111), pre-operative embolization, (HR=1.3, 95%CI[1.08-1.56], p= .00507), cerebro-spinal fluid shunt, (HR=2.48, 95%CI[2.04-3.01], p < .001), atypical (HR=1.3, 95%CI [1.09-1.54], p= .00307) or malignant histology (HR=1.86, 95%CI[1.56-2.22], p< .001), redo surgery (HR=1.19, 95%CI[1.04-1.36], p= .0122) and radiotherapy (HR=1.43, 95%CI[1.26-1.62], p < .001) were established as independent predictors of RS. CONCLUSION: This unique study highlights the excess mortality associated with meningioma disease. Many factors such as gender, age, location, histopathological grading, redo surgery influence the RS.

Association of COVID-19 Acute Respiratory Distress Syndrome With Symptoms of Posttraumatic Stress Disorder in Family Members After ICU Discharge.

IMPORTANCE: Persistent physical and mental disorders are frequent in survivors of COVID-19-related acute respiratory distress syndrome (ARDS). However, data on these disorders among family members are scarce. OBJECTIVE: To determine the association between patient hospitalization for COVID-19 ARDS vs ARDS from other causes and the risk of posttraumatic stress disorder (PTSD)-related symptoms in family members. DESIGN, SETTING, AND PARTICIPANTS: Prospective cohort study in 23 intensive care units (ICUs) in France (January 2020 to June 2020 with final follow-up ending in October 2020). ARDS survivors and family members (1 family member per patient) were enrolled. EXPOSURES: Family members of patients hospitalized for ARDS due to COVID-19 vs ARDS due to other causes. MAIN OUTCOMES AND MEASURES: The primary outcome was family member symptoms of PTSD at 90 days after ICU discharge, measured by the Impact of Events Scale-Revised (score range, 0 [best] to 88 [worst]; presence of PTSD symptoms defined by score >22). Secondary outcomes were family member symptoms of anxiety and depression at 90 days assessed by the Hospital Anxiety and Depression Scale (score range, 0 [best] to 42 [worst]; presence of anxiety or depression symptoms defined by subscale scores ≥7). Multivariable logistic regression models were used to determine the association between COVID-19 status and outcomes. RESULTS: Among 602 family members and 307 patients prospectively enrolled, 517 (86%) family members (median [IQR] age, 51 [40-63] years; 72% women; 48% spouses; 26% bereaved because of the study patient's death; 303 [50%] family members of COVID-19 patients) and 273 (89%) patients (median [IQR] age, 61 [50-69] years; 34% women; 181 [59%] with COVID-19) completed the day-90 assessment. Compared with non-COVID-19 ARDS, family members of patients with COVID-19 ARDS had a significantly higher prevalence of symptoms of PTSD (35% [103/293] vs 19% [40/211]; difference, 16% [95% CI, 8%-24%]; P < .001), symptoms of anxiety (41% [121/294] vs 34% [70/207]; difference, 8% [95% CI, 0%-16%]; P= .05), and symptoms of depression (31% [91/291] vs 18% [37/209]; difference, 13% [95% CI, 6%-21%]; P< .001). In multivariable models adjusting for age, sex, and level of social support, COVID-19 ARDS was significantly associated with increased risk of PTSD-related symptoms in family members (odds ratio, 2.05 [95% CI, 1.30 to 3.23]). CONCLUSIONS AND RELEVANCE: Among family members of patients hospitalized in the ICU with ARDS, COVID-19 disease, as compared with other causes of ARDS, was significantly associated with increased risk of symptoms of PTSD at 90 days after ICU discharge. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04341519.

Treatment for pure red cell aplasia after major ABO-incompatible allogeneic stem cell transplantation: a multicentre study.

Pure red cell aplasia (PRCA) following allogeneic haematopoietic stem cell transplantation (aHSCT) with major ABO incompatibility is responsible for transfusion dependent anaemia, impaired quality of life and iron overload. We conducted a retrospective study, over a 10-year period, which included all consecutive patients who received a major ABO mismatched aHSCT, to assess the impact of specific treatment on PRCA. We did not observe any PRCA in the 57 aHSCT issued from cord blood. Among the remaining 631 patients, cumulative incidence of PRCA was 10·5% [range 8·2-13.0]. The median duration of resolved PRCA was 171 days [IQR 116; 261]. Pre-transplant high isohaemagglutinins titre was associated with an increased risk of PRCA (P < 10-4 ). PRCA did not affect overall survival (P = 0·95). Twenty-two patients (33·3%) received at least one specific treatment. The most commonly used treatments were rituximab (17 patients) and donor lymphocyte infusion (DLI; seven patients). Regarding PRCA resolution, we did not observe a significant difference between treated or untreated subjects (HR = 0·93, 95% confidence interval (CI) 0·48- 1·80; P = 0·82). Similar results were observed with erythropoietin treatment (22 patients, HR = 0·86 95% CI: [0·47-1·57] P = 0·62). Our data do not support the use of erythropoietin, rituximab or DLI for the treatment of PRCA.

