Spine Injuries Sustained After Falls While Crossing the U.S.-Mexico Border.

This study is to report the demographics, incidence, and patterns of spinal injuries associated with border crossings resulting from a fall from a significant height. A retrospective cohort study was performed at a Level I trauma center from January 2016 to December 2021 to identify all patients who fell from a significant height while traversing the U.S.-Mexico border and were subsequently admitted. A total of 448 patients were identified. Of the 448 patients, 117 (26.2%) had spine injuries and 39 (33.3%) underwent operative fixation. Females had a significantly higher incidence of spine injuries (60% vs. 40%; p < 0.00330). Patients with a spine fracture fell from a higher median fall height (6.1 vs. 4.6 m; p < 0.001), which resulted in longer median length of stay (LOS; 12 vs. 7 days; p < 0.001), greater median Injury Severity Score (ISS; 20 vs. 9; p < 0.001), and greater relative risk (RR) of ISS >15 (RR = 3.2; p < 0.001). Patients with operative spine injuries had significantly longer median intensive care unit (ICU) LOS than patients with non-operative spine injuries (4 vs. 2 days; p < 0.001). Patients with spinal cord injuries and ISS >15 sustained falls from a higher distance (median 6.1 vs. 5.5 m) and had a longer length of ICU stay (median 3 vs. 0 days). All patients with operative spine injuries had an ISS >15 relative to 50% of patients with non-operative spine injuries (median ISS 20 vs. 15; p < 0.001). Patients with spine trauma requiring surgery had a higher incidence of head (RR = 3.5; p 0.0353) and chest injuries (RR = 6.0; p = 0.0238), but a lower incidence of lower extremity injuries (RR = 0.5; p < 0.001). Thoracolumbar injuries occurred in 68.4% of all patients with spine injuries. Patients with operative spine injuries had a higher incidence of burst fracture (RR = 15.5; p < 0.001) and flexion-distraction injury (RR = 25.7; p = 0.0257). All patients with non-operative spine injuries had American Spinal Injury Association (ASIA) D or E presentations, and patients with operative spine injuries had a higher incidence of spinal cord injury: ASIA D or lower at time of presentation (RR = 6.3; p < 0.001). Falls from walls in border crossings result in significant injuries to the head, spine, long bones, and body, resulting in polytrauma casualties. Falls from higher height were associated with a higher frequency and severity of spinal injuries, greater ISS, and longer ICU length of stay. Operative spine injuries, compared with non-operative spine injuries, had longer ICU length of stay, greater ISS, and different fracture morphology. Spine surgeons and neurocritical care teams should be prepared to care for injuries associated with falls from height in this unique population.

Acromial Morphology Does Not Correlate with Age at Time of Rotator Cuff Tear: A Cross-Sectional Study.

Background: The purpose of this study was to determine if scapular anatomy differs between younger and older patients with atraumatic full-thickness supraspinatus tears. Methods: The critical shoulder angle, acromial index and lateral acromial angle were measured on standardized radiographs of two groups of patients who underwent arthroscopic repair of full-thickness degenerative supraspinatus tears. Group 1 included 61 patients under the age of 50 years while Group 2 included 45 patients over the age of 70 years. The mean critical shoulder angle, acromial index, and lateral acromial angle were then compared. Results: There was no significant difference between groups for the critical shoulder angle (p = .433), acromial index (p = .881) or lateral acromial angle (p = .263). Interobserver reliability for critical shoulder angle, acromial index, and lateral acromial angle was nearly perfect (interclass correlation coefficient 0.996, 0.996, 0.998, respectively). No significant correlation existed between age and critical shoulder angle (p = .309), acromial index (p = .484) or lateral acromial angle (p = .685). Discussion: While the critical shoulder angle and acromial index were found to be high and in the typical range for patients with rotator cuff tears in both groups, there were no significant differences in acromial morphology between Groups 1 and 2.

Injuries Sustained With Falls From Height in Crossing the United States-Mexico Border at a Level I Trauma Center: A Prospective Cohort Study.

