Association between arterial oxygen and mortality across critically ill patients with hematologic malignancies: results from an international collaborative network.

PURPOSE: Patients with hematological malignancies are at high risk for life-threatening complications. To date, little attention has been paid to the impact of hyperoxemia and excess oxygen use on mortality. The aim of this study was to investigate the association between partial pressure of arterial oxygen (PaO2) and 28-day mortality in critically ill patients with hematologic malignancies. METHODS: Data from three international cohorts (Europe, Canada, Oceania) of patients who received respiratory support (noninvasive ventilation, high-flow nasal cannula, invasive mechanical ventilation) were obtained. We used mixed-effect Cox models to investigate the association between day one PaO2 or excess oxygen use (inspired fraction of oxygen ≥ 0.6 with PaO2 > 100 mmHg) on day-28 mortality. RESULTS: 11,249 patients were included. On day one, 5716 patients (50.8%) had normoxemia (60 ≤ PaO2 ≤ 100 mmHg), 1454 (12.9%) hypoxemia (PaO2 < 60 mmHg), and 4079 patients (36.3%) hyperoxemia (PaO2 > 100 mmHg). Excess oxygen was used in 2201 patients (20%). Crude day-28 mortality rate was 40.6%. There was a significant association between PaO2 and day-28 mortality with a U-shaped relationship (p < 0.001). Higher PaO2 levels (> 100 mmHg) were associated with day-28 mortality with a dose-effect relationship. Subgroup analyses showed an association between hyperoxemia and mortality in patients admitted with neurological disorders; however, the opposite relationship was seen across those admitted with sepsis and neutropenia. Excess oxygen use was also associated with subsequent day-28 mortality (adjusted hazard ratio (aHR) [95% confidence interval (CI)]: 1.11[1.04-1.19]). This result persisted after propensity score analysis (matched HR associated with excess oxygen:1.31 [1.20-1.1.44]). CONCLUSION: In critically-ill patients with hematological malignancies, exposure to hyperoxemia and excess oxygen use were associated with increased mortality, with variable magnitude across subgroups. This might be a modifiable factor to improve mortality.

ICU-acquired infections in immunocompromised patients.

Immunocompromised patients account for an increasing proportion of the typical intensive care unit (ICU) case-mix. Because of the increased availability of new drugs for cancer and auto-immune diseases, and improvement in the care of the most severely immunocompromised ICU patients (including those with hematologic malignancies), critically ill immunocompromised patients form a highly heterogeneous patient population. Furthermore, a large number of ICU patients with no apparent immunosuppression also harbor underlying conditions altering their immune response, or develop ICU-acquired immune deficiencies as a result of sepsis, trauma or major surgery. While infections are associated with significant morbidity and mortality in immunocompromised critically ill patients, little specific data are available on the incidence, microbiology, management and outcomes of ICU-acquired infections in this population. As a result, immunocompromised patients are usually excluded from trials and guidelines on the management of ICU-acquired infections. The most common ICU-acquired infections in immunocompromised patients are ventilator-associated lower respiratory tract infections (which include ventilator-associated pneumonia and tracheobronchitis) and bloodstream infections. Recently, several large observational studies have shed light on some of the epidemiological specificities of these infections-as well as on the dynamics of colonization and infection with multidrug-resistant bacteria-in these patients, and these will be discussed in this review. Immunocompromised patients are also at higher risk than non-immunocompromised hosts of fungal and viral infections, and the diagnostic and therapeutic management of these infections will be covered. Finally, we will suggest some important areas of future investigation.

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.

Severe infections requiring intensive care unit admission in patients receiving ibrutinib for hematological malignancies: a groupe de recherche respiratoire en réanimation onco-hématologique (GRRR-OH) study.

