Resilience and Mental-Health Symptoms in ICU Healthcare Professionals Facing Repeated COVID-19 Waves.

Rationale: Psychological resilience (the ability to thrive in adversity) may protect against mental-health symptoms in healthcare professionals during coronavirus disease (COVID-19) waves. Objectives: To identify determinants of resilience in ICU staff members. Methods: In this cross-sectional survey in 21 French ICUs, staff members completed the 10-item Connor-Davidson Resilience Scale, Hospital Anxiety and Depression Scale, and Impact of Event Scale-Revised (for post-traumatic stress disorder [PTSD]). Factors independently associated with resilience were identified. Measurements and Main Results: The response rate was 73.1% (950 of 1,300). The median 10-item Connor-Davidson Resilience Scale score was 29 (interquartile range, 25-32). Symptoms of anxiety, depression, and PTSD were present in 61%, 39%, and 36% of staff members, respectively. Distress associated with the COVID-19 infodemic was correlated with symptoms of depression and PTSD. More resilient respondents less often had symptoms of anxiety, depression, and PTSD. Greater resilience was independently associated with male sex, having provided intensive care during the early waves, having managed more than 50 patients with COVID-19, and, compared with earlier waves, working longer hours, having greater motivation, and more often involving families in end-of-life decisions. Independent risk factors for lower resilience were having managed more than 10 patients who died of COVID-19, having felt frightened or isolated, and greater distress from the COVID-19 infodemic. Conclusions: This study identifies modifiable determinants of resilience among ICU staff members. Longitudinal studies are needed to determine whether prior resilience decreases the risk of mental ill health during subsequent challenges. Hospital and ICU managers, for whom preserving mental well-being among staff members is a key duty, should pay careful attention to resilience.

Critically Ill Patients with Visceral Nocardia Infection, France and Belgium, 2004-2023.

We studied 50 patients with invasive nocardiosis treated during 2004-2023 in intensive care centers in France and Belgium. Most (65%) died in the intensive care unit or in the year after admission. Nocardia infections should be included in the differential diagnoses for patients in the intensive care setting.

Unchanged Characteristics and Survival among Critically Ill COVID-19 Patients during First, Second, and Third Waves: A Prospective Observational Cohort.

BACKGROUND: This study was carried out to compare characteristics and outcomes in patients with acute respiratory failure related to COVID-19 during first, second, and third waves. METHODS: We included consecutive adults admitted to the intensive care unit between March 2020 and July 2021. We compared three groups defined by the epidemic intake phase: waves 1 (W1), 2 (W2), and 3 (W3). RESULTS: We included 289 patients. Two hundred and eight (72%) patients were men with a median age of 63 years (IQR: 54-72), of whom 68 (23.6%) died in hospital. High-flow nasal oxygen (HFNO) was inversely associated with the need for invasive mechanical ventilation (MV) in multivariate analysis (p = 0.003) but not dexamethasone (p = 0.25). The day-90 mortality rate did not vary from W1 (27.4%) to W2 (23.9%) and W3 (22%), p = 0.67. By multivariate analysis, older age (odds ratio [OR]: 0.94/year, p < 0.001), immunodeficiency (OR: 0.33, p = 0.04), acute kidney injury (OR: 0.26, p < 0.001), and invasive MV (OR: 0.13, p < 0.001) were inversely associated with higher day-90 survival as opposed to the use of intermediate heparin thromboprophylaxis dose (OR: 3.21, p = 0.006). HFNO use and dexamethasone were not associated with higher day-90 survival (p = 0.24 and p = 0.56, respectively). CONCLUSIONS: In patients with acute respiratory failure due to COVID-19, survival did not change between first, second, and third waves while the use of invasive MV decreased. HFNO or intravenous steroids were not associated with better outcomes, whereas the use of intermediate dose of heparin for thromboprophylaxis was associated with higher day-90 survival. Larger multicentric studies are needed to confirm our findings.

