Der-Sheng Han

Early Versus Delayed Passive Range of Motion Exercise for Arthroscopic Rotator Cuff Repair: A Meta-analysis of Randomized Controlled Trials.

Background: Postoperative shoulder stiffness complicates functional recovery after arthroscopic rotator cuff repair. Purpose: To compare early passive range of motion (ROM) exercise with a delayed rehabilitation protocol with regard to the effectiveness of stiffness reduction and functional improvements and rates of improper healing in patients undergoing arthroscopic repair for torn rotator cuffs. Study Design: Systematic review and meta-analysis. Methods: Randomized controlled trials (RCTs) comparing both rehabilitation approaches were identified in PubMed and Scopus. Between-group differences in shoulder function were transformed to effect sizes for comparisons, whereas the effectiveness against stiffness and the risk of tendon failure were reported using standardized mean differences of ROM degrees and odds ratios (ORs) of recurrent tears, respectively. Results: Six RCTs were included, consisting of 482 patients. No significant difference in shoulder function existed across both protocols. The early ROM group demonstrated more improvement in shoulder forward flexion than the delayed rehabilitation group, with a standardized mean difference of 7.45° (95% CI, 3.20°-11.70°) at 6 months and 3.51° (95% CI, 0.31°-6.71°) at 12 months. Early ROM exercise tended to cause a higher rate of recurrent tendon tears (OR, 1.43; 95% CI, 0.90-2.28), and the effect became statistically significant (OR, 1.93; 95% CI, 1.04-3.60) after excluding 2 RCTs that recruited only those patients with small to medium-sized tears. Conclusion: Early ROM exercise accelerated recovery from postoperative stiffness for patients after arthroscopic rotator cuff repair but was likely to result in improper tendon healing in shoulders with large-sized tears. The choice of either protocol should be based on an accommodation of the risks of recurrent tears and postoperative shoulder stiffness.

Serum myostatin levels and grip strength in normal subjects and patients on maintenance haemodialysis.

Objective  Myostatin, a negative regulator of skeletal muscle growth, may modulate grip strength, an indicator of muscle function. Its serum levels could be modulated by maintenance haemodialysis (MHD).

Effectiveness of Bisphosphonate Analogues and Functional Electrical Stimulation on Attenuating Post-Injury Osteoporosis in Spinal Cord Injury Patients- a Systematic Review and Meta-Analysis

Background Various pharmacologic and non-pharmacologic approaches have been applied to reduce sublesional bone loss after spinal cord injury (SCI), and the results are inconsistent across the studies. The objective of this meta-analysis was to investigate whether the two most-studied interventions, bisphosphonate analogues and functional electrical stimulation (FES), could effectively decrease bone mineral density (BMD) attenuation and/or restore lost BMD in the SCI population. Methods Randomized controlled trials, quasi-experimental studies, and prospective follow-up studies employing bisphosphonates or FES to treat post-SCI osteoporosis were identified in PubMed and Scopus. The primary outcome was the percentage of BMD change from baseline measured by dual-energy X-ray absorptiometry (DEXA) or computed tomography (CT). Data were extracted from four points: the 3rd, 6th, 12th, and 18th month after intervention. Results A total of 19 studies were included in the analysis and involved 364 patients and 14 healthy individuals. Acute SCI participants treated with bisphosphonate therapy demonstrated a trend toward less bone loss than participants who received placebos or usual care. A significant difference in BMD decline was noted between both groups at the 3rd and 12th month post-medication. The subgroup analysis failed to show the superiority of intravenous bisphosphonate over oral administration. Regarding FES training, chronic SCI patients had 5.96% (95% CI, 2.08% to 9.84%), 7.21% (95%CI, 1.79% to 12.62%), and 9.56% (95% CI, 2.86% to 16.26%) increases in BMD at the 3rd, 6th, and 12th months post-treatment, respectively. The studies employing FES ≥5 days per week were likely to have better effectiveness than studies using FES ≤3 days per week. Conclusions Our meta-analysis indicated bisphosphonate administration early following SCI effectively attenuated sublesional bone loss. FES intervention for chronic SCI patients could significantly increase sublesional BMD near the site of maximal mechanical loading.