BACKGROUND: In the last decade, Ibrutinib has become the standard of care in the treatment of several lymphoproliferative diseases such as chronic lymphocytic leukemia (CLL) and several non-Hodgkin lymphoma. Beyond Bruton tyrosine kinase inhibition, Ibrutinib shows broad immunomodulatory effects that may promote the occurrence of infectious complications, including opportunistic infections. The infectious burden has been shown to vary by disease status, neutropenia, and prior therapy but data focusing on severe infections requiring intensive care unit (ICU) admission remain scarce. We sought to investigate features and outcomes of severe infections in a multicenter cohort of 69 patients receiving ibrutinib admitted to 10 French intensive care units (ICU) from 1 January 2015 to 31 December 2020. RESULTS: Median time from ibrutinib initiation was 6.6 [3-18] months. Invasive fungal infections (IFI) accounted for 19% (n = 13/69) of severe infections, including 9 (69%; n = 9/13) invasive aspergillosis, 3 (23%; n = 3/13) Pneumocystis pneumonia, and 1 (8%; n = 1/13) cryptococcosis. Most common organ injury was acute respiratory failure (ARF) (71%; n = 49/69) and 41% (n = 28/69) of patients required mechanical ventilation. Twenty (29%; n = 20/69) patients died in the ICU while day-90 mortality reached 55% (n = 35/64). In comparison with survivors, decedents displayed more severe organ dysfunctions (SOFA 7 [5-11] vs. 4 [3-7], p = 0.004) and were more likely to undergo mechanical ventilation (68% vs. 31%, p = 0.010). Sixty-three ibrutinib-treated patients were matched based on age and underlying malignancy with 63 controls receiving conventional chemotherapy from an historic cohort. Despite a higher median number of prior chemotherapy lines (2 [1-2] vs. 0 [0-2]; p < 0.001) and higher rates of fungal [21% vs. 8%, p = 0.001] and viral [17% vs. 5%, p = 0.027] infections in patients receiving ibrutinib, ICU (27% vs. 38%, p = 0.254) and day-90 mortality (52% vs. 48%, p = 0.785) were similar between the two groups. CONCLUSION: In ibrutinib-treated patients, severe infections requiring ICU admission were associated with a dismal prognosis, mostly impacted by initial organ failures. Opportunistic agents should be systematically screened by ICU clinicians in this immunocompromised population.

Thrombocytopenia and platelet transfusions in ICU patients: an international inception cohort study (PLOT-ICU).

PURPOSE: Thrombocytopenia (platelet count < 150 × 109/L) is common in intensive care unit (ICU) patients and is likely associated with worse outcomes. In this study we present international contemporary data on thrombocytopenia in ICU patients. METHODS: We conducted a prospective cohort study in adult ICU patients in 52 ICUs across 10 countries. We assessed frequencies of thrombocytopenia, use of platelet transfusions and clinical outcomes including mortality. We evaluated pre-selected potential risk factors for the development of thrombocytopenia during ICU stay and associations between thrombocytopenia at ICU admission and 90-day mortality using pre-specified logistic regression analyses. RESULTS: We analysed 1166 ICU patients; the median age was 63 years and 39.5% were female. Overall, 43.2% (95% confidence interval (CI) 40.4-46.1) had thrombocytopenia; 23.4% (20-26) had thrombocytopenia at ICU admission, and 19.8% (17.6-22.2) developed thrombocytopenia during their ICU stay. Absence of acquired immune deficiency syndrome (AIDS), non-cancer-related immune deficiency, liver failure, male sex, septic shock, and bleeding at ICU admission were associated with the development of thrombocytopenia during ICU stay. Among patients with thrombocytopenia, 22.6% received platelet transfusion(s), and 64.3% of in-ICU transfusions were prophylactic. Patients with thrombocytopenia had higher occurrences of bleeding and death, fewer days alive without the use of life-support, and fewer days alive and out of hospital. Thrombocytopenia at ICU admission was associated with 90-day mortality (adjusted odds ratio 1.7; 95% CI 1.19-2.42). CONCLUSION: Thrombocytopenia occurred in 43% of critically ill patients and was associated with worse outcomes including increased mortality. Platelet transfusions were given to 23% of patients with thrombocytopenia and most were prophylactic.

