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Reducing NF-κB Signaling Nutritionally is Associated with Expedited Recovery of Skeletal Muscle Function After Damage.
Jameson, TSO, Pavis, GF, Dirks, ML, Lee, BP, Abdelrahman, DR, Murton, AJ, Porter, C, Alamdari, N, Mikus, CR, Wall, BT, et al
The Journal of clinical endocrinology and metabolism. 2021;(7):2057-2076
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Abstract
CONTEXT The early events regulating the remodeling program following skeletal muscle damage are poorly understood. OBJECTIVE The objective of this study was to determine the association between myofibrillar protein synthesis (myoPS) and nuclear factor-kappa B (NF-κB) signaling by nutritionally accelerating the recovery of muscle function following damage. DESIGN, SETTING, PARTICIPANTS, AND INTERVENTIONS Healthy males and females consumed daily postexercise and prebed protein-polyphenol (PP; n = 9; 4 females) or isocaloric maltodextrin placebo (PLA; n = 9; 3 females) drinks (parallel design) 6 days before and 3 days after 300 unilateral eccentric contractions of the quadriceps during complete dietary control. MAIN OUTCOME MEASURES Muscle function was assessed daily, and skeletal muscle biopsies were taken after 24, 27, and 36 hours for measurements of myoPS rates using deuterated water, and gene ontology and NF-κB signaling analysis using a quantitative reverse transcription PCR (RT-qPCR) gene array. RESULTS Eccentric contractions impaired muscle function for 48 hours in PLA intervention, but just for 24 hours in PP intervention (P = 0.047). Eccentric quadricep contractions increased myoPS compared with the control leg during postexercise (24-27 hours; 0.14 ± 0.01 vs 0.11 ± 0.01%·h-1, respectively; P = 0.075) and overnight periods (27-36 hours; 0.10 ± 0.01 vs 0.07 ± 0.01%·h-1, respectively; P = 0.020), but was not further increased by PP drinks (P > 0.05). Protein-polyphenol drinks decreased postexercise and overnight muscle IL1R1 (PLA = 2.8 ± 0.4, PP = 1.1 ± 0.4 and PLA = 1.9 ± 0.4, PP = 0.3 ± 0.4 log2 fold-change, respectively) and IL1RL1 (PLA = 4.9 ± 0.7, PP = 1.6 ± 0.8 and PLA = 3.7 ± 0.6, PP = 0.7 ± 0.7 log2 fold-change, respectively) messenger RNA expression (P < 0.05) and downstream NF-κB signaling compared with PLA. CONCLUSION Protein-polyphenol drink ingestion likely accelerates recovery of muscle function by attenuating inflammatory NF-κB transcriptional signaling, possibly to reduce aberrant tissue degradation rather than increase myoPS rates.
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Improved recovery from skeletal muscle damage is largely unexplained by myofibrillar protein synthesis or inflammatory and regenerative gene expression pathways.
Pavis, GF, Jameson, TSO, Dirks, ML, Lee, BP, Abdelrahman, DR, Murton, AJ, Porter, C, Alamdari, N, Mikus, CR, Wall, BT, et al
American journal of physiology. Endocrinology and metabolism. 2021;(2):E291-E305
Abstract
The contribution of myofibrillar protein synthesis (MyoPS) to recovery from skeletal muscle damage in humans is unknown. Recreationally active men and women consumed a daily protein-polyphenol beverage targeted at increasing amino acid availability and reducing inflammation (PPB; n = 9), both known to affect MyoPS, or an isocaloric placebo (PLA; n = 9) during 168 h of recovery from 300 maximal unilateral eccentric contractions (EE). Muscle function was assessed daily. Muscle biopsies were collected for 24, 27, 36, 72, and 168 h for MyoPS measurements using 2H2O and expression of 224 genes using RT-qPCR and pathway analysis. PPB improved recovery of muscle function, which was impaired for 5 days after EE in PLA (interaction P < 0.05). Acute postprandial MyoPS rates were unaffected by nutritional intervention (24-27 h). EE increased overnight (27-36 h) MyoPS versus the control leg (PLA: 33 ± 19%; PPB: 79 ± 25%; leg P < 0.01), and PPB tended to increase this further (interaction P = 0.06). Daily MyoPS rates were greater with PPB between 72 and 168 h after EE, albeit after function had recovered. Inflammatory and regenerative signaling pathways were dramatically upregulated and clustered after EE but were unaffected by nutritional intervention. These results suggest that accelerated recovery from EE is not explained by elevated MyoPS or suppression of inflammation.NEW & NOTEWORTHY The present study investigated the contribution of myofibrillar protein synthesis (MyoPS) and associated gene signaling to recovery from 300 muscle-damaging, eccentric contractions. Measured with 2H2O, MyoPS rates were elevated during recovery and observed alongside expression of inflammatory and regenerative signaling pathways. A nutritional intervention accelerated recovery; however, MyoPS and gene signaling were unchanged compared with placebo. These data indicate that MyoPS and associated signaling do not explain accelerated recovery from muscle damage.
