Multicenter Retrospective Study of Invasive Fusariosis in Intensive Care Units, France.

Invasive fusariosis can be life-threatening, especially in immunocompromised patients who require intensive care unit (ICU) admission. We conducted a multicenter retrospective study to describe clinical and biologic characteristics, patient outcomes, and factors associated with death and response to antifungal therapy. We identified 55 patients with invasive fusariosis from 16 ICUs in France during 2002----2020. The mortality rate was high (56%). Fusariosis-related pneumonia occurred in 76% of patients, often leading to acute respiratory failure. Factors associated with death included elevated sequential organ failure assessment score at ICU admission or history of allogeneic hematopoietic stem cell transplantation or hematologic malignancies. Neither voriconazole treatment nor disseminated fusariosis were strongly associated with response to therapy. Invasive fusariosis can lead to multiorgan failure and is associated with high mortality rates in ICUs. Clinicians should closely monitor ICU patients with a history of hematologic malignancies or stem cell transplantation because of higher risk for death.

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.

Cancer and sepsis: future challenges for long-term outcome.

PURPOSE OF REVIEW: The purpose of this review is to investigate the long-term outcomes of cancer patients who experience sepsis or septic shock. RECENT FINDINGS: Sepsis is a frequent cause of ICU admission in cancer patients, accounting for approximately 15% of such cases. Short-term mortality rates among these patients vary widely across studies, but they are consistently found to be slightly higher than those of noncancer patients. However, there is a lack of evidence regarding the long-term outcomes of cancer patients who have experienced sepsis or septic shock. The few available studies have reported relatively high mortality rates, reaching around 80% in a few cohort studies. Although several observational studies have noted a decrease in 1-year mortality rates over time, observational data also suggest that sepsis may increase the risk of cancer in the long run. SUMMARY: As cancer is becoming a chronic disease, there is an urgent need for studies on the quality of life of cancer patients who have experienced sepsis. The relationship between sepsis and cancer extends beyond its impact on the progression of cancer, as sepsis might also contribute to the development of cancer.

Septic shock and biliary sepsis: 90-day mortality and associated risk factors.

BACKGROUND: Biliary sepsis is common in patients with digestive cancer. Recommendations call for antibiotic de-escalation (ADE) as a strategy for antibiotic treatment of sepsis or septic shock. The aim of this study was to identify factors influencing 90-day mortality and to evaluate the impact of ADE. METHODS: This retrospective study was conducted between November 2008 and December 2019 in a referral cancer center. Adults with biliary sepsis or septic shock admitted to the ICU were included. Variables associated with 90-day mortality were identified using univariate and multivariate Cox proportional hazards models. RESULTS: 122 patients were included. The 90-day mortality was 30.3% (n = 37). After multivariate analysis, the factors independently associated 90-day mortality were metastatic stage (p = 0.004), biliary tract tumour compression (p = 0.001), multi drug resistant (MDR) bacteria carriage on intensive care unit (ICU)admission (p = 0.048), serum lactate on ICU admission (p < 0.001), the use of extra-renal replacement (p = 0.008), factor V < 50% (p = 0.009) and performance status (ECOG-PS) > 2 (p < 0.001). ADE of the pivotal antibiotic (p = 0.041) and recent cancer surgery (p < 0.001) appeared to be associated with survival. CONCLUSION: The 90-day mortality of biliary sepsis seems to be favourable. The 90-day mortality is associated with organ dysfunctions, but also with ECOG-PS, cancer stage, MDR bacteria colonisation. ADE seems to be safe.

Factors Associated with 1-Year Mortality in Elderly Patients (Age ≥ 80 Years) with Cancer Undergoing Major Abdominal Surgery: A Retrospective Cohort Study.

