Acute respiratory failure in patients with hematological malignancies : outcomes according to initial ventilation strategy : a Groupe de recherche respiratoire en réanimation onco-hématologique (Grrr-OH) study

Background: In patients with hematological malignancies and acute respiratory failure (ARF), noninvasive ventilation was associated with a decreased mortality in older studies. However, mortality of intubated patients decreased in the last years. In this study, we assess outcomes in those patients according to the initial ventilation strategy. Methods: We performed a post hoc analysis of a prospective multicentre study of critically ill hematology patients, in 17 intensive care units in France and Belgium. Patients with hematological malignancies admitted for ARF in 2010 and 2011 and who were not intubated at admission were included in the study. A propensity score-based approach was used to assess the impact of NIV compared to oxygen only on hospital mortality. Results: Among 1011 patients admitted to ICU during the study period, 380 met inclusion criteria. Underlying diseases included lymphoid (n = 162, 42.6 %) or myeloid (n = 141, 37.1 %) diseases. ARF etiologies were pulmonary infections (n = 161, 43 %), malignant infiltration (n = 65, 17 %) or cardiac pulmonary edema (n = 40, 10 %). Mechanical ventilation was ultimately needed in 94 (24.7 %) patients, within 3 [2-5] days of ICU admission. Hospital mortality was 32 % (123 deaths). At ICU admission, 142 patients received first-line noninvasive ventilation (NIV), whereas 238 received oxygen only. Fifty-five patients in each group (NIV or oxygen only) were matched according the propensity score. NIV was not associated with decreased hospital mortality [OR 1.5 (0.62-3.65)]. Conclusions: In hematology patients with acute respiratory failure, initial treatment with NIV did not improve survival compared to oxygen only

Clinical features of H1N1 2009 infection in critically ill immunocompromised patients

Seasonal influenza virus has been described as an emerging and severe pathogen in immunocompromised hosts. Since the beginning of the 2009 influenza A novel H1N1 pandemic, several series have described the clinical course of the disease in various populations. We report the clinical course of H1N1 2009 infection in 10 immunocompromised patients. Half of the patients received long-term steroid therapy. Disease was characterized by a clinical picture similar to that of non-immunocompromised patients but with prolonged course and higher mortality

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

Neurological failure in ICU patients with hematological malignancies : a prospective cohort study

Background : Epidemiological studies of neurological complications in patients with hematological malignancies are scant. The objective of the study was to identify determinants of survival in patients with hematological malignancy and neurological failure. Methods : Post hoc analysis of a prospective study of adults with hematological malignancies admitted for any reason to one of 17 university or university-affiliated participating ICUs in France and Belgium (2010-2012). The primary outcome was vital status at hospital discharge. Results : Of the 1011 patients enrolled initially, 226 (22.4%) had neurological failure. Presenting manifestations were dominated by drowsiness or stupor (65%), coma (32%), weakness (26%), and seizures (19%). Neuroimaging, lumbar puncture, and electroencephalography were performed in 113 (50%), 73 (32%), and 63 (28%) patients, respectively. A neurosurgical biopsy was done in 1 patient. Hospital mortality was 50%. By multivariate analysis, factors independently associated with higher hospital mortality were poor performance status ( odds ratio [OR], 3.99; 95% CI, 1.82-9.39; P = 0.0009), non-Hodgkin's lymphoma ( OR, 2.60; 95% CI, 1.35-5.15; P = 0.005), shock ( OR, 1.95; 95% CI, 1.04-3.72; P = 0.04), and respiratory failure ( OR, 2.18; 95% CI, 1.140-4.25; P = 0.02); and factors independently associated with lower hospital mortality were GCS score on day 1 ( OR, 0.88/point; 95% CI, 0.81-0.95; P = 0.0009) and autologous stem cell transplantation ( OR, 0.25; 95% CI, 0.07-0.75; P = 0.02). Conclusions : In ICU patients with hematological malignancies, neurological failure is common and often fatal. Independent predictors of higher hospital mortality were type of underlying hematological malignancy, poor performance status, hemodynamic and respiratory failures, and severity of consciousness impairment. Knowledge of these risk factors might help to optimize management strategies

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

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

Réévaluation de l'antibiothérapie des pneumopathies sévères (la désescalade est-elle possible ?)

