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French-Belgian consensus statement to managing spinal deformities in children with spinal muscular atrophy treated with SMN restoring therapies
No full textInternational audienceBackground: Spinal muscular atrophy (SMA) affects the motor neurons of the anterior spinal cord, causing progressive muscle weakness and atrophy. SMN restoring therapies have led to the emergence of new phenotypes in spinal muscular atrophy (SMA), including early-onset scoliosis. Guidelines regarding the optimal treatment for scoliosis and its consequences are lacking. Objective: To provide guidelines to help clinical decision-making and to standardise the management of neuromuscular scoliosis (NMS) in children with SMA. Methods: We conducted a Delphi study with 31 experts between July 2023 and February 2024. Three rounds were conducted using anonymous electronic questionnaires to determine consensus on items grouped into 5 main domains: Respiratory monitoring (7 items), Trunk orthoses (4 items), Surgical approaches (13 items), Preoperative care (17), post-operative care (10 items). Experts were asked to rate their agreement with each item on a scale from 1 (strongly disagree) to 9 (strongly agree). Consensus was considered to have been achieved if the median value of the responses was ≥ 7. Items that did not reach consensus in one round were reformulated in the following round using comments provided by the experts. Results: The experts included 12 orthopaedic surgeons, 9 physical medicine and rehabilitation physicians and 10 paediatricians/child neurologists. Fourty-seven items achieved consensus. In the first round, consensus was achieved for 33 of the 51 items. The second round included 15 items, and a consensus was achieved for 11 items. In the third round, 3 of the 4 items included achieved consensus and the fourth item was dropped due to a lack of agreement. Conclusions: The recommendations generated from the questionnaire provide a relevant consensus-based guidance for the multidisciplinary management of spinal deformities in children with SMA
Evaluation of multidisciplinary care pathways on kidney function in patients with advanced chronic kidney disease: multicenter study
No full textInternational audienceBackground Chronic Kidney Disease (CKD) is a significant public health issue due to its increasing prevalence and associated high morbidity and mortality rates. MethodsThis study evaluates the impact of multidisciplinary care pathways consisting of medical, dietetic and coordinating nurse follow ups, on kidney function, survival, clinical biological parameters and quality of life in patients with advanced CKD (stages 4 and 5). A retrospective analysis of clinical and biological parameters was conducted, alongside a prospective assessment of quality of life using the EQ-5D-5L tool. ResultsAmong 359 patients, (141 with complete multidisciplinary follow-up, 100 with partial follow-up, and 118 with medical-only follow-up), mortality rates were significantly higher in the medical-only group (26%) compared to those who received complete (8%) and partial multidisciplinary follow-up (16%) (p < 0.001). No significant differences were observed in kidney function progression or dialysis initiation. Autonomy (Pearson's chi-square: 15.32, p = 0.05) and overall quality of life in the medical-only group were significantly lower (Cumulative Adjusted EQ-5D-5L-complete follow-up: 0.83, partial follow-up: 0.82 and medical only: 0.70-p = 0.037), as was the quality-of-life visual self-assessment (EQ VAS Scores-complete follow-up: 65, partial follow-up: 63 and medical only: 53 p = 0.024). The differences are important and clinically relevant. Conclusions The current study suggests that participation in a Multidisciplinary Care Pathway does not significantly change kidney function progression or dialysis initiation but may be associated with decreased mortality and better quality of life parameters
Étude de la mé canotrasduction au niveau des dents en utilisant les cultures primaires des cellules pé ri-dentales humaines soumises à des contraintes mécaniques sur bio-tribo-réacteur