BACKGROUND: The number of elderly patients undergoing major abdominal surgery is increasing, but the factors affecting their postoperative outcomes remain unclear. This study aimed to identify the factors associated with 1-year mortality among elderly patients (age ≥ 80 years) with cancer undergoing major abdominal surgery. METHODS: This retrospective cohort study was conducted from March 2009 to December 2020. The study enrolled 378 patients 80 years old or older who underwent major abdominal surgery. The main outcome was 1-year mortality, and the factors associated with mortality were analyzed. RESULTS: Of the 378 patients, 92 died at 1 year (24.3%), whereas the 30-day mortality rate was 4% (n = 15). In the multivariate analysis, the factors independently associated with 1-year mortality were preoperative Eastern Cooperative Oncology Group (ECOG) performance status (PS) score higher than 1 (odds ratio [OR], 3.189; 95% confidence interval [CI], 1.595-6.377; p = 0.001), preoperative weight loss greater than 3 kg (OR, 2.145; 95% CI, 1.044-4.404; p = 0.038), use of an intraoperative vasopressor (OR, 3.090; 95% CI, 1.188-8.042; p = 0.021), and postoperative red blood cell units (OR, 1.212; 95% CI, 1.045-1.405; p = 0.011). Survival was associated with perioperative management according to an enhanced recovery after surgery (ERAS) protocol (OR, 0.370; 95% CI, 0.160-0.854; p = 0.006) and supramesocolic surgery (OR, 0.371; 95% CI, 0.158-0.871; p = 0.023). CONCLUSION: The study identified several factors associated with an encouraging 1-year mortality rate in this setting. These results highlight the need for identification of suitable targets to optimize pre-, intra-, and postoperative management in order to improve outcomes for this vulnerable population.

Hepatic haemophagocytosis in haematology patients with hepatic dysfunction: prognostic impact and contribution of liver biopsy combined with the haemophagocytic syndrome diagnostic score (HScore).

Hepatic dysfunction (HD) is common in patients with haematological malignancies. Hepatic haemophagocytosis (HH) was detected in >50% of liver biopsies taken when HD remained unresolved after standard examination. We aimed to explore the contribution of liver biopsy in patients with both haematological malignancies and HD, describe the population of patients with HH, assess the prognostic impact of HH, and investigate haemophagocytic syndrome diagnostic score (HScore) utility in patients with HH. Between 2016 and 2019, 116 consecutive liver biopsies (76 transjugular, 40 percutaneous) were taken in 110 patients with haematological malignancy and HD (hyperbilirubinaemia, elevated transaminases, and/or cholestasis) and without a clear diagnosis. Liver biopsies were safe and diagnostically efficient. Predominant diagnoses included: HH (56%), graft-versus-host disease (55%), associated infections (24%), sinusoidal obstruction syndrome (15%), and tumoral infiltration (8%). Of patients, 35% were critically ill and 74% were allogeneic haematopoietic stem cell transplantation recipients, while 1-year overall survival (OS) was 35% with HH versus 58% without HH (p = 0.026). The 1-year OS was 24% with a HScore of ≥169 versus 50% with a HScore of <169 (p = 0.019). Liver biopsies are feasible in and contribute significantly to haematology patients with HD. HH occurred frequently and was associated with a poor prognosis. Combined with liver biopsy, the HScore may be helpful in refining haemophagocytic syndrome diagnosis.

Double purse-string telescoped pancreaticogastrostomy is not superior in preventing pancreatic fistula development in high-risk anastomosis: a 6-year single-center case-control study.

PURPOSE: The double purse-string telescoped pancreaticogastrostomy (PG) technique has been suggested as an alternative approach to reduce the risk of postoperative pancreatic fistula (POPF). Its efficacity in high-risk situations has not yet been explored. This study compared the incidence of clinically relevant POPF (CR-POPF) between patients with high-risk anastomosis undergoing PG and those undergoing pancreaticojejunostomy (PJ). METHODS: From 2013 to 2019, 198 consecutive patients with high-risk anastomosis, an updated alternative fistula risk score > 20%, and who underwent pancreatoduodenectomy with the PJ (165) or PG (33) technique were included. Optimal mitigation strategy (external stenting/octreotide omission) was applied for all patients. The primary endpoint was the incidence of CR-POPF. RESULTS: The mean ua-FRS was 33%. CR-POPF (grade B/C) was found in 42 patients (21%) and postoperative hemorrhage in 30 (15%); the mortality rate was 4%. CR-POPF rates were comparable between the PJ (19%) and PG (33%) groups (P = 0.062). The PG group had a higher rate of POPF grade C (24% vs. 10%; P = 0.036), longer operative time (P = 0.019), and a higher transfusion rate (P < 0.001), even after a matching process on ua-FRS. In the multivariate analysis, the type of anastomosis (P = 0.88), body mass index (P = 0.47), or main pancreatic duct diameter (P = 0.7) did not influence CR-POPF occurrence. CONCLUSIONS: For patients with high-risk anastomosis, the double purse-string telescoped PG technique was not superior to the PJ technique for preventing CR-POPF.

Survival in Immunocompromised Patients Ultimately Requiring Invasive Mechanical Ventilation: A Pooled Individual Patient Data Analysis.

