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Autoinflammatory diseases related to RIPK1 mutations have been recently described. Two distinct clinical phenotypes have been reported and depend on the type and location of the mutation. When the mutation is recessive with loss of function, patients develop a combined phenotype of immune deficiency with recurrent bacterial and fungal infections and signs of early inflammatory bowel disease, non-erosive polyarthritis and growth retardation. On the other hand, when the mutation is dominant, gain of function, the manifestations are only auto-inflammatory with extensive lymphoproliferation, oral lesions such as aphthosis or ulcers, abdominal pain and hepatosplenomegaly. The mutations described for the dominant form affect only the cleavage site of caspase 8 and the clinical phenotype is called CRIA for Cleavage-Resistant RIPK1-Induced Autoinflammatory syndrome. The recessive form is severe and life-threatening requiring hematopoietic stem cell transplantation while the dominant form responds well to interleukin-6 receptor antagonists. Thus, RIPK1 mutations can induce various clinical manifestations with two distinct phenotypes. Although still rare, because of their recent description, these diseases can be suspected by an internist, in front of recurrent digestive features and will be increasingly diagnosed in the future through the integration of this gene in the diagnostic chips dedicated to autoinflammatory diseases and early inflammatory bowel diseases, using next generation sequencing.

To describe the management of home oxygen therapy for infants with acute bronchiolitis through a home care network: Hospital at Home (HAH).A retrospective observational study was carried out during two consecutive winters from 2012 to 2014.A total of 141 patients were eligible for home oxygen therapy, and 54 were discharged on home oxygen therapy through HAH. The median age of patients was 2.5 months (0.75-13 months). The average length of hospital stay before discharge was 4.9 days (1-17 days). In total, 73% of the children received oxygen at home. There was an average of five nurse visits per patient. Each child was seen by a pediatrician during the HAH care. There were no deaths or readmissions to an intensive care unit. There were two conventional readmissions for increased respiratory distress and two emergency department visits. The median length of HAH was 6 days (1-33 days).Home oxygen for infants with acute bronchiolitis is a promising and safe alternative to reduce conventional hospitalizations. It is necessary to evaluate the cost of this treatment and its impact on nosocomial infections.

BackgroundPediatric Inflammatory Multisystemic Syndrome associated to SARS-CoV2 (PIMS) happens 4 to 6 weeks after SARS-CoV2 infection1-2. Its early diagnostic recognition as well as its early management is important to avoid cardiac complications related to this pathology.ObjectivesTo highlight a frequent symptom in PIMS and improve its therapeutic care.MethodsThe JIR Cohort database, an international registry collecting data on patients with pediatric inflammatory diseases, was consulted to include patients between 03/15/20 and 12/31/2021.ResultsOf the 140 patients in whom a diagnosis of PIMS was retained, we present a series of 38 patients (27%) who presented at diagnosis or during evolution, febrile torticollis or painful cervical involvement. These patients were on average 8.2 years old (0.6-15.2). The proportion of boys was 14 out of 38 (37%). Twenty-four patients out of 33 (73%) were hospitalized in intensive care. Ten patients out of 38 (26%) underwent cervical imaging, 5 (50%) had abnormalities such as collection or infiltration of the soft tissues. At the therapeutic level, 27/38 patients (71%) received corticosteroid therapy, 33/38 (87%) immunoglobulins, and 26/38 (68%) antibiotic therapy.ConclusionPIMS is a pathology with significant clinical heterogeneity and severe consequences in case of delay in therapeutic management. In this epidemic context, it is important to consider PIMS in any patient with febrile torticollis, especially if he does not respond to antibiotics.References[1]Feldstein LR, Rose EB, Horwitz SM, Collins JP, Newhams MM, Son MBF, et al. Multisystem Inflammatory Syndrome in U.S. Children and Adolescents. N Engl J Med. 23 juill 2020.[2]Whittaker E, Bamford A, Kenny J, Kaforou M, Jones CE, Shah P, et al. Clinical Characteristics of 58 Children With a Pediatric Inflammatory Multisystem Syndrome Temporally Associated With SARS-CoV-2. JAMA. 8 juin 2020Disclosure of InterestsNone declared