No full textInternational audienceIntroductionLe projet MIMIMed@Lyon est un projet stratégique de l’Institut Carnot Ingénierie@Lyon dans ledomaine de la santé visant à créer à terme une plateforme de modèles analogiques alternatifs pour ledéveloppement des Dispositifs Médicaux (DMs). La validation des DMs nécessite notamment devérifier leur biocompatibilité mais également leur durabilité et leur absence de toxicité. Le but de cetteétude est la fabrication et validation d’un modèle simulation la régénération du ligament parodontal.Matériel et méthodeUn bioréacteur biomimétique a été développé afin de reproduire les contraintes mécaniquesphysiologiques appliquées au niveau de la racine dentaire. Le dispositif repose sur un actuateurpiézoélectrique APA1000L monté sur une plateforme élévatrice, associé à un capteur de proximité àcourants de Foucault (type TQ 402/412) permettant de suivre précisément la position du modèle. Uncapteur de force Kistler 9345B nous renseigne sur la résistance du milieu.Trois séries de cultures de cémentoblastes sont réalisées pendant 10 jour sur une couche de céramiqueporeuse de Zircone ZrO2 et, une fois fixées, sont soumises ou non à des sollicitations mécaniquesconformes à celles mesurées par le simulateur de mastication Mario au sein de l’équipe BIO duLaboratoire des Multimatériaux et Interfaces (LMI).L’analyse des réponses obtenues se fait au niveau cellulaire (viabilité et profil inflammatoire), tissulaire(étude histologique) et mécanique.Une fois valide, ce modèle pourra permettre l’expérimentation de dispositif médicaux innovants et lestests cliniques sans nécessiter de modèle vivant. La viabilité cellulaire sera mesurée ainsi que la présencedes différents marqueurs de l’inflammation et de l’activité cémentoblastique
Minigene splicing reporter assay: a high-stake tool for genetic diagnosis in familial hypobetalipoproteinemia
No full textInternational audienceBackground & aims: Familial hypobetalipoproteinemia 1 (FHBL-SD2) is the most common monogenic form of primary hypocholesterolaemia, related to truncating variants in the APOB gene encoding apolipoprotein B. Due to its high level of complexity, variants of uncertain significance (VUS) require further investigations. This study aims to demonstrate the value of setting minigene assays in the FHBL-SD2's genetic diagnosis.Methods: Four APOB VUS occurring in patients with a FHBL-SD2 phenotype were considered. In silico analysis were performed with six software programs supposed to predict the potential splicing effect. Then, functional consequences were studied in vitro using a minigene splicing reporter assay.Results: An effect on splicing was predicted in silico for the 4 variants, with the activation of a cryptic acceptor site for c.694-13A>G and c.1471-6A>G variants, and the use of a cryptic donor site for c.1123A>G and c.1470G>A variants. Minigene study showed a complete effect on splicing for 3 mutations, confirming the in silico predictions. All of these transcripts result in premature truncated variants. Therefore, these variants were reclassified as likely pathogenic and causative of FHBL-SD2. However, no effect was shown either in HeLA and HuH7 cells for the c.1470G>A variant.Conclusions: Minigene study appears to be a promising and valuable tool to enhance the diagnostic accuracy of FHBL-SD2. It emphasizes the challenge in interpreting VUS and underscores the importance of establishing a clear strategy to assess their significance. Therefore, promoting minigene studies would be beneficial to understand precisely the impact of splicing variants
Predictors of poor outcome in acute stroke patients with posterior cerebral artery occlusion and medical management
No full textInternational audienceBackground and Aims: The clinical evolution of acute ischemic stroke patients with isolated proximal posterior cerebral artery (PCA) occlusion treated with medical management alone has been poorly described. We aimed to determine the clinical and radiological factors associated with poor functional outcome in this population. Methods: We conducted a multicenter international retrospective study of consecutive stroke patients with isolated occlusion of the first (P1) or second (P2) segment of PCA admitted within 6 h from symptoms onset in 26 stroke centers in France, Switzerland, and the United States, treated with the best medical management alone. Poor functional outcome was defined as a modified Rankin scale (mRS) ⩾2 at 3 months or no return to pre-stroke mRS. The associations between pretreatment variables and poor outcome were studied in univariable and then multivariable analyses, as well as the association between poor outcome and key follow-up radiological variables. Results: Overall, 585 patients were included. The median age was 74 years (interquartile range (IQR) = 63–83), median National Institutes of Health Stroke Scale (NIHSS) was 6 (3–10), 80% received intravenous thrombolysis (IVT), and 22% and 78% had P1 and P2 occlusions, respectively. Poor outcome occurred in 56% of patients. In multivariable analysis focusing on pretreatment variables, age (adjusted odds ratio (OR) = 1.12 per 5-year increase [95% confidence interval (CI) = 1.05–1.20]; p = 0.001), NIHSS score (aOR = 1.12 per each point increase [1.08–1.18]; p < 0.001), infarct volume (aOR = 1.16 per 5 mL increase [1.07-1.25]; p < 0.001), and the lack of IVT use (aOR = 1.79 [1.10-2.94], p = 0.020) were independently associated with poor outcome. Regarding 24-h follow-up radiological variables, complete recanalization (defined as no clot in the vascular tree at or beyond the primary occlusive lesion, aOR = 0.37 [95% CI = 0.21-0.65], p < 0.001) and parenchymal hematoma occurrence (aOR = 2.37 [95% CI = 1.01-5.56], p = 0.048) were independently associated with poor 3-month outcome. Conclusions: Poor outcome occurred in more than half of medically treated PCA-related acute stroke patients. Facilitating IVT use may improve functional outcome. Therapeutic approaches aimed at enhancing recanalization and reducing hemorrhagic transformation need to be studied in clinical trials
