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

ABSTRACT: 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 < 0.005), use of invasive mechanical ventilation (OR 1.65 (95% CI 1.07-2.55); p = 0.02), a SOFA score >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. ClinicalTrials.Gov NCT01172132.

SUBMITTER: Contejean A

PROVIDER: S-EPMC5080277 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature

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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.

Contejean Adrien A Lemiale Virginie V Resche-Rigon Matthieu M Mokart Djamel D Pène Frédéric F Kouatchet Achille A Mayaux Julien J Vincent François F Nyunga Martine M Bruneel Fabrice F Rabbat Antoine A Perez Pierre P Meert Anne-Pascale AP Benoit Dominique D Hamidfar Rebecca R Darmon Michael M Jourdain Mercé M Renault Anne A Schlemmer Benoît B Azoulay Elie E

Annals of intensive care 20161025 1

<h4>Background</h4>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.<h4>Methods</h4>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 ...[more]

PMID: 27783381

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Project description:ObjectivesTo assess outcomes at hospital discharge and day-120 after intensive care unit (ICU) discharge among patients with solid cancer admitted to ICU and to identify characteristics associated with in-hospital and day-120 after ICU discharge mortalities.DesignInternational, multicenter, retrospective study.SettingFive ICUs in France and Brazil, two located in cancer centers, two in university affiliated and one in general hospitals.PatientsConsecutive patients aged > 18 years, with underlying solid cancers (known before admission to the ICU or diagnosed during the stay in the ICU), admitted to the participating ICUs and discharged alive from the ICU from January 2006 to December 2011 were included in this study. Patients admitted after scheduled surgery or to secure procedure were excluded. Variables of interest were in-hospital and day-120 post-ICU mortality among patients discharged alive from the ICU.InterventionsNone.Measurements and resultsA total of 1053 patients aged 63 years (54-71) (median [IQR]) were included. Most of the patients were of the male gender (66.8%). The in-ICU, in-hospital, and four-month post-ICU discharge mortalities were, respectively, 41.3, 60.7, and 65.8%. Among patients discharged alive from the ICU, in multivariate analysis, factors associated with four months post-ICU discharge mortality were type of cancer (OR from 0.25 to 0.52 when compared to lung cancers), systemic extension of the disease (OR 2.54; 95% CI 1.87-3.45), need for invasive mechanical ventilation (OR 2.54; 95% CI 1.80-3.59), for vasopressors (OR 2.35; 95% CI 1.66-3.29), or renal replacement therapy (OR 1.54; 95% CI 0.99-2.38). A predictive score, "Oncoscore," was built performing fairly in predicting 4 months post-ICU discharge outcome (AUC 0.74; 95% CI 0.71-0.77).ConclusionDespite the high day-120 mortality following the ICU discharge, our study reports a meaningful medium-term survival rate after the ICU discharge of solid cancer patients. Of utmost importance, the "Oncoscore" must be validated in prospective studies and cannot be used, in its form without external validation, for individual decision making. Prospective studies to answer questions not provided by this study are needed, including only patients with solid cancers admitted in the ICU for medical reasons or after emergency surgery.

Project description:BACKGROUND: Neuraminidase inhibitors (NAIs) such as oseltamivir (O) and zanamivir (Z) play a central role in the control of influenza infections. However, the emergence and dissemination of antiviral resistance threaten the efficacy of this intervention and advocate for innovative therapeutic strategies. The objective of this study was to evaluate in mice the efficacy of O-Z combination compared to that of monotherapy, for the treatment of experimental infections with influenza A(H1N1)pdm09 viruses. METHODS: Recombinant A(H1N1)pdm09 wild-type (WT) and O-resistant H275Y NA mutant viruses were generated by reverse genetics. Groups of twelve C57BL/6 mice were inoculated intranasally with saline, the WT or H275Y viruses. To mimic the clinical condition, infected mice were treated 48h p.i. with either saline, O by gavage, Z intranasally, or an O-Z combination, twice daily for 5 days. Weight loss and mortality were monitored for 14 days. On day 4 p.i., four mice were sacrificed to determine lung viral titers (LVT) by plaque assay in ST6GalI-MDCK cells. RESULTS: In mice infected with the WT virus, treatment with Z or O-Z resulted in 100% survival, vs 50% for the O group and 12.5% for the untreated group. Z monotherapy also led to a significant reduction in weight loss compared to O as well as lower LVT (5.7E^6 vs 1.7E^7 PFU mL, respectively). Intermediate values were observed for the O-Z combination. In the H275Y group, the efficacy of O-Z was comparable to that of Z and significantly higher than that of O in terms of survival (85.7% and 100% vs 12.5%, respectively), weight loss and LVT (5.4E^6 and 3.5E^6 vs 2.8E^8 PFU/mL, respectively). The evaluation of these treatments in mice infected with influenza A(H3N2) is in progress. CONCLUSIONS: Z monotherapy had greater efficacy than O in mice infected with A(H1N1)pdm09. O-Z bitherapy conferred no significant advantage over Z monotherapy. Development of new molecules and synergistic combined therapies are a necessity.

Dataset Information

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

Publications

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.

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