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Quercetin Supplementation Improves Neuromuscular Function Recovery from Muscle Damage.
Bazzucchi, I, Patrizio, F, Ceci, R, Duranti, G, Sabatini, S, Sgrò, P, Di Luigi, L, Sacchetti, M
Nutrients. 2020;(9)
Abstract
This study was aimed at investigating whether quercetin (Q) may improve the recovery of neuromuscular function and biochemical parameters in the 7 days following an eccentric exercise-induced muscle damage (EEIMD). Sixteen men (25.9 ± 3.3 y) ingested Q (1000 mg/day) or placebo (PLA) for 14 days following a double-blind crossover study design. A neuromuscular (NM) test was performed pre-post, 24 h, 48 h, 72 h, 96 h and 7 days after an intense eccentric exercise. The force-velocity relationship of the elbow flexor muscles and their maximal voluntary isometric contraction (MVIC) were recorded simultaneously to the electromyographic signals (EMG). Pain, joint angle, arm circumference, plasma creatine kinase (CK) and lactate-dehydrogenase (LDH) were also assessed. The results showed that Q supplementation significantly attenuated the strength loss compared to PLA. During the recovery, force-velocity relationship and mean fibers conduction velocity (MFCV) persisted significantly less when participants consumed PLA rather than Q, especially at the highest angular velocities (p < 0.02). A greater increase in biomarkers of damage was also evident in PLA with respect to Q. Q supplementation for 14 days seems able to ameliorate the recovery of eccentric exercise-induced weakness, neuromuscular function impairment and biochemical parameters increase probably due to its strong anti-inflammatory and antioxidant action.
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Changing functional status within 6 months posttreatment is prognostic of overall survival in patients with head and neck cancer: NRG Oncology Study.
Eldridge, RC, Pugh, SL, Trotti, A, Hu, K, Spencer, S, Yom, SS, Rosenthal, D, Read, N, Desai, A, Gore, E, et al
Head & neck. 2019;(11):3924-3932
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Abstract
BACKGROUND Is posttreatment functional status prognostic of overall survival in patients with head and neck cancer (HNC). METHODS In an HNC clinical trial, 495 patients had two posttreatment functional assessments measuring diet, public eating, and speech within 6 months. Patients were grouped by impairment (highly, moderately, modestly, or not impaired) and determined if they improved, declined, or did not change from the first assessment to the second. Multivariable Cox models estimated overall mortality. RESULTS Across all three scales, the change in posttreatment patient function strongly predicted overall survival. In diet, patients who declined to highly impaired had three times the mortality of patients who were not impaired at both assessments (hazard ratio [HR] = 3.60; 95% confidence interval, 2.02-6.42). For patients improving from highly impaired, mortality was statistically similar to patients with no impairment (HR = 1.38; 95% CI, 0.82-2.31). CONCLUSIONS Posttreatment functional status is a strong prognostic marker of survival in patients with HNC.
