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Introduction: Non-small cell lung cancer (NSCLC) is often associated with compromised lung function. Real-world data on the impact of surgical approach in NSCLC patients with compromised lung function are still lacking. The objective of this study is to assess the potential impact of minimally invasive surgery (MIS) on 90-day post-operative mortality after anatomic lung resection in high-risk operable NSCLC patients., Methods: We conducted a retrospective multicentre study including all patients who underwent anatomic lung resection between January 2010 and October 2021 and registered in the Epithor database. High-risk patients were defined as those with a forced expiratory volume in 1 s (FEV 1 ) or diffusing capacity of the lung for carbon monoxide ( D LCO ) value below 50%. Co-primary end-points were the impact of risk status on 90-day mortality and the impact of MIS on 90-day mortality in high-risk patients., Results: Of the 46 909 patients who met the inclusion criteria, 42 214 patients (90%) with both preoperative FEV 1 and D LCO above 50% were included in the low-risk group, and 4695 patients (10%) with preoperative FEV 1 and/or preoperative D LCO below 50% were included in the high-risk group. The 90-day mortality rate was significantly higher in the high-risk group compared to the low-risk group (280 (5.96%) versus 1301 (3.18%); p<0.0001). In high-risk patients, MIS was associated with lower 90-day mortality compared to open surgery in univariate analysis (OR=0.04 (0.02-0.05), p<0.001) and in multivariable analysis after propensity score matching (OR=0.46 (0.30-0.69), p<0.001). High-risk patients operated through MIS had a similar 90-day mortality rate compared to low-risk patients in general (3.10% versus 3.18% respectively)., Conclusion: By examining the impact of surgical approaches on 90-day mortality using a nationwide database, we found that either preoperative FEV 1 or D LCO below 50% is associated with higher 90-day mortality, which can be reduced by using minimally invasive surgical approaches. High-risk patients operated through MIS have a similar 90-day mortality rate as low-risk patients., Competing Interests: Conflict of interest statement: The statistical analysis in this work was financially supported by the Marc Laskar grant. J-M. Baste and P-B. Pagès receive consulting fees from Medtronic and from Intuitive Surgical. P-A. Thomas is a consultant for Ethicon Endosurgery, AstraZeneca and Europrisme. A. Seguin-Givelet is a speaker for AstraZeneca and Medtronic. H. Etienne, J. Iquille, P.E. Falcoz, L. Brouchet, J-P. Berthet, F. Le Pimpec Barthes, J. Jougon, M. Filaire, V. Anne, S. Renaud, T. D'Annoville, J.P. Meunier, C. Jayle, C. Dromer, A. Legras, P. Rinieri, S. Jaillard, V. Margot, M. Dahan and P. Mordant have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright ©The authors 2024.)

Background: Clinical exam is the goldstandard for surgical indication. ENMG and conventional MRI are insufficient to understand the highly variable clinical presentation of brachial plexus (BP) lesions. DTI is based on motion of water molecules and can explore nerve function., Purpose: This pilot study of healthy subjects aimed to develop RESOLVE sequence for BP exploration using diffusion MRI. The main objective was to provide complete precise information from DTI cartography associated with anatomical data., Methods: Six healthy volunteers were scanned using 3T PRISMA scanner with anatomic 3D STIR SPACE and RESOLVE diffusion sequences. Diffusion parametric maps of fractional anisotropy (FA) were extracted from RESOLVE acquisitions. A reproducible method for roots volumes and angles measurements was created using 3DSlicer. ROI were segmented on Mean B0 sequences. FA measurements were obtained with ROI on Mean B0 sequences., Results: RESOLVE sequence was adapted to the BP. Mean FA was 0.30. Angles measurements on 3D STIR SPACE sequences showed increasing values from proximal to distal roots with an 0.6 ICC. Volume measurements on anatomic sequences varied widely from one root to another but did not show any significant difference on laterality., Conclusions: A new and reproducible method for BP exploration was developed, using MRI RESOLVE DTI sequences. Complete mapping was obtained but a low resolution of track density imaging did not allow to exploit distal nerves. Deterministic tractography principal limit was the lack of resolution. Extraction of diffusion, volumetric and angular parameters of the plexus roots, and scripts creation for image processing was adapted to the healthy BP., (© 2023. The Author(s), under exclusive licence to Springer-Verlag France SAS, part of Springer Nature.)

