Publications by authors named "Bernard Clair"

33 Publications

Valproic Acid as an Adjuvant Treatment for Generalized Convulsive Status Epilepticus in Adults Admitted to Intensive Care Units: Protocol for a Double-Blind, Multicenter Randomized Controlled Trial.

JMIR Res Protoc 2021 Feb 24;10(2):e22511. Epub 2021 Feb 24.

Centre Hospitalier Poissy Saint Germain en Laye, Poissy, France.

Background: Generalized convulsive status epilepticus (GCSE) is a frequent medical emergency. GCSE treatment focuses on the administration of benzodiazepines followed by a second-line antiepileptic drug (AED). Despite this stepwise strategy, GCSE is not controlled in one-quarter of patients and is associated with protracted hospitalization, high mortality, and long-term disability. Valproic acid (VPA) is an AED with good tolerability and neuroprotective properties.

Objective: This study aims to demonstrate that administration of VPA as an adjuvant for first- and second-line treatment in GCSE can improve outcomes.

Methods: A multicenter, double-blind, randomized controlled trial was conducted, comparing VPA with a placebo in adults admitted to intensive care units (ICUs) for GCSE in France. GCSE was diagnosed by specifically trained ICU physicians according to standard criteria. All patients received standard of care, including a benzodiazepine and a second-line AED (not VPA), at the discretion of the treating medical team. In the intervention arm, VPA was administered intravenously at a loading dose of 30 mg/kg over 15 minutes, followed by a continuous infusion of 1 mg/kg/hour over the next 12 hours. In the placebo group, an identical intravenous administration of 0.9% saline was used. The primary outcome was the proportion of patients discharged alive from the hospital by day 15. Secondary outcomes were frequency of refractory and super refractory GCSE, ICU-related morbidity, adverse events related to VPA, and cognitive dysfunction at 3 months. Statistical analyses will be performed according to the intent-to-treat principle.

Results: The first patient was randomized on February 18, 2013, and the last patient was randomized on July 7, 2018. Of 248 planned patients, 98.7% (245/248) were enrolled across 20 ICUs. At present, data management is still ongoing, and all parties involved in the trial remain blinded.

Conclusions: The Valproic Acid as an Adjuvant Treatment for Generalized Convulsive Status Epilepticus (VALSE) trial will evaluate whether the use of VPA as an adjuvant for first- and second-line treatment in GCSE improves outcomes.

Trial Registration: ClinicalTrials.gov NCT01791868; https://clinicaltrials.gov/ct2/show/NCT01791868.

International Registered Report Identifier (irrid): DERR1-10.2196/22511.
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http://dx.doi.org/10.2196/22511DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7946594PMC
February 2021

Impact of Coronavirus Disease 2019 in a French Cohort of Myasthenia Gravis.

Neurology 2021 Feb 10. Epub 2021 Feb 10.

Referral Center for Neuromuscular Diseases and ALS, Timone University Hospital, Aix-Marseille University, Marseille, France.

Objective: To describe the clinical characteristics and outcomes of COVID-19 among patients with MG and identify factors associated with COVID-19 severity in MG patients.

Methods: The CO-MY-COVID registry was a multicenter, retrospective, observational cohort study conducted in neuromuscular referral centers and general hospitals of the FILNEMUS network (between March 1, 2020, and June 8, 2020), including MG patients with a confirmed or highly-suspected diagnosis of COVID-19. COVID-19 was diagnosed based on a polymerase chain reaction (PCR) test from a nasopharyngeal swab and/or SARS-CoV-2 serology, thoracic computed tomography (CT-scan), or typical symptoms. The main outcome was COVID-19 severity based on location of treatment/management (home, hospitalized in a medical unit, or in an intensive care unit). We collected information on demographic variables, general history, and risk factors for severe COVID-19. Multivariate ordinal regression models were used to identify factors associated with severe COVID-19 outcomes.

Results: Among 3,558 MG patients registered in the French database for rare disorders, 34 (0.96%) had COVID-19. The mean age at COVID-19 onset was 55.0 ±19.9 years (mean MG duration: 8.5 ± 8.5 years). By the end of the study period, 28 patients recovered from COVID-19, 1 remained affected, and 5 died. Only high Myasthenia Gravis Foundation of America (MGFA) class (≥IV) before COVID-19 was associated with severe COVID-19 (p=0.004); factors that were not associated included gender, MG duration, and medium MGFA classes (≤IIIb). The type of MG treatment had no independent effect on COVID-19 severity.

Conclusions: This registry-based cohort study shows that COVID-19 had a limited effect on most patients, and immunosuppressive medications and corticosteroids used for MG management are not risk factors for poorer outcomes. However, the risk of severe COVID-19 is elevated in patients with high MGFA classes [odds ratio: 102.6 (4.4; 2,371.9)]. These results are important for establishing evidence-based guidelines for the management of MG patients during the COVID-19 pandemic.
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http://dx.doi.org/10.1212/WNL.0000000000011669DOI Listing
February 2021

Comparison of Corticosteroid Tapering Regimens in Myasthenia Gravis: A Randomized Clinical Trial.

JAMA Neurol 2021 Apr;78(4):426-433

General Intensive Care Unit, APHP, Raymond Poincaré Hospital, University of Versailles Saint-Quentin en Yvelines, Garches, France.

Importance: The tapering of prednisone therapy in generalized myasthenia gravis (MG) presents a therapeutic dilemma; however, the recommended regimen has not yet been validated.

Objective: To compare the efficacy of the standard slow-tapering regimen of prednisone therapy with a rapid-tapering regimen.

Design: From June 1, 2009, to July 31, 2013, a multicenter, parallel, single-blind randomized trial was conducted to compare 2 regimens of prednisone tapering. Data analysis was conducted from February 18, 2019, to January 23, 2020. A total of 2291 adults with a confirmed diagnosis of moderate to severe generalized MG at 7 specialized centers in France were assessed for eligibility.

Interventions: The slow-tapering arm included a gradual increase of the prednisone dose to 1.5 mg/kg every other day and a slow decrease once minimal manifestation status of MG was attained. The rapid-tapering arm consisted of immediate high-dose daily administration of prednisone, 0.75 mg/kg, followed by an earlier and rapid decrease once improved MG status was attained. Azathioprine, up to a maximum dose of 3 mg/kg/d, was prescribed for all participants.

Main Outcomes And Measures: The primary outcome was attainment of minimal manifestation status of MG without prednisone at 12 months and without clinical relapse at 15 months. Intention-to-treat analysis was conducted.

Results: Of the 2291 patients assessed, 2086 did not fulfill the inclusion criteria, 87 declined to participate, and 1 patient registered after trial closure. A total of 117 patients (58 in the slow-tapering arm and 59 in the rapid-tapering arm) were selected for inclusion by MG specialists and were randomized. The population included 62 men (53%); median age was 65 years (interquartile range, 35-69 years). The proportion of patients having met the primary outcome was higher in the rapid- vs slow-tapering arm (23 [39%] vs 5 [9%]), with a risk ratio of 3.61 (95% CI, 1.64-7.97; P < .001) after adjusting for center and thymectomy. The rapid-tapering regimen allowed sparing of a mean of 1898 mg (95% CI, -3121 to -461 mg) of prednisone over 1 year (ie, 5.3 mg/d per patient, P = .03). The number of serious adverse events did not differ significantly between the slow- vs rapid-tapering group (13 [22%] vs 21 [36%], P = .15).