Incidence of deep venous thrombosis in COVID-19 critically ill patients treated with intermediate-dose of heparin for thromboprophylaxis: The COVIDOP-DVT observational study.

INTRODUCTION: The high prevalence of deep vein thrombosis (DVT) in patients admitted to intensive care unit (ICU) for COVID-19-related acute respiratory distress syndrome (ARDS) would justify systematic screening of these patients or higher therapeutic dose of heparin for thromboprophylaxis. MATERIAL AND METHOD: We performed a systematic echo-Doppler of the lower limb proximal veins during the first 48 h (visit 1) and from 7 to 9 days after visit 1 (visit 2) in consecutive patients admitted to the ICU of a university-affiliated tertiary hospital for severe proven COVID-19 during the second wave. All patients received intermediate-dose heparin (IDH). The primary objective was to determine DVT incidence on venous Doppler ultrasound. Secondary objectives were to determine whether the presence of DVT modifies the anticoagulation regimen, the incidence of major bleeding according to International Society on Thrombosis and Haemostasis (ISTH) criteria, and the mortality rate of patients with and without DVT. RESULTS: We included 48 patients (30 [62.5%] men) with a median age of 63 years [IQR, 54-70]. The prevalence of proximal deep vein thrombosis was 4.2% (2/48). In these two patients, after DVT diagnosis, anticoagulation was changed from intermediate to curative dose. Two patients (4.2%) had a major bleeding complication according to ISTH criteria. Among the 48 patients, 9 (18.8%) died before hospital discharge. No DVT or pulmonary embolism was diagnosed in these deceased patients during their hospital stay. CONCLUSION: In critically ill patients with COVID-19, management with IDH results in a low incidence of DVT. Although our study is not designed to demonstrate any difference in outcome, our results do not suggest any signal of harm when using intermediate-dose heparin (IDH) COVID-19 with a frequency of major bleeding complications less than 5%.

Critically ill patients with severe infections related to Geotrichum species: A French retrospective multicentre study.

OBJECTIVES: Geotrichum spp can be responsible for severe infections in immunocompromised patients. We aim to describe Geotrichum-related infections in the ICU and to assess risk factors of mortality. METHODS: Retrospective multicentre study, conducted in 14 French ICUs between 2002 and 2018, including critically ill adult patients with proven or probable infection related to Geotrichum species. Data were obtained from the medical charts. RESULTS: Thirty-six patients, median age 60 years IQR [53; 66] were included. Most of the patients had haematological malignancies (78%). The reason for ICU admission was shock in half of the patients (n = 19, 53%) and respiratory failure in thirteen patients (36%). Median SOFA score was 8.5 IQR [7; 15]. Time between ICU admission and fungal diagnosis was 2.5 days [-1; 4]. Infection was disseminated in 27 (75%) patients with positive blood cultures in 25 patients (69%). Thirty patients (83%) received curative antifungal treatment in the ICU, in a median time of 1 day [0;1] after ICU admission. Twenty-four patients (67%) died in the ICU and hospital mortality rate was 69%. The number and extent of organ failures, as represented by SOFA score, were associated with mortality. CONCLUSIONS: This study demonstrates poor outcome in critically ill patients with Geotrichum-related infections, which encourages a high level of suspicion.

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.

Intravenous Artesunate for the Treatment of Severe Imported Malaria: Implementation, Efficacy, and Safety in 1391 Patients.