Competing Interests: Declaration of Competing Interest None.

Background: The Treatment of Brain Arteriovenous Malformations Study (TOBAS) is an all-inclusive pragmatic study comprising 2 randomized clinical trials (RCTs). Patients excluded from the RCTs are followed in parallel treatment and observation registries, allowing a comparison between RCT and registry patients., Methods: The first randomized clinical trial (RCT-1) offers 1:1 randomized allocation of intervention versus conservative management for patients with arteriovenous malformation (AVM). The second randomized clinical trial (RCT-2) allocates 1:1 pre-embolization or no pre-embolization to surgery or radiosurgery patients judged treatable with or without embolization. Characteristics of RCT patients are reported and compared to registry patients., Results: From June 2014 to May 2021, 1010 patients with AVM were recruited; 498 patients were observed and 373 were included in the treatment registries. Randomized allocation in RCT-1 was applied to 139 (26%) of the 512 patients (including 127 of 222 [57%] with unruptured AVMs) considered for curative treatment. RCT-1 AVM patients differed (in rupture status, Spetzler-Martin grade and baseline modified Rankin Score) from those in the observation or treatment registries (P < 0.001). Most patients had small (<3 cm; 71%) low-grade (Spetzler-Martin I-II; 64%) unruptured (91%) AVMs. The allocated management was conservative (n = 71) or curative (n = 68), using surgery (n = 39), embolization (n = 16), or stereotactic radiosurgery (n = 13). Pre-embolization was considered for 179/309 (58%) patients allocated/assigned to surgery or stereotactic radiosurgery; 87/179 (49%) were included in RCT-2. RCT-2 patient AVMs differed in size, eloquence and grade from patients of the pre-embolization registry (P < 0.01). Most had small (<3 cm in 82%) low-grade (83%) AVMs in non-eloquent brain (64%)., Conclusions: Patients included in the RCTs differ significantly from registry patients. Meaningful results can be obtained if multiple centers actively participate in the TOBAS RCTs., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Only three laryngeal transplants have been described in the literature to date, and none of the techniques has enabled a completely satisfactory functional result to be obtained. This article presents a new model of laryngeal transplantation, with quality of revascularisation of the transplant being the principal objective and optimisation of the various steps of the procedure, with the integration of a new reinnervation technique as a secondary objective. We present a preclinical animal study. Three pig larynges removed in vivo underwent allotransplantation according to the same protocol. The quality of the revascularisation was examined immediately after the surgery as well as by endoscopy for one animal on the fourth day after the operation. The mean time of cold ischaemia was 3 h 15 min. The anaesthetic tolerance of the pigs was excellent. Revascularisation was achieved and judged to be excellent for the three transplants immediately after the operation and the endoscopy performed for one pig on the fourth day after the operation confirmed this result. The anatomical similarities also enabled the application and integration of an innovative technique of laryngeal reinnervation into the various phases of the operation. We describe a reliable and reproducible animal model for laryngeal transplantation. Its application in humans can be envisaged.

