Publications by authors named "Francis Schneider"

77 Publications

A covariate-constraint method to map brain feature space into lower dimensional manifolds.

Netw Neurosci 2021 1;5(1):252-273. Epub 2021 Mar 1.

Université Grenoble Alpes, CNRS, Inria, Grenoble, France.

Human brain connectome studies aim to both explore healthy brains, and extract and analyze relevant features associated with pathologies of interest. Usually this consists of modeling the brain connectome as a graph and using graph metrics as features. A fine brain description requires graph metrics computation at the node level. Given the relatively reduced number of patients in standard cohorts, such data analysis problems fall in the high-dimension, low-sample-size framework. In this context, our goal is to provide a machine learning technique that exhibits flexibility, gives the investigator an understanding of the features and covariates, allows visualization and exploration, and yields insight into the data and the biological phenomena at stake. The retained approach is dimension reduction in a manifold learning methodology; the originality is that the investigator chooses one (or several) reduced variables. The proposed method is illustrated in two studies. The first one addresses comatose patients; the second one compares young and elderly populations. The method sheds light on the differences between brain connectivity graphs using graph metrics and potential clinical interpretations of these differences.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1162/netn_a_00176DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7935034PMC
March 2021

Factors associated with coinfections in invasive aspergillosis: a retrospective cohort study.

Clin Microbiol Infect 2021 Mar 2. Epub 2021 Mar 2.

Department of Haematology, Institut de Cancérologie de Strasbourg (ICANS), Strasbourg, France; Université de Strasbourg, Inserm UMR-S1113/IRFAC, Strasbourg, France. Electronic address:

Objectives: To describe the coinfections in invasive aspergillosis (IA), to identify factors associated with coinfections, and to evaluate the impact of coinfection on mortality.

Patients And Methods: We conducted a monocentric retrospective study of consecutive putative, probable, or proven IA that occurred between 1997 and 2017. All coinfections, with an onset within 7 days before or after the first sign of aspergillosis, were identified. Factors associated with coinfections and mortality were analysed by multivariable analysis.

Results: Among the 690 patients with IA included in the study, the median age was 57 years (range 7 days to 90 years). A coinfection was diagnosed in 272/690 patients (39.4%, 95%CI 35.8-43.2). The location of this coinfection was pulmonary only in 131/272 patients (48%), bloodstream only in 66/272 patients (24%) and other/multiple sites in 75/272 patients (28%). Coinfections were bacterial (110/272 patients, 40%), viral (58/272, 21%), fungal (57/272, 21%), parasitic (5/272, 2%) or due to multiple types of pathogens (42/272, 15%). Factors associated with a coinfection in adjusted analysis were: allogeneic haematopoietic stem-cell transplantation (OR 2.3 (1.2-4.4)), other haematological malignancies (OR 2.1 (1.2-3.8)), other underlying diseases (OR 4.3 (1.4-13.6)), lymphopenia (OR 1.7 (1.1-2.5)), C-reactive protein >180 mg/L (OR 1.9 (1.2-3.0)), fever (OR 2.4 (1.5-4.1)), tracheal intubation (OR 2.6 (1.5-4.7)), isolation of two or more different Aspergillus species (OR 2.7 (1.1-6.3)), and the presence of non-nodular lesions on chest computed tomography (OR 2.2 (1.3-3.7) and OR 2.2 (1.2-4.0)). Coinfections were independently associated with a higher mortality at week 12 (adjusted HR 1.5 (1.1-1.9), p < 0.01).

Conclusions: Coinfections are frequent in IA patients and are associated with higher mortality.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cmi.2021.02.021DOI Listing
March 2021

Cateslytin abrogates lipopolysaccharide-induced cardiomyocyte injury by reducing inflammation and oxidative stress through toll like receptor 4 interaction.

Int Immunopharmacol 2021 Feb 23;94:107487. Epub 2021 Feb 23.

Laboratory of Cellular and Molecular Cardiovascular Pathophysiology, Department of Biology, E and E.S., University of Calabria, Rende, CS, Italy; National Institute of Cardiovascular Research (INRC), Bologna, Italy. Electronic address:

Global public health is threatened by new pathogens, antimicrobial resistant microorganisms and a rapid decline of conventional antimicrobials efficacy. Thus, numerous medical procedures become life-threating. Sepsis can lead to tissue damage such as myocardium inflammation, associated with reduction of contractility and diastolic dysfunction, which may cause death. In this perspective, growing interest and attention are paid on host defence peptides considered as new potential antimicrobials. In the present study, we investigated the physiological and biochemical properties of Cateslytin (Ctl), an endogenous antimicrobial chromogranin A-derived peptide, in H9c2 cardiomyocytes exposed to lipopolysaccharide (LPS) infection. We showed that both Ctl (L and D) enantiomers, but not their scrambled counterparts, significantly increased cardiomyocytes viability following LPS, even if L-Ctl was effective at lower concentration (1 nM) compared to D-Ctl (10 nM). L-Ctl mitigated LPS-induced LDH release and oxidative stress, as visible by a reduction of MDA and protein carbonyl groups content, and by an increase of SOD activity. Molecular docking simulations strongly suggested that L-Ctl modulates TLR4 through a direct binding to the partner protein MD-2. Molecular analyses indicated that the protection mediated by L-Ctl against LPS-evoked sepsis targeted the TLR4/ERK/JNK/p38-MAPK pathway, regulating NFkB p65, NFkB p52 and COX2 expression and repressing the mRNA expression levels of the LPS-induced proinflammatory factors IL-1β, IL-6, TNF-α and NOS2. These findings indicate that Ctl could be considered as a possible candidate for the development of new antimicrobials strategies in the treatment of myocarditis. Interestingly, L-enantiomeric Ctl showed remarkable properties in strengthening the anti-inflammatory and anti-oxidant effects on cardiomyocytes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.intimp.2021.107487DOI Listing
February 2021

Acute-onset delirium in intensive care COVID patients: association of imperfect brain repair with foodborne micro-pollutants.

Eur J Neurol 2021 Feb 14. Epub 2021 Feb 14.

Plant Imaging and Mass Spectrometry, Institut de biologie moléculaire des plantes, CNRS, Strasbourg, France.

Background And Purpose: COVID-19 affects the brain in various ways, amongst which delirium is worrying. An assessment was made of whether a specific, long-lasting, COVID-19-related brain injury develops in acute respiratory distress syndrome patients after life-saving re-oxygenation.

Methods: Ten COVID+ patients (COVID+) with unusual delirium associated with neuroimaging suggestive of diffuse brain injury and seven controls with non-COVID encephalopathy were studied. The assessment took place when the intractable delirium started at weaning off ventilation support. Brain magnetic resonance imaging (MRI) was performed followed by standard cerebrospinal fluid (CSF) analyses and assessment of CSF erythropoietin concentrations (as a marker for the assessment of tissue repair), and of non-targeted CSF metabolomics using liquid chromatography high resolution mass spectrometry.

Results: Patients were similar as regards severity scores, but COVID+ were hospitalized longer (25 [11.75; 25] vs. 9 [4.5; 12.5] days, p = 0.03). On admission, but not at MRI and lumbar puncture performance, COVID+ were more hypoxic (p = 0.002). On MRI, there were leptomeningeal enhancement and diffuse white matter haemorrhages only in COVID+. In the latter, CSF erythropoietin concentration was lower (1.73 [1.6; 2.06] vs. 3.04 [2.9; 3.91] mIU/ml, p = 0.01), and CSF metabolomics indicated (a) increased compounds such as foodborne molecules (sesquiterpenes), molecules from industrialized beverages and micro-pollutants (diethanolamine); and (b) decreased molecules such as incomplete breakdown products of protein catabolism and foodborne molecules (glabridin). At 3-month discharge, fatigue, anxiety and depression as well as MRI lesions persisted in COVID+.

Conclusions: Some COVID+ are at risk of a specific delirium. Imperfect brain repair after re-oxygenation and lifestyle factors might influence long-lasting brain injuries in a context of foodborne micro-pollutants.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/ene.14776DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8014494PMC
February 2021

Impact of intravenous lidocaine on clinical outcomes of patients with ARDS during COVID-19 pandemia (LidoCovid): A structured summary of a study protocol for a randomised controlled trial.

Trials 2021 Feb 11;22(1):131. Epub 2021 Feb 11.

Hôpital de Hautepierre, Service d'Anesthésie-Réanimation et Médecine Péri-Opératoire, Hôpitaux Universitaires de Strasbourg, Strasbourg, France.

Objectives: The main objective of this study is to evaluate the effect of intravenous lidocaine on gas exchange and inflammation in acute respiratory distress syndrome due or not to Covid-19 pneumonia.

Trial Design: This is a prospective monocentric, randomized, quadruple-blinded and placebo-controlled superiority trial. This phase 3 clinical study is based on two parallel groups received either intravenous lidocaine 2% or intravenous NaCl 0.9%.

Participants: This study has been conducted at the University Hospitals of Strasbourg (medical and surgical Intensive Care Units in Hautepierre Hospital) since the 4th November 2020. The participants are 18 years-old and older, hospitalized in ICU for a moderate to severe ARDS according to the Berlin definition; they have to be intubated and sedated for mechanical protective ventilation. All participants are affiliated to the French Social security system and a dosage of beta HCG has to be negative for women of child bearing age . For the Covid-19 subgroup, the SARS-CoV2 infection is proved by RT-PCR <7 days before admission and/or another approved diagnostic technique and/or typical CT appearance pneumonia. The data are prospectively collected in e-Case Report Forms and extracted from clinical files.

Intervention And Comparator: The participants are randomised in two parallel groups with a 1:1 ratio. In the experimental group, patients receive intravenous lidocaine 2% (20mg/mL) (from FRESENIUS KABI France); the infusion protocol provide a bolus of 1 mg/kg (ideal weight), followed by 3 mg/kg/h for the first hour, 1.5 mg/kg/h for the second hour, 0.72 mg/kg/h for the next 22 hours and then 0.6 mg/kg/h for 14 days at most or 24 hours after extubation or ventilator-weaning. The patients in the control group receive intravenous NaCl 0.9% (9 mg/mL) (from Aguettant, France) as placebo comparator; the infusion protocol provide a bolus of 0.05 mL/kg (ideal weight), followed by 0.15 mL/kg/h for the first hour, 0.075 mL/kg/h for the second hour, 0.036 mL/kg/h for the next 22 hours, and the 0.03 mL/kg/h for up to 14 days or 24 hours after extubation or ventilator-weaning. Lidocaine level is assessed at H4, D2, D7 and D14 to prevent local anesthetics systemic toxicity. Clinical data and biological samples are collected to assess disease progression.

