Extending the clinical spectrum of X-linked Tonne-Kalscheuer syndrome (TOKAS):new insights from the fetal perspective

INTRODUCTION: Tonne-Kalscheuer syndrome (TOKAS) is a recessive X-linked multiple congenital anomaly disorder caused by RLIM variations. Of the 41 patients reported, only 7 antenatal cases were described.METHOD: After the antenatal diagnosis of TOKAS by exome analysis in a family followed for over 35 years because of multiple congenital anomalies in five male fetuses, a call for collaboration was made, resulting in a cohort of 11 previously unpublished cases.RESULTS: We present a TOKAS antenatal cohort, describing 11 new cases in 6 French families. We report a high frequency of diaphragmatic hernia (9 of 11), differences in sex development (10 of 11) and various visceral malformations. We report some recurrent dysmorphic features, but also pontocerebellar hypoplasia, pre-auricular skin tags and olfactory bulb abnormalities previously unreported in the literature. Although no clear genotype-phenotype correlation has yet emerged, we show that a recurrent p.(Arg611Cys) variant accounts for 66% of fetal TOKAS cases. We also report two new likely pathogenic variants in RLIM, outside of the two previously known mutational hotspots.CONCLUSION: Overall, we present the first fetal cohort of TOKAS, describe the clinical features that made it a recognisable syndrome at fetopathological examination, and extend the phenotypical spectrum and the known genotype of this rare disorder.</p

Analyse et prise en charge médico chirurgicale du sourire gingival

Le sourire gingival est un sourire découvrant de manière excessive de la gencive (plus de 3 mm de gencive visible). Il peut être le résultat d'anomalies dentaires, parodontales, musculaires et squelettiques. Parfois tous ces éléments s'ajoutent et se cumulent : leur distinction, leur analyse et leur appréciation sont donc primordiales pour arriver à un traitement efficace, esthétique, stable et bien accepté par le patient

Intérêt de la recherche du ganglion sentinelle dans la prise en charge des carcinomes épidermoïdes cutanés cN0 de haut grade de la face

Objectifs: Les carcinomes épidermoïdes cutanés (CEC) à haut risque présentent un risque élevé de métastases ganglionnaires. Actuel1ement la prise en charge des patients cNO consiste en une simple surveillance clinique. La rrecherche du ganglion sentinelle (GGS) permettrait une évaluation précise de l'état ganglionnaire du patient, une détection précoce des métastases occultes et la mise en place rapide d'un traitement approprié. Cette étude est la première analyse prospective pour la population porteuse d'un CEC à haut risque. L'objectifprincipal de cette étude était de montrer que la recherche du GGS (et l'adaptation du traitement en conséquence) permettait d'améliorer la survie sans récidive. Les objectifs secondaires étaient de montrer que le statut du GGS constituait un facteur pronostic, de donner les caractéristiques épidémiologiques de ces patients et de valider la technique de recherche du GGS. Matériels et Méthodes: Les patients présentant un CEC avec au moins un critère de haut risque ont été inclus de manière prospective entre Mai 2005 et Septembre 2010. Ils ont bénéficié de la recherche du GGS après localisation de ce dernier par lymphoscintigraphie. Un curage ganglionnaire +/- associé à une parotidectomie étaient réalisés en cas de GGS envahis. Les données recueillies concernaient les critères de haut risque présentés par le patient, la localisation du GGS en scintigraphie et en per opératoire, l'analyse histologique du GGS, les traitements reçus et l'évolution clinique. La comparaison entre les groupes était réalisée par un test de Student. La méthode de Kaplqn-Meier a été utilisée pour estimer la survie sans récidive. Le test de Log-Rank a été uti1isé pour comparer la survie sans récidive entre les groupes. Résultats: L'étude a permis d'inclure 18 patients de manière prospective. L'identification du GGS par lymphoscintigraphie était de 94%, le taux de détection in vivo de GGS était de 77%. Le taux de GGS positif était de 14%. Au terme de l'étude, il y avait 3 cas (16,7%) de récidive cutanée, 3 cas (16,7%) de récidive ganglionnaire et 5 patients (27,8%) étaient décédés des suites de l'évolution de la maladie. A 4 mois, la survie globale sans récidive était de 71% (50-93). Elle était meilleure pour les patients avec un GGS négatif que pour les patients avec un GGS positif (test de Rank, p=O,Ol). Le seul facteur pronostic corrélé au statut du GGS était la taille de la tumeur (test de Student, p=0,02). Conclusion: Le CEC à haut dsque apparaît comme une tumeur agressive marquée par une évolution fréquemment défavorable. La détermination du statut du GGS semble constituer un facteur pronostique. Aux termes d'études plus approfondies, son évaluation pourrait orienter la prise en charge thérapeutique de ces patients. A l 'heure actuelle, des études sont nécessaires pour identifier précisément la population de CEC à haut risque sur le plan épidémiologique et évaluer l'impact de la recherche du GGS sur la survie globale et sans récidive de ces patients. C'est dans ce sens que nous travaillons à l'élaboration d'un PHRC (Programme Hospitalier de Recherche Clinique) national.Objectives: High dsk squamous cell carcinoma (SCC) of the skin are weIl defined and present a significant higher risk to develop lymph no de metastasis. Actual management for those patients is just a clinical survey. The Sentinel Lymph Node (SLN) biopsy provides valuable staging information, allows early detection of occult metastasis and early treatment. This study is the first prospective analysis for this population. The (iim was to give epidemiology characteristic for this group, further validate sentinellymph node biopsy for high risk SCC of the skin face and give the outcomes and the characteristics of the patient with SLN+ or SLN- status. Methods: Patients with high risk SCC of the skin face were included in a prospective study from 2005 to 2010. They underwent SLN biopsy following a lymphoscintigraphy. Lymph node dissection (LND) (+/- radiotherapy) was done in the case of SLN+. Data from high-dsk criteria, SLN identification and localization, type oftreatment and outcome were collected. Results: We inc1uded 18 patients. The median follow-up was 20,4 months (range 3 to 42 m.). Identification ofthe SLN was 77,8%. Occults metastasis were identified in 14,3% of cases. There were 3 cases (16,7%) of cutaneous recurrence, 3 cases (16,6%) ofnodal metastasis and 5 patients (27,8%) died from disease evolution. In 4 months, the overall disease free survival was 71 % (CI 95%: [50-93]) and was better when the SLN was negative compared with the SLN positive (Rank test= 0,01). The size of the tumour was the only one factor correlated with the SLN status (Student Test, p=0,02). Conclusion: The high risk SCC population seemed to have a poor prognostic. The SLN biopsy for high risk SCC appeared to be a good staging method in cNO patients by detection of occults metastasis. The SLN + status seemed to be a poor prognostic factor. Studies are needed to accurately identify epidemiological characteristics of high risk sec and assess the impact of SLN research to the overall disease free survival.MONTPELLIER-BU Médecine UPM (341722108) / SudocMONTPELLIER-BU Médecine (341722104) / SudocSudocFranceF