Background: Transcatheter closure of a symptomatic prosthetic paravalvular leak (PVL) is feasible, but there is presently no conclusive evidence to show consistent efficacy. We aimed to identify predictors of clinical success after transcatheter PVL closure., Methods: Consecutive patients referred to 24 European centers for transcatheter PVL closure in 2017 to 2019 were included in a prospective registry ( Fermeture de Fuite ParaProthétique , FFPP). Clinical success was absence of any of the following within 1 month: re-admission for heart failure, blood transfusion, open-heart valvular surgery, and death., Results: We included 216 symptomatic patients, who underwent 238 percutaneous PVL closure procedures on the mitral (64.3%), aortic (34.0%), or tricuspid (1.7%) valve. Symptoms were heart failure, hemolytic anemia, or both in 48.9%, 7.8%, and 43.3% of patients, respectively. One, 2, and 3 leaks were treated during the same procedure in 69.6%, 26.6%, and 3.8% of patients, respectively. The PVL was pinpoint or involved 1/8 or 1/4 of the valve circumference in 18.6%, 52.4%, and 28.1% of cases, respectively. The most frequently used devices were the Vascular Plug 3, Ventricular Septal Defect Occluder, Vascular Plug 2, and Paravalvular Leak Device (45.0%, 16.6%, 14.2%, and 13.6% of cases, respectively). Successful device(s) implantation with leak reduction to ≤grade 2 was obtained in 85.0% of mitral and 91.4% of aortic procedures, respectively ( P =0.164); with major periprocedural adverse event rates of 3.3% and 1.2%, respectively ( P =0.371); and clinical success rates of 70.3% and 88.0%, respectively ( P =0.004). By multivariate analysis, technical failure, mechanical valve, and hemolytic anemia were independently associated with absence of clinical success (odds ratios [95% CIs], 7.7 [2.0-25.0]; P= 0.002; 3.6 [1.1-11.1]; P =0.036; and 3.7 [1.2-11.9]; P =0.025; respectively)., Conclusions: Transcatheter PVL closure is efficient and safe in symptomatic patients but is associated with a lower clinical success rate in patients with hemolysis and/or a mechanical valve., Registration: URL: https://www., Clinicaltrials: gov; Unique identifiers: NCT05089136.

Hard-to-heal wounds are a problem for both patients and caregivers. The biofi lm is one of the local factors of delayed healing. Wound hygiene carried out in 4 steps (cleansing, debridement, refashion - care of the edges, and dressing) constitutes the basis of proactive and curative anti-biofi lm strategies., (Copyright © 2022 Elsevier Masson SAS. All rights reserved.)

Background: In severe obesity, left ventricular (LV) and right ventricular (RV) remodeling and contractile dysfunction have been documented, but less is known regarding left atrial (LA) dysfunction and its association with LV/RV remodeling, especially in children., Purpose: To assess the effects of severe childhood obesity on cardiac function by using multichamber strain analysis with MRI., Study Type: Prospective., Subjects: Forty-five children aged 7-18 years (including 20 with severe obesity, defined as a body mass index values above the 99th percentile)., Field Strength: 5 T., Sequence: Steady-state-free-precession (SSFP) images in short-axis views and longitudinal two- and four-chamber views., Assessment: Cardiac strain measurements were derived from standard SSFP cine images by using a dedicated MR imaging feature tracking software. Inter- and intra-rater reliability were evaluated., Statistical Tests: Independent sample t test, Spearman's correlation coefficient, principal component analysis, Bland-Altman analysis, and intra-class correlation coefficients (ICC). A P value <0.05 was considered statistically significant., Results: As compared to children without obesity, those with obesity showed significantly reduced LA reservoir function (22.2% ± 6.4% vs. 33.8% ± 9.0%) and contractile function (5.4% ± 3.2% vs. 13.3% ± 8.0%) as well as significantly decreased absolute values for LA longitudinal strain in reservoir and contraction phases and LA radial motion fraction in reservoir and contraction phases. Children with severe obesity showed significantly reduced absolute RV radial motion fraction (-10.6% ± 2.9% vs. -18.2% ± 2.9%) and circumferential strain (-10.6% ± 2.9% vs. -16% ± 2.5%) as well as higher LV mass index (28.7% ± 5.1% vs. 21.7 ± 4.6 g/m 2 ) along with significantly reduced LV ejection fraction (56.4% ± 3.9% vs. 60% ± 4.1%), LV radial strain (56% ± 6% vs. 61.8% ± 11.3%), and longitudinal strain (-17.8% ± 1.8% vs. -20.3% ± 3.2%). Reliability was good to excellent, with ICC ranging from 79.1% to 97.7%., Data Conclusion: MR feature-tracking strain analysis revealed multichamber dysfunction in severely obese children with impaired LA reservoir and atrial contraction phases, which suggest an early loss in the compensatory ability of atrial contraction with severe obesity., Level of Evidence: 2 TECHNICAL EFFICACY STAGE: 3., (© 2021 International Society for Magnetic Resonance in Medicine.)