Rationale: Acute respiratory failure (ARF) is associated with high mortality in immunocompromised patients, particularly when invasive mechanical ventilation is needed. Therefore, noninvasive oxygenation/ventilation strategies have been developed to avoid intubation, with uncertain impact on mortality, especially when intubation is delayed. Objectives: We sought to report trends of survival over time in immunocompromised patients receiving invasive mechanical ventilation. The impact of delayed intubation after failure of noninvasive strategies was also assessed. Methods: Systematic review and meta-analysis using individual patient data of studies that focused on immunocompromised adult patients with ARF requiring invasive mechanical ventilation. Studies published in English were identified through PubMed, Web of Science, and Cochrane Central (2008-2018). Individual patient data were requested from corresponding authors for all identified studies. We used mixed-effect models to estimate the effect of delayed intubation on hospital mortality and described mortality rates over time. Measurements and Main Results: A total of 11,087 patients were included (24 studies, three controlled trials, and 21 cohorts), of whom 7,736 (74%) were intubated within 24 hours of ICU admission (early intubation). The crude mortality rate was 53.2%. Adjusted survivals improved over time (from 1995 to 2017, odds ratio [OR] for hospital mortality per year, 0.96 [0.95-0.97]). For each elapsed day between ICU admission and intubation, mortality was higher (OR, 1.38 [1.26-1.52]; P < 0.001). Early intubation was significantly associated with lower mortality (OR, 0.83 [0.72-0.96]), regardless of initial oxygenation strategy. These results persisted after propensity score analysis (matched OR associated with delayed intubation, 1.56 [1.44-1.70]). Conclusions: In immunocompromised intubated patients, survival has improved over time. Time between ICU admission and intubation is a strong predictor of mortality, suggesting a detrimental effect of late initial oxygenation failure.

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.

Sepsis and Cancer: An Interplay of Friends and Foes.

Sepsis and cancer share a number of pathophysiological features, and both result from the inability of the host's immune system to cope with the initial insult (tissue invasion by pathogens and malignant cell transformation, respectively). The common coexistence of both disorders and the profound related alterations in immune homeostasis raise the question of their mutual impact on each other's course. This translational review aims to discuss the interactions between cancer and sepsis supported by clinical data and the translation to experimental models. The dramatic improvement in cancer has come at a cost of increased risks of life-threatening infectious complications. Investigating the long-term outcomes of sepsis survivors has revealed an unexpected susceptibility to cancer long after discharge from the ICU. Nonetheless, it is noteworthy that an acute septic episode may harbor antitumoral properties under particular circumstances. Relevant double-hit animal models have provided clues to whether and how bacterial sepsis may impact malignant tumor growth. In sequential sepsis-then-cancer models, postseptic mice exhibited accelerated tumor growth. When using reverse cancer-then-sepsis models, bacterial sepsis applied to mice with cancer conversely resulted in inhibition or even regression of tumor growth. Experimental models thus highlight dual effects of sepsis on tumor growth, mostly depending on the sequence of insults, and allow deciphering the immune mechanisms and their relation with microorganisms.

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.

Antimicrobial Stewardship in Hematological Patients at the intensive care unit: a global cross-sectional survey from the Nine-i Investigators Network.

A global cross-sectional survey was performed to gather data on the current treatment of infections caused by multidrug-resistant (MDR) bacteria among hematological patients admitted to ICUs worldwide. The survey was performed in April 2019 using an electronic platform (SurveyMonkey®) being distributed among 83 physicians and completed by 48 (57.8%) responders. ESBL Enterobacteriaceae, carbapenem-resistant K. pneumoniae and carbapenem-resistant P. aeruginosa were the main concerns. Previous MDR infection (34% of responders), MDR colonization (20%) and previous antibiotic exposure within the last 3 months (20.5%) were considered the most relevant risk factors of bloodstream infection (BSI) due to MDR bacteria. In 48.8% of the ICUs, there was no antimicrobial stewardship (AMS) team focused on hematological patients. Updates on local epidemiology of MDR pathogens were provided in 98% of the centers, using phone or verbal communications (56.1% and 53.7%, respectively). In presence of febrile neutropenia, initial therapy consisted of anti-Gram-negative plus anti-Gram-positive antibiotics for 41% of participants. Antibiotic de-escalation and/or discontinuation of therapy were considered as a promising strategy for the prevention of MDR development (32.4%). Factors associated with antibiotic de-escalation were clinical improvement (43.6%) and neutrophil count recovery (12.8%). Infectious Disease consultation and AMS interventions were not determining factors for de-escalation decisions (more than 50% of responders). Infection control and educational programs were valued as necessary measures for implementation by ICU practitioners. These findings should guide future efforts on collaborative team working, improving compliance with adequate treatment protocols, implementing antimicrobial stewardship programs in critically ill hematological patients, and educational activities.

