Search

Resume Objectif Ce travail presente la strategie utilisee pour construire un programme d’education therapeutique des patients (ETP) sur la douleur liee au cancer, sa mise en œuvre en region et l’identification des freins et des leviers concernant son deploiement. Methodologie 10 binomes medecin-infirmiere des Structures « Douleur Chronique » de l’ex-Basse-Normandie, apres formation a l’ETP, ont concu et construit le programme EFFADOL (Ensemble Faire Face A la DOuLeur). Ils ont collaborativement elabore les outils d’apprentissage, d’evaluation et de communication mis en œuvre. Resultats Suite au diagnostic educatif, 3 seances sont proposees au patient pour lui permettre d’acquerir des competences selon les objectifs suivants (1) Comprendre les differents types de douleur (2) Comprendre les traitements antalgiques et mieux gerer leurs effets indesirables (3) S’adapter au mieux a la douleur au quotidien. Le patient peut associer un proche pour participer aux ateliers et en choisir le format (individuel et/ou collectif). La mise en œuvre du programme et l’importance accordee a la communication avec les oncologues hospitaliers mais aussi avec les professionnels de sante liberaux sont presentees. Discussion et conclusion Le programme, accessible aux patients a proximite de leur domicile, est en adequation avec les besoins educatifs, evalues en amont par une enquete regionale. Les freins a l’inclusion des patients et les strategies pour les pallier sont identifies. Les difficultes sont d’ordre organisationnel, structurel et communicationnel. Le defi essentiel est le remaniement des pratiques de soins et la modification de posture des soignants dans l’objectif d’autonomisation du patient.

Riassunto L’ipertermia maligna (IM) dell’anestesia e una patologia farmacogenetica che si manifesta in modo incostante con uno stato di ipermetabolismo del muscolo scheletrico in seguito all’esposizione a un agente anestetico volatile scatenante. I numerosi progressi nella fisiopatologia dell’IM hanno permesso di evidenziare il gene RYR1 principalmente implicato e l’implementazione di procedure di screening mediante test genetici o biologici. Tuttavia, forme di crisi di IM fruste o interrotte con il miglioramento del monitoraggio anestesiologico o ancora dei decessi perioperatori inspiegabili possono portare a sottovalutare l’incidenza delle manifestazioni di IM durante un’anestesia. Benche siano stati compiuti notevoli progressi negli strumenti di genetica molecolare nell’esplorazione dettagliata dei genomi degli individui, essi si accompagnano talvolta a maggiori difficolta nella diagnosi poiche mancano ancora le correlazioni genotipo-fenotipo che consentirebbero una diagnosi di certezza. Oggi, un’organizzazione nazionale ed europea relativa all’IM ha permesso l’implementazione di raccomandazioni in tutti i settori della patologia: procedura terapeutica urgente e uso del dantrolene in caso di crisi di IM, screening e valutazione del rischio di IM in un soggetto in visita anestesiologica, rischio di IM nei parenti, precauzioni anestetiche in pazienti con un’IM o considerati a rischio e procedura per diagnosticare la suscettibilita all’IM in un paziente in corso di valutazione o nei suoi parenti.

Resumen La hipertermia maligna (HM) de la anestesia es una enfermedad farmacogenetica que se manifiesta de manera inconstante por un estado de hipermetabolismo del musculo esqueletico durante la exposicion a un agente anestesico volatil desencadenante. Los numerosos avances referentes a la fisiopatologia de la HM han permitido evidenciar el gen RYR1, mayoritariamente implicado, y la instauracion de procedimientos de deteccion por genetica o prueba biologica. Sin embargo, formas de episodios de HM incompletas o abortadas por la mejoria de la monitorizacion anestesica o, tambien, fallecimientos perioperatorios inexplicados pueden conducir a una infravaloracion de la incidencia de manifestaciones de HM durante la anestesia. Aunque se hayan realizado progresos considerables en las herramientas de genetica molecular para la exploracion detallada de los genomas de individuos, a veces se acompanan de dificultades mayores en el diagnostico, porque las correlaciones genotipo-fenotipo que permitirian un diagnostico de certeza todavia no existen. Actualmente, una organizacion nacional y europea dedicada a la HM ha permitido el establecimiento de recomendaciones en todos los ambitos de la enfermedad: procedimiento terapeutico de urgencia y utilizacion del dantroleno en caso de episodios de HM, deteccion y evaluacion del riesgo de HM en un individuo en la consulta de anestesia, riesgo de HM en los parientes, precauciones anestesicas en pacientes con una HM o considerados de riesgo y procedimiento de diagnostico de la sensibilidad a la HM en un probando o sus parientes.

