Exercise rehabilitation to treat sarcopenia in pediatric transplant populations.

BACKGROUND: In adult transplant (Tx) populations, exercise rehabilitation strategies may improve sarcopenia components (muscle mass [MM], strength [MS], and physical performance [PP]). Limited data are available regarding exercise rehabilitation therapy in pediatric Tx populations. METHODS: The purpose of this review is to critically evaluate the feasibility and impact of exercise programs (EP) that include resistance exercise (RE) on markers of sarcopenia in pediatric Tx populations. Literature searches in SCOPUS and WEB OF SCIENCE were conducted to identify studies applying EP with a RE component in pediatric populations in the Tx setting. RESULTS: Twelve articles (2008-2022) met inclusion criteria. The exercise interventions varied in length (3 weeks-12 months), intensity (low to moderate), time pre/post Tx (0 days-5 years post Tx), age of participants (3-18 years), adherence (63%-94%), and methodologies to measure components of sarcopenia. No studies measured all three components of sarcopenia concurrently. Approximately, 60% of studies found positive effects on MS and PP. Only one pediatric study measured body composition, therefore, the effect of exercise programs with RE components on MM is unknown. CONCLUSIONS: Exercise programs may be a beneficial treatment for sarcopenia in Tx populations, particularly in components of MS and PP. Studies measuring all three aspects of sarcopenia together in response to RE training in pediatrics remains an important gap. Studies that include body composition measurements in response to exercise are needed. Special considerations for the development of RE programs in pediatrics Tx populations are safety, supervision, engagement through family/peer involvement and incorporation of game/play-based elements.

Challenges and physiological implications of sarcopenia in children and youth in health and disease.

PURPOSE OF REVIEW: Highlight the controversies and challenges associated with a sarcopenia diagnosis in infants and children and the potential physiological mechanisms contributing to this disorder. RECENT FINDINGS: Sarcopenia has been recently identified in infants and children with chronic diseases such as liver, cardiac, gastrointestinal, cancer and organ transplant recipients. However, there is no consensus regarding the definition of pediatric sarcopenia. Different sarcopenic phenotypes (sarcopenia and sarcopenic obesity) have been identified in healthy children and children with chronic disease. Both conditions have been associated with adverse clinical outcomes (e.g. delayed growth, increased hospitalization) in children and youth with chronic disease. The etiology of pediatric sarcopenia is likely multifactorial associated with malnutrition, physical inactivity and altered metabolic environments influencing skeletal muscle mass accumulation and function. Gaps in the literature include the lack of standard tools that should be used for the evaluation of skeletal muscular fitness and body composition in sarcopenia, particularly in infants and young children (<4years). SUMMARY: Longitudinal evaluation of sarcopenia expression and the underlying physiological and lifestyle factors contributing to pediatric sarcopenia are important to understand to ensure effective rehabilitation strategies can be developed and to avoid the adverse clinical consequences in children.

Skeletal muscle fibre morphology in childhood-insights into myopenia in pediatric liver disease.

TAKE-HOME MESSAGE: Skeletal muscle morphology in healthy children changes with age. Liver disease may preferentially affect type II fibres in adults with end-stage liver disease (ESLD). More research is needed on the effects of ESLD on muscle morphology in children.

Health-Related Quality of Life 10 Years after Liver Transplantation: A Longitudinal Retrospective Review.

As survival post-liver transplantation (LTx) improves, it becomes increasingly important to understand how long-term health-related quality of life (HRQOL) is impacted. This was a longitudinal review examining HRQOL measured by Pediatric Liver Transplant Quality of Life (PeLTQL) in children between 8-17 years who underwent LTx (1.4 [0.8-3.3] years) at least one year prior to assessment. Demographic, medical, anthropometric, and HRQOL data (self-reported and parent proxy) were retrospectively collected over four years (2014-2017) at annual LTx clinic visits. The study included 35 patients (18M, 17F) and their parents/guardians. Parent-proxy and child PeLTQL scores (total, subdomain) showed good to excellent agreement (p > 0.05) and did not change over four years (p > 0.05). Younger age (<12 years) and Caucasian ancestry were associated with higher parental and self-reported perceptions of HRQOL, respectively (future health, coping and adjustment, total scores). Parent perceived lower HRQOL in social-emotional sub-domain (p = 0.03) and the child reported lower sub-domain scores related to coping and adjustment (p = 0.04) when the child was noted to have co-morbid conditions related to mental health and neurocognitive development (25.7%). While child-parent perceptions of HRQOL in a multi-ethnic population of pediatric LTx recipients remain unchanged 10 years post-LTx, adolescents of non-Caucasian ancestry remain a population at risk for lower HRQOL.

Sarcopenia in Chronic Liver Disease: Impact on Outcomes.

