13 research outputs found
Transcatheter closure of patent ductus arteriosus in preterm infants: results from a single-center cohort
ObjectiveTo assess the success rate of patent ductus arteriosus (PDA) transcatheter closure in preterm infants and to describe the nature of procedural adverse events and short-term clinical status.Study designAll the preterm infants with PDA transcatheter closure were evaluated retrospectively between July 2019 and March 2023 in a single level III neonatal intensive care unit in France. The procedure was performed in the catheterization laboratory using venous canulation. We retrospectively collected data about the patients' characteristics, procedural outcomes and complications.ResultsTwenty-five infants born between 23.4 and 32.0 weeks of gestational age (meanâ±âSD 26.3â±â1.9 weeks) underwent transcatheter PDA closure. Their mean age and weight at the time of the procedure were 52 days (range 22â146 days) and 1,620â
g (range 890â3,700â
g), respectively. Successful closure was achieved in all but one patient. Procedure related complications were reported in 10 infants (40%), including 6 left pulmonary artery stenosis one of which required a balloon dilatation, two cardiac tamponades and two inferior vena cava thrombosis. Only two post-ligature syndromes occurred after the procedure. Two infants died one of which was related to the procedure.ConclusionTranscatheter closure of a PDA is a valid alternative to surgical ligation due to its high success rate and low incidence of post-ligature syndrome. Nevertheless, we also report rare, although serious complications
Therapeutic and Prognostic Implications of BRAF V600E in Pediatric Low-Grade Gliomas.
Purpose BRAF V600E is a potentially highly targetable mutation detected in a subset of pediatric low-grade gliomas (PLGGs). Its biologic and clinical effect within this diverse group of tumors remains unknown.
Patients and Methods A combined clinical and genetic institutional study of patients with PLGGs with long-term follow-up was performed (N = 510). Clinical and treatment data of patients with BRAF V600E mutated PLGG (n = 99) were compared with a large international independent cohort of patients with BRAF V600E mutated-PLGG (n = 180).
Results BRAF V600E mutation was detected in 69 of 405 patients (17%) with PLGG across a broad spectrum of histologies and sites, including midline locations, which are not often routinely biopsied in clinical practice. Patients with BRAF V600E PLGG exhibited poor outcomes after chemotherapy and radiation therapies that resulted in a 10-year progression-free survival of 27% (95% CI, 12.1% to 41.9%) and 60.2% (95% CI, 53.3% to 67.1%) for BRAF V600E and wild-type PLGG, respectively ( P \u3c .001). Additional multivariable clinical and molecular stratification revealed that the extent of resection and CDKN2A deletion contributed independently to poor outcome in BRAF V600E PLGG. A similar independent role for CDKN2A and resection on outcome were observed in the independent cohort. Quantitative imaging analysis revealed progressive disease and a lack of response to conventional chemotherapy in most patients with BRAF V600E PLGG.
Conclusion BRAF V600E PLGG constitutes a distinct entity with poor prognosis when treated with current adjuvant therapy
Therapeutic and Prognostic Implications of BRAF V600E in Pediatric Low-Grade Gliomas
Purpose BRAF V600E is a potentially highly targetable mutation detected in a subset of pediatric low-grade gliomas (PLGGs). Its biologic and clinical effect within this diverse group of tumors remains unknown. Patients and Methods A combined clinical and genetic institutional study of patients with PLGGs with long-term follow-up was performed (N = 510). Clinical and treatment data of patients with BRAF V600E mutated PLGG (n = 99) were compared with a large international independent cohort of patients with BRAF V600E mutated-PLGG (n = 180). Results BRAF V600E mutation was detected in 69 of 405 patients (17%) with PLGG across a broad spectrum of histologies and sites, including midline locations, which are not often routinely biopsied in clinical practice. Patients with BRAF V600E PLGG exhibited poor outcomes after chemotherapy and radiation therapies that resulted in a 10-year progression-free survival of 27% (95% CI, 12.1% to 41.9%) and 60.2% (95% CI, 53.3% to 67.1%) for BRAF V600E and wild-type PLGG, respectively (P < .001). Additional multivariable clinical and molecular stratification revealed that the extent of resection and CDKN2A deletion contributed independently to poor outcome in BRAF V600E PLGG. A similar independent role for CDKN2A and resection on outcome were observed in the independent cohort. Quantitative imaging analysis revealed progressive disease and a lack of response to conventional chemotherapy in most patients with BRAF V600E PLGG. Conclusion BRAF V600E PLGG constitutes a distinct entity with poor prognosis when treated with current adjuvant therapy. (C) 2017 by American Society of Clinical Oncolog
