1H-NMR-Based Metabolomic Profiling of CSF in Early Amyotrophic Lateral Sclerosis

Background: Pathophysiological mechanisms involved in amyotrophic lateral sclerosis (ALS) are complex and none has identified reliable markers useful in routine patient evaluation. The aim of this study was to analyze the CSF of patients with ALS by 1 H NMR (Nuclear Magnetic Resonance) spectroscopy in order to identify biomarkers in the early stages of the disease, and to evaluate the biochemical factors involved in ALS. Methodology: CSF samples were collected from patients with ALS at the time of diagnosis and from patients without neurodegenerative diseases. One and two-dimensional 1 H NMR analyses were performed and metabolites were quantified by the ERETIC method. We compared the concentrations of CSF metabolites between both groups. Finally, we performed principal component (PCA) and discriminant analyses. Principal Findings: Fifty CSF samples from ALS patients and 44 from controls were analyzed. We quantified 17 metabolites including amino-acids, organic acids, and ketone bodies. Quantitative analysis revealed significantly lower acetate concentrations (p = 0.0002) in ALS patients compared to controls. Concentration of acetone trended higher (p = 0.015), and those of pyruvate (p = 0.002) and ascorbate (p = 0.003) were higher in the ALS group. PCA demonstrated that the pattern of analyzed metabolites discriminated between groups. Discriminant analysis using an algorithm of 17 metabolites reveale

Birth during on-call period: Impact of care organization on mortality and morbidity of very premature neonates

International audienceObjectives The evidence that risks of morbidity and mortality are higher when very premature newborns are born during the on-call period is inconsistent. This study aimed to assess the impact of this situation among other determinants of outcomes, particularly newborn characteristics and care organization.Methods Observational study including all infants born < 30 weeks’ gestation in a French tertiary perinatal center between 2007 and 2020. On-call period corresponded to weekdays between 6:30 p.m. and 8:30 a.m., weekends, and public holidays. The primary endpoint was survival without severe morbidity, including grade 3–4 intraventricular hemorrhage (IVH), cystic periventricular leukomalacia, necrotizing enterocolitis, severe bronchopulmonary dysplasia (BPD), and severe retinopathy of prematurity. The relationship between admission and outcome was assessed by an adjusted odds ratio (aOR) on the propensity of being born during on-call period and expressed vs. weekday. Secondary analyses were carried out in extremely preterm newborns (<27 weeks’ gestation), in cases of early death (within 7 days), and before (2007–2013, 51.5% of the cohort) vs. after (2014–2020, 48.5% of the cohort) the implementation of a pediatrician-nurse team dedicated to newborn care in the delivery room.Results A total of 1,064 infants [27.9 (26.3; 28.9) weeks, 947 (760; 1,147) g] were included: 668 during the on-call period (63%) and 396 (37%) on weekdays. For infants born on weekdays, survival without severe morbidity was 54.5% and mortality 19.2%. During on-call, these rates were 57.3% [aOR 1.08 (0.84–1.40)] and 18.4% [aOR 0.93 (0.67–1.29)]. Comparable rates of survival without severe morbidity [aOR 1.42 (0.87–2.34)] or mortality [aOR 0.76 (0.47–1.22)] were observed in extremely preterm infants. The early death rate was 6.4% on weekdays vs. 8.2% during on-call [aOR 1.44 (0.84–2.48)]. Implementation of the dedicated team was associated with decreased rates of mortality [aOR 0.57 (0.38, 0.85)] and grade 3–4 IVH [aOR 0.48 (0.30, 0.75)], and an increased rate of severe BPD [aOR 2.16 (1.37, 3.41)], for infants born during on-call.Conclusion In this cohort, most births of very premature neonates occurred during the on-call period. A team dedicated to newborn care in the delivery room may have a favorable effect on the outcome of infants born in this situation

A call for promoting living kidney donation in France in 2023.

peer reviewedKidney transplantation from living donors is particularly under-developed in France in comparison with the US and most European countries. Among others, the lack of a proactive and evidence-based communication from French health providers is a potential cause that has been overlooked thus far. With this as a backdrop, the SFNDT Commission of transplantation has elaborated a 10 points-call for promoting living kidney transplantation in France in 2023 with the aims at (1) providing the entire nephrology community with a scientific rationale and (2) strenghtening the conviction of health providers, patients, and their relatives regarding the relevance of this modality of kidney transplantation.La transplantation rénale à partir de donneur vivant est une activité qui reste insuffisamment développée en France. Ceci est particulièrement vrai en comparaison à la majorité des pays nord-américains et européens. Les raisons en sont multiples et incluent un défaut de communication proactive et argumentée par les acteurs de soins. La communication, l’information et finalement la promotion de la greffe à partir de donneurs vivants sont l’affaire de l’ensemble de la communauté néphrologique et, au premier rang, des néphrologues non spécifiquement impliqués en transplantation. C’est dans cet esprit que la Commission Transplantation de la Société francophone de néphrologie, dialyse et transplantation (SFNDT) a travaillé à l’élaboration d’un plaidoyer en tentant de répondre, en dix points, à la question « Pourquoi faut-il développer la transplantation rénale à partir de donneurs vivants en France en 2023 ? ». L’objectif est double : (1) fournir les principales bases d’une information scientifiquement argumentée et (2) renforcer la conviction de l’ensemble des acteurs de soins et des patients du bien-fondé de cette modalité de greffe