Main Outcomes: The primary outcome is the evolution of alveolar-capillary gas exchange measured by the PaO2/FiO2 ratio after two days of treatment. The secondary endpoints of the study include the following: Evolution of PaO2/FiO2 ratio at admission and after 21 days of treatment Number of ventilator-free days Anti-inflammatory effects by dosing inflammatory markers at different timepoints (ferritin, bicarbonate, CRP, PCT, LDH, IL-6, Troponin HS, triglycerides, complete blood count, lymphocytes) Anti-thrombotic effects by dosing platelets, aPTT, fibrinogen, D-dimers, viscoelastic testing and identification of all thromboembolic events up to 4 weeks. Plasmatic concentration of lidocaine and albumin Incidence of adverse events like cardiac rhythm disorders, need of vasopressors, any modification of the QRS, QTc or PR intervals every day Ileus recovery time Consumption of hypnotics, opioids, neuromuscular blockers. Lengths of stay in the ICU, incidence of reintubation and complications due to intensive care unit care (mortality until 90 days, pneumothorax, bacterial pneumopathy, bronchospasm, cardiogenic shock, acute renal failure, need of renal dialysis, delirium, atrial fibrillation, stroke (CAM-ICU score), tetraplegia (MCR score)). Incidence of cough and sore throat at extubation or ventilator-weaning and within 24 hours. All these outcomes will be evaluated according to positivity to Sars-Cov-2.

Randomisation: The participants who meet the inclusion criteria and have signed written informed consent will be randomly allocated using a computer-generated random number to either intervention group or control group. The distribution ratio of the two groups will be 1:1, with a stratification according to positivity to Sars-Cov-2.

Blinding (masking): All participants, care providers, investigator and outcomes assessor are blinded.

Numbers To Be Randomised (sample Size): We planned to randomize fifty participants in each group, 100 participants total.

Trial Status: The amended protocol version 2.1 was approved by the Ethics Committee "Comité de Protection des Personnes Sud-Méditerranée II on January 8, 2021 and by the Commission Nationale de l'Informatique et des Libertés (CNIL) on November 10, 2020. The study is currently recruiting participants; the recruitment started in November 2020 and the planned recruitment period is three years.

Trial Registration: The trial was registered on clinicaltrials.gov on October 30, 2020 and identified by number NCT04609865 .

Full Protocol: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13063-021-05095-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7876973PMC
February 2021

Cerebrospinal Fluid Features in Patients With Coronavirus Disease 2019 and Neurological Manifestations: Correlation with Brain Magnetic Resonance Imaging Findings in 58 Patients.

J Infect Dis 2021 02;223(4):600-609

Service d'Imagerie, Hôpitaux Universitaires de Strasbourg, Strasbourg, France.

Background: Neurological manifestations are common in patients with coronavirus disease 2019 (COVID-19), but little is known about pathophysiological mechanisms. In this single-center study, we examined neurological manifestations in 58 patients, including cerebrospinal fluid (CSF) analysis and neuroimaging findings.

Methods: The study included 58 patients with COVID-19 and neurological manifestations in whom severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reverse-transcription polymerase chain reaction screening and on CSF analysis were performed. Clinical, laboratory, and brain magnetic resonance (MR) imaging data were retrospectively collected and analyzed.

Results: Patients were mostly men (66%), with a median age of 62 years. Encephalopathy was frequent (81%), followed by pyramidal dysfunction (16%), seizures (10%), and headaches (5%). CSF protein and albumin levels were increased in 38% and 23%, respectively. A total of 40% of patients displayed an elevated albumin quotient, suggesting impaired blood-brain barrier integrity. CSF-specific immunoglobulin G oligoclonal band was found in 5 patients (11%), suggesting an intrathecal synthesis of immunoglobulin G, and 26 patients (55%) presented identical oligoclonal bands in serum and CSF. Four patients (7%) had a positive CSF SARS-CoV-2 reverse-transcription polymerase chain reaction. Leptomeningeal enhancement was present on brain MR images in 20 patients (38%).

Conclusions: Brain MR imaging abnormalities, especially leptomeningeal enhancement, and increased inflammatory markers in CSF are frequent in patients with neurological manifestations related to COVID-19, whereas SARS-CoV-2 detection in CSF remained scanty.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/infdis/jiaa745DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7798956PMC
February 2021

Critical illness-associated cerebral microbleeds for patients with severe COVID-19: etiologic hypotheses.

J Neurol 2020 Nov 21. Epub 2020 Nov 21.

Hôpitaux Universitaires de Strasbourg, Service d'imagerie 2, Hôpital de Hautepierre, 1 avenue Molière, 67200, Strasbourg, France.

Background And Purpose: During the COVID-19 outbreak, the presence of extensive white matter microhemorrhages was detected by brain MRIs. The goal of this study was to investigate the origin of this atypical hemorrhagic complication.

Methods: Between March 17 and May 18, 2020, 80 patients with severe COVID-19 infections were admitted for acute respiratory distress syndrome to intensive care units at the University Hospitals of Strasbourg for whom a brain MRI for neurologic manifestations was performed. 19 patients (24%) with diffuse microhemorrhages were compared to 18 control patients with COVID-19 and normal brain MRI.

Results: The first hypothesis was hypoxemia. The latter seemed very likely since respiratory failure was longer and more pronounced in patients with microhemorrhages (prolonged endotracheal intubation (p = 0.0002), higher FiO (p = 0.03), increased use of extracorporeal membrane oxygenation (p = 0.04)). A relevant hypothesis, the role of microangiopathy, was also considered, since patients with microhemorrhages presented a higher increase of the D-Dimers (p = 0.01) and a tendency to more frequent thrombotic events (p = 0.12). Another hypothesis tested was the role of kidney failure, which was more severe in the group with diffuse microhemorrhages (higher creatinine level [median of 293 µmol/L versus 112 µmol/L, p = 0.04] and more dialysis were introduced in this group during ICU stay [12 versus 5 patients, p = 0.04]).

Conclusions: Blood-brain barrier dysfunction secondary to hypoxemia and high concentration of uremic toxins seems to be the main mechanism leading to critical illness-associated cerebral microbleeds, and this complication remains to be frequently described in severe COVID-19 patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00415-020-10313-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7679237PMC
November 2020

A novel, automated, quantification of abnormal lung parenchyma in patients with COVID-19 infection: Initial description of feasibility and association with clinical outcome.

Anaesth Crit Care Pain Med 2021 Feb 13;40(1):100780. Epub 2020 Nov 13.

Department of Anesthesiology and Intensive Care, Hautepierre Hospital, Strasbourg University Hospital, France; Institut Hospitalo-Universitaire "Image-Guided Surgery", Strasbourg University Hospital, Strasbourg, France; Equipe d'Accueil 3072, Medical School, Strasbourg University, Strasbourg, France.

Objective: Ground-glass opacities are the most frequent radiologic features of COVID-19 patients. We aimed to determine the feasibility of automated lung volume measurements, including ground-glass volumes, on the CT of suspected COVID-19 patients. Our goal was to create an automated and quantitative measure of ground-glass opacities from lung CT images that could be used clinically for diagnosis, triage and research.

Design: Single centre, retrospective, observational study.

Measurements: Demographic data, respiratory support treatment (synthetised in the maximal respiratory severity score) and CT-images were collected. Volume of abnormal lung parenchyma was measured with conventional semi-automatic software and with a novel automated algorithm based on voxels X-Ray attenuation. We looked for the relationship between the automated and semi-automated evaluations. The association between the ground-glass opacities volume and the maximal respiratory severity score was assessed.

Main Results: Thirty-seven patients were included in the main outcome analysis. The mean duration of automated and semi-automated volume measurement process were 15 (2) and 93 (41) min, respectively (p=8.05*10). The intraclass correlation coefficient between the semi-automated and automated measurement of ground-glass opacities and restricted normally aerated lung were both superior to 0.99. The association between the automated measured lung volume and the maximal clinical severity score was statistically significant for the restricted normally aerated (p=0.0097, effect-size: -385mL) volumes and for the ratio of ground-glass opacities/restricted normally aerated volumes (p=0.027, effect-size: 3.3).

Conclusion: The feasibility and preliminary validity of automated impaired lung volume measurements in a high-density COVID-19 cluster was confirmed by our results.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.accpm.2020.10.014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7664353PMC
February 2021

Evaluation of the performance of SARS-CoV-2 serological tools and their positioning in COVID-19 diagnostic strategies.

Diagn Microbiol Infect Dis 2020 Dec 21;98(4):115181. Epub 2020 Aug 21.

Laboratoire de Virologie, Hôpitaux Universitaires de Strasbourg, Strasbourg, France; INSERM, UMR_S1109, LabEx TRANSPLANTEX, Centre de Recherche d'Immunologie et d'Hématologie, Faculté de Médecine, Fédération Hospitalo-Universitaire (FHU) OMICARE, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg, Strasbourg, France. Electronic address:

Rapid and accurate diagnosis is crucial for successful outbreak containment. During the current coronavirus disease 2019 (COVID-19) public health emergency, the gold standard for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection diagnosis is the detection of viral RNA. Additional diagnostic methods õenabling the detection of current or past SARS-CoV-2 infection would be highly beneficial. We assessed 2 immunochromatographic lateral flow assays (LFA-1, LFA-2) and 2 enzyme-linked immunosorbent assay kits (IgA/IgG ELISA-1, IgM/IgG ELISA-2) using 325 samples: serum samples from polymerase chain reaction-confirmed COVID-19 hospitalized patients (n = 55) and healthcare workers (n = 143) and 127 samples from negative controls. Diagnostic performances were assessed according to days after symptom onset (dso) and the antigenic format used by manufacturers. Clinical sensitivities varied greatly among the assays, showing poor mutual agreement. After 15 dso, ELISA-1 (Euroimmun) and LFA-1 (Biosynex) combining IgM and IgG detection showed the best performances. A thorough selection of serological assays for the detection of ongoing or past infections is advisable.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.diagmicrobio.2020.115181DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7441068PMC
December 2020

Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial.

