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1. Sedation versus general anaesthesia in endovascular therapy for anterior circulation acute ischaemic stroke: the multicentre randomised controlled AMETIS trial study protocol

Author

Franck Verdonk, Bruno Pereira, Aurélie Masgrau, Anne-Claire Lukaszewicz, Serge Molliex, Samir Jaber, Ségolène Mrozek, Emmanuel Futier, Russell Chabanne, Lionel Velly, Elodie Caumon, Emmanuel Chabert, Charlotte Fernandez-Canal, Jean-Etienne Bazin, Anna Ferrier, Claire Dahyot-Fizelier, Pierre-François Perrigault, Marc Begard, Benoît Tavernier, Vincent Degos, CHU Clermont-Ferrand, Sorbonne Université - Faculté de Médecine (SU FM), Sorbonne Université (SU), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Physiopathologie de l'immunodépression associée aux réponses inflammatoires systémiques - EA 7426 (PI3), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Assistance Publique - Hôpitaux de Marseille (APHM), Département d'Anesthésie-Réanimation [Toulouse], Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse], CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Pharmacologie des anti-infectieux (PHAR), Université de Poitiers-Institut National de la Santé et de la Recherche Médicale (INSERM), Unité de Nutrition Humaine (UNH), Institut National de la Recherche Agronomique (INRA)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), CHU Gabriel Montpied [Clermont-Ferrand], Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service d'Anésthésie Réanimation [CHU Clermont-Ferrand], CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Unité de Biostatistiques [CHU Clermont-Ferrand], Direction de la recherche clinique et de l’innovation [CHU Clermont-Ferrand] (DRCI), MORNET, Dominique, Pôle Anesthésie Réanimation [CHU de Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Assistance Publique Hôpitaux de Paris (AP-HP)Assistance Publique Hôpitaux de Paris (AP-HP), Groupe Hospitalier Pitié-Salpêtrière, Paris, France., Centre Hospitalier Universitaire de Clermont-Ferrand, Unité de Nutrition Humaine - Clermont Auvergne (UNH), Institut National de la Recherche Agronomique (INRA)-Université Clermont Auvergne (UCA), CHU Gabriel Montpied (CHU), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Service de réanimation adulte, département d'anesthésie-réanimation, CHU Clermont-Ferrand-Hôtel Dieu, Unité de biostatistiques, CHU Clermont-Ferrand-Hôpital Montpied, Physiopathologie de l'immunodépression associée aux réponses inflammatoires systémiques / Pathophysiology of Injury-induced Immunosuppression (PI3), and Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E)

Subjects
Adult, Male, Mechanical Thrombolysis, Sedation, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Conscious Sedation, Anesthesia, General, Anaesthesia, 03 medical and health sciences, 0302 clinical medicine, Modified Rankin Scale, medicine, Protocol, Humans, Multicenter Studies as Topic, General anaesthesia, 030212 general & internal medicine, Myocardial infarction, Stroke, Randomized Controlled Trials as Topic, business.industry, Endovascular Procedures, General Medicine, Thrombolysis, Perioperative, medicine.disease, stroke, 3. Good health, anaesthesia in neurology, [SDV] Life Sciences [q-bio], sedation, thrombectomy, Anesthesia, Observational study, Female, medicine.symptom, business, 030217 neurology & neurosurgery
Abstract

IntroductionEndovascular thrombectomy is the standard of care for anterior circulation acute ischaemic stroke (AIS) secondary to emergent large vessel occlusion in patients who qualify. General anaesthesia (GA) or conscious sedation (CS) is usually required to ensure patient comfort and avoid agitation and movement during thrombectomy. However, the question of whether the use of GA or CS might influence functional outcome remains debated. Indeed, conflicting results exist between observational studies with better outcomes associated with CS and small monocentric randomised controlled trials favouring GA. Therefore, we aim to evaluate the effect of CS versus GA on functional outcome and periprocedural complications in endovascular mechanical thrombectomy for anterior circulation AIS.Methods and analysisAnesthesia Management in Endovascular Therapy for Ischemic Stroke (AMETIS) trial is an investigator initiated, multicentre, prospective, randomised controlled, two-arm trial. AMETIS trial will randomise 270 patients with anterior circulation AIS in a 1:1 ratio, stratified by centre, National Institutes of Health Stroke Scale (≤15 or >15) and association of intravenous thrombolysis or not to receive either CS or GA. The primary outcome is a composite of functional independence at 3 months and absence of perioperative complication occurring by day 7 after endovascular therapy for anterior circulation AIS. Functional independence is defined as a modified Rankin Scale score of 0–2 by day 90. Perioperative complications are defined as intervention-associated arterial perforation or dissection, pneumonia or myocardial infarction or cardiogenic acute pulmonary oedema or malignant stroke evolution occurring by day 7.Ethics and disseminationThe AMETIS trial was approved by an independent ethics committee. Study began in august 2017. Results will be published in an international peer-reviewed medical journal.Trial registration numberNCT03229148.