Conclusions And Relevance: In patients with moderate to severe generalized MG who require high-dose prednisone with azathioprine therapy, rapid tapering of prednisone appears to be feasible, well tolerated, and associated with a good outcome.

Trial Registration: ClinicalTrials.gov Identifier: NCT00987116.
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http://dx.doi.org/10.1001/jamaneurol.2020.5407DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7871208PMC
April 2021

Early mechanical ventilation in patients with Guillain-Barré syndrome at high risk of respiratory failure: a randomized trial.

Ann Intensive Care 2020 Sep 30;10(1):128. Epub 2020 Sep 30.

Medical Intensive Care Unit, Raymond Poincaré Teaching Hospital, 104 boulevard Raymond Poincaré, 92380, Garches, France.

Introduction: About 30% of patients with Guillain-Barré syndrome become ventilator dependent, of whom roughly 75% develop pneumonia. This trial aimed at assessing the impact of early mechanical ventilation (EMV) on pneumonia occurrence in GBS patients. We hypothesize that EMV will reduce the incidence of pneumonia.

Methods: This was a single centre, open-label, randomized controlled trial performed on two parallel groups. 50 intensive care unit adults admitted for Guillain-Barré syndrome and at risk for acute respiratory failure. Patients were randomized to early mechanical ventilation via face-mask or endotracheal intubation owing to the presence or absence of impaired swallowing (experimental arm), or to conventional care (control arm). The primary outcome was the incidence of pneumonia up to intensive care unit discharge (or 90 days, pending of which occurred first).

Findings: Twenty-five patients were randomized in each group. There was no significant difference between groups for the incidence of pneumonia (10/25 (40%) vs 9/25 (36%), P = 1). There was no significant difference between groups for the time to onset of pneumonia (P = 0.50, Gray test). During follow-up, there were 16/25 (64%) mechanically ventilated patients in the control group, and 25/25 (100%) in the experimental arm (P < 000·1). The time on ventilator was non-significantly shorter in the experimental arm (14 [7; 29] versus 21.5 [17.3; 35.5], P = 0.10). There were no significant differences between groups for length of hospital stay, neurological scores, the proportion of patients who needed tracheostomy, in-hospital death, or any serious adverse events.

Conclusions: In the present study including adults with Guillain-Barré syndrome at high risk of respiratory failure, we did not observe a prevention of pneumonia with early mechanical ventilation.

Trial Registration: ClinicalTrials.gov under the number NCT00167622. Registered 9 September 2005, https://clinicaltrials.gov/ct2/show/NCT00167622?cond=Guillain-Barre+Syndrome&cntry=FR&draw=2&rank=1.
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http://dx.doi.org/10.1186/s13613-020-00742-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7525233PMC
September 2020

Risk factors for respiratory tract bacterial colonization in adults with neuromuscular or neurological disorders and chronic tracheostomy.

Respir Med 2019 06 25;152:32-36. Epub 2019 Apr 25.

Laboratoire de microbiologie et unité d'hygiène hospitalière APHP, Hôpitaux Universitaires Paris Ile de France Ouest, site R. Poincaré, 92380, Garches, France; INSERM U1173, UFR Simone Veil, Versailles-Saint-Quentin University, 78180, Saint-Quentin en Yvelines, France. Electronic address:

The aim of this study was to describe the endotracheal respiratory flora in a population of adults suffering from neuromuscular or neurological disorders requiring a long-term tracheostomy and to identify risk factors for colonization. We conducted a prospective and single-center observational study among patients with chronic tracheostomy admitted for planned respiratory assessment between February 2015 and December 2016. Data were collected from patient interview and medical charts with a standardized questionnaire. A tracheal aspiration was performed for each patient. Humidifiers were analysed for bacteriological contamination. Overall 77 tracheal aspirates (TA) were obtained from patients included. Pathogenic bacteria were found in 90% of cases (69/77) with a majority of Pseudomonas aeruginosa (32/77, 41%), Staphylococcus aureus (34/77, 44%) and Serratia marcesens. (22/79, 38%) Amoxicillin + Clavulanic-acid and Cefotaxime were adapted for respectively in only 28% and 35% of the subjects due to the natural resistance of organisms. No pathogenic bacteria were isolated from humidifier samples. Risk factors significantly associated with P. aeruginosa colonization were residence in a medical-care home (p = 0.01, OR = 3.8 [1.1; 15.1]) and the presence of a cuff (p = 0.003, OR = 4.4 [1.1; 20.6]). Significant quantities of pathogenic bacteria are frequently isolated from TA of tracheostomised patients in the absence of infection. The frequent resistance of these pathogens to Amoxicillin + Clavulanic-acid precludes the use of this antibiotic in the empiric treatment of pneumonia in this population.
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http://dx.doi.org/10.1016/j.rmed.2019.04.015DOI Listing
June 2019

Diaphragm sniff ultrasound: Normal values, relationship with sniff nasal pressure and accuracy for predicting respiratory involvement in patients with neuromuscular disorders.

PLoS One 2019 24;14(4):e0214288. Epub 2019 Apr 24.

Service de Physiologie-Explorations fonctionnelles, CHU Raymond Poincaré, APHP, Université de Versailles saint Quentin en Yvelines, Garches, France.

Background: In patients with neuromuscular disorders, assessment of respiratory function relies on forced vital capacity (FVC) measurements. Providing complementary respiratory outcomes may be useful for clinical trials. Diaphragm sniff ultrasound (US) is a noninvasive technique that can assess diaphragm function that may be affected in patients with neuromuscular disorders.

Purpose: We aimed to provide normal values of sniff diaphragm ultrasound, to assess the relationship between sniff diaphragm US, vital capacity (VC) and sniff nasal pressure. Additionally, we aimed to evaluate the diagnostic accuracy of sniff diaphragm US for predicting restrictive pulmonary insufficiency.

Materials And Methods: We included patients with neuromuscular disorders that had been tested with a sniff diaphragm US and functional respiratory tests. Healthy subjects were also included to obtain normal diaphragm sniff ultrasound. We performed diaphragm tissue Doppler imaging (TDI) and time movement (TM) diaphragm echography combined with sniff maneuver.

Results: A total of 89 patients with neuromuscular diseases and 27 healthy subjects were included in our study. In patients, the median age was 32 years [25; 50] and the median FVC was 34% of predicted [18; 55]. Sniff diaphragm motion using TM ultrasound was significantly associated with sniff nasal pressure, both for the right hemidiaphragm (r = 0.6 p <0.0001) and the left hemidiaphragm (r = 0.63 p = 0.0008). Right sniff peak TDI velocity was also significantly associated with FVC (r = 0.72, p<0.0001) and with sniff nasal pressure (r = 0.66 p<0.0001). Sniff diaphragm ultrasound using either TM mode or TDI displayed significant accuracy for predicting FVC<60% with an area under curve (AUC) reaching 0.93 (p<0.0001) for the right sniff diaphragm ultrasound in TM mode and 0.86 (p<0.001) for right peak diaphragm TDI velocity.

Conclusion: Sniff diaphragm TM and TDI measures were significantly associated with sniff nasal pressure. Sniff diaphragm TM and TDI had a high level of accuracy to reveal respiratory involvement in patients with neuromuscular disorders. This technique is useful to assess and follow up diaphragm function in patients with neuromuscular disorders. It may be used as a respiratory outcome for clinical trials.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0214288PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6481788PMC
December 2019

Accuracy of B-natriuretic peptide for the diagnosis of decompensated heart failure in muscular dystrophies patients with chronic respiratory failure.