Characteristics and outcomes of patients with acute myeloid leukemia admitted to intensive care unit with acute respiratory failure: a post-hoc analysis of a prospective multicenter study.

BACKGROUND: Acute respiratory failure (ARF) is the leading cause of intensive care unit (ICU) admission in patients with Acute Myeloid Leukemia (AML) and data on prognostic factors affecting short-term outcome are needed. METHODS: This is a post-hoc analysis of a multicenter, international prospective cohort study on immunocompromised patients with ARF admitted to ICU. We evaluated hospital mortality and associated risk factors in patients with AML and ARF; secondly, we aimed to define specific subgroups within our study population through a cluster analysis. RESULTS: Overall, 201 of 1611 immunocompromised patients with ARF had AML and were included in the analysis. Hospital mortality was 46.8%. Variables independently associated with mortality were ECOG performance status ≥ 2 (OR = 2.79, p = 0.04), cough (OR = 2.94, p = 0.034), use of vasopressors (OR = 2.79, p = 0.044), leukemia-specific pulmonary involvement [namely leukostasis, pulmonary infiltration by blasts or acute lysis pneumopathy (OR = 4.76, p = 0.011)] and liver SOFA score (OR = 1.85, p = 0.014). Focal alveolar chest X-ray pattern was associated with survival (OR = 0.13, p = 0.001). We identified 3 clusters, that we named on the basis of the most frequently clinical, biological and radiological features found in each cluster: a "leukemic cluster", with high-risk AML patients with isolated, milder ARF; a "pulmonary cluster", consisting of symptomatic, highly oxygen-requiring, severe ARF with diffuse radiological findings in heavily immunocompromised patients; a clinical "inflammatory cluster", including patients with multi-organ failures in addition to ARF. When included in the multivariate analysis, cluster 2 and 3 were independently associated with hospital mortality. CONCLUSIONS: Among AML patients with ARF, factors associated with a worse outcome are related to patient's background (performance status, leukemic pulmonary involvement), symptoms, radiological findings, the need for vasopressors and the liver SOFA score. We identified three specific ARF syndromes in AML patients, which showed a prognostic significance and could guide clinicians to optimize management strategies.

Multiplex Polymerase Chain Reaction Assay to Detect Nasopharyngeal Viruses in Immunocompromised Patients With Acute Respiratory Failure.

BACKGROUND: In immunocompromised patients with acute respiratory failure (ARF), the clinical significance of respiratory virus detection in the nasopharynx remains uncertain. RESEARCH QUESTION: Is viral detection in nasopharyngeal swabs associated with causes and outcomes of ARF in immunocompromised patients? STUDY DESIGN AND METHODS: This preplanned post hoc analysis of a randomized controlled trial enrolled immunocompromised patients admitted to 32 ICUs for ARF between May 2016 and December 2017. Nasopharyngeal swabs sampled at inclusion were assessed for 23 respiratory pathogens using multiplex polymerase chain reaction (PCR) assay. Causes of ARF were established by managing physicians and were reviewed by three expert investigators masked to the multiplex PCR assay results. Associations between virus detection in nasopharyngeal swabs, causes of ARF, and composite outcome of day 28 mortality, invasive mechanical ventilation (IMV), or both were assessed. RESULTS: Among the 510 sampled patients, the multiplex PCR assay results were positive in 103 patients (20.2%), and a virus was detected in 102 samples: rhinoviruses or enteroviruses in 35.5%, coronaviruses in 10.9%, and flu-like viruses (influenza virus, parainfluenza virus, respiratory syncytial virus, human metapneumovirus) in 52.7%. The cause of ARF varied significantly according to the results of the multiplex PCR assay, especially the proportion of viral pneumonia: 50.0% with flu-like viruses, 14.0% with other viruses, and 3.6% when no virus was detected (P < .001). No difference was found in the composite outcome of day 28 mortality, IMV, or both according to positive assay findings (54.9% vs 54.7%; P = .965). In a pre-established subgroup analysis, flu-like virus detection was associated with a higher rate of day 28 mortality, IMV, or both among recipients of allogeneic hematopoietic stem cell transplantation compared with those without detected virus. INTERPRETATION: In immunocompromised patients with ARF, the results of nasopharyngeal multiplex PCR assays are not associated with IMV or mortality. A final diagnosis of viral pneumonia is retained in one-third of patients with positive assay results and in one-half of the patients with a flu-like virus.

