Acondroplasia: actualización en diagnóstico, seguimiento y tratamiento

Achondroplasia; Bone dysplasiaAcondroplasia; Displasia óseaAcondroplàsia; Displàsia òssiaAchondroplasia requieres multidisciplinary follow-up, with the aim of preventing and managing complications, improving the quality of life of people who suffer from it and favoring their independence and social inclusion. This review is justified by the multiple publications generated in recent years that have carried out a change in its management. Different guidelines and recommendations have been developed, among which the one made by the American Academy of Pediatrics in 2005 recently updated (2020), the Japanese guide (2020), the first European Consensus (2021) and the International Consensus on the diagnosis, approach multidisciplinary approach and management of individuals with achondroplasia throughout life (2021). However, and despite these recommendations, there is currently a great worldwide variability in the management of people with achondroplasia, with medical, functional and psychosocial consequences in patients and their families. Therefore, it is essential to integrate these recommendations into daily clinical practice, taking into account the particular situation of each health system.La acondroplasia requiere un seguimiento multidisciplinario, con el objetivo de prevenir y manejar las complicaciones, mejorar la calidad de vida de las personas que la padecen y favorecer su independencia e inclusión social. Esta revisión se justifica por las múltiples publicaciones generadas en los últimos años que han llevado a cabo un cambio en su gestión. Se han desarrollado diferentes guías y recomendaciones, entre las que destacan la realizada por la Academia Americana de Pediatría en 2005 recientemente actualizada (2020), la guía japonesa (2020), el primer Consenso Europeo (2021) y el Consenso Internacional sobre el diagnóstico, abordaje, enfoque multidisciplinario y manejo de individuos con acondroplasia a lo largo de la vida (2021). Sin embargo, y a pesar de estas recomendaciones, actualmente existe una gran variabilidad a nivel mundial en el manejo de las personas con acondroplasia, con consecuencias médicas, funcionales y psicosociales en los pacientes y sus familias. Por ello, es fundamental integrar estas recomendaciones en la práctica clínica diaria, teniendo en cuenta la situación particular de cada sistema sanitario

Planta de producción de ácido láctico

El presente proyecto trata sobre el diseño y el estudio de la viabilidad de construcción y funcionamiento de una planta para la producción de ácido láctico siguiendo las pertinentes normativas urbanísticas, sectoriales y medioambientales

Infigratinib in children with achondroplasia:the PROPEL and PROPEL 2 studies

BACKGROUND: Achondroplasia is the most common short-limbed skeletal dysplasia resulting from gain-of-function pathogenic variants in fibroblast growth factor receptor 3 (FGFR3) gene, a negative regulator of endochondral bone formation. Most treatment options are symptomatic, targeting medical complications. Infigratinib is an orally bioavailable, FGFR1–3 selective tyrosine kinase inhibitor being investigated as a direct therapeutic strategy to counteract FGFR3 overactivity in achondroplasia. OBJECTIVES: The main objective of PROPEL is to collect baseline data of children with achondroplasia being considered for future enrollment in interventional studies sponsored by QED Therapeutics. The objectives of PROPEL 2 are to obtain preliminary evidence of safety and efficacy of oral infigratinib in children with achondroplasia, to identify the infigratinib dose to be explored in future studies, and to characterize the pharmacokinetic (PK) profile of infigratinib and major metabolites. DESIGN: PROPEL (NCT04035811) is a prospective, noninterventional clinical study designed to characterize the natural history and collect baseline data of children with achondroplasia over 6−24 months. PROPEL 2 (NCT04265651), a prospective, phase II, open-label study of infigratinib in children with achondroplasia, consists of a dose-escalation, dose-finding, and dose-expansion phase to confirm the selected dose, and a PK substudy. METHODS AND ANALYSIS: Children aged 3−11 years with achondroplasia who completed ⩾6 months in PROPEL are eligible for PROPEL 2. Primary endpoints include treatment-emergent adverse events and change from baseline in annualized height velocity. Four cohorts at ascending dose levels are planned for dose escalation. The selected dose will be confirmed in the dose-expansion phase. ETHICS: PROPEL and PROPEL 2 are being conducted in accordance with the International Conference on Harmonization Good Clinical Practice guidelines, principles of the Declaration of Helsinki, and relevant human clinical research and data privacy regulations. Protocols have been approved by local health authorities, ethics committees, and institutions as applicable. Parents/legally authorized representatives are required to provide signed informed consent; signed informed assent by the child is also required, where applicable. DISCUSSION: PROPEL and PROPEL 2 will provide preliminary evidence of the safety and efficacy of infigratinib as precision treatment of children with achondroplasia and will inform the design of future studies of FGFR-targeted agents in achondroplasia. REGISTRATION: ClinicalTrials.gov: NCT04035811; NCT04265651