Introduction: Meibomian gland dysfunction (MGD) is the most common cause of dry eye syndrome. The goal of this study was to evaluate the efficacy of combined intense pulsed light (IPL) and low-level light therapy (LLLT) in symptomatic MGD., Materials and Methods: This retrospective study analyzed data from 30 patients with MGD causing dry eye symptoms not relieved by medical therapy and managed with combined IPL and LLLT. The primary endpoint was the Ocular Score Disease Index (OSDI) score at 1 month and 1 year. Secondary endpoints were visual acuity, intraocular pressure, tear film break-up time, Schirmer's test, Oxford score, and infrared meibographic score at 1 month after the conclusion of treatment., Results: The mean OSDI score decreased from 43±19 to 17±12 (1 month; p<0.0001) and then to 29±11 (12 months; p=0.013); 63% of patients were meibographic grade 2 before versus 7% after treatment (range, 1-4) (p=0.009); 75% of patients were Oxford grade 1 before versus 41% after treatment (p=0.004) (range, 1-3). No significant difference in the other secondary endpoints was noted., Conclusion: Over time, IPL therapy in combination with LLLT appears to improve patients with symptomatic MGD resistant to medical therapy., (Copyright © 2021 Elsevier Masson SAS. All rights reserved.)

Background: Mycophenolate mofetil (MMF) monotherapy following liver transplantation (LT) remains controversial due to a risk of acute rejection. The aim of this study was to report the largest multicenter experience of the use a MMF monotherapy guided by therapeutic drug monitoring using pharmacoslope modeling and Bayesian estimations of the MPA inter-dose AUC ( BE AUC MPA ) before withdrawing calcineurin inhibitors (CNI) and to evaluate the benefit of MMF monotherapy., Methods: MMF daily doses were adjusted to reach the BE AUC MPA target of 45μg.h/mL. Then CNI were withdrawn and patients were followed on liver test and clinical outcomes., Main Findings: From 2000-2014, in 2 transplantation centers, 94 liver transplant recipients received MMF monotherapy 6.5±4 years after LT. The mean BE AUC MPA was 45.5±16μg.h/mL. During follow-up, 4 patients experienced acute rejection (4%). During the first year, estimated glomerular filtration rate (eGFR) improved from 46.2±10.5 to 49.1±11.5mL/kg/min (P=0.025). Benefit persisted at year 5. In patients with metabolic syndrome, eGFR did not improve., Conclusion: MMF monotherapy regimen appears usually safe and beneficial, with low risk of acute rejection and eGFR improvement. Therapeutic drug monitoring strategy seemed useful by identifying 14% of patients with low MMF exposure., (Copyright © 2020. Published by Elsevier Masson SAS.)

Objective: To compare the efficacy and the risk of severe infectious events of immunosuppressive agents used early as first-line therapy in patients with neuromyelitis optica spectrum disorder (NMOSD)., Methods: We retrospectively included patients with NMOSD and a seropositive status for aquaporin 4 or myelin oligodendrocyte glycoprotein antibodies beginning first-line immunosuppressants within 3 years after the disease onset. The main outcome was occurrence of relapse after the initiation of immunosuppressants; the secondary outcome was the annual relapse rate (AAR)., Results: A total of 136 patients were included: 62 (45.6%) were treated with rituximab (RTX), 42 (30.9%) with mycophenolate mofetil (MMF), and 23 (16.9%) with azathioprine (AZA). Compared with RTX-treated patients, the risk of relapse was higher among MMF-treated patients (hazard ratio [HR], 2.74 [1.17-6.40]; p = 0.020) after adjusting for age at disease onset, sex, antibody status, disease duration, ARR before treatment, corticosteroid intake, and relapse location. We did not observe any difference between RTX-treated and AZA-treated patients (HR, 2.13 [0.72-6.28]; p = 0.17). No interaction was found between the antibody status and immunosuppressive treatments. ARR was lower with RTX than with MMF ( p = 0.039), but no difference was observed with AZA. We observed 9 serious infectious events with MMF, 6 with RTX, and none with AZA., Conclusions: The use of first-line RTX in NMOSD appears more effective than MMF in suppressing clinical activity, independent of the antibody status., Classification of Evidence: That study provides Class III evidence that for patients with NMOSD, first-line RTX is superior to MMF to reduce the risk of relapse., (© 2020 American Academy of Neurology.)