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Multimodal prehabilitation in colorectal cancer patients to improve functional capacity and reduce postoperative complications: the first international randomized controlled trial for multimodal prehabilitation.
van Rooijen, S, Carli, F, Dalton, S, Thomas, G, Bojesen, R, Le Guen, M, Barizien, N, Awasthi, R, Minnella, E, Beijer, S, et al
BMC cancer. 2019;(1):98
Abstract
BACKGROUND Colorectal cancer (CRC) is the second most prevalent type of cancer in the world. Surgery is the only curative option. However, postoperative complications occur in up to 50% of patients and are associated with higher morbidity and mortality rates, lower health related quality of life (HRQoL) and increased expenditure in health care. The number and severity of complications are closely related to preoperative functional capacity, nutritional state, psychological state, and smoking behavior. Traditional approaches have targeted the postoperative period for rehabilitation and lifestyle changes. However, recent evidence shows that the preoperative period might be the optimal moment for intervention. This study will determine the impact of multimodal prehabilitation on patients' functional capacity and postoperative complications. METHODS/DESIGN This international multicenter, prospective, randomized controlled trial will include 714 patients undergoing colorectal surgery for cancer. Patients will be allocated to the intervention group, which will receive 4 weeks of prehabilitation (group 1, prehab), or the control group, which will receive no prehabilitation (group 2, no prehab). Both groups will receive perioperative care in accordance with the enhanced recovery after surgery (ERAS) guidelines. The primary outcomes for measurement will be functional capacity (as assessed using the six-minute walk test (6MWT)) and postoperative status determined with the Comprehensive Complication Index (CCI). Secondary outcomes will include HRQoL, length of hospital stay (LOS) and a cost-effectiveness analysis. DISCUSSION Multimodal prehabilitation is expected to enhance patients' functional capacity and to reduce postoperative complications. It may therefore result in increased survival and improved HRQoL. This is the first international multicenter study investigating multimodal prehabilitation for patients undergoing colorectal surgery for cancer. TRIAL REGISTRATION Trial Registry: NTR5947 - date of registration: 1 August 2016.
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Timing of periarticular injection has no effect on postoperative pain and functional recovery in simultaneous bilateral total knee arthroplasty: a prospective randomized, double-blinded trial.
Laoruengthana, A, Jarusriwanna, A, Rattanaprichavej, P, Rasamimongkol, S, Varakornpipat, P, Pongpirul, K
BMC musculoskeletal disorders. 2019;(1):162
Abstract
BACKGROUND Given no consensus on optimal timeframe of periarticular multimodal drug injection (PMDI) in knee osteoarthritis patients undergoing total knee arthroplasty (TKA), this study was aimed to compare the postoperative pain and the functional recovery in patients who underwent simultaneous bilateral TKA (SBTKA) and received PMDI at the different intraoperative time points. METHODS This prospective, randomized, double-blinded controlled trial study included 48 patients who underwent SBTKA and received PMDI mixture, either before prosthetic implantation (late PMDI), or just after knee arthrotomy (early PMDI). Each subject's knees were randomly selected to different PMDI administration time points. The outcome parameters were postoperative pain assessed by using a visual analog scale (VAS), the maximal angle of knee flexion, and quadriceps function from day 1 to 6 weeks after surgery. RESULTS Late PMDI revealed slightly higher VAS at 6 and 12 h after the operation than early PMDI administration. Afterward, the VAS tended to be lower in the late than early PMDI administration until the end of the study, but without statistical significance. The time difference between early and late PMDI had no effect on postoperative VAS, while older age resulted in significantly less pain. No statistical differences between the two groups in all other outcome parameters were observed. CONCLUSIONS Postoperative pain reduction and functional recovery of SBTKA with early and late PMDI administration were not significantly different. The time interval of PMDI between knees did not confound the comparison of postoperative pain and functional recovery in SBTKA. TRIAL REGISTRATION The protocol of this study was retrospectively registered in the Thai Clinical Trials Registry database No. TCTR20170617001 on 16 June 2017.