BackgroundThe low prevalence of systemic autoimmune diseases and the diversity of their clinical manifestations make complex to conduct randomised clinical trials to assess the potential efficacy of targeted treatments.ObjectivesTo assess the tolerance and efficacy of targeted therapies prescribed off-label in refractory autoimmune diseases.MethodsThe TATA registry (TArgeted Therapy in Autoimmune Diseases) is a prospective, observational, national and independent cohort follow-up. The inclusion criteria in the registry are as follows: age > 18 years; rare systemic autoimmune disease (systemic lupus erythematosus, Sjögren’s syndrome, systemic scleroderma, inflammatory myopathy, vasculitis) or other refractory rheumatism treated with off-label drugs started after 1st January 2019.ResultsHundred (100) patients (79 females) were enrolled. The median age was 52.5 years [49;56], the median disease duration before enrolment was 5 years [3;7]. The targeted therapies at enrolment were as follows: JAK/STAT inhibitors (44%), anti-IL6R (22%), anti-IL12/23, anti-IL23 and anti-IL17 (9%), anti-BAFF (5%), abatacept (5%), other targeted treatments (9%), and combination of targeted treatments (6%). 73% of patients were receiving corticosteroid therapy at enrolment (median dose 10 mg/day). The current median follow-up time is 9 months [8;10].Safety: 11 serious infections (incidence rate of 14.8 /100 patient-years) and 1 cancer (1.3 cancers/100 patient-years) were observed. Two patients died from severe COVID-19 (2.7 deaths/100 patient-years).Efficacy: The targeted treatment was considered effective by the clinician in 56% of patients and allowed in responders a median reduction of oral corticosteroids of 15 [9-21] mg/day.ConclusionThese initial results of the TATA registry confirm the diversity of targeted treatments prescribed off-label in refractory autoimmune diseases and their corticosteroid-sparing effect when effective. Tolerance was acceptable in these refractory patients with a long history of treatment with immunosuppressive drugs.References[1]B. Terrier et al., Safety and efficacy of rituximab in systemic lupus erythematosus: results from 136 patients from the French AutoImmunity and Rituximab registry. Arthritis Rheum 62, 2458-2466 (2010).[2]J. E. Gottenberg et al., Efficacy of rituximab in systemic manifestations of primary Sjogren’s syndrome: results in 78 patients of the AutoImmune and Rituximab registry. Ann Rheum Dis 72, 1026-1031 (2013).[3]J. E. Gottenberg et al., Risk factors for severe infections in patients with rheumatoid arthritis treated with rituximab in the autoimmunity and rituximab registry. Arthritis Rheum 62, 2625-2632 (2010).[4]F. R. S. S. S. C. I. consortium, contributors, Severity of COVID-19 and survival in patients with rheumatic and inflammatory diseases: data from the French RMD COVID-19 cohort of 694 patients. Ann Rheum Dis, (2020).[5]R. Felten et al., B-cell targeted therapy is associated with severe COVID-19 among patients with inflammatory arthritides: a 1-year multicentre study in 1116 successive patients receiving intravenous biologics. Ann Rheum Dis 81, 143-145 (2022).[6]D. J. Wallace et al., Baricitinib for systemic lupus erythematosus: a double-blind, randomised, placebo-controlled, phase 2 trial. Lancet 392, 222-231 (2018).[7]J. J. Paik et al., Study of Tofacitinib in Refractory Dermatomyositis: An Open-Label Pilot Study of Ten Patients. Arthritis Rheumatol 73, 858-865 (2021).[8]S. Cole et al., Integrative analysis reveals CD38 as a therapeutic target for plasma cell-rich pre-disease and established rheumatoid arthritis and systemic lupus erythematosus. Arthritis Res Ther 20, 85 (2018).[9]S. J. Bowman et al., Safety and efficacy of subcutaneous ianalumab (VAY736) in patients with primary Sjogren’s syndrome: a randomised, double-blind, placebo-controlled, phase 2b dose-finding trial. Lancet 399, 161-171 (2022).AcknowledgementsFrench networks (FAI2R, CRI, IMIDIATE, SFR, SNFMI) focused on rare systemic autoimmune diseases contributed this work by the contribution of network-affiliated physicians.Disclosure of InterestsJacques-Eric Gottenberg Consultant of: Abbvie, BMS, Gilead, Galapagos, Novartis, Lilly Roche Chugai, Sanofi, Janssen, Pfizer, Grant/research support from: BMS.Lilly and Pfizer for this register (with no access to data)., Aurore Chaudier: None declared, Yves Allenbach: None declared, Arsene Mekinian: None declared, Zahir Amoura: None declared, Patrice cacoub: None declared, Divi Cornec: None declared, Eric Hachulla: None declared, Pierre Quartier: None declared, isabelle melki: None declared, Christophe Richez: None declared, Raphaèle Seror: None declared, Benjamin Terrier: None declared, Valerie Devauchelle-Pensec: None declared, Julien Henry: None declared, MARC GATFOSSE: None declared, LAURENCE BOUILLET: None declared, Emeline GAIGNEUX: None declared, Vincent ANDRE: None declared, Gildas BAULIER: None declared, Aurélie SAUNIER: None declared, Marie Desmurs: None declared, Antoine POULET: None declared, Mathieu ETE: None declared, Marie-Elise Truchetet: None declared, Martin Michaud: None declared, Claire Larroche: None declared, AZEDDINE DELLAL: None declared, Amelie LEURS: None declared, Sebastien Ottaviani: None declared, Hubert NIELLY: None declared, Guillaume VIAL: None declared, Roland JAUSSAUD: None declared, Benedicte ROUVIERE: None declared, Pierre-Yves JEANDEL: None declared, Aurelien GUFFROY: None declared, Anne-Sophie Korganow: None declared, Mathieu JOUVRAY: None declared, alain meyer: None declared, Emmanuel Chatelus: None declared, Christelle Sordet: None declared, Renaud FELTEN: None declared, Jean Sibilia: None declared, Samira AHMED YAHIA: None declared, Jean François Kleinmann: None declared, Xavier Mariette Consultant of: BMS, Galapagos, GSK, Janssen, Novartis, Pfizer, Sanofi, UCB

