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2. Necrotizing soft tissue infections in critically ill neutropenic patients: a French multicentre retrospective cohort study

Author

Romain Arrestier, Anis Chaba, Asma Mabrouki, Clément Saccheri, Emmanuel Canet, Marc Pineton de Chambrun, Annabelle Stoclin, Muriel Picard, Florent Wallet, François Perier, Matthieu Turpin, Laurent Argaud, Maxens Decavèle, Nahéma Issa, Cyril Cadoz, Kada Klouche, Johana Cohen, Djamel Mokart, Julien Grouille, Tomas Urbina, Camille Hua, Olivier Chosidow, Armand Mekontso-Dessap, Elie Azoulay, and Nicolas de Prost

Subjects
Critical Care and Intensive Care Medicine
Abstract

Background Necrotizing soft tissue infections (NSTIs) are rare life-threatening bacterial infections. Few data are available regarding neutropenic patients with NSTIs. Our objectives were to describe the characteristics and management of neutropenic patients with NSTIs in intensive care units (ICUs). We conducted a retrospective multicentre cohort study in 18 ICUs between 2011 and 2021. Patients admitted with NSTIs and concomitant neutropenia at diagnosis were included and compared to non-neutropenic patients with NSTIs. The relationship between therapeutic interventions and outcomes was assessed using Cox regression and propensity score matching. Results 76 neutropenic patients were included and compared to 165 non-neutropenic patients. Neutropenic patients were younger (54 ± 14 vs 60 ± 13 years, p = 0.002) and had less lower limb (44.7% vs 70.9%, p p p p = 0.010) and multivariable Cox (adjusted HR = 0.46 95% CI [0.22–0.94], p = 0.033) analyses and after overlap propensity score weighting (odds ratio = 0.25 95% CI [0.09; 0.68], p = 0.006). Conclusions Critically ill neutropenic patients with NSTIs present different clinical and microbiological characteristics and are associated with a higher hospital mortality than non-neutropenic patients. G-CSF administration was associated with hospital survival.

Published
2023

3. ICU admission for solid cancer patients treated with immune checkpoint inhibitors

Author

Anne-Claire Toffart, Anne-Pascale Meert, Florent Wallet, Aude Gibelin, Olivier Guisset, Frédéric Gonzalez, Amélie Seguin, Achille Kouatchet, Myriam Delaunay, Didier Debieuvre, Boris Duchemann, Gaëlle Rousseau-Bussac, Martine Nyunga, David Grimaldi, Albrice Levrat, Elie Azoulay, and Virginie Lemiale

Subjects
Critical Care and Intensive Care Medicine
Abstract

Background Immune checkpoint inhibitors (ICI) have revolutionized the management of cancer. They can induce immune-related adverse events (irAE) leading to intensive care unit (ICU) admission. We aimed to describe irAEs for ICU admissions in solid cancer patients treated with ICIs. Methods This prospective multicenter study was conducted in France and Belgium. Adult patients with solid tumor and treated with systemic ICIs within the last 6 months, requiring non-programmed ICU admission were included. Patients admitted for microbiologically documented sepsis were excluded. Imputability of irAEs in ICU admissions was described according to the WHO-UMC classification system at ICU admission and at ICU discharge. The use of immunosuppressant treatment was reported. Results 115 patients were eligible. Solid tumor was mainly lung cancer (n = 76, 66%) and melanoma (n = 18, 16%). They were mainly treated with an anti-PD-(L)1 alone (n = 110, 96%). Main ICU admission reasons were acute respiratory failure (n = 66, 57%), colitis (n = 14, 13%), and cardiovascular disease (n = 13, 11%). ICU admission was considered “likely” associated with irAE for 48% (n = 55) of patients. Factors independently associated with irAE were a good ECOG performance status (PS) (ECOG-PS of 0 or 1 vs. ECOG-PS of 2–3, odds ratio [OR] = 6.34, 95% confidence interval [95% CI] 2.13–18.90, and OR = 3.66, 95% CI 1.33–10.03, respectively), and a history of irAE (OR = 3.28, 95% CI 1.19–9.01). Steroids were prescribed for 41/55 (75%) patients with ICU admission “likely” related to irAE. Three patients were subsequently treated with immunosuppressants. Conclusion IrAEs accounted for half of ICU admissions in cancer patients receiving ICIs. They could be treated with steroids. Identifying the imputability of irAEs in ICU admissions remains a challenge.

