Single nucleus and spatial transcriptomic profiling of healthy human hamstring tendon.

The molecular and cellular basis of health in human tendons remains poorly understood. Among human tendons, hamstring tendon has markedly low pathology and can provide a prototypic healthy tendon reference. The aim of this study was to determine the transcriptomes and location of all cell types in healthy hamstring tendon. Using single nucleus RNA sequencing, we profiled the transcriptomes of 10 533 nuclei from four healthy donors and identified 12 distinct cell types. We confirmed the presence of two fibroblast cell types, endothelial cells, mural cells, and immune cells, and identified cell types previously unreported in tendons, including different skeletal muscle cell types, satellite cells, adipocytes, and undefined nervous system cells. The location of these cell types within tendon was defined using spatial transcriptomics and imaging, and potential transcriptional networks and cell-cell interactions were analyzed. We demonstrate that fibroblasts have the highest number of potential cell-cell interactions in our dataset, are present throughout the tendon, and play an important role in the production and organization of extracellular matrix, thus confirming their role as key regulators of hamstring tendon homeostasis. Overall, our findings underscore the complexity of the cellular networks that underpin healthy human tendon function and the central role of fibroblasts as key regulators of hamstring tendon tissue homeostasis.

Randomized feasibility study of an autologous protein solution versus corticosteroids injection for treating subacromial pain in the primary care setting - the SPiRIT trial.

Aims: The primary aim of this study was to assess the feasibility of recruiting and retaining patients to a patient-blinded randomized controlled trial comparing corticosteroid injection (CSI) to autologous protein solution (APS) injection for the treatment of subacromial shoulder pain in a community care setting. The study focused on recruitment rates and retention of participants throughout, and collected data on the interventions' safety and efficacy. Methods: Participants were recruited from two community musculoskeletal treatment centres in the UK. Patients were eligible if aged 18 years or older, and had a clinical diagnosis of subacromial impingement syndrome which the treating clinician thought was suitable for treatment with a subacromial injection. Consenting patients were randomly allocated 1:1 to a patient-blinded subacromial injection of CSI (standard care) or APS. The primary outcome measures of this study relate to rates of recruitment, retention, and compliance with intervention and follow-up to determine feasibility. Secondary outcome measures relate to the safety and efficacy of the interventions. Results: A total of 53 patients were deemed eligible, and 50 patients (94%) recruited between April 2022 and October 2022. Overall, 49 patients (98%) complied with treatment. Outcome data were collected in 100% of participants at three months and 94% at six months. There were no significant adverse events. Both groups demonstrated improvement in patient-reported outcome measures over the six-month period. Conclusion: Our study shows that it is feasible to recruit to a patient-blinded randomized controlled trial comparing APS and CSI for subacromial pain in terms of clinical outcomes and health-resource use in the UK. Safety and efficacy data are presented.

A protocol for the conduct of a multicentre, prospective, randomized superiority trial of surgical versus non-surgical interventions for humeral shaft fractures.

Aims: Fractures of the humeral shaft represent 3% to 5% of all fractures. The most common treatment for isolated humeral diaphysis fractures in the UK is non-operative using functional bracing, which carries a low risk of complications, but is associated with a longer healing time and a greater risk of nonunion than surgery. There is an increasing trend to surgical treatment, which may lead to quicker functional recovery and lower rates of fracture nonunion than functional bracing. However, surgery carries inherent risk, including infection, bleeding, and nerve damage. The aim of this trial is to evaluate the clinical and cost-effectiveness of functional bracing compared to surgical fixation for the treatment of humeral shaft fractures. Methods: The HUmeral SHaft (HUSH) fracture study is a multicentre, prospective randomized superiority trial of surgical versus non-surgical interventions for humeral shaft fractures in adult patients. Participants will be randomized to receive either functional bracing or surgery. With 334 participants, the trial will have 90% power to detect a clinically important difference for the Disabilities of the Arm, Shoulder and Hand questionnaire score, assuming 20% loss to follow-up. Secondary outcomes will include function, pain, quality of life, complications, cost-effectiveness, time off work, and ability to drive. Discussion: The results of this trial will provide evidence regarding clinical and cost-effectiveness between surgical and non-surgical treatment of humeral shaft fractures. Ethical approval has been obtained from East of England - Cambridge Central Research Ethics Committee. Publication is anticipated to occur in 2024.

