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Outcomes in adult critically ill cancer patients with and without neutropenia: a systematic review and meta-analysis of the Groupe de Recherche en Reanimation Respiratoire du patient d'Onco-Hematologie (GRRR-OH).

ABSTRACT: Whether neutropenia has an impact on the mortality of critically ill cancer patients remains controversial, yet it is widely used as an admission criterion and prognostic factor.Systematic review and meta-analysis. Studies on adult cancer patients and intensive care units were searched on PubMed and Cochrane databases (2005-2015). Summary estimates of mortality risk differences were calculated using the random-effects model.Among the 1,528 citations identified, 38 studies reporting on 6,054 patients (2,097 neutropenic patients) were included. Median mortality across the studies was 54% [45-64], with unadjusted mortality in neutropenic and non-neutropenic critically ill patients of 60% [53-74] and 47% [41-68], respectively. Overall, neutropenia was associated with a 10% increased mortality risk (6%-14%; I² = 50%). The admission period was not associated with how neutropenia affected mortality. Mortality significantly dropped throughout the study decade [-11% (-13.5 to -8.4)]. This mortality drop was observed in non-neutropenic patients [-12.1% (-15.2 to -9.0)] but not in neutropenic patients [-3.8% (-8.1 to +5.6)].Sensitivity analyses disclosed no differences in underlying malignancy, mechanical ventilation use, or Granulocyte-colony stimulating factor use. Seven studies allowed the adjustment of severity results (1,350 patients). Although pooled risk difference estimates were similar to non-adjusted results, there was no significant impact of neutropenia on mortality (risk difference of mortality, 9%; 95% CI, -15 to +33).Although the unadjusted mortality of neutropenic patients was 11% higher, this effect disappeared when adjusted for severity. Therefore, when cancer patients become critically ill, neutropenia cannot be considered as a decision-making criterion.

SUBMITTER: Bouteloup M

PROVIDER: S-EPMC5352103 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature

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Outcomes in adult critically ill cancer patients with and without neutropenia: a systematic review and meta-analysis of the Groupe de Recherche en Réanimation Respiratoire du patient d'Onco-Hématologie (GRRR-OH).

Bouteloup Marie M Perinel Sophie S Bourmaud Aurélie A Azoulay Elie E Mokart Djamel D Darmon Michael M

Oncotarget 20170101 1

<h4>Purpose</h4>Whether neutropenia has an impact on the mortality of critically ill cancer patients remains controversial, yet it is widely used as an admission criterion and prognostic factor.<h4>Methods</h4>Systematic review and meta-analysis. Studies on adult cancer patients and intensive care units were searched on PubMed and Cochrane databases (2005-2015). Summary estimates of mortality risk differences were calculated using the random-effects model.<h4>Results</h4>Among the 1,528 citation ...[more]

PMID: 27661125

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Project description:L’asthme est une maladie inflammatoire qui se traduit par une bronchoconstriction qui peut être modulée par l’action de médiateurs lipidiques endogènes (Prostaglandines, Leucotriènes, Éicosanoïdes). Bien que le mode d’action moléculaire et les effets physiologiques des époxy-eicosanoïdes (EET) soient relativement bien caractérisés (Morin et al, 2007 AJRCMB), les stimuli responsables de leur production sont mal identifiés. Le but du projet est d’identifier ces stimulis. Notre hypothèse de travail est qu’il existe une relation entre les effets de la Bradykinine et la synthèse des EET endogènes dans la paroi des bronchioles humaines. Les objectifs spécifiques sont : 1) Établir un nouveau modèle d’hyperréactivité bronchique (HRB) par la mise en culture de bronchioles humaines pendant 48h en utilisant l’ IL-1? et l’IL-13 en combinaison ou non avec le TNF?; 2) Quantifier les effets relaxants de la Bradykinine et les comparer à ceux du 14,15-EET exogène sur des bronches humaines hyper-réactives en absence ou en présence de différents inhibiteurs. Des mesures de tension mécanique dans des bains à organes isolés ont été réalisées sur des bronches provenant de résections pulmonaires humaines, disséquées et mises en culture pendant 48 h. Un traitement à l’IL-13 et au TNF-?; induit une hyperréactivité bronchique qui est abolie par un traitement de 48 h avec 100 nM de 14,15-EET. De plus, 1 ?M de Bradykinine ou 1 ?M de 14,15-EET relaxe le tonus contractile induit par 30 nM d’U-46619, un analogue du thromboxane A2. Cet effet relaxant est réduit de 25% par 10 nM d’Iberiotoxine (un bloqueur des BKCa). L’augmentation de la production et de la biodisponibilité du 14,15-EET est donc une stratégie qui pourrait se révéler intéressante pour minimiser l’HRB. En perspective, il nous reste à tester l’effet de la Bradykinine en présence de MSPPOH, un inhibiteur de CYP450 époxygénases ce qui minimiserait la production endogène des EET, et permettrait de confirmer notre hypothèse de travail.