Impacto del alargamiento de extremidades en la antropometría, funcionalidad, composición corporal, perfil metabólico y calidad de vida en población pediátrica y adolescente con acondroplasia

Resultados. En el primer estudio se incluyen 20 pacientes, de los cuales 10 completan s1 (grupo S1) y 10 finalizan s1 y s2 (grupo S2). Atendiendo a variables antropométricas se destaca en un incremento en la altura en cm y SDS (p<0.05) pasando de -5.8 (0.9) a -4.6 (0.6) y -5.5 (1) a -4.5 (0.7) SDS en los grupos S1 y S2 respectivamente, según las tablas de referencia para población no acondroplásica del CDC, y una mejora en la proporcionalidad corporal al relacionar el perímetro cefálico y la altura. Además, en el grupo S2 se observa un incremento de la brazada (p<0.05), pasando de 99.7 (3) cm a 123 (3.9) cm en varones y de 100.3 (6.2) a 122.3 (7.1) en mujeres, y un descenso del IMC (p<0.05). Atendiendo a variables radiológicas, se destaca una mejora en la alineación de miembros inferiores y un descenso de la lordosis lumbar de ambos grupos. En el segundo estudio se incluye un total de 30 pacientes. Los grupos S1 y S2 del estudio previo tras la finalización de los procedimientos quirúrgicos, y 10 pacientes sin alargamiento (grupo S0). Los grupos incluidos en el protocolo de alargamiento mantienen una mejora en variables antropométricas, de proporcionalidad corporal y relacionadas con la calidad de vida y salud (HrQoL), así como un descenso en variables como el IMC y el perímetro de cintura. Se establece un asociación positiva entre la antropometría y todas la variables de calidad de vida y salud, destacando el dominio funcional y emocional. Conclusiones. A pesar de la complejidad y las complicaciones relacionadas con el protocolo de alargamiento, dicho procedimiento permite una mejora en variables antropométricas entre las que se destaca la altura, la proporción corporal, la brazada y el IMC. Dichas variables se relacionan positivamente con la calidad de vida y funcionalidad (HrQoL).Introducción. La acondroplasia, displasia esquelética más frecuente, asocia diferentes comorbilidades entre las que destacan la talla baja desproporcionada, la cual puede afectar a la funcionalidad y calidad de vida (HrQoL) de dichos pacientes. A la espera de resultados a largo plazo de las terapias médicas actualmente autorizadas, hace del alargamiento quirúrgico una opción terapéutica posible con el objetivo de incrementar la longitud de las extremidades. Para ello, se propone un protocolo de alargamiento estratificado en un primer procedimiento de alargamiento simultáneo y bilateral de miembros inferiores (s1) y un segundo tiempo de alargamiento bilateral de húmeros (s2). Objetivo. Analizar el impacto del alargamiento de miembros inferiores y superiores en la antropometría, funcionalidad, composición corporal, perfil metabólico y calidad de vida en población pediátrica y adolescente con acondroplasia. Material y Métodos. Población acondroplásica infantil y adolescente con una talla en bipedestación inferior al percentil 50, según las tablas específicas. Se realiza un doble diseño. 1. Estudio observacional analítico, longitudinal, ambispectivo de cohortes con dos grupos incluidos en el protocolo de alargamiento (grupo S1: procedimiento s1; y el grupo S2: procedimientos s1 y s2). Se recogen variables quirúrgicas, antropométricas, de proporcionalidad corporal y radiológicas, y se analizan antes y después de los procedimientos y entre los dos grupos al final de los mismos. 2. Estudio observacional descriptivo, transversal o de corte con tres grupos de población acondroplásica entre 12 y 16 años (grupo S0: no se realiza cirugía de alargamiento; grupos S1 y S2 hacen referencia a los grupos del diseño previo al año de la cirugía). Se recogen y analizan entre los tres grupos variables antropométricas, de proporcionalidad corporal, radiológicas, calidad de vida, funcionalidad, composición corporal y metabólicas

Achondroplasia: Update on diagnosis, follow-up and treatment

Achondroplasia requieres a multidisciplinary follow-up, with the aim of preventing and managing complications, improving the quality of life and favoring their independence and social inclusion. This review is justified by the multiple publications generated in recent years that have carried out a change in its management. Different guidelines and recommendations have been developed, among which the one made by the American Academy of Pediatrics in 2005 recently updated (2020), the Japanese guide (2020), the first European Consensus (2021) and the International Consensus on the diagnosis, approach multidisciplinary approach and management of individuals with achondroplasia throughout life (2021). However, and despite these recommendations, there is currently a great worldwide variability in the management of people with achondroplasia, with medical, functional and psychosocial consequences in patients and their families. Therefore, it is essential to integrate these recommendations into daily clinical practice, taking into account the particular situation of each health system.(c) 2022 Asociacion Espanola de Pediatria. Published by Elsevier Espana, S.L.U. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/ 4.0/)

Gut Microbiota Differs in Composition and Functionality Between Children With Type 1 Diabetes and MODY2 and Healthy Control Subjects: A Case-Control Study.