Published
2019
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2. Personalised mechanical ventilation tailored to lung morphology versus low positive end-expiratory pressure for patients with acute respiratory distress syndrome in France (the LIVE study): a multicentre, single-blind, randomised controlled trial

Author

Jean-Michel Constantin, Matthieu Jabaudon, Jean-Yves Lefrant, Samir Jaber, Jean-Pierre Quenot, Olivier Langeron, Martine Ferrandière, Fabien Grelon, Philippe Seguin, Carole Ichai, Benoit Veber, Bertrand Souweine, Thomas Uberti, Sigismond Lasocki, François Legay, Marc Leone, Nathanael Eisenmann, Claire Dahyot-Fizelier, Hervé Dupont, Karim Asehnoune, Achille Sossou, Gérald Chanques, Laurent Muller, Jean-Etienne Bazin, Antoine Monsel, Lucile Borao, Jean-Marc Garcier, Jean-Jacques Rouby, Bruno Pereira, Emmanuel Futier, Cayot Sophie, Godet Thomas, Guerin Renaud, Verlac Camille, Chabanne Russel, Cosserant Bernard, Blondonnet Raiko, Lautrette Alexandre, Eisenmann Nathanael, Muller Laurent, Massanet Pablo, Boutin Caroline, Barbar Saber, Roger Claire, Belafia Fouad, Cisse Moussa, Monnin Marion, Conseil Matthieu, Carr Julie, De Jong Audrey, Dargent Auguste, Andreu Pascal, Lebouvrier Thomas, Launey Yoann, Roquilly Antoine, Cinotti Raphael, Tellier Anne-Charlotte, Barbaz Mathilde, Cohen Benjamin, Lemarche Edouard, Bertrand Pierre-Marie, Arberlot Charlotte, Zieleskiewicz Laurent, Hammad Emmanuelle, Duclos Garry, Mathie Calypso, Dupont Herve, Veber Benoit, Orban Jean-Christophe, Quintard Hervé, Rimmele Thomas, Crozon-Clauzel Julien, Le Core Marinne, Grelon Fabien, Assefi Mona, Petitas Frank, Morel Jerome, Molliex Serge, Hadanou Nanadougmar, CHU Clermont-Ferrand, Service d'Anésthésie Réanimation [CHU Clermont-Ferrand], CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Caractéristiques féminines des dysfonctions des interfaces cardio-vasculaires (EA 2992), Université Montpellier 1 (UM1)-Université de Montpellier (UM), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), 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 Régional Universitaire [Montpellier] (CHRU Montpellier), Service de Réanimation Médicale (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre Hospitalier Le Mans (CH Le Mans), CHU Pontchaillou [Rennes], Nutrition, Métabolismes et Cancer (NuMeCan), Institut National de la Recherche Agronomique (INRA)-Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de réanimation, Centre Hospitalier Universitaire de Nice (CHU Nice)-Hôpital St Roch, Département d'anesthésie-Réanimation-Samu, CHU Rouen, Normandie Université (NU)-Normandie Université (NU), Unité de soins intensifs [Clermont Ferrand], CHU Clermont-Ferrand-CHU Gabriel Montpied [Clermont-Ferrand], Edouard Herriot Hospital, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), CHU de Saint-Brieuc, Service Anesthésie et Réanimation [Hôpital Nord - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital Nord [CHU - APHM], Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), UNICANCER, Centre hospitalier universitaire de Poitiers (CHU Poitiers), Pharmacologie des anti-infectieux (PHAR), Université de Poitiers-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Amiens-Picardie, Thérapeutiques cliniques et expérimentales des infections (EA 3826) (EA 3826), Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Department of Anesthesiology and Critical Care Medicine, Emile-Roux general hospital, Le Puy-en-Velay, Université de Montpellier (UM), Immunologie - Immunopathologie - Immunothérapie (I3), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Unité de Biostatistiques [CHU Clermont-Ferrand], Direction de la recherche clinique et de l’innovation [CHU Clermont-Ferrand] (DRCI), Institut Pascal (IP), SIGMA Clermont (SIGMA Clermont)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), Génétique, Reproduction et Développement (GReD ), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), Department of Perioperative Medicine, CHU Clermont-Ferrand, CHU Pitié-Salpêtrière [APHP], Hopital Général, Le Mans, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Clermont-Ferrand-Hôpital Gabriel Montpied, Hospital General Saint-Brieuc, Hôpital Nord [CHU - APHM]-Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU), Centre Régional de Lutte Contre le Cancer Jean Perrin, Centre hospitalier universitaire d'Amiens (CHU Amiens-Picardie), Service de réanimation adulte, département d'anesthésie-réanimation, CHU Clermont-Ferrand-Hôtel Dieu, Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), University Hospital of Clermont-Ferrand, Institut Pascal - Clermont Auvergne (IP), Sigma CLERMONT (Sigma CLERMONT)-Université Clermont Auvergne (UCA)-Centre National de la Recherche Scientifique (CNRS), Unité de biostatistiques, CHU Clermont-Ferrand-Hôpital Montpied, Génétique, Reproduction et Développement - Clermont Auvergne (GReD ), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA)-Centre National de la Recherche Scientifique (CNRS), MORNET, Dominique, Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])

