Background
Atrioventricular valve regurgitation (AVVR) is a devastating complication in children and young adults with congenital heart disease (CHD), particularly in patients with single ventricle ...physiology. Transcatheter edge‐to‐edge repair (TEER) is a rapidly expanding, minimally invasive option for the treatment of AVVR in adults that avoids the morbidity and mortality associated with open heart surgery. However, application of TEER in in CHD and in children is quite novel. We describe the development of a peri‐procedural protocol including image‐derived pre‐intervention simulation, with successful application to four patients.
Aims
To describe the initial experience using the MitraClip system for TEER of dysfunctional systemic atrioventricular valves in patients with congential heart disease within a pediatric hospital.
Methods
A standardized screening and planning process was developed using cardiac magnetic resonance imaging, three dimensional echocardiography and both virtual and physical simulation. Procedures were performed using the MitraClip G4 system and patients were clinically followed post‐intervention.
Results
A series of four CHD patients with at least severe AVVR were screened for suitability for TEER with the MitraClip system: three patients had single ventricle physiology and Fontan palliation, and one had repair of a common atrioventricular canal defect. Each patient had at least severe systemic AVVR and was considered at prohibitively high risk for surgical repair. Each patient underwent a standardized preprocedural screening protocol and image‐derived modeling followed by the TEER procedure with successful clip placement at the intended location in all cases.
Conclusions
The early results of our protocolized efforts to introduce TEER repair of severe AV valve regurgitation with MitraClip into the CHD population within our institution are encouraging. Further investigations of the use of TEER in this challenging population are warranted.
Clinical Perspective
What is Known: Atrioventricular valve regurgitation (AVVR) is a devastating complication in children and young adults with congenital heart disease (CHD), particularly in patients with single ventricle physiology. Transcatheter edge‐to‐edge repair (TEER) is a rapidly expanding, minimally invasive option for the treatment of AVVR that avoids the morbidity and mortality associated with open heart surgery. AVVR in CHD patients is a complex problem. An organized approach is required if the potential of TEER therapy is ever to be realized in this heterogenous population. What is New: We demonstrate an image‐derived modeling protocol and clinically successful application of TEER in four patients with CHD including three patients with palliated single ventricle physiology and a Fontan circulation. What is Next: The protocolized approach to TEER in CHD described in this report may serve as a foundation for the safe initiation of TEER therapy at other free‐standing pediatric hospitals. Further collaborative investigations of the use of TEER in this challenging population are warranted. Ideally, a multicenter study will ensue.
Our objective was to assess cardiovascular risk and metabolic complications in adulthood in subjects with or without overweight and metabolic disturbances (i.e., elevated blood pressure, glucose, ...triglycerides, low HDL cholesterol, and high LDL cholesterol) and their combinations as youth.
Using data from the population-based Cardiovascular Risk in Young Finns study, we examined the utility of four age- and sex-specific youth phenotypes (group I: normal weight, no metabolic disturbances; group II: normal weight, one or more metabolic disturbances; group III: overweight/obese, no metabolic disturbances; group IV: overweight/obese, one or more metabolic disturbances) in predicting adult high carotid intima-media thickness (IMT), type 2 diabetes mellitus (T2DM), and metabolic syndrome (MetS). The study included 1,617 participants 9-24 years of age at baseline who were followed up 21-25 years later.
IMT (mean ± SEM) was higher among participants in groups II (0.627 ± 0.005 mm, P = 0.05), III (0.647 ± 0.010 mm, P = 0.005), and IV (0.670 ± 0.010 mm, P < 0.0001) compared with group I (0.616 ± 0.003 mm). In addition, subjects in group IV had significantly higher IMT compared with those in group II (P = 0.002). Participants in groups II, III, and IV were at increased risk of the development of MetS in adulthood compared with those in the control group. For group II participants, the difference was attenuated after risk factor adjustments. Additionally, participants in group III and IV were at increased risk of the development of T2DM compared with those in groups I and II.
While metabolic risk factors associated with overweight increase future risk for MetS, T2DM, and increased IMT, overweight in isolation is also a risk factor. Therefore, overweight should be prevented and treated wherever possible.
Purpose
Poor quality of life has been shown to occur in youth with obesity. This study aimed to assess associations between health-related quality of life, general mental health and general ...psychological distress measures, collectively termed psychosocial health questionnaires (PSH), with weight outcomes in a busy paediatric weight management service.