Resume Objectif Le pronostic des nouveau-nes porteurs d’une omphalocele depend de nombreux facteurs, en particulier de l’existence d’anomalies associees. Les syndromes de Wiedemann–Beckwith sont reputes presenter de petites omphaloceles. Cependant, aucun critere echographique ne permet de predire les autres anomalies associees. L’objectif de ce travail etait donc de decrire les issues globales des omphaloceles de diagnostic prenatal, et de rechercher une correlation eventuelle entre le contenu de l’omphalocele precocement evaluee et les anomalies associees constatees en postnatal. Methode Etude retrospective realisee a l’hopital Necker-Enfants Malades entre 2008 et 2018. Les issues de grossesses et le diagnostic post natal ont ete recueillis, et analyses en fonction du contenu de l’omphalocele au premier trimestre. Resultats Cent quatre-vingt-onze femmes avec diagnostic antenatal d’omphalocele ont ete incluses. Vingt-huit pour cent des cas etaient isoles a la naissance, 32 % presentaient un syndrome polymalformatif associe a une anomalie chromosomique, 13 % de syndrome polymalformatif sans cause genetique retrouvee, 9 % de syndrome de Wiedemann Beckwith, 7 % d’association a une cardiopathie, 6 % de sequence du cordon court, 3 % de sequence OEIS et une pentalogie de Cantrell. La presence du foie au 1er trimestre a ete un facteur predictif de cardiopathie (85,7 % vs 48,6 % p = 0,01). La presence des anses digestives au premier trimestre a ete un facteur predictif d’anomalies chromosomiques (69,6 % vs 37,2 % p Conclusion L’analyse en echographie au premier trimestre du contenu exhaustif de l’omphalocele est une aide precieuse pour l’evaluation du risque d’anomalies associees et donc le conseil prenatal.

Giant omphalocele often represents a major surgical challenge and is reported with high mortality and morbidity rates. The aim of this study was to assess the outcome of neonates with giant omphalocele managed with early operative surgical treatment, and subsequently to identify possible factors that could alter the prognosis.We reviewed the medical records of 29 consecutive newborns with prenatally diagnosed giant omphalocele. In these cases one of two procedures had been performed: either staged closure after silo, or immediate closure with a synthetic patch. The cases were separated into 2 groups: Isolated giant omphalocele (IO group) and giant omphalocele associated with malformation (NIO group).Infants in the IO group had a lower size of the omphalocele (p0,001), a shorter hospital stay (95 days [45-915] vs. 41.5 days [10-110] p= 0, 02), and a shorter median ventilation length (10 days [1-33] vs. 27, 5 [6-65] p = 0, 05). In the NIO group, 5 cases displayed a significantly more difficult course than the others. They were compared to the remaining cases for prenatal and anatomic features. Four factors associated with greater morbidity were identified: CONCLUSIONS: Isolated omphalocele, even containing the whole liver, has a very good prognosis with early surgical treatment. Without associated anomalies, 95% of giant omphaloceles can be discharged with a median of 41.5 days in hospital. However, associated anomalies (especially cardiopathies) may burden the prognosis and should be both carefully assessed during pregnancy and taken into account in parental information.Retrospective Study LEVEL OF EVIDENCE: Level I.