Subjects
Pulmonary and Respiratory Medicine, Male, medicine.medical_specialty, ARDS, medicine.medical_treatment, [SDV]Life Sciences [q-bio], law.invention, Positive-Pressure Respiration, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, law, Internal medicine, Fraction of inspired oxygen, Intensive care, medicine, Prone Position, Tidal Volume, Humans, Single-Blind Method, 030212 general & internal medicine, Prospective Studies, Precision Medicine, Lung, Positive end-expiratory pressure, Tidal volume, ComputingMilieux_MISCELLANEOUS, Proportional Hazards Models, Mechanical ventilation, Respiratory Distress Syndrome, business.industry, Hazard ratio, Middle Aged, medicine.disease, Respiration, Artificial, 3. Good health, [SDV] Life Sciences [q-bio], Intensive Care Units, Editorial Commentary, Treatment Outcome, 030228 respiratory system, Female, France, business
Abstract

The effect of personalised mechanical ventilation on clinical outcomes in patients with acute respiratory distress syndrome (ARDS) remains uncertain and needs to be evaluated. We aimed to test whether a mechanical ventilation strategy that was personalised to individual patients' lung morphology would improve the survival of patients with ARDS when compared with standard of care.We designed a multicentre, single-blind, stratified, parallel-group, randomised controlled trial enrolling patients with moderate-to-severe ARDS in 20 university or non-university intensive care units in France. Patients older than 18 years with early ARDS for less than 12 h were randomly assigned (1:1) to either the control group or the personalised group using a minimisation algorithm and stratified according to the study site, lung morphology, and duration of mechanical ventilation. Only the patients were masked to allocation. In the control group, patients received a tidal volume of 6 mL/kg per predicted bodyweight and positive end-expiratory pressure (PEEP) was selected according to a low PEEP and fraction of inspired oxygen table, and early prone position was encouraged. In the personalised group, the treatment approach was based on lung morphology; patients with focal ARDS received a tidal volume of 8 mL/kg, low PEEP, and prone position. Patients with non-focal ARDS received a tidal volume of 6 mL/kg, along with recruitment manoeuvres and high PEEP. The primary outcome was 90-day mortality as established by intention-to-treat analysis. This study is registered online with ClinicalTrials.gov, NCT02149589.From June 12, 2014, to Feb 2, 2017, 420 patients were randomly assigned to treatment. 11 patients were excluded in the personalised group and nine patients were excluded in the control group; 196 patients in the personalised group and 204 in the control group were included in the analysis. In a multivariate analysis, there was no difference in 90-day mortality between the group treated with personalised ventilation and the control group in the intention-to-treat analysis (hazard ratio [HR] 1·01; 95% CI 0·61-1·66; p=0·98). However, misclassification of patients as having focal or non-focal ARDS by the investigators was observed in 85 (21%) of 400 patients. We found a significant interaction between misclassification and randomised group allocation with respect to the primary outcome (p0·001). In the subgroup analysis, the 90-day mortality of the misclassified patients was higher in the personalised group (26 [65%] of 40 patients) than in the control group (18 [32%] of 57 patients; HR 2·8; 95% CI 1·5-5·1; p=0·012.Personalisation of mechanical ventilation did not decrease mortality in patients with ARDS, possibly because of the misclassification of 21% of patients. A ventilator strategy misaligned with lung morphology substantially increases mortality. Whether improvement in ARDS phenotyping can decrease mortality should be assessed in a future clinical trial.French Ministry of Health (Programme Hospitalier de Recherche Clinique InterRégional 2013).

Published
2019
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3. Elevated Plasma Levels of sRAGE Are Associated With Nonfocal CT-Based Lung Imaging in Patients With ARDS A Prospective Multicenter Study

Author

Mrozek, Segolene, Jabaudon, Matthieu, Jaber, Samir, Paugam-Burtz, Catherine, Lefrant, Jean-Yves, Rouby, Jean-Jacques, Asehnoune, Karim, Allaouchiche, Bernard, Baldesi, Olivier, Leone, Marc, Lu, Qin, Bazin, Jean-Etienne, Roszyk, Laurence, Sapin, Vincent, Futier, Emmanuel, Pereira, Bruno, Constantin, Jean-Michel, 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), Hôpital Beaujon, Hôpital Beaujon-Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Pôle d'anesthésie-réanimation-urgences, Centre Hospitalier Régional Universitaire de Nîmes (CHRU Nîmes)-Hôpital Universitaire Carémeau [Nîmes], Caractéristiques féminines des dysfonctions des interfaces cardio-vasculaires (EA 2992), Université Montpellier 1 (UM1)-Université de Montpellier (UM), CHU Pitié-Salpêtrière [APHP], Thérapeutiques cliniques et expérimentales des infections (EA 3826) (EA 3826), Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Service d'Anesthésie-Réanimation [CHU Limoges], CHU Limoges, Service de Réanimation, Hospices Civils de Lyon (HCL)-Hôpital E. Herriot, 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, INSB-INSB-Centre National de la Recherche Scientifique (CNRS), Service de réanimation adulte, département d'anesthésie-réanimation, CHU Clermont-Ferrand-Hôtel Dieu, Laboratoire de Biochimie, Centre Hospitalier Universitaire de Clermont-Ferrand, Département anesthésie et réanimation, CHU Clermont-Ferrand-Hôpital d'Estaing, Unité de biostatistiques, CHU Clermont-Ferrand, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes)-Hôpital Universitaire Carémeau [Nîmes] (CHU Nîmes), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut des sciences biologiques (INSB-CNRS)-Institut des sciences biologiques (INSB-CNRS)-Centre National de la Recherche Scientifique (CNRS), Service d'Anésthésie Réanimation [CHU Clermont-Ferrand], CHU Estaing [Clermont-Ferrand], and CHU Clermont-Ferrand-CHU Clermont-Ferrand