Symptoms of Anxiety, Depression, and Peritraumatic Dissociation in Critical Care Clinicians Managing Patients with COVID-19. A Cross-Sectional Study.

Rationale: Frontline healthcare providers (HCPs) during the coronavirus disease (COVID-19) pandemic are at high risk of mental morbidity.Objectives: To assess the prevalence of symptoms of anxiety, depression, and peritraumatic dissociation in HCPs.Methods: This was a cross-sectional study in 21 ICUs in France between April 20, 2020, and May 21, 2020. The Hospital Anxiety and Depression Scale and the Peritraumatic Dissociative Experience Questionnaire were used. Factors independently associated with reported symptoms of mental health disorders were identified.Measurements and Main Results: The response rate was 67%, with 1,058 respondents (median age 33 yr; 71% women; 68% nursing staff). The prevalence of symptoms of anxiety, depression, and peritraumatic dissociation was 50.4%, 30.4%, and 32%, respectively, with the highest rates in nurses. By multivariable analysis, male sex was independently associated with lower prevalence of symptoms of anxiety, depression, and peritraumatic dissociation (odds ratio of 0.58 [95% confidence interval, 0.42-0.79], 0.57 [95% confidence interval, 0.39-0.82], and 0.49 [95% confidence interval, 0.34-0.72], respectively). HCPs working in non-university-affiliated hospitals and nursing assistants were at high risk of symptoms of anxiety and peritraumatic dissociation. Importantly, we identified the following six modifiable determinants of symptoms of mental health disorders: fear of being infected, inability to rest, inability to care for family, struggling with difficult emotions, regret about the restrictions in visitation policies, and witnessing hasty end-of-life decisions.Conclusions: HCPs experience high levels of psychological burden during the COVID-19 pandemic. Hospitals, ICU directors, and ICU staff must devise strategies to overcome the modifiable determinants of adverse mental illness symptoms.

Comparative Efficacy of the Different Surgical Approaches in Total Knee Arthroplasty: A Systematic-Review and Network Meta-Analysis.

BACKGROUND: Several surgical approaches including midvastus, subvastus, mini-parapatellar, quadriceps-sparring (QS) and parapatellar are currently used to perform total knee arthroplasty (TKA). Since none of published study exhibited a simultaneous comparison of all of them, a network meta-analysis has been conducted to compare the most widely used knee surgical approaches regarding the improvement of functional outcomes and the range of motion (ROM). METHODS: Randomised controlled trials (RCTs) comparing TKA approaches were searched in electronic databases, major orthopedics journals, and oral communications, ClinicalTrials.gov and WHO International Clinical Trials Registry Platform until May 1st, 2020. Two reviewers independently selected trials and extracted data. The primary outcomes were functional scores at 6 months post-surgeryevaluated by KSS and WOMAC, and the ROM. RESULTS: Sixty RCTs involving 5042 patients with 5107 TKA were included. No significant differences between different approaches were found for the KSS assessment or the WOMAC at 6 months. The mean of ROM at 6 months post-surgery were higher in the subvastus group than in all the others surgical approaches. The difference of ROM with subvastus approach was 7.3° (95% CI -14.1 to -0.1) with the midvastus approach, 11.1° (95% CI -18.7 to -2.8) with mini-parapatellar, 8.9° (95% CI -14.2 to -3.1) with standard parapatellar, and 9.2° (95% CI -16.1 to -1.8) with QS. CONCLUSION: No differences were found in functional outcomes over short or medium terms but subvastus seemed to increase the ROM at 6 months post-surgery. Until or unless future studies can demonstrate a long-term benefit, based on these results all studied surgical approaches to perform a TKA are equal. LEVEL OF EVIDENCE: Network meta-analysis. Level 1.

Clustering with missing and left-censored data: A simulation study comparing multiple-imputation-based procedures.

