Evolución del riesgo cardiometabólico en pacientes supervivientes de leucemia aguda infantil

Introducción: los supervivientes de leucemia aguda (LA) infantil presentan un riesgo incrementado de alteraciones metabólicas y cardiovasculares que aumentan su morbimortalidad a largo plazo.Objetivo: estimar la prevalencia de obesidad, resistencia a la insulina, dislipemia e hipertensión arterial como factores de riesgo cardiometabólico (FRCM) en un grupo de supervivientes de LA infantil, y analizar las posibles causas asociadas a su desarrollo.Material y métodos: estudio observacional retrospectivo en 47 supervivientes de LA tratados en un periodo de 4 años, que recibieron seguimiento durante 10 años.Resultados: el 40% de los participantes presentaron al menos un FRCM durante el seguimiento, siendo la dislipemia (aumento LDL) el más frecuente (38, 3%), seguido de obesidad/sobrepeso (31, 9%) y HTA sistólica (23, 4%). El sexo femenino se estableció como factor de riesgo parael desarrollo de todos ellos (RR 1, 6; RR 3, 16; RR 1, 69; p < 0, 05). Ningún superviviente desarrolló diabetes mellitus, pero sí resistencia a la insulina el 19, 4%. Los pacientes con leucemias de peor pronóstico presentaron mayor riesgo de desarrollar obesidad, resistencia a la insulina y aumento de LDL (RR 3, 56; RR 4, 08; RR 2, 53; p < 0, 05). Los pacientes tratados con trasplante de progenitores hematopoyéticos presentaron mayor riesgo de obesidad, aumento de LDL e HTA sistólica (RR 2, 86; RR 2, 39; RR 3, 12; p<0, 05). La radioterapia se asoció de igual modo con un incremento de resistencia a la insulina e hipertensión arterial sistólica (RR 2, 47; RR 2, 53; p < 0, 05).Conclusiones: existe un aumento en la prevalencia de obesidad/sobrepeso, dislipemia, resistencia a la insulina y alteración de la tensión arterial sistólica en supervivientes de leucemia aguda infantil a lo largo del tiempo, especialmente en aquellos con enfermedades y tratamientos más agresivos. Background: Survivors of childhood acute leukemia (AL) face an increased risk of metabolic and cardiovascular late effects which increase their long-term morbimotality. Objective: To assess the prevalence of obesity, insulinresistance, dyslipidemia and hypertension as cardiometabolic risk factors in survivors of a childhood AL, and also to determine possible causes for these adverse cardiometabolic traits. Material and methods: A retrospective cohort study of 47 pediatric acute leukemia survivors diagnosed between 0-15 years, with a ten years follow-up. Results: Forty percent of participants had at least one cardiometabolic risk factor. Dyslipidemia (increased LDL cholesterol) was the most frequent (38.3%), secondly overweight/obese (31.9%), followed by systolic hypertension (23.4%). Females in contrast to males had an increased risk of developing all three risk factors (RR 1.6; RR 3.16; RR 1.69; p < 0.05). Only 19.4% of participants developed insulin resistance, while none were diagnosed with diabetes mellitus. High risk acute leukemia survivors were significantly more likely than low risk leukemia survivors to manifest multiple cardiometabolic traits like overweight/obesity, insulin resitance and dyslipidemia (RR 3.56; RR 2.39; RR 2.53; p < 0.05). Also, those who received hematopoietic cell trasplantation had an increased prevalence of overweight/obesity, increased LDL-cholesterol and systolic hypertension. Radiotherapy treatment was also associated with insulin resitance and systolic hypertension (RR 2.47; RR 2.53; p < 0.05). Conclusions: There is an increased risk of overweight/obesity, dyslipidemia, insulin resistance and systolic blood pressure modification in childhood acute leukemia survivors, specially in those who were diagnosed as a high risk acute leukemia and those treated with more aggressive treatments