Neurol Int 2018 Dec 20;10(4):7917. Epub 2018 Dec 20.

Service of Medical Resuscitation, Home Ventilation Unit, Raymond Poincaré, University of Versailles Saint Quentin en Yvelines, Garches.

Heart failure and restrictive respiratory insufficiency are complications in muscular dystrophies. We aimed to assess the accuracy of the B-natriuretic peptide (BNP) for the diagnosis of decompensated heart failure in muscular dystrophy. We included patients with muscular dystrophy and chronic respiratory insufficiency admitted in the Intensive Care Unit of the Raymond Poincare hospital (Garches, France) for suspected decompensated heart failure. Thirtyseven patients were included, among them, 23 Duchenne muscular dystrophy (DMD) (62%), 10 myotonic dystrophy type 1(DM1) (27%). Median age was 35 years [27.5; 48.5]. 86.5% of patients were on home mechanical ventilation (HMV). Median left ventricular ejection fraction (LVEF) was 47% [35.0; 59.5]. Median BNP blood level was 104 pg/mL [50; 399]. The BNP level was significantly inversely associated with LVEF (r= -0.37, p 0.03) and positively associated with the LVEDD (left ventricular end diastolic diameter) (r=0.59, P<0.001). The discriminative value of the BNP level for the diagnosis of decompensated heart failure was high with an AUROC=0.94 (P<0.001). The best discriminating BNP threshold was 307 pg/mL (Youden index 0.85). The BNP level measurement may add a supplemental key for the final diagnosis of decompensated heart failure.
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http://dx.doi.org/10.4081/ni.2018.7917DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6322051PMC
December 2018

Echographic Assessment of Diaphragmatic Function in Duchenne Muscular Dystrophy from Childhood to Adulthood.

J Neuromuscul Dis 2019;6(1):55-64

Service de Réanimation msédicale et unité de ventilation à domicile, CHU Raymond Poincaré, APHP, Université de Versailles Saint Quentin en Yvelines, Garches, France.

Background: Duchenne muscular dystrophy (DMD) is an X-linked recessive genetic muscle disorder. Respiratory muscle function is classically affected in this disease. Ultrasound recently emerged as a non-invasive tool to assess diaphragm function. However, there are only a few studies using diaphragm ultrasound (US) in DMD.

Purpose: We aimed to assess diaphragm ultrasound patterns in DMD, their relationship with age and their association with home mechanical ventilation (HMV).

Methods: We included DMD patients followed at Raymond Poincaré Hospital who benefited from diaphragm ultrasound and pulmonary function tests.

Results: There were 110 DMD patients and 17 male sex-matched healthy subjects included. In all, 94% of patients were permanent wheelchair users. Median body mass index (BMI) was 18 kg/m2. DMD patients disclosed a reduced forced vital capacity (VC) (12% of predicted value), and 78% of patients were on HMV. In patients, right and left diaphragmatic motions on deep inspiration were reduced and end expiratory diaphragm thickness was borderline normal. In patients, right and left diaphragmatic thickening fractions (TF) were reduced 12.7% and 15.5%, respectively. Age and end expiratory thickness were significantly inversely associated (p = 0.005 for the right diaphragm, p = 0.018 for the left diaphragm). Diaphragm TF was significantly inversely associated with age (p = 0.001 for the right side, p < 0.0001 for the left side). Right and left inspiratory diaphragm motions were significantly inversely associated with age (p < 0.0001).

Conclusion: This study describes the severity of diaphragm dysfunction in patients with DMD. Diaphragm US may be a non-invasive outcome measure for DMD.
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http://dx.doi.org/10.3233/JND-180326DOI Listing
January 2020

Natural history of cardiac function in Duchenne and Becker muscular dystrophies on home mechanical ventilation.

Medicine (Baltimore) 2018 Jul;97(27):e11381

Service de Réanimation Médicale et Unité de Ventilation à Domicile, CHU Raymond Poincaré, APHP, Université de Versailles Saint Quentin en Yvelines Centre d'Investigation Clinique et Innovation Technologique CIC 14.29, INSERM, Garches Institut de Myologie, CHU Pitié Salpetrière, Centre de Référence Neuro Musculaire Paris Est SBIM, CHU Saint Louis, APHP, Université Paris Diderot, Paris Service de Physiologie-Explorations Fonctionnelles, CHU Raymond Poincaré, APHP, Université de Versailles Saint Quentin en Yvelines, Garches, France.

Heart impairment is classical in dystrophinopathies and its management relies on medical drugs. Mechanical ventilation is used to treat respiratory failure, but can affect cardiac function. We aimed to investigate the natural history of cardiac function in patients with Duchenne (DMD) and Becker (BMD) muscular dystrophies on home mechanical ventilation (HMV).We reviewed the chart of DMD and BMD patients, followed in our institution, to obtain ventilation setting at HMV initiation and echocardiographic data at baseline and end follow up, as well as onset cardiac events and thoracic mechanical complication. We analyzed cumulative incidence of cardiac events as well as echocardiographic parameters evolution and its association with ventilation settings.We included 111 patients (101 DMD and 10 BMD). Median age was 21 years [18-26], median pulmonary vital capacity (VC) 15% of predicted [10-24]. All patients were on HMV and 46% ventilated using tracheostomy. After a median follow up of 6.3 years, we found a slight decrease of the left ventricular ejection fraction (LVEF) (45% at end follow up vs 50% at baseline P = .019) and a stabilization of the LV end diastolic diameter indexed (LVEDD indexed 29.4 mm/m vs 30.7 mm/m at end follow up, P = .17). Tidal volume (VT) level was inversely associated with the annual rate of the LVEF decline (r = -0.29, P = .025). Left atrium (LA) diameter decreased with mechanical ventilation (24 mm vs 20 mm, P = .039) and we found a reduction of systolic pulmonary pressure (35 mm Hg vs 25 mm Hg, P = .011). The cumulative incidence of cardiac events was 12.6%. Pneumothorax occurred in 4% of patients. Hypoxic arrest secondary to the presence of tracheal plugin occurred in 4% of patients with invasive ventilation.HMV is not harmful, decreases pulmonary pressure and may protect heart in dystrophinopathies, in addition with cardioprotective drugs. In patients with DMD and BMD on HMV, cumulative incidence of cardiac events remains moderate and incidence of pneumothorax is rare.
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http://dx.doi.org/10.1097/MD.0000000000011381DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6076049PMC
July 2018

Effects of Home Mechanical Ventilation on Left Ventricular Function in Sarcoglycanopathies (Limb Girdle Muscular Dystrophies).

Am J Cardiol 2018 07 16;122(2):353-355. Epub 2018 Apr 16.

CHU Raymond Poincaré, APHP, Université de Versailles Saint Quentin en Yvelines, Garches, France; Service de Neurologie, Institut de Myologie, APHP, CHU Pitié Salpetrière, Paris, France; Center of Clinical Investigation Paris-Est, Pitié Salpetrière, APHP, ICAN, Sorbonne Université, Paris, France; Service de Physiologie-Exploration fonctionnelles, CHU Raymond Poincaré, APHP, Université de Versailles Saint Quentin en Yvelines, Garches, France; Laboratoire de biochimie et génétique moléculaire, Hôpital Cochin, AP-HP, Université Paris Descartes-Sorbonne Paris Cité, Paris, France; Centre d'Investigation clinique et Innovation technologique CIC 14.29, APHP, CHU Raymond Poincaré, Garches, France.

