Familial hypercholesterolaemia in children and adolescents from 48 countries: a cross-sectional study

Background: Approximately 450 000 children are born with familial hypercholesterolaemia worldwide every year, yet only 2·1% of adults with familial hypercholesterolaemia were diagnosed before age 18 years via current diagnostic approaches, which are derived from observations in adults. We aimed to characterise children and adolescents with heterozygous familial hypercholesterolaemia (HeFH) and understand current approaches to the identification and management of familial hypercholesterolaemia to inform future public health strategies. Methods: For this cross-sectional study, we assessed children and adolescents younger than 18 years with a clinical or genetic diagnosis of HeFH at the time of entry into the Familial Hypercholesterolaemia Studies Collaboration (FHSC) registry between Oct 1, 2015, and Jan 31, 2021. Data in the registry were collected from 55 regional or national registries in 48 countries. Diagnoses relying on self-reported history of familial hypercholesterolaemia and suspected secondary hypercholesterolaemia were excluded from the registry; people with untreated LDL cholesterol (LDL-C) of at least 13·0 mmol/L were excluded from this study. Data were assessed overall and by WHO region, World Bank country income status, age, diagnostic criteria, and index-case status. The main outcome of this study was to assess current identification and management of children and adolescents with familial hypercholesterolaemia. Findings: Of 63 093 individuals in the FHSC registry, 11 848 (18·8%) were children or adolescents younger than 18 years with HeFH and were included in this study; 5756 (50·2%) of 11 476 included individuals were female and 5720 (49·8%) were male. Sex data were missing for 372 (3·1%) of 11 848 individuals. Median age at registry entry was 9·6 years (IQR 5·8-13·2). 10 099 (89·9%) of 11 235 included individuals had a final genetically confirmed diagnosis of familial hypercholesterolaemia and 1136 (10·1%) had a clinical diagnosis. Genetically confirmed diagnosis data or clinical diagnosis data were missing for 613 (5·2%) of 11 848 individuals. Genetic diagnosis was more common in children and adolescents from high-income countries (9427 [92·4%] of 10 202) than in children and adolescents from non-high-income countries (199 [48·0%] of 415). 3414 (31·6%) of 10 804 children or adolescents were index cases. Familial-hypercholesterolaemia-related physical signs, cardiovascular risk factors, and cardiovascular disease were uncommon, but were more common in non-high-income countries. 7557 (72·4%) of 10 428 included children or adolescents were not taking lipid-lowering medication (LLM) and had a median LDL-C of 5·00 mmol/L (IQR 4·05-6·08). Compared with genetic diagnosis, the use of unadapted clinical criteria intended for use in adults and reliant on more extreme phenotypes could result in 50-75% of children and adolescents with familial hypercholesterolaemia not being identified. Interpretation: Clinical characteristics observed in adults with familial hypercholesterolaemia are uncommon in children and adolescents with familial hypercholesterolaemia, hence detection in this age group relies on measurement of LDL-C and genetic confirmation. Where genetic testing is unavailable, increased availability and use of LDL-C measurements in the first few years of life could help reduce the current gap between prevalence and detection, enabling increased use of combination LLM to reach recommended LDL-C targets early in life

Clinical characterization of data-driven diabetes subgroups in Mexicans using a reproducible machine learning approach

Introduction Previous reports in European populations demonstrated the existence of five data-driven adult-onset diabetes subgroups. Here, we use self-normalizing neural networks (SNNN) to improve reproducibility of these data-driven diabetes subgroups in Mexican cohorts to extend its application to more diverse settings.Research design and methods We trained SNNN and compared it with k-means clustering to classify diabetes subgroups in a multiethnic and representative population-based National Health and Nutrition Examination Survey (NHANES) datasets with all available measures (training sample: NHANES-III, n=1132; validation sample: NHANES 1999–2006, n=626). SNNN models were then applied to four Mexican cohorts (SIGMA-UIEM, n=1521; Metabolic Syndrome cohort, n=6144; ENSANUT 2016, n=614 and CAIPaDi, n=1608) to characterize diabetes subgroups in Mexicans according to treatment response, risk for chronic complications and risk factors for the incidence of each subgroup.Results SNNN yielded four reproducible clinical profiles (obesity related, insulin deficient, insulin resistant, age related) in NHANES and Mexican cohorts even without C-peptide measurements. We observed in a population-based survey a high prevalence of the insulin-deficient form (41.25%, 95% CI 41.02% to 41.48%), followed by obesity-related (33.60%, 95% CI 33.40% to 33.79%), age-related (14.72%, 95% CI 14.63% to 14.82%) and severe insulin-resistant groups. A significant association was found between the SLC16A11 diabetes risk variant and the obesity-related subgroup (OR 1.42, 95% CI 1.10 to 1.83, p=0.008). Among incident cases, we observed a greater incidence of mild obesity-related diabetes (n=149, 45.0%). In a diabetes outpatient clinic cohort, we observed increased 1-year risk (HR 1.59, 95% CI 1.01 to 2.51) and 2-year risk (HR 1.94, 95% CI 1.13 to 3.31) for incident retinopathy in the insulin-deficient group and decreased 2-year diabetic retinopathy risk for the obesity-related subgroup (HR 0.49, 95% CI 0.27 to 0.89).Conclusions Diabetes subgroup phenotypes are reproducible using SNNN; our algorithm is available as web-based tool. Application of these models allowed for better characterization of diabetes subgroups and risk factors in Mexicans that could have clinical applications