An ALG12-CDG patient with a novel homozygous intronic mutation associated with low ALG12 mRNA
No full textInternational audienceAbstract Background Type I Congenital Disorders of Glycosylation (CDG-I) are inherited diseases presenting deficits in protein N -glycosylation involving either the biosynthesis of the lipid-linked oligosaccharide Glc 3 Man 9 Glc N Ac 2 -PP-dolichol or transfer of its oligosaccharide to protein. Results We describe a patient harbouring hypoglycosylated transferrin, a characteristic of CDG-I. NGS revealed a homozygous RFT1 (c.16G > T p.Val6Leu) variant of unknown significance that is predicted to be benign. Metabolic radiolabelling of the patient’s fibroblasts did not reveal the accumulation of truncated Man 5 Glc N Ac 2 -PP-dolichol expected of RFT1-CDG but rather an accumulation of Man 7 Glc N Ac 2 -PP-dolichol, characteristic of ALG12-CDG. Revaluation of the NGS data revealed a homozygous (22_50311909A_G, c.-79 + 2 T > C) variant that modifies the second nucleotide of the first intron of the ALG12 gene upstream of the first coding exon (exon 2). Sequencing of ALG12 cDNA revealed a 4-base insertion between exon 1 and exon 2 suggesting a shift in mRNA splicing in this intron to a putative new GU donor site. The patient’s fibroblasts display 3% of control ALG12 mRNA levels. Conclusion This is the first description of a pathogenic intronic ALG12 variant upstream of the first coding exon. The modification of the splicing process between intron 1 and exon 2, the very low transcript level and the absence of other mutations in the patient's ALG12 gene lead us to conclude that this ALG12 variant is a predicted Loss of Function (pLOF) variant
Influence of a multicomponent exercise intervention on fear of falling and gait parameters in community-dwelling older adults: a prospective study
No full textInternational audienceThe effects of exercise interventions on gait parameters and fear of falling (FOF) have been under-explored and the influence of FOF on exercise-induced adaptations of gait parameters is unclear. This interventional and comparative pilot study aimed to explore the influence of FOF status on gait parameters changes following a multicomponent exercise intervention in community-dwelling older adults at risk of mobility disability and implemented in routine care.NCT03667664 (registration date: 12/09/2018) and NCT06659484 (registration date: 26/10/2024)
Influence of geographical accessibility to specialist and primary care givers on excess mortality of multiple sclerosis patients in France
No full textInternational audienceAccess to healthcare and socioeconomic deprivation are intricately linked. No studies have been led to measure the effect of healthcare accessibility on mortality in patients with MS so far. The objective was to examine the influence of travel time to the expert MS centre and of the accessibility to primary healthcare services on excess mortality in MS.A retrospective observational cohort study recruited patients from 18 French MS expert centres, with an onset of MS between 1960 and 2015 and a follow-up of up to 30 years. Primary health facility accessibility was measured by the Spatial aCcessibility multiscAlar index. Specialist care accessibility was measured by road travel time to the expert MS centre. Excess death rates (EDR) and excess hazard ratios were studied using additive excess hazard models with multidimensional penalised splines.The study included 33,697 patients. Patients with relapsing-onset MS (R-MS) with a travel time of 40 min had the lowest EDR (Men: 1.2 deaths per 100 person-years (95%CI [0.8;1.8]), women: 0.8 deaths per 100 person-years 95%CI[0.6;1.2]), lower than patients who lived further from the centre. No effect of primary care access was found for patients with R-MS, and no effect of accessibility to primary or specialised care was found for patients with primary progressive MS.Conclusion: This study reveals the impact of travel time to neurologists on excess mortality in patients with R-MS in France. This distance bias association highlights the importance of preventing a potential selection of patients followed in MS expert centres
Prognosis of essential mixed cryoglobulinemia and connective tissue disease-related cryoglobulinemia after rituximab-induced remission.
