A Pharmacogenomics-Based In Silico Investigation of Opioid Prescribing in Post-operative Spine Pain Management and Personalized Therapy.

Considering the variability in individual responses to opioids and the growing concerns about opioid addiction, prescribing opioids for postoperative pain management after spine surgery presents significant challenges. Therefore, this study undertook a novel pharmacogenomics-based in silico investigation of FDA-approved opioid medications. The DrugBank database was employed to identify all FDA-approved opioids. Subsequently, the PharmGKB database was utilized to filter through all variant annotations associated with the relevant genes. In addition, the dpSNP ( https://www.ncbi.nlm.nih.gov/snp/ ), a publicly accessible repository, was used. Additional analyses were conducted using STRING-MODEL (version 12), Cytoscape (version 3.10.1), miRTargetLink.2, and NetworkAnalyst (version 3). The study identified 125 target genes of FDA-approved opioids, encompassing 7019 variant annotations. Of these, 3088 annotations were significant and pertained to 78 genes. During variant annotation assessments (VAA), 672 variants remained after filtration. Further in-depth filtration based on variant functions yielded 302 final filtered variants across 56 genes. The Monoamine GPCRs pathway emerged as the most significant signaling pathway. Protein-protein interaction (PPI) analysis revealed a fully connected network comprising 55 genes. Gene-miRNA Interaction (GMI) analysis of these 55 candidate genes identified miR-16-5p as a pivotal miRNA in this network. Protein-Drug Interaction (PDI) assessment showed that multiple drugs, including Ibuprofen, Nicotine, Tramadol, Haloperidol, Ketamine, L-Glutamic Acid, Caffeine, Citalopram, and Naloxone, had more than one interaction. Furthermore, Protein-Chemical Interaction (PCI) analysis highlighted that ABCB1, BCL2, CYP1A2, KCNH2, PTGS2, and DRD2 were key targets of the proposed chemicals. Notably, 10 chemicals, including carbamylhydrazine, tetrahydropalmatine, Terazosin, beta-methylcholine, rubimaillin, and quinelorane, demonstrated dual interactions with the aforementioned target genes. This comprehensive review offers multiple strong, evidence-based in silico findings regarding opioid prescribing in spine pain management, introducing 55 potential genes. The insights from this report can be applied in exome analysis as a pharmacogenomics (PGx) panel for pain susceptibility, facilitating individualized opioid prescribing through genotyping of related variants. The article also points out that African Americans represent an important group that displays a high catabolism of opioids and suggest the need for a personalized therapeutic approach based on genetic information.

Disability-adjusted life years from bone and joint infections associated with antimicrobial resistance: an insight from the 2019 Global Burden of Disease Study.

PURPOSE: Bone and joint infections, complicated by the burgeoning challenge of antimicrobial resistance (AMR), pose significant public health threats by amplifying the disease burden globally. We leveraged results from the 2019 Global Burden of Disease Study (GBD) to explore the impact of AMR attributed to bone and joint infections in terms of disability-adjusted life years (DALYs), elucidating the contemporary status and temporal trends. METHODS: Utilizing GBD 2019 data, we summarized the burden of bone and joint infections attributed to AMR across 195 countries and territories in the 30 years from 1990 to 2019. We review the epidemiology of AMR in terms of age-standardized rates, the estimated DALYs, comprising years of life lost (YLLs) and years lived with disability (YLDs), as well as associations between DALYs and socio-demographic indices. RESULTS: The GBD revealed that DALYs attributed to bone and joint infections associated with AMR have risen discernibly between 1990 and 2019 globally. Significant geographical disparities and a positive correlation with socio-demographic indicators were observed. Staphylococcus aureus infections, Group A Streptococcus, Group B Streptococcus, Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, and Enterobacter-related bone and joint infections were associated with the highest DALYs because of a high proportion of antimicrobial resistance. Countries with limited access to healthcare, suboptimal sanitary conditions, and inconsistent antibiotic stewardship were markedly impacted. CONCLUSIONS: The GBD underscores the escalating burden of bone and joint infections exacerbated by AMR, necessitating urgent, multi-faceted interventions. Strategies to mitigate the progression and impact of AMR should emphasize prudent antimicrobial usage and robust infection prevention and control measures, coupled with advancements in diagnostic and therapeutic modalities.