Introduction Hereditary heart diseases (cardiomyopathy & channelopathies) are most often characterized by autosomal dominant inheritance and delayed cardiac expression. The risk of complications of these diseases are sudden cardiac death and heart failure. Medical management allow to reduce significantly, but does not cancel, the risk of complications. If the causal mutation is known, couples with a pregnancy project may discuss the use of prenatal genetic diagnosis (PND) or preimplantation genetic diagnosis (PGD). The use of PND or PGD in these diseases is controversial and the medical, ethical and psychological issues are particularly complex. Purpose The aim of this study was (i) to collect at national level the procedures of PNDs and PGDs in the context of “isolated” hereditary heart disease; (ii) obtain the opinion of patients about this issue. Methods and Results The data collected with help of the French Biomedicine Agency show that 18 PND were carried out in France between 2009 and 2017 and 13 PGD between 2013 and 2017. So, number of PND and PGD for hereditary heart disease is rare in comparison of the relatively high prevalence of these diseases. The opinion of 20 patients (95% with cardiomyopathy), followed at Pitie-Salpetriere referral center for hereditary heart diseases, was prospectively collected via auto-questionnaires. Their answers show that few know the options (PND, PGD, gamete donation, adoption): only 25% are aware of all the alternatives. Despite this, 45% of patients mentioned that they did not want more information about these procreation options. Moreover, 45% consider the use of a PND to be fully acceptable or acceptable and 75% for the use of PGD, although they would not ask for themselves. Conclusions We report the first data about procreation procedures in France, and wishes of patients, in non-syndromic hereditary heart diseases. This may help to better manage these complex issues in clinical practice.

Arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) is a genetic disease predominantly caused by desmosomal gene mutations that account for only ~50% of cases. Ryanodine receptor 2 (RYR2) gene mutations usually cause catecholaminergic polymorphic ventricular tachycardia but have been associated with a peculiar phenotype named ARVC2.We aimed to determine the prevalence and phenotype associated with RYR2 mutations in a large ARVC/D population.We analyzed the whole RYR2 coding sequence by Sanger sequencing in 64 ARVC/D probands without desmosomal gene mutations.We have identified 6 rare missense variants: p.P1583S, p.A2213S, p.G2367R, p.Y2932H, p.V3219M, and p.L4670V. It corresponds to a 9% prevalence of rare RYR2 variants in the ARVC/D population (6 of 64 probands), which is significantly higher than the estimated frequency of rare RYR2 variants in controls (Fisher exact test, P = .03). Phenotypes associated with RYR2 variants were similar to desmosome-related ARVC/D, associating typical electrocardiographic abnormalities at rest, frequent monomorphic ventricular tachycardia, right ventricular dilatation, wall motion abnormalities, and fibrofatty replacement when histopathological examination was available.In this first systematic screening of the whole coding region of the RYR2 gene in a large ARVC/D cohort without mutation in desmosomal genes, we show that putative RYR2 mutations are frequent (9% of ARVC/D probands) and are associated with a conventional phenotype of ARVC/D, which is in contrast with previous findings. The results support the role of the RYR2 gene in conventional ARVC/D.

Distribution and behavior of many trace elements in the aquatic environment has been well characterized, but little is known about silver (Ag) concentrations in coastal waters, even though this element ranks among the most toxic to marine invertebrates (Calabrese et al., 1977 ; Fisher and Hook, 1997 ; Webb and Wood, 1998). Studies conducted by Flegal et al. (1995), River-Duarte et al. (1999), and Ndung'u et al. (2001), provided the first valuable data on Ag distribution in the oceanic environment, indicating that this element is found in very low concentrations in the dissolved phase. However, although silver concentrations in coastal waters do not reach the nanomolar range (Smith and Flegal, 1993 ; Squire et al., 2002), formation of a stable chloro complex enhances bioavailability and toxicity to biota (Luoma et al., 1995). Experimental studies have shown that Ag is toxic to some living organisms at environmentally realistic levels (Bryan and Langston, 1992). Silver found in the aquatic environment mainly originates in effluents from sewage treatment plants (Rozan and Hunter, 2001). Silver can therefore be used as a tracer of wastewater discharges in coastal waters (Martin et al., 1988 ; Sañudo-Wilhelmy and Flegal, 1992), for instance through the use of sentinel organisms, which concentrate bioavailable contaminants in their tissues (Stephenson and Leonard, 1994 ; Jiann and Presley, 1997 ; Riedel et al., 1998 ; Muñoz-Barbosa et al., 2000). This study concerns biological monitoring as a means of providing a synoptic view of silver contamination in French coastal waters. The National Network for the Observation of Marine Environment Quality (RNO, the French Mussel-Watch) which has been regularly measuring concentrations of various chemical contaminants in oyster and mussel tissues for 25 years (Claisse, 1989), has been monitoring silver levels since 2003. This valuable database including data collected at 80 sampling sites distributed along the French coasts (Fig. 1), is used as a reference to provide the spatial distribution of a given contaminant (Chiffoleau and Bonneau, 1994), identify trends of contamination/decontamination (Chiffoleau et al., 2001), and detect peak concentrations due to accidental events (Chiffoleau et al., 2004). Mussels (Mytilus edulis and Mytilus galloprovincialis) and oysters (Crassostrea gigas) are collected twice a year in February and November. Sample collection (size of samples, size of animals) and treatment (cleaning, depuration, removal of soft parts from the shells, draining, homogenization, and freeze-drying) are performed according to the OSPAR Convention guidelines and the method described by Claisse (1989).