Mutations in interleukin-10 receptor (IL-10R) genes are one cause of very early-onset inflammatory bowel disease with perianal lesions, which can be cured by hematopoietic stem cell transplantation. Using a functional test, which assesses responsiveness of peripheral monocytes to IL-10, we identified three unrelated Portuguese patients carrying two novel IL-10RB mutations. In the three patients, sequencing of genomic DNA identified the same large deletion of exon 3 which precluded protein expression. This mutation was homozygous in two patients born from consanguineous families and heterozygous in the third patient born from unrelated parents. Microsatellite analysis of the IL10RB genomic region revealed a common haplotype in the three Portuguese families pointing to a founder deletion inherited from a common ancestor 400 years ago. In the third patient, surface expression of IL-10R was normal but signaling in response to IL-10 was impaired. Complementary DNA sequencing and next-generation sequencing of IL10RB locus with custom-made probes revealed a ≈ 6 Kb duplication encompassing the exon 6 which leads to a frameshift mutation and a loss of the TYK2-interacting Box 2 motif. Altogether, we describe two novel copy number variations in IL10RB, one with founder effect and one preserving cell surface expression but abolishing signaling., Competing Interests: The authors have declared that no competing interests exist.

The implementation of pneumococal conjugate vaccines (PCVs) 7 then 13 valent (Prevenar13 ®) in 2010-2011 has significantly changed the profile of pneumococcal meningitis. Since 3 years, the National Pediatric Meningitis Network of the Pediatric Infectious Disease Group (GPIP) and the National Reference Centre of Pneumococci have reported no cases of meningitis due to pneumococcus resistant to third-generation cephalosporins (3GC): cefotaxime or ceftriaxone. In the light of these new data, vancomycin should no longer be prescribed at the initial phase of pneumococcal meningitis treatment (confirmed or only suspected) and this antibiotic should only be added when 3GC minimum inhibitory concentration of the strain isolated is greater than 0.5mg/L. For meningococcal meningitis, nearly 20% of strains have decreased susceptibility to penicillin and amoxicillin, but all remain susceptible to 3GC. The National Pediatric Meningitis Network is a valuable tool because it has been sufficiently exhaustive and sustainable over 15 years. Maintaining this epidemiologic surveillance will allow us to adapt, if necessary, new regimens for subsequent changes that could be induced by vaccination and/or antibiotic uses., (© 2017 Elsevier Masson SAS. Tous droits réservés.)

Among the biological markers of morbidity and mortality, albumin holds a key place in the range of criteria used by the High Authority for Health (HAS) for the assessment of malnutrition and the coding of information system medicalization program (PMSI). If the principle of quantification methods have not changed in recent years, the dispersion of external evaluations of the quality (EEQ) data shows that the standardization using the certified reference material (CRM) 470 is not optimal. The aim of this multicenter study involving 7 sites, conducted by a working group of the French Society of Clinical Biology (SFBC), was to assess whether the albuminemia values depend on the analytical system used. The albumin from plasma (n=30) and serum (n=8) pools was quantified by 5 different methods [bromocresol green (VBC) and bromocresol purple (PBC) colorimetry, immunoturbidimetry (IT), immunonephelometry (IN) and capillary electrophoresis (CE)] using 12 analyzers. Bland and Altman's test evaluated the difference between the results obtained by the different methods. For example, a difference as high as 13 g/L was observed for the same sample between the methods (p <0.001) in the concentration range of 30 to 35 g/L. The VBC overestimates albumin across the range of values tested compared to PBC (p <0.05). PBC method gives similar results to IN for values lower than 40 g/L. For IT methods, one of the technical/analyzer tandem underestimates the albumin values inducing a difference of performance between the immunoprecipitation methods (IT vs IN, p <0.05). Although, the albumin results are related to the technical/analyzer tandem used. This variability is usually not taken into account by the clinician. Thus, clinicians and biologists have to be aware and have to check, depending on the method used, the albumin thresholds identified as risk factors for complications related to malnutrition and PMSI coding.