Echocardiographic findings in haemodialysis patients according to their state of hydration

AbstractBackgroundChronic fluid overload is frequent in hemodialysis patients (P) and it associates with hypertension, left ventricular hypertrophy (LVH) and higher mortality. Moreover, echocardiographic data assessing fluid overload is limited. Our aim was to evaluate the relationship between fluid overload measured by bioimpedance spectroscopy (BIS) and different echocardiographic parameters.MethodsCross-sectional observational study including 76 stable patients. Dry weight was clinically assessed. BIS and echocardiography were performed. Weekly time-averaged fluid overload (TAFO) and relative fluid overload (FO/ECW) were calculated using BIS measurements.ResultsBased on TAFO three groups were defined: A- dehydrated, TAFO <-0.25 L 32 P (42%); B- normohydrated, TAFO between -0.25 and 1.5 l: 26 (34%); C- overhydrated, TAFO>1.5 l: 18 (24%). We found significant correlation between TAFO and left atrial volume index (LAVI) (r: 0.29; p=0.013) but not with FO/ECW (r 0.06; p=0.61). TAFO, but not FO/ECW kept a significant relationship with LAVI (p=0.03) using One-Way ANOVA test and linear regression methods. LVH was present in 73.7% (concentric 63.2%, eccentric in 10.5%). No differences between groups in the presence of LVH or left ventricular mass index were found.ConclusionsWe found that left atrial volume index determined by echocardiographic Area-length method, but not left ventricle hypertrophy or dimensions of cavities, are related on hydration status based on bioimpedance measured time-averaged fluid overload (TAFO), and not with FO/ECW

Dyskeratosis congenita: natural history of the disease through the study of a cohort of patients diagnosed in childhood

BackgroundDyskeratosis congenita (DC) is a multisystem and ultra-rare hereditary disease characterized by somatic involvement, bone marrow failure, and predisposition to cancer. The main objective of this study is to describe the natural history of DC through a cohort of patients diagnosed in childhood and followed up for a long period of time.Material and methodsMulticenter, retrospective, longitudinal study conducted in patients followed up to 24 years since being diagnosed in childhood (between 1998 and 2020).ResultsFourteen patients were diagnosed with DC between the ages of 3 and 17 years (median, 8.5 years). They all had hematologic manifestations at diagnosis, and nine developed mucocutaneous manifestations during the first decade of life. Seven presented severe DC variants. All developed non-hematologic manifestations during follow-up. Mutations were identified in 12 patients. Thirteen progressed to bone marrow failure at a median age of 8 years [range, 3–18 years], and eight received a hematopoietic stem cell transplant. Median follow-up time was 9 years [range, 2–24 years]. Six patients died, the median age was 13 years [range, 6–24 years]. As of November 2022, eight patients were still alive, with a median age of 18 years [range, 6–32 years]. None of them have developed myeloblastic syndrome or cancer.ConclusionsDC was associated with high morbidity and mortality in our series. Hematologic manifestations appeared early and consistently. Non-hematologic manifestations developed progressively. No patient developed cancer possibly due to their young age. Due to the complexity of the disease multidisciplinary follow-up and adequate transition to adult care are essential

Molecular Characterization of Haemaphysalis Species and a Molecular Genetic Key for the Identification of Haemaphysalis of North America

Haemaphysalis longicornis (Acari: Ixodidae), the Asian longhorned tick, is native to East Asia, but has become established in Australia and New Zealand, and more recently in the United States. In North America, there are other native Haemaphysalis species that share similar morphological characteristics and can be difficult to identify if the specimen is damaged. The goal of this study was to develop a cost-effective and rapid molecular diagnostic assay to differentiate between exotic and native Haemaphysalis species to aid in ongoing surveillance of H. longicornis within the United States and help prevent misidentification. We demonstrated that restriction fragment length polymorphisms (RFLPs) targeting the 16S ribosomal RNA and the cytochrome c oxidase subunit I (COI) can be used to differentiate H. longicornis from the other Haemaphysalis species found in North America. Furthermore, we show that this RFLP assay can be applied to Haemaphysalis species endemic to other regions of the world for the rapid identification of damaged specimens. The work presented in this study can serve as the foundation for region specific PCR-RFLP keys for Haemaphysalis and other tick species and can be further applied to other morphometrically challenging taxa

