Indicadores de salud perinatal. Diferencias de la información registrada por el INE y la de los hospitales que atienden los nacimientos

La búsqueda de medidas objetivas del estado de salud de la población es una tradición en salud pública que se realiza desde hace dos siglos. Inicialmente, la descripción y análisis del estado de salud se basaba en medidas de mortalidad y supervivencia. Con el paso del tiempo se reconoció la necesidad de considerar también otras dimensiones del estado de salud, en parte para el control de enfermedades y en parte por tener una visión más amplia del concepto de salud y de sus determinantes poblacionales..

Early assessment of cardiomyopathy in Duchenne patients by means of longitudinal strain echocardiography

Introduction: The diagnosis of Duchenne-linked cardiomyopathy may be challenging. Conventional echocardiographic measurements typically show deterioration beyond the second decade. Global longitudinal strain has been proposed as an earlier marker than left ventricular ejection fraction. Material and methods: A prospective, observational, cross-sectional, case-control study was carried out. Both Duchenne patients and control subjects underwent transthoracic echocardiogram in order to assess left ventricle function. Bayesian linear regression was the main tool for inference. Age effects were parameterised by means of a spline function because of its simplicity to characterise continuous variables and smooth contributions. The posterior distribution of the marginal age effects was used to assess the earliest age of deterioration of each marker. Results: Sixteen Duchenne patients and twenty-two healthy male subjects were enrolled. On overage, cardiac function measures were found for ejection fraction and longitudinal strain among different groups. Age effects on global longitudinal strain are more reliably found at ages of 6 and above, while ejection fraction starts to deteriorate at an older age. Progressive left ventricular dysfunction in Duchenne patients is one of the key issues and starts at an early age with subtle symptoms. Conclusion: This cross-sectional study provides supporting evidence that global longitudinal strain is an earlier marker of disease progression than ejection fraction in Duchenne patients

Three-Dimensional Printing and Navigation in Bone Tumor Resection

One of the most promising advances raised by the current computer age is performing research “in silico,” which means computer-assisted. The objective of this chapter is firstly to evaluate if a 3D in-silico model of an oncological patient could be used to make a 3D-printed prototype in real scale, discriminating precisely healthy tissues, tumoral tissues and oncological margins. Secondly, the objective is to evaluate if this prototype could be representative enough to allow testing osteotomies under navigated guidance based on images. A tumor resection for a patient with diagnosed metaphyseal osteosarcoma of the proximal tibia was transferred into a rapid prototyping model, fabricated using 3D printing and representing different structures in different colors. The planned osteotomy was executed using Stryker Navigator to guide the cutting saw and the prototype was opened to verify the precision of the performed osteotomy. Both osteotomy planes showed successful correspondence with the safe margin, with a maximum error of 1 mm. The application of these techniques in general orthopedics would help to reduce the incidence of unforeseen intraoperative failures, contributing to obtain predictable surgical procedures. This would implement a new way of performing development, research and training in orthopedics and traumatology by in-silico technology

Targeted gene sequencing, bone health, and body composition in Cornelia de Lange Syndrome

The aim of this study was to evaluate bone health and body composition by dual-energy X-ray absorptiometry (DXA) in individuals with Cornelia de Lange Syndrome (CdLS). Overall, nine individuals with CdLS (five females, all Caucasian, aged 5-38 years) were assessed. Total body less head (TBLH) and lumbar spine (LS) scans were performed, and bone serum biomarkers were determined. Molecular analyses were carried out and clinical scores and skeletal features were assessed. Based on deep sequencing of a custom target gene panel, it was discovered that eight of the nine CdLS patients had potentially causative genetic variants in NIPBL. Fat and lean mass indices (FMI and LMI) were 3.4-11.1 and 8.4-17.0 kgm2, respectively. For TBLH areal bone mineral density (aBMD), after adjusting for height for age Z-score of children and adolescents, two individuals (an adolescent and an adult) had low BMD (aBMD Z-scores less than -2.0 SD). Calcium, phosphorus, 25-OH-vitamin D, parathyroid hormone, and alkaline phosphatase levels were 2.08-2.49 nmolL, 2.10-3.75 nmolL, 39.94-78.37 nmolL, 23.4-80.3 pgmL, and 43-203 IUL, respectively. Individuals with CdLS might have normal adiposity and low levels of lean mass measured with DXA. Bone health in this population seems to be less of a concern during childhood and adolescence. However, they might be at risk for impaired bone health due to low aBMD in adulthood