Cardiac and respiratory function may be impaired in sarcoglycanopathies, a subgroup of muscular dystrophies due to sarcoglycan proteins (α, β, γ, and δ) genes mutations. Management of patients with restrictive respiratory failure mainly relies on home mechanical ventilation (HMV). Little is known about the cardiac effects of prolonged mechanical ventilation in patients with muscular dystrophy and restrictive respiratory insufficiency. We aimed to assess the effects of HMV on cardiac function in sarcoglycanopathies. We retrospectively included 10 genetically proven patients with sarcoglycanopathy followed at the HMV unit of the Raymond Poincare University Hospital (4 patients with α-sarcoglycanopathy and 6 patients with γ-sarcoglycanopathy). We collected cardiorespiratory clinical baseline data and left ventricular ejection fraction (LVEF) at baseline before initiation of HMV and at the end of follow-up. At baseline, median age was 30.5 years (27 to 39) and median pulmonary vital capacity was 27% of the predicted value (21 to 36). Forty percent of the patients had documented sleep apnea. Cardiomyopathy, defined as LVEF <50%, was found in 3 patients with γ-sarcoglycanopathy. After a median follow-up of 3 years (1.0 to 4.5), there was a significant increase in LVEF after initiation of HMV, that is, 62% (48 to 65) versus 53% (45.5 to 56.5) (p = 0.0039). In conclusion, HMV in sarcoglycanopathies is not harmful and may protect left ventricular function by its thoracic physiological effects.
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http://dx.doi.org/10.1016/j.amjcard.2018.04.001DOI Listing
July 2018

The benefits and tolerance of exercise in myasthenia gravis (MGEX): study protocol for a randomised controlled trial.

Trials 2018 Jan 18;19(1):49. Epub 2018 Jan 18.

Intensive Care Unit, Raymond Poincaré Hospital, AP-HP, Garches, France.

Background: Research exploring the effects of physical exercise in auto-immune myasthenia gravis (MG) is scarce. The few existing studies present methodological shortcomings limiting the conclusions and generalisability of results. It is hypothesised that exercise could have positive physical, psychological as well as immunomodulatory effects and may be a beneficial addition to current pharmacological management of this chronic disease. The aim of this study is to evaluate the benefits on perceived quality of life (QOL) and physical fitness of a home-based physical exercise program compared to usual care, for patients with stabilised, generalised auto-immune MG.

Methods: MGEX is a multi-centre, interventional, randomised, single-blind, two-arm parallel group, controlled trial. Forty-two patients will be recruited, aged 18-70 years. Following a three-month observation period, patients will be randomised into a control or experimental group. The experimental group will undertake a 40-min home-based physical exercise program using a rowing machine, three times a week for three months, as an add-on to usual care. The control group will receive usual care with no additional treatment. All patients will be followed up for a further three months. The primary outcome is the mean change in MGQOL-15-F score between three and six months (i.e. pre-intervention and immediately post-intervention periods). The MGQOL-15-F is an MG-specific patient-reported QOL questionnaire. Secondary outcomes include the evaluation of deficits and functional limitations via MG-specific clinical scores (Myasthenia Muscle Score and MG-Activities of Daily Living scale), muscle force and fatigue, respiratory function, free-living physical activity as well as evaluations of anxiety, depression, self-esteem and overall QOL with the WHO-QOL BREF questionnaire. Exercise workload will be assessed as well as multiple safety measures (ECG, biological markers, medication type and dosage and any disease exacerbation or crisis).

Discussion: This is the largest randomised controlled trial to date evaluating the benefits and tolerance of physical exercise in this patient population. The comprehensive evaluations using standardised outcome measures should provide much awaited information for both patients and the scientific community. This study is ongoing.

Trial Registration: ClinicalTrials.gov, NCT02066519 . Registered on 13 January 2014.
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http://dx.doi.org/10.1186/s13063-017-2433-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5774148PMC
January 2018

Left bundle branch block in Duchenne muscular dystrophy: Prevalence, genetic relationship and prognosis.

PLoS One 2018 5;13(1):e0190518. Epub 2018 Jan 5.

Service de Réanimation médicale et unité de ventilation à domicile, CHU Raymond Poincaré, APHP, Université de Versailles Saint Quentin en Yvelines, Garches, France.

Background: Duchenne muscular dystrophy (DMD) is an inherited myogenic disorder due to mutations in the dystrophin gene on chromosome Xp21.1. We designed this study to determine the prevalence of left bundle branch block (LBBB), whether there is a relationship between LBBB and genetic pattern, and to assess predictive factors for acute cardiac events and mortality in adult DMD patients.

Methods: We reviewed the charts of DMD followed at the Home Mechanical Ventilation Unit of the Raymond Poincare University Hospital.

Results: A total of 121 patients, aged from 18 to 41 years have been included in our study. Median vital capacity (VC) was 12% [7; 19.5] of predicted. Almost all patients were on home mechanical ventilation (95%). LBBB was present in 15 patients (13%); among them, 10 disclosed exonic deletions. After a median follow up of 6 years, 21 patients (17%) experienced acute heart failure (AHF), 7 patients (6%) supraventricular arrhythmia, 3 patients (2.4%) ventricular tachycardia, 4 patients (3%) significant electrical disturbances. LBBB was significantly associated with cardiac events (OR = 12.7; 95%CI [3.78-42.7]; p <0.0001) and mortality (OR = 4.4; 95%CI [1.44-13.7]; p 0.009). Presence of residual dystrophin protein was not associated with significant less cardiac events. Age and LVEF were also predictive factors for cardiac events and mortality.

Conclusion: LBBB is relatively frequent in DMD and is a major predictive factor for cardiac events and mortality. Presence of residual dystrophin protein was not associated with a lower incidence of cardiac events.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0190518PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5755816PMC
February 2018

Diaphragm: Pathophysiology and Ultrasound Imaging in Neuromuscular Disorders.

J Neuromuscul Dis 2018;5(1):1-10

APHP, Raymond Poincare University Hospital, Garches, France.

Respiratory muscles are classically involved in neuromuscular disorders, leading to a restrictive respiratory pattern. The diaphragm is the main respiratory muscle involved during inspiration. Ultrasound imaging is a noninvasive, radiation-free, accurate and safe technique allowing assessment of diaphragm anatomy and function. The authors review the pathophysiology of diaphragm in neuromuscular disorders, the methodology and indications of diaphragm ultrasound imaging as well as possible pitfalls in the interpretation of results.
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http://dx.doi.org/10.3233/JND-170276DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5836400PMC
June 2018

Clinical profiles and prognosis of acute heart failure in adult patients with dystrophinopathies on home mechanical ventilation.

ESC Heart Fail 2017 11 18;4(4):527-534. Epub 2017 May 18.

Service de Réanimation médicale et unité de ventilation à domicile, centre de référence neuromusculaire GNMH, CHU Raymond Poincaré, APHP, Université de Versailles Saint Quentin en Yvelines, Garches, France.

Aims: Duchenne muscular dystrophy (DMD) is characterized by respiratory and heart involvements. In the context of permanently wheelchair bound and on mechanical ventilation (MV) patients, the clinical presentation of acute heart failure (AHF) syndrome may be atypical. We sought to describe clinical and genetic profiles and to determine prognosis of DMD and Becker muscular dystrophy (BMD) patients on home MV (HMV), hospitalized for AHF.