Unhelpful thoughts and distress regarding symptoms are associated with recovery from upper extremity fracture.

BACKGROUND: There is evidence that thoughts and emotions regarding symptoms are strongly associated with levels of comfort and capability for a given injury or disease. Longitudinal data from a large cohort of people recovering from an upper extremity fracture provided an opportunity to study how these mindset factors evolve during recovery. METHODS: Seven hundred and four adults (66% women, mean age 59 ± 21 years) recovering from upper extremity fracture completed two measures of reaction to symptoms (the Pain Catastrophizing Scale and the Tampa Scale of Kinesiophobia), a visual analog scale of pain intensity, and two measures of magnitude of incapability 1 week, 3 to 4 weeks, and 6 to 9 months after fracture. RESULTS: Exploratory factor analysis identified distinct groupings of questions addressing unhelpful thoughts and feelings of distress regarding symptoms. The number of distinct question groupings of mindset factors diminished over time. Variations in those groupings of mindset factors were associated with a notable amount of the variation in comfort and capability at all time points. Questions pertaining to unhelpful thoughts about symptoms had stronger associations with comfort and capability than questions measuring distress about symptoms, more so as recovery progressed. CONCLUSIONS: The need to integrate mental health into musculoskeletal is bolstered by the observation that mindsets-interpretation of symptoms in particular-are key contributors to comfort and capability.

Understanding patient experience of distal tibia or ankle fracture: a qualitative systematic review.

To systematically review qualitative studies of patients with distal tibia or ankle fracture, and explore their experience of injury and recovery. We undertook a systematic review of qualitative studies. Five databases were searched from inception to 1 February 2022. All titles and abstracts were screened, and a subset were independently assessed. Methodological quality was appraised using the Critical Appraisal Skills Programme (CASP) checklist. The GRADE-CERQual checklist was used to assign confidence ratings. Thematic synthesis was used to analyze data with the identification of codes which were drawn together to form subthemes and then themes. From 2,682 records, 15 studies were reviewed in full and four included in the review. A total of 72 patients were included across the four studies (47 female; mean age 50 years (17 to 80)). Methodological quality was high for all studies, and the GRADE-CERQual checklist provided confidence that the findings were an adequate representation of patient experience of distal tibia or ankle fracture. A central concept of 'being the same but different' conveyed the substantial disruption to patients' self-identity caused by their injury. Patient experience of 'being the same but different' was expressed through three interrelated themes, with seven subthemes: i) being proactive where persistence, doing things differently and keeping busy prevailed; ii) living with change including symptoms, and living differently due to challenges at work and leisure; and iii) striving for normality, adapting while lacking in confidence, and feeling fearful and concerned about the future. Ankle injuries were disruptive, draining, and impacted on patients' wellbeing. Substantial short- and longer-term challenges were experienced during recovery. Rehabilitation and psychosocial treatment strategies may help to ameliorate these challenges. Patients may benefit from clinicians being cognisant of patient experience when assessing, treating, and discussing expectations and outcomes with patients.

A systematic review of outcome reporting in clinical trials of distal tibia and ankle fractures : the need for a core outcome set.

