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 Reanimation Onco-Hematologique 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

Increased mortality in hematological malignancy patients with acute respiratory failure from undetermined etiology : a Groupe de Recherche en Réanimation Respiratoire en Onco-Hématologique (Grrr-OH) study

Background: Acute respiratory failure (ARF) is the most frequent complication in patients with hematological malignancies and is associated with high morbidity and mortality. ARF etiologies are numerous, and despite extensive diagnostic workflow, some patients remain with undetermined ARF etiology. Methods: This is a post-hoc study of a prospective multicenter cohort performed on 1011 critically ill hematological patients. Relationship between ARF etiology and hospital mortality was assessed using a multivariable regression model adjusting for confounders. Results: This study included 604 patients with ARF. All patients underwent noninvasive diagnostic tests, and a bronchoscopy and bronchoalveolar lavage (BAL) was performed in 155 (25.6%). Definite diagnoses were classified into four exclusive etiological categories: pneumonia (44.4%), non-infectious diagnoses (32.6%), opportunistic infection (10.1%) and undetermined (12.9%), with corresponding hospital mortality rates of 40, 35, 55 and 59%, respectively. Overall hospital mortality was 42%. By multivariable analysis, factors associated with hospital mortality were invasive pulmonary aspergillosis (OR 7.57 (95% CI 3.06-21.62); p 7 (OR 3.32 (95% CI 2.15-5.15); p < 0.005) and an undetermined ARF etiology (OR 2.92 (95% CI 1.71-5.07); p < 0.005). Conclusions: In patients with hematological malignancies and ARF, up to 13% remain with undetermined ARF etiology despite comprehensive diagnostic workup. Undetermined ARF etiology is independently associated with hospital mortality. Studies to guide second-line diagnostic strategies are warranted

Determinants of 1-year survival in critically ill acute leukemia patients : a GRRR-OH study

Acute leukemia (AL) is the most common hematological malignancy requiring intensive care unit (ICU) management. Data on long-term survival are limited. This is a post hoc analysis of the prospective multicenter data from France and Belgium: A Groupe de Recherche Respiratoire en Reanimation Onco-Hematologique [A Research Group on Acute Respiratory Failure in Onco-Hematological Patients (French)] Study, to identify determinants of 1-year survival in critically ill AL patients. A total of 278 patients were admitted in the 17 participating ICUs. Median age was 58 years and 70% had newly diagnosed leukemia. ICU mortality rate was 28.6 and 39.6% of the patients alive at 1 year. Admission for intensive monitoring was independently associated with better 1-year survival by multivariate analysis. Conversely, relapsed/refractory disease, secondary leukemia, mechanical ventilation and renal replacement therapy were independently associated with 1-year mortality. This study confirms the impact of organ dysfunction on long-term survival in ICU patients with AL. Follow-up studies to assess respiratory and renal recovery are warranted

Enabling Astronaut Self-Scheduling using a Robust Advanced Modelling and Scheduling system: an assessment during a Mars analogue mission

Human long duration exploration missions (LDEMs) raise a number of technological challenges. This paper addresses the question of the crew autonomy: as the distances increase, the communication delays and constraints tend to prevent the astronauts from being monitored and supported by a real time ground control. Eventually, future planetary missions will necessarily require a form of astronaut self-scheduling. We study the usage of a computer decision-support tool by a crew of analog astronauts, during a Mars simulation mission conducted at the Mars Desert Research Station (MDRS, Mars Society) in Utah. The proposed tool, called Romie, belongs to the new category of Robust Advanced Modelling and Scheduling (RAMS) systems. It allows the crew members (i) to visually model their scientific objectives and constraints, (ii) to compute near-optimal operational schedules while taking uncertainty into account, (iii) to monitor the execution of past and current activities, and (iv) to modify scientific objectives/constraints w.r.t. unforeseen events and opportunistic science. In this study, we empirically measure how the astronauts, who are novice planners, perform at using such a tool when self-scheduling under the realistic assumptions of a simulated Martian planetary habitat