Published
2023

4. Description of neurotoxicity in a series of patients treated with CAR T-cell therapy

Author

Lila Sirven-Villaros, Sylvain Lamure, Thomas Gastinne, Florent Wallet, Antoine F. Carpentier, Benoit Tessoulin, David Laplaud, Claire Simard, Catherine Belin, Elie Azoulay, Adrien Paix, Catherine Thieblemont, Perrine Devic, Guillaume Cartron, Renata Ursu, Laura Platon, Xavier Ayrignac, Emmanuel Bachy, Colette Berger, Amélie Dos Santos, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hospices Civils de Lyon (HCL), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre hospitalier universitaire de Nantes (CHU Nantes), Institut de Radiothérapie de Bobigny, Institut de Génétique Moléculaire de Montpellier (IGMM), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), and Hopital Saint-Louis [AP-HP] (AP-HP)

Subjects
CAR-T cell therapy, Adult, Male, medicine.medical_specialty, Lymphoma, B-Cell, Lymphoma, medicine.medical_treatment, Receptors, Antigen, T-Cell, lcsh:Medicine, [SDV.CAN]Life Sciences [q-bio]/Cancer, Immunotherapy, Adoptive, Severity of Illness Index, Article, Cell therapy, 03 medical and health sciences, 0302 clinical medicine, Neurotoxicity syndromes, Internal medicine, Severity of illness, Neurotoxicity, medicine, Humans, Prospective Studies, lcsh:Science, Prospective cohort study, Survival analysis, Aged, 030304 developmental biology, 0303 health sciences, Multidisciplinary, business.industry, lcsh:R, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Immunotherapy, Middle Aged, medicine.disease, Survival Analysis, 3. Good health, Cytokine release syndrome, C-Reactive Protein, Treatment Outcome, 030220 oncology & carcinogenesis, [SDV.IMM]Life Sciences [q-bio]/Immunology, lcsh:Q, Female, business
Abstract

Chimeric antigen receptor-modified T (CAR T) cell therapy is a highly promising treatment for haematological malignancies but is frequently associated with cytokine release syndrome and neurotoxicity. Between July 2018 and July 2019, all patients treated with CD19-targeted CAR T-cell therapy for relapsing lymphoma were followed-up longitudinally to describe neurological symptoms and their evolution over time. Four different French centres participated and 84 patients (median age 59 years, 31% females) were included. Neurotoxicity, defined as the presence of at least one neurological symptom appearing after treatment infusion, was reported in 43% of the patients. The median time to onset was 7 days after infusion with a median duration of 6 days. More than half of the patients (64%) had grade 1–2 severity and 34% had grade 3–4. CRS was observed in 80% of all patients. The most frequent neurological symptoms were cognitive signs, being severe in 36%, and were equally distributed between language disorders and cognitive disorders without language impairment. Non-pyramidal motor disorders, severe in 11%, were reported in 42% of the patients. Elevation of C-reactive protein (CRP) within 4 days after treatment was significantly correlated with the occurrence of grade 3–4 neurotoxicity. Although sometimes severe, neurotoxicity was almost always reversible. The efficacy of steroids and antiepileptic drugs remains unproven in the management of neurotoxicity. Neurotoxicity associated with CAR T-cell therapies occurs in more than 40% of patients. The clinical pattern is heterogeneous but cognitive disorders (not limited to language disorders) and, to a minor degree, non-pyramidal motor disorders, appeared as a signature of severe neurotoxicity.