L'effet des antipaludeens de synthese sur les infections virales est etudie depuis plusieurs annees, y compris l'hypothese d'un effet sur le SARS [1]. L'efficacite in vitro de la chloroquine contre le SARS-CoV-2 a ete decrite [2] , ainsi que la superiorite potentielle de l'hydroxycholoroquine. De nombreuses etudes in vivo ont ete menees. Il existe peu de donnees sur l'impact d'un traitement au long cours par hydroxychloroquine (HCQ) sur l'infection a SARS CoV-2 et les tests diagnostiques. Nous avons pour cela analyse les donnees des patients atteints de COVID-19 et suivis pour un rhumatisme inflammatoire chronique et/ou une maladie auto-immune systemique (iRMD-COVID-19) selon la prise ou non d'hydroxychloroquine comme DMARD. Les patients ont ete inclus a partir de la cohorte francaise iRMD-COVID-19 [3]. Les donnees cliniques, diagnostiques et d'evolution de l'infection a SARS CoV-2 des patients traites au prealable par HCQ ont ete comparees a celle des patients n'ayant pas de traitement par HCQ au moment de l'infection. Les criteres d'appariement etaient l'âge, le sexe, les comorbidites, un traitement immunosuppresseur, et l'utilisation de la PCR nasale. Parmi les 871 patients, 82 patients etaient traites par HCQ. Soixante et onze cas traites par HCQ ont pu etre apparies et compares a 191 temoins. Le taux de PCR nasale positive etait de 85 % dans le groupe HCQ contre 81 % dans le groupe controle (absolute standardized difference = 6,0 %). Il n'y avait pas de difference significative entre les cas et les controles concernant les signes cliniques, le taux d'hospitalisation (33,8 % vs 27,7 % ;OR = 1,75 (0,86-3,56) ;p = 0,12), le taux d'admission en soins intensifs (11,3 % vs 9,4 % ;OR= 1,94 (0,69-5,41) ;p = 0,21) et le taux de deces (5,9 % vs 6,6 % ;OR = 1,10 (0,30-4,04) ;p = 0,89). Chez les patients atteints de COVID-19 et suivis pour un rhumatisme inflammatoire chronique et/ou une maladie auto-immune systemique de la cohorte French RMD Covid 19, la prise d'HCQ comme DMARD n'a pas modifie le taux de positivite de la PCR nasale, n'a pas modifie la presentation clinique et n'a pas prevenu la survenue de forme severe de l'infection a SARS CoV-2 comparativement aux patients sans HCQ. (French) [ABSTRACT FROM AUTHOR] Copyright of Revue de Medecine Interne is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Resume Le rotavirus est la cause la plus frequente de gastro-enterite (GEA) necessitant une hospitalisation chez l’enfant. C’est un virus tres resistant et contagieux a l’origine de nombreuses GEA nosocomiales (GEAN). En France, le vaccin contre le rotavirus est disponible depuis 2006, mais il n’est pas recommande. Le but de cette etude retrospective etait de decrire les GEAN a rotavirus et d’evaluer leur incidence chez les enfants hospitalises dans le service de pediatrie generale de l’hopital Robert-Debre (Paris) entre le 1 er janvier 2009 et le 31 decembre 2013. Nous avons evalue si ces enfants auraient pu beneficier de la vaccination contre le rotavirus. Resultats Au total, 136 enfants ont presente une GEAN a rotavirus, soit une incidence de 2,5 cas pour 1000 jours d’hospitalisation. Cette incidence est restee stable entre 2009 et 2013 malgre le renforcement des mesures d’hygiene. L’âge moyen des enfants etait de 7 mois (entre 0,5 et 111 mois). Les GEAN a rotavirus etaient survenues chez des enfants hospitalises le plus souvent pour une pathologie respiratoire aigue (65 %) et necessitant une hospitalisation prolongee (mediane = 18 jours). Un quart des enfants etaient nes prematures (25 %). L’hydratation a ete orale pour 80 enfants (59 %), par perfusion intraveineuse pour 18 (13 %) et par voie intra-osseuse pour 1 enfant. La moitie des patients etait âgee de moins de 5 mois et aurait pu beneficier de la protection fournie par la vaccination. Conclusion Les GEAN rotavirus sont frequentes. La vaccination des nourrissons contre le rotavirus permettrait de diminuer les hospitalisations pour gastro-enterite communautaire a rotavirus et, indirectement, de proteger les enfants porteurs de pathologies sous-jacentes trop jeunes pour etre vaccines.

Background The occurrence of a TMA during SLE is a rare event that complicates 1% to 4% of lupus. The full spectrum of TMA can be encountered in the course of SLE: acquired thrombotic thrombocytopenic purpura (PTT), TMA associated with glomerulonephritis (TMA GN), atypical hemolytic uremic syndrome (aHUS), microangiopathic antiphospholipid syndrome (MAPS; defined or probable catastrophic antiphospholipid syndrome) or HELLP syndrome during pregnancy. Objectives To describe the clinical phenotype of TMA in lupus, to specify the prognosis and to identify factors allowing early classification and management of the different subtypes. Methods We performed a French multicentric retrospective study from January 1987 to December 2017 in units of internal medicine, nephrology and ICU. Inclusion criteria associated SLE defined by the ACR and/or SLICC criteria and a TMA defined either by the presence of microangiopathic anaemia and peripheral thrombocytopenia, either by histological signs of TMA. Results 68 events of TMA occurred in 60 SLE patients; median age was 24 years; 56 women (F/M ratio: 14). Diagnosis of SLE was assessed at a paediatric age in 24 (35.8%) patients. Clinical manifestations of SLE were: acute cutaneous lupus (n=48, 71%), arthritis (n=36, 53%), pleuritis (n=13, 19%), pericarditis (n=25, 37%), renal involvement (n=39, 57% including 20 class IV glomerulonephritis) and auto-immune cytopenia (n=22, 32%). Triggering factors of TMA were: lupus flare (n=38), infections (n=12), pregnancy and peripartum (n=3), or therapeutic rupture (n=4). Clinical and biological features at diagnosis of each subtypes of TMA are presented in table 1. A platelet count lower than 28 000/mm3 was predictive of TTP diagnosis (Se=90,5%, Sp=88,5%), likewise a creatinine plasma level greater than 100 µmol/L was predictive of TMA GN (Se=88,5%, Sp=85%). The treatment of TMA included (alone or in combination): corticosteroids in all cases, plasma exchange (n=52), cyclophosphamide (n=28), Rituximab (n=15), Eculizumab (n=2), antiplatelet agent (n=36), and/or effective anticoagulation (n=26). The median duration of follow-up was 150 months. Among TMA GN patients, the final median GFR was 58 mL/min (range: 0–120) with 5 individuals on chronic dialysis and 1 kidney transplant. Among TTP patients, one died from TMA, whereas the final median GFR of survivors (n=59) was 97 mL/min (range: 64–150), without any patient requiring dialysis. Table 1 Comparisons of clinical and laboratory data in different subtypes of TMA in SLE Conclusions SLE-associated TMA is a heterogeneous syndrome. TTP with a decreased ADAMTS13 activity and a low platelets level ( 100 µmol/L) have a poor renal prognosis. Early subtypes classification is mandatory for the clinician to provide prompt and appropriate management of this life-threatening complication. Disclosure of Interest None declared

La Presse Medicale - In Press.Proof corrected by the author Available online since jeudi 5 fevrier 2015