Cluster analysis, commonly used to explore large biomedical datasets, can be challenging, notably due to missing data or left-censored data induced by the sensitivity limits of the biochemical measurement method. Usually, complete-case analysis, simple imputation, or stochastic simple imputation are applied before clustering. More recently, consensus methods following multiple imputation have been proposed. However, they ignore left-censoring and do not allow the number of clusters to vary across the partitions of each imputed dataset. Here, we developed a consensus-based clustering algorithm in which left-censored data are taken into account using a modified multiple imputation method and the number of clusters is estimated for each imputed dataset. A simulation study was conducted to assess the performance in terms of the number of clusters, the percentage of unclassified observations, and the adjusted Rand index. The simulation results showed that the investigated method works well compared to several alternative approaches. A real-world application in breast cancer patients showed that the proposed method may reveal novel clusters of patients.

Prognosis of large vessel involvement in large vessel vasculitis.

OBJECTIVES: To assess prognosis factors and outcome of large vessel involvement (LVI) in large vessels vasculitis (LVV) patients. METHODS: Retrospective multicenter study of characteristics and outcomes of 417 patients with LVI including 299 Takayasu arteritis (TAK) and 118 Giant cell arteritis (GCA-LVI) were analyzed. Logistic regression analysis assessed prognosis factors in LVV patients. Outcome of LVI among TAK and GCA-LVI patients (ischemic complications, aneurysms complications, relapses and revascularization) were assessed. RESULTS: In multivariable analysis, stroke/transient ischemic attack [HR: 3.63 (1.46-9.04), p = 0.006] was independently associated with vascular complications in LVV. The 10-years aneurysm free survival was significantly lower [67% (48-93) vs 89% (84-95), p = 0.02] in GCA-LVI compare to TAK patients. The 5-years relapse free survival was significantly lower [47% (37-60) vs 69% (63-75), p < 0.001,] in GCA-LVI compare to TAK patients. The 10-years revascularization free survival was significantly lower [55% (48-64) vs 76% (59-99), p < 0.001] in TAK compare to GCA-LVI patients. After a median follow-up of 5 years, 16 (5.4%) TAK and 7 (5.9%) GCA-LVI patients died, mainly of aneurysm (26%) and ischemic complications (26%). CONCLUSION: This large nationwide cohort of LVI provided prognosis factors of vascular complications in LVV patients. TAK and GCA-LVI have different long-term outcome in term of aneurysm development, relapse and revascularization.

Folliculitis decalvans is characterized by a persistent, abnormal subepidermal microbiota.

Folliculitis decalvans (FD) is a chronic inflammatory disease of unknown aetiology. Although Staphylococcus aureus, frequently found on lesional skin, is thought to play a causal role, the importance of its involvement remains controversial. To examine the role of S aureus, we compared superficial and subepidermal microbiota in 20 FD patients who had S aureus on lesional skin and in 20 healthy controls using culture techniques and genomic identification, before and after an anti-staphylococcal treatment; we also screened for S aureus virulence factors. When present on lesional skin, S aureus colonized non-lesional and subepidermal skin in 80% of cases. These data imply a break in the epidermal barrier integrity and that an abnormal non-lesional skin microbiota persists in FD. S aureus had no superantigenic toxin in 31% of cases and no toxin specificity. Clinical improvement obtained in most cases upon treatment was associated with the disappearance of S aureus in all studied areas, with an incomplete restoration of normal microbiota and a significant increase in negative bacterial samples. This persistent unbalanced, subepidermal microbiota may act as a reservoir of abnormal flora and explain the chronicity of FD, suggesting new avenues of research to restore normal microbiota.

Severe diffuse alveolar hemorrhage related to autoimmune disease: a multicenter study.

BACKGROUND: Diffuse alveolar hemorrhage (DAH) occurs during the course of autoimmune disease and may be life threatening. The objective was to assess characteristics and prognosis factors of DAH who required intensive care unit (ICU) admission in patients with autoimmune diseases. METHODS: French multicenter retrospective study including patients presenting DAH related to autoimmune diseases requiring ICU admission from 2000 to 2016. RESULTS: One hundred four patients (54% of men) with median age of 56 [32-68] years were included with 79 (76%) systemic vasculitis and 25 (24%) connective tissue disorders. All patients received steroids, and 72 (69%), 12 (11.5%), and 57 (55%) patients had cyclophosphamide, rituximab, and plasma exchanges, respectively. During ICU stay, 52 (50%), 36 (35%), and 55 (53%) patients required mechanical ventilation, vasopressor use, and renal replacement therapy, respectively. Factors associated with mechanical ventilation weaning were age (HR [95%CI] 0.97 [0.96-0.99] per 10 years, p < 0.0001), vasculitis-related DAH (0.52 [0.27-0.98], p = 0.04), and time from dyspnea onset to ICU admission (0.99 [0.99-1] per day, p = 0.03). ICU mortality was 15%. Factors associated with alive status at ICU discharge were chronic cardiac failure (HR [95%CI] 0.37 [0.15-0.94], p = 0.04), antiphospholipid syndrome-related DAH (3.17 [1.89-5.32], p < 0.0001), SAPS II (0.98 [0.97-0.99], p = 0.007), and oxygen flow at ICU admission (0.95 [0.91-0.99] per liter/min, p = 0.04). CONCLUSION: DAH in autoimmune diseases is a life-threatening complication which requires mechanical ventilation in half of the cases admitted to ICU.