A critical role for erythropoietin on vagus nerve Schwann cells in intestinal motility.

BACKGROUND: Dysmotility and postoperative ileus (POI) are frequent major clinical problems post-abdominal surgery. Erythropoietin (EPO) is a multifunctional tissue-protective cytokine that promotes recovery of the intestine in various injury models. While EPO receptors (EPOR) are present in vagal Schwann cells, the role of EPOR in POI recovery is unknown because of the lack of EPOR antagonists or Schwann-cell specific EPOR knockout animals. This study was designed to explore the effect of EPO via EPOR in vagal nerve Schwann cells in a mouse model of POI. RESULTS: The structural features of EPOR and its activation by EPO-mediated dimerization were understood using structural analysis. Later, using the Cre-loxP system, we developed a myelin protein zero (Mpz) promoter-driven knockout mouse model of Schwann cell EPOR (MpzCre-EPORflox/flox / Mpz-EPOR-KO) confirmed using PCR and qRT-PCR techniques. We then measured the intestinal transit time (ITT) at baseline and after induction of POI with and without EPO treatment. Although we have previously shown that EPO accelerates functional recovery in POI in wild type mice, EPO treatment did not improve functional recovery of ITT in POI of Mpz-EPOR-KO mice. CONCLUSIONS: To the best of our knowledge, this is the first pre-clinical study to demonstrate a novel mouse model of EPOR specific knock out on Schwan cells with an effect in the gut. We also showed novel beneficial effects of EPO through vagus nerve Schwann cell-EPOR in intestinal dysmotility. Our findings suggest that EPO-EPOR signaling in the vagus nerve after POI is important for the functional recovery of ITT.

Effects of 4-Aminopyridine on Combined Nerve and Muscle Injury and Bone Loss.

PURPOSE: Musculoskeletal injuries are common, and peripheral nerve injury (PNI) causes significant muscle and bone loss within weeks. After PNI, 4-aminopyridine (4-AP) improves functional recovery and muscle atrophy. However, it is unknown whether 4-AP has any effect on isolated traumatic muscle injury and PNI-induced bone loss. METHODS: A standardized crush injury was performed on the sciatic nerve and muscles in mice, and the mice were assigned to receive normal saline or 4-AP treatment daily for 21 days. The postinjury motor and sensory function recovery was assessed, injured muscles were processed for histomorphometry, and the tibial bone was scanned for bone density. RESULTS: 4-Aminopyridine significantly accelerated the postinjury motor and sensory function recovery, improved muscle histomorphometry, increased muscle satellite cell numbers, and shifted muscle fiber types after combined nerve and muscle injury. Importantly, the 4-AP treatment significantly reduced PNI-induced bone loss. In contrast, in the case of isolated muscle injury, 4-AP had no effect on functional recovery and bone density, but it improved muscle-specific histomorphometry to a limited extent. CONCLUSIONS: These findings demonstrate the potential beneficial effects of 4-AP on the recovery of muscle morphology and bone density after combined muscle and nerve injury. CLINICAL RELEVANCE: Nerve injuries frequently involve muscle and result in rapid muscle and bone atrophy. In this scenario, 4-AP, in addition to accelerating nerve functional recovery, might work as an adjunctive agent to improve the recovery of injured muscle and attenuate PNI-induced bone loss.

Erythropoietin-PLGA-PEG as a local treatment to promote functional recovery and neurovascular regeneration after peripheral nerve injury.