Methods
A cross-sectional longitudinal clinical cohort, ‘Childhood Overweight BioRepository of Australia (COBRA)’, was used (
n
= 250, median age 11, range 2–18 year, mean BMI
z
-score 2.5 ± 0.2). Clinical data were collected and HRQOL questionnaires; Pediatric Quality of Life 4.0 (PedsQL), ‘Sizing Me/Them Up’ (SMU/STU), and psychological well-being questionnaires; strengths and difficulties questionnaire (SDQ) and Kessler 10 (K10) were completed by the child and primary caregiver. PSH results were compared to age- and sex-adjusted BMI
z
-score at baseline and follow-up. Direct logistic regression modelling was performed to assess the impact of PSH factors on the likelihood of successful weight reduction over a period of ≥ 12 months.
Results
Mean self-report PSH scores were: 68.0 ± 15.28 (PedsQL, range 0-100), 64.8 ± 15.8, (SMU, range 0-100), 17.3 ± 4.4 (SDQ, range 0–40) and 20.0 ± 7.7 (K10, range 0–50). A significant negative correlation was observed between PSH scores and childhood obesity (baseline BMI
z
-scores (
p
< 0.01)). No correlations were observed between psychological well-being measures and BMI
z
-scores. Higher subscale scores of the PedsQL and SDQ, which measure impaired psychosocial health and more difficulties with hyperactivity and inattention, significantly predict weight loss in children with obesity after 12 months.
Conclusion
PSH questionnaires may be useful in identifying individuals who require additional support to achieve weight loss goals in a tertiary weight management service.
Abstract
Context
Passive smoke exposure has been linked to the risk of osteoporosis in adults.
Objective
We examined the independent effects of childhood passive smoke exposure on adult bone health.
...Design/Setting
Longitudinal, the Cardiovascular Risk in Young Finns Study.
Participants
The study cohort included 1422 individuals followed for 28 years since baseline in 1980 (age 3 to 18 years). Exposure to passive smoking was determined in childhood. In adulthood, peripheral bone traits were assessed with peripheral quantitative CT (pQCT) at the tibia and radius, and calcaneal mineral density was estimated with quantitative ultrasound. Fracture data were gathered by questionnaires.
Results
Parental smoking in childhood was associated with lower pQCT-derived bone sum index in adulthood (β± SE, −0.064 ± 0.023 per smoking parent; P = 0.004) in multivariate models adjusted for age, sex, active smoking, body mass index, serum 25-OH vitamin D concentration, physical activity, and parental socioeconomic position. Similarly, parental smoking was associated with lower heel ultrasound estimated bone mineral density in adulthood (β± SE, −0.097 ± 0.041 per smoking parent; P = 0.02). Parental smoking was also associated with the incidence of low-energy fractures (OR, 1.28; 95% CI, 1.01 to 1.62). Individuals with elevated cotinine levels (3 to 20 ng/mL) in childhood had lower bone sum index with pQCT (β± SE, −0.206 ± 0.057; P = 0.0003). Children whose parents smoked and had high cotinine levels (3 to 20 ng/mL) had significantly lower pQCT-derived bone sum index compared with those with smoking parents but had low cotinine levels (<3 ng/mL) (β± SE, −0.192 ± 0.072; P = 0.008).
Conclusions and Relevance
Children of parents who smoke have evidence of impaired bone health in adulthood.
In this longitudinal 28-year follow-up study including 1422 individuals, parental smoking and elevated cotinine levels in childhood were associated with lower bone mineral density in adulthood.
Aim
To determine the interplay between sleep and sedentary behaviours on body mass index (BMI) in children with obesity.
Methods
Cross‐sectional study of 343 children with obesity aged 4–17 years, ...from a tertiary care weight management clinic in Melbourne, Victoria, Australia. Multifaceted data relating to activity and sleep from child and parent questionnaires analysed with anthropometric data collected during routine clinical care. Associations between sleep duration and activity measures were examined via regression models with adjustment for potential confounders.