No full textInternational audienceObjectives: Rituximab (RTX) and glucocorticoids are the first line treatment for essential (EM) and connective tissue disease (CTD)-related mixed cryoglobulinemia vasculitis (CryoVas). Data on long term outcomes of these CryoVas are lacking. We aimed to describe the prognosis of patients with EM and CTD-related CryoVas.Methods: We conducted a retrospective study on patients with EM or CTD-related CryoVas in remission after RTX-based therapy.Results: We included 63 patients with a median follow-up of 58 months (IQR, 33-88 months). Relapse rates were 23% at 1 year, 42% at 2 years and 71% at 5 years after the initial flare. In univariate analysis, factors associated with relapse were purpura (HR, 2.2; 95% confidence interval (CI), 1.1-4.4; p = 0.02) and a previous flare of CryoVas (HR, 1.9; 95% CI, 1.0-3.7; p = 0.04). Maintenance therapy was associated with a lower risk of early relapse (HR, 0.3; 95% CI, 0.1-0.9; p = 0.03), but not of late relapse (HR, 2.0; 95% CI, 0.7-5.7; p = 0.21). In multivariable analysis, patients without purpura or previous flare remained at lower risk of relapse than those with at least one of the two (HR, 3.6; 95%CI, 1.6-8.2; p= 0.002). Maintenance regimen was associated with a lower risk of early relapse (HR, 0.3; 95% CI, 0.1-0.9; p = 0.03).Conclusion: In patients with EM and CTD-related CryoVas who received RTX as induction therapy, relapses were frequent and associated with purpura and a previous flare, but were reduced with maintenance therapy
Cervical radiculopathy due to intraforaminal vertebral artery loop – posterior microvascular decompression with graft interposition technique
No full textInternational audienceBackground: Vertebral artery (VA) kinking is an uncommon cause of cervical radiculopathy. Here, a 57-year-old patient with unilateral C6 radiculopathy due to an aberrant VA loop documented on both magnetic resonance (MR)/computed tomography angiography (CTA) studies, successfully underwent left-sided C56/C67 foraminotomies resulting in symptom resolution. Case Description: A 57-year-old presented with progressive left C6 and C7 radiculopathy and C6 weakness. Imaging revealed kinking of the VA at the C5–6 level, with the VA arterial loop compressing the left C6 nerve root within the foramen. In addition, degenerative C6–7 foraminal stenosis was noted. Through a C5–6 foraminotomy, meticulous dissection of adhesions between the VA artery and the C6 root was accomplished along with interposition of a Teflon ™ patch. At C6–7, a routine foraminotomy was performed to address C6–7 spondylosis. Postoperatively, the patient experienced complete resolution of his C6 and C7 radiculopathy and C6 motor deficit. Conclusion: Cervical nerve root compression may rarely be attributed to abnormal foraminal VA loops. Obtaining the appropriate preoperative MR imaging/CTA is critical to diagnose VA compromise, and plan for unilateral foraminal decompressions