Anticorps anti-NR1 dans lâencĂ©phalite anti-rĂ©cepteur N-mĂ©thyl-D-aspartate et la schizophrĂ©nie
La dĂ©couverte des anticorps anti-rĂ©cepteur N-mĂ©thyl-D-aspartate (NMDA) et la dĂ©monstration de leurs effets pathogĂšnes dans les encĂ©phalites limbiques ont suscitĂ© de nombreuses interrogations chez les psychiatres et les neuroscientifiques sâintĂ©ressant Ă la schizophrĂ©nie. Ces deux pathologies partagent en effet plusieurs caractĂ©ristiques cliniques, physiopathologiques, ou Ă©tiologiques majeures, et des auteurs tendent Ă considĂ©rer certaines schizophrĂ©nies comme des formes dâencĂ©phalite fruste. Certaines Ă©tudes ont rapportĂ© la prĂ©sence de ces anticorps dans le sĂ©rum de patients schizophrĂšnes, sans quâil y ait de manifestation neurologique. Ces rĂ©sultats suggĂšrent de nouvelles perspectives thĂ©rapeutiques chez certains patients schizophrĂšnes, bien que la sĂ©roprĂ©valence de ces anticorps soit faible et que leur pathogĂ©nicitĂ© reste Ă dĂ©montrer
Cell- and single molecule-based methods to detect Anti-N-Methyl-D-Aspartate receptor autoantibodies in first episode psychosis patients from the OPTiMiSE project
Relationship Between Serum NMDA Receptor Antibodies and Response to Antipsychotic Treatment in First-Episode Psychosis
International audienceBACKGROUND: When psychosis develops in NMDA receptor (NMDAR) antibody encephalitis, it usually has an acute or subacute onset, and antipsychotic treatment may be ineffective and associated with adverse effects. Serum NMDAR antibodies have been reported in a minority of patients with first-episode psychosis (FEP), but their role in psychosis onset and response to antipsychotic treatment is unclear. METHODS: Sera from 387 patients with FEP (duration of psychosis ,2 years, minimally or never treated with antipsychotics) undergoing initial treatment with amisulpride as part of the OPTiMiSE (Optimization of Treatment and Management of Schizophrenia in Europe) trial (ClinicalTrials.gov number NCT01248195) were tested for NMDAR IgG antibodies using a live cell-based assay. Symptom severity was assessed using the Positive and Negative Syndrome Scale and the Clinical Global Impressions Scale at baseline and again after 4 weeks of treatment with amisulpride. RESULTS: At baseline, 15 patients were seropositive for NMDAR antibodies and 372 were seronegative. The seropositive patients had similar symptom profiles and demographic features to seronegative patients but a shorter duration of psychosis (median 1.5 vs. 4.0 months; p = .031). Eleven seropositive and 284 seronegative patients completed 4 weeks of amisulpride treatment: after treatment, there was no between-groups difference in improvement in Positive and Negative Syndrome Scale scores or in the frequency of adverse medication effects. CONCLUSIONS: These data suggest that in FEP, NMDAR antibody seropositivity alone is not an indication for using immunotherapy instead of antipsychotic medications. Further studies are required to establish what proportion of patients with FEP who are NMDAR antibody seropositive have coexisting cerebrospinal fluid inflammatory changes or other paraclinical evidence suggestive of a likely benefit from immunotherapy
Clés cliniques et génétiques de l'ataxie cérébelleuse causée par des expansions GAA de FGF14