Biodiversity 2016. Status and Trends of Colombian Continental Biodiversity

This third volume of the annual report on biodiversity in Colombia continues the editorial line that begun in 2014. Using novel analytical and graphic proposals, these reports have the goal of communicating the contents to a broad public, making it available for discussion without sacrificing the quality of information. The challenge of communication continues to be a major part of the institutional project, and the new languages with which we are learning to communicate with society and other institutions are an experiment that we expect to be increasingly gratifying. The report for 2017 is already under construction and it counts on new digital technologies so the power of a colombian vital connection may be entirely expressed. The included content evidences that we are still far away from having a systematic follow-up about most of the topics related to the management of biodiversity and ecosystem services, which is the only way to evaluate the effectiveness of policies and investments made by society. In fact, a limitation that is recognized is that of identifying positive or negative changes that affect different levels of organization of life on this planet; therefore, our global navigation route of the Aichi targets is still to be verified. An additional purpose of this process includes the invitation of all Colombians to contribute in constructing and maintaining basic monitoring indicators for management since it is impossible to identify long-term trends of flora and fauna in the country without the support of institutions, researchers, and citizens. This challenge is immense in a megadiverse country such as Colombia. For this reason, the report will continue to open its pages to experts, and even indigenous peoples or local communities, for them to present their perspectives about environmental change and its effects on biodiversity in a systematic and documented manner. This has the objective of stimulating the commitment of everyone in the management of biodiversity and ecosystem services. The only way of overcoming the risk of extinction is through the active process of social learning in which all sectors assume a part of the complex responsibility in protecting the forms of life of the country, a roughly counted tenth of all creatures on Earth. I thank all the people that contributed in this Report, those who have supported us in the phases of production, and all readers and users, who are the ultimate judges of its utility.Bogotá, D. C

Biodiversidad 2016. Estado y Tendencias de la Biodiversidad Continental de Colombia

Esta tercera entrega del reporte anual de la biodiversidad en Colombia profundiza en la línea editorial iniciada el año 2014 mediante nuevas propuestas analíticas y gráficas, con la intención de garantizar que la información llegue a todos los públicos y pueda ser discutida de manera amena sin sacrificio de calidad. La apuesta comunicativa sigue siendo central en el proyecto institucional y los nuevos lenguajes con los que estamos aprendiendo a conversar con la sociedad y las instituciones son un experimento que esperamos sea cada vez más satisfactorio: ya estamos construyendo la versión 2017 con el apoyo de las nuevas tecnologías digitales de manera que la potencia de la conexión vital colombiana se exprese en toda su capacidad. Por los contenidos es evidente que aún distamos mucho de tener una capacidad de seguimiento sistemático para la mayoría de temas relativos a la gestión de la biodiversidad y los servicios ecosistémicos, la única manera de evaluar si las medidas de política y las inversiones que realiza la sociedad están teniendo los efectos deseados. De hecho, parte de las limitaciones reconocidas por robustamente los cambios positivos o negativos que afectan los diferentes niveles de organización de la vida planetaria, por lo cual las mismas metas de Aichi, nuestra carta de navegación global, están pendientes de verificación. Un propósito adicional de este proceso es la invitación a todos los colombianos para contribuir con la construcción y alimentación de los indicadores básicos de seguimiento a la gestión, ya que es imposible identificar las tendencias de largo plazo en que están inmersas la flora y fauna colombianas sin el apoyo de las instituciones, los investigadores y los ciudadanos: en el país de la megadiversidad, el reto es inmenso. Por este motivo, este reporte irá abriendo sus páginas a expertos, incluso indígenas o de comunidades locales, para que presenten de manera sistemática y documentada sus perspectivas del cambio ambiental y sus efectos en la biodiversidad, con el ánimo de promover el compromiso de todos en su gestión. La única manera de superar el riesgo de extinción es mediante un activo proceso de aprendizajes sociales que haga que todos los sectores asuman una parte de la compleja responsabilidad que significa proteger todas las formas de vida del país, una décima parte mal contada de las planetarias. Agradezco a las decenas de personas que contribuyeron con este reporte, a quienes nos han apoyado en todas las etapas de producción y a sus lectores y usuarios, quienes son en último término los jueces de su utilidad.Bogotá, D. C