Diffuse adult high-grade gliomas (HGGs) with necrosis encompass anaplastic oligodendrogliomas (AOs) with necrosis (grade III), glioblastomas (GBM, grade IV) and glioblastomas with an oligodendroglial component (GBMO, grade IV). Here, we aimed to search for prognostic relevance of histological classification and molecular alterations of these tumors. About 210 patients were included (63 AO, 56 GBM and 91 GBMO). GBMO group was split into "anaplastic oligoastrocytoma (AOA) with necrosis grade IV/GBMO," restricted to tumors showing intermingled astrocytic and oligodendroglial component, and "GBM/GBMO" based on tumors presenting oligodendroglial foci and features of GBM. Genomic arrays, IDH1 R132H expression analyses and IDH direct sequencing were performed. 1p/19q co-deletion characterized AO, whereas no IDH1 R132H expression and intact 1p/19q characterized both GBM and GBM/GBMO. AOA with necrosis/GBMO mainly demonstrated IDH1 R132H expression and intact 1p/19q. Other IDH1 or IDH2 mutations were extremely rare. Both histological and molecular classifications were predictive of progression free survival (PFS) and overall survival (OS) (P < 10(-4) ). Diffuse adult HGGs with necrosis can be split into three histomolecular groups of prognostic relevance: 1p/19q co-deleted AO, IDH1 R132H-GBM and 1p/19q intact IDH1 R132H+ gliomas that might be classified as IDH1 R132H+ GBM. Because of histomolecular heterogeneity, we suggest to remove the name GBMO., (© 2014 International Society of Neuropathology.)

Experimental research has always been the cornerstone of pathophysiological and therapeutic advances in critical care medicine, where clinical observations and basic research mutually fed each other in a so-called translational approach. The objective of this review is to address the different aspects of translational research in the field of critical care medicine. We herein highlighted some demonstrative examples including the animal-to-human approach to study host-pathogen interactions, the human-to-animal approach for sepsis-induced immunosuppression, the still restrictive human approach to study critical illness-related neuromyopathy, and the technological developments to assess the microcirculatory changes in critically ill patients. These examples not only emphasize how translational research resulted in major improvements in the comprehension of the pathophysiology of severe clinical conditions and offered promising perspectives in critical care medicine but also point out the obstacles to translate such achievements into clinical practice.

The type I interferon system is integral to human antiviral immunity. However, inappropriate stimulation or defective negative regulation of this system can lead to inflammatory disease. We sought to determine the molecular basis of genetically uncharacterized cases of the type I interferonopathy Aicardi-Goutières syndrome and of other undefined neurological and immunological phenotypes also demonstrating an upregulated type I interferon response. We found that heterozygous mutations in the cytosolic double-stranded RNA receptor gene IFIH1 (also called MDA5) cause a spectrum of neuroimmunological features consistently associated with an enhanced interferon state. Cellular and biochemical assays indicate that these mutations confer gain of function such that mutant IFIH1 binds RNA more avidly, leading to increased baseline and ligand-induced interferon signaling. Our results demonstrate that aberrant sensing of nucleic acids can cause immune upregulation.

