Human Motor Endplate Survival after Chronic Peripheral Nerve Injury.

Objective: Degeneration of motor endplates (MEPs) in denervated muscle is thought to be a key factor limiting functional regeneration after peripheral nerve injury (PNI) in humans. However, there is currently no paradigm to determine MEP status in denervated human muscle to estimate likelihood of reinnervation success. Here, we present a quantitative analysis of MEP status in biopsies of denervated muscles taken during nerve repair surgery and ensuing functional recovery. Methods: This is a retrospective single-surgeon cohort study of patients (n=22) with upper extremity PNI confirmed with electromyography (EMG), treated with nerve transfers. Muscle biopsies were obtained intra-operatively from 10 patients for MEP morphometric analysis. Age at time of surgery ranged from 22-77 years and time from injury to surgery ranged from 2.5-163 months. Shoulder range of motion (ROM) and Medical Research Council (MRC) scores were recorded pre-op and at final follow-up. Results: Surviving MEPs were observed in biopsies of denervated muscles from all patients, even those greater than six months from injury. Average postoperative ROM improvement (assessed between 6-9 months post-surgery) was: forward flexion 84.3 ± 51.8°, abduction 62.5 ± 47.9°, and external rotation 25.3 ± 28.0°. Interpretation: While it is believed that MEP degeneration 6 months post-injury prevents reinnervation, this data details MEP persistence beyond this timepoint along with significant functional recovery after nerve surgery. Accordingly, persistence of MEPs in denervated muscles may predict the extent of functional recovery from nerve repair surgery.

Preoperative Muscle Biopsy to Assess Motor End Plate Integrity as a Predictor for Successful Nerve Transfer: A Case Report.

CASE: A 60-year-old right-hand-dominant man was referred for persistent right deltoid weakness, lateral shoulder numbness, and severe functional deficit 3 months after undergoing proximal humerus open reduction and internal fixation with plate and fibular strut allograft. Deltoid muscle biopsy demonstrated motor end plate (MEP) degeneration. After partial radial-to-axillary nerve transfer, repeat deltoid muscle biopsy revealed successful regeneration of MEPs with reinnervation of deltoid confirmed with postnerve transfer electromyography. CONCLUSION: Selective nerve transfer can successfully rescue a denervated target muscle from further degeneration by restoration of healthy MEPs.

Surgeon-specific factors have a larger impact on decision-making for the management of proximal humerus fractures than patient-specific factors: a prospective cohort study.

BACKGROUND: There is significant variability both in how proximal humerus fractures (PHFs) are treated and the ensuing patient outcomes. The purpose of this study was to investigate which surgeon- and patient-specific factors contribute to decision-making in the treatment of adult PHFs. We hypothesized that orthopedic sub-specialty training creates inherent bias and plays an important role in management algorithms for PHFs. METHODS: We performed a prospective cohort investigation in 2 groups of surgeons-traumatologists (N = 25) and shoulder & elbow/sports surgeons (SES) (N = 26)-and asked them to provide treatment recommendations for 30 distinct clinical cases with standardized radiographic and clinical data. This is a population-based sample of surgeons who take trauma call and treat PHFs with different sub-specializations and practice settings including academic, hospital-employed, and private. Surgeons characterized based on subspecialty (trauma vs. SES), experience level (>10 vs. ≤10-years), and employment type (hospital- vs. non-hospital-employed). Chi-square analyses, logistic mixed-effects modeling, and relative importance analysis were used to evaluate the data. RESULTS: Of the patient-specific factors, we found that the management of PHFs is largely dependent on initial radiographs obtained. Traumatologists were more likely to offer open reduction internal fixation (ORIF) and less likely to offer arthroplasty: 69% ORIF (traumatologists) vs. 51% ORIF (SES, P < .001), 8% arthroplasty (traumatologists) vs. 17% (SES, P < .001). Traumatologists were less likely to change from operative (either ORIF or arthroplasty) to non-operative management compared to SES surgeons when presented with additional patient demographic data. Surgeon-specific factors contributed to more than one-half of the variability in decision-making of PHF management while patient-specific factors contributed to about one-third of the variability in decision-making. CONCLUSIONS: As physicians strive to advance the treatment for PHFs and optimize patient outcomes, our findings highlight the complex overlap between surgeon-, fracture-, and patient-specific factors in the final decision-making process.

Return to Play After Revision Anterior Shoulder Stabilization: A Systematic Review.