PREDICTORS OF LONG-TERM SURVIVAL AFTER STROKE IN TAIWAN

OBJECTIVE To determine the risk factors of long-term survival after stroke. DESIGN A prospective, hospital-based cohort study. SUBJECTS A total of 449 consecutive patients after acute stroke from 2 medical centres, within a 1-year period, were included. METHODS Dysphagia was confirmed with the water-swallow test within the first week after stroke. Data on co-morbidities and clinical risk factors were collected through chart review. Survival curves and independent risk factors were evaluated with Kaplan-Meier analysis and multivariate Cox proportion hazards analysis, respectively. RESULTS A total of 424 patients were followed for 10 years, and the survival was 54.2%. In univariate analysis, history of diabetes mellitus and recurrent stroke, dysphagia, urinary incontinence, cognitive impairment, tube feeding, dysarthria, and drooling were associated with higher mortality. In multivariate analysis, old age, history of recurrent stroke, and diabetes mellitus were independent predictors of long-term survival. The leading causes of death were cerebro-vascular diseases and malignancy during the 10-year post-stroke period. CONCLUSION Dysphagia was not an independent determinant of post-stroke survival. History of recurrent stroke and diabetes mellitus were independent predictors of long-term survival. These results suggest that differential treatment strategies should be used in the different stages of stroke.

Skeletal muscle mass adjusted by height correlated better with muscular functions than that adjusted by body weight in defining sarcopenia

Sarcopenia, characterized by low muscle mass and function, results in frailty, comorbidities and mortality. However, its prevalence varies according to the different criteria used in its diagnosis. This cross-sectional study investigated the difference in the number of sarcopenia cases recorded by two different measurement methods of low muscle mass to determine which measurement was better. We recruited 878 (54.2% female) individuals aged over 65 years and obtained their body composition and functional parameters. Low muscle mass was defined as two standard deviations below either the mean height-adjusted (hSMI) or weight-adjusted (wSMI) muscle mass of a young reference group. The prevalence of sarcopenia was 6.7% vs. 0.4% (male/female) by hSMI, and 4.0% vs. 10.7% (male/female) by wSMI. The κ coefficients for these two criteria were 0.39 vs. 0.03 (male/female), and 0.17 in all subjects. Serum myostatin levels correlated positively with gait speed (r = 0.142, p = 0.007) after adjustment for gender. hSMI correlated with grip strength, cardiopulmonary endurance, leg endurance, gait speed, and flexibility. wSMI correlated with grip strength, leg endurance, gait speed, and flexibility. Since hSMI correlated more closely with grip strength and more muscular functions, we recommend hSMI in the diagnosis of low muscle mass.

Transcription activation of myostatin by trichostatin A in differentiated C2C12 myocytes via ASK1‐MKK3/4/6‐JNK and p38 mitogen‐activated protein kinase pathways

Myostatin is a negative regulator of skeletal muscle mass. The pathways employed in modulating myostatin gene expression are scarcely known. We aimed to determine the signaling pathway of myostatin induction by a histone deacetylase (HDAC) inhibitor–trichostatin A (TSA) in differentiated C2C12 myocytes. TSA increased myostatin mRNA expression up to 40‐fold after treatment for 24 h, and induced myostatin promoter activity up to 3.8‐fold. Pretreatment with actinomycin D reduced the TSA‐induced myostatin mRNA by 93%, suggesting TSA‐induced myostatin expression mainly at the transcriptional level. Pretreatment with p38 MAPK (SB203580) and JNK (SP600125) inhibitors, but not ERK (PD98059) inhibitor, blocked TSA‐induced myostatin expression, respectively, by 72% and 43%. Knockdown of p38 MAPK by RNAi inhibited the TSA‐induced myostatin expression by 77% in C2C12 myoblasts. The protein levels of phosphorylated p38 MAPK, JNK, but not ERK, increased with TSA treatment in differentiated C2C12 cells. Direct activation of p38 MAPK and JNK by anisomycin in the absence of TSA increased myostatin mRNA by fourfold. The phosphorylated form of the kinase MKK3/4/6 and ASK1, upstream cascades of p38 MAPK and JNK, also increased with TSA treatment. We concluded that the induction of myostatin by TSA treatment in differentiated C2C12 cells is in part through ASK1‐MKK3/6‐p38 MAPK and ASK1‐MKK4‐JNK signaling pathways. Activation of p38 MAPK and JNK axis is necessary, but not sufficient for TSA‐induced myostatin expression. J. Cell. Biochem. 111: 564–573, 2010.