AIMS: To describe outcome reporting variation and trends in non-pharmacological randomized clinical trials (RCTs) of distal tibia and/or ankle fractures. METHODS: Five electronic databases and three clinical trial registries were searched (January 2000 to February 2022). Trials including patients with distal tibia and/or ankle fractures without concomitant injuries were included. One reviewer conducted all searches, screened titles and abstracts, assessed eligibility, and completed data extraction; a random 10% subset were independently assessed and extracted by a second reviewer at each stage. All extracted outcomes were mapped to a modified version of the International Classification of Functioning, Disability and Health framework. The quality of outcome reporting (reproducibility) was assessed. RESULTS: Overall, 105 trials (n = 16 to 669 participants) from 27 countries were included. Trials compared surgical interventions (n = 62), post-surgical management options (n = 17), rehabilitative interventions (n = 14), surgical versus non-surgical interventions (n = 6), and pre-surgical management strategies (n = 5). In total, 888 outcome assessments were reported across seven domains: 263 assessed body structure or function (85.7% of trials), 136 activities (68.6% of trials), 34 participation (23.8% of trials), 159 health-related quality of life (61.9% of trials), 247 processes of care (80% of trials), 21 patient experiences (15.2% of trials), and 28 economic impact (8.6% of trials). From these, 337 discrete outcomes were described. Outcome reporting was inconsistent across trials. The quality of reporting varied widely (reproducibility ranged 4.8% patient experience to 100% complications). CONCLUSION: Substantial heterogeneity in outcome selection, assessment methods, and reporting quality were described. Despite the large number of outcomes, few are reported across multiple trials. Most outcomes are clinically focused, with little attention to the long-term consequences important to patients. Poor reporting quality reduces confidence in data quality, inhibiting data synthesis by which to inform care decisions. Outcome reporting guidance and standardization, which captures the outcomes that matter to multiple stakeholders, are urgently required.Cite this article: Bone Jt Open 2022;3(10):832-840.

Thalamic atrophy associated with painful osteoarthritis of the hip is reversible after arthroplasty: a longitudinal voxel-based morphometric study.

OBJECTIVE: Voxel-based morphometry (VBM) is a method of assessing brain gray matter volume that has previously been applied to various chronic pain conditions. From this previous work, it appears that chronic pain is associated with altered brain morphology. The present study was undertaken to assess these potential alterations in patients with painful hip osteoarthritis (OA). METHODS: We studied 16 patients with unilateral right-sided hip pain, before and 9 months after hip arthroplasty. This enabled comparison of gray matter volume in patients with chronic musculoskeletal pain versus healthy controls, as well as identification of any changes in volume following alleviation of pain (after surgery). Assessment involved self-completion questionnaires to assess pain, function, and psychosocial variables, and magnetic resonance imaging scanning of the brain for VBM analysis. RESULTS: Significant differences in brain gray matter volume between healthy controls and patients with painful hip arthritis were seen. Specifically, areas of the thalamus in patients with chronic OA pain exhibited decreased gray matter volume. Furthermore, when these preoperative changes were compared with the brain morphology of the patients 9 months after surgery, the areas of reduced thalamic gray matter volume were found to have "reversed" to levels seen in healthy controls. CONCLUSION: Our findings confirm that gray matter volume decreases within the left thalamus in the presence of chronic pain and disability in patients with hip OA. The results also show that these thalamic volume changes reverse after hip arthroplasty and are associated with decreased pain and increased function. These findings have potential implications with regard to optimizing the timing of orthopedic interventions such as arthroplasty.

Functional and oncological outcome following marginal excision of well-differentiated forearm liposarcoma with nerve involvement.

PURPOSE: Liposarcoma is one of the most common soft tissue sarcomas in adults. It is often low-grade and can occasionally involve neurovascular structures. We present the functional and oncological outcome resulting from planned marginal excision of a series of forearm low-grade liposarcomas with nerve involvement. METHODS: The Oxford tumor registry was used to identify cases of histologically proven, well-differentiated liposarcoma of the forearm, with nerve involvement, treated surgically between 1997 and 2006. Nerve involvement was identified clinically with symptoms or signs of nerve compression, or by images showing direct contact of the tumor with a nerve on magnetic resonance imaging. This was then further defined at the time of surgery as tumor abutting (capsular involvement) or encasing a peripheral nerve. Demographic and clinical data were collected and oncological outcome was assessed by noting local and distant recurrence during follow-up. Postoperative functional outcome was assessed using the Toronto Extremity Salvage Scores. RESULTS: Eight cases were identified, 6 with preoperative neurological symptoms. The total group comprised 6 men and 2 women with a mean age of 61 (range, 30-71) years. At surgery, all had their tumors successfully excised, with preservation of the involved nerves. In those with preoperative neurological symptoms, complete recovery occurred by 18 months after surgery. The average follow-up was 5 years (range, 3-9 y). There were no cases of either local or distant recurrence of disease, with a mean Toronto Extremity Salvage Score of 99%. CONCLUSIONS: Planned marginal excision of a well-differentiated liposarcoma, arising in the forearm and involving nerve, can result in excellent functional and oncological outcome. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