Introduction Les auto-anticorps anti-ARN polymerases III (ARNpol3) sont des anticorps specifiques de la sclerodermie systemique, principalement associes a des formes viscerales graves. Nous avons recemment identifie la presence d’ARNpol3 chez des patients presentant des myopericardites virales aigues severes, en l’absence de sclerodermie systemique evidente. L’objectif de ce travail etait d’etudier la presentation clinique des patients presentant l’association ARNpol3 et myopericardites virales et la signification de cette association. Patients et methodes Nous avons conduit une etude retrospective monocentrique entre janvier 2013 et janvier 2019 incluant les patients admis dans un service de medecine intensive-reanimation ou de medecine interne d’un centre hospitalier universitaire tertiaire et presentant une myopericardite aigue d’origine virale prouvee ou suspectee et la positivite d’ARNpol3. Resultats Dix patients ayant presente 15 episodes de myopericardites aigues ont ete inclus dans l’etude. L’âge moyen ± DS a la premiere detection des anticorps etait de 35,9 ± 8,2 ans avec un ratio femme/homme de 9. Tous les malades ont ete admis au moins une fois en reanimation. La FEVG minimale mediane [valeurs extremes] etait de 5 [4–40] % avec une troponine maximale mediane [valeurs extremes] de 58,8 [1,8–1666,7] fois la limite superieure de la valeur normale. En reanimation ; 80 % des patients etaient sous vasopresseurs, 70 % ont ete ventiles, 60 % ont necessites l’implantation d’une ECMO venoarterielle et 20 % ont eu un drainage pericardique. Tous les malades presentaient un syndrome pseudo-grippal et 7 (70 %) avaient une infection grippale (grippe B 71,4 % et grippe A 28,6 %) documentee lors d’au moins un episode. La FEVG s’est normalisee chez 80 % des malades. Une patiente n’a jamais recupere de la myocardite et une autre a developpe une cardiopathie dilatee sur des episodes de myocardites recidivante ; elles ont ete transplantees toutes les deux. Quatre patients ont eu au moins une recidive avec un delai median [valeurs extremes] de 1 [0,3–13] ans. Les anticorps anti-nucleaires etaient positifs chez tous les malades ainsi que les ARNpol3. Ils etaient confirmes en ≥ 2 occasions chez 8 malades (un perdu de vue et un malade incident). La duree mediane [valeurs extremes] de positivite etait de 6,5 [1–68] mois. Les ARNpol3 n’ont disparu chez aucun malade. La mise en evidence de la positivite des ARNpol3 avant l’episode virale n’a ete possible pour aucun malade, cependant, une patiente est decedee d’une myocardite grippale 4 ans apres un premier episode de myopericardite virale associee a des ARNpol3. Apres une duree de suivi mediane [valeurs extremes] de 49 [1,9–71,7] mois seuls deux malades repondaient aux criteres de sclerodermie l’ACR/EULAR et avaient un phenotype peu severe et sans atteinte viscerale. Aucun malade n’avait d’ARNpol3 au sein d’une cohorte controle de 20 patients admis pour une pneumonie grippale grave en reanimation. Il y a eu 1114 recherches d’ARNpol3 chez des patients uniques dans notre laboratoire d’immunochimie entre 2013 et 2018 : 1059 (95,1 %) etaient negatives, 9 (0,8 %) douteuses et 46 (4,1 %) positives. Les diagnostics cliniques associes aux prelevements positifs etaient : sclerodermie systemique n = 20 (43,5 %), myopericardite n = 11 (23,9 %), neoplasie n = 5 (10,9 %), autres maladies systemiques n = 5 (10,9 %), inconnu n = 5 (10,9 %). Conclusion Nous rapportons pour la premiere fois la positivite d’ARNpol3 chez des patients avec une myopericardite virale aigue, principalement d’origine grippale. Il est peu probable que l’association entre ces deux evenements rares soit fortuite. Chez ces malades, la presence d’ARNpol3 pourrait donc traduire un risque accrue de manifestations myopericardiques graves au cours d’injection virales, notamment grippales.

BackgroundMycophenolate mofetil (MMF) is increasingly used in children with systemic lupus erythematosus (SLE). Monitoring of its active metabolite, mycophenolic acid (MPA), is performed for individual dosage adjustment of MMF and is based on determination of area under the plasma concentration-time curve (AUC12h) of MPA. The objective of this monocentric study is to describe the pharmacokinetics (PK) of MPA in paediatric patients with SLE or lupus nephritis.MethodsPatients with lupus treated by MMF between January 2009 and July 2018 were included. MPA plasma concentrations (T0, T0.5h, T1h, T2h, T3h, T8h and T12h) were determined by EMIT (enzyme-multiplied immunotechnique) and MPA AUC12h calculated according to trapezoid rule.ResultsTwenty-two patients were diagnosed with lupus at 11.5 ± 2.9 years. Clinical presentation was SLE (n=18) or isolated lupus nephritis (n=4). Treatments prior to MMF were steroids and/or immunosuppressants (endoxan, rituximab). Age at initiation of MMF (Cellcept®n=20, Myfortic®n=2) was 12.9 ± 2.6 years.PK of MPA was performed after 8.2 ± 14.8 months of treatment, under MMF dose of 840 ± 218 mg (577 ± 98 mg/m2). A large interindividual variability in MPA concentration-time profiles was observed with the following mean parameters: Cmax=4.60 ± 11.70 µg/mL, tmax=80 ± 77 min, trough plasma concentration (C0) = 2.30 ± 1.60 µg/mL and AUC0-12h=46.29 ± 17.39 µg*h/mL.ConclusionData on the PK of MPA in lupus children are limited. Our results show the high interindividual variability in MPA exposure after oral administration of MMF. Monitoring of exposure based on AUC in combination with immunological disease parameters will allow to individualise treatment to optimiseDisclosure(s)Nothing to disclose