BACKGROUND: Intravenous artesunate is the World Health Organization-recommended first-line treatment for severe malaria worldwide, but it is still not fully licensed in Europe. Observational studies documenting its safety and efficacy in imported malaria are thus essential. METHODS: We prospectively collected clinical and epidemiological features of 1391 artesunate-treated patients among 110 participant centers during the first 7 years (2011-2017) of a national program implemented by the French Drug Agency. RESULTS: Artesunate became the most frequent treatment for severe malaria in France, rising from 9.9% in 2011 to 71.4% in 2017. Mortality was estimated at 4.1%. Treatment failure was recorded in 27 patients, but mutations in the Kelch-13 gene were not observed. Main reported adverse events (AEs) were anemia (136 cases), cardiac events (24, including 20 episodes of conduction disorders and/or arrhythmia), and liver enzyme elevation (23). Mortality and AEs were similar in the general population and in people with human immunodeficiency virus, who were overweight, or were pregnant, but the only pregnant woman treated in the first trimester experimented a hemorrhagic miscarriage. The incidence of post-artesunate-delayed hemolysis (PADH) was 42.8% when specifically assessed in a 98-patient subgroup, but was not associated with fatal outcomes or sequelae. PADH was twice as frequent in patients of European compared with African origin. CONCLUSIONS: Artesunate was rapidly deployed and displayed a robust clinical benefit in patients with severe imported malaria, despite a high frequency of mild to moderate PADH. Further explorations in the context of importation should assess outcomes during the first trimester of pregnancy and collect rare but potentially severe cardiac AEs.

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.

Rapid screening of COVID-19 patients using white blood cell scattergrams, a study on 381 patients.

Complementary tools are warranted to increase the sensitivity of the initial testing for COVID-19. We identified a specific 'sandglass' aspect on the white blood cell scattergram of COVID-19 patients reflecting the presence of circulating plasmacytoid lymphocytes. Patients were dichotomized as COVID-19-positive or -negative based on reverse transcriptase polymerase chain reaction (RT-PCR) and chest computed tomography (CT) scan results. Sensitivity and specificity of the 'sandglass' aspect were 85·9% and 83·5% respectively. The positive predictive value was 94·3%. Our findings provide a non-invasive and simple tool to quickly categorize symptomatic patients as either COVID-19-probable or -improbable especially when RT-PCR and/or chest CT are not rapidly available.

Oxygenation Strategy During Acute Respiratory Failure in Critically-Ill Immunocompromised Patients.

OBJECTIVES: To assess the response to initial oxygenation strategy according to clinical variables available at admission. DESIGN: Multicenter cohort study. SETTING: Thirty French and Belgium medical ICU. SUBJECTS: Immunocompromised patients with hypoxemic acute respiratory failure. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Data were extracted from the Groupe de Recherche en Reanimation Respiratoire du patient d'Onco-Hématologie database. Need for invasive mechanical ventilation was the primary endpoint. Secondary endpoint was day-28 mortality. Six-hundred forty-nine patients were included. First oxygenation strategies included standard oxygen (n = 245, 38%), noninvasive ventilation (n = 285; 44%), high-flow nasal cannula oxygen (n = 55; 8%), and noninvasive ventilation + high-flow nasal cannula oxygen (n = 64; 10%). Bilateral alveolar pattern (odds ratio = 1.67 [1.03-2.69]; p = 0.04), bacterial (odds ratio = 1.98 [1.07-3.65]; p = 0.03) or opportunistic infection (odds ratio = 4.75 [2.23-10.1]; p < 0.001), noninvasive ventilation use (odds ratio = 2.85 [1.73-4.70]; p < 0.001), Sequential Organ Failure Assessment score (odds ratio = 1.19 [1.10-1.28]; p < 0.001), and ratio of PaO2 and FIO2 less than 100 at ICU admission (odds ratio = 1.96 [1.27-3.02]; p = 0.0002) were independently associated with intubation rate. Day-28 mortality was independently associated with bacterial (odds ratio = 2.34 [1.10-4.97]; p = 0.03) or opportunistic infection (odds ratio = 4.96 [2.11-11.6]; p < 0.001), noninvasive ventilation use (odds ratio = 2.35 [1.35-4.09]; p = 0.003), Sequential Organ Failure Assessment score (odds ratio = 1.19 [1.10-1.28]; p < 0.001), and ratio of PaO2 and FIO2 less than 100 at ICU admission (odds ratio = 1.97 [1.26-3.09]; p = 0.003). High-flow nasal cannula oxygen use was neither associated with intubation nor mortality rates. CONCLUSIONS: Some clinical characteristics at ICU admission including etiology and severity of acute respiratory failure enable to identify patients at high risk for intubation.