Identification and Functional Characterization of Two Intronic NIPBL Mutations in Two Patients with Cornelia de Lange Syndrome

Cornelia de Lange syndrome (CdLS) is a rare genetically heterogeneous disorder with a high phenotypic variability including mental retardation, developmental delay, and limb malformations. The genetic causes in about 30% of patients with CdLS are still unknown. We report on the functional characterization of two intronic NIPBL mutations in two patients with CdLS that do not affect a conserved splice-donor or acceptor site. Interestingly, mRNA analyses showed aberrantly spliced transcripts missing exon 28 or 37, suggesting the loss of the branch site by the c.5329-15A>G transition and a disruption of the polypyrimidine by the c.6344del(-13)-(-8) deletion. While the loss of exon 28 retains the reading frame of the NIBPL transcript resulting in a shortened protein, the loss of exon 37 shifts the reading frame with the consequence of a premature stop of translation. Subsequent quantitative PCR analysis demonstrated a 30% decrease of the total NIPBL mRNA levels associated with the frameshift transcript. Consistent with our results, this patient shows a more severe phenotype compared to the patient with the aberrant transcript that retains its reading frame. Thus, intronic variants identified by sequencing analysis in CdLS diagnostics should carefully be examined before excluding them as nonrelevant to disease

Clinical relevance of postzygotic mosaicism in Cornelia de Lange syndrome and purifying selection of NIPBL variants in blood

Postzygotic mosaicism (PZM) in NIPBL is a strong source of causality for Cornelia de Lange syndrome (CdLS) that can have major clinical implications. Here, we further delineate the role of somatic mosaicism in CdLS by describing a series of 11 unreported patients with mosaic disease-causing variants in NIPBL and performing a retrospective cohort study from a Spanish CdLS diagnostic center. By reviewing the literature and combining our findings with previously published data, we demonstrate a negative selection against somatic deleterious NIPBL variants in blood. Furthermore, the analysis of all reported cases indicates an unusual high prevalence of mosaicism in CdLS, occurring in 13.1% of patients with a positive molecular diagnosis. It is worth noting that most of the affected individuals with mosaicism have a clinical phenotype at least as severe as those with constitutive pathogenic variants. However, the type of genetic change does not vary between germline and somatic events and, even in the presence of mosaicism, missense substitutions are located preferentially within the HEAT repeat domain of NIPBL. In conclusion, the high prevalence of mosaicism in CdLS as well as the disparity in tissue distribution provide a novel orientation for the clinical management and genetic counselling of families

Modificaciones en variables antropométricas, analíticas de riesgo metabólico y composición corporal en pequeños para la edad gestacional en tratamiento con hormona de crecimiento

Introducción Los niños pequeños para la edad gestacional (PEG) sin crecimiento recuperador pueden beneficiarse del tratamiento con hormona de crecimiento (rhGH). Sin embargo, deben ser monitorizados de forma muy estrecha ya que son población de riesgo metabólico. Material y métodos Se han incluido 28 niños PEG, con una media de edad de 8, 79 años, sin crecimiento recuperador, tratados con rhGH. Hemos evaluado las modificaciones producidas en la antropometría, variables de riesgo metabólico y composición corporal durante 4 años de tratamiento. Resultados El tratamiento con rhGH se acompañó de un aumento de talla (–2, 76 ± 0, 11 DE hasta –1, 53 ± 0, 17 DE; p = 0, 000), peso (–1, 50 ± 0, 09 DE hasta –1, 21 ± 0, 13 DE; p = 0, 016) y velocidad de crecimiento (–1, 43 ± 0, 35 DE hasta 0, 41 ± 0, 41 DE; p = 0, 009), sin producir modificaciones en el índice de masa corporal (IMC). Se han visto aumentos significativos de la insulinemia (9, 33 ± 1, 93 mU/ml hasta 16, 55 ± 1, 72 mU/ml; p = 0, 044) y del índice HOMA (3, 63 ± 0, 76 hasta 6, 43 ± 0, 67; p = 0, 042), sin producirse modificaciones en el perfil lipídico. En el estudio de composición corporal se ha comprobado un aumento significativo de la masa magra (73, 19 ± 1, 26 hasta 78, 74 ± 1, 31; p = 0, 037) con una disminución de la masa grasa (26, 81 ± 1, 26 hasta 21, 26 ± 1, 31; p = 0, 021). Conclusión El tratamiento con rhGH se ha acompañado de una ganancia en la talla sin producir alteraciones en el IMC. Asimismo, se han observado cambios en la composición corporal, con un aumento de la proporción de masa magra a expensas de una disminución de la de masa grasa, que podrían conducir a un descenso del riesgo metabólico de estos pacientes. Sin embargo, se ha detectado cierta resistencia insulínica. Es importante continuar el seguimiento de estos niños para determinar las posibles repercusiones en la edad adulta. Introduction and objectives Small for gestational age (SGA) children without catch-up growth can benefit from treatment with growth hormone (rhGH). However, they should be monitored very closely because they are at increased risk of metabolic syndrome. Material and method A group of 28 SGA children with a mean age of 8.79 years and undergoing treatment with rhGH were selected for evaluation. Over the course of 4 years, an annual evaluation was performed on the anthropometric variables (weight, height, body mass index [BMI], growth rate, blood pressure and waist perimeter), metabolic risk variables (glycaemia, glycosylated haemoglobin, cholesterol ratio, insulinaemia, insulin-like growth factor 1[IGF1], IGF binding protein-3 [IGFBP-3], IGF1/IGFBP3 ratio, and HOMA index), and body composition variables. Results Treatment with rhGH was associated with a significant increase in height (–2.76 ± .11 SD to –1.53 ± .17 SD, P = .000), weight (–1.50 ± .09 SD to –1.21 ± .13 SD; P = .016), and growth rate (–1.43 ± .35 SD to .41 ± .41 SD; P = .009), without a corresponding change in the BMI. Insulinaemia (9.33 ± 1.93 mU/ml to 16.55 ± 1.72 mU/ml; P = .044) and the HOMA index (3.63 ± .76 to 6.43 ± .67; P = .042) increased, approaching insulin resistance levels. No changes were observed in the lipid profile. Body composition changes were observed, with a significant increase in lean mass (73.19 ± 1.26 to 78.74 ± 1.31; P = .037), and a reduction of fat mass (26.81 ± 1.26 to 21.26 ± 1.31; P = .021). Conclusion Treatment with rhGH is effective for improving anthropometric variables in SGA patients who have not experienced a catch-up growth. It also produces changes in body composition, which may lead to a reduction in risk of metabolic syndrome. However, some insulin resistance was observed. It is important to follow up this patient group in order to find out whether these changes persist into adulthood

Ewing sarcoma of the bone. Multidisciplinary approach and oncological results in 88 patients

El sarcoma de Ewing óseo es un tumor poco frecuente, agresivo, que afecta principalmente a niñosy adultos jóvenes. Existe ausencia de registros en nuestro país respecto de la prevalencia de estaenfermedad, los esquemas de tratamiento utilizados y sus resultados. El objetivo fue analizar, en un grupode pacientes con sarcoma de Ewing óseo tratados con quimioterapia y cirugía de conservación de miembro,las tasas de supervivencia global, de recurrencia local y los factores de riesgo oncológicos. Se incluyó a 88pacientes. La edad media de la serie fue de 14.5 años y el seguimiento promedio de 8.8 años. La tasa de supervivencia global fue de 79.5% a los 2 años, de 69% a 5 años y de 64% a 10 años. Los factores pronósticosnegativos asociados a menor supervivencia fueron: mala respuesta a la quimioterapia, edad ≥ de 16 años,localización central, y recurrencia local. En el análisis multivariable únicamente la respuesta a la quimioterapiatuvo significancia estadística. La tasa libre de recurrencia local a 2 y 5 años fue del 87%. La mala respuesta ala quimioterapia fue el único factor significativo para la recurrencia local. Consideramos que la cirugía de conservación de miembro asociada a quimioterapia pre y postoperatoria debe ser el tratamiento para el sarcomade Ewing óseo, alcanzando de esta manera una supervivencia global a 5 años del 69%. En nuestra serie, larespuesta a la quimioterapia ha sido el factor pronóstico más relevante para supervivencia y recurrencia local.Ewing sarcoma of the bone is a rare, highly aggressive tumor that typically affects children and young adults. In Argentina, the lack of Ewing’s sarcoma registries reflects in the absence of information regarding prevalence, treatment protocols and patient´s outcome. The purpose of this study was to analyze, in a group of patients diagnosed with Ewing sarcoma of the bone, treated with chemotherapy and limb-conserving surgery, their overall survival rate, local recurrence rate, and oncological risk factors. A retrospective research was conducted between 1990 and 2017. Eighty-eight patients with Ewing sarcoma of the bone matched the inclusion criteria. Median age was 14.5 years and median follow-up was 8.8 years. Overall survival rate was 79.5%, 69% and 64% at 2, 5 and 10 years respectively. Negative prognostic factors, associated with less survival rate after univariate analysis, were: bad response to chemotherapy (tumoral necrosis 0-89%), age > 16 years-old, central tumor localization and local recurrence. Gender and tumor size were not significant prognostic factors. After multivariate analysis, response to chemotherapy remained statistical significant. Local recurrence-free survival rate at 2 and 5 years was 87%. Tumor response to chemotherapy (0-89%) was the only significant factor for local recurrence. We consider that limb-salvage surgery, with neoadjuvant and adjuvant chemotherapy, are the mainstays of treatment for Ewing’s sarcoma, with an overall survival rate, at 5 years, of 69%. In this population, response to chemotherapy is the most relevant prognostic factor, being associated with both local recurrence and overall survival.Fil: Sanchez Saba, Javier E.. Instituto Universidad Escuela de Medicina del Hospital Italiano; ArgentinaFil: Abrego, Mariano O.. Instituto Universidad Escuela de Medicina del Hospital Italiano; ArgentinaFil: Albergo, José I.. Instituto Universidad Escuela de Medicina del Hospital Italiano; ArgentinaFil: Farfalli, Germán Luis. Instituto Universidad Escuela de Medicina del Hospital Italiano; ArgentinaFil: Aponte Tinao, Luis A.. Instituto Universidad Escuela de Medicina del Hospital Italiano; ArgentinaFil: Ayerza, Miguel A.. Instituto Universidad Escuela de Medicina del Hospital Italiano; ArgentinaFil: Cayol, Federico. Instituto Universidad Escuela de Medicina del Hospital Italiano; ArgentinaFil: Streitenberger, Patricia. Instituto Universidad Escuela de Medicina del Hospital Italiano; ArgentinaFil: Risk, Marcelo. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Instituto de Medicina Traslacional E Ingenieria Biomedica. - Hospital Italiano. Instituto de Medicina Traslacional E Ingenieria Biomedica. - Instituto Universitario Hospital Italiano de Buenos Aires. Instituto de Medicina Traslacional E Ingenieria Biomedica.; ArgentinaFil: Roitman, Pablo Daniel. Instituto Universidad Escuela de Medicina del Hospital Italiano; Argentin

The relationship of myocardial contraction and electrical excitation—the correlation between scintigraphic phase image analysis and electrophysiologic mapping

Phase imaging derived from equilibrium radionuclide angiography presents the ventricular contraction sequence. It has been widely but only indirectly correlated with the sequence of electrical myocardial activation. We sought to determine the specific relationship between the sequence of phase progression and the sequence of myocardial activation, contraction and conduction, in order to document a noninvasive method that could monitor both. In 7 normal and 9 infarcted dogs, the sequence of phase angle was correlated with the epicardial activation map in 126 episodes of sinus rhythm and pacing from three ventricular sites. In each episode, the site of earliest phase angle was identical to the focus of initial epicardial activation. Similarly, the serial contraction pattern by phase image analysis matched the electrical epicardial activation sequence completely or demonstrated good agreement in approximately 85% of pacing episodes, without differences between normal or infarct groups. A noninvasive method to accurately determine the sequence of contraction may serve as a surrogate for the associated electrical activation sequence or be applied to identify their differences