The Economic Burden of Severe Acute Malnutrition with Complications: A Cost Analysis for Inpatient Children Aged 6 to 59 Months in Northern Senegal

Severe acute malnutrition (SAM) is a high-fatality condition that affected 13.7 million children under five years of age worldwide in 2022, with complicated cases requiring extensive inpatient stay with an accompanying caregiver. Our objective was to assess the costs of inpatient treatment for complicated SAM in children aged 6 to 59 months in Northern Senegal and identify cost predictors. We performed a retrospective cost analysis, including 140 children hospitalized from January to December 2020 in five SAM inpatient treatment facilities. We adopted a societal perspective, including direct medical and non-medical costs and indirect costs. We extracted patients’ sociodemographic and clinical data from medical records and conducted semi-structured interviews with healthcare staff to capture information on time allocation and care management. A multivariable generalized linear model with gamma family and a log link was used to investigate the factors associated with direct costs. Costs are expressed in 2020 international USD using purchasing power parity. Mean length of stay was 5.3 (SD = 3.2) days and diarrhoea was the cause of the admission in 55.7% of cases. Mean total cost was USD 431.9 (SD = 203.9), with personnel being the largest cost item (33% of the total). Households’ out-of-pocket expenses represented 45.3% of total costs and amounted to USD 195.6 (SD = 103.6). Costs were significantly associated with gender (20.3% lower in boys), diarrhoea (27% increase), anaemia (49.4% increase), inpatient death (44.9% decrease), and type of facility (26% higher in hospitals vs. health centre). Our study highlights the financial burden of complicated SAM in Senegal in particular for families. This underscores the need for tailored prevention and social policies to protect families from the disease’s financial burden and improve treatment adherence, both in Senegal and similar contexts

The Economic Burden of Severe Acute Malnutrition with Complications: A Cost Analysis for Inpatient Children Aged 6 to 59 Months in Northern Senegal

International audienceSevere acute malnutrition (SAM) is a high-fatality condition that affected 13.7 million children under five years of age worldwide in 2022, with complicated cases requiring extensive inpatient stay with an accompanying caregiver. Our objective was to assess the costs of inpatient treatment for complicated SAM in children aged 6 to 59 months in Northern Senegal and identify cost predictors. We performed a retrospective cost analysis, including 140 children hospitalized from January to December 2020 in five SAM inpatient treatment facilities. We adopted a societal perspective, including direct medical and non-medical costs and indirect costs. We extracted patients' sociodemographic and clinical data from medical records and conducted semi-structured interviews with healthcare staff to capture information on time allocation and care management. A multivariable generalized linear model with gamma family and a log link was used to investigate the factors associated with direct costs. Costs are expressed in 2020 international USD using purchasing power parity. Mean length of stay was 5.3 (SD = 3.2) days and diarrhoea was the cause of the admission in 55.7% of cases. Mean total cost was USD 431.9 (SD = 203.9), with personnel being the largest cost item (33% of the total). Households' out-of-pocket expenses represented 45.3% of total costs and amounted to USD 195.6 (SD = 103.6). Costs were significantly associated with gender (20.3% lower in boys), diarrhoea (27% increase), anaemia (49.4% increase), inpatient death (44.9% decrease), and type of facility (26% higher in hospitals vs. health centre). Our study highlights the financial burden of complicated SAM in Senegal in particular for families. This underscores the need for tailored prevention and social policies to protect families from the disease's financial burden and improve treatment adherence, both in Senegal and similar contexts.</div

