Heterozygous junctophilin-2 (JPH2) p.(Thr161Lys) is a monogenic cause for HCM with heart failure.

During the last two decades, mutations in sarcomere genes have found to comprise the most common cause for hypertrophic cardiomyopathy (HCM), but still significant number of patients with dominant HCM in the family are left without molecular genetic diagnosis. Next generation sequencing (NGS) does not only enable evaluation of established HCM genes but also candidate genes for cardiomyopathy are frequently tested which may lead to a situation where conclusive interpretation of the variant requires extensive family studies. We aimed to characterize the phenotype related to a variant in the junctophilin-2 (JPH2) gene, which is less known non-sarcomeric candidate gene. In addition, we did extensive review of the literature and databases about JPH2 variation in association with cardiac disease. We characterize nine Finnish index patients with HCM and heterozygous for JPH2 c.482C>A, p.(Thr161Lys) variant were included and segregation studies were performed. We identified 20 individuals affected with HCM with or without systolic heart failure and conduction abnormalities in the nine Finnish families with JPH2 p.(Thr161Lys) variant. We found 26 heterozygotes with the variant and penetrance was 71% by age 60 and 100% by age 80. Co-segregation of the variant with HCM phenotype was observed in six families. Main clinical features were left ventricular hypertrophy, arrhythmia vulnerability and conduction abnormalities including third degree AV-block. In some patients end-stage severe left ventricular heart failure with normal or mildly enlarged diastolic dimensions was detected. In conclusion, we propose that the heterozygous JPH2 p.(Thr161Lys) variant is a new Finnish mutation causing atypical HCM.

Velocity vector imaging shows normal cardiac systolic function in survivors of severe bronchopulmonary dysplasia at six to 16 years of age.

AIM: This study evaluated global myocardial function and associations between cardiac function and lung function in very low birth weight (VLBW) children, with and without severe radiographic bronchopulmonary dysplasia (BPD), at six to 14 years of age. METHODS: We studied 34 VLBW and 19 term-born controls, and the VLBW group was further divided into a BPD group with severe radiographic BPD and those without radiographic BPD in infancy. Detailed right and left ventricular myocardial functions were analysed by velocity vector imaging, and the left ventricular mass was calculated. The associations between cardiac function and lung function were assessed by impulse oscillometry. RESULTS: The right and left ventricular myocardial systolic functions and the left ventricular mass were similar in the three groups. Lung function was not associated with cardiac systolic function. Neonatal exposure to dexamethasone treatment was negatively associated with right ventricular function, as measured by the automated fractional area change, with an odds ratio of 7.9 and 95% confidence interval of 1.9-33.5 (p = 0.005). CONCLUSION: Lung function measurements were not associated with cardiac systolic function in preterm infants at six to 14 years of age. Neonatal exposure to dexamethasone, used for weaning from the ventilator, was negatively associated with right ventricular function.

Very low birthweight bronchopulmonary dysplasia survivors had similar cardiac outcomes to controls at six years to 14 years of age.

AIM: This study evaluated cardiac function and its associations with lung function and neonatal pulmonary morbidity in very low birthweight (VLBW) children, with and without severe radiographic bronchopulmonary dysplasia (radBPD), at school age. METHODS: We examined 18 VLBW children with radBPD, 17 VLBW children without radBPD and 18 healthy term-born children using conventional echocardiography, tissue Doppler imaging, speckle tracking echocardiography and real-time three-dimensional echocardiography at six years to 14 years of age. Lung function was studied by impulse oscillometry. Plasma N-terminal-proBNP concentrations were measured. RESULTS: Cardiac function and N-terminal-proBNP concentrations did not differ between the groups. No associations were found between cardiac function and neonatal dexamethasone, oxygen or ventilator therapies. In VLBW children, poorer reactance correlated with larger left ventricle (LV) end-systolic (Spearman's ρ = -0.45) and end-diastolic (ρ = -0.50) volumes and higher resistance correlated with higher LV dyssynchrony indexes, with ρ ranging from 0.37 to 0.48. Greater bronchodilation responses correlated with lower early diastolic myocardial relaxation velocities, with ρ ranging from 0.39 to 0.42. CONCLUSION: BPD survivors had normal cardiac function at the age of six years to 14 years. No associations were found between neonatal pulmonary morbidity and cardiac parameters. Poorer lung function correlated modestly with LV echocardiographic parameters in VLBW children.

Severe Bronchopulmonary Dysplasia, Growth, Nutrition, and Adipokines at School Age.