Factors associated with persistent opioid use after an upper extremity fracture.

AIMS: The increase in prescription opioid misuse and dependence is now a public health crisis in the UK. It is recognized as a whole-person problem that involves both the medical and the psychosocial needs of patients. Analyzing aspects of pathophysiology, emotional health, and social wellbeing associated with persistent opioid use after injury may inform safe and effective alleviation of pain while minimizing risk of misuse or dependence. Our objectives were to investigate patient factors associated with opioid use two to four weeks and six to nine months after an upper limb fracture. METHODS: A total of 734 patients recovering from an isolated upper limb fracture were recruited in this study. Opioid prescription was documented retrospectively for the period preceding the injury, and prospectively at the two- to four-week post-injury visit and six- to nine-month post-injury visit. Bivariate and multivariate analysis sought factors associated with opioid prescription from demographics, injury-specific data, Patient Reported Outcome Measurement Instrumentation System (PROMIS), Depression computer adaptive test (CAT), PROMIS Anxiety CAT, PROMIS Instrumental Support CAT, the Pain Catastrophizing Scale (PCS), the Pain Self-efficacy Questionnaire (PSEQ-2), Tampa Scale for Kinesiophobia (TSK-11), and measures that investigate levels of social support. RESULTS: A new prescription of opioids two to four weeks after injury was independently associated with less social support (odds ratio (OR) 0.26, p < 0.001), less instrumental support (OR 0.91, p < 0.001), and greater symptoms of anxiety (OR 1.1, p < 0.001). A new prescription of opioids six to nine months after injury was independently associated with less instrumental support (OR 0.9, p < 0.001) and greater symptoms of anxiety (OR 1.1, p < 0.001). CONCLUSION: This study demonstrates that potentially modifiable psychosocial factors are associated with increased acute and chronic opioid prescriptions following upper limb fracture. Surgeons prescribing opioids for upper limb fractures should be made aware of the screening and management of emotional and social health. Cite this article: Bone Jt Open 2021;2(2):119-124.

The role of classification of chronic low back pain.

STUDY DESIGN: Systematic review. OBJECTIVE: To describe the various ways chronic low back pain (CLBP) is classified, to determine if the classification systems are reliable and to assess whether classification-specific interventions have been shown to be effective in treating CLBP. SUMMARY OF BACKGROUND DATA: A classification system by which individual patients with CLBP could be identified and directed to an effective treatment protocol would be beneficial. Those systems that direct treatment have the greatest potential influence on patient outcomes. METHODS: A systematic search was conducted in MEDLINE and the Cochrane Collaboration Library for English language literature published through January 2011. We included articles that specifically described a clinical classification system for CLBP, reported on the reliability of a classification system, or evaluated the effectiveness of classification-specific interventions. RESULTS: A total of 60 articles were initially reviewed. We identified 28 classification systems that met inclusion criteria: 16 diagnostic systems, 7 prognostic systems, and 5 treatment-based systems. In addition, we found 10 randomized controlled trials of CLBP treatment from which we compared inclusion and exclusion criteria. Treatment-based systems were all directed at nonoperative management. Four of the 5 treatment-based systems underwent reliability testing and were found to have interobserver agreement of 70% to 100%. Reliability increased with training and familiarity with a given classification. As the number of subgroups within a classification increased, interobserver agreement decreased. Function and pain were similar between patients treated with the McKenzie classification system and those treated with dynamic strengthening training after 8 months of follow-up in one randomized controlled trial. One prospective cohort study reported better pain and function using the Canadian Back Institute Classification system than with standard rehabilitation. An analysis of the admission criteria to recent randomized studies with either nonoperative care or another surgical intervention provided a methodology for refining criteria to be met by patients considering surgery. CONCLUSION: There currently are many classification systems for CLBP; some that are descriptive, some prognostic, and some that attempt to direct treatment. We recommend that no one classification system be adopted for all purposes. We further recommend that future efforts in developing a classification system focus on one that helps to direct both surgical and nonsurgical treatments. CLINICAL RECOMMENDATIONS: There currently are many classification systems for CLBP; some that are descriptive, some prognostic, and some that attempt to direct treatment. We recommend that no one classification system be adopted for all purposes. We further recommend that future efforts in developing a classification system focus on one that helps to direct both surgical and nonsurgical treatments.