Subjects
[SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases
Abstract

International audience; BACKGROUND: During ARDS, CT can reveal two distinct lung imaging patterns, focal or non-focal, with different responses to positive end-expiratory pressure, recruitment maneuvers, and prone position. Nevertheless, their association with plasma biomarkers and their distinct functional/pathobiological mechanisms are unknown. The objective of this study was to characterize focal and nonfocal patterns of lung CT-based imaging with plasma markers of lung injury. METHODS: A prospective multicenter cohort study involving 119 consecutive patients with ARDS. Plasma biomarkers (soluble form of the receptor for advanced glycation end product [sRAGE], plasminogen activator inhibitor-1, soluble intercellular adhesion molecule-1, and surfactant protein-D) were measured within 24 h of ARDS onset. Lung CT scan was performed within the first 48 h to assess lung morphology. RESULTS: Thirty-two (27%) and 87 (73%) patients had focal and nonfocal ARDS, respectively. Plasma levels of sRAGE were significantly higher in nonfocal ARDS, compared with focal ARDS. A cut-off of 1,188 pg/mL differentiated focal from nonfocal ARDS with a sensitivity of 94% and a specificity of 84%. Nonfocal patterns were associated with higher 28- and 90-day mortality than focal patterns (31% vs 12%, P = .038 and 46% vs 21%, P = .026, respectively). Plasma levels of plasminogen activator inhibitor-1 were significantly higher in nonfocal ARDS. There was no difference in other biomarkers. CONCLUSIONS: Plasma sRAGE is associated with a nonfocal ARDS. Such novel findings may suggest a role for RAGE pathway in an underlying endotype of impaired alveolar fluid clearance and stimulate future research on the association between ARDS phenotypes and therapeutic responses.

Published
2016
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4. Effect of early postextubation high-flow nasal cannula vs conventional oxygen therapy on hypoxaemia in patients after major abdominal surgery: a French multicentre randomised controlled trial (OPERA)

Author

Linda Khoy-Ear, Thomas Godet, Samir Jaber, Gerald Chanques, Jean-Michel Constantin, Sacha Rozencwajg, Jean-Marc Delay, Catherine Paugam-Burtz, Emmanuel Futier, Bruno Pereira, Daniel Verzilli, Jeremie Dupuis, Jean-Etienne Bazin, Génétique, Reproduction et Développement (GReD ), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Hôpital Beaujon, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Laboratoire de Biologie Moléculaire de la Cellule (LBMC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (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)-Sorbonne Université (SU), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), CHU Clermont-Ferrand, 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), Service d'Anésthésie Réanimation [CHU Clermont-Ferrand], CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Génétique, Reproduction et Développement - Clermont Auvergne (GReD ), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA)-Centre National de la Recherche Scientifique (CNRS), Hôpital Beaujon-Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [APHP], Service de réanimation adulte, département d'anesthésie-réanimation, CHU Clermont-Ferrand-Hôtel Dieu, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), and Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN)

Subjects
Male, Time Factors, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Critical Care and Intensive Care Medicine, medicine.disease_cause, law.invention, Perioperative medicine, 0302 clinical medicine, Postoperative Complications, Randomized controlled trial, Interquartile range, law, Oxygen therapy, Abdomen, Clinical endpoint, Medicine, 030212 general & internal medicine, Hospital Mortality, Postoperative Period, Hypoxia, ComputingMilieux_MISCELLANEOUS, education.field_of_study, Postoperative pulmonary complications, Middle Aged, 3. Good health, Intention to Treat Analysis, Anesthesia, Female, France, Nasal cannula, Ventilator Weaning, medicine.medical_specialty, High-risk surgery, Population, 03 medical and health sciences, Postoperative hypoxaemia, Humans, education, Aged, business.industry, Oxygen Inhalation Therapy, Length of Stay, Respiration, Artificial, Surgery, Discontinuation, 030228 respiratory system, Airway Extubation, business, Abdominal surgery
Abstract