Authors:
Derek C Angus Lennie Derde Farah Al-Beidh Djillali Annane Yaseen Arabi Abigail Beane Wilma van Bentum-Puijk Lindsay Berry Zahra Bhimani Marc Bonten Charlotte Bradbury Frank Brunkhorst Meredith Buxton Adrian Buzgau Allen C Cheng Menno de Jong Michelle Detry Lise Estcourt Mark Fitzgerald Herman Goossens Cameron Green Rashan Haniffa Alisa M Higgins Christopher Horvat Sebastiaan J Hullegie Peter Kruger Francois Lamontagne Patrick R Lawler Kelsey Linstrum Edward Litton Elizabeth Lorenzi John Marshall Daniel McAuley Anna McGlothin Shay McGuinness Bryan McVerry Stephanie Montgomery Paul Mouncey Srinivas Murthy Alistair Nichol Rachael Parke Jane Parker Kathryn Rowan Ashish Sanil Marlene Santos Christina Saunders Christopher Seymour Anne Turner Frank van de Veerdonk Balasubramanian Venkatesh Ryan Zarychanski Scott Berry Roger J Lewis Colin McArthur Steven A Webb Anthony C Gordon Farah Al-Beidh Derek Angus Djillali Annane Yaseen Arabi Wilma van Bentum-Puijk Scott Berry Abigail Beane Zahra Bhimani Marc Bonten Charlotte Bradbury Frank Brunkhorst Meredith Buxton Allen Cheng Menno De Jong Lennie Derde Lise Estcourt Herman Goossens Anthony Gordon Cameron Green Rashan Haniffa Francois Lamontagne Patrick Lawler Edward Litton John Marshall Colin McArthur Daniel McAuley Shay McGuinness Bryan McVerry Stephanie Montgomery Paul Mouncey Srinivas Murthy Alistair Nichol Rachael Parke Kathryn Rowan Christopher Seymour Anne Turner Frank van de Veerdonk Steve Webb Ryan Zarychanski Lewis Campbell Andrew Forbes David Gattas Stephane Heritier Lisa Higgins Peter Kruger Sandra Peake Jeffrey Presneill Ian Seppelt Tony Trapani Paul Young Sean Bagshaw Nick Daneman Niall Ferguson Cheryl Misak Marlene Santos Sebastiaan Hullegie Mathias Pletz Gernot Rohde Kathy Rowan Brian Alexander Kim Basile Timothy Girard Christopher Horvat David Huang Kelsey Linstrum Jennifer Vates Richard Beasley Robert Fowler Steve McGloughlin Susan Morpeth David Paterson Bala Venkatesh Tim Uyeki Kenneth Baillie Eamon Duffy Rob Fowler Thomas Hills Katrina Orr Asad Patanwala Steve Tong Mihai Netea Shilesh Bihari Marc Carrier Dean Fergusson Ewan Goligher Ghady Haidar Beverley Hunt Anand Kumar Mike Laffan Patrick Lawless Sylvain Lother Peter McCallum Saskia Middeldopr Zoe McQuilten Matthew Neal John Pasi Roger Schutgens Simon Stanworth Alexis Turgeon Alexandra Weissman Neill Adhikari Matthew Anstey Emily Brant Angelique de Man Francois Lamonagne Marie-Helene Masse Andrew Udy Donald Arnold Phillipe Begin Richard Charlewood Michael Chasse Mark Coyne Jamie Cooper James Daly Iain Gosbell Heli Harvala-Simmonds Tom Hills Sheila MacLennan David Menon John McDyer Nicole Pridee David Roberts Manu Shankar-Hari Helen Thomas Alan Tinmouth Darrell Triulzi Tim Walsh Erica Wood Carolyn Calfee Cecilia O’Kane Murali Shyamsundar Pratik Sinha Taylor Thompson Ian Young Shailesh Bihari Carol Hodgson John Laffey Danny McAuley Neil Orford Ary Neto Michelle Detry Mark Fitzgerald Roger Lewis Anna McGlothlin Ashish Sanil Christina Saunders Lindsay Berry Elizabeth Lorenzi Eliza Miller Vanessa Singh Claire Zammit Wilma van Bentum Puijk Wietske Bouwman Yara Mangindaan Lorraine Parker Svenja Peters Ilse Rietveld Kik Raymakers Radhika Ganpat Nicole Brillinger Rene Markgraf Kate Ainscough Kathy Brickell Aisha Anjum Janis-Best Lane Alvin Richards-Belle Michelle Saull Daisy Wiley Julian Bion Jason Connor Simon Gates Victoria Manax Tom van der Poll John Reynolds Marloes van Beurden Evelien Effelaar Joost Schotsman Craig Boyd Cain Harland Audrey Shearer Jess Wren Giles Clermont William Garrard Kyle Kalchthaler Andrew King Daniel Ricketts Salim Malakoutis Oscar Marroquin Edvin Music Kevin Quinn Heidi Cate Karen Pearson Joanne Collins Jane Hanson Penny Williams Shane Jackson Adeeba Asghar Sarah Dyas Mihaela Sutu Sheenagh Murphy Dawn Williamson Nhlanhla Mguni Alison Potter David Porter Jayne Goodwin Clare Rook Susie Harrison Hannah Williams Hilary Campbell Kaatje Lomme James Williamson Jonathan Sheffield Willian van’t Hoff Phobe McCracken Meredith Young Jasmin Board Emma Mart Cameron Knott Julie Smith Catherine Boschert Julia Affleck Mahesh Ramanan Ramsy D’Souza Kelsey Pateman Arif Shakih Winston Cheung Mark Kol Helen Wong Asim Shah Atul Wagh Joanne Simpson Graeme Duke Peter Chan Brittney Cartner Stephanie Hunter Russell Laver Tapaswi Shrestha Adrian Regli Annamaria Pellicano James McCullough Mandy Tallott Nikhil Kumar Rakshit Panwar Gail Brinkerhoff Cassandra Koppen Federica Cazzola Matthew Brain Sarah Mineall Roy Fischer Vishwanath Biradar Natalie Soar Hayden White Kristen Estensen Lynette Morrison Joanne Smith Melanie Cooper Monash Health Yahya Shehabi Wisam Al-Bassam Amanda Hulley Christina Whitehead Julie Lowrey Rebecca Gresha James Walsham Jason Meyer Meg Harward Ellen Venz Patricia Williams Catherine Kurenda Kirsy Smith Margaret Smith Rebecca Garcia Deborah Barge Deborah Byrne Kathleen Byrne Alana Driscoll Louise Fortune Pierre Janin Elizabeth Yarad Naomi Hammond Frances Bass Angela Ashelford Sharon Waterson Steve Wedd Robert McNamara Heidi Buhr Jennifer Coles Sacha Schweikert Bradley Wibrow Rashmi Rauniyar Erina Myers Ed Fysh Ashlish Dawda Bhaumik Mevavala Ed Litton Janet Ferrier Priya Nair Hergen Buscher Claire Reynolds John Santamaria Leanne Barbazza Jennifer Homes Roger Smith Lauren Murray Jane Brailsford Loretta Forbes Teena Maguire Vasanth Mariappa Judith Smith Scott Simpson Matthew Maiden Allsion Bone Michelle Horton Tania Salerno Martin Sterba Wenli Geng Pieter Depuydt Jan De Waele Liesbet De Bus Jan Fierens Stephanie Bracke Brenda Reeve William Dechert Michaël Chassé François Martin Carrier Dounia Boumahni Fatna Benettaib Ali Ghamraoui David Bellemare Ève Cloutier Charles Francoeur François Lamontagne Frédérick D’Aragon Elaine Carbonneau Julie Leblond Gloria Vazquez-Grande Nicole Marten Maggie Wilson Martin Albert Karim Serri Alexandros Cavayas Mathilde Duplaix Virginie Williams Bram Rochwerg Tim Karachi Simon Oczkowski John Centofanti Tina Millen Erick Duan Jennifer Tsang Lisa Patterson Shane English Irene Watpool Rebecca Porteous Sydney Miezitis Lauralyn McIntyre Laurent Brochard Karen Burns Gyan Sandhu Imrana Khalid Alexandra Binnie Elizabeth Powell Alexandra McMillan Tracy Luk Noah Aref Zdravko Andric Sabina Cviljevic Renata Đimoti Marija Zapalac Gordan Mirković Bruno Baršić Marko Kutleša Viktor Kotarski Ana Vujaklija Brajković Jakša Babel Helena Sever Lidija Dragija Ira Kušan Suvi Vaara Leena Pettilä Jonna Heinonen Anne Kuitunen Sari Karlsson Annukka Vahtera Heikki Kiiski Sanna Ristimäki Amine Azaiz Cyril Charron Mathieu Godement Guillaume Geri Antoine Vieillard-Baron Franck Pourcine Mehran Monchi David Luis Romain Mercier Anne Sagnier Nathalie Verrier Cecile Caplin Shidasp Siami Christelle Aparicio Sarah Vautier Asma Jeblaoui Muriel Fartoukh Laura Courtin Vincent Labbe Cécile Leparco Grégoire Muller Mai-Anh Nay Toufik Kamel Dalila Benzekri Sophie Jacquier Emmanuelle Mercier Delphine Chartier Charlotte Salmon PierreFrançois Dequin Francis Schneider Guillaume Morel Sylvie L’Hotellier Julio Badie Fernando Daniel Berdaguer Sylvain Malfroy Chaouki Mezher Charlotte Bourgoin Bruno Megarbane Sebastian Voicu Nicolas Deye Isabelle Malissin Laetitia Sutterlin Christophe Guitton Cédric Darreau Mickaël Landais Nicolas Chudeau Alain Robert Pierre Moine Nicholas Heming Virginie Maxime Isabelle Bossard Tiphaine Barbarin Nicholier Gwenhael Colin Vanessa Zinzoni Natacham Maquigneau André Finn Gabriele Kreß Uwe Hoff Carl Friedrich Hinrichs Jens Nee Mathias Pletz Stefan Hagel Juliane Ankert Steffi Kolanos Frank Bloos Sirak Petros Bastian Pasieka Kevin Kunz Peter Appelt Bianka Schütze Stefan Kluge Axel Nierhaus Dominik Jarczak Kevin Roedl Dirk Weismann Anna Frey Vivantes Klinikum Neukölln Lorenz Reill Michael Distler Astrid Maselli János Bélteczki István Magyar Ágnes Fazekas Sándor Kovács Viktória Szőke Gábor Szigligeti János Leszkoven Daniel Collins Patrick Breen Stephen Frohlich Ruth Whelan Bairbre