BACKGROUND: Traumatic peripheral nerve injury (TPNI) is a major medical problem with no universally accepted pharmacologic treatment. We hypothesized that encapsulation of pro-angiogenic erythropoietin (EPO) in amphiphilic PLGA-PEG block copolymers could serve as a local controlled-release drug delivery system to enhance neurovascular regeneration after nerve injury. METHODS: In this study, we synthesized an EPO-PLGA-PEG block copolymer formulation. We characterized its physiochemical and release properties and examined its effects on functional recovery, neural regeneration, and blood vessel formation after sciatic nerve crush injury in mice. RESULTS: EPO-PLGA-PEG underwent solution-to-gel transition within the physiologically relevant temperature window and released stable EPO for up to 18 days. EPO-PLGA-PEG significantly enhanced sciatic function index (SFI), grip strength, and withdrawal reflex post-sciatic nerve crush injury. Furthermore, EPO-PLGA-PEG significantly increased blood vessel density, number of junctions, and myelinated nerve fibers after injury. CONCLUSION: This study provides promising preclinical evidence for using EPO-PLGA-PEG as a local controlled-release treatment to enhance functional outcomes and neurovascular regeneration in TPNI.

Animal model detects early pathologic changes of Charcot neuropathic arthropathy.

Charcot neuropathic arthropathy is a degenerative, debilitating disease that affects the foot and ankle in patients with diabetes and peripheral neuropathy, often resulting in destruction, amputation. Proposed etiologies include neurotraumatic, inflammatory, and neurovascular. There has been no previous animal model for Charcot. This study proposes a novel rodent model of induced neuropathic arthropathy to understand the earliest progressive pathologic changes of human Charcot. High-fat-diet-induced obese (DIO) Wild-type C57BL/6J mice (n = 8, diabetic) and age-matched low-fat-diet controls (n = 6) were run on an inclined high-intensity treadmill protocol four times per week for 7 weeks to induce mechanical neurotrauma to the hind-paw, creating Charcot neuropathic arthropathy. Sensory function and radiologic correlation were assessed; animals were sacrificed to evaluate hindpaw soft tissue and joint pathology. With this model, Charcot-DIO mice reveals early pathologic features of Charcot neuropathic arthropathy, a distinctive subchondral microfracture callus, perichondral/subchondral osseous hypertrophy/osteosclerosis, that precedes fragmentation/destruction observed in human surgical pathology specimens. There is intraneural vacuolar-myxoid change and arteriolosclerosis. The DIO mice demonstrated significant hot plate sensory neuropathy compared (P < 0.01), radiographic collapse of the longitudinal arch in DIO mice (P < 0.001), and diminished bone density in DIO, compared with normal controls. Despite exercise, high-fat-DIO mice increased body weight and percentage of body fat (P < 0.001). This murine model of diet-induced obesity and peripheral neuropathy, combined with repetitive mechanical trauma, simulates the earliest changes observed in human Charcot neuropathic arthropathy, of vasculopathic-neuropathic etiology. An understanding of early pathophysiology may assist early diagnosis and intervention and reduce patient morbidity and mortality in Charcot neuropathic arthropathy.

Obligatory role of Schwann cell-specific erythropoietin receptors in erythropoietin-induced functional recovery and neurogenic muscle atrophy after nerve injury.

BACKGROUND: Erythropoietin (EPO) promotes myelination and functional recovery in rodent peripheral nerve injury (PNI). While EPO receptors (EpoR) are present in Schwann cells, the role of EpoR in PNI recovery is unknown because of the lack of EpoR antagonists or Schwann cell-specific EpoR knockout animals. METHODS: Using the Cre-loxP system, we developed a myelin protein zero (Mpz) promoter-driven knockout mouse model of Schwann cell EpoR (MpzCre-EpoRflox/flox , Mpz-EpoR-KO). Mpz-EpoR-KO and control mice were assigned to sciatic nerve crush injury followed by EPO treatment. RESULTS: EPO treatment significantly accelerated functional recovery in control mice in contrast to significantly reduced functional recovery in Mpz-EpoR-KO mice. Significant muscle atrophy was found in the injured hindlimb of EPO-treated Mpz-EpoR-KO mice but not in EPO-treated control mice. CONCLUSIONS: These preliminary findings provide direct evidence for an obligatory role of Schwann-cell specific EpoR for EPO-induced functional recovery and muscle atrophy following PNI.

Process Mapping Total Knee Arthroplasty: A Comparison of Instrument Designs.