Project description:Contexte: La surveillance régulière du cancer est essentielle pour comprendre où des progrès sont réalisés et où il faut en faire plus. Nous avons cherché à donner un aperçu du fardeau attendu du cancer au Canada, en 2022. Méthodes: Nous avons obtenu les nouvelles données sur l’incidence du cancer à partir du Système national de déclaration des cas de cancer (1984–1991) et du Registre canadien du cancer (1992–2018). Les données sur la mortalité (1984–2019) sont extraites de la Base canadienne de données sur les décès de la Statistique de l’état civil. Nous avons projeté les nombres et les taux d’incidence du cancer et de mortalité jusqu’en 2022 pour 22 types de cancer, par sexe et par province ou territoire. Les taux ont été normalisés selon l’âge de la population type canadienne de 2011. Résultats: On estime à 233 900 le nombre de nouveaux cas de cancer et à 85 100 le nombre de décès des suites du cancer au Canada en 2022. Nous nous attendons à ce que les cancers les plus fréquemment diagnostiqués soient le cancer du poumon en général (30 000), le cancer du sein chez les femmes (28 600) et le cancer de la prostate chez les hommes (24 600). De plus, le cancer du poumon devrait être la principale cause de décès lié au cancer, représentant 24,3 % de l’ensemble des décès par cancer, suivi des cancers colorectal (11,0 %), du pancréas (6,7 %) et du sein (6,5 %). On s’attend généralement à ce que les taux d’incidence et de mortalité soient plus élevés dans les provinces de l’est du Canada que dans celles de l’ouest. Interprétation: Bien que les taux globaux de cancer soient en baisse, le nombre de cas et de décès continue de grimper, en raison de la croissance démographique et du vieillissement démographique. Le fardeau élevé projeté du cancer du poumon indique qu’il est nécessaire de renforcer la lutte contre le tabagisme et d’améliorer la détection précoce et le traitement. Les progrès réalisés en matière de dépistage et de traitement du cancer du sein et du cancer colorectal expliquent probablement la diminution continue de leur fardeau. Les progrès limités en matière de détection précoce et de nouveaux traitements du cancer du pancréas expliquent pourquoi on s’attend à ce qu’il soit la troisième cause de décès par cancer au Canada.

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.

Project description:BACKGROUND:The study objective was to assess the influence of neutropenia on outcome of critically ill cancer patients by meta-analysis of individual data. Secondary objectives were to assess the influence of neutropenia on outcome of critically ill patients in prespecified subgroups (according to underlying tumor, period of admission, need for mechanical ventilation and use of granulocyte colony stimulating factor (G-CSF)). METHODS:Data sources were PubMed and the Cochrane database. Study selection included articles focusing on critically ill cancer patients published in English and studies in humans from May 2005 to May 2015. For study selection, the study eligibility was assessed by two investigators. Individual data from selected studies were obtained from corresponding authors. RESULTS:Overall, 114 studies were identified and authors of 30 studies (26.3% of selected studies) agreed to participate in this study. Of the 7515 included patients, three were excluded due to a missing major variable (neutropenia or mortality) leading to analysis of 7512 patients, including 1702 neutropenic patients (22.6%). After adjustment for confounders, and taking study effect into account, neutropenia was independently associated with mortality (OR 1.41; 95% CI 1.23-1.62; P = 0.03). When analyzed separately, neither admission period, underlying malignancy nor need for mechanical ventilation modified the prognostic influence of neutropenia on outcome. However, among patients for whom data on G-CSF administration were available (n?=?1949; 25.9%), neutropenia was no longer associated with outcome in patients receiving G-CSF (OR 1.03; 95% CI 0.70-1.51; P?=?0.90). CONCLUSION:Among 7512 critically ill cancer patients included in this systematic review, neutropenia was independently associated with poor outcome despite a meaningful survival. Neutropenia was no longer significantly associated with outcome in patients treated by G-CSF, which may suggest a beneficial effect of G-CSF in neutropenic critically ill cancer patients. SYSTEMATIC REVIEW REGISTRATION:PROSPERO CRD42015026347 . Date of registration: Sept 18 2015.

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Dataset Information

Outcomes in adult critically ill cancer patients with and without neutropenia: a systematic review and meta-analysis of the Groupe de Recherche en Reanimation Respiratoire du patient d'Onco-Hematologie (GRRR-OH).

Publications

Outcomes in adult critically ill cancer patients with and without neutropenia: a systematic review and meta-analysis of the Groupe de Recherche en Réanimation Respiratoire du patient d'Onco-Hématologie (GRRR-OH).

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