INTRODUCTION: The US Department of Homeland Security has reported increases in encounters and apprehensions at the US Southwest border for the past several years. The purposes of this study were to assess the demographics, patterns of injuries, and surgical interventions, associated with falls from height along the US-Mexico border. METHODS: A prospective cohort study was conducted at a Level I trauma center from January 2016 through December 2021 of all patients who fell from height crossing the US-Mexico border and presented with injuries requiring admission. RESULTS: A total of 448 patients were admitted with a median age of 30 years (interquartile range [IQR] 16, range 6 to 65). Monthly frequency of admissions increased markedly with a median of 18.5 (IQR 5.3) in 2021. Patients presented with limited health data, and comorbidities were identified in 111 patients (24.7%). Median height fallen was 5.5 m (18 ft). Patients sustaining a fall from ≥ 5.5 m were markedly more likely to have an Injury Severity Score (ISS) of > 15. Median length of stay was 9 days (IQR 11). There were a total of 1,066 injuries with 723 extremity and pelvic; 236 spine; and 107 head or neck, face, thorax, or abdominal injuries. Median ISS was 9.0 (IQR 7, range 1 to 75, 33% > 15). Tibial plafond fracture and spine injury were markedly associated with longer lengths of stay and ISS > 15. All injuries resulted in 635 separate surgical events and 930 procedures. Clinical follow-up occurred in 55 patients (12.2%), with median duration of 28 days (range 6 days to 8 months). DISCUSSION: Injuries associated with border crossings and falls from height were serious and increased in frequency. As the US policy on border security evolves, surgeons in these regions should be prepared to handle the associated injuries and sequelae. Prevention of these serious and debilitating injuries should be undertaken to decrease the burden of disease.

Correction of Cubitus Varus Using Computer-Assisted Hexapod Multiplanar External Fixators: A Report of 3 Cases.

CASE: Three male patients, 8-, 13-, and 18-year-old, all developed posttraumatic cubitus varus elbow deformity after distal humerus supracondylar fractures. Each underwent a distal humerus osteotomy with application of a hexapod external fixator to gradually correct the deformity. CONCLUSION: In patients with cubitus varus malunion, the stability of the hexapod external fixation, percutaneous nature of the osteotomy, and availability of running a residual computer-assisted program provides a consistent technique for deformity correction.

Traumatic Finger Amputation in the U.S. Military.

INTRODUCTION: Finger amputations can lead to loss of work time and suboptimal function, particularly in the active duty military. There is a paucity of epidemiologic and outcome data for these injuries. The purposes of this study are to define key demographic data pertaining to transphalangeal finger amputations in the U.S. Military and to assess epidemiological data to define risk factors for medical readiness following finger injuries. MATERIALS AND METHODS: This was a retrospective review of the military electronic medical record of encounters between 2016 and 2019 with traumatic transphalangeal amputation ICD 10 codes S68.5 (thumb) and S68.6 (finger). Primary outcomes included median military occupational activity limitation length, ability to return to duty, and medical separation from the military. RESULTS: A total of 235 patients were included in the final dataset. 221 (94.0%) of these service members were able to return to full duty, although 14 (6.0%) underwent medical separation from the military because of their finger injuries. The median limited duty timeline was 6 weeks. Significant risk factors identified that led to increased rates of medical separation were the use of tobacco (odds ratio [OR] of 5.53, 95% CI 1.21-25.29), junior enlisted status (OR of 5.51, 95% CI 1.67-18.17), and thumb or index finger involvement (OR of 3.50, 95% CI 1.13-10.83). CONCLUSIONS: Within a physically high-demand population, traumatic finger amputation can limit duties and may lead to medical separation from service. Traumatic finger amputations are common and often require 6 weeks of restricted short-term disability, particularly in a tobacco-using, young, physically active cohort.

Qualitative analysis of randomized controlled trials informing recommendations for venous thromboembolism prophylaxis after distal lower extremity injuries.