Iron-refractory iron deficiency anemia (Irida): a propósito de un caso

Poster [PC-130] Introducción: IRIDA es una entidad que cursa con anemia ferropénica, de herencia autosómica recesiva, aunque se han reportado algunos casos que son sólo heterocigotos (herencia autosómica dominante), debidos a mutaciones en el gen TMPRSS6 que codifica la proteína matriptasa-2. Se cree que la prevalencia de IRIDA es inferior a 1: 1.000.000, pero probablemente está infradiagnosticada. Caso clínico: Mujer de 17 años con antecedentes personales de retraso psicomotor y trastorno de espectro autista. Cariotipo 46 XX, descartándose síndrome X-frágil FRAXA, síndrome de Angelman y síndrome de Rett. Ha presentado varios episodios de trastornos de conducta con desorganización motora y dificultad de convivencia. Controlada en Hematología desde 2015 por anemia microcítica hipocrómica ferropénica sin respuesta al hierro oral y con respuesta parcial al hierro intravenoso. A lo largo del seguimiento en esta consulta se han descartado enfermedad celiaca (anticuerpos anti-gliadina (IgG e IgA), anti-transglutaminasa (IgA) negativos), helicobacter pylori (test del aliento negativo), pérdidas digestivas de hierro (sangre oculta en heces negativa), pérdidas urinarias y pulmonares. Ha presentado niveles bajos de hemoglobina (máximo 69 g/L) con microcitosis importante (máximo VCM 68, 50 fl) e índices de saturación de hasta 2, 5%. Desarrollo ponderoestatural y puberal normal. Tras recibir diferentes compuestos de hierro oral, sin respuesta a ninguno de ellos, se inicia tratamiento con hierro endovenoso, precisando medidas de contención para la administración del mismo, motivo por el que ha recibido tratamiento con hierro-carboximaltosa (Ferinject®) 500 mg, permitiendo administrar mayor cantidad de hierro en una sola dosis (Figura 1 y 2). Ante la sospecha de IRIDA se solicita un análisis de mutaciones puntuales en el gen TMPRSS6 que codifica la proteína matriptasa-2. La paciente no presenta mutaciones puntuales en las regiones analizadas, sin embargo, en el análisis de las secuencias se observan los siguientes polimorfismos (SNPs) en el gen TMPRSS6: p.Lys253Glu (exón 7), IVS7+23A>G (intrón 7), p.Val736Ala (exón17) interpretados como variantes benignas (no patogénicas). Conclusiones: Existen aproximadamente 69 defectos diferentes del gen TMPRSS6 en 65 familias diferentes. Sin embargo, están apareciendo nuevas mutaciones, no descritas por el momento y que podrían ser causa IRIDA, respaldando la hipótesis de que este síndrome clínico puede ser más común de lo que se pensaba anteriormente y su genética ser más heterogénea de lo que se describió inicialmente. Además se han descrito nuevos polimorfimos como p.Val736Ala que asocian mayor susceptibilidad al desarrollo de anemia ferropénica. Dado que su cuadro neurológico sigue sin diagnóstico preciso, ante la presencia concomitante de estos polimorfismos, se decide el estudio de secuenciación del exoma completo

Detrended Fluctuation Analysis in the prediction of type 2 diabetes mellitus in patients at risk: Model optimization and comparison with other metrics

