BMQ

BMQ: Boston Medical Quarterly was published from 1950-1966 by the Boston University School of Medicine and the Massachusetts Memorial Hospitals

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

Detección de diabetes entre familiares consanguíneos de pacientes diabéticos

The two hours pst prandial blood sugar of 209 blood relatives, fifteen years or older, of the diabetic patients from the files at the University Hospital has been studied, as a pilot program in Community Medicine.  Forty seven (22.5%) of the probands had levels of 130 mgm% or more and were unwire considered suspicious of diabetes. Six (2.8%) had 175mg% or more, and were clasified as diabetics.  The search for the probands was done by house visits for one group, and bry motivation at the time of the out-patient visit of the diabetic patient in another. The house visit program gave better results, with a larger number of probands per family studied. The major obstacle to the house visit program was inadecuate recording of the patients address at the hospital files. The advantages of the house visit program, and the importance of the detection of diabetes as a medical program directed to the Community, in the field of the non-infections diseases are discussed.Se ha determinado la glicemia postprandial por el método del Destrostix, en 209 familiares de diabéticos mayores de 15años. Un alto porcentaje de probandos (22.5%) tuvo niveles de glicemia sospechosos o anormales. El 36.4% tuvo un sobrepeso de 15 a 70% del peso idel.  El contacto con los individuos estudiados, se hizo por visita domiciliaria en unos casos y por motivación indirecta a través del pariente diabético en otros. Se otuvieron mejores resultados con las visitas domiciliarias tanto en porcentaje de familias que colaboraron: 85.9% versus 36%, como en la intensidad de esta colaboración: 3.4 personas por familia que colabora para los casos de visita domiciliaria y 1.5 personas por familia que colabora para el grupo de motivación a través del pariente. El obstáculo mayor a la visita domiciliaria estriba en el bajo porcentaje de direcciones verdaderas (36%), del registro hospitalario, lo que indica que debe cambiarse el sistema en uso para obtener un dato utilizable para estudios que empleen esta metodología. Se destacan las ventajas de la visita domiciliaria como método de reclutamiento y la importancia de los programas de detección de diabetes como acción médica en términos de familia/comunidad en el campo de la patología no infecciosa.

La Captación de Yodo Radioactivo y la Excreción Urinaria de Yodo Estable en la Altura

Hemos determinado la captación de iodo radioactivo por contaje epitiroideo directo en nativos de Huancayo (3,200 m. SNM) y Cerro de Pasco (4,300 m. SNM) ciudades de los Andes centrales del Perú, encontrando valores de 53.9±31 % (Media ± ESM) para Huancayo y de 42.8± 2.0 % para Cerro de Pasco. Ambos valores son mas elevados (P«0.001) que los que se encuentran en Lima: 34.8 ± 0.87 %, ciudad ubicada en la costa a 150 m. SNM. La mayor captación corresponde a Huancayo, ubicada en una altitud intermedia. La excreción urinaria de iodo estable se encuentra disminuida en Cerro de Pasco (64.6 ± 14.4 ugm/24 hs_). Se discute la influencia de los factores altura y carencia de ¡odo en la distribución del bocio endémico en relación a la altura. SUMMARY The Thyroidal uptake of I131 has been studied in Huancayo (3,200 m. SNM) and Cerro de Pasco (4,200 m. SNM), two cities on the Central Andean plateau. Subjects living in Huancayo had a Mean ± SEM of 53.9 ± 3.1 % and those of Cerro de Pasco: 42.8 ± 2.0 %. These values are higher (P<<0.001) than those reported for Lima: 34.8 ± 0.87 %, the coastal (150 m. SNM) capitay city of Perú. The highest uptake is that of Huancayo, located at an intermediate altitude. The urinary excretion of stable iodine by natives from Cerro de Pasco is 64.6±14.4 ugm/24 hs ( Mean ± SEM).  The influence of altitude and iodine deficiency on the distribution of endemic goiter in the Central Andean plateau is discussed

Baja excreción urinaria de Serotonina como índice de malnutrición.

Fragmento INTRODUCCION El impacto de la malnutrición materna en el feto no necesita ser enfatizado: es bien conocido que determina un incremento considerable en la morbilidad y mortalidad durante el período neonatal  y de una mayor trascendencia, que ella afecta un período muy importante en el desarrollo del cerebro y otras importantes estructuras del feto, como ha sido demostrado por Winninck y otros. Por estas razones y para iluminar otras áreas de nuestra investigación sobre el embarazo en la altura, nos hemos interesado en la búsqueda de parámetros bioquímicos que puedan ser de ayuda en indicar cuáles son los fetos que están sufriendo de manera importante por la malnutrición materna

Genomic Profile in a Non-Seminoma Testicular Germ-Cell Tumor Cohort Reveals a Potential Biomarker of Sensitivity to Platinum-Based Therapy

SIMPLE SUMMARY: Despite having a favorable response to platinum-based chemotherapies, ~15% of Testicular Germ-Cell Tumor (TGCT) patients are platinum-resistant. Incidence and mortality of this disease has remained unchanged in Latin populations unlike the rest of the world. To date, the search for genetic variants in our population remains unexplored. The aim of this study is to identify predictive biomarkers of resistance to platinum-based therapy, whether general or specific to the Latin population. We observed that sensitivity to chemotherapy does not seem to be explained by any of the mutations detected. However, we identified amplifications on segment 2q11.1 as a novel variant with chemosensitivity biomarker potential. Our data shed light into understanding platinum resistance in a Latin-origin population. ABSTRACT: Despite having a favorable response to platinum-based chemotherapies, ~15% of Testicular Germ-Cell Tumor (TGCT) patients are platinum-resistant. Mortality rates among Latin American countries have remained constant over time, which makes the study of this population of particular interest. To gain insight into this phenomenon, we conducted whole-exome sequencing, microarray-based comparative genomic hybridization, and copy number analysis of 32 tumors from a Mexican cohort, of which 18 were platinum-sensitive and 14 were platinum-resistant. We incorporated analyses of mutational burden, driver mutations, and SNV and CNV signatures. DNA breakpoints in genes were also investigated and might represent an interesting research opportunity. We observed that sensitivity to chemotherapy does not seem to be explained by any of the mutations detected. Instead, we uncovered CNVs, particularly amplifications on segment 2q11.1 as a novel variant with chemosensitivity biomarker potential. Our data shed light into understanding platinum resistance in a Latin-origin population