Purpose: The purpose of this study is to assess the quality of evidence to stratify recommendations for chemoprophylaxis following distal lower extremity trauma. Methods: Literature review identified primary studies investigating venous thromboembolism (VTE) chemoprophylaxis following traumatic injury distal to the knee. Inclusion criteria were randomized controlled trials in adult patients treated with and without operative intervention. Each primary study was assessed by the Consolidated Standards of Reporting Trials 2010 checklist and Modified Coleman methodology score. Results: Literature review resulted in 462 studies, of which 9 met inclusion and exclusion criteria. All studies included low molecular weight heparin as a treatment group with 2 (22%) also including a treatment group with a direct factor Xa inhibitor. Five studies (56%) used placebo as a control group. The mean Modified Coleman Methodology score was 63% (range 51%-72%), a categorical rating of Fair. The mean Consolidated Standards of Reporting Trials score was 78% (range 56%-97%). Most studies (89%) screened all asymptomatic subjects for deep venous thrombosis. Statistical significance in VTE incidence among prophylactic treatment groups was not achieved in 78%. Conclusions: Development of consensus for VTE prophylaxis recommendations following traumatic injury distal to the knee is complicated by heterogenous study populations, low incidence of VTE in study populations, and inconsistent definitions of clinically important VTE. Low molecular weight heparin is not consistently superior for preventing VTE. Chemoprophylaxis should be considered on an individual basis in the presence of additional risk factors, although an externally validated, evidence-based risk assessment tool does not currently exist.Level of Evidence: IV, therapeutic.

Ten-Year Trends in Level of Evidence in Hand Surgery.

BACKGROUND: The purposes of this study were to analyze the trends in Oxford level of evidence (LOE), LOE of most-cited articles, and association between LOE and journal impact factor (IF) and SCImago Journal Rank (SJR) over a 10-year period (2009-2018) in 3 prominent hand surgery journals, specifically HAND, Journal of Hand Surgery (American Volume) (JHS), and Journal of Hand Surgery (European Volume) (JHSE). METHODS: All articles published from 2009 to 2018 in HAND, JHS, and JHSE were reviewed for assigned or available LOE. Data were pooled and analyzed for trends in LOE; relationship among IF, SJR, and LOE; and citation density. RESULTS: A total of 3921 total publications were tabulated from 2009 to 2018, with the majority of studies being level V (1700, 43%) and fewer studies being level I (146, 4%). Over the 10-year study period, there was no significant change in frequency of level I studies for any journal. HAND trended significantly toward higher LOE, JHS trended toward higher LOE, and JHSE trended toward decreased LOE without significance. Among all journals, the annual number of articles and the average LOE were independent significant predictors of IF and SJR. Statistically significant correlations were found between citation density and LOE for JHS and HAND. CONCLUSIONS: Higher quality evidence is becoming more prevalent in the hand surgery literature over the past 10 years. Annual articles, average LOE, and level I and II and level IV articles were significant predictors of increasing IF and SJR.

Post-operative Immobilization in Total Elbow Arthroplasty for Rheumatoid Arthritis: A Systematic Review of Outcomes.

The purpose of this analysis is to determine the effect of length of immobilization following total elbow arthroplasty (TEA) for rheumatoid arthritis on the outcomes, complications, and survival of the implant. A review of TEA literature was performed. Post-operative motion was categorized into three groups: no post-operative immobilization (group 1), short-term 2-5 days immobilization (group 2), and extended 7-14 days immobilization (group 3). Thirty-six articles reporting on 43 studies involving 2,346 elbows in 2015 patients were included. Total complication rates were 23% at 8.9 years for group 1, 31% at 6.8 years for group 2, and 31% at 6.9 years for group 3. Survival rates were 79% at 15.3 years, 75% at 10.4 years, and 92% at 9.1 years for each group, respectively. Total complication rates were lowest in elbows without post-operative immobilization. However, survival rates were greatest in elbows with extended post-operative immobilization. (Journal of Surgical Orthopaedic Advances 31(4):209-217, 2022).