BACKGROUND: Total knee arthroplasty (TKA) is commonly performed with proprietary, manual instrumentation provided by the surgical implant manufacturer. Registry studies and meta-analysis, with few outliers, have consistently shown similar functional outcomes and implant survival after TKA regardless of implant manufacturer, implant design, or surgical technique. We hypothesized that process mapping could identify areas for improvement in TKA instrumentation. METHODS: Seventeen TKA implant systems from 10 companies representing over 90% of all TKAs performed in the United States were evaluated. Instrumentation required for femoral, tibial, and patellar preparation was compared. The number of steps including surgical technician assembly steps, instrument handoffs, and surgeon steps were tabulated based off application of a standardized surgical flow, adjusted for manufacturer-recommended steps during completion of a TKA operation. RESULTS: Cruciate-retaining (CR) knee instrumentation in studied systems required 158-225 discrete steps and posterior-stabilized (PS) knees required 181-230 steps. With the fewest steps for femoral, tibial, and patellar instrumentation, CR and PS knee systems could be improved to 145 and 163 steps, respectively. The Arthrex iBalance and the Biomet Vanguard Microplasty required fewest steps among CR systems; the OrthoDevelopment Balanced and the Corin Unity required fewest steps among PS systems. CONCLUSIONS: Process mapping identified potential areas for improved instrumentation in all studied systems, suggesting the possibility to reduce operative steps broadly across the TKA industry. Patient outcomes were not evaluated by system. Future implant system design changes may do well to reduce unnecessary steps and instrumentation.

Peripheral nerve injury and myelination: Potential therapeutic strategies.

Traumatic peripheral nerve injury represents a major clinical and public health problem that often leads to significant functional impairment and permanent disability. Despite modern diagnostic procedures and advanced microsurgical techniques, functional recovery after peripheral nerve repair is often unsatisfactory. Therefore, there is an unmet need for new therapeutic or adjunctive strategies to promote the functional recovery in nerve injury patients. In contrast to the central nervous system, Schwann cells in the peripheral nervous system play a pivotal role in several aspects of nerve repair such as degeneration, remyelination, and axonal growth. Several non-surgical approaches, including pharmacological, electrical, cell-based, and laser therapies, have been employed to promote myelination and enhance functional recovery after peripheral nerve injury. This review will succinctly discuss the potential therapeutic strategies in the context of myelination following peripheral neurotrauma.

Novel FEMASK-score, a histopathologic assessment for destructive Charcot neuropathic arthropathy, reveals intraneural vasculopathy and correlates with progression and best treatment.

BACKGROUND: Charcot neuropathic arthropathy is a debilitating, rapidly destructive degenerative joint disease that occurs in diabetic, neuropathic midfoot. Clinicoradiologic assessment for Charcot neuropathic arthropathy previously relied on Eichenholtz stage. There is limited histopathologic data on this entity. We wanted to independently develop a histopathologic scoring system for Charcot neuropathic arthropathy. DESIGN: Retrieval of surgical pathology midfoot specimens from Charcot patients (2012-2019) were analyzed to evaluate joint soft tissue and bone. Considering progression from large (≥half 40× hpf) to small (

4-Aminopyridine attenuates muscle atrophy after sciatic nerve crush injury in mice.

INTRODUCTION: We recently demonstrated the beneficial effects of 4-aminopyridine (4-AP), a potassium channel blocker, in enhancing remyelination and recovery of nerve conduction velocity and motor function after sciatic nerve crush injury in mice. Although muscle atrophy occurs very rapidly after nerve injury, the effect of 4-AP on muscle atrophy and intrinsic muscle contractile function is largely unknown. METHODS: Mice were assigned to sciatic nerve crush injury and no-injury groups and were followed for 3, 7, and 14 days with/without 4-AP or saline treatment. Morphological, functional, and transcriptional properties of skeletal muscle were assessed. RESULTS: In addition to improving in vivo function, 4-AP significantly reduced muscle atrophy with increased muscle fiber diameter and contractile force. Reduced muscle atrophy was associated with attenuated expression of atrophy-related genes and increased expression of proliferating stem cells. DISCUSSION: These findings provide new insights into the potential therapeutic benefits of 4-AP against nerve injury-induced muscle atrophy and dysfunction. Muscle Nerve 60: 192-201, 2019.