Prediction of early discharge after gynaecological oncology surgery within ERAS.

OBJECTIVES: Enhanced recovery after surgery programs (ERAS) have been proven to decrease the length of hospital stay without increasing readmission rates or complications. However, the patient and operative characteristics that improve the chance of a successful early hospital discharge are not well established. The aim of this study was to design a nomogram which could be used before surgery, using the characteristics of patients, to establish who could benefit from early discharge (POD ≤ 2 days). METHODS: This observational study has been prospectively conducted. All the included patients were referred for surgical treatment of gynecologic cancer. We defined two sub-groups of patients on surgical procedure characteristics: isolated procedures (hysterectomy or lymphadenectomy) and combined procedures (at least the association of two procedures). RESULTS: 230 patients were enrolled during the study protocol. 83.9% of patients were treated with a minimally invasive surgery (MIS). 159 patients (69.1%) were discharged on or before POD 2. On multivariate analysis, the surgical approach (open surgery vs. laparoscopy, OR 0.02 (95% CI [0-0.07]), p < 0.001) and the type of surgery (combined procedure versus isolated procedure, OR 0.41 (95% CI [0.18-0.91]), p = 0.028) were found to be significant predictors of increased hospital stay. A nomogram has been built for the purpose of predicting eligible patients for early post-operative discharge based on the multivariate analysis results (AUC = 0.86, 95% CI [0.81-0.92]). CONCLUSION: The use of MIS for isolated procedures in oncologic indications constitutes an independent factor of early discharge in a setting of ERAS. These promising preliminary results still require to be validated on a prospective cohort.

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.

Thiotepa, Fludarabine, and Busulfan Conditioning Regimen before T Cell-Replete Haploidentical Transplantation with Post-Transplant Cyclophosphamide for Acute Myeloid Leukemia: A Bicentric Experience of 100 Patients.

Haploidentical stem cell transplantation (haplo-SCT) with post-transplant cyclophosphamide (PT-Cy) is an alternative treatment for acute myeloid leukemia (AML) patients who lack HLA-matched donors. Relapse after haplo-SCT remains a major concern, especially after nonmyeloablative conditioning regimens. Promising results were reported for TBF-based conditioning regimens (thiotepa, busulfan, and fludarabine) in patients transplanted from different categories of donors and for various disease types but not specifically in PT-Cy haplo-SCT for AML. Here we evaluate the outcome of 100 AML patients who received haplo-SCT with PT-Cy after TBF conditioning regimens (reduced-intensity conditioning, n = 77; myeloablative conditioning, n = 23) in 2 transplant programs. Cumulative incidences of grades III to IV acute and moderate or severe chronic graft-versus-host disease (GVHD) were 7% and 14%, respectively. NRM at 2 years was 28%, significantly influenced by disease status at haplo-SCT (first complete response [CR1] versus advanced AML: 16% versus 38%, P = .016) but not by conditioning intensity or age. The cumulative incidences of relapse at 2 years were 17% and 24% in CR1 and advanced AML, respectively (not significant). Progression-free survival, overall survival, and GVHD and relapse-free survival at 2 years were 67%, 71%, and 49% in CR1 patients, respectively, whereas comparative values in patients with advanced disease were 37%, 41%, and 32%. Our study suggests that TBF conditioning for PT-Cy haplo-SCT is safe and effective for AML patients in CR1. In patients with more advanced disease, the relatively low incidence of relapse seems counterbalanced by a high nonrelapse mortality, underlining the need for alternative strategies to decrease relapse risk, without increasing the intensity of conditioning regimen.

Diagnosis and outcome of acute respiratory failure in immunocompromised patients after bronchoscopy.

