Arterial Structure and Function Following Viral Myocarditis.

Acute viral myocarditis is an uncommon inflammatory disease of the myocardium. Little is known about the long-term cardiovascular risk for individuals who have recovered from the acute illness. We compared intermediate vascular phenotypes relating to arterial structure (aortic and carotid intima-media thickness) and function (pulse wave velocity, carotid arterial distensibility and compliance) in 15 participants, a median of 9.1 years after an episode of acute viral myocarditis, and 45 control participants. Following adjustment for age, sex and triglycerides, there were no differences in mean and maximum carotid and aortic intima-media thickness, pulse wave velocity, carotid artery distensibility and compliance between viral myocarditis participants and controls. In conclusion, we found no evidence of changes in intermediate vascular phenotypes indicative of increased cardiovascular risk in individuals who had fully recovered from viral myocarditis.

High-Sensitivity C-Reactive Protein and Leptin Levels Related to Body Mass Index Changes Throughout Childhood.

OBJECTIVES: To analyze the association between high-sensitivity C-reactive protein (hs-CRP) levels and cardiovascular risk factors in healthy school children, and to evaluate whether changes in body mass index (BMI) category throughout childhood affect hs-CRP levels. STUDY DESIGN: We measured serum hs-CRP levels, lipid profile, insulin levels, and leptin levels in 683 prepubertal children and 748 adolescents. A total of 272 children participated in the study in both cohorts, prepubertal (baseline; age 6-8 years) and adolescents (follow-up; age 12-16 years). RESULTS: Compared with their normal weight (NW) counterparts, hs-CRP levels were significantly higher in obese and overweight (OW) adolescents and obese prepubertal children. The highest hs-CRP levels were seen in children who were OW at baseline and at follow-up, and the lowest levels in those who transitioned from OW at baseline to NW at follow-up. High-density lipoprotein cholesterol and apolipoprotein A-I levels decreased across the hs-CRP tertile in both prepubertal children and adolescents, with significant differences (P < .001) in concentrations between the highest and lowest tertiles in 6- to 8-year-old boys and girls and in 12- to 16-year-old boys. The hs-CRP levels were also significantly associated with leptin levels in both prepubertal children and adolescents, with a significant increase across hs-CRP tertiles (P < .001). CONCLUSIONS: The shift from OW to NW throughout childhood is associated with a decrease in hs-CRP level to below that observed in children who maintain NW throughout childhood. Leptin levels were strongly associated with hs-CRP levels in our population independent of BMI. Our findings suggest that an obesity-related chronic inflammatory state may be reversible by improving weight status.

Inflammatory Bowel Disease in Children.

Inflammatory bowel disease is an important cause of chronic diarrhea in children, with a rising incidence, globally. The two main subtypes include Crohn's disease and ulcerative colitis. The clinical features are variable, and diagnosis requires initial first-line investigations followed by the involvement of specialist input for targeted imaging and endoscopy with biopsy, to confirm the diagnosis. Despite detailed investigation, inflammatory bowel disease may be clinically indistinguishable from chronic infections such as intestinal tuberculosis, and anti-tuberculosis treatment may be considered prior to further management considerations. The medical management of inflammatory bowel disease depends on subtype classification and severity, and may involve a step-wise approach to immunosuppressive therapies. In children, the consequences of poorly controlled disease are wide ranging, from psychosocial impacts and school non-attendance, to growth impairment and pubertal delay with subsequent impacts on bone health. In addition, an increased need for hospitalization and surgical intervention, and ultimately risk of cancer long-term. A multi-disciplinary team with expertise in inflammatory bowel disease is recommended to mitigate these risks and help to achieve the goal of sustained remission with endoscopic healing. This review focuses on updates on best clinical practice on the diagnosis and management of inflammatory bowel disease in children.

Arterial structure and function in children with inflammatory bowel disease.

Background and Aim: People with inflammatory bowel disease (IBD) have an increased risk of cardiovascular disease, including in younger adulthood. This may arise in part from chronic, systemic low-grade inflammation. The process of atherosclerosis may begin in childhood. We sought to determine whether pediatric IBD is associated with adverse changes in arterial structure and function as a marker of early increased cardiovascular risk. Methods: We performed a case-control study comparing children with IBD for a median disease duration of 2.49 (interquartile range 1.23, 4.38) years with healthy children. In a single visit, we collected baseline clinical and anthropometric data, and measured blood pressure, pulse wave velocity, carotid artery distensibility, and aortic and carotid intima-media thickness. High-sensitivity C-reactive protein and fasting lipids were measured. Results: We enrolled 81 children with IBD (40 with Crohn's disease, 40 with ulcerative colitis, and 1 with unspecified IBD) and 82 control participants. After adjusting for age, sex, body mass index z-score, blood pressure, and low-density lipoprotein cholesterol, there was no difference in measures of arterial structure and function in children with IBD compared with controls, nor between those with Crohn's disease or ulcerative colitis. Conclusion: We did not show any differences in arterial structure and function in children with a history of IBD for less than 5 years compared with healthy controls. IBD diagnosed in childhood may provide a window of opportunity to actively reduce standard cardiovascular risk factors and improve future cardiovascular outcomes.

Use of Dual-Energy X-ray Absorptiometry in Children with Inflammatory Bowel Disease: A Large Single Centre Study.