With production activity tending rapidly towards international fragmentation, this study examines the consequences for labour countries of the forms of specialisation brought about by fragmentation processes. It further addresses the risk that fragmented sectors may become excluded from greater developments within the manufacturing industry as a whole. An empirical analysis using panel data reveals that, contrary to expectation, the textile and clothing sector in labour countries does not always reap the positive benefits of this form of international trade integration. Rather, we observe a phenomenon of immiserising specialisation, due to a drop in relative wages within this sector.

Cardiac contraction is triggered when a membrane depolarisation induces a massive increase in intracellular calcium concentration. This process called “excitation-contraction (E-C) coupling” relies on a multimolecular protein complex, the calcium release complex (CRC) organized around the sarcoplasmic reticulum calcium channel, the ryanodine receptor (RyR2). Among the proteins involved in the efficient function of the CRC, calsequestrin, triadin and junctin are sarcoplasmic reticulum proteins able to interact with RyR2 and regulate calcium release.Mutations in RyR2 and calsequestrin are associated to a rare but fatal cardiac arrhythmia: catecholaminergic polymorphic ventricular tachycardia (CPVT). Nevertheless, variations in these two genes (RYR2 and CASQ2) account so far for only 50 to 70% of the cases, suggesting that other genes are most probably involved. To reveal new genes involved in CPVT, we have based a candidate gene approach on the hypothesis that the pathology could be considered as a disease of the calcium release complex. We therefore searched for variations in the genes encoding proteins of the CRC in a large French cohort of CPVT patients with no detected mutations in RYR2 or CASQ2. We have identified for the first time mutations in the human triadin gene TRDN, and studied the functional consequences of a missense mutation both in a cell model and in vivo after expression in triadin KO mice. Our results confirmed the hypothesis that CPVT can be more generally considered as a defect in the CRC.

Recurrent rhabdomyolysis episodes in adults are commonly caused by glycogenosis or fatty-acid oxidation disorders. However, in many cases the etiology remains unknown, and recently mutations in RYR1 appeared as a possible cause of exercise induced rhabdomyolysis. We studied 14 adults who presented acute rhabdomyolysis (CK above 10,000 UI/l) triggered by exercise or fever, in whom McArdle disease, fatty acid oxidation disorders, and LPIN1 mutations were excluded. All patients underwent muscle biopsy in order to screen RYR1 mutation on cDNA. Potentially pathogenic mutations in RYR1 gene were detected in 5 unrelated patients. Mutations were the following: p.Val4847Leu, p.G593R, p R3539H, Gly2434Arg, p.Gln3461Pro, p.A1352T, p.A933T and p.Ser1342Gly. Two patients presented each 2 and 3 heterozygous variants. Baseline CK levels were elevated in all cases but one (400–700 UI/l). None of them complained of myalgia or exercise intolerance. Rhabdomyolysis were triggered by weight-training in two patients, viral infection in two cases, and retinoic acid treatment in the last case. Higher recorded CK levels were between 28,000 and 94,000 UI/l, without renal failure. Three patients had a unique episode, whereas two other had several rhabdomyolysis episodes. Muscle biopsies were either normal, or showed moderate structure disorganization. Two siblings of a patient, the father of another patient, and the brother of a third patient, also presented mutations in the RYR1 gene and high baseline CK level. Per-anesthetic malignant hyperthermia was noticed in a grand-mother of one patient. Mutations in RYR1 gene should be systematically searched in patients with exercise or fever induced rhabdomyolysis episodes, after having excluded common metabolic disorders. This diagnostic implies major consequences for genetic counselling in the families, due to the potential risk of anesthetic malignant for the patients and their relatives.