BACKGROUND: Revision shoulder stabilizations are becoming increasingly common. Returning to play after revision shoulder stabilizations is important to patients. PURPOSE: To evaluate the return-to-play rate after revision anterior shoulder stabilization using arthroscopic, open, coracoid transfer, or free bone block procedures. STUDY DESIGN: Systematic review; Level of evidence, 4. METHODS: All English-language studies published between 2000 and 2020 that reported on return to play after revision anterior shoulder stabilization were reviewed. Clinical outcomes that were evaluated included rate of overall return to play, level of return to play, and time to return to play. Study quality was evaluated using the Downs and Black quality assessment score. RESULTS: Eighteen studies (1 level 2; 17 level 4; mean Downs and Black score, 10.1/31) on revision anterior shoulder stabilization reported on return to play and met inclusion criteria (7 arthroscopic, 5 open, 3 Latarjet, and 3 bony augmentation), with a total of 564 revision cases (mean age, 27.9 years; 84.1% male). The weighted mean length of follow-up was 52.5 months. The overall weighted rate of return to play was 80.1%. The weighted mean rate of return to play was 84.0% (n = 153) after arthroscopic revision, 91.5% (n = 153) after open revision, 88.1% (n = 149) after Latarjet, and 73.8% (n = 65) after bone augmentation. The weighted mean rate of return to same level of play was 69.7% for arthroscopic revision, 70.0% for open revision, 67.1% for Latarjet revision, and 61.8% after bone block revision. There were 5 studies that reported on time to return to play, with a weighted mean of 7.75 months (4 arthroscopic) and 5.2 months (1 Latarjet). The weighted mean rates of complication (for studies that provided it) were 3.3% after arthroscopic revision (n = 174), 3.5% after open revision (n = 110), 9.3% after Latarjet revision (n = 108), and 45.8% after bone block revision (n = 72). CONCLUSION: Revision using open stabilization demonstrated the highest return-to-play rate. Revision using Latarjet had the quickest time to return to play but had higher complication rates. When evaluated for return to same level of play, arthroscopic, open, and Latarjet had similar rates, and bone block had lower rates. The choice of an optimal revision shoulder stabilization technique, however, depends on patient goals. Higher-quality studies are needed to compare treatments regarding return to play after revision shoulder stabilization.

Reverse shoulder arthroplasty in rheumatoid arthritis: survival and outcomes.

BACKGROUND: Despite its potential biomechanical advantages, reverse shoulder arthroplasty (RSA) is still considered to be particularly high risk in rheumatoid patients who are osteoporotic and immunodeficient. Our purpose was to report prosthesis survival, complications, and outcomes of RSA in patients with rheumatoid arthritis (RA) at minimum 5-year follow-up. METHODS: We conducted a retrospective multicenter study including 65 consecutive primary RSAs performed in 59 patients with RA between 1991 and 2010. We excluded rheumatoid patients with previous failed anatomic shoulder arthroplasty. Age at surgery averaged 69 years (range, 46-86 years). A structural bone grafting was performed in 18 cases (45%), using the humeral head in 15 cases (BIO-RSA technique), the iliac crest in 2 cases (Norris technique), and an allograft in 1 case. The mean follow-up was 92 months (range, 60-147 months) or until revision surgery. RESULTS: Revision-free survivorship, using Kaplan-Meier curves, was 96% at 7 years. Two patients had revision surgeries for infections, with associated glenoid loosening in 1 case. No humeral loosening was recorded. The mean adjusted Constant score improved from 36% ± 23% preoperatively to 90% ± 26% postoperatively, and mean Subjective Shoulder Value improved from 21% ± 13% to 85% ± 12%, respectively (P < .001). Active anterior elevation increased from 65° ± 43° to 132° ± 27°, active external rotation increased from 10° ± 26° to 22° ± 27°, and internal rotation improved from buttocks to waist (P < .001). Stable fixation of the baseplate was achieved in all cases (including the 6 patients with end-stage RA), and we did not observe bone graft nonunion or resorption. Preoperative radiologic pattern (centered, ascending, or destructive), presence of acromial fractures or tilt (4 cases, 10%), and scapular notching (55%) on final radiographs were not found to influence outcomes or complication rate. Patients with absent/atrophied teres minor had lower functional results. Overall, 95% of the patients were satisfied with the procedure. CONCLUSION: RSA is a safe and effective procedure for the treatment of RA patients, with a low risk of complications and low rate of revision, regardless of the radiologic presentation and stage of the disease. Rheumatoid patients undergoing primary RSA, with or without glenoid bone grafting, can expect a revision-free survival rate of 96% at 7-year follow-up. RSA offers the benefit of solving 2 key problems encountered in rheumatoid shoulders: glenoid bone destruction and rotator cuff deficiency.