Prediction of an Acute Hypotensive Episode During an ICU Hospitalization With a Super Learner Machine-Learning Algorithm.

BACKGROUND: Acute hypotensive episodes (AHE), defined as a drop in the mean arterial pressure (MAP) <65 mm Hg lasting at least 5 consecutive minutes, are among the most critical events in the intensive care unit (ICU). They are known to be associated with adverse outcome in critically ill patients. AHE prediction is of prime interest because it could allow for treatment adjustment to predict or shorten AHE. METHODS: The Super Learner (SL) algorithm is an ensemble machine-learning algorithm that we specifically trained to predict an AHE 10 minutes in advance. Potential predictors included age, sex, type of care unit, severity scores, and time-evolving characteristics such as mechanical ventilation, vasopressors, or sedation medication as well as features extracted from physiological signals: heart rate, pulse oximetry, and arterial blood pressure. The algorithm was trained on the Medical Information Mart for Intensive Care dataset (MIMIC II) database. Internal validation was based on the area under the receiver operating characteristic curve (AUROC) and the Brier score (BS). External validation was performed using an external dataset from Lariboisière hospital, Paris, France. RESULTS: Among 1151 patients included, 826 (72%) patients had at least 1 AHE during their ICU stay. Using 1 single random period per patient, the SL algorithm with Haar wavelets transform preprocessing was associated with an AUROC of 0.929 (95% confidence interval [CI], 0.899-0.958) and a BS of 0.08. Using all available periods for each patient, SL with Haar wavelets transform preprocessing was associated with an AUROC of 0.890 (95% CI, 0.886-0.895) and a BS of 0.11. In the external validation cohort, the AUROC reached 0.884 (95% CI, 0.775-0.993) with 1 random period per patient and 0.889 (0.768-1) with all available periods and BSs <0.1. CONCLUSIONS: The SL algorithm exhibits good performance for the prediction of an AHE 10 minutes ahead of time. It allows an efficient, robust, and rapid evaluation of the risk of hypotension that opens the way to routine use.

Clinical Significance of Upper Airway Virus Detection in Critically Ill Hematology Patients.

RATIONALE: Noninvasive diagnostic multiplex molecular tests may enable the early identification and treatment of viral infections in critically ill immunocompromised patients. OBJECTIVES: To assess the association between viral detection in nasopharyngeal swabs and ICU mortality in critically ill hematology patients. METHODS: This was a post hoc analysis of a prospective cohort of critically ill hematology patients admitted to 17 ICUs. Nasal swabs sampled and frozen at ICU admission were tested using a multiplex PCR assay. Predictors of ICU mortality and assay positivity were identified. MEASUREMENTS AND MAIN RESULTS: Of the 747 patients (447 with acute respiratory failure [ARF]), 21.3% had a virus detected (56.4% rhinovirus/enterovirus and 30.7% influenza/parainfluenza/respiratory syncytial viruses). Overall ICU and hospital mortality rates were 26% and 37%, respectively. Assay positivity was associated with lymphoproliferative disorders, hematopoietic stem cell transplantation, treatment with steroids or other immunosuppressants, ARF (25.5% vs. 16.3%; P = 0.004), and death in the ICU (28.9% vs. 19.3%; P = 0.008). The association with ICU mortality was significant for all viruses and was strongest for influenza/parainfluenza/respiratory syncytial viruses. In patients with ARF, detection of any respiratory virus was independently associated with ICU mortality (odds ratio, 2.07; 95% confidence interval, 1.22-3.50). CONCLUSIONS: Respiratory virus detection in the upper airway by multiplex PCR assay is common in critically ill hematology patients. In patients with ARF, respiratory virus detection was independently associated with ICU mortality. Multiplex PCR assay may prove helpful for the risk stratification of hematology patients with ARF. Studies to understand whether respiratory tract viruses play a causal role in outcomes are warranted.