Sepsis and Septic Shock in Patients With Malignancies: A Groupe de Recherche Respiratoire en Réanimation Onco-Hématologique Study.

OBJECTIVES: Cancer affects up to 20% of critically ill patients, and sepsis is one of the leading reasons for ICU admission in this setting. Early signals suggested that survival might be increasing in this population. However, confirmation studies have been lacking. The goal of this study was to assess trends in survival rates over time in cancer patients admitted to the ICU for sepsis or septic shock over the last 2 decades. DATA SOURCE: Seven European ICUs. STUDY SELECTION: A hierarchical model taking into account the year of admission and the source dataset as random variables was used to identify risk factors for day 30 mortality. DATA EXTRACTION: Data from cancer patients admitted to ICUs for sepsis or septic shock were extracted from the Groupe de Recherche Respiratoire en Réanimation Onco-Hématologique database (1994-2015). DATA SYNTHESIS: Overall, 2,062 patients (62% men, median [interquartile range] age 59 yr [48-67 yr]) were included in the study. Underlying malignancies were solid tumors (n = 362; 17.6%) or hematologic malignancies (n = 1,700; 82.4%), including acute leukemia (n = 591; 28.7%), non-Hodgkin lymphoma (n = 461; 22.3%), and myeloma (n = 244; 11.8%). Two-hundred fifty patients (12%) underwent allogeneic hematopoietic stem cell transplantation and 640 (31.0%) were neutropenic at ICU admission. Day 30 mortality was 39.9% (823 deaths). The year of ICU admission was associated with significant decrease in day 30 mortality over time (odds ratio, 0.96; 95% CI, 0.93-0.98; p = 0.001). Mechanical ventilation (odds ratio, 3.25; 95% CI, 2.52-4.19; p < 0.01) and vasopressors use (odds ratio, 1.42; 95% CI, 1.10-1.83; p < 0.01) were independently associated with day 30 mortality, whereas underlying malignancy, allogeneic hematopoietic stem cell transplantation, and neutropenia were not. CONCLUSIONS: Survival in critically ill oncology and hematology patients with sepsis improved significantly over time. As outcomes improve, clinicians should consider updating admission policies and goals of care in this population.

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.

Center effect in intubation risk in critically ill immunocompromised patients with acute hypoxemic respiratory failure.

BACKGROUND: Acute respiratory failure is the leading reason for intensive care unit (ICU) admission in immunocompromised patients, and the need for invasive mechanical ventilation has become a major clinical endpoint in randomized controlled trials (RCTs). However, data are lacking on whether intubation is an objective criteria that is used unbiasedly across centers. This study explores how this outcome varies across ICUs. METHODS: Hierarchical models and permutation procedures for testing multiple random effects were applied on both data from an observational cohort (the TRIAL-OH study: 703 patients, 17 ICUs) and a randomized controlled trial (the HIGH trial: 776 patients, 31 ICUs) to characterize ICU variation in intubation risk across centers. RESULTS: The crude intubation rate varied across ICUs from 29 to 80% in the observational cohort and from 0 to 86% in the RCT. This center effect on the mean ICU intubation rate was statistically significant, even after adjustment on individual patient characteristics (observational cohort: p value = 0.013, median OR 1.48 [1.30-1.72]; RCT: p value 0.004, median OR 1.51 [1.36-1.68]). Two ICU-level characteristics were associated with intubation risk (the annual rate of intubation procedure per center and the time from respiratory symptoms to ICU admission) and could partly explain this center effect. In the RCT that controlled for the use of high-flow oxygen therapy, we did not find significant variation in the effect of oxygenation strategy on intubation risk across centers, despite a significant variation in the need for invasive mechanical ventilation. CONCLUSION: Intubation rates varied considerably among ICUs, even after adjustment on individual characteristics.