This study evaluated nutrition and growth in relation to plasma adipokine levels in 21 very-low-birth-weight (VLBW) children with radiographic bronchopulmonary dysplasia (BPD), 19 VLBW controls, and 19 term controls with a median age of 11.3 years. We took anthropometric measurements; assessed plasma levels of adipsin, resistin, adiponectin, and leptin; and analyzed the children's 3-day food records. Children with BPD had a smaller age-adjusted head circumference and more microcephaly but no other significant growth differences. Daily recommended nutritional intake levels were poorly met but did not differ between the groups. Leptin levels correlated positively with the body mass index standard deviation score in VLBW children. No other associations between adipokine concentrations and growth were found. There were negative correlations between leptin concentrations and fat intake, resistin levels and carbohydrate intake, and adiponectin, adipsin, and leptin levels and energy intake.

Very low birthweight bronchopulmonary dysplasia survivors show no substantial association between lung function and current inflammatory markers.

AIM: The role of inflammation in the bronchopulmonary dysplasia (BPD) survivors is indistinct. We evaluated lung function in relation to inflammatory markers in plasma, exhaled breath condensate and exhaled air in school-aged very low birthweight (VLBW) survivors with and without radiographic BPD. METHODS: Pre- and postbronchodilator impulse oscillometry were performed by 21 six to 14-year-old VLBW children with radiographic BPD, 19 VLBW children without radiographic BPD and 19 age-matched nonasthmatic term controls. Eosinophilic cationic protein, interleukins 6 and 8, adiponectin, adipsin, leptin and resistin in plasma, leukotriene B4 and 8-isoprostane in exhaled breath condensate, and bronchial and alveolar nitric oxide output were measured. RESULTS: Abnormal lung function was found in 12.5% of the former VLBW children. Airway resistance at 5 Hz was highest in the radiographic BPD, but bronchodilator responses were most prominent in the non-BPD group. Plasma adiponectin had a modest positive correlation with obstruction and with bronchodilator responses, and alveolar nitric oxide and plasma interleukin 6 with bronchodilator responses. CONCLUSION: Very low birthweight children with radiographic BPD had poorest lung function. The most pronounced bronchodilator responses were found in VLBW children without radiographic BPD. Current detected inflammatory markers had only a minor association with lung function in school-aged BPD survivors.

Inflammatory activity at school age in very low birth weight bronchopulmonary dysplasia survivors.

OBJECTIVE: Airway inflammation is involved in the pathogenesis of bronchopulmonary dysplasia (BPD). The aim of the study was to evaluate the inflammatory activity in plasma and exhaled air in very low birth weight (VLBW) BPD survivors at school age. METHODS: Twenty-one 6-14-year-old former VLBW (birth weight ≤1,500 g) children with severe radiographic BPD (radBPD), 19 without radBPD (nonBPD group) and 19 non-asthmatic term controls underwent measurement of eosinophil cationic protein, IL-6, IL-8, adiponectin, adipsin, leptin, and resistin in plasma, leukotriene B4 and 8-isoprostane in exhaled breath condensate, and NO in exhaled breath. Background data were obtained from patient records, clinical examination and parental questionnaire. Both univariate and multivariate models were applied in the statistical analysis. RESULTS: There were no significant differences between the groups in any of the inflammatory markers measured. Five (25%) radBPD and 2 (11%) nonBPD children reported asthma (P = 0.058). In logistic regression analysis, exposure to chorioamnionitis was associated with low IL-8 (OR 29.0, 95% CI 3.27-258) and postnatal corticosteroid therapy with high adiponectin (OR 32.0, 95% CI 1.29-793). High body mass index standard deviation score (BMI-SDS) was associated with high plasma adipsin (OR 2.47, 95% CI 1.07-5.75) and leptin (OR 5.76, 95%CI 1.83-18.2) levels. CONCLUSIONS: The inflammatory activity seems to decrease by school age in VLBW BPD survivors. Chorioamnionitis and postnatal corticosteroid treatment may modulate the inflammatory responsiveness in VLBW subjects even up to school age. The respiratory outcome in VLBW infants might be improved by preventing excessive weight gain.

[Evidence-based methods of medicine in specialization training: a neonatologic problem as an example]. / Näyttöön perustuvan lääketieteen menetelmät erikoistumiskoulutuksessa: esimerkkinä neonatologinen ongelma.

One of the objectives of the qualification of medical specialists is familiarization to the scientific literature of the future special field. We describe a training project, in which doctors specializing in pediatrics collected and evaluated the current scientific data on the closure of the arterial duct in premature infants. Main emphasis in the article is put on the setting of the questions to be elucidated, acquisition of the required information, evaluation of the degree of evidence, and how reliably these questions can be answered on the basis of the current information. We recommend arranging evidence-based medical training for specializing doctors.