The Association of H-index and Academic Rank Among Full-time Academic Foot and Ankle Surgeons Affiliated with Fellowship Programs.

The purpose of this study is to investigate the association between Hirsch index (h-index) and academic rank among foot and ankle surgeons affiliated with American Orthopaedic Foot and Ankle Society (AOFAS) fellowship programs. The total number of publications, academic rank, years in practice, fellowship training pedigree, and h-indices of 176 foot and ankle surgeons from 48 AOFAS fellowship programs were recorded, and statistical analysis was performed. We found a strong association between total number of publications and h-index. Number of publications, h-index and training program affiliation were associated with higher academic rank, except at the chair/director position. Overall, h-index is a stronger predictor of academic rank than number of publications. The results of this study suggest that h-index and total number of publications are associated with a higher academic rank for full-time foot and ankle fellowship affiliated surgeons. (Journal of Surgical Orthopaedic Advances 31(4):263-267, 2022).

Bone Morphogenetic Protein in Scaphoid Nonunion: A Systematic Review.

Background Scaphoid nonunion can lead to carpal collapse and osteoarthritis, a painfully debilitating problem. Bone morphogenetic protein (BMP) has been successfully implemented to augment bone healing in other circumstances, but its use in scaphoid nonunion has yielded conflicting results. Case Description The purpose of this study is to assess the outcomes and complications of scaphoid nonunion treated surgically with BMP. Literature Review A literature review of all available journal articles citing the use of BMP in scaphoid nonunion surgery from 2002 to 2019 was conducted. We included studies that used BMP as an adjunct to surgical treatment for scaphoid nonunions in both the primary and revision settings with computed tomography determination of union. Demographic information, dose of BMP, tobacco use, outcomes, and complications were recorded. A total of 21 cases were included from four different studies meeting inclusion criteria. Clinical Relevance The union rates were 90.5% overall, 100% for primary surgeries, and 77.8% for revision surgeries. Five patients (24%) experienced 11 complications, including four cases (19%) of heterotrophic ossification. Use of BMP in scaphoid nonunion surgery resulted in a 90.5% overall union rate but was also associated with complications such as heterotopic ossification. All included studies used BMP to augment bone graft, screw or wire fixation, or a combination of methods. The efficacy of BMP in scaphoid nonunion is unclear, and a sufficiently powered, randomized controlled trial is needed to determine optimal fixation methods, dosing, and morbidity of the use of BMP. Level of Evidence This is a Level IC, therapeutic interventional study.

Variation in state and federal reimbursement in the United States in the treatment of upper extremity fractures.

BACKGROUND: Medicare and Medicaid are 2 of the largest government-run health care programs in the United States. Although Medicare reimbursement is determined at the federal level by the Centers for Medicare & Medicaid Services, Medicaid reimbursement rates are set by each individual state. The purpose of this study is to compare Medicaid reimbursement rates with regional Medicare reimbursement rates for 12 orthopedic procedures performed to treat common fractures of the upper extremity. METHODS: Twelve orthopedic procedures were selected and their Medicare reimbursement rates were collected from the 2020 Medicare Physician Fee Schedule. Medicaid reimbursement rates were obtained from each state's physician fee schedule. Reimbursement rates were then compared by assessing the ratio of Medicaid to Medicare, the dollar difference in Medicaid to Medicare reimbursement, and the difference per relative value unit. The range of variation in Medicaid reimbursement and Medicare wage index-adjusted Medicaid reimbursement was calculated. Comparisons in reimbursement were calculated using coefficient of variation and Student t tests to evaluate the differences between the mean Medicaid and Medicare reimbursements. Two-sample coefficient of variation testing was used to determine whether dispersion in Medicare and Medicaid reimbursement rates differed significantly. RESULTS: There was significant difference in reimbursement rates between Medicare and Medicaid for all 12 procedures, with Medicare reimbursing on average 46.5% more than Medicaid. In 40 states, Medicaid reimbursed less than Medicare for all 12 procedures. Regarding the dollar difference per relative value unit, Medicaid reimbursed on average $18.03 less per relative value unit than Medicare. The coefficient of variation for Medicaid reimbursement rates ranged from 0.26-0.33. This is in stark contrast with the significantly lower variability observed in Medicare reimbursement, which ranged from 0.06-0.07. CONCLUSION: Our findings highlight the variation in reimbursement that exists among state Medicaid programs for 12 orthopedic procedures commonly used to treat fractures of the upper extremity. Furthermore, average Medicaid reimbursement rates were significantly lower than Medicare rates for all 12 procedures. Such discrepancies in reimbursement may act as a barrier, impeding many Medicaid patients from accessing timely orthopedic care.