Comparison of disordered swallowing patterns in patients with recurrent cortical/subcortical stroke and first-time brainstem stroke.

OBJECTIVE To describe the disordered swallowing patterns in recurrent cortical/subcortical stroke and first-time brainstem stroke. DESIGN A retrospective study. SUBJECTS Forty-seven consecutive patients, 28 with recurrent cortical/subcortical stroke and 19 with first-time brainstem stroke, referred for dysphagic evaluation to the rehabilitation department of a medical centre. METHODS Thirty-five male and 12 female patients with a mean age of 62.0+/-11.5 years were included. The median post-stroke duration was 17.0 days. The records of clinical examination and a videofluoroscopic study of swallowing were collected through chart review. The percentages of abnormalities seen at clinical examination and videofluoroscopic swallowing study between recurrent cortical/subcortical stroke and first-time brainstem stroke patients were compared using a chi-square test. RESULTS The recurrent cortical/subcortical patients suffered from a higher rate of impaired tongue movement, drooling and aphasia at clinical examination and a higher percentage of swallowing abnormalities in oral-preparatory and oral phases in the videofluoroscopic swallowing study. The abnormal videofluoroscopic findings in first-time brainstem stroke patients predominantly occurred in the pharyngeal phase. Both groups had more difficulties swallowing thin barium than they did swallowing the thick and paste barium. CONCLUSION The recurrent cortical/subcortical stroke and first-time brainstem stroke patients show different manifestations in some parameters of both clinical examination and videofluoroscopic swallowing study.

Serum myostatin is reduced in individuals with metabolic syndrome.

Aims Myostatin is a negative regulator of skeletal muscle mass and may also modulate energy metabolism secondarily. We aim to investigate the relationship between serum myostatin and the metabolic variables in diabetic (DM) and non-diabetic subjects. Materials and Methods A cross-sectional study recruiting 246 consecutive DM patients and 82 age- and gender-matched non-diabetic individuals at a medical center was conducted. The variables of anthropometry and blood chemistry were obtained. Serum myostatin level was measured with enzyme immunoassay. Results DM group had lower serum myostatin compared with non-diabetics (7.82 versus 9.28 ng/ml, p<0.01). Sixty-two percent of the recruited individuals had metabolic syndrome (MetS). The patients with MetS had significantly lower serum myostatin than those without (7.39 versus 9.49 ng/ml, p<0.001). The serum myostatin level decreased with increasing numbers of the MetS components (p for trend<0.001). The patients with higher body mass index, larger abdominal girth, lower high-density lipoprotein cholesterol (HDL-C), and higher triglycerides had lower serum myostatin than those without. The serum myostatin level was independently negatively related to larger abdominal girth, higher triglycerides, and lower HDL-C after adjustment. The odds ratios for MetS, central obesity, low HDL-C, high triglycerides, and DM were 0.85, 0.88, 0.89, 0.85, and 0.92, respectively, when serum myostatin increased per 1 ng/mL, in the binary logistic regression models. Conclusions Lower serum myostatin independently associated with MetS, central obesity, low HDL-C, and high triglycerides after adjustment. Higher serum myostatin is associated with favorable metabolic profiles.