Purpose: Low bone mineral density (BMD) is a complication in children with inflammatory bowel disease (IBD). There are limited data evaluating dual-energy x-ray absorptiometry (DXA) as a screening tool for low BMD in children with IBD. We performed a single site retrospective analysis of DXA use. Methods: Children aged 5-18 years with IBD diagnosed between 2013 to 2017 at the Royal Children's Hospital, Australia, were included. Patient demographics, measures of disease activity, DXA scores, and factors related to BMD were collected. Results: Over a median follow up of 5.1 (4-6.4) years, 72/239 (30.1%) children underwent DXA, and 28/239 (11.7%) children had a second DXA. Our DXA practice differed to consensus guidelines regarding initial screening based on height and/or body mass index (BMI) z-score (8/17 [47.1%]), and repeat surveillance (13/42 [31.0%]). Children had a median lumbar spine (LS) z-score -0.80 (-1.65-0.075). Children with LS z-score≤-2.0 (n=14) had lower weight (6.57 [1.78-23.7] vs. 51.1 [26.5-68.7], p=0.0002) and height centiles (3.62 [1.17-17.1] vs. 42 [16.9-67.1], p=0.0001), and higher faecal calprotectin (FCP) (3041 [1182-4192] vs. 585 [139-2419], p=0.009) compared to children with LS z-score>-2.0. No fractures were reported. Of 28 children who underwent a second DXA 1.6 (1.1-2.2) years following initial DXA, no significant change in z-scores occurred. Conclusion: Children with IBD had low BMD. In addition to height centile and weight centile, FCP was associated with lower BMD, and should be considered in DXA screening guidelines. Greater clinician awareness of DXA consensus guidelines is required. Future prospective studies are required.

Therapeutic Drug Monitoring of Subcutaneous Infliximab in Inflammatory Bowel Disease-Understanding Pharmacokinetics and Exposure Response Relationships in a New Era of Subcutaneous Biologics.

CT-P13 is the first subcutaneous infliximab molecule approved for the management of inflammatory bowel disease (IBD). Compared to intravenous therapy, SC infliximab offers a range of practical, micro- and macroeconomic advantages. Data from the rheumatological literature suggest that subcutaneous CT-P13 may lead to superior disease outcomes in comparison to intravenous infliximab. Existing studies in IBD have focussed on pharmacokinetic comparisons and are inadequately powered to evaluate efficacy and safety differences between the two modes of administration. However, emerging clinical trial and real-world data support comparable clinical, biochemical, endoscopic and safety outcomes between subcutaneous and intravenous infliximab in both luminal Crohn's disease and ulcerative colitis. Across the available data, subcutaneous CT-P13 provides relative pharmacokinetic stability and higher trough drug levels when compared to intravenous administration. The clinical impact of this observation on immunogenicity and treatment persistence is yet to be determined. Trough levels between the two methods of administration should not be compared in isolation as any subcutaneous advantage must be considered in the context of comparable total drug exposure and the theoretical disadvantage of lower peak concentrations compared to intravenous therapy. Furthermore, target drug levels for subcutaneous CT-P13 associated with remission are not known. In this review, we present the available literature surrounding the pharmacokinetics of subcutaneous CT-P13 in the context of therapeutic drug monitoring and highlight the potential significance of these observations on the clinical management of patients with IBD.

Opposite Association of Adropin Concentrations with Obesity in Prepubertal Children Compared with Adolescents.

OBJECTIVE: The aim of this study was to evaluate the association between obesity and plasma adropin levels in two cohorts of children at two different ages. METHODS: Adropin concentrations were measured in 71 prepubertal and 41 pubertal children with obesity and their age- and sex-matched normal weight counterparts (69 prepubertal and 42 pubertal children). Information was available in these children on insulin levels, lipid profile, and leptin levels. Adropin levels were measured by using a commercial enzyme-linked immunosorbent assay kit. RESULTS: Plasma adropin levels were significantly higher (P < 0.001) in prepubertal than pubertal children. Adropin concentrations were significantly higher (P < 0.001) in prepubertal girls than in prepubertal boys but significantly lower (P < 0.001) in pubertal girls than in pubertal boys. Prepubertal boys and girls with obesity had significantly higher adropin levels (P < 0.001) than their normal weight counterparts. In contrast, no differences in adropin levels were observed in pubertal children when comparing children with obesity and normal weight boys and girls. CONCLUSIONS: An important decrease in adropin levels in pubertal children compared with prepubertal children was shown as well as a differing association of adropin with obesity depending on age. These findings suggest a possible relationship between adropin levels and centrally regulated sex hormones involved in pubertal development.

Vegetable and Fruit Intakes Are Associated with hs-CRP Levels in Pre-Pubertal Girls.

The influence of diet on inflammation in children remains unclear. We aimed to analyze the influence of diet on high-sensitivity C-reactive protein (hs-CRP) levels in a pre-pubertal population free of other influences that may affect hs-CRP levels. We determined hs-CRP levels in 571 six- to eight-year-old children using an hs-CRP ELISA kit. Information on food and nutrient intake was obtained through a food-frequency questionnaire. Overall dietary quality was assessed using the Healthy Eating Index (HEI). We found that girls in the highest tertile of hs-CRP levels had a higher intake of saturated fatty acid, and lower intakes of fiber and vitamin E and a lower HEI score when compared to those in tertiles 1 and 2. We also observed a significant decrease in fruit and vegetable intakes by hs-CRP tertile. Factor analysis showed that a dietary pattern that was loaded most strongly with vegetable, fruit, fiber and vitamin A and E intakes correlated negatively (-0.132, p < 0.05) with hs-CRP. No such association was found in boys. In conclusion, our data show that girls with a poorer quality diet show higher hs-CRP levels already at a pre-pubertal age.