Published
2020

5. Outcome of acute mesenteric ischemia in the intensive care unit: a retrospective, multicenter study of 780 cases

Author

Mourad Boufi, Eric Kipnis, Oriane Martinez, Alexandra Piton, Djillali Annane, Nicolas Bruder, Olivier Baldesi, Didier Demory, Matthieu Legrand, Jean-Michel Constantin, Claude Martin, Bernard Allaouchiche, Florent Wallet, Karim Asehnoune, Olivier Mimoz, Karine Baumstarck, Baptiste Hengy, Jean-Yves Lefrant, Charlotte Arbelot, Laurence Delapierre, Alexandre Ouattara, Bruno Levy, Carole Ichai, Simon Bourcier, Fanny Klasen, Elisa Richter, Thomas Rimmelé, Kamel Toufik, Carole Bechis, Marc Leone, Sigismond Lasocki, Emilie Friou, Pascal Augustin, Jugurtha Aliane, Olivier Collange, Etienne Brasdefer, Marie-Charlotte Vogler, Samir Jaber, Eric Peytel, Pierre-Marie Bertrand, Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes (URMITE), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR48, Institut des sciences biologiques (INSB-CNRS)-Institut des sciences biologiques (INSB-CNRS)-Centre National de la Recherche Scientifique (CNRS), Service d’anesthésie et de réanimation, Santé Publique et maladies Chroniques : Qualité de vie Concepts, Usages et Limites, Déterminants (SPMC), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM), Service d’Anesthésie-Réanimation II Bordeaux, Services de soins intensifs, CHU Strasbourg, Département d’Anesthésie Réanimation Chirurgicale, CIT-IT Garches, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Raymond Poincaré [AP-HP]-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service d'anesthésie et réanimation chirurgicale [Nantes], Hôtel-Dieu-Centre hospitalier universitaire de Nantes (CHU Nantes), Service de réanimation, CHU Saint-Antoine [AP-HP], Service de Réanimation Polyvalente, Centre Hospitalier Henri Duffaut (Avignon), Centre Hospitalier Intercommunal Toulon-La Seyne sur Mer - Hôpital Sainte-Musse, Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Sektion Anästhesiologische Pathophysiologie und Verfahrensentwicklung, Universitätsklinikum Ulm - University Hospital of Ulm, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre Hospitalier Universitaire de Lille (CHU de Lille), Pôle d'Anesthésie Réanimation, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Biomarqueurs CArdioNeuroVASCulaires (BioCANVAS), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Pharmacologie des anti-infectieux (PHAR), Université de Poitiers-Institut National de la Santé et de la Recherche Médicale (INSERM), Agressions vasculaires et réponses tissulaires, Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), Retinoids, Development and Developmental Diseases (R2D2), Université d'Auvergne - Clermont-Ferrand I (UdA), Intensive Care Unit, Cannes general hospital, Cannes, Réanimation Polyvalente, Hôpital de la Timone [CHU - APHM] (TIMONE), Unité médicale de soins intensifs, Department of Medical Intensive Care and Hyperbaric Medicine, Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Service de Réanimation Médicale [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Service d’Anesthésiologie et Réanimation [H.I.A Laveran, Marseille], Hôpital d'instruction des armées Laveran [Marseille], Pôle Anesthésie Réanimation [CHU de Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Département d’Anesthésie et de Réanimation, Medical-surgical Intensive Care Unit, Service d’anesthésie réanimation, Aix-Marseille Université - Faculté de médecine (AMU MED), Aix Marseille Université (AMU), CHU Clermont-Ferrand, CHU Marseille, Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Caractéristiques féminines des dysfonctions des interfaces cardio-vasculaires (EA 2992), Université Montpellier 1 (UM1)-Université de Montpellier (UM), INSB-INSB-Centre National de la Recherche Scientifique (CNRS), Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU), Surgical Critical Care Unit, Department of Anesthesiology and Critical Care, Département d'anesthésie et de soins intensifs, and MORNET, Dominique

Subjects
medicine.medical_specialty, [SDV]Life Sciences [q-bio], health care facilities, manpower, and services, Recursive partitioning, 030204 cardiovascular system & hematology, Critical Care and Intensive Care Medicine, law.invention, 03 medical and health sciences, 0302 clinical medicine, law, Anesthesiology, Severity of illness, medicine, Risk factor, Intensive care medicine, ComputingMilieux_MISCELLANEOUS, business.industry, Mortality rate, 030208 emergency & critical care medicine, Retrospective cohort study, medicine.disease, Intensive care unit, 3. Good health, [SDV] Life Sciences [q-bio], Mesenteric ischemia, Emergency medicine, business
Abstract

In the intensive care unit (ICU), the outcomes of patients with acute mesenteric ischemia (AMI) are poorly documented. This study aimed to determine the risk factors for death in ICU patients with AMI. A retrospective, observational, non-interventional, multicenter study was conducted in 43 ICUs of 38 public institutions in France. From January 2008 to December 2013, all adult patients with a diagnosis of AMI during their hospitalization in ICU were included in a database. The diagnosis was confirmed by at least one of three procedures (computed tomography scan, gastrointestinal endoscopy, or upon surgery). To determine factors associated with ICU death, we established a logistic regression model. Recursive partitioning analysis was applied to construct a decision tree regarding risk factors and their interactions most critical to determining outcomes. The death rate of the 780 included patients was 58 %. Being older, having a higher sequential organ failure assessment (SOFA) severity score at diagnosis, and a plasma lactate concentration over 2.7 mmol/l at diagnosis were independent risk factors of ICU mortality. In contrast, having a prior history of peripheral vascular disease or an initial surgical treatment were independent protective factors against ICU mortality. Using age and SOFA severity score, we established an ICU mortality score at diagnosis based on the cutoffs provided by recursive partitioning analysis. Probability of survival was statistically different (p

Published
2015

6. Lemierre’s syndrome: when a contralateral thrombosis stirs the debate

Author

M. Freichet, Florent Wallet, S. Ledochowski, and Arnaud Friggeri

Subjects
Adult, Male, medicine.medical_specialty, Heparin, business.industry, Septic shock, Pain medicine, Lemierre Syndrome, Thrombophlebitis, Critical Care and Intensive Care Medicine, medicine.disease, Thrombosis, Anti-Bacterial Agents, Surgery, Anesthesiology, Lemierre's syndrome, medicine, Humans, Jugular Veins, Tomography, X-Ray Computed, business, Internal jugular vein
Published
2014

7. Thrombosis during lepirudin therapy: a case report

Author

Véronique Leray, Gael Bourdin, Florent Wallet, Jean-Christophe Richard, Claude Guérin, and Frédérique Bayle

Subjects
medicine.medical_specialty, business.industry, Pain medicine, Anesthesiology, medicine, Lepirudin, Critical Care and Intensive Care Medicine, business, medicine.disease, Intensive care medicine, Thrombosis, medicine.drug
Published
2008

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