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Effect of Enhanced Recovery After Surgery program on pancreaticoduodenectomy: a randomized controlled trial.
Hwang, DW, Kim, HJ, Lee, JH, Song, KB, Kim, MH, Lee, SK, Choi, KT, Jun, IG, Bang, JY, Kim, SC
Journal of hepato-biliary-pancreatic sciences. 2019;(8):360-369
Abstract
BACKGROUND This study aims to investigate the noninferiority of Enhanced Recovery After Surgery (ERAS) for pancreaticoduodenectomy (PD). METHODS In this single-center trial, we randomly assigned 276 adult patients who underwent open PD into ERAS and conventional groups with 138 patients in each, from 2015 through 2017. The primary endpoint was the incidence of overall morbidity until postoperative 3 months. The secondary endpoints were in-hospital or 30-day mortality, postoperative length of stay (LOS), nutritional status and overall hospital costs. RESULTS Overall morbidity was reported in 64 patients (52.0%, ERAS group) and in 68 patients (54.8%, conventional group) (risk difference [RD] -2.81 percentage points (pp); 90% two-sided confidence interval -13.24 to 7.63). Mortality did not occur in any patients. The two groups did not differ significantly in median postoperative LOS (both 11 days; RD -8.46 pp), body mass index (22.4 ± 2.75 vs. 22.4 ± 2.65 kg/m2 ; RD -3.48 pp), Patient-Generated Subjective Global Assessment score over 4 (45 [40.5%] vs. 50 [43.1%] patients; RD -2.56 pp), and median overall hospital cost (15.61 vs. 16.04, ×106 KRW; RD -6.08 pp). CONCLUSIONS Even in PD, modified ERAS protocol was not inferior to conventional protocol, while reducing treatment burden.
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Timeline of functional recovery after hip fracture in seniors aged 65 and older: a prospective observational analysis.
Fischer, K, Trombik, M, Freystätter, G, Egli, A, Theiler, R, Bischoff-Ferrari, HA
Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA. 2019;(7):1371-1381
Abstract
UNLABELLED We investigated the timeline of functional recovery after hip fracture over 12 months in adults age ≥ 65 years using objective lower extremity function tests and subjective physical functioning. Objective functional recovery was largely complete in the first 6 months, whereas subjective recovery improved up to 9 months after hip fracture. INTRODUCTION Hip fractures are a major cause of loss of function among seniors. We assessed the timeline of objective and subjective functional recovery after hip fracture. METHODS We conducted a prospective observational secondary analysis of a 1-year clinical trial on vitamin D and home exercise treatment and complications after hip fracture among 173 patients age ≥ 65 years (mean age 84 years; 79.2% women; 77.4% community-dwelling) conducted from January 2005 through December 2007. Lower extremity function (Timed Up and Go test (TUG), knee extensor and flexor strength) and grip strength was assessed at baseline and at 6 and 12 months follow-up. Subjective physical functioning was assessed using the SF-36 questionnaire also at 3 and 9 months follow-up. Multivariable-adjusted repeated-measures models were used to assess the timeline of functional recovery in the total population and in subgroups of patients. RESULTS Lower extremity function including TUG (- 61.1%), knee extensor (+ 17.6%), and knee flexor (+ 11.6%) strength improved significantly in the first 6 months (P < 0.001). However, between 6 and 12 months, there was no further significant improvement for any of the functional tests. Grip strength decreased from baseline to 6 months (- 7.9%; P < 0.001) and from 6 to 12 months (- 10.8%; P < 0.001). Subjective physical functioning improved from 3 to 9 months (+ 15.2%, P < 0.001), but no longer thereafter. CONCLUSIONS Functional recovery after hip fracture may be largely complete in the first 6 months for objective functional tests, whereas may extend up to 9 months for subjective recovery, with oldest-old, female, institutionalized, and cognitively impaired patients recovering most poorly. CLINICAL TRIALS REGISTRY (ORIGINAL TRIAL): NCT00133640.