Results
Higher BMI was associated with more hours spent watching television (P = 0.04), as well as less reported enjoyment of physical activity (P = 0.005) and less time spent in organised sport activity (P = 0.005). Higher BMI was also associated with higher levels of obstructive sleep apnoea (P = 0.002). Less time in bed was associated with higher levels of BMI (P = 0.03) but analysis by sex revealed this association to only hold for males. In the whole group, a significant television and sleep interaction was seen, such that increasing television watching was associated with higher BMI, but only in those with shortest sleep duration.
Conclusions
Both poor sleep and increasing screen time (including television viewing, smart‐phone use, internet use or video‐gaming) appear to impact BMI in children with obesity, with a particular detrimental effect of television viewing in those who sleep less. Efforts to improve sleep time and quality in children may minimise negative effects of screen time on increasing BMI and should be included in public health strategies to combat obesity in childhood.
To estimate and compare tri-ponderal mass index (TMI) and body mass index (BMI) at each age from childhood to young adulthood in the prediction of adulthood obesity-related outcomes.
Participants of ...this observational study (n = 432) were from a 20-year infancy-onset randomized atherosclerosis prevention trial. BMI and TMI were calculated using weight and height measured annually from participants between ages 2 and 20 years. Outcomes were aortic intima-media thickness (at the age of 15, 17, or 19 years), impaired fasting glucose and elevated insulin levels, homeostasis model assessment of insulin resistance index, serum lipids, and hypertension at the age of 20 years. Poisson regressions, Pearson correlation, logistic regression, and area under the curve (AUC) were used to estimate and/or compare associations and predictive utilities between BMI and TMI with all outcomes.
The associations and predictive utilities of BMI and TMI with all outcomes were stronger at older ages. BMI had significantly stronger correlations than TMI with insulin (at age 16 years), systolic blood pressure (age 5-20 years), and triglycerides (age 18 years). BMI had significantly greater predictive utilities than TMI for insulin resistance (at age 14-16 years; difference in AUC = 0.018-0.024), elevated insulin levels (age 14-16 years; difference in AUC = 0.018 and 0.025), and hypertension (age 16 to 20 years; difference in AUC = 0.017-0.022) but they were similar for other outcomes.
TMI is not superior to BMI at any ages from childhood to young adulthood in the prediction of obesity-related outcomes in young adulthood.
Context:
Low vitamin D levels in adulthood have been associated with cardiovascular disease.
Objective:
To investigate if low vitamin D levels in childhood are related with increased carotid artery ...intima-media thickness (IMT) in adulthood.
Design, Setting, and Participants:
The analyses included 2148 subjects from the Cardiovascular Risk in Young Finns Study, aged 3–18 years at baseline (in 1980). Subjects were re-examined at age 30–45 years (in 2007). Childhood levels of 25-hydroxy-vitamin D were measured from stored serum in 2010.
Main Outcome Measure:
The carotid artery IMT from 2007 was used.
Results:
When adjusted for age, sex, and childhood risk factors, continuous data of childhood 25-OH vitamin was inversely associated with adulthood carotid IMT levels among females (β ± SE −0.006 ± 0.003, P = 0.03), but not among males (0.001 ± 0.004, P = 0.88). Children with 25-OH vitamin D levels in the lowest quartile (<40 nmol/L) had significantly increased odds of having high-risk IMT (highest decile of common carotid or carotid bulb IMT or carotid plaque) as adults, in analyses adjusted for age, sex and either childhood risk factors (odds ratio 1.70 95 % CI 1.15–2.31, P = 0.0007) or adult risk factors, including adult vitamin D levels (odds ratio 1.80 1.30–2.48, P = 0.0004). In sex-specific analyses, these associations were significant both in females and males (P always <0.05). In sensitivity analyses, those with childhood vitamin D levels in the lowest quintile (<37 nmol/L), gave similar results to those using a quartile cut-point.
Conclusions:
Low 25-OH vitamin D levels in childhood were associated with increased carotid IMT in adulthood.
Abstract
Context
The influence of dietary pattern trajectories from youth to adulthood on adult glucose metabolism is unknown.
Objective
To identify dietary pattern trajectories from youth to ...adulthood and examine their associations with adult impaired fasting glucose (IFG).
Methods
Thirty-one-year population-based cohort study among 1007 youths aged 3-18 years at baseline in Finland. Diet intake was assessed in 1980, 1986, 2001, 2007, and 2011. Group-based trajectory modelling was used to identify dietary pattern (identified by factor analysis) trajectories. Adult IFG was measured by the latest available data from 2001, 2007, and 2011.
