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. Funding Pfizer, Amgen, Merck Sharp & Dohme, Sanofi–Aventis, Daiichi Sankyo, and Regeneron

Outcomes from elective colorectal cancer surgery during the SARS-CoV-2 pandemic

This study aimed to describe the change in surgical practice and the impact of SARS-CoV-2 on mortality after surgical resection of colorectal cancer during the initial phases of the SARS-CoV-2 pandemic

Estudo comparativo dos meios de contraste baritado e iodado-iônico e não-iônico no trato respiratório de ratos Comparative study of barium and iodine agents - ionic and nonionic on the respiratory tract of the rats

OBJETIVO: Durante estudos radiológicos pode ocorrer a passagem do meio de contraste para a árvore traqueo-brônquica, determinando reações adversas e até fatais. O objetivo deste estudo é conhecer as alterações desencadeadas no trato respiratório pela presença do meio de contraste. MÉTODOS: Utilizaram-se 91 ratos divididos, aleatoriamente, em 4 grupos. Um grupo de controle não manipulado com 7 animais e os demais grupos com 21 ratos. O grupo controle manipulado recebeu solução fisiológica e os grupos de experimento: bário, iodo ônico e iodo não iônico conforme o grupo a que pertenciam. Sob anestesia e visibilização direta da traquéia, injetou-se 0,75 ml/kg (0,25 ml) do meio de contraste de acordo com o grupo ao qual pertencesse o animal. Realizaram-se as aferições com 1 hora, 1 dia e 1 semana. Os ratos foram sorteados para a autanásia nos três tempos estudados. Fez-se documentação radiográfica seguida da ressecção dos pulmões e exame histo-patológico. RESULTADOS: Na primeira hora, no grupo que recebeu bário, os campos médios e o superior direito ficaram acometidos. Nos grupos que receberam iodo iônico e iodo não iônico, todo o pulmão direito mostrava-se opacificado. Nas avaliações de uma dia e 1 semana os grupos que receberam iodo estavam normais enquanto que o grupo que recebeu bário mostrava comprometimento dos campos médios. No estudo histo-patológico observou-se, no grupo que recebeu bário, na avaliação de uma semana, grande quantidade de macrófagos intra-alveolares, perivasculares e peribrônquicos. CONCLUSÃO: Os contrastes iodados iônico e não iônico levam a alterações passageiras enquanto que o bário promove reação inflamatória crônica com manutenção da tradução radiográfica, no rato.<br>PURPOSE: During roadiologic studies, passage of the contrast medium to the tracheobronchial tree may occur, causibng adverse or even fatal reactions. The objective of the present study was to determine the changes in the respiratory tract triggered by the presence of contrast medium. METHODS: Ninety-one rats were divided at random into 5 groups, i.e., an intact control group of 7 animals and 4 groups of 21 rats each. The manipulated control group received physiological saline and the experimental groups respectively received barium, ionic iodine and non-ionic iodine. Under anesthesia and direct visualization of the trachea, 0.75 ml/kg (0.25 ml) of the contrast medium was injected into the animals of each group. The effects of the procedure were determined after 1 hour, 1 day and 1 week, with the animals being sacrificed at each time point by drawing lots. Radiographic documentation was obtained, followed by resection and histopathologic examination of the lungs. RESULTS: After 1 hour, the middle fields and the right upper field were involved in the group injected with barium. In the groups injected with ionic iodine and non-ionic iodine, the entire right lung was found to be opacified. After 1 day and 1 week, the groups injected with iodine were normal, whereas the group injected with barium showed involvement of the middle fields. After 1 week, histopathologic examination revealed that the group injected with barium exhibited large amounts of intra-alveolar, perivascular and peribronchial macrophages CONCLUSION: The ionic and non-ionic iodine contrast media led to temporary changes, whereas barium promoted a chronic inflammatory reaction with maintenance of radiographic translation