[EN] Complexity analysis of glucose time series with Detrended Fluctuation Analysis (DFA) has been proved to be useful for the prediction of type 2 diabetes mellitus (T2DM) development. We propose a modified DFA algorithm, review some of its characteristics and compare it with other metrics derived from continuous glucose monitorization in this setting. Several issues of the DFA algorithm were evaluated: (1) Time windowing: the best predictive value was obtained including all time-windows from 15 minutes to 24 hours. (2) Influence of circadian rhythms: for 48-hour glucometries, DFA alpha scaling exponent was calculated on 24hour sliding segments (1-hour gap, 23-hour overlap), with a median coefficient of variation of 3.2%, which suggests that analysing time series of at least 24-hour length avoids the influence of circadian rhythms. (3) Influence of pretreatment of the time series through integration: DFA without integration was more sensitive to the introduction of white noise and it showed significant predictive power to forecast the development of T2DM, while the pretreated time series did not. (4) Robustness of an interpolation algorithm for missing values: The modified DFA algorithm evaluates the percentage of missing values in a time series. Establishing a 2% error threshold, we estimated the number and length of missing segments that could be admitted to consider a time series as suitable for DFA analysis. For comparison with other metrics, a Principal Component Analysis was performed and the results neatly tease out four different components. The first vector carries information concerned with variability, the second represents mainly DFA alpha exponent, while the third and fourth vectors carry essentially information related to the two "pre-diabetic behaviours" (impaired fasting glucose and impaired glucose tolerance). The scaling exponent obtained with the modified DFA algorithm proposed has significant predictive power for the development of T2DM in a high-risk population compared with other variability metrics or with the standard DFA algorithm.This study has been funded by Instituto de Salud Carlos III through the project PI17/00856 (Co-funded by the European Regional Development Fund, A way to make Europe). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Colás, A.; Vigil, L.; Vargas, B.; Cuesta Frau, D.; Varela, M. (2019). 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Altered Complexity and Correlation Properties of R-R Interval Dynamics Before the Spontaneous Onset of Paroxysmal Atrial Fibrillation. Circulation, 100(20), 2079-2084. doi:10.1161/01.cir.100.20.2079Wang, H., Naghavi, M., Allen, C., Barber, R. M., Bhutta, Z. A., Carter, A., … Coates, M. M. (2016). Global, regional, and national life expectancy, all-cause mortality, and cause-specific mortality for 249 causes of death, 1980–2015: a systematic analysis for the Global Burden of Disease Study 2015. The Lancet, 388(10053), 1459-1544. doi:10.1016/s0140-6736(16)31012-1Saudek, C. D., Derr, R. L., & Kalyani, R. R. (2006). Assessing Glycemia in Diabetes Using Self-monitoring Blood Glucose and Hemoglobin A1c. JAMA, 295(14), 1688. doi:10.1001/jama.295.14.1688Monnier, L., Colette, C., & Owens, D. R. (2008). Glycemic Variability: The Third Component of the Dysglycemia in Diabetes. Is it Important? How to Measure it? Journal of Diabetes Science and Technology, 2(6), 1094-1100. doi:10.1177/193229680800200618Abdul-Ghani, M. A., Tripathy, D., & DeFronzo, R. A. (2006). Contributions of  -Cell Dysfunction and Insulin Resistance to the Pathogenesis of Impaired Glucose Tolerance and Impaired Fasting Glucose. Diabetes Care, 29(5), 1130-1139. doi:10.2337/dc05-2179(2017). 2. Classification and Diagnosis of Diabetes:Standards of Medical Care in Diabetes—2018. Diabetes Care, 41(Supplement 1), S13-S27. doi:10.2337/dc18-s002Tabák, A. G., Herder, C., Rathmann, W., Brunner, E. J., & Kivimäki, M. (2012). Prediabetes: a high-risk state for diabetes development. The Lancet, 379(9833), 2279-2290. doi:10.1016/s0140-6736(12)60283-9DeFronzo, R. A., Banerji, M. A., Bray, G. A., Buchanan, T. A., Clement, S., … Tripathy, D. (2009). Determinants of glucose tolerance in impaired glucose tolerance at baseline in the Actos Now for Prevention of Diabetes (ACT NOW) study. 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Proceedings of the 3rd Biennial Conference of the Society for Implementation Research Collaboration (SIRC) 2015: advancing efficient methodologies through community partnerships and team science

