Reduced skeletal muscle protein balance in paediatric Crohn's disease

Davies, A. S.; Nixon, Aline; Muhammed, Rafeeq; Tsintzas, Kostas; Kirkham, Sian; Stephens, Francis B.; Moran, Gordon W

doi:10.1016/j.clnu.2019.05.017

“…Research has shown that elevation of serum cytokines, such as tumor necrosis factor- α (TNF- α ) and interleukin 6, reduces insulin-like growth factor-1 (IGF-1) in the serum and muscle of CD patients. This reduction, in turn, results in growth hormone resistance in the liver and skeletal muscle, leading to a downward moderation of the mTOR pathway into activation of the ubiquitin ligand and expression of proteolytic enzyme, which cause skeletal muscle mass reduction and impairment of muscle contraction [ 13 , 14 ]. Current interventions for sarcopenia include exercise therapy, nutrition therapy, and medication.…”

Section: Discussionmentioning

confidence: 99%

Prevalence of Sarcopenia and Its Effect on Postoperative Complications in Patients with Crohn’s Disease

Zhang

¹

,

Yu

²

,

Hong

³

et al. 2021

Gastroenterology Research and Practice

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Background and Aims. Sarcopenia is a prognostic factor of outcomes for various diseases, but reports on sarcopenia in patients with Crohn’s disease (CD) are few. We aim to determine the prevalence of sarcopenia and assess the role of sarcopenia in postoperative complications in patients with CD at a tertiary referral center. Methods. Patients who underwent intestinal surgery for CD from January 2013 to October 2019 were retrospectively enrolled. The L3 skeletal muscle mass index (SMI) was used to identify sarcopenia. Demographic data, preoperative laboratory data, surgical details, and hospital outcomes were recorded. The factors associated with postoperative complications were evaluated through univariate and multivariate analyses. Results. One hundred and twenty-four patients were enrolled. Thirty-four of them (27.4%), including 11 males, were diagnosed with sarcopenia. Compared with patients without sarcopenia, sarcopenic patients had a significantly lower BMI ( P < 0.001 ); lower preoperative serum albumin ( P = 0.006 ), prealbumin ( P = 0.030 ), and hemoglobin levels ( P < 0.001 ); longer hospital stay ( 34.4 ± 26.8 days vs. 22.8 ± 15.6 days, P = 0.003 ); and more occurrences of complications (41.2% vs. 23.3%, P = 0.049 ). The overall incidence of postoperative complications was 28.2%. Infection (51.4%) and intestinal fistula (22.9%) were the most common among such complications. Through the multivariate analysis, sarcopenia was identified as an independent risk factor for major postoperative complications ( odds ratio = 3.974 , 95 % CI = 1.171 –13.489, P = 0.027 ). Conclusion. Sarcopenia is common in patients with CD requiring bowel resection, and it significantly increases the risk of major postoperative complications.

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“…27,28 Lean mass was determined by the balance between muscle protein synthesis and breakdown, but loss of lean mass driven by inflammation and a suboptimal muscle protein synthetic response to enteral nutrition, termed anabolic resistance, may destroy this mechanism and finally lead to reduced lean mass. 29 Recently, Davies and colleagues 30 confirmed the theory in adolescent CD patients that inability to respond to nutrition could be implicated in low muscle mass in CD. Those CD patients with anabolic resistance cannot maintain a positive protein balance, even in remission.…”

Section: Discussionmentioning

confidence: 94%

A nomogram for predicting the response to exclusive enteral nutrition in adult patients with isolated colonic Crohn’s disease