Introduction Le syndrome huit et demi de Fisher est une pathologie rare caracterisee par l’association d’une ophtalmoplegie internucleaire d’un cote et d’une paralysie de la lateralite de l’autre cote avec une paralysie faciale peripherique. Nous illustrons l’aspect en IRM d’un cas de syndrome de huit et demi de Fisher. Materiels et methodes Patiente âgee de 40 ans, hypertendue, a ete hospitalisee pour instabilite locomotrice avec vertige et une diplopie horizontale d’installation brutale. L’examen clinique a l’admission a trouve un syndrome vestibulaire d’allure peripherique, une paralysie de l’abduction de l’œil gauche et une ophtalmoplegie internucleaire bilaterale avec un nystagmus qui augmente a la fixation, une paralysie faciale peripherique gauche avec un signe de Charles Bell. Le bilan biologique notamment du LCR etait sans anomalie. Une TDM et une IRM cerebrale etaient realisees. Resultats La tomodensitometrie cerebrale etait sans anomalie. L’IRM cerebrale avec sequences ponderees en T1, T2, Flair et diffusion a mis en evidence une lacune ischemique pontique paramediane posterieure gauche en hyposignal T1, hypersignal T2 et diffusion. L’aspect bien localise de la lesion sur l’IRM au niveau de la region paramediane du pont cerebral, qui explique cette symptomatologie clinique tres specifique avec la paralysie faciale nous a permis de retenir chez notre patiente le diagnostic de huit et demi de Fisher. Conclusion Notre patiente avait un “syndrome huit et demi” qui est une pathologie rare et qui correspond a un syndrome d’un et demi de Fisher plus une paralysie du septieme nerf crânien. Le diagnostic est pose grâce aux donnees de l’examen clinique et confirme par l’IRM cerebrale.

Objectifs L’apoplexie hypophysaire est une complication rare, grave et aigue des adenomes hypophysaires, revele par un syndrome tumoral, des troubles visuels et des deficits hormonaux dans 60 % des cas. Nous rapportons 2 cas de macroadenome hypophysaire reveles par une apoplexie hypophysaire et precisons l’interet incontournable de l’IRM dans l’approche diagnostique et pronostique de cette pathologie rare. Materiels et methodes Il s’agit de deux patients une femme et un homme âges respectivement de 30 et 70 ans. Le motif de consultation etait un syndrome dysmorphique pour le 1er cas avec une hypersecretion non freinable de GH. Des cephalees intenses depuis evoluant depuis 2 semaines, sans signes d’insuffisance ni d’hypersecretion hypophysaire pour le deuxieme cas. Une IRM de l’axe hypothalamo hypophysaire etait realisee dans les deux cas. Resultats Dans le 1er cas l’IRM a montre une lesion hypophysaire nodulaire d’environ 15 mm de grand axe en hypersignal T1, hypersignal franc T2 ne prenant pas le contraste. Dans le 2e cas, L’IRM a objective un macroadenome hypophysaire de 30 × 25 × 20 mm en hypersignal T1 heterogene, hypersignal T2, avec un rehaussement peripherique, a developpement essentiellement supra-sellaire comprimant le chiasma optique et comblant les citernes peri-sellaires. Le diagnostic d’apoplexie hypophysaire a ete retenu. Une adenomectomie par voie trans-sphenoidale a ete realisee de suites operatoires simples dans les deux cas. Conclusion L’apoplexie hypophysaire est une complication rare mais grave des adenomes hypophysaires. Elle concerne 3 % des patients porteurs d’adenome hypophysaire. L’imagerie par resonance magnetique, est devenue un outil indispensable dans la recherche des adenomes de l’hypophyse et de leurs complications.

Objectif Illustrer l’interet de la TDM cerebrale avec injection et l’IRM cerebrale dans le diagnostic precoce des thromboses veineuses cerebrales profondes(TVCP). Materiels et methodes Etude retrospective concernant 4 patients âges de 20 a 70 ans, 3 hommes et une femme, se plaignant de fievre (n = 4), cephalees (n = 4), troubles de la conscience (n = 4), troubles du comportement (n = 1). Tous les patients ont beneficie d’une TDM cerebrale injectee. Une IRM cerebrale avec des sequences conventionnelles (T1, T2, FLAIR, T2 ou SWI) et d’angio-IRM avec ou sans injection de gadolinium (temps de vol ou contraste de phase) a ete pratiquee chez deux patients. Resultats Dans cette etude, la TDM cerebrale injectee initiale a montre des signes directs tels que la visualisation de thrombus spontanement hyperdense au niveau du reseau veineux profond (n = 3). Des signes indirects a type d’ischemie cerebrale : hypodensite cortico-sous corticale (n = 3), des noyaux gris centraux (n = 2) et de la substance blanche peri ventriculaire (n = 3) Des foyers hemorragiques (n = 1). Une IRM cerebrale avec sequence angio-MR veineuse a montre un thrombus massif des sinus veineux : longitudinal (n = 1), lateraux (n = 2), sinus droit (n = 1) et une anomalie des noyaux gris centraux (n = 1) et de la substance blanche peri ventriculaire (n = 2). L’evolution etait defavorable avec deces (n = 3). Conclusion Les TVC profondes sont des causes rares d’ischemie cerebrale. Leur diagnostic est rendu difficile par le manque de specificite des signes cliniques retrouves a l’examen clinique. L’IRM cerebrale couplee a l’angio-MR veineuse permet d’asseoir le diagnostic et d’eliminer les principaux diagnostics differentiels.

Introduction La radionecrose cerebrale est une complication rare et tardive de la radiotherapie. L’atteinte des lobes temporaux et frontaux est plus frequente que celle des voies optiques et du tronc cerebral. Devant une symptomatologie souvent pauvre et non specifique, les radionecroses cerebrales posent le probleme de diagnostic differentiel avec une recidive tumorale. L’IRM, dans ce cas, occupe une place importante pour l’orientation diagnostique. Materiels et methodes Il s’agit d’une patiente âgee de 29 ans suivi en ORL pour esthesioneuroblastome olfactif, traitee par radiotherapie exclusive avec une remission complete. Deux ans apres le traitement, elle a presente une cecite bilaterale d’installation progressive suivie par une deterioration de l’etat neurologique. Une IRM cerebrale etait realisee. Resultats L’IRM a montre un hypersignal T2 et Flair interessant les nerfs optiques en pre chiasmatique, les tractus optiques, les corps mamillaires et la partie anterieure de l’hemi protuberance droite. Ces lesions etaient en hyposignal T1, se rehaussant apres injection de Gadolinium. L’aspect etait evocateur d’une radionecrose cerebrale. L’evolution a ete marquee par le deces de la patiente au bout d’un mois. Conclusion La radionecrose cerebrale est une complication rare de la radiotherapie appliquee pour des cancers du massif facial ou du cavum. Il faut savoir l’evoquer dans un contexte de tumeur irradiee. Actuellement, l’IRM est l’examen de choix, son role est double : diagnostique et de surveillance de l’evolutivite des lesions.