Objectifs de l étude : Evaluer l épidémiologie microbiologique et la gestion de l'antibiothérapie des pneumopathies communautaires sévères admises en réanimation (PACS) et nosocomiales sévères acquises en dehors de la ventilation mécanique (PNOS). Méthodologie: Il s'agit d'une étude prospective observationnelle pendant quarante et un mois dans une unité de réanimation médicale à orientation respiratoire. Le service dispose de recommandations d'antibiothérapie et les prescriptions sont réévaluées lors d'une réunion hebdomadaire multidisciplinaire d'infectiologie. Sont analysés : l'adéquation de l'antibiothérapie empirique initiale (AEI) aux recommandations, l'activité de l AEI sur les germes identifiés dans les prélèvements microbiologiques initiaux et la possibilité de réduire le spectre de l'AEI (désescalade). Résultats : Cent soixante seize patients, âge médian 64 +- 14 ans, IGS2 45 +- 17, ont présenté une pneumopathie sévère hospitalisée en réanimation. La prescription antibiotique empirique initiale a été réévaluée au cours de la réunion multidisciplinaire hebdomadaire dans 113 cas (64,2% des pneumopathies sévères). Parmi ces 113 cas, il y avait 58 PACS (51,3%) dont 10 PACS avec présence de facteurs de risque de Pseudomonas aeruginosa (8,9%) et 55 PNOS (48,7%). Une documentation microbiologique a été obtenue chez 72 patients (63,7%). L épidémiologie microbiologique retrouve principalement dans les PACS : S. pneumoniae (47,2%), Haemophilus (25%), entérobactéries du groupe 1 et 2 (11,1%) et Pseudomonas aeruginosa (8,3%) dont 9 co-infections et une incidence de bactéries multi-résistantes (BMR) de 1,7% ; et dans les PNOS: Staphylococcus aureus meticilline sensible (33 %), entérobactéries (35 %), Haemophilus (25 %) et Pseudomonas aeruginosa (19,4%) dont 12 co-infections et une incidence des BMR de 17%. L'AEI était conforme à nos recommandations chez 79/113 patients (69,9%). L'AEI était active chez 63 des 72 patients (87,5%) dont la pneumopathie était documentée. Une désescalade de la prescription de l'antibiothérapie a été réalisée chez 49 patients (43,4 %). La mortalité globale hospitalière observée est de 33,6 %, respectivement 55,6 % en cas d'AEI inactive et 31,7% en cas d'AEI active (p=0,06). Les facteurs de risque indépendants de mortalité sont: le SAPS II, le recours à la ventilation mécanique (en particulier invasive), une pneumonie acquise à l'hôpital et les surinfections à BMR. Conclusion : Les pneumopathies communautaires et nosocomiales non acquises sous ventilation mécanique admises en réanimation sont associées à une mortalité élevée. Elles justifient une stratégie diagnostique microbiologique semi-invasive et l application de recommandations d'antibiothérapie initiale empirique reposant sur les données épidémiologiques locales. Une réunion d infectiologie hebdomadaire permet une réévaluation et une désescalade de l antibiothérapie initiale empirique dans 43,4% des casStudy objectives: To describe the major pathogens isolated from severe community-acquired pneumonia (SCAP) and non ventilator associated hospital-acquired pneumonia (non VA-HAP) and to evaluate the management of antibiotic therapy and it's de-escalation in a real life setting. Method: A prospective forty-one months observational cohort study including all patients with severe SCAP or non VA-HAP admitted in respiratory intensive care unit (RICU) of a university teaching hospital. Local guidelines for microbiological samplings and initial empirical antibiotic therapy (IEAT) for SCAP and non VA-HAP are available in the RICU. Clinical history and microbiological results are reviewed and all IEAT prescriptions are evaluated during a multidisciplinary weekly meeting for infectious diseases. Are therefore analysed: the adequacy of the IEAT to the guidelines, the antibacterial activity of IEAT regarding the documented pathogens and the possibility of de-escalation in the spectrum of antibiotic therapy. Results: One hundred seventy six patients, median age = 64 +- 14 years, SAPS2 = 45 +- 17, with SCAP or non VA-HAP where hospitalised in the RICU. The IEAT was re-evaluated during the weekly multidisciplinary meeting in 113 cases (64,2 % of all severe pneumonia). These 113 cases, consisted of 48 SCAP (42,5 %), including 10 SCAP with presence of risk factors for Pseudomonas aeruginosa and 55 non VA-HAP (48,7 %). A microbiologic documentation was obtained in 72 patients (63,7 %). The main following pathogens were identified in SCAP: S. pneumoniae (47,2 %), Haemophilus (25 %), Enterobacteriaceae (11,1 %) and Pseudomonas aeruginosa (8,3 %) including 9 co-infections and an incidence of antibiotic multi-resistant bacterial strains (MRB) of 1,7 % . In non VA-HAP the following bacteria were identified: meticilline-sensitive Staphylococcus aureus (33 %), Enterobacteriaceae (35 %), Haemophilus (25 %) and Pseudomonas aeruginosa (19,4 %) 12 co-infections and an incidence of the MRB of 17 %. The IAET was in adequacy with our guidelines in 79/113 patients (69,9 %). The IAET was appropriate in 63 of 72 patients (87,5 %) with microbiologically documented pneumonia. De-escalation in the spectrum of the IEAT is performed in 49 patient's (43,4 %). Hospital mortality is 33,6 %, respectively 55,6 % in case of inappropriate IEAT and 31,7 % in case of appropriate IEAT (p=0,06). The risk factors independently associated with in hospital death are: SAPS II, mechanical ventilation, invasive mechanical ventilation, hospital-acquired pneumonia and secondary hospital acquired infections with multi-resistant bacterial strains. Conclusion: severe community-acquired pneumonia (SCAP) and non ventilator-associated hospital acquired pneumonia (non VA-HAP) requiring ICU admission are associated with a poor outcome. As in VAP the management of these severe pneumonia must rely on a semi-invasive microbiological diagnostic strategy and recommendations for the initial empirical antibiotic therapy based on local epidemiological data. Our re-evaluation strategy (based on weekly meeting) leads to a de-escalation of the initial empiric antibacterial therapy spectrum in 43,4 % of the documented casesPARIS12-CRETEIL BU Médecine (940282101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Défaillance respiratoire des patients atteints de leucémie aiguë myéloblastique admis en réanimation (facteurs pronostiques et intérêt de la VNI)