McNicholas Michael Scully Siobhan Casey Maeve Kernan Peter Doran Michael O’Dywer Michelle Smyth Leanne Hayes Oscar Hoiting Marco Peters Els Rengers Mirjam Evers Anton Prinssen Jeroen Bosch Ziekenhuis Koen Simons Wim Rozendaal F Polderman P de Jager M Moviat A Paling A Salet Emma Rademaker Anna Linda Peters E de Jonge J Wigbers E Guilder M Butler Keri-Anne Cowdrey Lynette Newby Yan Chen Catherine Simmonds Rachael McConnochie Jay Ritzema Carter Seton Henderson Kym Van Der Heyden Jan Mehrtens Tony Williams Alex Kazemi Rima Song Vivian Lai Dinu Girijadevi Robert Everitt Robert Russell Danielle Hacking Ulrike Buehner Erin Williams Troy Browne Kate Grimwade Jennifer Goodson Owen Keet Owen Callender Robert Martynoga Kara Trask Amelia Butler Livia Schischka Chelsea Young Eden Lesona Shaanti Olatunji Yvonne Robertson Nuno José Teodoro Amaro dos Santos Catorze Tiago Nuno Alfaro de Lima Pereira Lucilia Maria Neves Pessoa Ricardo Manuel Castro Ferreira Joana Margarida Pereira Sousa Bastos Simin Aysel Florescu Delia Stanciu Miahela Florentina Zaharia Alma Gabriela Kosa Daniel Codreanu Yaseen Marabi Eman Al Qasim Mohamned Moneer Hagazy Lolowa Al Swaidan Hatim Arishi Rosana Muñoz-Bermúdez Judith Marin-Corral Anna Salazar Degracia Francisco Parrilla Gómez Maria Isabel Mateo López Jorge Rodriguez Fernandez Sheila Cárcel Fernández Rosario Carmona Flores Rafael León López Carmen de la Fuente Martos Angela Allan Petra Polgarova Neda Farahi Stephen McWilliam Daniel Hawcutt Laura Rad Laura O’Malley Jennifer Whitbread Olivia Kelsall Laura Wild Jessica Thrush Hannah Wood Karen Austin Adrian Donnelly Martin Kelly Sinéad O’Kane Declan McClintock Majella Warnock Paul Johnston Linda Jude Gallagher Clare Mc Goldrick Moyra Mc Master Anna Strzelecka Rajeev Jha Michael Kalogirou Christine Ellis Vinodh Krishnamurthy Vashish Deelchand Jon Silversides Peter McGuigan Kathryn Ward Aisling O’Neill Stephanie Finn Barbara Phillips Dee Mullan Laura Oritz-Ruiz de Gordoa Matthew Thomas Katie Sweet Lisa Grimmer Rebekah Johnson Jez Pinnell Matt Robinson Lisa Gledhill Tracy Wood Matt Morgan Jade Cole Helen Hill Michelle Davies David Antcliffe Maie Templeton Roceld Rojo Phoebe Coghlan Joanna Smee Euan Mackay Jon Cort Amanda Whileman Thomas Spencer Nick Spittle Vidya Kasipandian Amit Patel Suzanne Allibone Roman Mary Genetu Mohamed Ramali Alison Ghosh Peter Bamford Emily London Kathryn Cawley Maria Faulkner Helen Jeffrey Tim Smith Chris Brewer Jane Gregory James Limb Amanda Cowton Julie O’Brien Nikitas Nikitas Colin Wells Liana Lankester Mark Pulletz Patricia Williams Jenny Birch Sophie Wiseman Sarah Horton Ana Alegria Salah Turki Tarek Elsefi Nikki Crisp Louise Allen Iain McCullagh Philip Robinson Carole Hays Maite Babio-Galan Hannah Stevenson Divya Khare Meredith Pinder Selvin Selvamoni Amitha Gopinath Richard Pugh Daniel Menzies Callum Mackay Elizabeth Allan Gwyneth Davies Kathryn Puxty Claire McCue Susanne Cathcart Naomi Hickey Jane Ireland Hakeem Yusuff Graziella Isgro Chris Brightling Michelle Bourne Michelle Craner Malcolm Watters Rachel Prout Louisa Davies Suzannah Pegler Lynsey Kyeremeh Gill Arbane Karen Wilson Linda Gomm Federica Francia Stephen Brett Sonia Sousa Arias Rebecca Elin Hall Joanna Budd Charlotte Small Janine Birch Emma Collins Jeremy Henning Stephen Bonner Keith Hugill Emanuel Cirstea Dean Wilkinson Michal Karlikowski Helen Sutherland Elva Wilhelmsen Jane Woods Julie North Dhinesh Sundaran Laszlo Hollos Susan Coburn Joanne Walsh Margaret Turns Phil Hopkins John Smith Harriet Noble Maria Theresa Depante Emma Clarey Shondipon Laha Mark Verlander Alexandra Williams Abby Huckle Andrew Hall Jill Cooke Caroline Gardiner-Hill Carolyn Maloney Hafiz Qureshi Neil Flint Sarah Nicholson Sara Southin Andrew Nicholson Barbara Borgatta Ian Turner-Bone Amie Reddy Laura Wilding Loku Chamara Warnapura Ronan Agno Sathianathan David Golden Ciaran Hart Jo Jones Jonathan Bannard-Smith Joanne Henry Katie Birchall Fiona Pomeroy Rachael Quayle Arystarch Makowski Beata Misztal Iram Ahmed Thyra KyereDiabour Kevin Naiker Richard Stewart Esther Mwaura Louise Mew Lynn Wren Felicity Willams Richard Innes Patricia Doble Joanne Hutter Charmaine Shovelton Benjamin Plumb Tamas Szakmany Vincent Hamlyn Nancy Hawkins Sarah Lewis Amanda Dell Shameer Gopal Saibal Ganguly Andrew Smallwood Nichola Harris Stella Metherell Juan Martin Lazaro Tabitha Newman Simon Fletcher Jurgens Nortje Deirdre Fottrell-Gould Georgina Randell Mohsin Zaman Einas Elmahi Andrea Jones Kathryn Hall Gary Mills Kim Ryalls Helen Bowler Jas Sall Richard Bourne Zoe Borrill Tracey Duncan Thomas Lamb Joanne Shaw Claire Fox Jeronimo Moreno Cuesta Kugan Xavier Dharam Purohit Munzir Elhassan Dhanalakshmi Bakthavatsalam Matthew Rowland Paula Hutton Archana Bashyal Neil Davidson Clare Hird Manish Chhablani Gunjan Phalod Amy Kirkby Simon Archer Kimberley Netherton Henrik Reschreiter Julie Camsooksai Sarah Patch Sarah Jenkins David Pogson Steve Rose Zoe Daly Lutece Brimfield Helen Claridge Dhruv Parekh Colin Bergin Michelle Bates Joanne Dasgin Christopher McGhee Malcolm Sim Sophie Kennedy Hay Steven Henderson Mandeep-Kaur Phull Abbas Zaidi Tatiana Pogreban Lace Paulyn Rosaroso Daniel Harvey Benjamin Lowe Megan Meredith Lucy Ryan Anil Hormis Rachel Walker Dawn Collier Sarah Kimpton Susan Oakley Kevin Rooney Natalie Rodden Emma Hughes Nicola Thomson Deborah McGlynn Andrew Walden Nicola Jacques Holly Coles Emma Tilney Emma Vowell Martin Schuster-Bruce Sally Pitts Rebecca Miln Laura Purandare Luke Vamplew Michael Spivey Sarah Bean Karen Burt Lorraine Moore Christopher Day Charly Gibson Elizabeth Gordon Letizia Zitter Samantha Keenan Evelyn Baker Shiney Cherian Sean Cutler Anna Roynon-Reed Kate Harrington Ajay Raithatha Kris Bauchmuller Norfaizan Ahmad Irina Grecu Dawn Trodd Jane Martin Caroline Wrey Brown Ana-Marie Arias Thomas Craven David Hope Jo Singleton Sarah Clark Nicola Rae Ingeborg Welters David Oliver Hamilton Karen Williams Victoria Waugh David Shaw Zudin Puthucheary Timothy Martin Filipa Santos Ruzena Uddin Alastair Somerville Kate Colette Tatham Shaman Jhanji Ethel Black Arnold Dela Rosa Ryan Howle Redmond Tully Andrew Drummond Joy Dearden Jennifer Philbin Sheila Munt Alain Vuylsteke Charles Chan Saji Victor Ramprasad Matsa Minerva Gellamucho Ben Creagh-Brown Joe Tooley Laura Montague Fiona De Beaux Laetitia Bullman Ian Kersiake Carrie Demetriou Sarah Mitchard Lidia Ramos Katie White Phil Donnison Maggie Johns Ruth Casey Lehentha Mattocks Sarah Salisbury Paul Dark Andrew Claxton Danielle McLachlan Kathryn Slevin Stephanie Lee Jonathan Hulme Sibet Joseph Fiona Kinney Ho Jan Senya Aneta Oborska Abdul Kayani Bernard Hadebe Rajalakshmi Orath Prabakaran Lesley Nichols Matt Thomas Ruth Worner Beverley Faulkner Emma Gendall Kati Hayes Colin Hamilton-Davies Carmen Chan Celina Mfuko Hakam Abbass Vineela Mandadapu Susannah Leaver Daniel Forton Kamal Patel Elankumaran Paramasivam Matthew Powell Richard Gould Elizabeth Wilby Clare Howcroft Dorota Banach Ziortza Fernández de Pinedo Artaraz Leilani Cabreros Ian White Maria Croft Nicky Holland Rita Pereira Ahmed Zaki David Johnson Matthew Jackson Hywel Garrard Vera Juhaz Alistair Roy Anthony Rostron Lindsey Woods Sarah Cornell Suresh Pillai Rachel Harford Tabitha Rees Helen Ivatt Ajay Sundara Raman Miriam Davey Kelvin Lee Russell Barber Manish Chablani Farooq Brohi Vijay Jagannathan Michele Clark Sarah Purvis Bill Wetherill Ahilanandan Dushianthan Rebecca Cusack Kim de Courcy-Golder Simon Smith Susan Jackson Ben Attwood Penny Parsons Valerie Page Xiao Bei Zhao Deepali Oza Jonathan Rhodes Tom Anderson Sheila Morris Charlotte Xia Le Tai Amy Thomas Alexandra Keen Stephen Digby Nicholas Cowley Laura Wild David Southern Harsha Reddy Andy Campbell Claire Watkins Sara Smuts Omar Touma Nicky Barnes Peter Alexander Tim Felton Susan Ferguson Katharine Sellers Joanne Bradley-Potts David Yates Isobel Birkinshaw Kay Kell Nicola Marshall Lisa Carr-Knott Charlotte Summers