Resume Depuis quelques annees, on observe une augmentation importante de l’obesite et des anomalies metaboliques qui l’accompagnent, ainsi que des maladies cardiovasculaires. Des etudes recentes montrent que les facteurs de risque de maladies cardiovasculaires apparaissent des l’enfance. Ces atteintes sont dans de nombreuses situations programmees tres tot pendant la vie embryonnaire et fœtale. C’est le concept du determinisme fœtal ou « programming » des anglo-saxons. Les premieres etudes sur ce sujet ont souligne le lien entre la restriction de croissance fœtale et le risque de developper des troubles nutritionnels et metaboliques a l’âge adulte. Mais, il apparait a l’heure actuelle que l’exces d’apports nutritionnels in utero avec un exces de croissance a la naissance comme cela se produit en cas de diabete maternel expose aux memes risques. L’ensemble des anomalies qui constituent les facteurs de risque de maladies cardiovasculaires est regroupe sous le terme de syndrome metabolique ou syndrome X. Ce syndrome initialement decrit chez l’adulte a fait l’objet d’etudes de plus en plus nombreuses chez l’enfant et l’adolescent car dans des populations a risque, des elements de ce syndrome sont observes des les periodes precoces de la vie. L’alteration du milieu intra-uterin entraine des modifications au cours du developpement qui sont des mecanismes d’adaptation a court terme et qui se transmettent de generation en generation. Ce phenomene transgenerationnel contribue a l’extension rapide des anomalies metaboliques et des maladies cardiovasculaires. De nombreux arguments existent en faveur de mecanismes epigenetiques a l’origine de ces modifications et de leur transmission transgenerationnelle. Un des defis dans les annees a venir sera de mettre en place des programmes de prevention permettant d’enrayer les consequences a long terme du determinisme fœtal.

Rotavirus is the most common cause of gastroenteritis in children requiring hospitalization. It is a very resistant and contagious virus causing nosocomial gastroenteritis. In France, the vaccine against rotavirus has been available since 2006, but the vaccine is not recommended for infant vaccination. The aim of this retrospective study was to describe nosocomial rotavirus gastroenteritis (NRGE) and to assess its impact on children hospitalized in the General Pediatrics Department of Robert-Debré Hospital (Paris) between 1 January 2009 and 31 December 2013. We analyzed the demographic characteristics of children (age, term birth, underlying diseases) and the severity of the NRGE (oral or intravenous hydration), and assessed whether these children could benefit from vaccination against rotavirus.One hundred thirty-six children presented nosocomial rotavirus infection, with an incidence of 2.5 NRGE per 1000 days of hospitalization. The incidence of NRGE was stable between 2009 and 2013 despite the introduction of specific hygiene measures. The average age of the children was 7 months (range: 0.5-111 months). Most often NRGE occurred in children hospitalized for respiratory diseases (65% of cases) and requiring prolonged hospitalization (median: 18 days). One-third of children were born premature (25%). Hydration was oral in 80 patients (59%), by intravenous infusion in 18 patients (13%), and intraosseous in one patient. Half of the patients were aged less than 5 months and could benefit from the protection afforded by vaccination.NRGE are common. Rotavirus mass vaccination should have a positive impact on the incidence of NRGE by reducing the number of children hospitalized for gastroenteritis, therefore indirectly reducing the number of hospital cross-infections of hospitalized children who are too young to be vaccinated.

A case of fetal congenital cardiac diverticulum, diagnosed at 36 weeks of gestation. The fetus presented with a large cardiac effusion one day before his birth, and an active pericardial bleeding with tamponade and severe bradycardia right before the urgent C-section. Drainage of the effusion done right after the delivery, with good neonatal outcome.

During the last years, obesity and subsequent metabolic disorders and cardiovascular diseases have tremendously increased. Recent studies have shown that risk factors of cardiovascular diseases appear as soon as in infancy. In many situations, these disorders are programmed in early life during fetal development. These observations have lead to the concept of programming. The first studies on this subject underlined the link between poor fetal growth and the risk of nutritional and metabolic disorders during adulthood. But, it is now evident that excess of fetal growth as it is observed during pregnancy with maternal diabetes leads to the same consequences. The metabolic syndrome or syndrome X is the name for a clustering of risk factors for cardiovascular diseases and type II diabetes that are of metabolic origin. This syndrome, first described in the adults, is more and more studied during childhood and adolescence. Metabolic syndrome is now described in youth, particularly in subjects with risk factors as obesity. Alterations of intra-uterine environment lead to modified early development and represent short-term adaptations transmitted from one generation to another. This intergeneration effect contributes to the burden of adult metabolic disorders and cardiovascular diseases, as seen in the last decades. There is considerable evidence for the contribution of epigenetic mechanisms for the lifelong and the intergenerational alteration of gene transcription by variation in the early life environment. One of the major challenges in the following years is to promote public health programs which are aimed at prevention of long-term consequences of fetal programming.

We hereby report the third case of antenatal diagnosis of congenital cyst of the pancreas. It is a very rare lesion and could present as a differential diagnosis of any intra-abdominal cystic mass. Early treatment is easy and prevents complications such as ascites and pancreatitis in case of intra-pancreatic enteric duplication.

Summary: Purpose: To evaluate the efficacy of vigabatrin (VGB) in the treatment of infantile spasms (ISs) associated with Down syndrome (DS) and to assess the feasibility of early discontinuation to reduce the possible retinal toxicity. Methods: Five children with ISs with DS were treated with vigabatrin as first-line monotherapy in an open prospective study. The short-term response was evaluated, and VGB was continued in responders. The treatment was stopped after 6 months in children who were still spasm free. Results: Four children of five became spasm free with VGB, three of them responding within 1 week. This response was maintained during the 6 months of VGB treatment. After VGB discontinuation, and with a follow-up ranging from 2 to 4 years, none of the responders experienced spasm recurrence or other types of seizures. Conclusions: This study confirms the efficacy of VGB in ISs associated with DS. Moreover, it shows that the duration of VGB treatment can be reduced to 6 months without relapse of ISs. This short treatment might reduce the risk of developing visual field constriction.