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Brain Motor Control Assessment Post Early Intensive Hand Rehabilitation After Spinal Cord Injury.
Zoghi, M, Galea, M
Topics in spinal cord injury rehabilitation. 2018;(2):157-166
Abstract
Background: The Brain Motor Control Assessment (BMCA) is a surface electromyography (sEMG)-based measure of motor output from the central nervous system during a variety of reflex and voluntary motor tasks. Objective: The aim of this study was to assess the pattern of voluntary movements in patients with spinal cord injury (SCI) to investigate whether BMCA could add more resolution to clinical assessments and the recovery path of these patients. Method: Ten participants were recruited from the Royal Talbot Rehabilitation Centre as part of a multicenter randomized controlled trial. Four participants received usual care while the other 3 participants received usual care plus an intensive task-specific hand training program in conjunction with functional electrical stimulation for 8 weeks. BMCA assessments were completed for 7 participants at this center 4 times over a period of 1 year. Results: Generalized linear model analysis showed a significant main effect of task (p < .001) and assessment time (p = .003) on the Similarity Index. However, there were no significant interactions among the factors (p > .05). Based on ARAT or summed upper limb strength scores, some participants showed significant improvement after 8 weeks of rehabilitation, however this improvement was not reflected in the pattern of muscle activation that was captured by BMCA. Conclusion: The quantifiable features of BMCA through surface EMG may increase the resolution of SCI characterization by adding subclinical details to the clinical picture of lesion severity and progression during rehabilitation.
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The effects of the herbal medicine Daikenchuto (TJ-100) after esophageal cancer resection, open-label, randomized controlled trial.
Nishino, T, Yoshida, T, Goto, M, Inoue, S, Minato, T, Fujiwara, S, Yamamoto, Y, Furukita, Y, Yuasa, Y, Yamai, H, et al
Esophagus : official journal of the Japan Esophageal Society. 2018;(2):75-82
Abstract
BACKGROUND Daikenchuto (TJ-100), a traditional Japanese herbal medicine, is widely used in Japan. Its effects on gastrointestinal motility and microcirculation and its anti-inflammatory effect are known. The purpose of this prospective randomized controlled trial was to investigate the effect of TJ-100 after esophagectomy in esophageal cancer patients. METHODS Forty patients for whom subtotal esophageal resection for esophageal cancer was planned at our institute from March 2011 to August 2013 were enrolled and divided into two groups at the point of determination of the operation schedule after informed consent was obtained: a TJ-100 (15 g/day)-treated group (n = 20) and a control group (n = 20). The primary efficacy end-points were maintenance of the nutrition condition and the recovery of gastrointestinal function. The secondary efficacy end-points were the serum C-reactive protein (CRP) level and adrenomedullin level during the postoperative course, the incidence of postoperative complications, and the length of hospital stay after surgery. RESULTS We examined 39 patients because one patient in the TJ-100 group was judged as having unresectable cancer after surgery. The mean age of the TJ-100 group patients was significantly older than that of the control group patients.The rate of body weight decrease at postoperative day 21 was significantly suppressed in the TJ-100 group (3.6% vs. the control group: 7.0%, p = 0.014), but the serum albumin level was not significantly different between the groups. The recovery of gastrointestinal function regarding flatus, defecation, and oral intake showed no significant between-group differences, but postoperative bowel symptoms tended to be rare in the TJ-100 group. There was no significant between-group difference in the length of hospital stay after surgery. The serum CRP level at postoperative day 3 was 4.9 mg/dl in the TJ-100 group and 6.9 mg/dl in the control group, showing a tendency of a suppressed serum CRP level in the TJ-100 group (p = 0.126). The rate of increase in adrenomedullin tended to be high postoperatively, but there was no significant difference between the two groups. CONCLUSIONS TJ-100 treatment after esophageal cancer resection has the effects of prompting the recovery of gastrointestinal motility and minimizing body weight loss, and it might suppress the excess inflammatory reaction related to surgery.