Pippa Simpson

Introduction: Pain constitutes the chief complaint of some functional gastrointestinal disorders (FGIDs). The endocannabinoid (EC) and peroxisome proliferator–activated receptors (PPARs) agonist systems have not been explored as possible contributors. Objective: To determine if EC and PPAR agonist abnormalities occur in adolescents with FGID. Methods: Institutional Review Board approved study compared 33 children (12-18 years) with a FGID to 18 healthy controls (HC). Clinical measures: functional disability inventory and pediatric pain questionnaire (PPQ). Endocannabinoid and PPAR agonist concentrations were determined in serum from blood. Data were analyzed using Mann–Whitney and Fisher exact tests (2-sided P < 0.05 considered significant). Results: When compared to HC, FGID subjects used different terms to describe their pain, which also occurred in more body areas. Functional gastrointestinal disorder subjects exhibited higher palmitoylethanolamide (PEA) and N-oleoylethanolamide, while EC did not differ. Interestingly, PEA correlated significantly with PPQ “worst pain the week before” in the HC group with Spearman ρ = 0.519, P = 0.003, but not in the FGID group (ρ = 0.079, P = 0.66). Conclusion: Children with FGID exhibit significant pain in nongastrointestinal regions. The higher concentrations of PEA found in the FGID subjects, also occurring in other chronic pain conditions, could reflect a compensatory response due to feedback loops from a downregulated or nonresponsive PPAR system, while the absence of the expected relationship between pain intensity and PEA levels in the FGID group suggests that the PPAR system may not be functioning normally.

Background: MYH6 variants are the most well-known genetic risk factor (10%) for hypoplastic left heart syndrome (HLHS) and are associated with decreased cardiac transplant-free survival. MYH6 encodes for α-myosin heavy chain (α-MHC), a contractile protein expressed in the neonatal atria. We therefore assessed atrial function in HLHS patients with MYH6 variants. Methods: We performed a retrospective, blinded assessment of pre-stage I atrial function using 2D speckle-tracking echocardiography (2D-STE). Variant carriers were control-matched based on AV valve anatomy, sex, and birth year. Studies were obtained postnatally from awake patients prior to surgical intervention. Right atrial (RA) and right ventricular (RV) strain and strain rate (SR) were measured from the apical four-chamber view. Results: A total of 19 HLHS patients with MYH6 variants had echocardiograms available; 18 were matched to two controls each, and one had a single control. RA active strain (ASct) was decreased in variant carriers (−1.41%, IQR −2.13, −0.25) vs. controls (−3.53%, IQR −5.53, −1.28; p = 0.008). No significant differences were identified in RV strain between the groups. RA reservoir strain (ASr) and conduit strain (AScd) positively correlated with heart rate (HR) in MYH6 variant carriers only (ASr R = 0.499, p = 0.029; AScd R = 0.469, p = 0.043). RV global longitudinal strain (GLS) as well as RV systolic strain (VSs) and strain rate (VSRs) correlated with HR in controls only (GLS R = 0.325, p = 0.050; VSs R = 0.419, p = 0.010; VSRs R = 0.410, p = 0.012). Conclusions: We identified functional consequences associated with MYH6 variants, a known risk factor for poor outcomes in HLHS. MYH6 variant carriers exhibit impaired RA contractility despite there being no differences in RV function between variant carriers and controls. MYH6 variants are also associated with an ineffective RA reservoir and conduit function at high heart rates, despite preserved RV diastolic function. RA dysfunction and reduced atrial “kick” may therefore be a significant contributor to RV failure and worse clinical outcomes in HLHS patients with MYH6 variants.

Physical activity is critical to functional rehabilitation for youth with chronic pain, which may be especially true for those with co-occurring obesity. To facilitate the development of physical activity interventions for youth with chronic pain, the newly developed “Rating of Perceived Exertion—Pediatric” scale was modeled after the widely used pain numeric rating scale-11. This study is an initial evaluation of the scale in a sample of adolescents (n = 157, 13–17 years, 51% female) with four subgroups: (1) healthy controls (healthy weight/no pain); (2) chronic pain/healthy weight; (3) obese (no pain); (4) chronic pain/obese. Participants rated perceived exertion using the new scale and the Borg 6–20 Scale of Perceived Exertion while holding a three-minute yoga pose (Warrior II). In the whole sample, the Perceived Exertion—Pediatric scale showed good concurrent (p < 0.001), convergent (all ps < 0.05), discriminant (p = 0.431), and known-groups validity (all ps < 0.05). The chronic pain subgroup also showed good concurrent (p < 0.001), mixed convergent (ps < 0.001 to 0.315), and good discriminant validity (p = 0.607). Limitations include the restricted age range, lack of diversity, and lack of test-retest reliability. The RPE-P shows promise as an assessment tool for perceived exertion in adolescents with and without chronic pain.