Type 1 diabetes is associated with compositional differences in gut microbiota. To date, no microbiome studies have been performed in maturity-onset diabetes of the young 2 (MODY2), a monogenic cause of diabetes. Gut microbiota of type 1 diabetes, MODY2, and healthy control subjects was compared. This was a case-control study in 15 children with type 1 diabetes, 15 children with MODY2, and 13 healthy children. Metabolic control and potential factors modifying gut microbiota were controlled. Microbiome composition was determined by 16S rRNA pyrosequencing. Compared with healthy control subjects, type 1 diabetes was associated with a significantly lower microbiota diversity, a significantly higher relative abundance of Bacteroides, Ruminococcus, Veillonella, Blautia, and Streptococcus genera, and a lower relative abundance of Bifidobacterium, Roseburia, Faecalibacterium, and Lachnospira. Children with MODY2 showed a significantly higher Prevotella abundance and a lower Ruminococcus and Bacteroides abundance. Proinflammatory cytokines and lipopolysaccharides were increased in type 1 diabetes, and gut permeability (determined by zonulin levels) was significantly increased in type 1 diabetes and MODY2. The PICRUSt analysis found an increment of genes related to lipid and amino acid metabolism, ABC transport, lipopolysaccharide biosynthesis, arachidonic acid metabolism, antigen processing and presentation, and chemokine signaling pathways in type 1 diabetes. Gut microbiota in type 1 diabetes differs at taxonomic and functional levels not only in comparison with healthy subjects but fundamentally with regard to a model of nonautoimmune diabetes. Future longitudinal studies should be aimed at evaluating if the modulation of gut microbiota in patients with a high risk of type 1 diabetes could modify the natural history of this autoimmune disease

Planta de producción de ácido láctico

El presente proyecto trata sobre el diseño y el estudio de la viabilidad de construcción y funcionamiento de una planta para la producción de ácido láctico siguiendo las pertinentes normativas urbanísticas, sectoriales y medioambientales

Connection between the Gut Microbiome, Systemic Inflammation, Gut Permeability and FOXP3 Expression in Patients with Primary Sjögren's Syndrome.

The aims of this study were to explore intestinal microbial composition and functionality in primary Sjögren's syndrome (pSS) and to relate these findings to inflammation, permeability and the transcription factor Forkhead box protein P3 (FOXP3) gene expression in peripheral blood. The study included 19 pSS patients and 19 healthy controls matched for age, sex, and body mass index. Fecal bacterial DNA was extracted and analyzed by 16S rRNA sequencing using an Ion S5 platform followed by a bioinformatics analysis using Quantitative Insights into Microbial Ecology (QIIME II) and Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt). Our data suggest that the gut microbiota of pSS patients differs at both the taxonomic and functional levels with respect to healthy controls. The gut microbiota profile of our pSS patients was characterized by a lower diversity and richness and with Bacteroidetes dominating at the phylum level. The pSS patients had less beneficial or commensal butyrate-producing bacteria and a higher proportion of opportunistic pathogens with proinflammatory activity, which may impair intestinal barrier function and therefore contribute to inflammatory processes associated with pSS by increasing the production of proinflammatory cytokines and decreasing the release of the anti-inflammatory cytokine IL-10 and the peripheral FOXP3 mRNA expression, implicated in the development and function of regulatory T cells (Treg) cells. Further studies are needed to better understand the real impact of dysbiosis on the course of pSS and to conceive preventive or therapeutic strategies to counteract microbiome-driven inflammation

Adipokines Profile and Inflammation Biomarkers in Prepubertal Population with Obesity and Healthy Metabolic State.

(1) Background and aims: Obesity and high body max index (BMI) have been linked to elevated levels of inflammation serum markers such as C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-alpha), adiponectin, and resistin. It has been described that adipose tissue presents a high production and secretion of these diverse pro-inflammatory molecules, which may have local effects on the physiology of the fat cell and also systemic effects on other organs. Our aim was to evaluate the impact that lifestyle modifications, following a Mediterranean Diet (MedDiet) program and physical activity (PA) training, would have on inflammatory biomarkers in a metabolically healthy prepubertal population with obesity (MHOPp) from Malaga (Andalusia, Spain). (2) Methods: 144 MHOPp subjects (aged 5-9 years) were included in this study as they met ≤1 of the following criteria: waist circumference and blood pressure ≥ 90 percentile, triglycerides > 90 mg/dL, high-density lipoprotein cholesterol (HDL-c) 90 mg/dL, high-density lipoprotein cholesterol (HDL-c