Dorsal Bridge Plate for Distal Radius Fractures: A Systematic Review.

PURPOSE: This study presents patient demographics, injury characteristics, outcomes, and complications associated with dorsal bridge plating (DBP) in the treatment of distal radius fractures. METHODS: A literature search performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines identified 206 articles, 12 of which met inclusion criteria, accounting for 310 patients. Included articles contained the results of DBP for treatment of distal radius fractures with reported outcomes between 1988 and 2018. Data were pooled and analyzed focusing on patient demographics, as well as 3 primary outcomes of complications, range of motion (ROM), and Disabilities of the Arm, Shoulder, and Hand (DASH) and QuickDASH scores. RESULTS: Average age was 55 years, median follow-up was 24 months, and the most common use was in comminuted (92%) intra-articular (92%) distal radius fracture caused by fall (58%), or motor vehicle collision or motorcycle collision (27%). A minority of patients had open fractures (16%) and most were cases of polytrauma (65%). Median time from placement to DBP removal was 17 weeks (mean, 119 days). At final follow-up, mean wrist ROM was 45° flexion, 50° extension, 75° pronation, and 73° supination. Mean DASH score was 26.1, and mean QuickDASH score was 19.8. The overall rate for any complication was 13%; the most common was hardware failure (3%) followed by symptomatic malunion or nonunion (3%), and persistent pain after hardware removal (2%). CONCLUSIONS: Dorsal bridge plating was found to be used most commonly in intra-articular, comminuted distal radius fractures with overall functional wrist ROM, moderate patient-reported disability, and a 13% complication rate at follow-up. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

Prospective Single-Blinded Randomized Controlled Trial Comparing Pericapsular Injection Versus Lumbar Plexus Peripheral Nerve Block for Hip Arthroscopy.

BACKGROUND: Hip arthroscopy has become the standard for the operative treatment of symptomatic femoroacetabular impingement. Given the high levels of postoperative pain associated with hip arthroscopy, optimal analgesia is critical to ensure patient comfort and safety after discharge. PURPOSE/HYPOTHESIS: Our purpose was to perform a single-blinded randomized controlled trial comparing the use of pericapsular injection versus lumbar plexus blockade for postoperative pain control after arthroscopic surgery on the hip. We hypothesized that pericapsular injection would provide equivalent pain relief to that of lumbar plexus blockade while minimizing adverse effects and alleviating the dependence on a qualified individual to administer. STUDY DESIGN: Randomized controlled trial; Level of evidence, 1. METHODS: A total of 64 consecutive patients undergoing hip arthroscopy were prospectively assessed over a 6-month period between 2017 and 2018. Patients were randomly allocated to 1 of 2 groups: 32 patients received a lumbar plexus blockade by a single anesthesiologist, while 32 patients received a pericapsular injection of 30 mL of ropivacaine and 12 mg of morphine. Postoperative pain in the postanesthesia care unit (PACU) as measured using the numeric rating scale, time to discharge, PACU morphine equivalents, and adverse effects were collected by PACU staff. Postoperative day 1 and 2 narcotic use was obtained through a telephone call with the patient on postoperative day 3. RESULTS: We found no statistically significant difference in PACU pain scores at all time points, although there was a trend toward lower pain for patients receiving a pericapsular injection. PACU and short-term narcotic demand did not vary across the 2 arms. Time to discharge from the PACU did not differ. There were no major adverse events reported for either intervention. CONCLUSION: Pericapsular injection provides equivalent analgesia when compared with lumbar plexus blockade. It is a safe intervention that allows for efficient postoperative analgesia for patients undergoing hip arthroscopy. REGISTRATION: ClinicalTrials.gov ID: NCT03244631.

