RESUMO
Perinatal asphyxia triggers an acute inflammatory response in the injured brain. Complement activation and neuroinflammation worsen brain damage after a systemic ischemia/reperfusion insult. The increase of mannose binding lectin (MBL) during asphyxia may contribute to the brain damage, via activation of the complement lectin pathway. The possible role of MBL2 gene variants in influencing the severity of post-asphyxia brain injuries is still unexplored. This retrospective study included 53 asphyxiated neonates: 42 underwent therapeutic hypothermia (TH) and 11 did not because they were admitted to the NICU later than 6 h after the hypoxic insult. Blood samples from TH-treated and untreated patients were genotyped for MBL2 gene variants, and biomarker plasma levels (MBL and S100 B protein) were measured at different time points: during hypothermia, during rewarming, and at 7-10 days of life. The timing of blood sampling, except for the T1 sample, was the same in untreated infants. Highest (peak) levels of MBL and MBL2 genotypes were correlated to neuroimaging brain damage or death and long-term neurodevelopmental delay. MBL2 wild-type genotype was associated with the highest MBL levels and worst brain damage on MRI (p = 0.046) at 7-10 days after hypoxia. MBL increased in both groups and S100B decreased, slightly more in treated than in untreated neonates. The progressive increase of MBL (p = 0.08) and to be untreated with TH (p = 0.08) increased the risk of brain damage or death at 7-10 days of life, without affecting neurodevelopmental outcomes at 1 year. The effect of TH on MBL plasma profiles is uncertain.
RESUMO
BACKGROUND: The post-surgical history of repaired congenital heart disease (rCHD), in particular tetralogy of Fallot (TOF), is often complicated by sudden death. Electrical myocardial abnormalities could be a substrate for malignant ventricular arrhythmias. METHODS AND RESULTS: 146 patients with TOF or other rCHD involving a subpulmonary right ventricle, considered to be at high arrhythmic risk, underwent right ventricular (RV) electroanatomic voltage mapping (EVM). Maps showed endocardial scars (<0.5mV) in all cases, mainly involving the RV outflow tract (n=141, 96.6%). In 28 cases (19.2%), other areas were involved. Total scar extension, expressed as % of total endocardial area, was significantly higher in patients with QRS ≥180ms [4.5% (±2.5) vs 2.8% (±2.4), p=0.014], left and right ventricular systolic dysfunction [4.5% (±3.2) vs 2.8% (±2.3), p=0.016 and 3.5% (±3.0) vs 2.6% (±1.9), p=0.03, respectively], premature ventricular contractions (PVCs) [3.2% (±2.6) vs 2.2% (±1.8), p<0.05], exercise-induced PVCs [3.8% (±2.4) vs 2.6% (±2.2), p=0.01], previous shunt [4.0% (±2.7) vs 2.6% (±2.2), p=0.01] and reintervention [4.2% (±3.2) vs 2.6% (±2.0), p=0.008]. Scar size also showed a positive correlation with duration of post-surgical follow-up (ρ=0.01), age at correction (ρ=0.01) and absolute QRS duration (ρ=0.05). CONCLUSIONS: Patients with rCHD involving the right ventricle show electrical scars with variable distribution, not necessarily matching with sites of surgical lesions. Scar extension correlates with some of the risk factors for life-threatening arrhythmias in CHD, such as prolonged QRS. Thus EVM could be considered an additional tool in the assessment of risk stratification in this particular population.
Assuntos
Mapeamento Potencial de Superfície Corporal/métodos , Sistema de Condução Cardíaco/fisiopatologia , Imageamento Tridimensional/métodos , Tetralogia de Fallot/fisiopatologia , Disfunção Ventricular Direita/fisiopatologia , Adolescente , Adulto , Criança , Feminino , Sistema de Condução Cardíaco/diagnóstico por imagem , Cardiopatias Congênitas/diagnóstico , Cardiopatias Congênitas/fisiopatologia , Humanos , Masculino , Medição de Risco , Tetralogia de Fallot/diagnóstico , Disfunção Ventricular Direita/diagnóstico , Obstrução do Fluxo Ventricular Externo/diagnóstico , Obstrução do Fluxo Ventricular Externo/fisiopatologia , Adulto JovemRESUMO
CONTEXT: In our Allergy Unit, we incidentally observed that a low Nickel diet, prescribed for delayed allergy to Nickel sulfate, reduced body mass index (BMI) and waist circumference in overweight patients. OBJECTIVES: This pilot cross-sectional analysis was undertaken to compare the prevalence of Nickel allergy of overweight individuals versus the general population. We also had the chance to report the efficacy of a low Nickel diet on BMI and waist circumference in Nickel-sensitive overweight subjects. METHODS: Eighty-seven overweight subjects, with a BMI > 26 Kg/m2, were consecutively enrolled in a health prevention program, and screened for the presence of Nickel allergy. The enrolled population was mostly females (72/87) (82.8%). Forty-three overweight women and two men showed a Nickel allergy and started a low Nickel diet. After 6-months of dieting, 24 overweight allergic women could be traced and changes in BMI and waist circumference were calculated. MAIN OUTCOME MEASUREMENTS: Prevalence of Nickel allergy in overweight. RESULTS: Prevalence of Nickel allergy in overweight female was 59.7%, compared with a prevalence rate of 12.5% in the general population. A significant reduction in BMI was observed in 24 out of 43 overweight females with Nickel allergy after 24 weeks of a low Nickel diet. Relative to baseline, mean BMI decrease was 4.2 ± 0.5 (P < 0.001) and the mean decline in waist circumference was 11.7 ± 0.6 cm (P < 0.001). CONCLUSIONS: This pilot observational analysis showed a substantially higher prevalence of Nickel allergy among overweight females, especially those with metabolic syndrome and fatty liver disease. A normocaloric low Nickel diet was effective in reducing BMI in this population. Further research is strongly needed to confirm these preliminary findings.