Influenza and associated co-infections in critically ill immunosuppressed patients.

BACKGROUND: It is unclear whether influenza infection and associated co-infection are associated with patient-important outcomes in critically ill immunocompromised patients with acute respiratory failure. METHODS: Preplanned secondary analysis of EFRAIM, a prospective cohort study of 68 hospitals in 16 countries. We included 1611 patients aged 18 years or older with non-AIDS-related immunocompromise, who were admitted to the ICU with acute hypoxemic respiratory failure. The main exposure of interest was influenza infection status. The primary outcome of interest was all-cause hospital mortality, and secondary outcomes ICU length of stay (LOS) and 90-day mortality. RESULTS: Influenza infection status was categorized into four groups: patients with influenza alone (n = 95, 5.8%), patients with influenza plus pulmonary co-infection (n = 58, 3.6%), patients with non-influenza pulmonary infection (n = 820, 50.9%), and patients without pulmonary infection (n = 638, 39.6%). Influenza infection status was associated with a requirement for intubation and with LOS in ICU (P < 0.001). Patients with influenza plus co-infection had the highest rates of intubation and longest ICU LOS. On crude analysis, influenza infection status was associated with ICU mortality (P < 0.001) but not hospital mortality (P = 0.09). Patients with influenza plus co-infection and patients with non-influenza infection alone had similar ICU mortality (41% and 37% respectively) that was higher than patients with influenza alone or those without infection (33% and 26% respectively). A propensity score-matched analysis did not show a difference in hospital mortality attributable to influenza infection (OR = 1.01, 95%CI 0.90-1.13, P = 0.85). Age, severity scores, ARDS, and performance status were all associated with ICU, hospital, and 90-day mortality. CONCLUSIONS: Category of infectious etiology of respiratory failure (influenza, non-influenza, influenza plus co-infection, and non-infectious) was associated with ICU but not hospital mortality. In a propensity score-matched analysis, influenza infection was not associated with the primary outcome of hospital mortality. Overall, influenza infection alone may not be an independent risk factor for hospital mortality in immunosuppressed patients.

A Multivariable Prediction Model for Pneumocystis jirovecii Pneumonia in Hematology Patients with Acute Respiratory Failure.

RATIONALE: The incidence of Pneumocystis jirovecii pneumonia (PjP) is rising. Longer time to treatment is associated with higher mortality. OBJECTIVES: To develop a multivariable risk prediction model for PjP diagnosis. METHODS: In a prospective multicenter cohort of ICU patients with hematological malignancies and acute respiratory failure, factors associated with documented PjP were identified. The risk prediction model was tested in an independent prospective multicenter cohort. We assessed discrimination (by areas under the receiver operating characteristic curves [AUCs]) and goodness of fit (by Hosmer-Lemeshow statistics). Model performance was assessed using 30 sets of imputed data sets. MEASUREMENTS AND MAIN RESULTS: Among the 1,330 patients, 134 of 1,092 (12.3%; 95% confidence interval [CI], 10.4-14.4%) had proven PjP in the derivation cohort, as did 15 of 238 (6.3%, 95% CI, 3.6-10.2%) in the validation cohort. The model included age, lymphoproliferative disease, anti-Pneumocystis prophylaxis, the number of days between respiratory symptom onset and ICU admission, shock, chest radiograph pattern, and pleural effusion. The median (interquartile range) score was 3.5 (1.5-5.0) (range, -3.5 to 8.5) in the derivation cohort and 1.0 (0-2.0) (range, -3.5 to 6.0) in the validation cohort. The best threshold was defined on the validation sample as 3, allowing us to reach 86.7% sensitivity and 67.7% specificity for PjP, with a negative predictive value of 97.9% in the case of 10% prevalence. The score had good calibration (goodness of fit, -0.75) and discrimination in the derivation cohort (mean AUC, 0.80; 95% CI, 0.76-0.84) and validation cohort (mean AUC, 0.83; 95% CI, 0.72-0.93). CONCLUSIONS: The PjP score for hematology patients with acute respiratory failure can be computed at admission, based on readily available variables. Potential clinical benefits of using this score deserve assessment.