Importance: The leukodystrophies comprise a clinically and genetically heterogeneous group of progressive hereditary neurological disorders mainly affecting the myelin in the central nervous system. Their onset is variable from childhood to adulthood and presentation can be with a variety of clinical features that include mainly for adult-onset cases cognitive decline, seizures, parkinsonism, muscle weakness, neuropathy, spastic paraplegia, personality/behavioral problems, and dystonia. Recently, Rademakers and colleagues identified mutations in the CSF1R gene as the cause of hereditary diffuse leukoencephalopathy with spheroids (HDLS), offering the possibility for an in-life diagnosis. The detection of mutations in this gene in cases diagnosed with different clinical entities further demonstrated the difficulties in the clinical diagnosis of HDLS., Objective: To better understand the genetic role of mutations in this gene, we sequenced a large cohort of adult-onset leukodystrophy cases., Design: Whole-exome sequencing and follow up-screening by Sanger sequencing., Setting: Collaborative study between the Institute of Neurology, University College London and the Inserm, Paris, France., Participants: A total of 114 probands, mostly European patients, with a diagnosis of adult-onset leukodystrophy or atypical cases that could fit within a picture of leukodystrophy. These included 3 extended families within the spectrum of leukodystrophy phenotype., Interventions: Whole-exome sequencing in a family and Sanger sequencing of CSF1R., Main Outcomes and Measures: Mutations in CSF1R., Results: We identified 12 probands with mutations in CSF1R. The clinical diagnoses given to these patients included dementia with spastic paraplegia, corticobasal degeneration syndrome, and stroke disorders. Our study shows that CSF1R mutations are responsible for a significant proportion of clinically and pathologically proven HDLS., Conclusions and Relevance: These results give an indication of the frequency of CSF1R mutations in a European leukodystrophy series and expand the phenotypic spectrum of disorders that should be screened for this gene.

Objectives: The objective of this study was to show that although transcutaneous electrical tibial nerve stimulation (TENS) is being increasingly used to treat fecal incontinence (FI), its efficacy has never been proved using controlled trials., Methods: In this randomized, double-blind, sham-controlled trial, 144 patients aged 30-82 years from nine centers were randomly assigned to receive either active or sham stimulations for 3 months. The primary end point was the response to treatment based on the number of incontinence and urgency episodes. Secondary end points were severity scores, quality of life scores, delay to postpone defecation, patient self-assessment of treatment efficacy, physician assessment of TENS efficacy, anorectal manometry, and adverse events., Results: No statistically significant difference was seen between active and sham TENS in terms of an improvement in the median number of FI/urgency episodes per week. Thirty-four patients (47%) who received the active TENS treatment exhibited a >30% decrease in the FI severity score compared with 19 patients (27%) who received the sham treatment (odds ratio 2.4, 95% confidence interval 1.1-5.1, P=0.02). No differences in delay to postpone defecation, patient self-assessment of treatment efficacy, or anorectal manometry were seen between the two groups. The evaluating physicians rated the active stimulations as more effective than the sham stimulations (P=0.01). One minor therapy-related adverse event was observed (1.5%) (see Supplementary Consort 1b)., Conclusions: We failed to demonstrate any benefit of TENS on our primary end-point.

Objectives: Endoscopy and imaging are necessary to diagnose glottis carcinoma. Today, CT scan is the gold standard but MR imaging should be more sensitive for neoplastic invasion detection. The purpose of this study was to determine which exam to perform (CT scan or MRI) for neoplastic invasion., Material and Methods: This prospective study span a 18 months period. Seven patients with glottis carcinoma (TI-T2) underwent CT and MR imaging before surgery. Findings at imaging and pathologic examination were compared., Results: Both CT and MR imaging were interesting, more specific (90%) than sensitive (74%). The anterior commissure, ventricles, subglottis, thyroid and arytenoid cartilages are the more difficult area analyzing., Conclusion: CT imaging stays the gold standard. MR imaging is more effective on second intention to refine the data. Indications are being improved, with complete cure and more preserved laryngealfunctions.

Recent legislative texts have changed vaccinal policy and reinforced the role of midwives in vaccine prevention in perinatal healthcare. Quite as paediatricians and obstetricians-gynecologists, midwives can now prescribe and carry out, for the mothers, vaccines against rubella, tetanus, poliomyelitis, diphtheria, hepatitis B, influenza and whooping-cough and for the newborns vaccines against hepatitis B and tuberculosis. Concerning vaccinations, practitioners have to respect the vaccination calendar and a collaborative action is useful and necessary. These national guidelines are regularly updated when new vaccines and new recommendations come to light, for example for children (papillomavirus, tuberculosis, pneumococcus...), young adults (varicella, whooping-cough) and health professions in contact with very young children (varicella, measles, influenza and whooping-cough). The recent changes in tuberculosis prevention from routine vaccination of all newborn infants to selective vaccination lead to reinforce measures to detect the infants at higher risk, for them to be vaccinated before discharge at home. Midwives and nurses occupy a central place in family policy and become, with obstetricians-gynecologists and pediatricians, key actors for the effectiveness and the success of vaccine strategies in perinatal health.