Surgical options for patients with shoulder pain.

Shoulder pain is a common musculoskeletal complaint in the community, which can arise from diverse causes. Regardless of the cause, mild cases can often be effectively treated conservatively, with options including rest, physiotherapy, pain relief and glucocorticoid injections. If conservative strategies fail after a 3-6 month period then surgery might be considered. Generally, the proportion of patients with shoulder pain who require surgery is small. When surgery is considered, a clear diagnosis and structural information from imaging are required. The indications for surgery, and success rate, depend on the specific diagnosis as well as on the individual clinical presentation. Evidence from case series suggest that surgical interventions for shoulder pain are effective when used appropriately. This article outlines the surgical management of the most common painful conditions that affect the shoulder, including impingement, rotator cuff tear, frozen shoulder, osteoarthritis, rheumatoid arthritis and calcific tendonitis.

Psychophysical and functional imaging evidence supporting the presence of central sensitization in a cohort of osteoarthritis patients.

OBJECTIVE: The groin pain experienced by patients with hip osteoarthritis (OA) is often accompanied by areas of referred pain and changes in skin sensitivity. We aimed to identify the supraspinal influences that underlie these clinical manifestations that we consider indicative of possible central sensitization. METHODS: Twenty patients with hip OA awaiting joint replacement and displaying signs of referred pain were recruited into the study, together with age-matched controls. All subjects completed pain psychology questionnaires and underwent quantitative sensory testing (QST) in their area of referred pain. Twelve of 20 patients and their age- and sex-matched controls underwent functional magnetic resonance imaging (MRI) while the areas of referred pain were stimulated using cold stimuli (12 degrees C) and punctate stimuli (256 mN). The remaining 8 of 20 patients underwent punctate stimulation only. RESULTS: Patients were found to have significantly lower threshold perception to punctate stimuli and were hyperalgesic to the noxious punctate stimulus in their areas of referred pain. Functional brain imaging illustrated significantly greater activation in the brainstem of OA patients in response to punctate stimulation of their referred pain areas compared with healthy controls, and the magnitude of this activation positively correlated with the extent of neuropathic-like elements to the patient's pain, as indicated by the PainDETECT score. DISCUSSION: Using psychophysical (QST) and brain imaging methods (functional MRI), we have identified increased activity with the periaqueductal grey matter associated with stimulation of the skin in referred pain areas of patients with hip OA. This offers a central target for analgesia aimed at improving the treatment of this largely peripheral disease.

Treatment of nevoid hyperkeratosis of the nipple and areola by shave excision.

The case is presented of a 29-year-old female who, at the age of 13 years, developed bilateral verrucous thickening of her areolae. Despite the condition causing her significant psychosocial morbidity, a specialist referral was initially denied on the grounds that no treatment was apparently available. The condition progressively deteriorated over the subsequent 14 years. She was eventually referred for a dermatology opinion, and the diagnosis of nevoid hyperkeratosis was made. Topical therapy with keratolytics was unsuccessful, and she was referred for a plastic surgery review. Bilateral shave excision of the lesion was performed under general anesthesia, with a satisfactory outcome and no evidence of recurrence at 10 months.