The FOXO1 Transcription Factor Instructs the Germinal Center Dark Zone Program

SummaryThe pathways regulating formation of the germinal center (GC) dark zone (DZ) and light zone (LZ) are unknown. In this study we show that FOXO1 transcription factor expression was restricted to the GC DZ and was required for DZ formation, since its absence in mice led to the loss of DZ gene programs and the formation of LZ-only GCs. FOXO1-negative GC B cells displayed normal somatic hypermutation but defective affinity maturation and class switch recombination. The function of FOXO1 in sustaining the DZ program involved the trans-activation of the chemokine receptor CXCR4, and cooperation with the BCL6 transcription factor in the trans-repression of genes involved in immune activation, DNA repair, and plasma cell differentiation. These results also have implications for the role of FOXO1 in lymphomagenesis because they suggest that constitutive FOXO1 activity might be required for the oncogenic activity of deregulated BCL6 expression

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

An Easy-To-Use External Fixator for All Hostile Environments, from Space to War Medicine: Is It Meant for Everyone's Hands?

Long bone fractures in hostile environments pose unique challenges due to limited resources, restricted access to healthcare facilities, and absence of surgical expertise. While external fixation has shown promise, the availability of trained surgeons is limited, and the procedure may frighten unexperienced personnel. Therefore, an easy-to-use external fixator (EZExFix) that can be performed by nonsurgeon individuals could provide timely and life-saving treatment in hostile environments; however, its efficacy and accuracy remain to be demonstrated. This study tested the learning curve and surgical performance of nonsurgeon analog astronauts ( = 6) in managing tibial shaft fractures by the EZExFix during a simulated Mars inhabited mission, at the Mars Desert Research Station (Hanksville, UT, USA). The reduction was achievable in the different 3D axis, although rotational reductions were more challenging. Astronauts reached similar bone-to-bone contact compared to the surgical control, indicating potential for successful fracture healing. The learning curve was not significant within the limited timeframe of the study (N = 4 surgeries lasting <1 h), but the performance was similar to surgical control. The results of this study could have important implications for fracture treatment in challenging or hostile conditions on Earth, such as war or natural disaster zones, developing countries, or settings with limited resources

Acute respiratory distress syndrome in patients with malignancies

Little attention has been given to ARDS in cancer patients, despite their high risk for pulmonary complications. We sought to describe outcomes in cancer patients with ARDS meeting the Berlin definition. Data from a cohort of patients admitted to 14 ICUs between 1990 and 2011 were used for a multivariable analysis of risk factors for hospital mortality. Of 1,004 included patients (86 % with hematological malignancies and 14 % with solid tumors), 444 (44.2 %) had neutropenia. Admission SOFA score was 12 (10-13). Etiological categories were primary infection-related ARDS (n = 662, 65.9 %; 385 bacterial infections, 213 invasive aspergillosis, 64 Pneumocystis pneumonia); extrapulmonary septic shock-related ARDS (n = 225, 22.4 %; 33 % candidemia); noninfectious ARDS (n = 76, 7.6 %); and undetermined cause (n = 41, 4.1 %). Of 387 (38.6 %) patients given noninvasive ventilation (NIV), 276 (71 %) subsequently required endotracheal ventilation. Hospital mortality was 64 % overall. According to the Berlin definition, 252 (25.1 %) patients had mild, 426 (42.4 %) moderate and 326 (32.5 %) severe ARDS; mortality was 59, 63 and 68.5 %, respectively (p = 0.06). Mortality dropped from 89 % in 1990-1995 to 52 % in 2006-2011 (p < 0.0001). Solid tumors, primary ARDS, and later admission period were associated with lower mortality. Risk factors for higher mortality were allogeneic bone-marrow transplantation, modified SOFA, NIV failure, severe ARDS, and invasive fungal infection. In cancer patients, 90 % of ARDS cases are infection-related, including one-third due to invasive fungal infections. Mortality has decreased over time. NIV failure is associated with increased mortality. The high mortality associated with invasive fungal infections warrants specific studies of early treatment strategies