Survival Benefit of Renin-Angiotensin System Blockers in Critically Ill Cancer Patients: A Retrospective Study.

Increasing evidence argues for the promotion of tumorigenesis through activation of the renin-angiotensin system pathway. Accordingly, a benefit of renin-angiotensin system blockers (RABs) treatments has been suggested in patients with solid cancers in terms of survival. We aimed to evaluate in-ICU survival and one-year survival in cancer patients admitted to the ICU with respect to the use of RABs. We conducted a retrospective observational single-center study in a 24-bed medical ICU. We included all solid cancer patients (age ≥ 18 years) requiring unplanned ICU admission. From 2007 to 2020, 1845 patients with solid malignancies were admitted (median age 67 years (59-75), males 61.7%). The most frequent primary tumor sites were the gastrointestinal tract (26.8%), the lung (24.7%), the urological tract (20.1%), and gynecologic and breast cancers (13.9%). RABs were used in 414 patients, distributed into 220 (53.1%) with angiotensin-receptor blockers (ARBs) and 194 (46.9%) with angiotensin-converting enzyme inhibitors (ACEis). After multivariate adjustment, ARBs use (OR = 0.62, 95%CI (0.40-0.92), p = 0.03) and ACEis use (OR = 0.52, 95%CI (0.32-0.82), p = 0.006) were both associated with improved in-ICU survival. Treatment with ARBs was independently associated with decreased one-year mortality (OR = 0.6, 95%CI (0.4-0.9), p = 0.02), whereas treatment with ACEis was not. In conclusion, this study argues for a beneficial impact of RABs use on the prognosis of critically ill cancer patients.

When breast cancer comes to the ICU: outcomes and prognostic factors.

BACKGROUND: Breast cancer is the most prevalent neoplasm in women in North American and European countries. Data about intensive care unit (ICU) requirements and the related outcomes are scarce. Furthermore, long-term outcome after ICU discharge has not been described. MATERIAL AND METHODS: We conducted a retrospective monocenter study including patients with breast cancer requiring unplanned ICU admission over a 14-year period (2007-2020). RESULTS: 177 patients (age = 65[57-75] years) were analyzed. Breast cancer was at a metastatic stage for 122 (68.9%) patients, recently diagnosed in 25 (14.1%) patients or in progression under treatment in 76 (42.9%) patients. Admissions were related to sepsis in 56 (31.6%) patients, to iatrogenic/procedural complication in 19 (10.7%) patients and to specific oncological complications in 47 (26.6%) patients. Seventy-two (40.7%) patients required invasive mechanical ventilation, 57 (32.2%) vasopressors/inotropes, and 26 (14.7%) renal replacement therapy. In-ICU and one-year mortality rates were 20.9% and 57.1%, respectively. Independent factors associated with in-ICU mortality were invasive mechanical ventilation and impaired performance status. One-year mortality in ICU survivors was independently associated with specific complications, triple negative cancer, and impaired performance status. After hospital discharge, most patients (77.4%) were able to continue or initiate antitumoral treatment. CONCLUSION: ICU admission was linked to the underlying malignancy in one-quarter of breast cancer patients. Despite the low in-ICU mortality rate (20.9%) and thereafter continuation of cancer treatment in most survivors (77.4%), one-year mortality reached 57.1%. Impaired performance status prior to the acute complication was a potent predictor of both short-term and long-term outcomes.

Etiologies and Outcome of Patients with Solid Tumors Admitted to ICU with Acute Respiratory Failure: A Secondary Analysis of the EFRAIM Study.