JAMA 2020 10;324(13):1317-1329

Division of Anaesthetics, Pain Medicine and Intensive Care Medicine, Department of Surgery and Cancer, Imperial College London and Imperial College Healthcare NHS Trust, London, United Kingdom.

Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited.

Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19.

Design, Setting, And Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020.

Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108).

Main Outcomes And Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%).

Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively.

Conclusions And Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions.

Trial Registration: ClinicalTrials.gov Identifier: NCT02735707.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1001/jama.2020.17022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7489418PMC
October 2020

Epidural analgesia in ICU chest trauma patients with fractured ribs: retrospective study of pain control and intubation requirements.

Ann Intensive Care 2020 Aug 27;10(1):116. Epub 2020 Aug 27.

Médecine Intensive Réanimation, University Hospital, Nantes, France.

Background: Nonintubated chest trauma patients with fractured ribs admitted to the intensive care unit (ICU) are at risk for complications and may require invasive ventilation at some point. Effective pain control is essential. We assessed whether epidural analgesia (EA) in patients with fractured ribs who were not intubated at ICU admission decreased the need for invasive mechanical ventilation (IMV). We also looked for risk factors for IMV.

Study Design And Methods: This retrospective, observational, multicenter study conducted in 40 ICUs in France included consecutive patients with three or more fractured ribs who were not intubated at admission between July 2013 and July 2015.

Results: Of the 974 study patients, 788 were included in the analysis of intubation predictors. EA was used in 130 (16.5%) patients, and 65 (8.2%) patients required IMV. Factors independently associated with IMV were chronic respiratory disease (P = 0.008), worse SAPS II (P < 0.0001), flail chest (P = 0.02), worse Injury Severity Score (P = 0.0003), higher respiratory rate at admission (P = 0.02), alcohol withdrawal syndrome (P < 0.001), and noninvasive ventilation (P = 0.04). EA was not associated with decreases in IMV requirements, median numerical rating scale pain score, or intravenous morphine requirements from day 1 to day 7.

Conclusions: EA was not associated with a lower risk of IMV in chest trauma patients with at least 3 fractured ribs, moderate pain, and no intubation on admission. Further studies are needed to clarify the optimal pain control strategy in chest trauma patients admitted to the ICU, notably those with severe pain or high opioid requirements.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13613-020-00733-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7450151PMC
August 2020

Delirium and encephalopathy in severe COVID-19: a cohort analysis of ICU patients.

Crit Care 2020 08 8;24(1):491. Epub 2020 Aug 8.

Hôpitaux Universitaires de Strasbourg, Service de Médecine Intensive-Réanimation, Nouvel Hôpital Civil, 1, place de l'Hôpital, F-67091, Strasbourg, Cedex, France.

Background: Neurotropism of SARS-CoV-2 and its neurological manifestations have now been confirmed. We aimed at describing delirium and neurological symptoms of COVID-19 in ICU patients.

Methods: We conducted a bicentric cohort study in two French ICUs of Strasbourg University Hospital. All the 150 patients referred for acute respiratory distress syndrome due to SARS-CoV-2 between March 3 and May 5, 2020, were included at their admission. Ten patients (6.7%) were excluded because they remained under neuromuscular blockers during their entire ICU stay. Neurological examination, including CAM-ICU, and cerebrospinal fluid analysis, electroencephalography, and magnetic resonance imaging (MRI) were performed in some of the patients with delirium and/or abnormal neurological examination. The primary endpoint was to describe the incidence of delirium and/or abnormal neurological examination. The secondary endpoints were to describe the characteristics of delirium, to compare the duration of invasive mechanical ventilation and ICU length of stay in patients with and without delirium and/or abnormal neurological symptoms.

Results: The 140 patients were aged in median of 62 [IQR 52; 70] years old, with a median SAPSII of 49 [IQR 37; 64] points. Neurological examination was normal in 22 patients (15.7%). One hundred eighteen patients (84.3%) developed a delirium with a combination of acute attention, awareness, and cognition disturbances. Eighty-eight patients (69.3%) presented an unexpected state of agitation despite high infusion rates of sedative treatments and neuroleptics, and 89 (63.6%) patients had corticospinal tract signs. Brain MRI performed in 28 patients demonstrated enhancement of subarachnoid spaces in 17/28 patients (60.7%), intraparenchymal, predominantly white matter abnormalities in 8 patients, and perfusion abnormalities in 17/26 patients (65.4%). The 42 electroencephalograms mostly revealed unspecific abnormalities or diffuse, especially bifrontal, slow activity. Cerebrospinal fluid examination revealed inflammatory disturbances in 18/28 patients, including oligoclonal bands with mirror pattern and elevated IL-6. The CSF RT-PCR SARS-CoV-2 was positive in one patient. The delirium/neurological symptoms in COVID-19 patients were responsible for longer mechanical ventilation compared to the patients without delirium/neurological symptoms. Delirium/neurological symptoms could be secondary to systemic inflammatory reaction to SARS-CoV-2.

Conclusions And Relevance: Delirium/neurological symptoms in COVID-19 patients are a major issue in ICUs, especially in the context of insufficient human and material resources.

Trial Registration: NA.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13054-020-03200-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7414289PMC
August 2020

Neurologic and neuroimaging findings in patients with COVID-19: A retrospective multicenter study.

Neurology 2020 09 17;95(13):e1868-e1882. Epub 2020 Jul 17.

From the Hôpitaux Universitaires de Strasbourg (S.K., F.L., S.B., F.-D.A., T.W.), Service d'imagerie 2, Hôpital de Hautepierre; Engineering Science, Computer Science and Imaging Laboratory (S.K., N.M.), UMR 7357, University of Strasbourg-CNRS; Service de Neurologie (M. Anheim), Hôpitaux Universitaires de Strasbourg; Institut de Génétique et de Biologie Moléculaire et Cellulaire (M. Anheim), INSERM-U964/CNRS-UMR7104/Université de Strasbourg, Illkirch; Fédération de Médecine Translationnelle de Strasbourg (M. Anheim), Université de Strasbourg; Hôpitaux universitaires de Strasbourg (H.M., F.M., J.H.), Service de Médecine Intensive Réanimation, Nouvel Hôpital Civil; INSERM (French National Institute of Health and Medical Research) (H.M., F.M.), UMR 1260, Regenerative Nanomedicine, Fédération de Médecine Translationnelle de Strasbourg; Médecine Intensive-Réanimation (M.S., F.S.), Hôpital de Hautepierre, Hôpitaux Universitaires de Strasbourg; Service de Neuroradiologie (H.O., F.B., J.M.), Hôpitaux Civils de Colmar; Service d'Imagerie (A. Khalil, A.G.), Unité de Neuroradiologie, Assistance Publique-Hôpitaux de Paris, Hôpital Bichat Claude Bernard; Université Paris Diderot (A. Khalil), Paris; Service de Neurologie (S. Carré, C.L.), Centre Hospitalier de Haguenau; Service de Radiologie (M. Alleg), Centre Hospitalier de Haguenau; Service de Neuroradiologie, (E.S., R.A., F.Z.) Hôpital Central, CHU de Nancy; CHIC Unisanté (L.J., P.N., Y.T.M.), Hôpital Marie Madeleine, Forbach; Neuroimaging Department (G.H., J. Benzakoun, C.O., G. Boulouis, M.E.-G., B.K.), GHU Paris Psychiatrie et Neurosciences, Hôpital Sainte-Anne, Université de Paris, INSERM U1266, F-75014; CHU Rennes (J.-C.F., B.C.-N.), Department of Neuroradiology; CHU Rennes (A.M.), Medical Intensive Care Unit; Department of Neuroradiology (P.-O.C., F.R., P.T.), University Hospital of Dijon, Hôpital François Mitterrand; Service de Radiologie (C.B.), CHU de Saint-Etienne; Service de Réanimation (X.F.), CH de Roanne; Service de Neuroradiologie (G.F., S.S.), CHU de Limoges; Radiology Department (I.d.B., G. Bornet), Hôpital Privé d'Antony; Department of Diagnostic and Interventional Neuroradiology (H.D.), University Hospital, Nantes; Neuroradiology Department (J. Berge), CHU de Bordeaux; Service de Neuroradiologie (A. Kazémi), CHU de Lille; Assistance Publique Hôpitaux de Paris (N.P.), Service de Neuroradiologie, Hôpital Pitié-Salpêtrière; Sorbonne Université (N.P.), Univ Paris 06, UMR S 1127, CNRS UMR 7225, ICM, F-75013; Service de Neuroradiologie Diagnostique (A.L.), Foundation A. Rothschild Hospital, Paris; EA CHIMERE 7516 (J.-M.C.), Université de Picardie Jules Verne; Service de NeuroRadiologie, pôle Imagerie Médicale, Centre Hospitalo-Universitaire d'Amiens; Hôpitaux Universitaires de Strasbourg (P.-E.Z., M.M.), UCIEC, Pôle d'Imagerie, Strasbourg; Observatoire Français de la Sclérose en Plaques (J.-C.B.), Lyon; Nephrology and Transplantation Department (S. Caillard), Hôpitaux Universitaires de Strasbourg; Inserm UMR S1109 (S. Caillard), LabEx Transplantex, Fédération de Médecine Translationnelle de Strasbourg, Université de Strasbourg; Hôpitaux Universitaires de Strasbourg (O.C., P.M.M.), Service d'Anesthésie-Réanimation, Nouvel Hôpital Civil; Hôpitaux Universitaires de Strasbourg (S.F.-K.), Laboratoire de Virologie Médicale; Radiology Department (M.O.), Nouvel Hôpital Civil, Strasbourg University Hospital; CHU de Strasbourg (N.M.), Service de Santé Publique, GMRC, F-67091 Strasbourg; Immuno-Rhumatologie Moléculaire (S.F.-K., J.H.), INSERM UMR_S1109, LabEx TRANSPLANTEX, Centre de Recherche d'Immunologie et d'Hématologie, Faculté de Médecine, Fédération Hospitalo-Universitaire OMICARE, Fédération de Médecine Translationnelle de Strasbourg, Université de Strasbourg; MRI Center (F.C.), Centre Hospitalier Lyon Sud, Hospices Civils de Lyon; and Université Lyon 1 (F.C.), CREATIS-LRMN, CNRS/UMR/5220-INSERM U630, Villeurbanne, France.