Results
Among 1007 participants, 202 (20.1%) developed IFG and 27 (2.7%) developed type 2 diabetes in adulthood (mean follow-up of 30.7 years; mean SD age 40.5 5.0 years). Three dietary patterns were identified at baseline and were retained in 1986 and 2001: “Traditional Finnish,” “High carbohydrate,” and “Vegetables and dairy products.” Three different patterns were identified in 2007, which remained similar in 2011: “Traditional Finnish and high carbohydrate,” “Red meat,” and “Healthy.” Trajectories of increased or stably medium “red meat” pattern scores from youth to adulthood were detrimentally associated with IFG (relative risk 1.46, 95% CI 1.12-1.90 for Medium (M)-stable/M-large increase vs low-stable trajectory) after adjusting for confounders. This association was slightly reduced after further adjusting for long-term dietary fiber intake.
Conclusion
Trajectories of an increased or stably moderate adherence to a “red meat” dietary pattern from youth to adulthood are associated with higher risk of adult IFG. This association is partly explained by low dietary fiber intake.
Background. Cellular insulin resistance is the hallmark of type 2 diabetes and predominantly affects adipose and muscle cells. The saturated free fatty acid palmitate is elevated in insulin-resistant ...states and may directly contribute to cellular insulin resistance. A spectrum of renal disease is associated with increased markers of insulin resistance, although direct causal mechanisms are not known. In the kidney, glomerular podocytes are novel insulin-sensitive cells that have the ability to rapidly transport glucose. In this study, we tested the hypothesis that palmitate would induce insulin resistance in podocytes. Methods. Conditionally immortalized human podocytes were cultured for up to 24 h with 375–750 μM palmitate. Functional effects on glucose uptake and ceramide production were measured. Gene expression was investigated using a focused gene array, and protein signalling and trafficking were studied with Western blotting and immunofluorescence. Results. We found that palmitate blocked insulin-stimulated glucose uptake in human podocytes. This was associated with increased ceramide production, and use of the ceramide inhibitors myriocin and fumonisin B1 partially recovered the insulin sensitivity. At the level of transcription, palmitate downregulated genes associated with several pathways involved in insulin signalling. At the protein level, phosphorylation of the insulin receptor, IRS1 and PKB was reduced and there was impaired translocation of GLUT4 to the cell surface. Conclusion. This is the first study to demonstrate a direct effect of saturated fatty acids on podocyte function. These findings may represent a novel link between systemic insulin resistance and the development of nephropathy.
Abstract
Purpose
To investigate whether exposure to systemic antibiotics influences the risk of developing type 2 diabetes and overweight/obesity.
Methods
The study sample comprised 2209 (110 with ...incident diabetes) participants from the population-based Cardiovascular Risk in Young Finns Study (YFS) aged 24–39 years in 2001. The exposure was national linked register data on purchased antibiotic courses between 1993 and 2001. Clinical examinations including BMI were conducted in 2001, 2007 and 2011. Participants with prevalent diabetes in 2001 were excluded. Data on type 2 diabetes was also obtained from two national registers until 2017. Data from four population-based National FINRISK studies were used for replication (
N
= 24,674, 1866 with incident diabetes).
Results
Prior antibiotic exposure (> 5 versus 0–1 antibiotic courses) was associated with subsequent type 2 diabetes in both YFS (OR 2.29; 95%CI 1.33–3.96) and FINRISK (HR 1.73; 95%CI 1.51–1.99). An increased risk for type 2 diabetes was observed in YFS (OR 1.043; 95%CI 1.013–1.074) and FINRISK (HR 1.022; 95%CI 1.016–1.029) per course. Exposure to antibiotics increased the risk of overweight/obesity (BMI > 25 kg/m
2
) after a 10-year follow-up in YFS (OR 1.043; 95%CI 1.019–1.068) and in FINRISK (OR 1.023; 95%CI 1.018–1.029) at baseline per antibiotic course. Adjustments for confounders from early life in YFS and at baseline in FINRISK, including BMI, socioeconomic status, smoking, insulin, blood pressure, and physical activity, did not appreciably alter the findings.
Conclusion
Our results show that exposure to antibiotics was associated with increased risk for future type 2 diabetes and overweight/obesity and support judicious antibiotic prescribing.
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