BACKGROUND: Acute respiratory failure (ARF) remains the most frequent reason for ICU admission in patients who are immunocompromised. This study reports etiologies and outcomes of ARF in subjects with solid tumors. METHODS: This study was a post hoc analysis of the EFRAIM study, a prospective multinational cohort study that included 1611 subjects who were immunocompromised and with ARF admitted to the ICU. Subjects with solid tumors admitted to the ICU with ARF were included in the analysis. RESULTS: Among the subjects from the EFRAIM cohort, 529 subjects with solid tumors (32.8%) were included in the analysis. At ICU admission, the median (interquartile range) Sequential Organ Failure Assessment score was 5 (3-9). The types of solid tumor were mostly lung cancer (n = 111, 21%), breast cancer (n = 52, 9.8%), and digestive cancer (n = 47, 8.9%). A majority, 379 subjects (71.6%) were full code at ICU admission. The ARF was caused by bacterial or viral infection (n = 220, 41.6%), extrapulmonary sepsis (n = 62, 11.7%), or related to cancer or treatment toxicity (n = 83, 15.7%), or fungal infection (n = 23, 4.3%). For 63 subjects (11.9%), the ARF etiology remained unknown after an extensive diagnostic workup. The hospital mortality rate was 45.7% (n = 232/508). Hospital mortality was independently associated with chronic cardiac failure (odds ratio 1.78, 95% CI 1.09-2.92; P = .02), lung cancer (odds ratio 2.50, 95% CI 1.51-4.19; P < .001), day 1 Sequential Organ Failure Assessment score (odds ratio 1.97, 95% CI 1.32-2.96; P < .001). ARF etiologies other than infectious, related to cancer, or treatment toxicity were associated with better outcomes (odds ratio 0.32, 95% CI 0.16-0.61; P < .001). CONCLUSIONS: Infectious diseases remained the most frequent cause of ARF in subjects with solid tumors admitted to the ICU. Hospital mortality was related to severity at ICU admission, previous comorbidities, and ARF etiologies related to non-malignant causes or pulmonary embolism. Lung tumor was also independently associated with higher mortality.

Extracorporeal membrane oxygenation in adults receiving haematopoietic cell transplantation: an international expert statement.

Combined advances in haematopoietic cell transplantation (HCT) and intensive care management have improved the survival of patients with haematological malignancies admitted to the intensive care unit. In cases of refractory respiratory failure or refractory cardiac failure, these advances have led to a renewed interest in advanced life support therapies, such as extracorporeal membrane oxygenation (ECMO), previously considered inappropriate for these patients due to their poor prognosis. Given the scarcity of evidence-based guidelines on the use of ECMO in patients receiving HCT and the need to provide equitable and sustainable access to ECMO, the European Society of Intensive Care Medicine, the Extracorporeal Life Support Organization, and the International ECMO Network aimed to develop an expert consensus statement on the use of ECMO in adult patients receiving HCT. A steering committee with expertise in ECMO and HCT searched the literature for relevant articles on ECMO, HCT, and immune effector cell therapy, and developed opinion statements through discussions following a Quaker-based consensus approach. An international panel of experts was convened to vote on these expert opinion statements following the Research and Development/University of California, Los Angeles Appropriateness Method. The Appraisal of Guidelines for Research and Evaluation statement was followed to prepare this Position Paper. 36 statements were drafted by the steering committee, 33 of which reached strong agreement after the first voting round. The remaining three statements were discussed by all members of the steering committee and expert panel, and rephrased before an additional round of voting. At the conclusion of the process, 33 statements received strong agreement and three weak agreement. This Position Paper could help to guide intensivists and haematologists during the difficult decision-making process regarding ECMO candidacy in adult patients receiving HCT. The statements could also serve as a basis for future research focused on ECMO selection criteria and bedside management.

Sepsis-associated coagulopathy in onco-hematology patients presenting with thrombocytopenia: a multicentric observational study.