PARIS-BIUM (751062103) / SudocCentre Technique Livre Ens. Sup. (774682301) / SudocSudocFranceF

Place de la 16S rDNA PCR dans le diagnostic microbiologique de la pleurésie infectieuse bactérienne

La pleurésie infectieuse est une pathologie courante qui pose de nombreux problèmes diagnostiques et thérapeutiques. Les recommandations actuelles incitent à une prise en charge rapide en cas de pleurésie dans un contexte fébrile, consistant à la réalisation d une ponction pleurale pour un examen bactériologique standard. Cependant, cet examen est peu rentable car les cultures sont lentes et il existe de nombreux faux négatifs du fait d une antibiothérapie préalable. La Broad range PCR est un nouvel outil diagnostic qui est basée sur la séquence 16S de l ADN ribosomal, séquence commune à toutes les espèces bactériennes.Ainsi, elle peut détecter toutes les espèces bactériennes sur une analyse unique. Cependant, sa valeur diagnostique n a jamais été établie sur les prélèvements pleuraux chez l adulte. Entre juin 2007 et juin 2008, des liquides pleuraux ont été prélevés chez 44 patients présentant une pleurésie fébrile ou des pleurésies transsudatives ou post opératoires non fébriles (groupe contrôle). Une analyse en culture et par 16 S rDNA PCR a été réalisée sur chacun de ces prélèvements. Sur 18 cas de pleurésie cliniquement infectieuse bactérienne, 8 ont été documentées par la culture et/ou la PCR. Cinq prélèvements ont été documentés par la PCR seule, 2 par la PCR et la culture avec une concordance dans les germes retrouvés, un prélèvement poly microbien a été documenté en culture seul. Chez les patients présentant des pleurésies non fébriles et chez ceux présentant une pleurésie fébrile pour laquelle un autre diagnostic a été retrouvé, la PCR a toujours été négative. La sensibilité et la spécificité de la 16 S rDNA PCR est de 39% et de 100%. Dans 28% des cas, la PCR apporte le diagnostic là où la culture était négative. Cette étude montre un intérêt modeste de la 16 S rDNA PCR dans la prise en charge en pratique courante de la pleurésie infectieuse chez l adulte.PARIS6-Bibl.Pitié-Salpêtrie (751132101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF