At-Risk Phenotype of Neurofibromatose-1 Patients: A Multicentre Case-Control Study

<p>Abstract</p> <p>Objectives</p> <p>To assess associations between subcutaneous neurofibromas (SC-NFs) and internal neurofibromas in patients with neurofibromatosis type 1 (NF-1) and to determine whether the association between SC-NFs and peripheral neuropathy was ascribable to internal neurofibromas.</p> <p>Patients and methods</p> <p>Prospective multicentre case-control study. Between 2005 and 2008, 110 NF-1 adults having two or more SC-NFs were individually matched for age, sex and hospital with 110 controls who had no SC-NF. Patients underwent standardized MRI of the spinal cord, nerve roots and sciatic nerves and an electrophysiological study. Analyses used adjusted multinomial logistic regression (ORa) to estimate the risk of the presence of internal neurofibromas or peripheral neuropathies associated with patients presented 2 to 9 SC-NFs, at least 10 SC-NFs as compared to patients without any (referential category).</p> <p>Results</p> <p>Cases had a mean age of 41 (± 13) years; 85 (80%) had two to nine SC-NFs and 21 (19%) at least ten SC-NFs. SC-NFs were more strongly associated with internal neurofibromas in patients with ten or more SC-NFs than in patients with fewer NF-SCs (e.g., sciatic nerve, aOR = 29.1 [8.5 to 100] vs. 4.3 [2.1 to 9.0]). The association with SC-NFs was stronger for diffuse, intradural, and > 3 cm internal neurofibromas than with other internal neurofibromas. Axonal neuropathy with slowed conduction velocities (SCV) was more strongly associated with having at least ten SC-NFs (aOR = 29.9, 5.5 to 162.3) than with having fewer SC-NFs (aOR = 4.4, 0.9 to 22.0). Bivariate analyses showed that the association between axonal neuropathy with SCV and sciatic neurofibromas was mediated by the association between SC-NFs and sciatic neurofibromas.</p> <p>Conclusion</p> <p>The at-risk phenotype of NF-1 patients (i.e. NF-1 patients with SC-NFs) is ascribable to associations linking SC-NFs to internal neurofibromas at risk for malignant transformation and to axonal neuropathies with slowed conduction velocities. Axonal neuropathies with SCV are particularly common in patients with at least ten SC-NFs.</p> <p>Registration details</p> <p>ORPHA86301</p

Assessment of the Utility of Kidney Histology as a Basis for Discarding Organs in the United States: A Comparison of International Transplant Practices and Outcomes.

peer reviewedBACKGROUND: Many kidneys donated for transplant in the United States are discarded because of abnormal histology. Whether histology adds incremental value beyond usual donor attributes in assessing allograft quality is unknown. METHODS: This population-based study included patients who received a deceased donor kidney that had been biopsied before implantation according to a prespecified protocol in France and Belgium, where preimplantation biopsy findings are generally not used for decision making in the allocation process. We also studied kidneys that had been acquired from deceased United States donors for transplantation that were biopsied during allocation and discarded because of low organ quality. Using donor and recipient characteristics, we fit multivariable Cox models for death-censored graft failure and examined whether predictive accuracy (C index) improved after adding donor histology. We matched the discarded United States kidneys to similar kidneys transplanted in Europe and calculated predicted allograft survival. RESULTS: In the development cohort of 1629 kidney recipients at two French centers, adding donor histology to the model did not significantly improve prediction of long-term allograft failure. Analyses using an external validation cohort from two Belgian centers confirmed the lack of improved accuracy from adding histology. About 45% of 1103 United States kidneys discarded because of histologic findings could be accurately matched to very similar kidneys that had been transplanted in France; these discarded kidneys would be expected to have allograft survival of 93.1% at 1 year, 80.7% at 5 years, and 68.9% at 10 years. CONCLUSIONS: In this multicenter study, donor kidney histology assessment during allocation did not provide substantial incremental value in ascertaining organ quality. Many kidneys discarded on the basis of biopsy findings would likely benefit United States patients who are wait listed

The Banff 2019 Kidney Meeting Report (I): Updates on and clarification of criteria for T cell– and antibody-mediated rejection