Coagulation disorders increase mortality rate during septic shock, but the impact of concomitant hematological malignancies remains unknown. The study assessed coagulation disorders in onco-hematological patients with thrombocytopenia (<100 G/L) admitted to ICU for septic shock. Among 146 included patients, 50 patients had lymphoma and 49 patients had acute leukemia. ICU mortality rate was 43.8% (n = 64). Median increase in prothrombin time (PT) at day(d) 1 was 4.7 s (IQR 3.2-7.9) in ICU survivors vs. 6.4 s (IQR 4.5-13.7; p < 0.01) in non-survivors. Fibrinogen kinetics (increase in fibrinogen levels between d1 and d2) was +0.55 (-0.22-1.55) vs. +0.10 g/L (-0.40-0.50; p = 0.03) in surviving and non-surviving patients, respectively. PT increase ≥6 s at d1 (OR 5.5; 95% CI 1.1-6.0; p = 0.03) and mechanical ventilation (OR 7.4; 95% CI 3.3-17.7; p < 0.001) were independently associated with ICU mortality. This study provides information and new ways to identify hematological patients with high-risk mortality.

Assessment of Functional and Nutritional Status and Skeletal Muscle Mass for the Prognosis of Critically Ill Solid Cancer Patients.

Simple and accessible prognostic factors are paramount for solid cancer patients experiencing life-threatening complications. The aim of this study is to appraise the impact of functional and nutritional status and skeletal muscle mass in this population. We conducted a retrospective (2007−2020) single-center study by enrolling adult patients with solid cancers requiring unplanned ICU admission. Performance status, body weight, and albumin level were collected at ICU admission and over six months. Skeletal muscle mass was assessed at ICU admission by measuring muscle areas normalized by height (SMI). Four-hundred and sixty-two patients were analyzed, mainly with gastro-intestinal (34.8%) and lung (29.9%) neoplasms. Moreover, 92.8% of men and 67.3% of women were deemed cachectic. In the multivariate analysis, performance status at ICU admission (CSH 1.74 [1.27−2.39], p < 0.001) and the six month increase in albumin level (CSH 0.38 [0.16−0.87], p = 0.02) were independent predictors of ICU mortality. In the subgroup of mechanically ventilated patients, the psoas SMI was independently associated with ICU mortality (CSH 0.82 [0.67−0.98], p = 0.04). Among the 368 ICU-survivors, the performance status at ICU admission (CSH 1.34 [1.14−1.59], p < 0.001) and the six-month weight loss (CSH 1.33 [1.17−2.99], p = 0.01) were associated with a one-year mortality rate. Most cancer patients displayed cachexia at ICU admission. Time courses of nutritional parameters may aid the prediction of short- and long-term outcomes.

Specific circulating neutrophils subsets are present in clinically stable adults with cystic fibrosis and are further modulated by pulmonary exacerbations.

The progressive lung destruction in cystic fibrosis (CF) is tightly associated with chronic bacterial infection and neutrophil-dominated airway inflammation. CF pulmonary disease is complicated by episodes of acute exacerbations, contributing to irreversible lung damage. We hypothesized that circulating subsets of neutrophils from clinically stable adults with CF present some phenotypic specificities that could amplify their activation during an infectious episode. The aim of the present study was to examine the different neutrophil subsets in whole blood and in the low density neutrophils (LDN) that co-purify with peripheral blood mononuclear cells (PBMC) in clinically stable adults with CF and in CF adults during pulmonary exacerbations compared to healthy donors. Blood samples were obtained from 22 adults with CF (16 in stable state and 6 during pulmonary exacerbations) and from 20 healthy donors. Flow cytometry analysis of 13 different markers related to lineage (CD45, CD15), maturity (CD16, CD10, and CD33), activation (CD62L, CD11b, CD66b, and CD114), metabolism (GLUT-1, LOX1) and immunosuppression (PD1, PD-L1) was carried out within whole blood and within the LDN fraction. Unsupervised analysis of flow cytometry data was performed using visual t-distributed stochastic neighbor embedding (vi-tSNE). A significant increase in the CD11b expression in neutrophils from CF patients during exacerbations was observed compared to neutrophils from stable CF patients or to healthy donors, indicative of a circulating activation state due to an infectious status. The percentage of LDN was not increased in stable CF patients but increased during exacerbations. Analysis of neutrophil subsets using the double CD16/CD62L labeling revealed a significant increase in the CD16high/CD62Llow subset in all CF patients compared to healthy donors. In contrast, an increase in the CD16low/CD62Lhigh subset was observed only in CF patients during exacerbations. Unsupervised analysis identified a PD-L1high/CD114high population that was present in stable CF patients and as well as in CF patients during exacerbations.