Xu

¹

,

Guo

²

,

Huang

³

et al. 2019

Therap Adv Gastroenterol

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Background:Isolated colonic Crohn’s disease (cCD) responds less well to induction therapy with exclusive enteral nutrition (EEN) compared with ileal or ileocolonic disease in adult patients; therefore, we aimed to identify the factors that influence the response to EEN and develop a predictive nomogram model to optimize the use of EEN in cCD patients.Materials and methods:Eighty-five cCD patients treated with EEN as first-line therapy at our center between 1 June 2012 and 30 June 2018 were retrospectively analyzed as the primary cohort. The primary endpoint was clinical remission after EEN therapy. Potential predictive factors for the efficacy of EEN were assessed by univariate and multivariate analyses, and a nomogram to predict the response to EEN therapy in cCD patients was designed. Another 19 cCD patients were retrospectively included in the validation cohort to verify the accuracy of the nomogram model.Results:The clinical remission rates for the primary cohort and validation cohort were 52.9% and 47.4%, respectively. Pancolitis was the greatest contributor to the risk of failure to respond to EEN [odds ratio (OR) = 4.896; 95% confidence interval (CI) = 1.223–19.607; p = 0.025], lean body mass index (LBMI), colonic lesion features, simple endoscopic scores for Crohn’s disease, C-reactive protein before treatment and ∆prealbumin were also related to the efficacy of EEN in cCD. The nomogram model showed robust discrimination, with an area under the receiving operating characteristic curve of 0.906.Conclusion:Several predictive factors for response to EEN therapy in cCD adult patients were identified, and a promising nomogram that can predict the effect of EEN in cCD was developed.

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“…The precise mechanism of muscle deficits in CD remains unclear, with some suggesting impaired muscle protein synthesis [43,44], potentially linked to reduced systemic IGF-1 [44].…”

Section: Discussionmentioning

confidence: 99%

Muscle deficits with normal bone microarchitecture and geometry in young adults with well-controlled childhood-onset Crohn’s disease

Steell

¹

,

Johnston²,

Dewantoro

³

et al. 2020

European Journal of Gastroenterology &Amp; Hepatology

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Muscle-bone deficits are common in children with Crohn's disease (CD); however, few studies have assessed long-term musculoskeletal outcomes in adults with childhood onset CD. This study assessed the prevalence of musculoskeletal deficits in a cohort of young adults with childhood onset CD in comparison with healthy age and sex matched controls.This case-control study used 3-Tesla MRI and MRS to assess bone microarchitecture, cortical geometry and muscle area and adiposity at distal femur, and bone marrow adiposity of the lumbar spine, together with functional muscle tests and biochemical markers of the musclebone unit.Twenty-seven adults with CD with median (range) age 23.2 years (18.0, 36.1) and 27 controls with median age 22.9 years (18.2, 37.0) were recruited. Trabecular microarchitecture and cortical geometry of the distal femur and bone marrow adiposity of the lumbar spine were not different between CD and controls (p > 0.05 for all). Muscle cross sectional area was lower (p = 0.01) and muscle fat fraction was higher (p = 0.04) at the distal femur in CD compared to controls. CD participants had significantly lower grip strength (-4.3 kg [95% CI: -6.8, -1.8], p = 0.001) and lower limb muscle power relative to bodyweight (-5.0 W/kg [95% CI: -8.8, -1.2], p = 0.01). CD activity scores were negatively associated with trabecular bone volume (r = -0.40, p = 0.04) and muscle area (r = -0.41, p = 0.03).Young adults with well controlled CD managed with contemporary treatment strategies do not display abnormal bone microarchitecture or geometry at the distal femur but exhibit muscle deficits. The observed muscle deficits may predispose to musculoskeletal morbidity in future and interventions to improve muscle mass and function should be investigated.

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Reduced skeletal muscle protein balance in paediatric Crohn's disease

Cited by 20 publications

References 71 publications

Prevalence of Sarcopenia and Its Effect on Postoperative Complications in Patients with Crohn’s Disease

Prevalence of Sarcopenia and Its Effect on Postoperative Complications in Patients with Crohn’s Disease

A nomogram for predicting the response to exclusive enteral nutrition in adult patients with isolated colonic Crohn’s disease

Muscle deficits with normal bone microarchitecture and geometry in young adults with well-controlled childhood-onset Crohn’s disease

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