The Fontan procedure results in chronic hepatic congestion and Fontan-associated liver disease (FALD) characterized by progressive liver fibrosis and cirrhosis. Exercise is recommended in this population, but may accelerate the progression of FALD from abrupt elevations in central venous pressure. The aim of this study was to assess if acute liver injury occurs after high-intensity exercise in patients with Fontan physiology. Ten patients were enrolled. Nine had normal systolic ventricular function and one had an ejection fraction < 40%. During cardiopulmonary exercise testing, patients had near-infrared spectroscopy (NIRS) to measure oxygen saturation of multiple organs, including the liver, and underwent pre- and post-exercise testing with liver elastography, laboratory markers, and cytokines to assess liver injury. The hepatic and renal NIRS showed a statistically significant decrease in oxygenation during exercise, and the hepatic NIRS had the slowest recovery compared to renal, cerebral, and peripheral muscle NIRS. A clinically significant increase in shear wave velocity occurred after exercise testing only in the one patient with systolic dysfunction. There was a statistically significant, albeit trivial, increase in ALT and GGT after exercise. Fibrogenic cytokines traditionally associated with FALD did not increase significantly in our cohort; however, pro-inflammatory cytokines that predispose to fibrogenesis did significantly rise during exercise. Although patients with Fontan circulation demonstrated a significant reduction in hepatic tissue oxygenation based on NIRS saturations during exercise, there was no clinical evidence of acute increase in liver congestion or acute liver injury following high-intensity exercise.

Hypoplastic left heart syndrome (HLHS) is a severe congenital heart disease (CHD) with complex genetic inheritance. HLHS segregates with other left ventricular outflow tract (LVOT) malformations in families, and can present as either an isolated phenotype or as a feature of a larger genetic disorder. The multifactorial etiology of HLHS makes it difficult to interpret the clinical significance of genetic variants. Specific genes have been implicated in HLHS, including rare, predicted damaging MYH6 variants that are present in >10% of HLHS patients, and which have been shown to be associated with decreased transplant-free survival in our previous studies. MYH6 (α-myosin heavy chain, α-MHC) variants have been reported in HLHS and numerous other CHDs, including LVOT malformations, and may provide a genetic link to these disorders. In this paper, we outline the MYH6 variants that have been identified, discuss how bioinformatic and functional studies can inform clinical decision making, and highlight the importance of genetic testing in HLHS.

Introduction: The negative effects of chronic pain and obesity are compounded in those with both conditions. Despite this, little research has focused on the pathophysiology in pediatric samples. Objective: To examine the effects of comorbid chronic pain and obesity on the concentration of circulating inflammatory biomarkers. Methods: We used a multiple-cohort observational design, with 4 groups defined by the presence or absence of obesity and chronic pain: healthy controls, chronic pain alone, obesity alone, as well as chronic pain and obesity. Biomarkers measured were leptin, adiponectin, leptin/adiponectin ratio (primary outcome), tumor necrosis factor-alpha, interleukin 6, and C-reactive protein (CRP). Results: Data on 125 adolescents (13–17 years) were analyzed. In females, there was an interaction between chronic pain and obesity such that leptin and CRP were higher in the chronic pain and obesity group than in chronic pain or obesity alone. Within the chronic pain and obesity group, biomarkers were correlated with worsened pain attributes, and females reported worse pain than males. The highest levels of interleukin 6 and CRP were found in youth with elevated weight and functional disability. We conclude that in adolescents, chronic pain and obesity interact to cause dysregulation of the inflammatory system, and this effect is more pronounced in females. Conclusion: The augmented levels of inflammatory biomarkers are associated with pain and functional disability, and may be an early marker of future pain and disability.

Factors such as gender, ethnicity, and age affect pain processing in children and adolescents with chronic pain. Although obesity has been shown to affect pain processing in adults, almost nothing is known about pediatric populations. The aim of this pilot study was to explore whether obesity alters sensory processing in adolescents with chronic pain. Participants were recruited from a chronic pain clinic (Chronic Pain (CP), n = 12 normal weight; Chronic Pain + Obesity (CPO), n = 19 overweight/obesity) and from an obesity clinic (Obesity alone (O), n = 14). The quantitative sensory testing protocol included assessments of thermal and mechanical pain thresholds and perceptual sensitization at two sites with little adiposity. The heat pain threshold at the hand was significantly higher in the CPO group than in either the CP or O groups. Mechanical pain threshold (foot) was significantly higher in the CPO group than the CP group. No differences were found on tests of perceptual sensitization. Correlations between experimental pain and clinical pain parameters were found for the CPO group, but not for the CP group. This preliminary study provides important lessons learned for subsequent, larger-scale studies of sensory processing for youth with co-occurring chronic pain and obesity.