Muscle stem cells and rotator cuff injury.

The incidence of reinjury after treatment of rotator cuff tears (RCTs) remains very high despite the variety of nonoperative treatments and the high volume of surgical interventions performed. Muscle stem cells (MuSCs), also known as satellite cells, have risen to the forefront of rotator cuff tear research as a potential adjuvant therapy to aid unsatisfactory surgical outcomes. MuSCs are adult stem cells exhibiting the capacity to proliferate and self-renew, both symmetrically and asymmetrically. As part of this niche, they have been shown to adopt an activated phenotype in response to musculoskeletal injury and decrease their cellular populations during aging, implicating them as key players in both pathologic and normal physiological processes. While commonly connected to the regenerative phase of muscle healing, MuSCs also have the potential to differentiate into adverse morphologies. For instance, if MuSCs differentiate into adipocytes, the ensuing fatty infiltration serves as an obstacle to proper muscle healing and has been associated with the failure of surgical management of RCTs. With the potential to both harm and heal, we have identified MuSCs as a key player in RCT repair. To better understand this dichotomy, the following review will identify key studies regarding the morphology, function, and behavior of MuSCs with respect to RCTs and healing.

Outcomes After Revision Anterior Shoulder Stabilization: A Systematic Review.

BACKGROUND: Primary shoulder stabilization is successful, but there continues to be a risk of recurrence after operative repair, particularly in the young athlete. It is important for surgeons to understand the outcomes after various revision stabilization techniques to best counsel patients and manage expectations. PURPOSE: To analyze recurrent instability and revision surgery rates in patients who underwent revision anterior glenohumeral stabilization procedures with either arthroscopic repair, open repair, coracoid transfer, free bone block, or capsular reconstruction. STUDY DESIGN: Systematic review; Level of evidence, 4. METHODS: We performed a systematic review of level 2 to 4 evidence studies using PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Clinical studies of revision anterior glenohumeral stabilization (arthroscopic repair, open repair, coracoid transfer, free bone block, or capsular reconstruction) with a minimum 2-year follow-up were analyzed. The rate of recurrent instability, rate of revision surgery, patient-reported outcomes, and range of motion were extracted and reported. Study methodological quality was evaluated using the Downs and Black quality assessment score. RESULTS: A total of 37 studies met inclusion criteria and were available for analysis: 20 studies evaluated arthroscopic repair, 8 evaluated open repair, 5 evaluated Latarjet procedure, 3 evaluated bone block, and 2 evaluated capsular reconstruction. There was 1 study included in both arthroscopic and Latarjet procedures, for a total of 1110 revision cases. There was 1 level 2 study, and the remainder were level 3 or 4 with poor Downs and Black scores. Participants analyzed were most commonly young (weighted mean age, 26.1 years) and male (78.4%). The weighted mean clinical follow-up after revision surgery was 47.8 months. The weighted mean rate of recurrent instability was 3.8% (n = 245) after the Latarjet procedure, 13.4% (n = 260) after open repair, 16.0% (n = 531) after arthroscopic repair, 20.8% (n = 72) after bone block, and 31.0% (n = 35) after capsular reconstruction. The weighted mean rate of additional revision surgery was 0.0% after bone block, 0.02% after the Latarjet procedure, 9.0% after arthroscopic repair, 9.3% after open repair, and 22.8% after capsular reconstruction. Patient-reported outcomes and objective measures of range of motion and strength improved with all revision techniques. CONCLUSION: The current review identifies a deficiency in the literature pertaining to consistent meaningful outcomes and the effect of bone loss after revision shoulder stabilization. Published studies demonstrate, however, that revision shoulder stabilization using arthroscopic, open, coracoid transfer, or bone block techniques yielded satisfactory objective and patient-reported outcomes. The Latarjet procedure exhibited the lowest recurrent instability rate. This study confirms that recurrent instability remains a common problem, despite revision shoulder stabilization. The quality of research in revision shoulder stabilization remains poor, and higher quality studies are needed to establish best practices for treatment of this complex problem.

Local versus distal transplantation of human neural stem cells following chronic spinal cord injury.