Erythropoietin accelerates functional recovery after moderate sciatic nerve crush injury.

INTRODUCTION: Erythropoietin (EPO) has been identified as a neuroregenerative agent. We hypothesize that it may accelerate recovery after crush injury and may vary with crush severity. METHODS: Mice were randomized to mild, moderate, or severe crush of the sciatic nerve and were treated with EPO or vehicle control after injury. The sciatic function index (SFI) was monitored over the first week. Microstructural changes were analyzed by immunofluorescence for neurofilament (NF) and myelin (P0 ), and electron microscopy was used to assess ultrastructural changes. RESULTS: In moderate crush injuries, EPO significantly improved SFI at 7 days post-injury, an effect not observed with other severity levels. Increases in the ratio of P0 to NF were observed after EPO treatment in moderate crush injuries. Electron microscopy demonstrated endothelial cell hypertrophy in the EPO group. CONCLUSIONS: EPO accelerates recovery in moderately crushed nerves, which may be through effects on myelination and vascularization. Injury severity may influence the efficacy of EPO. Muscle Nerve 56: 143-151, 2017.

Elbow Instability: Anatomy, Biomechanics, Diagnostic Maneuvers, and Testing.

The elbow comprises a complex of bony and ligamentous stabilizers that provide both primary and secondary constraints to elbow instability. Through trauma and overuse, classic instability patterns arise by loss of these important stabilizers. The diagnosis of elbow instability can made using specific examination maneuvers and testing to diagnose the clinical pattern. This article reviews the elbow's unique anatomy and biomechanical characteristics and these are applied when reviewing the maneuvers and testing used to diagnose elbow instability.

Differences in the Treatment of Distal Radius Fractures by Hand Fellowship Trained Surgeons: A Study of ABOS Candidate Data.

PURPOSE: The management of distal radius fractures differs based on the nature of the fracture and the experience of the surgeon. We hypothesized that patients requiring surgical intervention would undergo different procedures when in the care of a surgeon with subspecialty training in hand surgery as compared with surgeons with no subspecialty training in hand surgery. METHODS: We queried the ABOS database for case log information submitted for part II of the ABOS examination. Queries for all codes involved with distal radius fracture management were combined with associated codes for the management of median nerve neuropathy, triangular fibrocartilage complex tears, ulnar shaft, and styloid fractures. Hand fellowship trained orthopedic surgeons were compared with those completing other fellowships and non-fellowship trained orthopedic surgeons during their board collection period. RESULTS: During the study period, 2,317 orthopedic surgeons reported treatment of 15,433 distal radius fractures. Of these surgeons, 411 had hand fellowship training. On a per surgeon basis, fellowship trained hand surgeons operatively treated more multifragment intra-articular distal radius fractures than their non-hand fellowship trained counterparts (5.3 vs 1.2). Additional procedures associated with the management of distal radius fractures were also associated with the fellowship training of the treating surgeon. CONCLUSIONS: Among orthopedic surgeons taking part II of the ABOS certifying examination, differences exist in the type, management, and reporting of distal radius fractures among surgeons with different areas of fellowship training. CLINICAL RELEVANCE: This study describes the association of hand surgery fellowship training on the choice of intervention for distal radius fractures and associated conditions.

Is medial elbow pain correlated with cubital tunnel syndrome? An electrodiagnostic study.

INTRODUCTION: Medial elbow pain is often considered to be a symptom associated with ulnar neuropathy at the elbow (UNE). We examined the relationship between medial elbow pain and a positive electrodiagnostic (EDx) test result for UNE. METHODS: We performed a retrospective review of 884 patients referred for EDx evaluation of UNE. Regression models were used to determine the odds ratios between clinical findings and a positive EDx result for UNE. RESULTS: Patients reported medial elbow pain in 44.3% of cases. Clinical factors that correlated with a positive EDx study result for UNE included male gender, small and ring finger numbness, ulnar intrinsic weakness, and age. Medial elbow pain was negatively correlated with a positive EDx result. CONCLUSIONS: This study demonstrates a negative correlation between medial elbow pain and a positive EDx result for UNE. Medial elbow pain should not be considered a clear diagnostic symptom of UNE.