Diagnostic Accuracy of Procalcitonin for Early Aspiration Pneumonia in Critically Ill Patients with Coma: A Prospective Study.

BACKGROUND: Early diagnostic orientation for differentiating pneumonia from pneumonitis at the early stage after aspiration would be valuable to avoid unnecessary antibiotic therapy. We assessed the accuracy of procalcitonin (PCT) in diagnosing aspiration pneumonia (AP) in intensive care unit (ICU) patients requiring mechanical ventilation after out-of-hospital coma. METHODS: Prospective observational 2-year cohort study in a medical-surgical ICU. PCT, C-reactive protein (CRP) and white blood cell count (WBC) were measured at admission (H0) and 6 h (H), H12, H24, H48, H96, and H120 after inclusion. Lower respiratory tract microbiological investigations performed routinely in patients with aspiration syndrome were the reference standard for diagnosing AP. Performance of PCT, CRP, and WBC up to H48 in diagnosing AP was compared based on the areas under the ROC curves (AUC) and likelihood ratios (LR+ and LR-) computed for the best cutoff values. RESULTS: Of 103 patients with coma, 45 (44%) had AP. Repeated PCT assays demonstrated a significant increase in patients with AP versus without AP from H0 to H120. Among the three biomarkers, PCT showed the earliest change. ROC-AUC values were poor for all three biomarkers. Best ROC-AUC values for diagnosing AP were for CRP at H24 [0.73 (95%CI 0.61-0.84)] and PCT at H48 [0.73 (95%CI 0.61-0.84)]. LR+ was best for PCT at H24 (3.5) and LR- for CRP and WBC at H24 (0.4 and 0.4, respectively). CONCLUSIONS: Early and repeated assays of PCT, CRP, and WBC demonstrated significant increases in all three biomarkers in patients with versus without AP. All three biomarkers had poor diagnostic performance for ruling out AP. Whereas PCT had the fastest kinetics, PCT assays within 48 h after ICU admission do not help to diagnose AP in ICU patients with coma.

Endothelial Cell-Specific Molecule-1 in Critically Ill Patients With Hematologic Malignancy.

OBJECTIVES: To assess whether serum concentration of endothelial cell-specific molecule-1 (Endocan) at ICU admission is associated with the use of ICU resources and outcomes in critically ill hematology patients. DESIGN: Prospective multicenter cohort study. SETTING: Seventeen ICUs in France and Belgium. PATIENTS: Seven hundred forty-four consecutive critically ill hematology patients; 72 critically ill septic patients without hematologic malignancy; 276 healthy subjects. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: Median total endocan concentrations were 4.46 (2.7-7.8) ng/mL. Endocan concentrations were higher in patients who had received chemotherapy before ICU admission (4.7 [2.8-8.1] ng/mL vs. 3.7 [2.5-6.3] ng/mL [p = 0.002]). In patients with acute respiratory failure, endocan levels were increased in patients with drug-induced pulmonary toxicity compared with other etiologies (p = 0.038). Total endocan levels higher than 4.46 ng/mL were associated with a higher cumulative probability of renal replacement therapy requirement (p = 0.006), a higher requirement of mechanical ventilation (p = 0.01) and a higher requirement of vasopressors throughout ICU stay (p < 0.0001). By multivariate analysis, total endocan levels at admission were independently associated with ICU mortality (odds ratios, 1.39; 95% CI, 1.06-1.83; p = 0.018). The predictive value of endocan peptide fragments of 14 kDa in terms of mortality and life-sustaining therapies requirement was inferior to that of total endocan. Endocan levels were higher in critically ill hematology patients compared with healthy subjects (p < 0.0001) but lower than endocan values in critically ill septic patients without hematologic malignancy (p = 0.005) CONCLUSIONS:: Serum concentrations of endocan at admission are associated with the use of ICU resources and mortality in critically ill hematology patients. Studies to risk-stratify patients in the emergency department or in the hematology wards based on endocan concentrations to identify those likely to benefit from early ICU management are warranted.