Maxillary hypoplasia is a common sequel in cleft lip and palate deformities. After primary surgery to close lip and palate, patients routinely need extensive treatment particularly orthodontic management. With this type of approach, maxillary hypoplasia is less frequent and severe and subsequent orthognathic surgery is efficient in most cases. Without the proper management maxillary hypoplasia may be severe and patients will need a modified management and specific revision. At the end of maxillar growth, the first aim of treatment is to achieve continuity of the maxillary arch with gingivoperiosteoplasty. The transversal insufficiency can then be treated by distraction osteogenesis. Orthodontic treatment should leave place for missing teeth.

Routine othodontic management is unavoidable in all patients with cleft lip and palate after primary surgery. This management combines dental arch alignment with maxillary expansion of the lesser fragment before alveolar bone grafting. To treat dental arch asymmetry, the space of the missing lateral incisor is preserved until the age of dental implant. Otherwise, dento-orthopedic treatment attempts to normalize transversal dental dimension once alveolar bone grafting is done in order to prepare the surgical advancement of the maxilla.

We describe a 45-year-old male patient with an atypical unilateral optic neuropathy who was diagnosed with primary antiphospholipid syndrome. The initially poor vision lasting several months completely recovered and long-term oral anticoagulation therapy prevented potential further systemic thrombotic complications.

Brain natriuretic peptide is one member of the natriuretic peptide family, including also ANP, CNP, DNP and urodilatin. In human, brain natriuretic peptide is mainly secreted by the cardiac ventricles. BNP is synthetized as pre-proBNP form, secondary cleaved in proBNP, itself equimolarly cleaved in BNP and NT-proBNP. The biological action of BNP is mediated by the NPR-A receptor. This peptide is eliminated from the systemic circulation by a neutral endopeptidase and by a clearance receptor (NPR-C). The BNP and NT-proBNP concentrations are measured using automated rapid immunoassay techniques. Plasma concentrations of the two peptides physiologically increase with age and are found to be higher in women than in men. The action of BNP against fluid expansion is explained by its vascular (vasodilatation), renal (diuretic and natriuretic) and cerebral activities. The measurement of these two peptides contributes to the diagnosis of heart failure. These peptides are prognostic markers both in heart failure and in acute coronary syndromes. In renal insufficiency, the interpretation of the increase in these two peptide concentrations may be difficult, particularly with the NT-proBNP which is mainly excreted by the kidneys.

Introduction: The clinical efficacy of non-invasive ventilation (NIV) has now been demonstrated in the management of acute-on-chronic respiratory failure (ACRF) in various etiologies. Endotracheal mechanical ventilation (ETMV) can lead to numerous complications and weaning difficulties increasing the risk of prolonged ETMV, morbidity and mortality as well as excess cost of intensive care. Therefore, it could be useful to consider NIV for delivering effective ventilatory support to reduce the length of ETMV in ACRF patients who are still not capable of maintaining spontaneous breathing. From the interesting but discordant results of two recent randomised controlled trials, a working group from the Société de Réanimation de Langue Française (SRLF) decided to perform a new prospective randomised controlled multicenter trial. The aim of the study will be to assess the usefulness of NIV as an extubation and weaning technique in ventilated ACRF patients., Methods: The methodology used will compare three parallel weaning strategies in ACRF patients considered difficult to wean: invasive conventional weaning (group A), extubation relayed by nasal oxygentherapy (group B), and extubation relayed by NIV (group C). Based on the main end-point defined as the weaning success rate, 208 patients from 17 investigator centers are planned to be included. Results of the study will also allow to assess the respective impact of the three weaning strategies on the length of ETMV and weaning, the mechanical ventilation-related morbidity, the patients lengths of stay and mortality., Expected Results: Results of the VENISE trial should permit to improve the management of the difficult to wean ACRF patients and thus contribute to more precisely define the place of NIV in the weaning and prevention of re-intubation strategies in these patients.