A Peculiar Primary Paraganglioma of the Distal Thumb.

A paraganglioma is a highly vascularized neuroendocrine tumor most commonly found within the adrenal gland as a pheochromocytoma. Extra-adrenal paragangliomas are frequently located in the head, neck, thorax, and abdomen. We report the first documented case of a primary paraganglioma found within the appendicular skeleton. Only 2 additional cases of paragangliomas in the extremities have been documented, one in the soft tissue of the forearm and other within the median nerve. Our patient underwent amputation of the distal phalanx, with no sign of recurrence at greater than 1 year of follow-up. Because of the geographic and clinical similarity to a benign enchondroma, radiographic imaging alone may not be sufficient to rule out malignancies inside bones. Thus paraganglioma should remain in the differential and immunohistochemistry is both vital and necessary to confirm the diagnosis. Vigilant and appropriate follow-up is necessary to detect metastases early in these patients.

Erythropoietin Enhanced Recovery After Traumatic Nerve Injury: Myelination and Localized Effects.

PURPOSE: We previously found that administration of erythropoietin (EPO) shortens the course of recovery after experimental crush injury to the mouse sciatic nerve. The course of recovery was more rapid than would be expected if EPO's effects were caused by axonal regeneration, which raised the question of whether recovery was instead the result of promoting remyelination and/or preserving myelin on injured neurons. This study tested the hypothesis that EPO has a direct and local effect on myelination in vivo and in vitro. METHODS: Animals were treated with EPO after standard calibrated sciatic nerve crush injury; immunohistochemical analysis was performed to assay for myelinated axons. Combined in vitro neuron-Schwann cell co-cultures were performed to assess EPO-mediated effects directly on myelination and putative protective effects against oxidative stress. In vivo local administration of EPO in a fibrin glue carrier was used to demonstrate early local effects of EPO treatment well in advance of possible neuroregenerative effects. RESULTS: Systemic Administration of EPO maintained more in vivo myelinated axons at the site of nerve crush injury. In vitro, EPO treatment promoted myelin formation and protected myelin from the effects of nitric oxide exposure in co-cultures of Schwann cells and dorsal root ganglion neurons. In a novel, surgically applicable local treatment using Food and Drug Administration-approved fibrin glue as a vehicle, EPO was as effective as systemic EPO administration at time points earlier than those explainable using standard models of neuroregeneration. CONCLUSIONS: In nerve crush injury, EPO may be exerting a primary influence on myelin status to promote functional recovery. CLINICAL RELEVANCE: Mixed injury to myelin and axons may allow the opportunity for the repurposing of EPO for use as a myeloprotective agent in which injuries spare a requisite number of axons to allow early functional recovery.

Radiographic Parameters to Predict Union After Volar Percutaneous Fixation of Herbert Type B1 and B2 Scaphoid Fractures.

PURPOSE: To study the angle of screw placement in relation to the scaphoid fracture plane and its effect on union after percutaneous fixation of scaphoid waist fractures. METHODS: Twenty-four consecutive scaphoid waist fractures were retrospectively evaluated for the orientation of screws in relation to the fracture plane using a method in which the sum-of-smaller angles (SSA) in 3 different radiographs were used to correlate with time to fracture union. RESULTS: All but one patient achieved union after percutaneous fixation of the scaphoid. Another patient required revision surgery within the study period for inadequate fixation. A shortened time to union was significantly correlated to larger SSA. CONCLUSIONS: SSA may be a reasonable predictor of union after percutaneous fixation of scaphoid waist fracture. It can be reliably calculated using plain radiographs. An SSA of 190° or more correlated with union by 8 weeks postoperatively.

What Is the Impact of Comorbidities on Self-rated Hand Function in Patients With Symptomatic Trapeziometacarpal Arthritis?