Effect of High-Flow Nasal Oxygen vs Standard Oxygen on 28-Day Mortality in Immunocompromised Patients With Acute Respiratory Failure: The HIGH Randomized Clinical Trial.

Importance: High-flow nasal oxygen therapy is increasingly used for acute hypoxemic respiratory failure (AHRF). Objective: To determine whether high-flow oxygen therapy decreases mortality among immunocompromised patients with AHRF compared with standard oxygen therapy. Design, Setting, and Participants: The HIGH randomized clinical trial enrolled 776 adult immunocompromised patients with AHRF (Pao2 <60 mm Hg or Spo2 <90% on room air, or tachypnea >30/min or labored breathing or respiratory distress, and need for oxygen ≥6 L/min) at 32 intensive care units (ICUs) in France between May 19, 2016, and December 31, 2017. Interventions: Patients were randomized 1:1 to continuous high-flow oxygen therapy (n = 388) or to standard oxygen therapy (n = 388). Main Outcomes and Measures: The primary outcome was day-28 mortality. Secondary outcomes included intubation and mechanical ventilation by day 28, Pao2:Fio2 ratio over the 3 days after intubation, respiratory rate, ICU and hospital lengths of stay, ICU-acquired infections, and patient comfort and dyspnea. Results: Of 778 randomized patients (median age, 64 [IQR, 54-71] years; 259 [33.3%] women), 776 (99.7%) completed the trial. At randomization, median respiratory rate was 33/min (IQR, 28-39) vs 32 (IQR, 27-38) and Pao2:Fio2 was 136 (IQR, 96-187) vs 128 (IQR, 92-164) in the intervention and control groups, respectively. Median SOFA score was 6 (IQR, 4-8) in both groups. Mortality on day 28 was not significantly different between groups (35.6% vs 36.1%; difference, -0.5% [95% CI, -7.3% to +6.3%]; hazard ratio, 0.98 [95% CI, 0.77 to 1.24]; P = .94). Intubation rate was not significantly different between groups (38.7% vs 43.8%; difference, -5.1% [95% CI, -12.3% to +2.0%]). Compared with controls, patients randomized to high-flow oxygen therapy had a higher Pao2:Fio2 (150 vs 119; difference, 19.5 [95% CI, 4.4 to 34.6]) and lower respiratory rate after 6 hours (25/min vs 26/min; difference, -1.8/min [95% CI, -3.2 to -0.2]). No significant difference was observed in ICU length of stay (8 vs 6 days; difference, 0.6 [95% CI, -1.0 to +2.2]), ICU-acquired infections (10.0% vs 10.6%; difference, -0.6% [95% CI, -4.6 to +4.1]), hospital length of stay (24 vs 27 days; difference, -2 days [95% CI, -7.3 to +3.3]), or patient comfort and dyspnea scores. Conclusions and Relevance: Among critically ill immunocompromised patients with acute respiratory failure, high-flow oxygen therapy did not significantly decrease day-28 mortality compared with standard oxygen therapy. Trial Registration: clinicaltrials.gov Identifier: NCT02739451.

Urgent Chemotherapy for Life-Threatening Complications Related to Solid Neoplasms.