Objective: To describe neuroimaging findings and to report the epidemiologic and clinical characteristics of patients with coronavirus disease 2019 (COVID-19) with neurologic manifestations.

Methods: In this retrospective multicenter study (11 hospitals), we included 64 patients with confirmed COVID-19 with neurologic manifestations who underwent a brain MRI.

Results: The cohort included 43 men (67%) and 21 women (33%); their median age was 66 (range 20-92) years. Thirty-six (56%) brain MRIs were considered abnormal, possibly related to severe acute respiratory syndrome coronavirus. Ischemic strokes (27%), leptomeningeal enhancement (17%), and encephalitis (13%) were the most frequent neuroimaging findings. Confusion (53%) was the most common neurologic manifestation, followed by impaired consciousness (39%), presence of clinical signs of corticospinal tract involvement (31%), agitation (31%), and headache (16%). The profile of patients experiencing ischemic stroke was different from that of other patients with abnormal brain imaging: the former less frequently had acute respiratory distress syndrome ( = 0.006) and more frequently had corticospinal tract signs ( = 0.02). Patients with encephalitis were younger ( = 0.007), whereas agitation was more frequent for patients with leptomeningeal enhancement ( = 0.009).

Conclusions: Patients with COVID-19 may develop a wide range of neurologic symptoms, which can be associated with severe and fatal complications such as ischemic stroke or encephalitis. In terms of meningoencephalitis involvement, even if a direct effect of the virus cannot be excluded, the pathophysiology seems to involve an immune or inflammatory process given the presence of signs of inflammation in both CSF and neuroimaging but the lack of virus in CSF.

Clinicaltrialsgov Identifier: NCT04368390.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1212/WNL.0000000000010112DOI Listing
September 2020

Brain MRI Findings in Severe COVID-19: A Retrospective Observational Study.

Radiology 2020 11 16;297(2):E242-E251. Epub 2020 Jun 16.

From the Hôpitaux Universitaires de Strasbourg, Service d'Imagerie 2, Hôpital de Hautepierre, Strasbourg, France (S.K.).

Background Brain MRI parenchymal signal abnormalities have been associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Purpose To describe the neuroimaging findings (excluding ischemic infarcts) in patients with severe coronavirus disease 2019 (COVID-19) infection. Materials and Methods This was a retrospective study of patients evaluated from March 23, 2020, to April 27, 2020, at 16 hospitals. Inclusion criteria were () positive nasopharyngeal or lower respiratory tract reverse transcriptase polymerase chain reaction assays, () severe COVID-19 infection defined as a requirement for hospitalization and oxygen therapy, () neurologic manifestations, and () abnormal brain MRI findings. Exclusion criteria were patients with missing or noncontributory data regarding brain MRI or brain MRI showing ischemic infarcts, cerebral venous thrombosis, or chronic lesions unrelated to the current event. Categorical data were compared using the Fisher exact test. Quantitative data were compared using the Student test or Wilcoxon test. < .05 represented a significant difference. Results Thirty men (81%) and seven women (19%) met the inclusion criteria, with a mean age of 61 years ± 12 (standard deviation) (age range, 8-78 years). The most common neurologic manifestations were alteration of consciousness (27 of 37, 73%), abnormal wakefulness when sedation was stopped (15 of 37, 41%), confusion (12 of 37, 32%), and agitation (seven of 37, 19%). The most frequent MRI findings were signal abnormalities located in the medial temporal lobe in 16 of 37 patients (43%; 95% confidence interval [CI]: 27%, 59%), nonconfluent multifocal white matter hyperintense lesions seen with fluid-attenuated inversion recovery and diffusion-weighted sequences with variable enhancement, with associated hemorrhagic lesions in 11 of 37 patients (30%; 95% CI: 15%, 45%), and extensive and isolated white matter microhemorrhages in nine of 37 patients (24%; 95% CI: 10%, 38%). A majority of patients (20 of 37, 54%) had intracerebral hemorrhagic lesions with a more severe clinical presentation and a higher admission rate in intensive care units (20 of 20 patients [100%] vs 12 of 17 patients without hemorrhage [71%], = .01) and development of the acute respiratory distress syndrome (20 of 20 patients [100%] vs 11 of 17 patients [65%], = .005). Only one patient had SARS-CoV-2 RNA in the cerebrospinal fluid. Conclusion Patients with severe coronavirus disease 2019 and without ischemic infarcts had a wide range of neurologic manifestations that were associated with abnormal brain MRI scans. Eight distinctive neuroradiologic patterns were described. © RSNA, 2020.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1148/radiol.2020202222DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7301613PMC
November 2020

Refractory non-variceal upper gastrointestinal bleeding in a liver-transplant patient: Everolimus withdrawal should be considered.

Therapie 2020 May 8. Epub 2020 May 8.

Service de médecine intensive réanimation & Inserm U1121 & FMTS, faculté de médecine de strasbourg, avenue Molière, hôpitaux universitaires de Strasbourg, 67098 Strasbourg, France; Centre régional de pharmacovigilance, hôpitaux universitaires de Strasbourg, 67091, Strasbourg, France. Electronic address:

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.therap.2020.04.006DOI Listing
May 2020

High risk of thrombosis in patients with severe SARS-CoV-2 infection: a multicenter prospective cohort study.

Intensive Care Med 2020 06 4;46(6):1089-1098. Epub 2020 May 4.

Service de Médecine Intensive Réanimation, Nouvel Hôpital Civil, Hôpitaux universitaires de Strasbourg, 1, Place de l'Hôpital, 67091, Strasbourg Cedex, France.

Purpose: Little evidence of increased thrombotic risk is available in COVID-19 patients. Our purpose was to assess thrombotic risk in severe forms of SARS-CoV-2 infection.

Methods: All patients referred to 4 intensive care units (ICUs) from two centers of a French tertiary hospital for acute respiratory distress syndrome (ARDS) due to COVID-19 between March 3rd and 31st 2020 were included. Medical history, symptoms, biological data and imaging were prospectively collected. Propensity score matching was performed to analyze the occurrence of thromboembolic events between non-COVID-19 ARDS and COVID-19 ARDS patients.

Results: 150 COVID-19 patients were included (122 men, median age 63 [53; 71] years, SAPSII 49 [37; 64] points). Sixty-four clinically relevant thrombotic complications were diagnosed in 150 patients, mainly pulmonary embolisms (16.7%). 28/29 patients (96.6%) receiving continuous renal replacement therapy experienced circuit clotting. Three thrombotic occlusions (in 2 patients) of centrifugal pump occurred in 12 patients (8%) supported by ECMO. Most patients (> 95%) had elevated D-dimer and fibrinogen. No patient developed disseminated intravascular coagulation. Von Willebrand (vWF) activity, vWF antigen and FVIII were considerably increased, and 50/57 tested patients (87.7%) had positive lupus anticoagulant. Comparison with non-COVID-19 ARDS patients (n = 145) confirmed that COVID-19 ARDS patients (n = 77) developed significantly more thrombotic complications, mainly pulmonary embolisms (11.7 vs. 2.1%, p < 0.008). Coagulation parameters significantly differed between the two groups.

Conclusion: Despite anticoagulation, a high number of patients with ARDS secondary to COVID-19 developed life-threatening thrombotic complications. Higher anticoagulation targets than in usual critically ill patients should therefore probably be suggested.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00134-020-06062-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7197634PMC
June 2020

Acute Pulmonary Embolism in Patients with COVID-19 at CT Angiography and Relationship to d-Dimer Levels.

Radiology 2020 09 23;296(3):E189-E191. Epub 2020 Apr 23.

From the Hôpitaux Universitaires de Strasbourg, Service de Radiologie, Nouvel Hôpital Civil, 1 place de l'Hôpital, 67000, Strasbourg, France (I.L.L., A.L., P.L., C.R., M.O.); Hôpitaux Universitaires de Strasbourg, Service de Réanimation Polyvalente, Nouvel Hôpital Civil, Strasbourg, France (X.D., C.P., O.C.); Hôpitaux universitaires de Strasbourg, Groupe Méthodes en Recherche Clinique (GMRC), Hôpital Civil, Strasbourg, France (F. Séverac); Hôpitaux Universitaires de Strasbourg, Service de Médecine Intensive et Réanimation, Nouvel Hôpital Civil, Strasbourg, France (J.H.); ImmunoRhumatologie Moléculaire, INSERM UMR_S1109, LabEx TRANSPLANTEX, Centre de Recherche d'Immunologie et d'Hématologie, Faculté de Médecine, Fédération Hospitalo-Universitaire (FHU) OMICARE, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg (UNISTRA), Strasbourg, France (J.H.); Hôpitaux Universitaires de Strasbourg, Service de Médecine Intensive-Réanimation, Hôpital de Hautepierre I, Strasbourg, France (F. Schneider); Hôpitaux Universitaires de Strasbourg, Service d'Accueil des Urgences, Nouvel Hôpital Civil, Strasbourg, France (P.B.); and Hôpitaux Universitaires de Strasbourg, Service de Radiologie, Hôpital de Hautepierre I, Strasbourg, France (S.M.).