International audienceSCA27B caused by FGF14 intronic heterozygous GAA expansions with at least 250 repeats accounts for 10-60% of cases with unresolved cerebellar ataxia. We aimed to assess the size and frequency of FGF14 expanded alleles in individuals with cerebellar ataxia as compared with controls and to characterize genetic and clinical variability.We sized this repeat in 1876 individuals from France sampled for research purposes in this cross-sectional study: 845 index cases with cerebellar ataxia and 324 affected relatives, 475 controls, as well as 119 cases with spastic paraplegia, and 113 with familial essential tremor.A higher frequency of expanded allele carriers in index cases with ataxia was significant only above 300 GAA repeats (10.1%, n = 85) compared with controls (1.1%, n = 5) (p < 0.0001) whereas GAA250-299 alleles were detected in 1.7% of both groups. Eight of 14 index cases with GAA250-299 repeats had other causal pathogenic variants (4/14) and/or discordance of co-segregation (5/14), arguing against GAA causality. We compared the clinical signs in 127 GAAâ„300 carriers to cases with non-expanded GAA ataxia resulting in defining a key phenotype triad: onset after 45 years, downbeat nystagmus, episodic ataxic features including diplopia; and a frequent absence of dysarthria. All maternally transmitted alleles above 100 GAA were unstable with a median expansion of +18 repeats per generation (r2 = 0.44; p < 0.0001). In comparison, paternally transmitted alleles above 100 GAA mostly decreased in size (-15 GAA (r2 = 0.63; p < 0.0001)), resulting in the transmission bias observed in SCA27B pedigrees.SCA27B diagnosis must consider both the phenotype and GAA expansion size. In carriers of GAA250-299 repeats, the absence of documented familial transmission and a presentation deviating from the key SCA27B phenotype, should prompt the search for an alternative cause. Affected fathers have a reduced risk of having affected children, which has potential implications for genetic counseling
Clinical and genetic keys to cerebellar ataxia due to FGF14 GAA expansionsResearch in context
Summary: Background: SCA27B caused by FGF14 intronic heterozygous GAA expansions with at least 250 repeats accounts for 10â60% of cases with unresolved cerebellar ataxia. We aimed to assess the size and frequency of FGF14 expanded alleles in individuals with cerebellar ataxia as compared with controls and to characterize genetic and clinical variability. Methods: We sized this repeat in 1876 individuals from France sampled for research purposes in this cross-sectional study: 845 index cases with cerebellar ataxia and 324 affected relatives, 475 controls, as well as 119 cases with spastic paraplegia, and 113 with familial essential tremor. Findings: A higher frequency of expanded allele carriers in index cases with ataxia was significant only above 300 GAA repeats (10.1%, n = 85) compared with controls (1.1%, n = 5) (p < 0.0001) whereas GAA250â299 alleles were detected in 1.7% of both groups. Eight of 14 index cases with GAA250-299 repeats had other causal pathogenic variants (4/14) and/or discordance of co-segregation (5/14), arguing against GAA causality. We compared the clinical signs in 127 GAAâ„300 carriers to cases with non-expanded GAA ataxia resulting in defining a key phenotype triad: onset after 45 years, downbeat nystagmus, episodic ataxic features including diplopia; and a frequent absence of dysarthria. All maternally transmitted alleles above 100 GAA were unstable with a median expansion of +18 repeats per generation (r2 = 0.44; p < 0.0001). In comparison, paternally transmitted alleles above 100 GAA mostly decreased in size (â15 GAA (r2 = 0.63; p < 0.0001)), resulting in the transmission bias observed in SCA27B pedigrees. Interpretation: SCA27B diagnosis must consider both the phenotype and GAA expansion size. In carriers of GAA250-299 repeats, the absence of documented familial transmission and a presentation deviating from the key SCA27B phenotype, should prompt the search for an alternative cause. Affected fathers have a reduced risk of having affected children, which has potential implications for genetic counseling. Funding: This work was supported by the Fondation pour la Recherche MĂ©dicale, grant number 13338 to JLM, the Association ConnaĂźtre les Syndrome CĂ©rĂ©belleux â France (to GS) and by the European Unionâs Horizon 2020 research and innovation program under grant agreement No 779257 (âSOLVE-RDâ to GS). DP holds a Fellowship award from the Canadian Institutes of Health Research (CIHR). SK received a grant (01GM1905C) from the Federal Ministry of Education and Research, Germany, through the TreatHSP network. This work was supported by the Australian Government National Health and Medical Research Council grants (GNT2001513 and MRFF2007677) to MB and PJL