Methods And Results: We included genetically proven DMD and BMD patients on HMV admitted for AHF. A total of 13 patients (11 DMD and 2 BMD) fulfilled the inclusion criteria. Median age was 34.0 [interquartile range (IQR) 26.0; 40.0] years. Median pulmonary vital capacity was 9.0% (6.0; 15.0) of predicted value. Long-term invasive ventilation was performed in 69% of patients. All the 11 DMD patients carried out-of-frame DMD gene mutations. At admission, dyspnoea was present in 46%, lipothymia in 23%, and abdominal discomfort in 38.4% of patients. A total of 53.8% of patients showed anasarca. Cardiogenic shock presentation was found in six patients (46%). Ejection fraction was severely altered [median 25% (IQR 20; 30)]. Intra-hospital mortality rate was 30%, reaching 53.8 % after 1 year. Previous episodes of AHF ≥ 2 were associated with intra-hospital mortality (P = 0.025). In patients with cardiogenic shock, intra-hospital mortality rate was 66.6%, reaching 83.3% after 1 year.

Conclusions: In adult DMD and BMD patients with severe ejection fraction alteration and on HMV, admitted for AHF, right cardiac signs are frequent. The intra-hospital and 1 year mortality rate was high and was associated with previous episodes of AHF ≥ 2.
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http://dx.doi.org/10.1002/ehf2.12165DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5695197PMC
November 2017

Cardiac implantable electronic devices in tracheotomized muscular dystrophy patients: Safety and risks.

Int J Cardiol 2016 Nov 6;222:975-977. Epub 2016 Aug 6.

Intensive Care Unit, GNHM Neuromuscular Center, Raymond Poincare Hospital, Garches, France.

Background/objectives: Muscular dystrophies are genetic muscle disorders, in which heart involvement and chronic respiratory impairment affect survival. Cardiac conduction disturbances require implantable cardiac pacemaker. Implantable defibrillators may also be necessary to prevent cardiac sudden death. The safety and risk of cardiac electronic devices' implantation are not known in patients with muscular dystrophy. We aimed to assess the risks related to cardiac implantable electronic devices (CIED) in muscular dystrophy patients ventilated by tracheostomy.

Methods: We reviewed all medical charts of neuromuscular patients and identified all CIED implantations of pacemakers (PM) or defibrillators (ICD) in patients ventilated using tracheostomy.

Results: Twelve device implantations were included, performed in 9 patients (5 DMD, 1 Becker muscular dystrophy and 3 DM1). Mean age was 39.9years±13.0. All patients were wheel-chair bound and tracheotomized. Six pacemakers (PM) and 6 cardiac resynchronization (CRT) devices, including 2 defibrillators (CRT-D) were implanted. Following device implantation, two patients had a pneumothorax and one died from severe heart failure after an unsuccessful CRT implant attempt. Follow-up lasted up to 8years (mean 2.6±2.9years), during which one patient presented a PM pocket infection, requiring PM explantation and epicardial reimplantation.

Conclusion: We found a high prevalence of early complications (16.6% pneumothorax) after CIED implantation and an acceptable long-term infectious risk (8.3%). These results highlight the feasibility of CIED implantation in tracheotomized patients with muscular dystrophies and the need for a particular caution in the management of these patients during invasive procedures. ClinicalTrials.gov (identifier: NCT02501083).
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http://dx.doi.org/10.1016/j.ijcard.2016.08.040DOI Listing
November 2016

Fatal tramadol-induced multiple organ failure.

Therapie 2016 Sep 9;71(4):435-7. Epub 2016 Feb 9.

Service de réanimation médicale, hôpital Raymond-Poincaré, hôpitaux universitaires Paris Île-de-France Ouest, AP-HP, 92380 Garches, France.

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http://dx.doi.org/10.1016/j.therap.2016.02.017DOI Listing
September 2016

Natural History of Cardiac and Respiratory Involvement, Prognosis and Predictive Factors for Long-Term Survival in Adult Patients with Limb Girdle Muscular Dystrophies Type 2C and 2D.

PLoS One 2016 27;11(4):e0153095. Epub 2016 Apr 27.

Service de Réanimation médicale et unité de ventilation à domicile, centre de référence neuromusculaire GNHM, CHU Raymond Poincaré, APHP, Université de Versailles Saint Quentin en Yvelines, Garches, France.

Background: Type 2C and 2D limb girdle muscular dystrophies (LGMD) are a group of autosomal recessive limb girdle muscular dystrophies manifested by proximal myopathy, impaired respiratory muscle function and cardiomyopathy. The correlation and the prognostic impact of respiratory and heart impairment are poorly described. We aimed to describe the long-term cardiac and respiratory follow-up of these patients and to determine predictive factors of cardio-respiratory events and mortality in LGMD 2C and 2D.

Methods: We reviewed the charts of 34 LGMD patients, followed from 2005 to 2015, to obtain echocardiographic, respiratory function and sleep recording data. We considered respiratory events (acute respiratory failure, pulmonary sepsis, atelectasis or pneumothorax), cardiac events (acute heart failure, significant cardiac arrhythmia or conduction block, ischemic stroke) and mortality as outcomes of interest for the present analysis.

Results: A total of 21 patients had type 2C LGMD and 13 patients had type 2D. Median age was 30 years [IQR 24-38]. At baseline, median pulmonary vital capacity (VC) was 31% of predicted value [20-40]. Median maximal inspiratory pressure (MIP) was 31 cmH2O [IQR 20.25-39.75]. Median maximal expiratory pressure (MEP) was 30 cm H2O [20-36]. Median left ventricular ejection fraction (LVEF) was 55% [45-64] with 38% of patients with LVEF <50%. Over a median follow-up of 6 years, we observed 38% respiratory events, 14% cardiac events and 20% mortality. Among baseline characteristics, LVEF and left ventricular end diastolic diameter (LVEDD) were associated with mortality, whilst respiratory parameters (VC, MIP, MEP) and the need for home mechanical ventilation (HMV) were associated with respiratory events.

Conclusion: In our cohort of severely respiratory impaired type 2C and 2D LGMD, respiratory morbidity was high. Cardiac dysfunction was frequent in particular in LGMD 2C and had an impact on long-term mortality.

Trial Registration: ClinicalTrials.gov NCT02501083.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0153095PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4847860PMC
February 2017

Pseudomonas aeruginosa nosocomial pneumonia: impact of pneumonia classification.

Infect Control Hosp Epidemiol 2015 Oct 20;36(10):1190-7. Epub 2015 Jul 20.

14Cubist Pharmaceuticals,Lexington,Massachusetts.

Objective: To describe and compare the mortality associated with nosocomial pneumonia due to Pseudomonas aeruginosa (Pa-NP) according to pneumonia classification (community-onset pneumonia [COP], hospital-acquired pneumonia [(HAP], and ventilator-associated pneumonia [VAP]).

Design: We conducted a retrospective cohort study of adults with Pa-NP. We compared mortality for Pa-NP among patients with COP, HAP, and VAP and used logistic regression to identify risk factors for hospital mortality and inappropriate initial antibiotic therapy (IIAT).

Setting: Twelve acute care hospitals in 5 countries (United States, 3; France, 2; Germany, 2; Italy, 2; and Spain, 3).

Patients/participants: A total of 742 patients with Pa-NP.