Assuntos
Hipersensibilidade/epidemiologia , Níquel/efeitos adversos , Sobrepeso/fisiopatologia , Índice de Massa Corporal , Estudos Transversais , Feminino , Humanos , Síndrome Metabólica/fisiopatologia , Pessoa de Meia-Idade , Projetos Piloto , Prevalência , Fatores de Risco , Circunferência da Cintura/fisiologiaRESUMO
Studies on HRQOL on kidney-transplanted young adults who had a diagnosis of chronic renal failure (CRF) in the pediatric age are uncommon. We studied HRQOL and its predictors in a sample of young adults with CRF in childhood who underwent a renal transplant. We recruited patients ≥18 yr old with renal transplant. We measured HRQOL by a standardized questionnaire on lifestyle, Short Form-36 (SF-36; including a PCS and a MCS; scale: 0-100), the GHQ (for short-term changes in mental health; scale: 0-36), and the MSPSS (with scales for family, friends, and significant others; scale: 0-100). We assessed the association of potential predictors of HRQOL through multiple linear regression models. We studied 66 patients aged 18-34 yr. The average PCS score was 76.4, and the average MCS score was 73.9. The mean GHQ total score was 14.8, and the total scale MSPSS mean score was 70. Severe comorbidities significantly affected the PCS score. Individuals with severe comorbidities had lower PCS scores.
Assuntos
Falência Renal Crônica/psicologia , Falência Renal Crônica/terapia , Transplante de Rim/métodos , Qualidade de Vida , Adolescente , Adulto , Criança , Estudos de Coortes , Estudos Transversais , Feminino , Humanos , Masculino , Escalas de Graduação Psiquiátrica , Análise de Regressão , Diálise Renal , Adulto JovemRESUMO
BACKGROUND: Guanidinoacetate (GAA) and creatine are reliable biochemical markers for primary and secondary creatine defects. We describe a method by liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) for simultaneous determination of plasma GAA and creatine. We analyzed 283 healthy subjects from 0 to 63 years old to obtain age-related control values. METHODS: Plasma samples were extracted with acetonitrile containing 13C2-GAA and d3-creatine. Samples were analyzed by LC-MS/MS in positive ionisation mode, after derivatization to butyl-esters. Optimal chromatographic separation was achieved using a column Supelcosil™ LC-4.6mm with isocratic elution in 5min. RESULTS: Run time was 5min. Standard curves were linear from 0.05 to 200µmol/L for creatine and from 0.02 to 40µmol/L for GAA. Limit of detection (LOD) and limit of quantitation (LOQ) were respectively 0.005 and 0.05µmol/L for creatine; LOD and LOQ were 0.002 and 0.02µmol/L respectively for GAA. Intra and inter-assay CVs for creatine and GAA were <8%. Recovery experiments adding 50 and 100µmol/L creatine and 10 and 20µmol/L GAA were 102.1% and 101.2%, for creatine; 102.95% and 96.45% for GAA. The method was applied to 283 plasma controls from healthy subjects to obtain control values in three specific age ranges: 0-12, 13-20, >20 years old. CONCLUSION: A rapid and high sensitive LC-MS/MS method was developed and validated for determination of creatine and GAA in plasma and it could also be applied to other biological materials, such as CFS and urines. This method is useful for diagnoses of primary and also for secondary creatine defects that may occur in inherited metabolic diseases in which precursors of creatine biosynthesis are involved.
Assuntos
Creatina/sangue , Glicina/análogos & derivados , Espectrometria de Massas em Tandem/métodos , Adolescente , Adulto , Criança , Pré-Escolar , Cromatografia Líquida/métodos , Glicina/sangue , Guanidinoacetato N-Metiltransferase/deficiência , Humanos , Lactente , Recém-Nascido , Pessoa de Meia-Idade , Padrões de Referência , Adulto JovemRESUMO
Despite advances in intensive care, congenital diaphragmatic hernia (CDH) maintains a risk of death >35%. Mortality predictors have been claimed, using logistic regression. When the outcome of interest is rare (i.e. <20%), the odds ratio, measured by logistic regression, is approximately equal to the relative risk, calculated by log-binomial model. However, for common events, the odds ratio misleads the exposition risk. The aims are to identify independent predictors of mortality in high-risk CDH, using the log-binomial model and disclose if the exposition risks could differ applying in comparison the logistic regression. Details of 113 consecutive high-risk CDH neonates, baseline demographics and disease features were collected retrospectively. Log-binomial model and logistic regression were applied and compared. Overall mortality rate was 41.6% (47/113). The log-binomial model identified preoperative pneumothorax (pnx), birth weight < or = 2,500 g and liver herniation as independent mortality predictors; female gender, an advanced gestational age and a PaO(2) > or = 90 mmHg as protective factors. Using logistic regression, liver herniation and birth weight did not maintain the significance. The exposition risks for pnx, female gender and gestational age were overestimated. The odds ratio measured by logistic regression overestimated the exposition risks. Since the mortality rate is confirmed to be >20% and the exposition risks, measured by logistic regression, are misleading, the log-binomial model should be consider in CDH binary outcome studies. According to the mortality predictors identified, making every effort to plan delivery at term and lowering the risk of pnx could improve the outcome.