The XV. Banff conference for allograft pathology was held in conjunction with the annual meeting of the American Society for Histocompatibility and Immunogenetics in Pittsburgh, PA (USA) and focused on refining recent updates to the classification, advances from the Banff working groups, and standardization of molecular diagnostics. This report on kidney transplant pathology details clarifications and refinements to the criteria for chronic active (CA) T cell–mediated rejection (TCMR), borderline, and antibody-mediated rejection (ABMR). The main focus of kidney sessions was on how to address biopsies meeting criteria for CA TCMR plus borderline or acute TCMR. Recent studies on the clinical impact of borderline infiltrates were also presented to clarify whether the threshold for interstitial inflammation in diagnosis of borderline should be i0 or i1. Sessions on ABMR focused on biopsies showing microvascular inflammation in the absence of C4d staining or detectable donor-specific antibodies; the potential value of molecular diagnostics in such cases and recommendations for use of the latter in the setting of solid organ transplantation are presented in the accompanying meeting report. Finally, several speakers discussed the capabilities of artificial intelligence and the potential for use of machine learning algorithms in diagnosis and personalized therapeutics in solid organ transplantation

Transmission in Heteronymous Spinal Pathways Is Modified after Stroke and Related to Motor Incoordination

Changes in reflex spinal pathways after stroke have been shown to affect motor activity in agonist and antagonist muscles acting at the same joint. However, only a few studies have evaluated the heteronymous reflex pathways modulating motoneuronal activity at different joints. This study investigates whether there are changes in the spinal facilitatory and inhibitory pathways linking knee to ankle extensors and if such changes may be related to motor deficits after stroke. The early facilitation and later inhibition of soleus H reflex evoked by the stimulation of femoral nerve at 2 times the motor threshold of the quadriceps were assessed in 15 healthy participants and on the paretic and the non-paretic sides of 15 stroke participants. The relationships between this reflex modulation and the levels of motor recovery, coordination and spasticity were then studied. Results show a significant (Mann-Whitney U; P<0.05) increase in both the peak amplitude (mean±SEM: 80±22% enhancement of the control H reflex) and duration (4.2±0.5 ms) of the facilitation on the paretic side of the stroke individuals compared to their non-paretic side (36±6% and 2.9±0.4 ms) and to the values of the control subjects (33±4% and 2.8±0.4 ms, respectively). Moreover, the later strong inhibition observed in all control subjects was decreased in the stroke subjects. Both the peak amplitude and the duration of the increased facilitation were inversely correlated (Spearman r = −0.65; P = 0.009 and r = −0.67; P = 0.007, respectively) with the level of coordination (LEMOCOT) of the paretic leg. Duration of this facilitation was also correlated (r = −0.58, P = 0.024) with the level of motor recovery (CMSA). These results confirm changes in transmission in heteronymous spinal pathways that are related to motor deficits after stroke

Long-term outcomes of CLIPPERS (chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids) in a consecutive series of 12 patients.

BACKGROUND: Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is a central nervous system inflammatory disease. OBJECTIVE: To describe the disease course of CLIPPERS. DESIGN: A nationwide study was implemented to collect clinical, magnetic resonance imaging, cerebrospinal fluid, and brain biopsy specimen characteristics of patients with CLIPPERS. SETTING: Academic research. PATIENTS: Twelve patients with CLIPPERS. MAIN OUTCOME MEASURES: The therapeutic management of CLIPPERS was evaluated. RESULTS: Among 12 patients, 42 relapses were analyzed. Relapses lasted a mean duration of 2.5 months, manifested frequent cerebellar ataxia and diplopia, and were associated with a mean Expanded Disability Status Scale (EDSS) score of 4. Besides typical findings of CLIPPERS, magnetic resonance imaging showed brainstem mass effect in 5 patients, extensive myelitis in 3 patients, and closed ring enhancement in 1 patient. Inconstant oligoclonal bands were found on cerebrospinal fluid investigation in 4 patients, with an increased T-cell ratio of CD4 to CD8. Among 7 available brain biopsy specimens, staining was positive for perivascular CD4 T lymphocytes in 5 samples. Thirty-eight of 42 relapses were treated with pulse corticosteroid therapy, which led to improvement, with a mean residual EDSS score of 1.9 (range, 0-7). In 1 patient with untreated relapses, scores on the EDSS progressively increased to a score of 10 at death. Among 5 patients without long-term corticosteroid therapy, the mean annualized relapse rate was 0.5 (range, 0.25-2.8). Among 7 patients taking oral corticosteroids, no relapses occurred in those whose daily dose was 20 mg or higher. No progressive course of CLIPPERS was observed. Four patients with a final EDSS score of 4 or higher had experienced previous severe relapses (EDSS score, ≥5) and brainstem and spinal cord atrophy. CONCLUSIONS: CLIPPERS is a relapsing-remitting disorder without progressive forms. Long-term disability is correlated with the severity of previous relapses. Further studies are needed to confirm that prolonged corticosteroid therapy prevents further relapses.journal article2012 Julimporte

Phenotypic and genetic parameters for longissimus muscle fiber characteristics in relation to growth, carcass, and meat quality traits in Large White pigs