In right congenital diaphragmatic hernia (RCDH), several clinical diagnostic pitfalls are possible and should be known to those caring for infants and children with this disorder. The records of the 18 patients at Hotel Dieu de France Hospital with a history of CDH between 1990 and 1999 were collected; those of the ten who had a RCDH were reviewed retrospectively. The mean age at diagnosis was 6 months; the male-to-female ratio was 2:3. The delay between the first symptom and the diagnosis ranged between 0 and 10.5 months (mean 4.5 months). An acute presentation was observed in four cases, consisting of respiratory distress in three; the 4th presented with gastric volvulus and intestinal obstruction. The presenting symptoms were mild in four cases; recurrent respiratory infections in three and failure to thrive in one. The diagnosis was incidental in two cases during the evaluation of respiratory symptoms attributed to an atrial septal defect. The radiologic findings provided by a chest radiograph (CxR) were sufficient to make an accurate diagnosis in eight cases and peritoneography was useful in one. In six cases, the presenting CxR had been misinterpreted as normal or acute lobar pneumonia. Pathologic findings at surgery consisted of lateral and posterior right diaphragmatic defects in nine cases; the defect was lateral and anterior in one. A hernia sac was found in seven cases; malrotation was present in three. Surgical correction was done by an abdominal approach in nine cases and a thoracic approach in one. The diaphragmatic defect was repaired by transverse closure in six cases, diaphragm plication in three and prosthetic closure in one. The postoperative outcome was uneventful in eight cases. Two patients died. Thus, RCDH seems to cause less severe symptoms than left-sided LCDH. It usually manifests beyond the neonatal period as respiratory or gastrointestinal symptoms. The diagnosis should be made easily by a CxR. The presence of a hernia sac correlated with a mild presentation. An abdominal surgical approach is preferred.

We hereby report the second case of antenatally diagnosed "neurenteric cyst" in the literature. The patient we describe presented as a neonatal respiratory distress syndrome (NRDS) which did not respond to a vigorous resuscitation. Anomaly of the antenatal ultrasonography and of the initial chest x-ray added to the non-response to therapy, led us to an urgent thoracic scan and to a lifesaving thoracotomy. We think that every posterior mediastinal cystic mass, with or without vertebral malformations, diagnosed antenatally, should raise the possibility of neurenteric cyst. The perinatal management of the newborn to be, will thus be simplified. This will lead to a better outcome.

The authors describe their own experience about using a siliconed percutaneous central venous catheter in the newborn, experience performed in their neonatal intensive care unit in Beirut. The technique consists in introducing this sort of device centrally by using a peripheral vein. The authors performed a prospective study on thirty-two newborns: Their results seem to indicate, in accordance to the literature review, that this technique offers many advantages such as sparing the newborn veins, prolonged hyperalimentation and treatment, and less incidents than the other perfusion techniques (peripheral and central). Few inconveniences are encountered: limitation of the amount of daily perfusion, impossibility of transfusing blood or derivatives across the silicone catheter.

Right-sided infectious endocarditis in the neonate, due to staphylococcus aureus, is a rare entity. A high index of suspicion should be used when dealing with a very sick neonate, especially with aggressive reanimation. Although the diagnosis is clinical, echocardiography is essential to confirm the diagnosis and also is an excellent mean to follow the evolution of the disease. The pathogenesis of the infection is due to bacteremia with implantation of the staphylococcus on a normal endothelium. The prognosis is poor with a high mortality rate and possibility of sequelae (essentially cardiac and neurologic). The prognosis depends essentially on early diagnosis and treatment which should last for at least 4-6 weeks. The authors present the case of a 2-week-old girl who developed a right-sided staphylococcal endocarditis following treatment of neonatal jaundice with i.v. perfusion of albumin. The patient survived with cardiac and central nervous system sequelae.

Near drowning in a bathtub occurred to a 3 years 7 months old boy. He was resuscitated at home by the firemen before admission in hospital, where he presented coma, convulsions and a massive distension of the abdomen. Surgical procedure revealed a 3 cm long perforation on the smaller curvature, which was repaired. This aspect and the localisation of the rupture resemble those related to resuscitation procedures: oxygenotherapy by nasal catheter, external cardiac massage, mouth-to-mouth ventilation. The stomach is filled with air because inadequate position of the catheter. It also may be related to relaxation of crico-pharyngeal sphincter during anesthesia or coma.

Thirty-one infants and children aged 1 month to 15 years 3 months were treated with ceftriaxone once a day for the treatment of a meningitis related to Neisseria meningitidis (19 cases), haemophilus influenzae (7 cases), streptococcus pneumoniae (1 case), not identified bacteria (4 cases). All identified bacteria were sensitive to ceftriaxone. Twenty children were treated with 100 mg/kg/day, 11 with 50 mg/kg/day. CSF was sterile at the first control-generally performed 30 h after the onset of treatment-in all cases. Despite a great number of severe forms (fulminans purpura and septic shock; 11 cases; severe neurologic disturbances: 6 cases), all patients survived and recovered after a treatment of 9 to 22 days. Two infants exhibited neurologic sequelae: deafness, delayed development and hydrocephalus. Tolerance to ceftriaxone appeared to be good. With a 100 mg/kg/day dosage, mean CSF level at 6 h was 3.3 mg/l (0.8-7.7), on the first day of treatment. At the end of treatment, mean CSF level at 24h was 0.47 (0.15-2.5). With a 50 mg/kg/day dosage, mean CSF level at 6 h was 2,1 mg/l (1.1-3.9) in the first day of treatment. At the end of the treatment, mean CSF level at 24h was 0.22 mg/l (0.08-0.5). Once a day administration of ceftriaxone is adequate for the treatment of meningitis in infants and children. Though a 50 mg/kg/day dosage is probably sufficient in most cases, it seems to be more secure to use a 100 mg/kg/day dosage.