High-flow nasal cannula (HFNC) oxygen therapy is attracting increasing interest in acute medicine as an alternative to standard oxygen therapy; however, its use to prevent hypoxaemia after major abdominal surgery has not been evaluated. Our trial was designed to close this evidence gap. A multicentre randomised controlled trial was carried out at three university hospitals in France. Adult patients at moderate to high risk of postoperative pulmonary complications who had undergone major abdominal surgery using lung-protective ventilation were randomly assigned using a computer-generated sequence to receive either HFNC oxygen therapy or standard oxygen therapy (low-flow oxygen delivered via nasal prongs or facemask) directly after extubation. The primary endpoint was absolute risk reduction (ARR) for hypoxaemia at 1 h after extubation and after treatment discontinuation. Secondary outcomes included occurrence of postoperative pulmonary complications within 7 days after surgery, the duration of hospital stay, and in-hospital mortality. The analysis was performed on data from the modified intention-to-treat population. This trial was registered with ClinicalTrials.gov (NCT01887015). Between 6 November 2013 and 1 March 2015, 220 patients were randomly assigned to receive either HFNC (n = 108) or standard oxygen therapy (n = 112); all of these patients completed follow-up. The median duration of the allocated treatment was 16 h (interquartile range 14–18 h) with standard oxygen therapy and 15 h (interquartile range 12–18) with HFNC therapy. Twenty-three (21 %) of the 108 patients treated with HFNC 1 h after extubation and 29 (27 %) of the 108 patients after treatment discontinuation had postextubation hypoxaemia, compared with 27 (24 %) and 34 (30 %) of the 112 patients treated with standard oxygen (ARR 4, 95 % CI –8 to 15 %; p = 0.57; adjusted relative risk [RR] 0.87, 95 % CI 0.53–1.43; p = 0.58). Over the 7-day postoperative follow-up period, there was no statistically significant difference between the groups in the proportion of patients who remained free of any pulmonary complication (ARR 7, 95 % CI –6 to 20 %; p = 0.40). Other secondary outcomes also did not differ significantly between the two groups. Among patients undergoing major abdominal surgery, early preventive application of high-flow nasal cannula oxygen therapy after extubation did not result in improved pulmonary outcomes compared with standard oxygen therapy.

Published
2016
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5. Liver Venous Deprivation or Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy?: A Retrospective Multicentric Study.

Author

Chebaro A, Buc E, Durin T, Chiche L, Brustia R, Didier A, Pruvot FR, Kitano Y, Muscari F, Lecolle K, Sulpice L, Sonmez E, Bougard M, El Amrani M, Sommacale D, Maulat C, Ayav A, Adam R, Laurent C, and Truant S

Subjects
Adult, Aged, Aged, 80 and over, Feasibility Studies, Female, Humans, Ligation methods, Male, Middle Aged, Retrospective Studies, Treatment Outcome, Young Adult, Carcinoma, Hepatocellular therapy, Embolization, Therapeutic methods, Hepatectomy methods, Hepatic Veins surgery, Intention to Treat Analysis methods, Liver Neoplasms therapy, Portal Vein surgery
Abstract

Objective: To compare 2 techniques of remnant liver hypertrophy in candidates for extended hepatectomy: radiological simultaneous portal vein embolization and hepatic vein embolization (HVE); namely LVD, and ALPPS., Background: Recent advances in chemotherapy and surgical techniques have widened indications for extended hepatectomy, before which remnant liver augmentation is mandatory. ALPPS and LVD typically show higher hypertrophy rates than portal vein embolization, but their respective places in patient management remain unclear., Methods: All consecutive ALPPS and LVD procedures performed in 8 French centers between 2011 and 2020 were included. The main endpoint was the successful resection rate (resection rate without 90-day mortality) analyzed according to an intention-to-treat principle. Secondary endpoints were hypertrophy rates, intra and postoperative outcomes., Results: Among 209 patients, 124 had LVD 37 [13,1015] days before surgery, whereas 85 underwent ALPPS with an inter-stages period of 10 [6, 69] days. ALPPS was mostly-performed for colorectal liver metastases (CRLM), LVD for CRLM and perihilar cholangiocarcinoma. Hypertrophy was faster for ALPPS. Successful resection rates were 72.6% for LVD ± rescue ALPPS (n = 6) versus 90.6% for ALPPS (P < 0.001). Operative duration, blood losses and length-of-stay were lower for LVD, whereas 90-day major complications and mortality were comparable. Results were globally unchanged for CRLM patients, or after excluding the early 2 years of experience (learning-curve effect)., Conclusions: This study is the first 1 comparing LVD versus ALPPS in the largest cohort so far. Despite its retrospective design, it yields original results that may serve as the basis for a prospective study., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Published
2021
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6. Early Enteral Versus Total Parenteral Nutrition in Patients Undergoing Pancreaticoduodenectomy: A Randomized Multicenter Controlled Trial (Nutri-DPC).

Author

Perinel J, Mariette C, Dousset B, Sielezneff I, Gainant A, Mabrut JY, Bin-Dorel S, Bechwaty ME, Delaunay D, Bernard L, Sauvanet A, Pocard M, Buc E, and Adham M

Subjects
Aged, Female, Humans, Length of Stay, Male, Middle Aged, Pancreatic Neoplasms complications, Pancreatic Neoplasms pathology, Prospective Studies, Recovery of Function, Treatment Outcome, Enteral Nutrition, Pancreatic Neoplasms surgery, Pancreaticoduodenectomy adverse effects, Parenteral Nutrition, Total, Postoperative Care, Postoperative Complications epidemiology
Abstract