76 ref. 6 tablesInternational audienc

Sélection pour un abaissement du potentiel glycolytique du muscle chez le porc Large White pigs. 2. Réponses corrélatives pour la qualité de la viande et la composition du muscle

National audienceA selection experiment was conducted over six generations in a purebred French Large White population presumably free of the HALn and RN- alleles. Two lines were taken from the same base population and were contemporarily bred: one control line (C) and one line (S) selected for reduced in vivo glycolytic potential (IVGP) of the longissimus muscle. Throughout the experiment, second-parity animals were slaughtered at 100 kg body weight in order to evaluate the correlated effects of selection on meat quality and muscle compositional traits. Heritability values, genetic correlations with the selection criterion and average genetic trends per generation were estimated for all traits. Heritability values for the traits measured on several muscles depended on the muscle. Within muscle heritability, estimates for ultimate pH and lightness L* value were of the same order. For enzyme activities, estimates of heritability were from 0.12 to 0.44 for lactate dehydrogenase (LDH), from 0.22 to 0.44 for citrate synthase (CS) and from 0.06 to 0.26 for the LDH/CS ratio. Heritability values for longissimus muscle compositional traits were of medium range (from 0.33 to 0.59), except for nitrogen content. The heritability estimate for the technological yield of cured-cook ham processing was 0.32 ± 0.09. Most physiological and chemical characteristics of the longissimus muscle were not significantly affected by selection. No genetic change was found for technological yield, though the genetic correlation of this trait with IVGP was in the medium range (-0.42 ± 0.12). The S line showed significant genetic trends for longissimus muscle enzyme activities and fibre characteristics, indicating that it had a more glycolytic muscle metabolism than the C line, with a lower proportion of oxido-glycolytic fibres, a higher proportion of glycolytic fibres, a higher LDH/CS ratio and a lower haem pigment content.Une expérience de sélection a été conduite sur six générations dans une population de porcs de race pure Large White français, présumée indemne des allèles HALn et RN-. Deux lignées ont été formées à partir de la même population de base, et ont été conduites de manière contemporaine : une lignée témoin (C) et une lignée sélectionnée (S) pour diminuer le potentiel glycolytique mesuré in vivo (IVGP) sur le muscle longissimus. Au cours de cette expérience, des animaux issus des deuxièmes portées ont été abattus à 100 kg de poids vif afin d’étudier les effets de la sélection sur la qualité de la viande et les caractères de composition du muscle. Pour tous les caractères, les valeurs d’héritabilité, les corrélations génétiques avec IVGP et les réponses génétiques moyennes par génération ont été estimées. Pour les caractères mesurés sur plusieurs muscles différents, les valeurs d’héritabilité varient d’un muscle à l’autre. Pour un même muscle, les héritabilités du pH ultime et de la valeur de luminosité L* sont du même ordre de grandeur. Les héritabilités des activités enzymatiques varient selon le muscle de 0,12 à 0,44 pour la lactate déshydrogénase (LDH), de 0,22 à 0,44 pour la citrate synthase (CS) et de 0,06 à 0,26 pour le rapport LDH/CS. Les héritabilités estimées pour la composition chimique du muscle longissimus sont moyennes (0,33 à 0,59), excepté pour la teneur en azote. L’héritabilité du rendement technologique de la fabrication du jambon cuit est de 0, 32 ± 0,09. La plupart des caractéristiques physiologiques et chimiques du muscle longissimus ont peu évolué sous l’effet de la sélection. Il en a été de même pour le rendement technologique, bien que la corrélation génétique estimée entre ce caractère et IVGP soit de valeur moyenne (-0, 42 ± 0, 12).De plus, la lignée S a montré une réponse génétique significative pour les activités enzymatiques et pour la typologie des fibres du muscle longissimus. Les animaux de la lignée S avaient un métabolisme musculaire plus glycolytique que ceux de la lignée C, avec une proportion plus faible de fibres oxydo-glycolytiques, une proportion plus importante de fibres glycolytiques, une valeur plus forte du rapport LDH/CS et une teneur plus faible en pigment

A case of POEMS syndrome treated by autologous hematopoietic stem-cell transplantation.

International audienceBACKGROUND: A 55-year-old woman with no remarkable medical history presented to a neurology ward with a 17-week history of rapidly progressive gait difficulties that confined her to a wheelchair. INVESTIGATIONS: Electroneuromyography, immunoelectrophoresis, bone radiography, lesion-targeted bone-marrow examination, blood tests. DIAGNOSIS: Neuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome. MANAGEMENT: High-dose chemotherapy and autologous hematopoietic stem-cell transplantation