A case of hyperexplexia is reported in a newborn. Hyperexplexia or "startle disease" is very uncommon and is of autosomal dominant transmission. Clinical features consist in particular physical features during the neonatal period and subsequently in an abnormal startle reaction; the electromyogram shows particular patterns.

Though conventional coronary angiography (CCA) has been the standard of reference for diagnosing coronary artery disease in the past decades, computed tomography angiography (CIA) has rapidly emerged, and is nowadays widely used in clinical practice. Here, we introduce a standardized evaluation framework to reliably evaluate and compare the performance of the algorithms devised to detect and quantify the coronary artery stenoses, and to segment the coronary artery lumen in CIA data. The objective of this evaluation framework is to demonstrate the feasibility of dedicated algorithms to: (I) (semi-)automatically detect and quantify stenosis on CIA, in comparison with quantitative coronary angiography (QCA) and CIA consensus reading, and (2) (semi-)automatically segment the coronary lumen on CIA, in comparison with expert's manual annotation. A database consisting of 48 multicenter multivendor cardiac CIA datasets with corresponding reference standards are described and made available. The algorithms from 11 research groups were quantitatively evaluated and compared. The results show that (1) some of the current stenosis detection/quantification algorithms may be used for triage or as a second-reader in clinical practice, and that (2) automatic lumen segmentation is possible with a precision similar to that obtained by experts. The framework is open for new submissions through the website, at http://coronary.bigr.nl/stenoses/. (C) 2013 Elsevier B.V. All rights reserved.

L'epidemie actuelle de maladie a coronavirus 2019 (COVID-19) peut toucher tous les patients atteints de maladies auto-immunes et systemiques. Les patients souffrant d'un lupus systemique (LS) ont des facteurs de risque de developper des formes severes de COVID-19 en raison des comorbidites frequemment associees au LS (insuffisance renale chronique, syndrome metabolique notamment) et des traitements corticoides et immunosuppresseurs. Jusqu'a present, l'analyse des facteurs de risque de developper une COVID-19 severe au cours du LS a ete biaisee par le mode de recrutement des patients, puisque seuls les malades les plus symptomatiques ont ete inclus dans les etudes. Nous avons realise une etude observationnelle de la COVID-19 chez les patients suivis pour un LS en incluant les malades asymptomatiques ou paucisymptomatiques dans le but d'analyser les facteurs associes a une forme grave de cette maladie. Les cas etaient recrutes de 3 facons differentes : declarations spontanees au niveau local et au niveau national par les malades ou les medecins concernes ;declaration a la cohorte french RMD COVID-19 (etude ancillaire organisee sous l'egide de la filiere FAI2R) et depistage par serologie SARS-CoV-2 des malades avec lupus vus en consultation. Pour etre inclus, les patients devaient remplir les criteres de classification de lupus systemique de 1997 de l'ACR et/ou les criteres actualises de 2019 de l'EULAR/ACR et devaient avoir une infection a SARS-CoV-2 prouvee biologiquement par RT-PCR naso-pharyngee ou par serologie sanguine. Les malades asymptomatiques ou paucisymptomatiques etaient recrutes au cours des consultations de suivi habituelles du LS. 109 patients (dont 89 % de femmes) ont ete inclus entre le 1er mars 2020 et le 31 decembre 2020. L'âge median (Q1, Q3) des cas etait de 40 ans (33-56). Le score median de sequelle (SLICC damage index) etait de 0 (0-2). Les principales comorbidites etaient le surpoids (22 %), l'obesite (25 %), l'hypertension arterielle (22 %) et une maladie renale chronique (21 %). 7 % etaient fumeurs actifs. 42 % avaient un antecedent de nephropathie lupique. 87 % etaient traites par hydroxychloroquine (HCQ), 63 % par corticoide a la posologie moyenne de 8 mg/j (IC 95 % [6 ;10]) et 34 % par immunosuppresseur. Au moment de l'infection, 26 % rapportaient des signes d'activite clinique du LS, 51 % avaient une elevation des anticorps anti ADN double brin et 19 % une baisse du C3. Lors de la survenue de la COVID-19, L'HCQ, le corticoide et l'immunosuppresseur etaient maintenus respectivement dans 92 %, 93 % et 79 % des cas. 9 patients (8 %) ont eu une infection asymptomatique par le SARS-CoV-2. La COVID-19 s'est manifestee pour 40 patients (40 %) par une simple infection des voies aeriennes superieures, pour 31 (29 %) par une bronchite et pour 32 (30 %) par une pneumonie. 29 patients (26 %) ont ete hospitalises, 22 (21 %) ont necessite une oxygenotherapie, 12 (12 %) ont ete transferes en unite de soins intensifs (USI), 9 (8 %) ont developpe un syndrome de detresse respiratoire aigue et 4 (4 %) sont decedes. En analyses multivariees par regression logistique, les deux seuls facteurs associes au recours a une oxygenotherapie etaient l'âge (p = 0,047) et l'obesite (p = 0,02). Le seul facteur associe a une admission en USI etait l'âge (p = 0,01). Les corticoides, les immunosuppresseurs et l'antecedent de nephropathie lupique n'etaient pas independamment associes au risque de developper une forme necessitant le recours a l'oxygenotherapie ou une hospitalisation en USI. La consultation medicale de surveillance au cours du LS a permis d'inclure un grand nombre de malade paucisymptomatique ou asymptomatique habituellement non etudies dans ce type de travail. Cette serie fournit des elements rassurants quant aux facteurs de risque propres au LS de developper une forme grave de COVID-19. Ces facteurs de risque ne semblent en effet pas differents de ceux de la populat on generale, a savoir l'âge et l'obesite. Une maladie renale chronique, une nephropathie lupique, un traitement par corticoide et immunosuppresseur ne sont pas, dans cette cohorte, des facteurs independamment associes a une forme severe de la maladie. (French) [ABSTRACT FROM AUTHOR] Copyright of Revue de Medecine Interne is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)