OBJECTIVE: We wished to explore the use, diagnostic capability and outcomes of bronchoscopy added to noninvasive testing in immunocompromised patients. In this setting, an inability to identify the cause of acute hypoxaemic respiratory failure is associated with worse outcome. Every effort should be made to obtain a diagnosis, either with noninvasive testing alone or combined with bronchoscopy. However, our understanding of the risks and benefits of bronchoscopy remains uncertain. PATIENTS AND METHODS: This was a pre-planned secondary analysis of Efraim, a prospective, multinational, observational study of 1611 immunocompromised patients with acute respiratory failure admitted to the intensive care unit (ICU). We compared patients with noninvasive testing only to those who had also received bronchoscopy by bivariate analysis and after propensity score matching. RESULTS: Bronchoscopy was performed in 618 (39%) patients who were more likely to have haematological malignancy and a higher severity of illness score. Bronchoscopy alone achieved a diagnosis in 165 patients (27% adjusted diagnostic yield). Bronchoscopy resulted in a management change in 236 patients (38% therapeutic yield). Bronchoscopy was associated with worsening of respiratory status in 69 (11%) patients. Bronchoscopy was associated with higher ICU (40% versus 28%; p<0.0001) and hospital mortality (49% versus 41%; p=0.003). The overall rate of undiagnosed causes was 13%. After propensity score matching, bronchoscopy remained associated with increased risk of hospital mortality (OR 1.41, 95% CI 1.08-1.81). CONCLUSIONS: Bronchoscopy was associated with improved diagnosis and changes in management, but also increased hospital mortality. Balancing risk and benefit in individualised cases should be investigated further.

Center Effects in Hospital Mortality of Critically Ill Patients With Hematologic Malignancies.

OBJECTIVES: We aimed to investigate center effects on hospital mortality of ICU patients with hematologic malignancies and to explore interactions between center and patients characteristics. DESIGN: Multicenter prospective cohort. SETTING: Seventeen ICUs across France and Belgium. PATIENTS: One-thousand eleven patients with hematologic malignancies hospitalized in ICUs. INTERVENTIONS: Reanalysis of the original data using state-of-the-art statistical methods with permutation procedures for testing multiple random effects. MEASUREMENTS AND MAIN RESULTS: Average crude mortality was 39% and varied from 11% to 58% across centers. There was a significant center effect on the mean hospital mortality, after adjustment on individual prognostic factors (p < 0.001; median adjusted odds ratio for center effect 1.57 [interquartile range, 1.24-2.18]). There was also a quantitative interaction between center and the effect of the Sequential Organ Failure Assessment score: higher scores were associated with higher mortality (odds ratio for 1 point = 1.24 on average; 95% CI, 1.15-1.33) but with a magnitude that depended on center (p = 0.028). CONCLUSIONS: Between-center heterogeneity in hospital mortality was confirmed after adjustment for individual prognostic factors. It was partially explained by center experience in treating oncology patients. Interestingly, center effect was similar in magnitude to that of known mortality risk factors.

Neutropenic Enterocolitis in Critically Ill Patients: Spectrum of the Disease and Risk of Invasive Fungal Disease.

OBJECTIVES: Neutropenic enterocolitis occurs in about 5.3% of patients hospitalized for hematologic malignancies receiving chemotherapy. Data from critically ill patients with neutropenic enterocolitis are scarce. Our objectives were to describe the population of patients with neutropenic enterocolitis admitted to an ICU and to investigate the risk factors of invasive fungal disease. DESIGN: A multicentric retrospective cohort study between January 2010 and August 2017. SETTING: Six French ICUs members of the Groupe de Recherche Respiratoire en Onco-Hématologie research network. PATIENTS: Adult neutropenic patients hospitalized in the ICU with a diagnosis of enteritis and/or colitis. Patients with differential diagnosis (Clostridium difficile colitis, viral colitis, inflammatory enterocolitis, mesenteric ischemia, radiation-induced gastrointestinal toxicity, and Graft vs Host Disease) were excluded. INTERVENTIONS: None. MEASUREMENT AND MAIN RESULTS: We included 134 patients (median Sequential Organ Failure Assessment 10 [8-12]), with 38.8% hospital mortality and 32.1% ICU mortality rates. The main underlying malignancies were acute leukemia (n = 65, 48.5%), lymphoma (n = 49, 36.6%), solid tumor (n = 14, 10.4%), and myeloma (n = 4, 3.0%). Patients were neutropenic during a median of 14 days (9-22 d). Infection was documented in 81 patients (60.4%), including an isolated bacterial infection in 64 patients (47.8%), an isolated fungal infection in nine patients (6.7%), and a coinfection with both pathogens in eight patients (5.0%). Radiologically assessed enteritis (odds ratio, 2.60; 95% CI, 1.32-7.56; p = 0.015) and HIV infection (odds ratio, 2.03; 95% CI, 1.21-3.31; p = 0.016) were independently associated with invasive fungal disease. CONCLUSIONS: The rate of invasive fungal disease reaches 20% in patients with neutropenic enterocolitis when enteritis is considered. To avoid treatment delay, antifungal therapy might be systematically discussed in ICU patients admitted for neutropenic enterocolitis with radiologically assessed enteritis.