BACKGROUND: The thumb trapeziometacarpal joint is one of the most common sites of arthritic degeneration prompting specialty care. Surgical treatment algorithms are based on radiographic arthritic progression. However, the pain and disability attributable to trapeziometacarpal arthritis do not correlate with arthritic stage, and depression has independently predicted poorer self-rated hand function both at baseline and after treatment in patients' atraumatic hand conditions. QUESTIONS/PURPOSES: (1) Does thumb trapeziometacarpal osteoarthritis impact both self-perceived general health and hand function? (2) Do depression and other comorbid conditions differentially impact patient-rated hand function based on the presence or absence of symptomatic trapeziometacarpal arthritis? (3) How do disease-specific, patient demographics and comorbid conditions impact self-reported hand function in patients with trapeziometacarpal osteoarthritis? METHODS: This cross-sectional study compared patients with symptomatic trapeziometacarpal osteoarthritis (n = 47) with matched control subjects without a symptomatic hand condition (n = 47). All participants self-reported medical (including depression) and musculoskeletal comorbidities and completed the SF-36 and the Michigan Hand Questionnaire (MHQ). Bivariate statistical analyses contrasted the patients with trapeziometacarpal osteoarthritis to control subjects. Linear regression modeling determined the impact of subject demographic data, comorbidity burden, and examination findings on total MHQ scores in patients with trapeziometacarpal arthritis. RESULTS: Patients with scored trapeziometacarpal osteoarthritis indicated poorer perceived general health on the SF-36 categories of limitations resulting from physical health (52 ± 29 versus 71 ± 31, mean difference 19 [95% confidence interval {CI}, 7-31], p = 0.003) and limitations resulting from emotional problems (50 ± 27 versus 67 ± 50, mean difference 17 [95% CI, 3-33], p = 0.022) compared with control subjects. Self-reported depression was associated with worse hand function (total MHQ score) in patients with trapeziometacarpal arthritis (69 ± 20 versus 49 ± 22: mean difference -20 [95% CI, -5 to-36], p = 0.012) but not in control patients (90 ± 13 versus 84 ± 20: mean difference -5 [95% CI, -8 to 19], p = 0.404). In multivariate modeling, depression (ß -20, [95% CI, -5 to -34], p = 0.009) and upper extremity comorbidities (ß -25, [95% CI, -10 to -40], p = 0.002) were both associated with reduced total MHQ scores in patients with trapeziometacarpal osteoarthritis, and those factors accounted for 34% of the variance in the MHQ score. CONCLUSIONS: When interpreting patient-rated hand disability in patients presenting with symptomatic trapeziometacarpal osteoarthritis, scores should be interpreted after accounting for the presence of depression and upper extremity comorbidities. LEVEL OF EVIDENCE: Level III, prognostic study.

Hand Sensibility, Strength, and Laxity of High-Level Musicians Compared to Nonmusicians.

PURPOSE: To determine whether musicians have more sensitive, stronger, and flexible hands than nonmusicians. METHODS: A total of 100 musicians and 100 control subjects were assessed for 2-point discrimination, Semmes-Weinstein monofilament light touch, grip and pinch strength, and laxity. Musicians were included if enrolled as instrumental performance majors at a 4-year accredited conservatory of music. Nonmusician controls were university students who never or rarely engaged in playing an instrument. All subjects were between the ages of 18 and 28. The exclusion criterion was history of any hand condition, trauma, surgery, or diabetes. Statistical analyses were carried out using the t test, analysis of variance, and correlation coefficients as appropriate. RESULTS: High-level musicians in our cohort showed the same handedness (dominance) as the general population. The musicians were weaker than the nonmusicians. Male musicians were significantly weaker in pinch and grip bilaterally than nonmusicians, whereas female musicians were significantly weaker only in grip on the right/dominant side. Two-point discrimination was significantly less in musicians for the left/nondominant index, ring, and small fingers, and the right/dominant small and dominant index finger. Semmes-Weinstein testing was significantly better for the right/dominant digits, including the thumb, but not the left digits with the exception of the ring and nondominant middle and ring. There was no difference in laxity between the 2 groups. CONCLUSIONS: High-level musicians have, in general, more sensitive but weaker hands than nonmusicians, but the differences seem small and may not be clinically important.