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. Non-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.publishedVersio

Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Distress Syndrome associated with COVID-19: An Emulated Target Trial Analysis.

RATIONALE: Whether COVID patients may benefit from extracorporeal membrane oxygenation (ECMO) compared with conventional invasive mechanical ventilation (IMV) remains unknown. OBJECTIVES: To estimate the effect of ECMO on 90-Day mortality vs IMV only Methods: Among 4,244 critically ill adult patients with COVID-19 included in a multicenter cohort study, we emulated a target trial comparing the treatment strategies of initiating ECMO vs. no ECMO within 7 days of IMV in patients with severe acute respiratory distress syndrome (PaO2/FiO2 <80 or PaCO2 ≥60 mmHg). We controlled for confounding using a multivariable Cox model based on predefined variables. MAIN RESULTS: 1,235 patients met the full eligibility criteria for the emulated trial, among whom 164 patients initiated ECMO. The ECMO strategy had a higher survival probability at Day-7 from the onset of eligibility criteria (87% vs 83%, risk difference: 4%, 95% CI 0;9%) which decreased during follow-up (survival at Day-90: 63% vs 65%, risk difference: -2%, 95% CI -10;5%). However, ECMO was associated with higher survival when performed in high-volume ECMO centers or in regions where a specific ECMO network organization was set up to handle high demand, and when initiated within the first 4 days of MV and in profoundly hypoxemic patients. CONCLUSIONS: In an emulated trial based on a nationwide COVID-19 cohort, we found differential survival over time of an ECMO compared with a no-ECMO strategy. However, ECMO was consistently associated with better outcomes when performed in high-volume centers and in regions with ECMO capacities specifically organized to handle high demand. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/)

Etude des mécanismes de l'inflammation pulmonaire au cours de la sclérodermie systémique

La détection précoce de l'atteinte pulmonaire par les marqueurs biologiques a reposé sur le ciblage des macrophages activés grâce à une technique isotopique non invasive reposant sur l'administration par aérosol d'un galactosyl encapsulé marqué au Technetium 99m, le J00IX, permettant le ciblage des macrophages activés. L'étude du métabolisme du collagène I et III a constitué une autre approche pour la détection précoce de l'inflammation pulmonaire. L'étude des mécanismes immunologiques de la fibrogénèse a consisté en l'évaluation de la contribution de l'atteinte pulmonaire dans l'élévation de l'anti-topoisomérase I. Pour apprécier le retentissement de la fibrose sur l'architecture anatomique du poumon, nous avons optimisé la spécificité de l'examen en tomodensitométrie fine à haute résolution en validant un score basé sur l'analyse pondérée des images. Nous nous sommes ensuite intéressés à la signification de l'altération du transfert de monoxyde de carbone grâce à un traceur radioactif administré par aérosol et dont la clairance est exclusivement dépendante de la perméabilité épithéliale, le diethylènetriamine pentaacétate. Le rôle potentiel de facteurs extrinsèques a fait appel une étude prospective professionnelle cas-témoins.The early detection of pulmonary damage by biological markers relied on the targeting of the activated macrophages by a non-invasive isotopic method based on the aerosol administration of an encapsulated galactosyl labelled with Technetium 99m, the J001X, which allowed the targeting of the activated macrophages. The study of the collagen III and I metabolism represented another approach for the early detection of the pulmonary inflammation. The study of the immunological mechanisms of fibrinogenesis consisted in the evaluation of the pulmonary implication of the anti-topoisomerase I enhancement.In order to evaluate the consequences of fibrosis on the anatomic lung structure, we have optimised the specificity high-resolution CT scanning by validating a score based on the balanced analysis of the images. We were then interested by the meaning of the alteration of the carbon monoxide transfer. To discriminate the vascular or epithelial possible mechanisms we have used a radioactive tracer administrated by aerosol, the diethylenetriamine pentaacetate. For the potential role of extrinsic factors we carried out a prospective professional case-control study.TOURS-BU Médecine (372612103) / SudocPARIS-BIUP (751062107) / SudocSudocFranceF

Effet thérapeutique du Cetuximab administré par aérosol dans un modèle animal de tumeur broncho-pulmonaire (importance du récepteur Fc Rn dans la réponse anti-tumorale à cet anticorps)

Le but de cette étude a été d analyser l intérêt de l aérosolthérapie d anticorps monoclonaux (AcM) dans le traitement du cancer broncho-pulmonaire non à petites cellules (CBNPC) en utilisant le cetuximab, un AcM anti-EGFR. L expression du récepteur FcRn, essentiel dans la pharmacocinétique et la biodistribution des IgGs thérapeutiques a été étudiée dans le CBNPC. Nos résultats montrent que l AcM peut résister aux contraintes physiques de la nébulisation. Les données de biodistribution et pharmacocinétique, obtenues dans un modèle animal, indiquent que l Ac administré par aérosol, s accumule de façon prolongée au niveau pulmonaire. De plus, les tumeurs chez la souris paraissent sensibles à l aérosolthérapie avec l AcM. Par ailleurs, le récepteur FcRn est moins exprimé au niveau transcriptionnel et protéique dans le tissu tumoral que dans le tissu sain adjacent à la tumeur dans le CBNPC. Cette altération de l expression pourrait être due à l hyperméthylation du promoteur de ce gène.TOURS-BU Médecine (372612103) / SudocSudocFranceAustraliaFRA

LYMPHANGIOLEIOMYOMATOSE (RELATION ENTRE UN SCORE TOMODENSITOMETRIQUE ET L'ANATOMO-PATHOLOGIE)

TOURS-BU Médecine (372612103) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

ETUDE DE LA REPRODUCTIBILITE INTRA ET INTERLECTEUR DANS L'APPRECIATION TOMODENSITOMETRIQUE DU VOLUME DES TUMEURS BRONCHOPULMONAIRES

TOURS-BU Médecine (372612103) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF