Surgical treatment for congenital heart defects in down syndrome patients

Abstract Objective: To analyze data related to surgical treatment in patients with congenital heart defects (CHD) and Down syndrome (DS) based on information from International Quality Improvement Collaborative Database for Congenital Heart Disease (IQIC). Methods: Between July 1, 2010 and December 31, 2017, 139 patients with CHD and DS underwent surgery at Hospital de Base and Hospital da Criança e Maternidade de São José do Rio Preto (FUNFARME)/Faculdade de Medicina de São José do Rio Preto - SP (FAMERP). A quantitative, observational and cross-sectional study was performed in which the pre, intra and postoperative data were analyzed in an IQIC database. The data included gender, age, prematurity, weight, preoperative procedures, diagnosis, associated cardiac and non-cardiac anomalies, Risk Adjustment for Congenital Heart Surgery (RACHS-1), type of surgery, cardiopulmonary bypass (CPB), perfusion time, aortic clamping time and CPB temperature, bacterial sepsis, surgical site infection and other infections, length of stay in intensive care unit (ICU), length of hospital stay and in-hospital mortality. Results: The most prevalent procedures were complete atrioventricular septal defect repair (58 - 39.45%), followed by closure of ventricular septal defect (36 - 24.49%). The RACHS-1 categories 1, 2, 3 and 4 were distributed as 22 (15%); 49 (33.3%); 72 (49%) and 4 (2.7%), respectively. There were no procedures classified as categories 5 or 6. Bacterial sepsis occurred in 10.2% of cases, surgical site infection in 6.1%, other infections in 14.3%. The median length of ICU stay was 5 days and the median length of hospital stay was 11 days. In-hospital mortality was 6.8%. Conclusion: Surgical treatment in patients with CHD and DS usually does not require highly complex surgical procedures, but are affected by infectious complications, resulting in a longer ICU and hospital length of stay with considerable mortality.

Aumento de la mortalidad infantil en niños con síndrome de Down: Chile 1997-2013 / Rising infant mortality in down syndrome in Chile from 1997 to 2013

Background: Down syndrome (DS) is associated with higher child mortality especially due to cardiac malformations. Aim: To describe the trend in Chilean infant mortality in DS in the period 1997-2013 as compared to the general population without DS. Material and Methods: Raw data on infant deaths were extracted from the yearbooks of vital statistics of the National Institute of Statistics. The mortality risk associated to DS, relative to population without DS was estimated. Results: There were 456 deaths in infants with DS during the study period (59 early neonatal deaths, 70 late neonatal deaths and 327 post-neonatal deaths). The trend in infant mortality rate in DS was ascending (r: 0.53, p = 0.03), with an average annual percentage change of 4.6% (95% confidence interval (CI) 0.4-9.0%; p < 0.01). Compared to the population without DS, the risk of early neonatal death was lower in DS (Odds ratio (OR) 0.14, 95% CI 0.11-0.19; p < 0.01) whereas the risk of post-neonatal death was higher (OR 4.74, 95% CI 3.85-5.85; p < 0.01). Conclusions: Infant mortality in Down syndrome has an increasing trend. We postulate that these children are not accessing timely cardiac surgery, the main therapeutic tool to reduce the death risk in the first year of life.

Intrauterine death in singleton pregnancies with trisomy 21, 18, 13 and monosomy X / Óbito fetal em gestações únicas com diagnóstico de trissomias dos cromossomos 21, 18, 13 e monossomia do X

Summary A retrospective study from November 2004 to May 2012, conducted at the Obstetric Clinic of Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo (HC-FMUSP), which included 92 singleton pregnancies with prenatal diagnosis of trisomy of chromosome 21 (T21), 18, 13 (T13/18) and monosomy X (45X), with diagnosis performed until the 26th week of pregnancy. The aim of the study was to describe the frequency and to investigate predictors of spontaneous fetal death (FD). Diagnosis (T21, n=36; T13/18, n=25; 45X, n=31) was made at a mean gestational age of 18.3±3.7 weeks, through chorionic villus biopsy (n=22,24%), amniocentesis (n=66, 72%) and cordocentesis (n=4, 4%). Major malformations were present in 45 (49%); with hydrops in 32 (35%) fetuses, more frequently in 45X [n=24/31, 77% vs. T21 (n=6/36, 17%) and T13/18 (n=2/25, 8%), p<0.001]. Specialized fetal echocardiography was performed in 60% (55/92). Of these, 60% (33/55) showed changes in heart morphology and/or function. Fetuses with T13/18 had a higher incidence of cardiac anomalies [60 vs. 25% (T21) and 29% (45X), p= 0.01]. FD occurred in 55 (60%) gestations, being more frequent in 45X [n=26/31, 84% vs. T21 (n=13/36, 36%) and T13/18 (n=16/25, 64%), p<0.01]. Stepwise analysis showed a correlation between hydrops and death in fetuses with T21 (LR= 4.29; 95CI=1.9-8.0, p<0.0001). In fetuses with 45X, the presence of echocardiographic abnormalities was associated with lower risk of FD (LR= 0.56; 95CI=0.27- 0.85, p=0.005). No predictive factors were identified in the T13/18 group. Intra- uterine lethality of aneuploid fetuses is high. Occurrence of hydrops increases risk of FD in pregnancies with T21. In pregnancies with 45X, the occurrence of echocardiographic changes reduces this risk.

Resumo Estudo retrospectivo, de novembro de 2004 a maio de 2012, na Clínica Obstétrica do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, incluindo 92 gestações únicas com diagnóstico pré-natal de trissomia dos cromossomos 21 (T21), 18, 13 (T13/18) e monossomia do X (45X), realizado até a 26a semana, com o objetivo de descrever a frequência e investigar preditores do óbito fetal espontâneo (OF). O diagnóstico (T21: n=36; T13/T18: n=25; 45X: n=31) foi realizado em idade gestacional média de 18,3±3,7 semanas, por biópsia de vilo corial (n=22; 24%), amniocentese (n=66; 72%) e cordocentese (n=4; 4%). Malformação major presente em 45 (49%) fetos e hidropisia em 32 (35%), mais frequente no grupo 45X [n=24/31, 77% vs. T21 (n=6/36, 17%) e T13/18 (n=2/25, 8%); p<0,001]. Ecocardiografia fetal especializada foi realizada em 60% (55/92). Destes, 60% (33/55) tinham alterações na morfologia e/ou na função cardíaca. Fetos com T13/18 apresentaram incidência maior de anomalias cardíacas [60 vs. 25% (T21) e 29% (45X); p=0,01]. Ocorrência de OF em 55 (60%) gestações e mais frequente no grupo 45X [n=26/31, 84% vs. T21 (n=13/36, 36%) e T13/18 (n=16/25, 64%); p<0,01]. Análise stepwise demonstrou associação entre hidropisia e óbito em fetos com T21 (LR=4,29; IC95%=1,9-8,0; p<0,0001). Em fetos com 45X, a presença de alterações ecocardiográficas esteve associada com menor risco de OF (LR=0,56; IC95%=0,27-0,85; p=0,005). Não foram identificados fatores preditores no grupo T13/18. A letalidade intrauterina de fetos aneuploides é elevada. A presença de hidropisia aumenta o risco de OF em gestações com T21. Em gestações com 45X, a ocorrência de alterações ecocardiográficas reduz esse risco.

The effects of 6-gingerol on proliferation, differentiation, and maturation of osteoblast-like MG-63 cells

We investigated whether 6-gingerol affects the maturation and proliferation of osteoblast-like MG63 cells in vitro. Osteoblast-like MG63 cells were treated with 6-gingerol under control conditions, and experimental inflammation was induced by tumor necrosis factor-α (TNF-α). Expression of different osteogenic markers and cytokines was analyzed by real-time PCR, Western blotting, and enzyme-linked immunosorbent assay. In addition, alkaline phosphatase (ALP) enzyme activity and biomineralization as markers for differentiation were measured. Treatment with 6-gingerol resulted in insignificant effects on the proliferation rate. 6-Gingerol induced the differentiation of osteoblast-like cells with increased transcription levels of osteogenic markers, upregulated ALP enzyme activity, and enhanced mineralized nodule formation. Stimulation with TNF-α led to enhanced interleukin-6 and nuclear factor-κB expression and downregulated markers of osteoblastic differentiation. 6-Gingerol reduced the degree of inflammation in TNF-α-treated MG-63 cells. In conclusion, 6-gingerol stimulated osteoblast differentiation in normal physiological and inflammatory settings, and therefore, 6-gingerol represents a promising agent for treating osteoporosis or bone inflammation.

Morbilidad y mortalidad durante el primer año de vida en pacientes con síndrome de Down / Down' syndrome patient morbidity and mortality during the first year of life

Objective: Down' Syndrome (DS) is the most common chromosomal abnormality. It carries an increased risk of concurrent congenital malformations as well as increased risk of mortality when compared to the general population. Objective: To determine the characteristics of morbidity and mortality in patients with DS during the first year of life. Patients and Methods: A prospective study of a cohort of children born with DS was performed. All children born in 2006 in two Chilean hospitals who were given a clinical diagnosis of DS were included. Infant mortality, morbidity and nutritional diagnosis were determined and recorded every two months. Results: 33 patients were included, 78.8 percent were full term newborns. Average age of the mother at childbirth was 33.2 +/- 7.8 years. Among the 33 patients, 64.5 percent had congenital heart disease, the most common cause being atrio-ventricular defects (25 percent), 35 percent of the patients with CHD required cardiac surgery. Gastrointestinal disorders were diagnosed among 35 percent of these children, atresia or intestinal stenosis being the most frequent diagnosis. 25.8 percent of the population suffered from hypothyroidism. Follow-up showed that after two months, 54.8 percent of these children were malnourished, however at one year old, 22.5 percent were overweight. By the first year, children had shown 5.38 +/- 1.83 episodes of Acute Respiratory Tract Infections per patient per year, and 1.22 +/- 1.14 non neonatal hospitalizations per child/year. Half of these hospitalizations were due to lower respiratory tract infection. Two patients died during the study due to infectious disorders, resulting on a survival rate of 93.6 percent at 12 months. Conclusions: This information should assist physicians in improving patient follow-up. The study should also make evident the need to create national standards to supervise the care of patients with DS.

Objetivos: El Síndrome de Down (SD) corresponde a la anomalía cromosómica más frecuente, con mayor riesgo de malformaciones asociadas y mortalidad que la población general. Nuestro objetivo fue caracterizar la morbimortalidad durante el primer año de vida en pacientes con SD. Material y Método: Estudio de cohorte prospectivo en niños con SD. Se incluyeron todos los niños nacidos durante el año 2006 con diagnóstico clínico de SD en dos hospitales chilenos. Se realizó registro de morbimortalidad, hospitalizaciones y diagnóstico nutricional cada 2 meses hasta los 12 meses de vida. Resultados: Se incluyeron 33 pacientes. El 78,8 por ciento fueron recién nacidos de término. La edad materna promedio fue de 33,2 +/- 7,8 años. El 64,5 por ciento presentó cardiopatía congénita, siendo más frecuentes los defectos aurículo-ventriculares (25 por ciento). El 35 por ciento requirió cardiocirugía. Las patologías digestivas asociadas se presentaron en el 35 por ciento. El 25,8 por ciento presentó hipotiroidismo. A los 2 meses el 54,8 por ciento tenía desnutrición. El 22,5 por ciento tenía obesidad/sobrepeso a los 12 meses. Hubo un promedio de 5,38 +/- 1,83 infecciones respiratorias agudas (IRA) por paciente/año y 1,22 +/- 1,14 hospitalizaciones no neonatales por niño/año. El 50 por ciento de las hospitalizaciones fueron por IRA baja. Dos pacientes fallecieron, ambos por causa infecciosa, con una sobrevida de 93,6 por ciento a 12 meses. Conclusiones: El conocimiento de esta información nos permitirá mejorar el seguimiento actual de este grupo de niños, además de hacer evidente la necesidad de crear un programa nacional de evaluación y supervisión estandarizado de salud para niños con SD.

Morbimortalidade em indivíduos portadores da síndrome de Down / Morbidity and mortality in patients with Down sindrome

Trabalho de revisäo, no qual säo relatados os principais achados clínico nos acometidos pela síndrome de Down, com destaque maior para as alteraçöes do sistema imunitário, doenças caradiovasculares e leucemia, que säo as principais causadoras da morbidade e mortalidade nestes indivíduos. As curvas de mortalidade e sobrevida, ao mesmo tempo que mostram uma menor expectativa de vida em relaçäo a outros deficientes mentais e à populaçäo geral, ressaltam o aumento da longevidade, fato importante para a melhor compreensäo desta síndrome também em pacientes mais velhos.