It is well documented that the majority of adults, children and families in need of evidence-based behavioral health interventionsi do not receive them [1, 2] and that few robust empirically supported methods for implementing evidence-based practices (EBPs) exist. The Society for Implementation Research Collaboration (SIRC) represents a burgeoning effort to advance the innovation and rigor of implementation research and is uniquely focused on bringing together researchers and stakeholders committed to evaluating the implementation of complex evidence-based behavioral health interventions. Through its diverse activities and membership, SIRC aims to foster the promise of implementation research to better serve the behavioral health needs of the population by identifying rigorous, relevant, and efficient strategies that successfully transfer scientific evidence to clinical knowledge for use in real world settings [3]. SIRC began as a National Institute of Mental Health (NIMH)-funded conference series in 2010 (previously titled the “Seattle Implementation Research Conference”; $150,000 USD for 3 conferences in 2011, 2013, and 2015) with the recognition that there were multiple researchers and stakeholdersi working in parallel on innovative implementation science projects in behavioral health, but that formal channels for communicating and collaborating with one another were relatively unavailable. There was a significant need for a forum within which implementation researchers and stakeholders could learn from one another, refine approaches to science and practice, and develop an implementation research agenda using common measures, methods, and research principles to improve both the frequency and quality with which behavioral health treatment implementation is evaluated. SIRC’s membership growth is a testament to this identified need with more than 1000 members from 2011 to the present.ii SIRC’s primary objectives are to: (1) foster communication and collaboration across diverse groups, including implementation researchers, intermediariesi, as well as community stakeholders (SIRC uses the term “EBP champions” for these groups) – and to do so across multiple career levels (e.g., students, early career faculty, established investigators); and (2) enhance and disseminate rigorous measures and methodologies for implementing EBPs and evaluating EBP implementation efforts. These objectives are well aligned with Glasgow and colleagues’ [4] five core tenets deemed critical for advancing implementation science: collaboration, efficiency and speed, rigor and relevance, improved capacity, and cumulative knowledge. SIRC advances these objectives and tenets through in-person conferences, which bring together multidisciplinary implementation researchers and those implementing evidence-based behavioral health interventions in the community to share their work and create professional connections and collaborations

Genome biology of a novel lineage of planctomycetes widespread in anoxic aquatic environments.

Anaerobic strains affiliated with a novel order-level lineage of the Phycisphaerae class were retrieved from the suboxic zone of a hypersaline cyanobacterial mat and anoxic sediments of solar salterns. Genome sequences of five isolates were obtained and compared with metagenome-assembled genomes representing related uncultured bacteria from various anoxic aquatic environments. Gene content surveys suggest a strictly fermentative saccharolytic metabolism for members of this lineage, which could be confirmed by the phenotypic characterization of isolates. Genetic analyses indicate that the retrieved isolates do not have a canonical origin of DNA replication, but initiate chromosome replication at alternative sites possibly leading to an accelerated evolution. Further potential factors driving evolution and speciation within this clade include genome reduction by metabolic specialization and rearrangements of the genome by mobile genetic elements, which have a high prevalence in strains from hypersaline sediments and mats. Based on genetic and phenotypic data a distinct group of strictly anaerobic heterotrophic planctomycetes within the Phycisphaerae class could be assigned to a novel order that is represented by the proposed genus Sedimentisphaera gen. nov. comprising two novel species, S. salicampi gen. nov., sp. nov. and S. cyanobacteriorum gen. nov., sp. nov. This article is protected by copyright. All rights reserved