Results: Hospital mortality was greater for those with VAP (41.9%) and HAP (40.1%) compared with COP (24.5%) (P<.001). In multivariate analyses, independent predictors of hospital mortality differed by pneumonia classification (COP: need for mechanical ventilation and intensive care; HAP: multidrug-resistant isolate; VAP: IIAT, increasing age, increasing Charlson comorbidity score, bacteremia, and use of vasopressors). Presence of multidrug resistance was identified as an independent predictor of IIAT for patients with COP and HAP, whereas recent antibiotic administration was protective in patients with VAP.

Conclusions: Among patients with Pa-NP, pneumonia classification identified patients with different risks for hospital mortality. Specific risk factors for hospital mortality also differed by pneumonia classification and multidrug resistance appeared to be an important risk factor for IIAT. These findings suggest that pneumonia classification for P. aeruginosa identifies patients with different mortality risks and specific risk factors for outcome and IIAT.
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http://dx.doi.org/10.1017/ice.2015.167DOI Listing
October 2015

An international multicenter retrospective study of Pseudomonas aeruginosa nosocomial pneumonia: impact of multidrug resistance.

Crit Care 2015 May 6;19:219. Epub 2015 May 6.

Cubist Pharmaceuticals, Inc., 65 Hayden Avenue, Lexington, MA, 02421, USA.

Introduction: Pseudomonas aeruginosa nosocomial pneumonia (Pa-NP) is associated with considerable morbidity, prolonged hospitalization, increased costs, and mortality.

Methods: We conducted a retrospective cohort study of adult patients with Pa-NP to determine 1) risk factors for multidrug-resistant (MDR) strains and 2) whether MDR increases the risk for hospital death. Twelve hospitals in 5 countries (United States, n = 3; France, n = 2; Germany, n = 2; Italy, n = 2; and Spain, n = 3) participated. We compared characteristics of patients who had MDR strains to those who did not and derived regression models to identify predictors of MDR and hospital mortality.

Results: Of 740 patients with Pa-NP, 226 patients (30.5%) were infected with MDR strains. In multivariable analyses, independent predictors of multidrug-resistance included decreasing age (adjusted odds ratio [AOR] 0.91, 95% confidence interval [CI] 0.96-0.98), diabetes mellitus (AOR 1.90, 95% CI 1.21-3.00) and ICU admission (AOR 1.73, 95% CI 1.06-2.81). Multidrug-resistance, heart failure, increasing age, mechanical ventilation, and bacteremia were independently associated with in-hospital mortality in the Cox Proportional Hazards Model analysis.

Conclusions: Among patients with Pa-NP the presence of infection with a MDR strain is associated with increased in-hospital mortality. Identification of patients at risk of MDR Pa-NP could facilitate appropriate empiric antibiotic decisions that in turn could lead to improved hospital survival.
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http://dx.doi.org/10.1186/s13054-015-0926-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4446947PMC
May 2015

Induced hypothermia in severe bacterial meningitis: a randomized clinical trial.

JAMA 2013 Nov;310(20):2174-83

Réanimation Médicale et Infectieuse, Assistance Publique-Hôpitaux de Paris, Groupe Hospitalier Bichat-Claude Bernard, Université Paris Diderot, Sorbonne Paris Cité, Paris, France.

Importance: Despite advances in care, mortality and morbidity remain high in adults with acute bacterial meningitis, particularly when due to Streptococcus pneumoniae. Induced hypothermia is beneficial in other conditions with global cerebral hypoxia.

Objective: To test the hypothesis that induced hypothermia improves outcome in patients with severe bacterial meningitis.

Design, Setting, And Patients: An open-label, multicenter, randomized clinical trial in 49 intensive care units in France, February 2009-November 2011. In total, 130 patients were assessed for eligibility and 98 comatose adults (Glasgow Coma Scale [GCS] score of ≤8 for <12 hours) with community-acquired bacterial meningitis were randomized.

Interventions: Hypothermia group received a loading dose of 4°C cold saline and were cooled to 32°C to 34°C for 48 hours. The rewarming phase was passive. Controls received standard care.

Main Outcomes And Measures: Primary outcome measure was the Glasgow Outcome Scale score at 3 months (a score of 5 [favorable outcome] vs a score of 1-4 [unfavorable outcome]). All patients received appropriate antimicrobial therapy and vital support. Analyses were performed on an intention-to-treat basis. The data and safety monitoring board (DSMB) reviewed severe adverse events and mortality rate every 50 enrolled patients.

Results: After inclusion of 98 comatose patients, the trial was stopped early at the request of the DSMB because of concerns over excess mortality in the hypothermia group (25 of 49 patients [51%]) vs the control group (15 of 49 patients [31%]; relative risk [RR], 1.99; 95% CI, 1.05-3.77; P = .04). Pneumococcal meningitis was diagnosed in 77% of patients. Mean (SD) temperatures achieved 24 hours after randomization were 33.3°C (0.9°C) and 37.0°C (0.9°C) in the hypothermia and control group, respectively. At 3 months, 86% in the hypothermia group compared with 74% of controls had an unfavorable outcome (RR, 2.17; 95% CI, 0.78-6.01; P = .13). After adjustment for age, score on GCS at inclusion, and the presence of septic shock at inclusion, mortality remained higher, although not significantly, in the hypothermia group (hazard ratio, 1.76; 95% CI, 0.89-3.45; P = .10). Subgroup analysis on patients with pneumococcal meningitis showed similar results. Post hoc analysis showed a low probability to reach statistically significant difference in favor of hypothermia at the end of the 3 planned sequential analyses (probability to conclude in favor of futility, 0.977).

Conclusions And Relevance: Moderate hypothermia did not improve outcome in patients with severe bacterial meningitis and may even be harmful. Careful evaluation of safety issues in future trials on hypothermia are needed and may have important implications in patients presenting with septic shock or stroke.

Trial Registration: clinicaltrials.gov Identifier: NCT00774631.
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http://dx.doi.org/10.1001/jama.2013.280506DOI Listing
November 2013

StO₂ guided early resuscitation in subjects with severe sepsis or septic shock: a pilot randomised trial.

J Clin Monit Comput 2013 Jun 5;27(3):215-21. Epub 2013 Feb 5.

General Intensive Care Unit, Raymond Poincaré Hospital (AP-HP), 104 boulevard Raymond Poincaré, 92380 Garches, France.

The scientific community has agreed upon developing accurate monitoring of tissue perfusion and oxygenation to improve the management of subjects with sepsis. This pilot study aimed to investigate the feasibility of targeting tissue oxygen saturation (StO₂) in addition to the currently recommended resuscitation goals, central venous pressure, mean arterial pressure and central venous oxygen saturation, in patients with severe sepsis or septic shock. A pilot, single-centre, randomised, non-blinded trial recruited 30 subjects with severe sepsis upon intensive care unit admission at an academic medical centre in France. Subjects were randomly assigned to a 6 h resuscitation strategy following the Surviving Sepsis Campaign guidelines with (experimental) or without (control) StO₂. StO₂ was measured over several muscles (masseter, deltoid and pectoral or thenar muscles), and a StO₂ above 80 % over at least 2 muscles was the therapeutic goal. The primary outcome was evaluated as follows: 7-day mortality or worsening of SOFA score between day 7 and study onset, i.e., DSOFA > 0). Thirty subjects were included in the study over a period of 40 weeks. Fifteen subjects were included in each group. Monitoring of StO₂ over three areas was performed in the experimental group. However, measures over the pectoral muscle provided poor results. At study day 7, there were 5/15 (33.3 %) subjects who died or had a DSOFA > 0 in the experimental arm and 4/15 (26.6 %) who died or had a DSOFA > 0 in the control arm (p = 1.00). This pilot study was the first randomised controlled trial using an algorithm derived from the SSC recommendations, which included StO₂ as a treatment goal. However, the protocol showed no clear trend for or against targeting StO₂.
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http://dx.doi.org/10.1007/s10877-013-9432-yDOI Listing
June 2013

Artesunate for severe acute Plasmodium falciparum infection in a patient with myasthenia gravis.