OBJECTIVES: Solid neoplasms can be directly responsible for organ failures at the time of diagnosis or relapse. The management of such specific complications relies on urgent chemotherapy and eventual instrumental or surgical procedures, combined with advanced life support. We conducted a multicenter study to address the prognosis of this condition. DESIGN: A multicenter retrospective (2001-2015) chart review. SETTING: Medical and respiratory ICUs. PATIENTS: Adult patients who received urgent chemotherapy in the ICU for organ failure related to solid neoplasms were included. The modalities of chemotherapy, requirements of adjuvant instrumental or surgical procedures, and organ supports were collected. Endpoints were short- and long-term survival rates. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: One hundred thirty-six patients were included. Lung cancer was the most common malignancy distributed into small cell lung cancer (n = 57) and non-small cell lung cancer (n = 33). The main reason for ICU admission was acute respiratory failure in 111 patients (81.6%), of whom 89 required invasive mechanical ventilation. Compression and tissue infiltration by tumor cells were the leading mechanisms resulting in organ involvement in 78 (57.4%) and 47 (34.6%) patients. The overall in-ICU, in-hospital, 6-month, and 1-year mortality rates were 37%, 58%, 74%, and 88%, respectively. Small cell lung cancer was identified as an independent predictor of hospital survival. However, this gain in survival was not sustained since the 1-year survival rates of small cell lung cancer, non-small cell lung cancer, and non-lung cancer patients all dropped below 20%. CONCLUSIONS: Urgent chemotherapy along with aggressive management of organ failures in the ICU can be lifesaving in very selected cancer patients, most especially with small cell lung cancer, although the long-term survival is hardly sustainable.

High-Flow Nasal Cannula Oxygenation in Immunocompromised Patients With Acute Hypoxemic Respiratory Failure: A Groupe de Recherche Respiratoire en Réanimation Onco-Hématologique Study.

OBJECTIVE: In immunocompromised patients with acute respiratory failure, invasive mechanical ventilation remains associated with high mortality. Choosing the adequate oxygenation strategy is of the utmost importance in that setting. High-flow nasal oxygen has recently shown survival benefits in unselected patients with acute respiratory failure. The objective was to assess outcomes of immunocompromised patients with hypoxemic acute respiratory failure treated with high-flow nasal oxygen. DESIGN: We performed a post hoc analysis of a randomized controlled trial of noninvasive ventilation in critically ill immunocompromised patients with hypoxemic acute respiratory failure. SETTING: Twenty-nine ICUs in France and Belgium. PATIENTS: Critically ill immunocompromised patients with hypoxemic acute respiratory failure. INTERVENTION: A propensity score-based approach was used to assess the impact of high-flow nasal oxygen compared with standard oxygen on day 28 mortality. MEASUREMENTS AND MAIN RESULTS: Among 374 patients included in the study, 353 met inclusion criteria. Underlying disease included mostly malignancies (n = 296; 84%). Acute respiratory failure etiologies were mostly pneumonia (n = 157; 44.4%) or opportunistic infection (n = 76; 21.5%). Noninvasive ventilation was administered to 180 patients (51%). Invasive mechanical ventilation was ultimately needed in 142 patients (40.2%). Day 28 mortality was 22.6% (80 deaths). Throughout the ICU stay, 127 patients (36%) received high-flow nasal oxygen whereas 226 patients received standard oxygen. Ninety patients in each group (high-flow nasal oxygen or standard oxygen) were matched according to the propensity score, including 91 of 180 (51%) who received noninvasive ventilation. High-flow nasal oxygen was neither associated with a lower intubation rate (hazard ratio, 0.42; 95% CI, 0.11-1.61; p = 0.2) nor day 28 mortality (hazard ratio, 0.80; 95% CI, 0.45-1.42; p = 0.45). CONCLUSIONS: In immunocompromised patients with hypoxemic acute respiratory failure, high-flow nasal oxygen when compared with standard oxygen did not reduce intubation or survival rates. However, these results could be due to low statistical power or unknown confounders associated with the subgroup analysis. A randomized trial is needed.