miR-206 enforces a slow muscle phenotype.

Striated muscle is a highly specialized collection of tissues with contractile properties that vary according to functional needs. Although muscle fiber types are established postnatally, lifelong plasticity facilitates stimulus-dependent adaptation. Functional adaptation requires molecular adaptation, which is partially provided by miRNA-mediated post-transcriptional regulation. miR-206 is a muscle-specific miRNA enriched in slow muscles. We investigated whether miR-206 drives the slow muscle phenotype or is merely an outcome. We found that miR-206 expression increases in both physiological (including female sex and endurance exercise) and pathological conditions (muscular dystrophy and adrenergic agonism) that promote a slow phenotype. Consistent with that observation, the slow soleus muscle of male miR-206-knockout mice displays a faster phenotype than wild-type mice. Moreover, left ventricles of male miR-206 knockout mice have a faster myosin profile, accompanied by dilation and systolic dysfunction. Thus, miR-206 appears to be necessary to enforce a slow skeletal and cardiac muscle phenotype and to play a key role in muscle sexual dimorphisms.

Primary and Revision Circumferential Labral Reconstruction for Femoroacetabular Impingement in Athletes: Return to Sport and Technique.

PURPOSE: To determine return-to-play rates and hip-specific outcomes in athlete hips with femoroacetabular impingement syndrome treated with circumferential labral reconstruction (CLR). METHODS: All consecutive patients who underwent CLR from January through December 2016 performed by the senior surgeon with complete 2-year outcome scores were identified. The hips of 57 non-athletes who underwent CLR were excluded from analysis, as were 165 patients who underwent labral repair and 4 patients who underwent labral debridement. Outcome measures were completed by patients within 1 week prior to surgery and between 22 and 26 months postoperatively. Thirty patients met the inclusion criteria for this study. All 30 participated in regular, competitive athletic events and had magnetic resonance arthrogram-confirmed labral tears, and nonsurgical measures had failed. Of the 30 patients, 5 (16.7%) participated in cutting sports; 5 (16.7%), asymmetrical or overhead sports; 4 (13.3%), contact sports; 13 (43.3%), endurance sports; and 3 (10.0%), flexibility sports. Moreover, 25 of 30 (83.3%) were high-level athletes. Both primary (n = 23) and revision (n = 7) procedures were included. RESULTS: As determined by the International Hip Outcome Tool 12 score, 28 of 30 patients (93.3%) met the patient acceptable symptomatic state whereas 30 of 30 (100%) achieved substantial clinical benefit and exceeded the minimal clinically important difference for their operative hip. In addition, 23 of 30 patients (76.6%) met the patient acceptable symptomatic state whereas 30 of 30 (100%) achieved substantial clinical benefit and exceeded the minimal clinically important difference for the operative hip as determined by the visual analog scale pain score. Of 30 patients, 26 (86.7%) were able to return to play. The mean time to return to play was 6.6 months (standard deviation, 2.4 months). CONCLUSIONS: Two-year outcomes in this population of athletes undergoing CLR for femoroacetabular impingement syndrome show a statistically and clinically significant improvement in patient-reported outcomes, a statistically and clinically significant decrease in pain, and an overall return-to-play rate of 86.7%. LEVEL OF EVIDENCE: Level IV, therapeutic case series.

Surgical Repair of Acute TFCC Injury.