Am J Trop Med Hyg 2012 Sep 23;87(3):435-6. Epub 2012 Jul 23.

Infectious and Tropical Diseases Unit, Parasitology and Mycology Unit, and French National Center for Metropolitan Malaria, Pitié-Salpêtrière Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France.

We report a case of severe malaria in a patient with underlying myasthenia gravis who was successfully treated with artesunate. The outcome was favorable. Artesunate seems to be a good option for patients with underlying myasthenia gravis disease because they benefit from a better toxicity profile than quinine.
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http://dx.doi.org/10.4269/ajtmh.2012.12-0114DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3435344PMC
September 2012

Masseter tissue oxygen saturation predicts normal central venous oxygen saturation during early goal-directed therapy and predicts mortality in patients with severe sepsis.

Crit Care Med 2012 Feb;40(2):435-40

General Intensive Care Unit, Raymond Poincaré Hospital (AP-HP), Garches, France.

Objective: This study aimed to investigate, in patients with severe sepsis, the correlation between central venous oxygen saturation and tissue oxygen saturation at different levels.

Design: Prospective observational study.

Setting: General intensive care unit at an academic medical center in France.

Patients: Thirty-eight patients with underresuscitated severe sepsis and septic shock on intensive care unit admission.

Interventions: None.

Measurements And Main Results: During early resuscitation according to the 6-hr bundles of the Surviving Sepsis Campaign guidelines, tissue oxygen saturation was recorded every other hour at the level of the thenar, masseter, and deltoid muscles along with central hemodynamics, arterial lactate concentrations, and central venous oxygen saturation. Over the 6-hr resuscitation period, thenar tissue oxygen saturation was consistently higher than masseter tissue oxygen saturation (p = .04) and deltoid tissue oxygen saturation (p = .002), and masseter tissue oxygen saturation was consistently higher than deltoid tissue oxygen saturation (p = .04). Receiver operating characteristic curves analyses showed that masseter tissue oxygen saturation was better predictor of central venous oxygen saturation >70% than thenar tissue oxygen saturation (area under the curve, 0.80; 95% confidence interval 0.71-0.89 vs. 0.67; 95% confidence interval 0.56-0.77; p = .02). The crude 28-day mortality was 36.8%. Receiver operating characteristic curve analysis showed that masseter tissue oxygen saturation (area under the curve 0.87; 0.75-0.98) and deltoid tissue oxygen saturation (area under the curve 0.88; 0.77-0.98) but not thenar tissue oxygen saturation (area under the curve 0.66; 0.46-0.86) or central venous oxygen saturation (area under the curve 0.56; 0.38-0.80) were strong predictors of 28-day mortality.

Conclusions: This study suggested that in the early 6-hr resuscitation period, masseter tissue oxygen saturation accurately identified patients with severe sepsis and central venous oxygen saturation >70%. Both masseter tissue oxygen saturation and deltoid tissue oxygen saturation but not central venous oxygen saturation or thenar tissue oxygen saturation are strong predictors of 28-day mortality.
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http://dx.doi.org/10.1097/CCM.0b013e3182329645DOI Listing
February 2012

Brainstem responses can predict death and delirium in sedated patients in intensive care unit.

Crit Care Med 2011 Aug;39(8):1960-7

General Intensive Care Unit, University of Versailles Saint-Quentin en Yvelines, Garches, France.

Objectives: In critically ill patients, the assessment of neurologic function can be difficult because of the use of sedative agents. It is not known whether neurologic signs observed under sedation can predict short-term outcomes. The objective of this study was to assess whether abnormal brainstem responses within the first 24 hrs of sedation are associated with mortality and altered mental status postsedation.

Design: Observational prospective study including an initial single-center and a subsequent multicenter study to develop and then validate the prognostic models.

Setting: Three mixed and two medical intensive care units.

Patients: Mechanically ventilated intensive care unit patients sedated with midazolam (± sufentanyl).

Interventions: Neurologic examination including the Glasgow Coma Scale, the Assessment to Intensive Care Environment score, cranial nerve examination, response to noxious stimuli, and the cough reflex was performed.

Measurements And Main Results: Seventy-two patients were included in the initial group and 72 in a subsequent validation study. Neurologic responses were independent of sedative dose. Twenty-two patients in the development cohort and 21 (29%) in the validation group died within 28 days of inclusion. Adjusted for Simplified Acute Physiology Score II score, absent cough reflex was independently associated with 28-day mortality in the development (adjusted odds ratio [OR], 7.80; 95% confidence interval [CI], 2.00-30.4; p = .003) and validation groups (adjusted OR, 5.44; 95% CI, 1.35-22.0; p = .017). Absent oculocephalic response, adjusted for Simplified Acute Physiology Score II score, was independently associated with altered mental status after the withdrawal of sedation in the development (adjusted OR, 4.54; 95% CI, 1.34-15.4; p = .015) and validation groups (adjusted OR, 6.10; 95% CI, 1.18-25.5; p = .012).

Conclusions: Assessment of brainstem responses is feasible in sedated critically ill patients and loss of selected responses is predictive of mortality and altered mental status.
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http://dx.doi.org/10.1097/CCM.0b013e31821b843bDOI Listing
August 2011

A lethal case of meningitis due to Lactobacillus rhamnosus as a late complication of anterior cervical spine surgery.

J Infect 2011 Apr 23;62(4):309-10. Epub 2011 Feb 23.

Service de Réanimation, Assistance Publique, Hôpitaux de Paris, Raymond Poincaré Hospital, Garches, France.

We reported a lethal case of meningitis due to Lactobacillus rhamnosus as a late complication of anterior cervical spine surgery in an 80 years old lady. The anterior plate graft was responsible for a fistula between the oesophagus and meningeal space. This case illustrated the difficulty of early diagnosis of such infrequent complication and suggested that dysphagia following anterior cervical spine surgery should prompt cervical imaging.
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http://dx.doi.org/10.1016/j.jinf.2011.02.006DOI Listing
April 2011

New onset of myasthenia gravis after treatment of systemic sclerosis by autologous hematopoietic stem cell transplantation: sustained autoimmunity or inadequate reset of tolerance?

Hum Immunol 2010 Apr 4;71(4):363-5. Epub 2010 Feb 4.

Department of Internal Medicine and Rheumatology, La Meynard Hospital, Fort de France, France.

Autologous hematopoietic stem-cell transplantation (HSCT) showed promising results for the treatment of primary severe autoimmune diseases (ADs). In this context, development of secondary AD after HSCT has exceptionally been observed, further questioning the roles of patient propensity for AD and of the HSCT procedure. Herein, we report new onset of myasthenia gravis 3 years after successful HSCT in a patient with severe systemic sclerosis, while in complete remission from her first AD. The de novo occurrence of secondary AD (myasthenia gravis) after HSCT was accompanied by the appearance of clonal T-cell expansions measured by the "immunoscope" technique in the context of an ongoing T-cell immune reconstitution. Secondary ADs are increasingly recognized after HSCT for AD. In our case, development of myasthenia followed clonal T-cell expansion. Detailed T-cell repertoire analysis may shed light on autoreactivity mechanisms after HSCT and may help to identify patients at risk.
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http://dx.doi.org/10.1016/j.humimm.2010.01.013DOI Listing
April 2010

Noninvasive ventilation as an alternative to endotracheal intubation during tracheotomy in advanced neuromuscular disease.