End of life decisions in immunocompromised patients with acute respiratory failure.

PURPOSE: To identify patient, disease and organizational factors associated with decisions to forgo life-sustaining therapies (DFLSTs) in critically ill immunocompromised patients admitted to the intensive care unit (ICU) for acute respiratory failure. MATERIAL AND METHODS: We performed a secondary analysis of the international EFRAIM prospective study, which enrolled 1611 immunocompromised patients with acute respiratory failure admitted to 68 ICUs in 16 countries between October 2015 and June 2016. Multivariate logistic analysis was performed to identify independent predictors of DFLSTs. RESULTS: The main causes of immunosuppression were hematological malignancies (50%) and solid tumor (38%). Patients had a median age of 63 yo (54-71). A pulmonologist was involved in the patient management in 38% of cases. DFLSTs had been implemented in 28% of the patients. The following variables were independently associated with DFLSTs: 1) patient-related: older age (OR 1.02 per one year increase, 95% confidence interval(CI) 1.01-1.03,P < 0.001), poor performance status (OR 2.79, 95% CI 1.98-3.93, P < 0.001); 2) disease-related: shock (OR 2.00, 95% CI 1.45-2.75, P < 0.001), liver failure (OR 1.59, 95% CI 1.14-2.21, P = 0.006), invasive mechanical ventilation (OR 1.79, 95% CI 1.31-2.46, P < 0.001); 3) organizational: having a pulmonologist involved in patient management (OR 1.85, 95% CI 1.36-2.52, P < 0.001), and the presence of a critical care outreach services (OR 1.63, 95% CI 1.11-2.38, P = 0.012). CONCLUSIONS: A DFLST is made in one in four immunocompromised patient admitted to the ICU for acute respiratory failure. Involving a pulmonologist in patient's management is associated with less non beneficial care.

Antimicrobial stewardship in high-risk febrile neutropenia patients.

BACKGROUND: The 2011 4th European Conference on Infections in Leukemia (ECIL4) guidelines recommend antibiotics de-escalation/discontinuation in selected febrile neutropenia (FN) patients. We aimed to assess the impact of an antimicrobial stewardship (AMS) program based on these guidelines on antibiotics use and clinical outcomes in high-risk FN patients. METHODS: We conducted an observational study in the hematology department of Cochin University Hospital in Paris, France. An ECIL4-based antibiotics de-escalation and discontinuation strategy was implemented jointly by the hematologists and the AMS team. The pre-intervention (January-October 2018) and post-intervention (January-October 2019) periods were compared. We retrospectively collected clinical and microbiological data. We compiled antibiotics consumptions via hospital pharmacy data and standardized them by calculating defined daily doses per 1000 patient-days. We analyzed the two-monthly antibiotic consumption using an interrupted time series method and built a composite endpoint for clinical outcomes based on transfer to the intensive care unit (ICU) and/or hospital death. RESULTS: Overall, 273 hospital stays (164 patients) in the pre-intervention and 217 (148 patients) in the post-intervention periods were analyzed. Patients were mainly hospitalized for intensive chemotherapy for acute leukemia or autologous stem-cell transplant for myeloma. Patients were slightly younger in the pre-intervention compared to the post-intervention period (median age 60.4 vs 65.2 years, p = 0.049), but otherwise comparable. After implementation of the AMS program, glycopeptide and carbapenem use decreased by 85% (p = 0.03) and 72% (p = 0.04), respectively. After adjustment on confounders, the risk of transfer to the ICU/death decreased significantly after implementation of the AMS program (post-intervention period: odds-ratio = 0.29, 95% Confidence Interval: 0.15-0.53, p < 0.001). CONCLUSION: Implementation of a multidisciplinary AMS program for high-risk neutropenic patients was associated with lower carbapenem and glycopeptide use and improved clinical outcomes.