ENGIU: Encuentro Nacional de Grupos de Investigación de UNIMINUTO.

El desarrollo del prototipo para el sistema de detección de Mina Antipersona (MAP), inicia desde el semillero ADSSOF perteneciente al programa de Administración en Seguridad y Salud en el trabajo de la UNIMINUTO, se realiza a partir de un detector de metales que emite una señal audible, que el usuario puede interpretar como aviso de presencia de un objeto metálico, en este caso una MAP. La señal audible se interpreta como un dato, como ese dato no es perceptible a 5 metros de distancia, se implementa el transmisor de Frecuencia Modulada FM por la facilidad de modulación y la escogencia de frecuencia de transmisión de acuerdo con las normas y resolución del Ministerio de Comunicaciones; de manera que esta sea la plataforma base para enviar los datos obtenidos a una frecuencia establecida. La idea es que el ser humano no explore zonas peligrosas y buscar la forma de crear un sistema que permita eliminar ese riesgo, por otro lado, buscar la facilidad de uso de elementos ya disponibles en el mercado

Surgical outcomes of gallbladder cancer: the OMEGA retrospective, multicentre, international cohort study

Background Gallbladder cancer (GBC) is rare but aggressive. The extent of surgical intervention for different GBC stages is non-uniform, ranging from cholecystectomy alone to extended resections including major hepatectomy, resection of adjacent organs and routine extrahepatic bile duct resection (EBDR). Robust evidence here is lacking, however, and survival benefit poorly defined. This study assesses factors associated with recurrence-free survival (RFS), overall survival (OS) and morbidity and mortality following GBC surgery in high income countries (HIC) and low and middle income countries (LMIC).Methods The multicentre, retrospective Operative Management of Gallbladder Cancer (OMEGA) cohort study included all patients who underwent GBC resection across 133 centres between 1st January 2010 and 31st December 2020. Regression analyses assessed factors associated with OS, RFS and morbidity.Findings On multivariable analysis of all 3676 patients, wedge resection and segment IVb/V resection failed to improve RFS (HR 1.04 [0.84-1.29], p = 0.711 and HR 1.18 [0.95-1.46], p = 0.13 respectively) or OS (HR 0.96 [0.79-1.17], p = 0.67 and HR 1.48 [1.16-1.88], p = 0.49 respectively), while major hepatectomy was associated with worse RFS (HR 1.33 [1.02-1.74], p = 0.037) and OS (HR 1.26 [1.03-1.53], p = 0.022). Furthermore, EBDR (OR 2.86 [2.3-3.52], p < 0.0010), resection of additional organs (OR 2.22 [1.62-3.02], p < 0.0010) and major hepatectomy (OR 3.81 [2.55-5.73], p < 0.0010) were all associated with increased morbidity and mortality. Compared to LMIC, patients in HIC were associated with poorer RFS (HR 1.18 [1.02-1.37], p = 0.031) but not OS (HR 1.05 [0.91-1.22], p = 0.48). Adjuvant and neoadjuvant treatments were infrequently used.Interpretation In this large, multicentre analysis of GBC surgical outcomes, liver resection was not conclusively associated with improved survival, and extended resections were associated with greater morbidity and mortality without oncological benefit. Aggressive upfront resections do not benefit higher stage GBC, and international col-laborations are needed to develop evidence-based neoadjuvant and adjuvant treatment strategies to minimise surgical morbidity and prioritise prognostic benefit.Funding Cambridge Hepatopancreatobiliary Department Research Fund.Copyright & COPY; 2023 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)