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1148/radiol.2020201561DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7233397PMC
September 2020

Liver transplantation for critically ill cirrhotic patients: Stratifying utility based on pretransplant factors.

Am J Transplant 2020 09 15;20(9):2437-2448. Epub 2020 Apr 15.

Service de Chirurgie Hépatobiliaire et Transplantation, Hôpital de Hautepierre, Hôpitaux Universitaires de Strasbourg, Strasbourg, France.

The aim of this study was to produce a prognostic model to help predict posttransplant survival in patients transplanted with grade-3 acute-on-chronic liver failure (ACLF-3). Patients with ACLF-3 who underwent liver transplantation (LT) between 2007 and 2017 in 5 transplant centers were included (n = 152). Predictors of 1-year mortality were retrospectively screened and tested on a single center training cohort and subsequently tested on an independent multicenter cohort composed of the 4 other centers. Four independent pretransplant risk factors were associated with 1-year mortality after transplantation in the training cohort: age ≥53 years (P = .044), pre-LT arterial lactate level ≥4 mml/L (P = .013), mechanical ventilation with PaO /FiO  ≤ 200 mm Hg (P = .026), and pre-LT leukocyte count ≤10 G/L (P = .004). A simplified version of the model was derived by assigning 1 point to each risk factor: the transplantation for Aclf-3 model (TAM) score. A cut-off at 2 points distinguished a high-risk group (score >2) from a low-risk group (score ≤2) with 1-year survival of 8.3% vs 83.9% respectively (P < .001). This model was subsequently validated in the independent multicenter cohort. The TAM score can help stratify posttransplant survival and identify an optimal transplantation window for patients with ACLF-3.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/ajt.15852DOI Listing
September 2020

A Pilot Study on Continuous Infusion of 4% Albumin in Critically Ill Patients: Impact on Nosocomial Infection via a Reduction Mechanism for Oxidized Substrates.

Crit Care Explor 2019 Sep 19;1(9):e0044. Epub 2019 Sep 19.

Inserm UMR 1121, Biomatériaux et Bioingénierie, département 11, Strasbourg, France.

Care-related infections affect up to 11% of ICU patients. Running therapeutic albumin is sometimes associated to less infection: whether a specific method of its infusion is of any interest to modulate innate defense is unknown. Our objectives were: 1) to test whether the method for albumin infusion is important to prevent care-related infections and 2) to analyze in vitro the antioxidative role of albumin on host defense proteins during shock (using vasostatin-I as an example).

Design: In a prospective, randomized, open-label trial, shock patients were allocated to receive either continuously 4% albumin or intermittently 20% albumin, as long as they were infused with norepinephrine. A translational study including in vivo and in vitro analyses of albumin-vasostatin-I interactions is reported.

Setting: A tertiary ICU caring for 1,000 patients per year.

Patients: Fifty shock patients with serum albumin less than 20 g/L.

Interventions: In vivo colonization and nosocomial infections were recorded and time-dependent changes in serum albumin, chromogranin A, and vasostatin-I concentrations as well. In vitro, we studied biochemical albumin-vasostatin-I relationship using biochemical methods.

Measurements And Main Results: Over 18 days, we recorded a decrease in colonization (four vs 12 episodes; = 0.035) and nosocomial infection frequency (two vs 13 episodes; = 0.002) in patients infused continuously 4% albumin versus controls. In vitro, albumin interacts with the disulfide loop vasostatin-I (residues 17-40) and continuous 4% albumin infusion restores its oxidative status required for antimicrobial activity.

Conclusions: Continuous 4% albumin is effective in reducing care-related infections in shock patients by increasing the availability of antimicrobial vasostatin-I. This might guide future care of shock patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/CCE.0000000000000044DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7063941PMC
September 2019

Adrenal gland-released vasostatin-I is a myocardial depressant factor.

Br J Clin Pharmacol 2020 04 3;86(4):825-828. Epub 2020 Feb 3.

Inserm UMR 1121, Faculté de Chirurgie Dentaire, Hôpital Civil, 1 Place de l'Hôpital, Strasbourg, France.

Pheochromocytoma crisis is an exceptional consequence of the release of storage vesicles of the adrenal medulla. It is complicated by fulminant adrenergic myocarditis. It offers a unique opportunity to detect inotropic negative factors from neuroendocrine origin. Our objectives were (a) to describe a pheochromocytoma crisis, (b) to investigate in vivo myocardial depressant activities for the N-terminal 1-76 Chromogranin A-derived peptide, vasostatin-I (VS-I). A patient with a pheochromocytoma crisis was treated, including extracorporeal membrane oxygenation, until mass resection. Plasma concentrations of VS-I were time-dependently assessed with a specific immunoassay; correlations with invasive cardiovascular parameters were investigated. Increased VS-I concentrations were observed over 7 days until tumour resection. VS-I concentrations correlated positively with Chromogranin A levels, negatively with cardiac output and left ventricular stroke work index, but not with heart rate. This case illustrates the pharmacokinetics of VS-I in a pheochromocytoma crisis. It highlights myocardial depressant activity for this peptide at high concentrations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/bcp.14173DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7098871PMC
April 2020

Effect of fluid balance control in critically ill patients: Design of the stepped wedge trial POINCARE-2.

Contemp Clin Trials 2019 08 29;83:109-116. Epub 2019 Jun 29.

Université de Lorraine, CHRU-Nancy, Service de Médecine Intensive Réanimation, F-54000 Nancy, France.

A high number of recent studies have shown that a positive fluid balance is independently associated with impaired prognosis in specific populations of patients hospitalized in intensive care unit (ICU): acute kidney injury, acute respiratory distress syndrome (ARDS), sepsis, high risk surgery. However, to date, there is no evidence that control of fluid overload reduces mortality in critically ill patients. The main objective is to assess the efficacy of a strategy limiting fluid overload on mortality in unselected critically ill patients hospitalized in ICU. We hypothesized that a strategy based on a weight-driven recommendation of restricted fluid intake, diuretics, and ultrafiltration initiated from 48 h up to 14 days after admission in critically ill patients would reduce all-cause mortality as compared to usual care. We use a stepped wedge cluster randomized controlled trial combined with a quasi-experimental (before-and-after) study. Patients under mechanical ventilation, admitted since >48 h and < 72 h in ICU, and with no discharge planned for the next 24 h are eligible. A total of 1440 patients are expected to be enrolled in 12 ICUs. Sociodemographic and clinical data are collected at inclusion, and outcomes are collected during the follow-up. Primary outcome is all-cause mortality at 60 days after admission. Secondary outcomes are patients weight differences between admission and day7 (or day 14), 28-day, in-hospital, and 1-year mortality, end-organ damages, and unintended harmful events. Analyses will be held in intention-to-treat. If POINCARE-2 strategy proves effective, then guidelines on fluid balance control might be extended to all critically ill patients. Trial registration: ClinicalTrials.govNCT02765009.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cct.2019.06.020DOI Listing
August 2019

Intensive care for patients with gastric cancers: outcome and survival prognostic factors.

J Gastrointest Oncol 2019 Apr;10(2):292-299

Service de Réanimation Médicale, Hôpital de Hautepierre, Hôpitaux Universitaires de Strasbourg, Strasbourg, France.

Background: Admission and management of patients with solid malignancies in intensive care unit (ICU) is a controversial topic. To this day, there is no data published concerning patients with gastric cancers hospitalized in ICU. This single center retrospective study reports the characteristics, outcome and prognostic factors of patients hospitalized in ICU for medical reasons over a period of 10 years.

Methods: We performed a single center retrospective study which reports the characteristics, outcome and prognostic factors of patients hospitalized in ICU for medical reasons over a period of 10 years.

Results: Thirty-seven patients were included, among whom 24 (64.9%) had metastatic cancer. The most frequent diagnosis on admission was septic shock (48.6%) and 24 patients (64.9%) required intubation. Ten patients (27.0%) were alive 3 months after their admission in ICU. Metastatic cancer and intubation were independently associated with a higher risk of dying within 3 months of admission in multivariate analysis: odds ratio (OR) =13.7; 95% confidence interval (CI), 1.7-108 (P<0.01). Seventeen patients (45.9%) died during their ICU stay. Metastatic cancer: OR =89; 95% CI, 2.7-6,588, therapeutic intensification: OR =1,471; 95% CI, 9.8-811,973 and the logistic organ dysfunction score (LODS) on admission: OR =1.4; 95% CI, 1.1-2.3 were independently associated with mortality within the ICU in multivariate analysis (P<0.01).

Conclusions: This is the first study that examines the outcome and prognostic factors of patients with gastric cancers who require life-sustaining therapy in ICU. The identification of 3 months and ICU mortality prognostic factors could contribute to guiding clinicians in the management of these patients and assist health professionals in their discussions with these patients and their families.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.21037/jgo.2018.10.11DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6465480PMC
April 2019

Diffusion tensor imaging reveals diffuse white matter injuries in locked-in syndrome patients.

PLoS One 2019 10;14(4):e0213528. Epub 2019 Apr 10.

Service d'imagerie 2, Hopitaux Universitaires de Strasbourg, Strabourg, France.

