Interleukin-15 facilitates muscle regeneration through modulation of fibro/adipogenic progenitors.

BACKGROUND: Chronic muscle injury is characteristics of fatty infiltration and fibrosis. Recently, fibro/adipogenic progenitors (FAPs) were found to be indispensable for muscular regeneration while were also responsible for fibrosis and fatty infiltration in muscle injury. Many myokines have been proven to regulate the adipose or cell proliferation. Because the fate of FAPs is largely dependent on microenvironment and the regulation of myokines on FAPs is still unclear. We screened the potential myokines and found Interleukin-15 (IL-15) may regulate the fatty infiltration in muscle injury. In this study, we investigated how IL-15 regulated FAPs in muscle injury and the effect on muscle regeneration. METHODS: Cell proliferation assay, western blots, qRT-PCR, immunohistochemistry, flow cytometric analysis were performed to investigate the effect of IL-15 on proliferation and adipogensis of FAPs. Acute muscle injury was induced by injection of glycerol or cardiotoxin to analyze how IL-15 effected on FAPs in vivo and its function on fatty infiltration or muscle regeneration. RESULTS: We identified that the expression of IL-15 in injured muscle was negatively associated with fatty infiltration. IL-15 can stimulate the proliferation of FAPs and prevent the adipogenesis of FAPs in vitro and in vivo. The growth of FAPs caused by IL-15 was mediated through JAK-STAT pathway. In addition, desert hedgehog pathway may participate in IL-15 inhibiting adipogenesis of FAPs. Our study showed IL-15 can cause the fibrosis after muscle damage and promote the myofiber regeneration. Finally, the expression of IL-15 was positively associated with severity of fibrosis and number of FAPs in patients with chronic rotator cuff tear. CONCLUSIONS: These findings supported the potential role of IL-15 as a modulator on fate of FAPs in injured muscle and as a novel therapy for chronic muscle injury.

Effectiveness and safety of endoscopic versus open carpal tunnel decompression.

PURPOSE: To evaluate the effectiveness and safety of endoscopic carpal tunnel release (ECTR) and open carpal tunnel release (OCTR) using a meta-analysis of data from randomized controlled trials. MATERIALS AND METHODS: Electronic searches of the Cochrane Register of Controlled Trials (CENTRAL, Issue 11 of 12, Nov 2012), PUBMED (1980 to Dec 2012), and EMBASE (1980 to Dec 2012) were used to identify randomized controlled trials that evaluated endoscopic vs open methods for treatment of carpal tunnel syndrome. Studies to be used were independently identified by two researchers. The methodological quality of the studies was assessed by the Cochrane Collaboration tool for assessing risk of bias. RESULTS: Fifteen randomized controlled trials involving 1,596 hands were included. Based on the Cochrane Collaboration tool for assessing risk of bias, four studies were rated as high quality, five studies were rated as moderate quality, and six were rated as low quality. Our meta-analysis indicated that ECTR resulted in better recovery of pinch strength, earlier time of return to work, but a higher rate of reversible nerve problems (including neurapraxia and numbness) than OCTR. ECTR also resulted in a lower rate of irreversible nerve damage (P > 0.05), wound problems (including wound infection, wound hematoma and wound dehiscence) and reflex sympathetic dystrophy (P > 0.05) compared with OCTR. Our meta-analysis revealed no obvious statistical differences in relief of symptoms (pain and paraesthesia), recovery of grip strength and reoperation rate. CONCLUSION: Our meta-analysis of available randomized controlled trials demonstrated that ECTR and OCTR were similar in relief of symptoms, but ECTR resulted in better recovery of function and earlier return to work and was safer than OCTR.

Surgical interventions for treating radial head fractures in adults.