Increasing HPV vaccination rates may decrease the disproportionately high HPV-associated disease incidence and mortality in African Americans (AA) and lower socioeconomic individuals. Data from a community-based participatory research (CBPR) study addressing immunization disparities among 19–35 month old children was analyzed to identify ancillary benefits in HPV immunization rates for adolescent siblings. Sub-study analysis inclusion criteria: AA (N = 118), 13–17 years old, younger sibling enrolled in parent study, and enrolled ≥ 9 months. Parent/caregiver interventions included: a web-based immunization toolkit with information on age-appropriate vaccines; a multimedia community outreach campaign; and reminder mailings. HPV up-to-date (UTD) status was defined as Wisconsin Immunization Registry (WIR) documentation of at least three HPV vaccines. McNemar’s test compared pre/post intervention HPV status. Two dependent proportions testing compared the proportion of adolescents that became UTD in the study cohort, City of Milwaukee, and State of Wisconsin. Parents/caregivers perceived that 92% of adolescents were HPV-UTD, while only 24% had a WIR-verified HPV-UTD status. Baseline UTD status of the younger siblings 19–35 month old 4:3:1:3:3:1:4 antigen series was 63%, which increased to 86% at study completion. Adolescent’s HPV-UTD immunization status increased from 30 (25%) at enrollment to 54 (46%) at study completion [p = 0.004]. A statistically significant larger proportion of adolescents became HPV-UTD in the study cohort (20%) compared to the City of Milwaukee [14%, p = 0.042] and the State of Wisconsin [14%, p = 0.046]. A culturally-tailored CBPR approach targeting parents/caregivers of younger AA children can have significant ancillary benefit to increase HPV immunization rates in adolescent siblings.

Nontuberculous mycobacteria (NTM) infections in patients with cystic fibrosis (CF) is increasing globally. However, the related epidemiology, comorbidities, and clinical impact of NTM infection remains unclear in the progress of CF lung disease and patient survival. We performed a retrospective, case-control, cohort study (10 years), comparing NTM culture-positive CF patients (N = 28) to matched controls (N = 26). NTM positive patients were divided in to two groups of slow-growing (N = 17) and rapid- growing NTM (N = 8). Three patients were positive for both slow and rapid NTM. For independent group comparisons, a non-parametric Mann-Whitney test (Kruskal-Wallis test for more than two groups) was used to compare the continuous variables, and a Fisher’s exact test was used for the categorical variables. Paired comparisons were performed using a Wilcoxon signed-rank test. The prevalence of NTM isolation was 8%. The age at CF diagnosis was significantly lower in the slow-growing NTM group compared to the rapidly growing NTM group (P = 0.04). The median percent predicted forced expiratory flow of 25% − 75% (FEF25–75) was significantly higher before NTM acquisition in slow-growing (P = 0.013) and rapidly growing NTM group (P = 0.028). The slow-growing NTM group received significantly more penicillin/beta lactamase (P = 0.010) and rifampin (P = 0.042) following isolation. Macrolide use was significantly higher after isolation in both the slow-growing NTM (P = 0.018) and rapidly growing NTM groups (P = 0.042). An earlier CF diagnosis was associated with a higher isolation of slow-growing NTM and greater antimicrobial use after infection. NTM acquisition is associated with a worsening of FEF25–75. Thus, both the early diagnosis and treatment of an NTM infection in patients with CF may positively impact lung function.

Obesity negatively impacts the kinematics and kinetics of the lower extremities in children and adolescents. Although yoga has the potential to provide several distinct benefits for children with obesity, this is the first study to examine the benefits of yoga for gait (primary outcome) in youths with obesity. Secondary outcomes included health-related quality of life (HRQoL), physical activity, and pain. Feasibility and acceptability were also assessed. Nine youths (11–17 years) participated in an eight-week Iyengar yoga intervention (bi-weekly 1-h classes). Gait, HRQOL (self and parent-proxy reports), and physical activity were assessed at baseline and post-yoga. Pain was self-reported at the beginning of each class. Significant improvements were found in multiple gait parameters, including hip, knee, and ankle motion and moments. Self-reported and parent-proxy reports of emotional functioning significantly improved. Time spent in physical activity and weight did not change. This study demonstrates that a relatively brief, non-invasive Iyengar yoga intervention can result in improved malalignment of the lower extremities during ambulation, as well as in clinically meaningful improvements in emotional functioning. This study extends current evidence that supports a role for yoga in pediatric obesity.