Respir Care 2007 Dec;52(12):1728-33

Service de Réanimation Médicale, Hôpital Raymond Poincaré, 104 Boulevard Raymond Poincaré, 92380 Garches, France.

Objective: To compare conventional tracheotomy with endotracheal intubation to tracheotomy with noninvasive positive-pressure ventilation (NPPV) in advanced neuromuscular disease.

Methods: This was a retrospective study of a historical cohort of patients tracheotomized while sedated and intubated versus patients tracheotomized under NPPV and local anesthesia. We recorded previous intubation difficulties, complications (eg, aspiration pneumonia), and hospital stay.

Results: Conventional tracheotomy was performed in 7 patients. We performed tracheotomy during NPPV with local anesthesia in 13 patients. All but 3 patients had risk factors for difficult intubation. Hospital stay was 23.3 +/- 10.3 d in the conventional group and 25.3 +/- 12.9 d in the NPPV group (p = 0.87). The number of pneumonias was higher in the conventional-tracheotomy group (4 vs 1, p = 0.03).

Conclusion: In neuromuscular patients, performing tracheotomy with NPPV and local anesthesia may help avoid endotracheal intubation and reduce morbidity.
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December 2007

Clinical and electrophysiological predictors of respiratory failure in Guillain-Barré syndrome: a prospective study.

Lancet Neurol 2006 Dec;5(12):1021-8

Functional Testing Department, Raymond Poincaré Teaching Hospital, Garches, France.

Background: Respiratory failure is the most serious short-term complication of Guillain-Barré syndrome and can require invasive mechanical ventilation in 20-30% of patients. We sought to identify clinical and electrophysiological predictors of respiratory failure in the disease.

Methods: We prospectively assessed electrophysiological data and clinical factors, including identified predictors of delay between disease onset and admission, inability to lift head, and vital capacity, in patients admitted with Guillain-Barré syndrome. We related these factors to subsequent need for ventilatory support. Neurophysiological findings were classified as demyelinating, axonal, equivocal, unexcitable, or normal. Predictive values of clinical and electrophysiological data were tested using classification trees to build up a predictive model. This model was initially built up in a two-third (fitting set) then validated in a one-third (validation set) of the total sample. The fitting and validation sets were randomly selected. We also assessed the predictive value of this model for disability at 6 months.

Findings: From 1998, to 2006, 154 patients with Guillain-Barré syndrome were included in the study and 34 (22%) were subsequently ventilated. Demyelinating Guillain-Barré syndrome was more common in patients who went on to be ventilated than in those who were not (85%vs 51%, p=0.0003). Vital capacity and the proximal/distal compound muscular amplitude potential (p/dCMAP) ratio of the common peroneal nerve were retained in the tree model, with a probability of needing ventilation of less than 2.5% in patients with a ratio of greater than 55.6% and a vital capacity more than 81% of predicted. A p/dCMAP ratio of the peroneal nerve less than 55.6% and age older than 40 years were retained as independent predictors of disability at 6 months.

Interpretation: Neurophysiological testing is helpful for assessing risk of respiratory failure, which is highest in patients with evidence of demyelination and very low in those without both 55.6% conduction block of the common peroneal nerve and a 20% reduction in vital capacity.
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http://dx.doi.org/10.1016/S1474-4422(06)70603-2DOI Listing
December 2006

Prognosis and risk factors of early onset pneumonia in ventilated patients with Guillain-Barré syndrome.

Intensive Care Med 2006 Dec 21;32(12):1962-9. Epub 2006 Sep 21.

Medical Intensive Care Unit, Raymond Poincaré Teaching Hospital, 104 Boulevard Raymond Poincaré, Garches, France.

Objective: Invasive mechanical ventilation is required in 30% of patients with Guillain-Barré syndrome (GBS) and is associated with pneumonia and increased mortality. Our objective was to determine the incidence, characteristics, outcomes, and risk factors of pneumonia in GBS patients receiving mechanical ventilation.

Design And Setting: Study of a prospective database in an intensive care unit of a university hospital.

Patients: The study included 81 patients who required intubation for GBS. Neurological findings, vital capacity, and signs of respiratory distress were recorded at admission and at intubation. A score predicting the risk of intubation (0-4) was calculated for each patient. Pneumonia was diagnosed based on predefined criteria and retrospectively confirmed by two observers. Early-onset pneumonia was defined as pneumonia diagnosed within 5 days after intubation.

Measurements And Results: Mean vital capacity was 57 +/- 22% of predicted at admission and 33 +/- 11% at intubation. Pneumonia developed in 63 patients (78%), including 48 with early-onset pneumonia. Bacteria were consistent with aspiration. Of the 63 patients with pneumonia 11 (18%) had septic shock, 6 (10%) had acute respiratory distress syndrome, and 9 (14%) died. In the univariate analysis milder weakness, a lower risk of intubation (score < 2), and time from admission to intubation longer than 2 days were associated with early-onset pneumonia. Time from admission to intubation was the only independent predictor in the multivariate logistic regression model.

Conclusions: Early-onset pneumonia is a common and severe complication that is related to aspiration in patients with GBS. Delaying intubation may increase the risk of early-onset pneumonia.
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http://dx.doi.org/10.1007/s00134-006-0332-1DOI Listing
December 2006

Treatment of myasthenia gravis exacerbation with intravenous immunoglobulin: a randomized double-blind clinical trial.

Arch Neurol 2005 Nov;62(11):1689-93

Medical Intensive Care Unit, Raymond Poincaré Teaching Hospital, Assistance publique-Hôpitaux de Paris, Garches, France.

Background: The optimal dose of intravenous immunoglobulin (IVIG) in acute exacerbation of myasthenia gravis remains unknown. Increasing the treatment duration might provide added efficacy.

Objective: To determine the optimal dose of IVIG for treating myasthenia gravis exacerbation.

Design: Randomized double-blind placebo-controlled multicenter trial designed to demonstrate superiority of the 2 g/kg dose over the 1 g/kg dose of IVIG, conducted between November 13, 1996, and October 26, 2002.

Participants: One hundred seventy-three patients aged 15 to 85 years with acute exacerbation of myasthenia gravis.

Intervention: Participants were randomly assigned to receive 1 g/kg of IVIG on day 1 and placebo on day 2 (group 1) vs 1 g/kg of IVIG on 2 consecutive days (group 2).

Main Outcome Measure: Improvement in the myasthenic muscular score after 2 weeks.

Results: The mean improvements in the myasthenic muscular scores after 2 weeks were 15.49 points (95% confidence interval, 12.09-18.90 points) in group 1 and 19.33 points (95% confidence interval, 15.82-22.85 points) in group 2. However, the difference between the 2 groups was not significant (effect size, 3.84 [95% confidence interval, -1.03 to 8.71]; P = .12).

Conclusion: This trial found no significant superiority of 2 g/kg over 1 g/kg of IVIG in the treatment of myasthenia gravis exacerbation.
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http://dx.doi.org/10.1001/archneur.62.11.1689DOI Listing
November 2005