BACKGROUND: Radial head fractures are the most common type of elbow fracture and can severely affect the function of the elbow. There is uncertainty and controversy about when surgery is indicated as well as what type of surgical intervention is best. OBJECTIVES: To assess the effects of surgical interventions for treating radial head fractures in adults. We aimed to compare surgical versus non-surgical treatment, and different methods of surgical intervention. SEARCH METHODS: We searched the Cochrane Bone, Joint and Muscle Trauma Group Specialised Register (May 2012), the Cochrane Central Register of Controlled Trials (The Cochrane Library; 2012 Issue 4), MEDLINE (1946 to May 2012), EMBASE (1980 to 2012 Week 19) and trial registers (November 2011). No language restrictions were applied. SELECTION CRITERIA: All randomised and quasi-randomised controlled trials evaluating surgical interventions for treating radial head fractures. DATA COLLECTION AND ANALYSIS: Two review authors independently selected trials, assessed risk of bias and extracted data. Where appropriate, results were pooled. MAIN RESULTS: We included three randomised controlled trials, involving a total of 251 participants. All three trials were at high risk of performance bias reflecting the fact that surgeons could not be blinded. One trial was at low risk of selection bias but was undermined by a high attrition bias, in part resulting from post-randomisation exclusions. There were incomplete details of methodology for the other two trials, which usually resulted in unclear risk of bias judgements.Two trials compared radial head replacement with open reduction and internal fixation (ORIF) for treating Mason type III radial head fractures. The trial authors reported outcomes at a mean of 2.8 years and 15 months respectively. There were significant differences between the two groups in favour of radial head replacement in the Broberg and Morrey elbow scores (92.1 versus 72.4, mean difference (MD) 19.70; 95% confidence interval (CI) 15.64 to 23.76; one trial, 45 participants), excellent or good Broberg and Morrey elbow scores (33/36 versus 16/31, risk ratio (RR) 1.88; 95% CI 1.27 to 2.77; two trials), and overall adverse events (6/36 versus 15/31, RR 0.33; 95% CI 0.14 to 0.77; two trials). No statistically significant difference was found between the two groups in any of the reported individual adverse events.One trial compared biodegradable pins with standard metal screws in treating radial head fractures of AO-classification 21 B2. The two types of fixation devices yielded similar results, with no significant between-group differences in the Broberg and Morrey scores (93.3 versus 90.9, MD 2.40; 95% CI -0.10 to 4.90), excellent or good Broberg and Morrey elbow scores (72/74 versus 56/61, RR 1.06; 95% CI 0.97 to 1.15), and adverse events (13/82 versus 16/82, RR 0.81; 95% CI 0.42 to 1.58) at two-year follow-up. AUTHORS' CONCLUSIONS: Only tentative conclusions can be drawn from the available evidence in this review. Compared with ORIF, there was some evidence that radial head replacement had better elbow function and fewer adverse events for Mason type III radial head fractures in the short term. However, the evidence is of low quality and it is unknown whether these results would apply in the longer term or more generally. Using biodegradable implants may be as good as metallic implants for fixation of some usually more stable fractures but more evidence is needed to confirm this. There is a need for good quality evidence for addressing the areas of uncertainty for the surgical treatment of radial head fractures.

Treatment of compartment syndrome of the thigh associated with acute renal failure after the Wenchuan earthquake.

Compartment syndrome of the thigh is a rare emergency often treated operatively. The purpose of this study was to evaluate the effects of nonoperative treatment for compartment syndrome of the thigh associated with acute renal failure after the 2008 Wenchuan earthquake. Nonoperative treatment, which primarily involves continuous renal replacement therapy, was performed in 6 patients (3 men and 3 women) who presented with compartment syndrome of the thigh associated with acute renal failure. The mean mangled extremity severity score (MESS) and laboratory data regarding renal function were analyzed before and after treatment, and the clinical outcome was evaluated at 17-month follow-up. Laboratory data regarding renal function showed improvements. All 6 patients survived with the affected lower limbs intact after nonoperative treatment. Follow-up revealed active knee range of motion and increased muscle strength, as well as a recovery of sensation. A positive linear correlation was found between MESS and the time required to achieve a reduction in swelling, as well as the time required for the recovery of sensation and knee range of motion (r>0.8; P<.05). Satisfactory clinical outcomes were obtained in patients with compartment syndrome of the thigh associated with acute renal failure.Urine alkalization, electrolyte and water balance, and continuous renal replacement therapy have played an important role in saving lives and extremities. Nonoperative treatment should be considered in the treatment of compartment syndrome of the thigh associated with acute renal failure.