Objectives: The aim of this study was to compare nasojejunal early enteral nutrition (NJEEN) with total parenteral nutrition (TPN), after pancreaticoduodenectomy (PD), in terms of postoperative complications., Background: Current nutritional guidelines recommend the use of enteral over parenteral nutrition in patients undergoing gastrointestinal surgery. However, the NJEEN remains controversial in patients undergoing PD., Methods: Multicenter, randomized, controlled trial was conducted between 2011 and 2014. Nine centers in France analyzed 204 patients undergoing PD to NJEEN (n = 103) or TPN (n = 101). Primary outcome was the rate of postoperative complications according to Clavien-Dindo classification. Successful NJEEN was defined as insertion of a nasojejunal feeding tube, delivering at least 50% of nutritional needs on PoD 5, and no TPN for more than consecutive 48 hours., Results: Postoperative complications occurred in 77.5% [95% confidence interval (95% CI) 68.1-85.1] patients in the NJEEN group versus 64.4% (95% CI 54.2-73.6) in TPN group (P = 0.040). NJEEN was associated with higher frequency of postoperative pancreatic fistula (POPF) (48.1% vs 27.7%, P = 0.012) and higher severity (grade B/C 29.4% vs 13.9%; P = 0.007). There was no significant difference in the incidence of post-pancreatectomy hemorrhage, delayed gastric emptying, infectious complications, the grade of postoperative complications, and the length of postoperative stay. A successful NJEEN was achieved in 63% patients. In TPN group, average energy intake was significantly higher (P < 0.001) and patients had an earlier recovery of oral feeding (P = 0.0009)., Conclusions: In patients undergoing PD, NJEEN was associated with an increased overall postoperative complications rate. The frequency and the severity of POPF were also significantly increased after NJEEN. In terms of safety and feasibility, NJEEN should not be recommended.

Published
2016
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7. [Favourable outcome after fetoscopic laser surgery for twin-twin transfusion syndrome: experience of an emerging centre].

Author

Delabaere A, Accoceberry M, Niro J, Velemir L, Laurichesse-Delmas H, Coste K, Bœuf B, Labbe A, Storme B, Lemery D, and Gallot D

Subjects
Female, Gestational Age, Humans, Infant, Newborn, Pregnancy, Pregnancy Outcome, Retrospective Studies, Survival Rate, Fetofetal Transfusion surgery, Fetoscopy, Laser Therapy methods
Abstract

Objectives: Our objective was to report perinatal outcome during the first three years of an emerging centre for laser photocoagulation in twin-twin transfusion syndrome (TTTS) and to compare with outcome observed earlier in the same centre when management consisted in recurrent amniodrainage., Patients and Methods: We conducted a single centre retrospective study. We compared perinatal outcome of 19 consecutive cases of mid trimester TTTS managed by amniodrainage over a 10-year period with 49 cases of TTTS managed by laser photocoagulation over a 3-year period., Results: Laser photocoagulation increased survival rate at birth (P=0.02) and at postnatal day 28 (P=0.01). Neurologic and cardiologic complications did not differ significantly (P=0.5 and P=0.3 respectively). We observed a significant increase in survival of the donor after laser coagulation at birth (P=0.04)., Discussion and Conclusion: Our study demonstrated better outcome after laser photocoagulation. Early results of an emerging centre appeared comparable to those of more experienced centres., (Copyright © 2011 Elsevier Masson SAS. All rights reserved.)

Published
2011
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8. Peng's binding pancreaticojejunostomy after pancreaticoduodenectomy: a French prospective study.

Author

Buc E, Flamein R, Golffier C, Dubois A, Nagarajan G, Futier E, and Pezet D

Subjects
Adult, Aged, Aged, 80 and over, Female, France, Humans, Male, Middle Aged, Pancreatic Fistula prevention & control, Postoperative Complications prevention & control, Prospective Studies, Treatment Outcome, Pancreatic Diseases surgery, Pancreatic Fistula etiology, Pancreaticoduodenectomy, Pancreaticojejunostomy methods, Postoperative Complications etiology
Abstract

Background: Pancreatic fistula (PF) is the single most important complication after pancreaticoduodenectomy. Recently, a 0% rate of PF was reported using a binding pancreaticojejunostomy with intussusception of the pancreatic stump. The aim of this study was to assess the safety of this new binding pancreaticojejunostomy in condition most susceptible to PF, i.e. soft pancreas and non-dilated main pancreatic duct., Methods: Forty-five consecutive patients with soft pancreas and non-dilated main pancreatic duct underwent a binding pancreaticojejunostomy. Post-operative PF was defined according to the International Study Group of Pancreatic Fistula., Results: Four patients (8.9%) developed a PF. In one case, PF developed on post-operative day 3 due to a technical deficiency. In the three other cases, pancreatic fistula developed after the tenth post-operative day; all the patients had local and/or general co-morbidities before PF occurrence., Conclusions: Binding pancreaticojejunostomy according to Peng is a safe and secure technique that improves the rate of pancreatic fistula, especially in case of soft texture of the pancreas remnant. However, a 0% rate seems to be hard to achieve because other abdominal and general complications are frequent and can lead to secondary leakage of the pancreatic anastomosis.

Published
2010
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9. Effect of lingual nerve block on burning mouth syndrome (stomatodynia): a randomized crossover trial.