Impact of post-brentuximab vedotin consolidation on relapsed/refractory CD30+ Hodgkin lymphomas: a large retrospective study on 240 patients enrolled in the French Named-Patient Program

International audienceBrentuximab vedotin was reported to be effective and safe against refractory/relapsed Hodgkin lymphoma in cohorts of 12 to 102 patients. Herein we report our retrospective analysis of the French experience with brentuximab vedotin used alone to treat 240 refractory/relapsed Hodgkin lymphoma patients enrolled in a named patient program between 2011 and 2013. All patients had histologically documented CD30+ Hodgkin lymphoma; 74% had refractory disease or early relapses. After a median of 3 chemotherapy lines, brentuximab vedotin was infused intravenously (1.8 mg/kg every 3 weeks). The primary endpoint was best response. Response at the end of treatment, its duration, survival data and toxicity profile were secondary endpoints. Patients received a median of 6 cycles; 68 underwent a consolidation thereafter. The best response was observed after a median of 4 cycles in 145 (60.4%) patients: 33.8% complete response/unconfirmed complete response, 26.7% partial response. Objective responses were observed decreased (39.3%) in the 28 patients \textgreater60 years. Median response duration was 8.4 months. With median follow-up at 16.1 months, median progression free-survival was 6.8 months and significantly longer for patients transplanted after brentuximab vedotin (median at 18,8 months); median overall survival was not reached. No death has been linked to brentuximab vedotin toxicity. The most common adverse events were peripheral sensory neuropathy (29.3%) and hematological toxicity. The results of this analysis support the previously reported brentuximab vedotin efficacy with manageable toxicity. Because short-term responses in most patients, high-dose therapy with stem-cell transplantation for responders should be considered rapidl

The P413L chromogranin B variation in French patients with sporadic amyotrophic lateral sclerosis.

International audienceChromogranins interact with mutant forms of superoxide dismutase 1 (SOD1) responsible for a portion of familial amyotrophic lateral sclerosis (ALS). A particular variation (P413L) in the chromogranin B gene, CHGB, has been recently associated with an earlier age at onset in both familial and sporadic ALS. The aim of our study was to evaluate the P413L chromogranin variation in French patients with sporadic amyotrophic lateral sclerosis. We developed a High Resolution DNA Melting (HRM) protocol to analyse the P413L variation in the CHGB gene in 540 French patients with sporadic ALS and 504 controls. The clinical characteristics of patients were analysed in relation to their genotype. Results showed that our study on a large cohort of French-Caucasian patients with SALS and controls failed to confirm an increased frequency of the 413L variant in SALS patients. This frequency was 5.3% in the SALS population and 5.5% in the control group. Moreover, we did not observe a previous observation of a difference of age at onset between T-allele carriers and non-carriers (median age of onset 60.4 vs. 62.0 years of age, respectively). Thus, our findings do not support the 413L variant of rs742710 as a risk factor for sporadic ALS in the French population

Long-term surgical oncological and functional outcome of large petroclival and cerebellopontine angle epidermoid cysts: a multicenter study

International audienceCranial nerve (CN) disorders are the foremost symptoms in cerebellopontine angle (CPA) and petroclival area (PCA) epidermoid cysts (EC).The aim of this work was to assess the long-term surgical results on CN function and tumor control in these patients. We performed a retrospective cohort study about 56 consecutive patients operated on for a CPA or PCA EC between January 2001 and July 2019 in six participating French cranial base referral centers. Sixteen patients (29%) presented a PCA EC and 40 a CPA EC (71%). The median clinical and radiological follow-up was 46 months (range 0-409). Preoperative CN disorders were present in 84% of patients (n = 47), 72% of them experienced CN deficits improvement at the last follow-up consultation (n = 34): 60% of cochlear and vestibular deficits (n = 9/15 in both groups), 67% of trigeminal neuralgia (n = 10/15), 53% of trigeminal hypoesthesia (n = 8/15), 44% of lower cranial nerve disorders (n = 4/9), 38% of facial nerve deficits (n = 5/8) and 43% of oculomotor deficits (n = 3/7) improved or were cured after surgery. New postoperative CN deficits occurred in 48% of patients (n = 27). Most of them resolved at the last follow-up, except for cochlear deficits which improved in only 14% of cases (n = 1/7). Twenty-six patients (46%) showed evidence of tumor progression after a median duration of 63 months (range 7-210). The extent of resection, tumor location, and tumor size was not associated with the occurrence of new postoperative CN deficit or tumor progression. A functional nerve-sparing resection of posterior fossa EC is an effective strategy to optimize the results on preexisting CN deficits and reduce the risk of permanent de novo deficits

Principal Component Analysis score plot for ALS (n = 50) and non ALS patients (n = 44).

<p>Principal Component Analysis score plot for ALS (n = 50) and non ALS patients (n = 44).</p

CSF spectra by ¹H NMR from ALS patient (A) and non ALS patient (B).

<p>CSF spectra by ¹H NMR from ALS patient (A) and non ALS patient (B).</p