Triangular fibrocartilage complex tears are a common source of ulnar-sided wrist pain and distal radioulnar joint instability. Symptoms recalcitrant to conservative management or injuries in high-demand athletes may indicate surgical management. Both open and arthroscopic techniques offer improvements in objective measures, patient-centered outcome scores, and return to work, but may be complicated by nerve irritation, persistent wrist instability, and pain. Recently developed knotless arthroscopic techniques are not well studied but may limit morbidity.

Capitolunate Arthrodesis: A Systematic Review.

PURPOSE: To compile and review the indications, outcomes, and complications of capitolunate arthrodesis (CLA). METHODS: We performed a literature search identifying 33 articles, 6 of which met inclusion criteria, including 80 patients. Included publications contained the results of CLA with minimum 12-month follow-up between 2000 and 2018. Data were pooled and analyzed focusing on the primary outcomes of union and complications. RESULTS: Average age of patients was 48 years (range, 22-86 years), median follow-up was 34 months (range, 12-198 months), and most common indication was scaphoid nonunion advanced collapse (59%). Nearly half underwent a concomitant triquetrum excision (49%). Most patients were pain-free (78%) and returned to work (92%). Grip strength and visual analog pain scale both improved after CLA. Whereas 96% fused within a reported 42 to 210 days (median, 70 days), 11% of patients had complications including nonunion (3.8%) and loose hardware (6.3%). The reoperation rate was 14%, including wrist arthrodeses and wrist arthroplasty. CONCLUSIONS: Capitolunate arthrodesis is a feasible option for scapholunate advanced collapse and scaphoid nonunion advanced collapse wrists with complications similar to those encountered in 4-corner arthrodesis. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

miR-1/206 downregulates splicing factor Srsf9 to promote C2C12 differentiation.

BACKGROUND: Myogenesis is driven by specific changes in the transcriptome that occur during the different stages of muscle differentiation. In addition to controlled transcriptional transitions, several other post-transcriptional mechanisms direct muscle differentiation. Both alternative splicing and miRNA activity regulate gene expression and production of specialized protein isoforms. Importantly, disruption of either process often results in severe phenotypes as reported for several muscle diseases. Thus, broadening our understanding of the post-transcriptional pathways that operate in muscles will lay the foundation for future therapeutic interventions. METHODS: We employed bioinformatics analysis in concert with the well-established C2C12 cell system for predicting and validating novel miR-1 and miR-206 targets engaged in muscle differentiation. We used reporter gene assays to test direct miRNA targeting and studied C2C12 cells stably expressing one of the cDNA candidates fused to a heterologous, miRNA-resistant 3' UTR. We monitored effects on differentiation by measuring fusion index, myotube area, and myogenic gene expression during time course differentiation experiments. RESULTS: Gene ontology analysis revealed a strongly enriched set of putative miR-1 and miR-206 targets associated with RNA metabolism. Notably, the expression levels of several candidates decreased during C2C12 differentiation. We discovered that the splicing factor Srsf9 is a direct target of both miRNAs during myogenesis. Persistent Srsf9 expression during differentiation impaired myotube formation and blunted induction of the early pro-differentiation factor myogenin as well as the late differentiation marker sarcomeric myosin, Myh8. CONCLUSIONS: Our data uncover novel miR-1 and miR-206 cellular targets and establish a functional link between the splicing factor Srsf9 and myoblast differentiation. The finding that miRNA-mediated clearance of Srsf9 is a key myogenic event illustrates the coordinated and sophisticated interplay between the diverse components of the gene regulatory network.

Dispelling the Myth of Work-Related de Quervain's Tenosynovitis.

De Quervain's Tenosynovitis (DQT) is a common condition characterized by pain about the dorsal-radial aspect of the wrist, just proximal to the radial styloid. The condition is precipitated by a thickened first dorsal compartment and its tendons. The impression that DQT is caused from work-related injury is misdirected, as no study has established an association between hand usage at work or trauma with DQT. Physicians should exercise caution when discussing the causes and natural history of DQT with symptomatic patients.