Severe COVID-19 is associated with hyperactivation of the alternative complement pathway.

BACKGROUND: Severe coronavirus disease 2019 (COVID-19) is characterized by impaired type I interferon activity and a state of hyperinflammation leading to acute respiratory distress syndrome. The complement system has recently emerged as a key player in triggering and maintaining the inflammatory state, but the role of this molecular cascade in severe COVID-19 is still poorly characterized. OBJECTIVE: We aimed at assessing the contribution of complement pathways at both the protein and transcriptomic levels. METHODS: To this end, we systematically assessed the RNA levels of 28 complement genes in the circulating whole blood of patients with COVID-19 and healthy controls, including genes of the alternative pathway, for which data remain scarce. RESULTS: We found differential expression of genes involved in the complement system, yet with various expression patterns: whereas patients displaying moderate disease had elevated expression of classical pathway genes, severe disease was associated with increased lectin and alternative pathway activation, which correlated with inflammation and coagulopathy markers. Additionally, properdin, a pivotal positive regulator of the alternative pathway, showed high RNA expression but was found at low protein concentrations in patients with a severe and critical disease, suggesting its deposition at the sites of complement activation. Notably, low properdin levels were significantly associated with the use of mechanical ventilation (area under the curve = 0.82; P = .002). CONCLUSION: This study sheds light on the role of the alternative pathway in severe COVID-19 and provides additional rationale for the testing of drugs inhibiting the alternative pathway of the complement system.

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.

Patterns of ICU admissions and outcomes in patients with solid malignancies over the revolution of cancer treatment.

BACKGROUND: Major therapeutic advances including immunotherapy and targeted therapies have been changing the face of oncology and resulted in improved prognosis as well as in new toxic complications. The aim of this study is to appraise the trends in intensive care unit (ICU) admissions and outcomes of critically ill patients with solid malignancies. We performed a retrospective single-centre study over a 12-year period (2007-2018) including adult patients with solid malignancies requiring unplanned ICU admission. Admission patterns were classified as: (i) specific if directly related to the underlying cancer; (ii) non-specific; (iii) drug-related or procedural adverse events. RESULTS: 1525 patients were analysed. Lung and gastro-intestinal tract accounted for the two main tumour sites. The proportion of patients with metastatic diseases increased from 48.6% in 2007-2008 to 60.2% in 2017-2018 (p = 0.004). Critical conditions were increasingly related to drug- or procedure-related adverse events, from 8.8% of ICU admissions in 2007-2008 to 16% in 2017-2018 (p = 0.01). The crude severity of critical illness at ICU admission did not change over time. The ICU survival rate was 77.4%, without any significant changes over the study period. Among the 1279 patients with complete follow-up, the 1-year survival rate was 33.2%. Independent determinants of ICU mortality were metastatic disease, cancer in progression under treatment, admission for specific complications and the extent of organ failures (invasive and non-invasive ventilation, inotropes/vasopressors, renal replacement therapy and SOFA score). One-year mortality in ICU-survivors was independently associated with lung cancer, metastatic disease, cancer in progression under treatment, admission for specific complications and decision to forgo life-sustaining therapies. CONCLUSION: Advances in the management and the prognosis of solid malignancies substantially modified the ICU admission patterns of cancer patients. Despite underlying advanced and often metastatic malignancies, encouraging short-term and long-term outcomes should help changing the dismal perception of critically ill cancer patients.