BACKGROUND CONTEXT: Previous studies have demonstrated functional recovery of rats with spinal cord contusions after transplantation of neural stem cells adjacent to the site of acute injury. PURPOSE: The purpose of the study was to determine if the local or distal injection of neural stem cells can cause functional difference in recovery after chronic spinal cord injury. STUDY DESIGN/SETTING: Twenty-four adult female Long-Evans hooded rats were randomized into four groups, with six animals in each group: two experimental and two control groups. Functional assessment was measured after injury and then weekly for 6 weeks using the Basso, Beattie, and Bresnahan locomotor rating score. Data were analyzed using two-sample t test and linear mixed-effects model analysis. METHODS: Posterior exposure and laminectomy at the T10 level was used. Moderate spinal cord contusion was induced by the Multicenter Animal Spinal Cord Injury Study Impactor with 10-g weight dropped from a height of 25 mm. Experimental subjects received either a subdural injection of human neural stem cells (hNSCs) locally at the injury site or intrathecal injection of hNSCs through a separate distal laminotomy 4 weeks after injury. Controls received control media injection either locally or distally. RESULTS: A statistically significant functional improvement in subjects that received hNSCs injected distally to the site of injury was observed when compared with the control (p=.042). The difference between subjects that received hNSCs locally and the control did not reach statistical significance (p=.085). CONCLUSIONS: The transplantation of hNSCs into the contused spinal cord of a rat led to significant functional recovery of the spinal cord when injected distally but not locally to the site of chronic spinal cord injury.

Inhibition of chondrocyte and synovial cell death after exposure to commonly used anesthetics: chondrocyte apoptosis after anesthetics.

BACKGROUND: An intra-articular injection of local anesthetics is a common procedure for diagnostic and therapeutic purposes. It has been shown that these agents are toxic to articular cartilage and synovial tissue in a dose- and time-dependent fashion, and in some cases, they may lead to postarthroscopic glenohumeral chondrolysis (PAGCL). However, the role of apoptosis in cell death is still unclear, and the potential role of apoptosis inhibition in minimizing chondrocyte and synovial cell death has not been reported. PURPOSE: (1) To quantify the degree of apoptotic cell death in chondrocytes and synovial cells exposed to local anesthetics, and (2) to determine whether caspase inhibition could reduce cell death. STUDY DESIGN: Controlled laboratory study. METHODS: Human chondrocytes and synovial cells were expanded in vitro and exposed to normal saline, 0.5% bupivacaine, 0.5% ropivacaine, 1% lidocaine, or 1:1000 epinephrine for 90 minutes. Apoptosis was then detected at 1, 3, 5, and 7 days after exposure using terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end labeling (TUNEL) and immunohistochemistry. Apoptosis was then inhibited using the pan-caspase inhibitor z-vad-fmk. Results were normalized to normal saline controls and analyzed by generalized regression models and pairwise confidence intervals. RESULTS: Analysis of cumulative chondrocyte apoptosis relative to controls after anesthetic exposure demonstrated more than 60% cell death with 0.5% bupivacaine and 1:1000 epinephrine. The greatest chondroprotective effect of caspase inhibition occurred with 0.5% ropivacaine. Similarly, in synovial cells, epinephrine was also very cytotoxic; however, 1% lidocaine induced the most apoptosis. Synovial cells exposed to 0.5% ropivacaine were again most sensitive to protective caspase inhibition. CONCLUSION: Local anesthetics induce chondrocyte and synovial cell apoptosis in a time-dependent fashion, with peak apoptosis occurring 5 days after exposure. Both chondrocytes and synovial cells are most sensitive to caspase inhibition after exposure to 0.5% ropivacaine. CLINICAL RELEVANCE: Apoptosis inhibition may be an effective strategy in minimizing chondrocyte and synovial cell death after exposure to anesthetics. Further investigation is clinically warranted.

Primary cilia mediate mechanosensing in bone cells by a calcium-independent mechanism.

Primary cilia are sensory organelles that translate extracellular chemical and mechanical cues into cellular responses. Bone is an exquisitely mechanosensitive organ, and its homeostasis depends on the ability of bone cells to sense and respond to mechanical stimuli. One such stimulus is dynamic fluid flow, which triggers biochemical and transcriptional changes in bone cells by an unknown mechanism. Here we report that bone cells possess primary cilia that project from the cell surface and deflect during fluid flow and that these primary cilia are required for osteogenic and bone resorptive responses to dynamic fluid flow. We also show that, unlike in kidney cells, primary cilia in bone translate fluid flow into cellular responses in bone cells independently of Ca(2+) flux and stretch-activated ion channels. These results suggest that primary cilia might regulate homeostasis in diverse tissues by allowing mechanical signals to alter cellular activity via tissue-specific pathways. Our identification of a mechanism for mechanotransduction in bone could lead to therapeutic approaches for combating bone loss due to osteoporosis and disuse.