Locked-in syndrome (LIS) is a state of quadriplegia and anarthria with preserved consciousness, which is generally triggered by a disruption of specific white matter fiber tracts, following a lesion in the ventral part of the pons. However, the impact of focal lesions on the whole brain white matter microstructure and structural connectivity pathways remains unknown. We used diffusion tensor magnetic resonance imaging (DT-MRI) and tract-based statistics to characterise the whole white matter tracts in seven consecutive LIS patients, with ventral pontine injuries but no significant supratentorial lesions detected with morphological MRI. The imaging was performed in the acute phase of the disease (26 ± 13 days after the accident). DT-MRI-derived metrics were used to quantitatively assess global white matter alterations. All diffusion coefficient Z-scores were decreased for almost all fiber tracts in all LIS patients, with diffuse white matter alterations in both infratentorial and supratentorial areas. A mixture model of two multidimensional Gaussian distributions was fitted to cluster the white matter fiber tracts studied in two groups: the least (group 1) and most injured white matter fiber tracts (group 2). The greatest injuries were revealed along pathways crossing the lesion responsible for the LIS: left and right medial lemniscus (98.4% and 97.9% probability of belonging to group 2, respectively), left and right superior cerebellar peduncles (69.3% and 45.7% probability) and left and right corticospinal tract (20.6% and 46.5% probability). This approach demonstrated globally compromised white matter tracts in the acute phase of LIS, potentially underlying cognitive deficits.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0213528PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6457498PMC
December 2019

Clinical features and outcome of patients with acute respiratory failure revealing anti-synthetase or anti-MDA-5 dermato-pulmonary syndrome: a French multicenter retrospective study.

Ann Intensive Care 2018 Sep 11;8(1):87. Epub 2018 Sep 11.

Service de Réanimation Polyvalente, Centre Hospitalier Victor Dupouy, 69 rue du Lieutenant Colonel Prudhon, 95100, Argenteuil, France.

Background: Anti-synthetase (AS) and dermato-pulmonary associated with anti-MDA-5 antibodies (aMDA-5) syndromes are near one of the other autoimmune inflammatory myopathies potentially responsible for severe acute interstitial lung disease. We undertook a 13-year retrospective multicenter study in 35 French ICUs in order to describe the clinical presentation and the outcome of patients admitted to the ICU for acute respiratory failure (ARF) revealing AS or aMDA-5 syndromes.

Results: From 2005 to 2017, 47 patients (23 males; median age 60 [1st-3rd quartiles 52-69] years, no comorbidity 85%) were admitted to the ICU for ARF revealing AS (n = 28, 60%) or aMDA-5 (n = 19, 40%) syndromes. Muscular, articular and cutaneous manifestations occurred in 11 patients (23%), 14 (30%) and 20 (43%) patients, respectively. Seventeen of them (36%) had no extra-pulmonary manifestations. C-reactive protein was increased (139 [40-208] mg/L), whereas procalcitonine was not (0.30 [0.12-0.56] ng/mL). Proportion of patients with creatine kinase ≥ 2N was 20% (n = 9/47). Forty-two patients (89%) had ARDS, which was severe in 86%, with a rate of 17% (n = 8/47) of extra-corporeal membrane oxygenation requirement. Proportion of patients who received corticosteroids, cyclophosphamide, rituximab, intravenous immunoglobulins and plasma exchange were 100%, 72%, 15%, 21% and 17%, respectively. ICU and hospital mortality rates were 45% (n = 21/47) and 51% (n = 24/47), respectively. Patients with aMDA-5 dermato-pulmonary syndrome had a higher hospital mortality than those with AS syndrome (n = 16/19, 84% vs. n = 8/28, 29%; p = 0.001).

Conclusions: Intensivists should consider inflammatory myopathies as a cause of ARF of unknown origin. Extra-pulmonary manifestations are commonly lacking. Mortality is high, especially in aMDA-5 dermato-pulmonary syndrome.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13613-018-0433-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6131681PMC
September 2018

Critically ill elderly patients (≥ 90 years): Clinical characteristics, outcome and financial implications.

PLoS One 2018 1;13(6):e0198360. Epub 2018 Jun 1.

Medical Intensive Care Unit and UMR 1121, Hautepierre Hospital, University Hospital of Strasbourg, Strasbourg, France.

Background: Patients aged over 90 are being admitted to intensive care units (ICUs) with increasing frequency. The appropriateness of such decisions still remains controversial due to questionable outcome, limited resources and costs. Our objective was to determine the clinical characteristics and outcome in elderly patients (≥ 90 years) admitted in a medical ICU, with an additional focus on medico-economic implications.

Methods: We reviewed the charts of all patients (≥ 90 years) admitted to our ICU. We compared them with all other ICU patients (< 90 years), sought to identify ICU mortality predictors and also performed a long-term survival follow-up.

Results: In the study group of 317 stays: median age was 92 years (IQR: 91-94 years); most patients were female (71.3%.). Acute respiratory failure (52.4%) was the main admission diagnosis; mean SAPS II was 55.6±21.3; half the stays (49.2%) required mechanical ventilation (duration: 7.2±8.8 days); withholding and withdrawing decisions were made for 33.4% of all stays. ICU and hospital mortality rates were 35.7% and 42.6% respectively. Mechanical ventilation (OR = 4.83, CI95%: 1.59-15.82) was an independent predictor of ICU mortality whereas age was not (OR = 0.88, CI95%: 0.72-1.08). Social security reimbursement was significantly lower in the study group compared with all other ICU stays, both per stay (13,160 vs 22,092 Euros, p< 0.01) and per day of stay (p = 0.03).

Conclusion: Among critically ill elderly patients (≥ 90 years), chronological age was not an independent factor of ICU mortality. ICU care-related costs in this population should not be considered as a limiting factor for ICU admission.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0198360PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5983531PMC
January 2019

D-Cateslytin, a new antimicrobial peptide with therapeutic potential.

Sci Rep 2017 11 9;7(1):15199. Epub 2017 Nov 9.

Université de Strasbourg, Faculté de Chirurgie Dentaire, 3 rue Sainte Elisabeth, 67000, Strasbourg, France.

The rise of antimicrobial resistant microorganisms constitutes an increasingly serious threat to global public health. As a consequence, the efficacy of conventional antimicrobials is rapidly declining, threatening the ability of healthcare professionals to cure common infections. Over the last two decades host defense peptides have been identified as an attractive source of new antimicrobials. In the present study, we characterized the antibacterial and mechanistic properties of D-Cateslytin (D-Ctl), a new epipeptide derived from L-Cateslytin, where all L-amino acids were replaced by D-amino acids. We demonstrated that D-Ctl emerges as a potent, safe and robust peptide antimicrobial with undetectable susceptibility to resistance. Using Escherichia coli as a model, we reveal that D-Ctl targets the bacterial cell wall leading to the permeabilization of the membrane and the death of the bacteria. Overall, D-Ctl offers many assets that make it an attractive candidate for the biopharmaceutical development of new antimicrobials either as a single therapy or as a combination therapy as D-Ctl also has the remarkable property to potentiate several antimicrobials of reference such as cefotaxime, amoxicillin and methicillin.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-017-15436-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5680178PMC
November 2017

In Trauma Patients, the Occurrence of Early-Onset Nosocomial Infections is Associated With Increased Plasma Concentrations of Chromogranin A.

Shock 2018 05;49(5):522-528

Inserm UMR 1121 Biomaterials and Bioengineering, University of Strasbourg, Faculty of Odontology, Federation of Translational Medicine, Civil Hospital, Strasbourg, France.

In previously healthy persons suffering from acute illnesses, nosocomial infections (NIs) are frequent. Their prevalence suggests the existence of as yet unknown conditions that may promote care-related infection. This study assessed whether the measurement of plasma chromogranin A, a stress-related protein involved in innate defense, is related to NI risk, and whether any chromogranin A-derived fragment included in vasostatin-I displays immunosuppressive activities related to AP-1 or NF-kappa B downregulation. At the clinical level, trauma patients and healthy controls were recruited to be eligible. Clinical histories were recorded, and standard biological tests (including plasma chromogranin A) were performed. For 9 randomly chosen patients and 16 controls, the time-dependent concentrations of chromogranin A (CGA) were assessed twice a day over 66 h. The data show that trauma patients present a higher value of CGA concentration during 66 h in comparison with healthy controls. In addition, patients maintaining this significant increase in CGA readily develop NIs. We therefore studied the effects of chromogranin A-derived peptides on monocytes, focusing on transcription factors that play a central role in inflammation. In vitro assay demonstrated that a chromogranin A-derived fragment (CGA47-70) displays a significant inhibition of NF-kappa B and AP-1 transcriptional activities in these cells. In conclusion, the occurrence of NI in trauma patients is associated with significantly increased plasma CGA concentrations. Downregulation of the two transcription factors by CGA47-70 might induce early acquired immune defect after a serious medical stress.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/SHK.0000000000001000DOI Listing
May 2018

Liver transplantation in critically ill patients: Preoperative predictive factors of post-transplant mortality to avoid futility.

Clin Transplant 2017 Dec 31;31(12). Epub 2017 Oct 31.

Service de Réanimation Médicale, Hôpital de Hautepierre, Hôpitaux Universitaires de Strasbourg, Strasbourg, France.

Background: The allocation of liver transplants to patients with acute liver failure (ALF) and acute-on-chronic liver failure (ACLF) with multi-organ failure who are admitted in ICU remains controversial due to their high post-transplant mortality rate and the absence of identified mortality risk factors.

Methods: We performed a single-center retrospective cohort study to determine the post-transplant mortality rate of patients with ALF and ACLF requiring ICU care prior to liver transplant (LT) and identified pretransplant factors of post-transplant mortality.

Results: Eighty-four patients (29 with ALF and 55 with ACLF) received a liver transplant while they were hospitalized at the ICU. Their mean model for end-stage liver disease (MELD) score was 41, and their mean sequential organ failure assessment (SOFA) was 15 the day before transplant. The overall 1-year survival rate was 66%. In multivariate analysis, pretransplant lactate level and acute respiratory distress syndrome (ARDS) were the only two independent factors associated with post-transplant mortality. The absence of ARDS and a pretransplant lactate level< 5 mmol/L led to the identification of a subgroup of ICU patients with a good 1-year post-transplant survival (>80%).

Conclusions: Low lactatemia lactate level and the absence of ARDS could be useful criteria in selecting those patients in ICU who could be eligible for liver transplant.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/ctr.13115DOI Listing
December 2017