Malnutrition is a common complication in patients with end-stage liver disease (ESLD) awaiting liver transplantation (LT). Malnutrition and sarcopenia overlap in etiology and outcomes, with sarcopenia being defined as reduced skeletal muscle mass and muscle function. The purpose of this review was to identify the prevalence of sarcopenia with and without obesity in adults and children with ESLD and to assess the methodological considerations in sarcopenia diagnosis and the association of sarcopenia with pre- and post-LT outcomes. A total of 38 articles (35 adult and 3 pediatric articles) retrieved from PubMed or Web of Science databases were included. In adults, the prevalence rates of pre-LT sarcopenia, pre-LT sarcopenic obesity (SO), post-LT sarcopenia, and post-LT SO were 14%-78%, 2%-42%, 30%-100%, and 88%, respectively. Only 2 adult studies assessed muscle function in patients diagnosed with sarcopenia. The presence of pre-LT sarcopenia is associated with higher wait-list mortality, greater postoperative mortality, higher infection risk and postoperative complications, longer intensive care unit (ICU) stay, and ventilator dependency. The emerging pediatric data suggest that sarcopenia is prevalent in pre- and post-LT periods. In 1 pediatric study, sarcopenia was associated with poor growth, longer perioperative length of stay (total/ICU) and ventilator dependency, and increased rehospitalization in children after LT. In conclusion, there is a high prevalence of sarcopenia in adults and children with ESLD. Sarcopenia is associated with adverse clinical outcomes. The present review is limited by heterogeneity in the definition of sarcopenia and in the methodological approaches in assessing sarcopenia. Future studies are needed to standardize the sarcopenia diagnosis and muscle function assessment, particularly in the pediatric population, to enable early identification and treatment of sarcopenia in adults and children with ESLD.

Healthy Body Weights With Corticosteroid-free Immunosuppression Is the Best Predictor of Cardiovascular Health in Children After Liver Transplantation.

INTRODUCTION: Cardiometabolic dysregulation (CMD) influences morbidity and mortality risk in adults post-liver transplantation (LTx). CMD is reported in 10% to 25% of pediatric LTx recipients, but no information regarding the longitudinal expression of CMD is available. The study objective was to examine the longitudinal expression of CMD and associations with body composition and growth in children post-LTx. METHODS: A retrospective review was conducted in youth (34 F/30 M) who underwent LTx between 1994 and 2015 at the Stollery Children's Hospital. Primary outcomes included serum markers of CMD (insulin, glucose, hemoglobin A1C [A1C], homeostasis model assessment for insulin resistance [abnormal >3], lipid panel triglycerides, total cholesterol, high-density lipoprotein-cholesterol, low-density lipoprotein-cholesterol) and systolic/diastolic blood pressure (BP: absolute/z scores). RESULTS: Mean (±SD) age, weight z, height z, body mass index z was 9.7 ±â€Š3.4 years (3.5-17.9), 0.26 ±â€Š1.03, 0.017 ±â€Š1.2, and 0.41 ±â€Š1.05, respectively. The majority of children had percentage fat mass, percentage fat-free mass within normal reference ranges. Systolic/diastolic BP was within healthy references ranges in 83.1% and 93.5% of children, respectively. Serum insulin (83.4%) and high-density lipoprotein-cholesterol (43.9%) concentrations were low, with abnormal findings of other laboratory markers found in <5% of participants. Abnormal findings for metabolic parameters were independent of weight z, body mass index z, fat mass, and corticosteroids but were positively related to child's age (>9.7 years) and fat-free mass (total, arms). Insulin levels decreased significantly in the first 4 years post-LTx, but no changes in lipid panel, A1C and glucose were noted over 10 years. CONCLUSIONS: Pediatric LTx recipients with healthy body weights and corticosteroid-free immunosuppression have a low expression of CMD over 10 years.

Persistence of Sarcopenia After Pediatric Liver Transplantation Is Associated With Poorer Growth and Recurrent Hospital Admissions.

INTRODUCTION: Sarcopenia is prevalent in adults pre-liver transplantation (LTx) and post-LTx contributing to adverse outcomes. Little is known regarding the prevalence of sarcopenia in pediatric LTx recipients. This novel study examined sarcopenia prevalence and associations with post-LTx growth and healthcare utilization in pediatric LTx recipients. METHODS: We prospectively assessed body composition at annual clinical appointments in children (0.5-17 years; n = 58) by Dual-energy-X-ray absorptiometry (absolute/regional/percent fat mass [FM], fat-free mass [FFM], skeletal muscle mass [SMM]). Sarcopenia was defined as SMM z scores ≤2. Additional variables measured included age, gender, PELD, immunosuppressive therapies (dose/type), weight, weight-z, height, height-z, serum aspartate aminotransferase, alanine aminotransferase, γ-glutamyltransferase, albumin, total/conjugated bilirubin, prothrombin time, international normalized ratio, albumin, creatinine clearance, urea and creatinine at LTx assessment, LTx and annual clinic appointments. Healthcare variables studied included rejection (number/type/severity), length of in-patient stay (total, intensive care unit [ICU], emergency, readmission) and ventilator dependency. RESULTS: Sarcopenia occurred in 41% (n = 17) at 7.6 (± 3.1) years; with a mean time post-LTx of 1.1 ± 1.9 (1-8) years. Female children ≤9.8 years had a higher sarcopenia prevalence than children >9.8 years (83.1% vs 17.1%; p = 0.004). Sarcopenia was associated with lower weight velocity standard deviation scores, lower weight-z/height-z scores at 2-10 years post LTx, increased hospitalization (total, ICU, emergency and readmission) and ventilator dependency (p < 0.05), but not to rejection and/or corticosteroid therapy (p > 0.05). CONCLUSIONS: This is the first study demonstrating persistent sarcopenia associated with poorer growth and recurrent hospitalization in children post-LTx.