Extending the clinical spectrum of X-linked Tonne-Kalscheuer syndrome (TOKAS): new insights from the fetal perspective

International audienceIntroduction: Tonne-Kalscheuer syndrome (TOKAS) is a recessive X-linked multiple congenital anomaly disorder caused by RLIM variations. Of the 41 patients reported, only 7 antenatal cases were described.Method: After the antenatal diagnosis of TOKAS by exome analysis in a family followed for over 35 years because of multiple congenital anomalies in five male fetuses, a call for collaboration was made, resulting in a cohort of 11 previously unpublished cases.Results: We present a TOKAS antenatal cohort, describing 11 new cases in 6 French families. We report a high frequency of diaphragmatic hernia (9 of 11), differences in sex development (10 of 11) and various visceral malformations. We report some recurrent dysmorphic features, but also pontocerebellar hypoplasia, pre-auricular skin tags and olfactory bulb abnormalities previously unreported in the literature. Although no clear genotype-phenotype correlation has yet emerged, we show that a recurrent p.(Arg611Cys) variant accounts for 66% of fetal TOKAS cases. We also report two new likely pathogenic variants in RLIM, outside of the two previously known mutational hotspots.Conclusion: Overall, we present the first fetal cohort of TOKAS, describe the clinical features that made it a recognisable syndrome at fetopathological examination, and extend the phenotypical spectrum and the known genotype of this rare disorder

Seed exchange networks for agrobiodiversity conservation. A review

The circulation of seed among farmers is central to agrobiodiversity conservation and dynamics. Agrobiodiversity, the diversity of agricultural systems from genes to varieties and crop species, from farming methods to landscape composition, is part of humanity's cultural heritage. Whereas agrobiodiversity conservation has received much attention from researchers and policy makers over the last decades, the methods available to study the role of seed exchange networks in preserving crop biodiversity have only recently begun to be considered. In this overview, we present key concepts, methods, and challenges to better understand seed exchange networks so as to improve the chances that traditional crop varieties (landraces) will be preserved and used sustainably around the world. The available literature suggests that there is insufficient knowledge about the social, cultural, and methodological dimensions of environmental change, including how seed exchange networks will cope with changes in climates, socio-economic factors, and family structures that have supported seed exchange systems to date. Methods available to study the role of seed exchange networks in the preservation and adaptation of crop specific and genetic diversity range from meta-analysis to modelling, from participatory approaches to the development of bio-indicators, from genetic to biogeographical studies, from anthropological and ethnographic research to the use of network theory. We advocate a diversity of approaches, so as to foster the creation of robust and policy-relevant knowledge. Open challenges in the study of the role of seed exchange networks in biodiversity conservation include the development of methods to (i) enhance farmers' participation to decision-making in agro-ecosystems, (ii) integrate ex situ and in situ approaches, (iii) achieve interdisciplinary research collaboration between social and natural scientists, and (iv) use network analysis as a conceptual framework to bridge boundaries among researchers, farmers and policy makers, as well as other stakeholders

Seed exchange networks for agrobiodiversity conservation. A review

The circulation of seed among farmers is central to agrobiodiversity conservation and dynamics. Agrobiodiversity, the diversity of agricultural systems from genes to varieties and crop species, from farming methods to landscape composition, is part of humanity's cultural heritage. Whereas agrobiodiversity conservation has received much attention from researchers and policy makers over the last decades, the methods available to study the role of seed exchange networks in preserving crop biodiversity have only recently begun to be considered. In this overview, we present key concepts, methods, and challenges to better understand seed exchange networks so as to improve the chances that traditional crop varieties (landraces) will be preserved and used sustainably around the world. The available literature suggests that there is insufficient knowledge about the social, cultural, and methodological dimensions of environmental change, including how seed exchange networks will cope with changes in climates, socio-economic factors, and family structures that have supported seed exchange systems to date. Methods available to study the role of seed exchange networks in the preservation and adaptation of crop specific and genetic diversity range from meta-analysis to modelling, from participatory approaches to the development of bio-indicators, from genetic to biogeographical studies, from anthropological and ethnographic research to the use of network theory. We advocate a diversity of approaches, so as to foster the creation of robust and policy-relevant knowledge. Open challenges in the study of the role of seed exchange networks in biodiversity conservation include the development of methods to (i) enhance farmers' participation to decision-making in agro-ecosystems, (ii) integrate ex situ and in situ approaches, (iii) achieve interdisciplinary research collaboration between social and natural scientists, and (iv) use network analysis as a conceptual framework to bridge boundaries among researchers, farmers and policy makers, as well as other stakeholders