Myostatin and its association with abdominal obesity, androgen and follistatin levels in women with polycystic ovary syndrome

STUDY QUESTION What is the role of myostatin and its relationship with obesity, androgens and follistatin levels in women with polycystic ovary syndrome (PCOS)? SUMMARY ANSWERS: The myostatin level was positively correlated to the risk of abdominal obesity, but negatively associated with circulating levels of dehydroepiandrosterone sulfate (DHEAS) and follistatin in women with PCOS. WHAT IS KNOWN AND WHAT THIS PAPER ADDS Myostatin is a well-known negative regulator of skeletal muscle and is involved in metabolism; however, little is known about the role of myostatin in women with PCOS. In this study, we found that the myostatin level was positively related to the risk of abdominal obesity, but negatively related to the circulating levels of DHEAS and follistatin in women with PCOS. Such a relationship might imply a potential regulatory role of androgens and follistatin in the metabolism of skeletal muscle in women with PCOS. DESIGN A cross-sectional case-control study. PARTICIPANTS AND SETTING A total of 239 untreated, consecutive women with PCOS and 38 healthy volunteer women without PCOS were enrolled and studied in a tertiary medical center. MAIN RESULTS AND THE ROLE OF CHANCE Myostatin level was higher in women with PCOS than those without PCOS (16.6±15.6 and 14.2±9.7, P=0.025), but were not significantly different between non-obese women with and without PCOS after considering the effect of obesity (P=0.09). Stepwise multivariate regression analysis in women revealed that only the presence of PCOS (β=0.256, P=0.0001), total testosterone (β=0.159, P=0.031), DHEAS (β=-0.188, P=0.0003) and follistatin (β=-0.171, P=0.0001) levels were left in the final model and were significantly related to the myostatin level after considering all the explanatory variables. By using stepwise multivariate regression analysis, the total testosterone levels (β=0.196, P=0.003) were positively, but the DHEAS (β=-0.196, P<0.0001) and follistatin (β=-0.151, P=0.0001) levels were negatively, related to myostatin levels in women with PCOS after adjustment for age, anthropometric measurements, insulin sensitivity index and hormonal profiles. The high myostatin level was associated with the increased risk of abdominal obesity after further adjusting the androgens and follistatin levels in women with PCOS. LIMITATION, REASONS FOR CAUTION This study is a cross-sectional case-control design, and therefore, cannot answer the cause-effect relationship among the androgens, follistatin and myostatin levels. The small sample size and non-obese control group may also limit the application of the conclusion of the present study to general population other than women with PCOS. In addition, lack of data regarding muscle mass is another limitation in this study that prevents clarification of the relationship between myostatin, lean mass and obesity and therefore restricts the clinical application of the results. WIDER IMPLICATIONS OF THE FINDINGS Future studies to investigate the efficacy of exercise and lifestyle modification in treating women with PCOS should consider the myostatin, follistatin and androgen levels as well as the effect of muscle mass and BMI. STUDY FUNDING/COMPETING INTEREST This study was supported by grants NSC97-2314-B002-079-MY3, NSC98-2314-B002-105-MY3 and NSC 100-2314-B002-027-MY3 from the National Science Council of Taiwan. There is no competing interest declared in this study.

Is sarcopenia associated with depression? A systematic review and meta-analysis of observational studies.

Objectives to explore whether sarcopenia is associated with depression. Design electronic literature databases from PubMed, Scopus, Embase and Google Scholar were searched. A systematic review and meta-analysis of observational studies was conducted. Setting community and outpatient clinic. Participants people with and without diagnoses of sarcopenia. Measurements outcome measures of depression. Results about 15 articles were included, 5 of which were retrieved for narrative review. The crude odds ratios (ORs) between sarcopenia and depression were extracted from the remaining 10 studies, 6 of which also included adjusted ORs. Sarcopenia was associated with depression without adjusting covariates (crude OR, 1.640; 95% confidence interval (CI), 1.247-2.155). After adjusting for potential confounders such as age, gender, cognitive performance and physical activity, sarcopenia still demonstrated a significant positive association with depression (adjusted OR, 1.821; 95% CI, 1.160-2.859). A stratified analysis showed that the studies that used bioelectrical impedance analysis for measurement of body composition tended to have an elevated association between sarcopenia and depression compared with those that used dual-energy X-ray absorptiometry or equation estimation. Conclusion sarcopenia was independently associated with depression. The causal relationship between the two clinical conditions requires future validation with cohort studies.