Author

Grémeau-Richard C, Dubray C, Aublet-Cuvelier B, Ughetto S, and Woda A

Subjects
Anticonvulsants administration & dosage, Cross-Over Studies, Double-Blind Method, Female, Humans, Male, Treatment Outcome, Burning Mouth Syndrome diagnosis, Burning Mouth Syndrome drug therapy, Clonazepam administration & dosage, Lingual Nerve drug effects, Nerve Block methods, Pain Measurement drug effects
Abstract

Burning mouth syndrome (stomatodynia) is associated with changes of a neuropathic nature the main location of which, peripheral or central, remains unknown. A randomised, double-blind crossover design was used to investigate the effects of lingual nerve block on spontaneous burning pain and a possible correlation with the effects of topical clonazepam, the patient's response to a psychological questionnaire, and the taste and heat thresholds. The spontaneous burning was measured with a visual analogue scale (VAS) just before and 15 min after injection. The decreases in VAS score after lidocaine or saline injection were not significantly different (2.7+/-3.9 and 2.0+/-2.6, respectively; n=20). However, two groups of patients could be identified: in a "peripheral group" (n=10) the VAS decrease due to lingual nerve injection was 4.3+/-3.1cm after lidocaine and 0.9+/-0.3 cm after saline (p=0.02). In a "central group" (n=7), there were an increase in pain intensity score (-0.8+/-2.6 cm) after lidocaine and a decrease (1.5+/-3.0 cm) after saline (p=0.15). An increase in the hospital anxiety and depression (HAD) score and a decreased taste sensitivity and heat pain threshold of painful oral area were seen in patients compared with age-and-sex-matched controls (p<0.05). Topical clonazepam treatment tended to be more effective (p=0.07) and HAD score lower (p<0.03) in the peripheral than in the central group. These results suggest that the neuropathic disorder associated with stomatodynia may be predominantly peripheral, central or mixed depending on the individual. Topical application of clonazepam and HAD may serve as indicators of which mechanism is dominating., (Copyright 2009 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.)

Published
2010
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10. [Which invasive diagnostic procedure should we use for twin pregnancies: chorionic villous sampling or amniocentesis?].

Author

Gallot D, Vélémir L, Delabaere A, Accoceberry M, Niro J, Vendittelli F, Laurichesse-Delmas H, Jacquetin B, and Lémery D

Subjects
Female, Humans, Practice Guidelines as Topic, Pregnancy, Amniocentesis methods, Chorionic Villi Sampling methods, Diseases in Twins diagnosis, Fetal Diseases diagnosis, Pregnancy, Twin
Abstract

Objective: To describe invasive diagnostic procedures (amniocentesis/choriocentesis) and subsequent risks in twin pregnancies., Material and Methods: PubMed and Cochrane database investigations were conducted using following key words: twin gestation, amniocentesis, chorionic villous sampling, karyotype. Guidelines for twin management edicted by different societies were reviewed., Results: Risk of pregnancy loss after invasive diagnostic procedure in twin pregnancies seems to be slightly higher to singletons, i.e about 1.5-2% after mid-trimester amniocentesis and about 2% after first trimester choriocentesis. Dual sampling is not always mandatory but can be performed on parent's request. Specific risks are associated with twins: redundant sampling, permutation or misidentification of affected twin in case of discordant status. Procedures should be performed by highly-skilled operators under permanent ultrasound-guidance. A scheme describing placental locations and funicular insertions appears to be useful for correct identification. If foeticide can be anticipated, diagnostic procedure and foeticide should be performed by the same operators. For amniocentesis, one or two needles can be used except for cases with infectious disease (two needles and two separate insertions required). For choriocentesis, sampling should be performed close to funicular insertions., Conclusion: First-trimester choriocentesis makes earlier diagnosis and earlier foeticide possible compared with mid-trimester amniocentesis. Both techniques require highly-skilled operators to reduce subsequent risks in the context of twin pregnancies., (Copyright © 2009 Elsevier Masson SAS. All rights reserved.)

Published
2009
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11. [Laparoscopy during pregnancy: experience of the French university hospital of Clermont-Ferrand].

Author

Azuar AS, Bouillet-Dejou L, Jardon K, Lenglet Y, Canis M, Bolandard F, Storme B, Bonnin M, Pezet D, Buc E, Lemery D, and Gallot D

Subjects
Adnexal Diseases surgery, Adult, Appendicitis surgery, Female, Gallstones surgery, Humans, Laparoscopy adverse effects, Perinatal Care, Perioperative Care, Pregnancy, Pregnancy Trimester, First, Pregnancy Trimester, Second, Retrospective Studies, Torsion Abnormality surgery, Treatment Outcome, Young Adult, Laparoscopy methods, Pregnancy Complications surgery, Pregnancy Outcome
Abstract

Objective: To describe perioperative management and perinatal outcome for patients undergoing laparoscopy during pregnancy., Patients and Methods: We conducted a retrospective study of all cases of laparoscopy during pregnancy performed in our university hospital over a period of six years (from February 2000 to February 2006)., Results: We observed 34 cases managed from five to 30 weeks of gestation (11 cases of adnexal torsion, ten adnexal masses, eight appendicitis, one cholecystitis, one sigmoid volvulus, one pelvic peritonitis, two heterotopic pregnancies). Open laparoscopy was used in 12 cases. Conversion was required in two cases mainly due to adherences (one borderline lesion at 16 weeks and one tubal cyst torsion at 24 weeks). No maternal complication was observed. One miscarriage occurred at Day 1 (peritonitis, five weeks of gestation) and one patient opted for abortion. No threatened preterm labour occurred after the perioperative course and no neonate required admission in neonatology unit., Discussion and Conclusion: This study illustrates safety and efficacy of laparoscopy in management of surgical diseases in the gravid patient. Emergent indications are the most common, highlighting the need for all physicians to know specific recommendations related to laparoscopy during pregnancy.

Published
2009
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12. [To induce labor or to wait in case of term PROM? Don't be afraid of expectant management!].

Author

Accoceberry M, Gallot D, Velemir L, Sapin V, Laurichesse-Delmas H, Vendittelli F, Coste K, Vanlieferinghen P, Jacquetin B, and Lemery D

Subjects
Adult, Female, Fetal Distress epidemiology, Fever epidemiology, Humans, Infant, Newborn, Labor, Obstetric, Pregnancy, Pregnancy Outcome, Risk Factors, Time Factors, Cesarean Section, Fetal Membranes, Premature Rupture prevention & control, Fetal Membranes, Premature Rupture therapy, Gestational Age, Labor, Induced
Published
2008
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13. Band and port-related morbidity after bariatric surgery: an underestimated problem.

Author

Launay-Savary MV, Slim K, Brugère C, Buc E, Nini E, Forestier D, and Chipponi J

Subjects
Body Mass Index, Equipment Design, Humans, Morbidity, Reoperation, Gastroplasty adverse effects
Abstract

Objective: To evaluate the magnitude of the morbidity related to the system used for gastric banding Methods Between January 1997 and December 2004, 286 consecutive patients underwent laparoscopic gastric banding (LAGB) in one center. We used 4 models of LapBand 9.75, 10, 11 and Vanguard with pars flacida route. Recalibration of band was performed in our consultation unit without systematic radiologic control. We considered four kinds of complication: port displacement, port rupture, band rupture and others problems., Results: The mean follow up was 3.3+/-2.8 years with a median 2.9 years. Complications occurred within a mean time of 2.2+/-1.9 years. For the models vanguard and size 11, there were no rupture and 15 (27.7%) displacements whereas for size 9.75 and 10 there were 39 ruptures (14.7%) and 15 (5.6%) displacements. Types of complications were related to the bands used i.e. more port displacements for the models vanguard and size 11 and more band and port ruptures for the models size 9.75 and 10. But when we considered the respective follow up according to the type of band these differences were no longer significant. Moreover rupture rate was significantly high but decreased after March 2002 because of changing of junction between port and catheter. Mean excess weight loss (35.2+/-27.7%) was not different in group whether the patients were reoperated or not., Conclusion: Band and port related morbidity is an important aspect of bariatric surgery. We have to pay attention to material evolution and to our follow up for calibration. Some new recent technical advancement could improve the management of these patients.

Published
2008
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14. [Peritoneal serous borderline tumors: report of two cases].

Author

Joubert-Zakeyh J, Roaelfils I, Darcha C, and Déchelotte PJ

Subjects
Adult, Carcinoma surgery, Cell Division, Female, Humans, Peritoneal Neoplasms surgery, Carcinoma pathology, Peritoneal Neoplasms pathology
Abstract

Two cases of serous borderline tumors of the peritoneum are reported. These rare tumors may show variable histological features. The lack of peritoneal invasion, which may be difficult to assess, with minimal or no ovarian involvement are major features for the diagnosis. These tumors should be distinguished from other peritoneal neoplasms such as serous carcinomas because of their good prognosis after surgical therapy alone.

Published
2006
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15. Glutathione S-transferase M1 and GST T1 genetic polymorphisms and Raynaud's phenomenon in French vinyl chloride monomer-exposed workers.

Author

Fontana L, Marion MJ, Ughetto S, and Catilina P

Subjects
Aged, Case-Control Studies, France, Genotype, Humans, Male, Middle Aged, Raynaud Disease chemically induced, White People, Genetic Predisposition to Disease, Glutathione Transferase genetics, Occupational Exposure, Polymorphism, Genetic, Raynaud Disease genetics, Vinyl Chloride toxicity
Abstract

Occupational vinyl chloride monomer (VCM) exposure can induce Raynaud's phenomenon (RP). However, not all VCM workers developed RP, which suggests an underlying genetic susceptibility. Genetic polymorphisms of glutathione S-transferases (GSTs), involved in VCM metabolism, have been shown to influence certain VCM-related health effects. We have conducted a case-control study of 58 subjects with RP along with 247 subjects without RP, from a population of 305 French workers exposed or formerly exposed to VCM, to assess any association between GST M1 and GST T1 gene polymorphisms, either separately or in combination, and the presence of RP. None of the GST M1 or GST T1 genotypes were significantly associated with the presence of RP among studied VCM workers. A combination of positive genotypes for both GST M1 and GST T1 was significantly associated with RP presence, compared to the other combinations of genotypes (OR=2.1, 95% CI=1.1-3.8). OR adjusted for age, smoking status, alcohol consumption and history of treated hypertension did not reach significance (OR=2.0, 95% CI=0.9-5.2). None of the GST M1 and GST T1 genotypes seem to contribute separately to the presence of RP, suggesting that they are not, when taken alone, a major determinant of interindividual variability for VCM-induced PR. However, the combination of both positive GST M1 and GST T1 genotypes appears to contribute slightly to susceptibility to RP in VCM-exposed subjects. Nevertheless, our study-the first to examine the role of a genetic component in the occurrence of RP secondary to occupational exposure to a chemical-corroborates the previous considerations that interaction between the genetic constitution and environmental factors is of importance in determining the health-adverse effects of VCM exposure.

Published
2006
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