Mortality and pulmonary complications in patients undergoing upper extremity surgery at the peak of the SARS-CoV-2 pandemic in the UK: a national cohort study.

INTRODUCTION: This study reports the 30-day mortality, SARS-CoV-2 complication rate and SARS-CoV-2-related hospital processes at the peak of the first wave of the pandemic in the UK. METHODS: This national, multicentre, cohort study at 74 centres in the UK included all patients undergoing any surgery below the elbow at the peak of the UK pandemic. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The secondary outcomes were SARS-CoV-2 complication rates and overall complication rates. A clinician survey relating to SARS-CoV-2 safety processes was carried out for each participating centre. RESULTS: This analysis includes 1093 patients who underwent upper limb surgery from the 1 to 14 April 2020 inclusively. The overall 30-day mortality was 0.09% (1 pre-existing SARS-CoV-2 pneumonia) and the mortality of day case surgery was zero. Most centres (96%) screened patients for symptoms prior to admission, only 22% routinely tested for SARS-CoV-2 prior to admission. The SARS-CoV-2 complication rate was 0.18% (2 pneumonias) and the overall complication rate was 6.6% (72 patients). Both SARS-CoV-2-related complications occurred in patients who had been hospitalised for a prolonged period before their surgery and a total of 19 patients (1.7%) were SARS-CoV-2 positive. CONCLUSIONS: The SARS-CoV-2-related complication rate for upper limb surgery even at the peak of the UK pandemic was low at 0.18% and the mortality was zero for patients admitted on the day of surgery. Urgent surgery should not be delayed pending the results of SARS-CoV-2 testing. Routine SARS-CoV-2 testing for day case upper limb surgery not requiring general anaesthesia may be excessive and have unintended negative impacts.

Current management strategies in Osgood Schlatter: A cross-sectional mixed-method study.

BACKGROUND: Osgood Schlatter disease (OSD) is the most common knee condition in adolescent athletes aged 9-16. Without evidence to guide clinical practice, it is unclear how OSD is managed. The aim of this study was to investigate how international healthcare professionals (general practitioners, physiotherapists, rheumatologists, sports and exercise medicine doctors, and orthopedic surgeons) diagnose and manage OSD. METHODS: This mixed-method study used a convergent parallel design. A quantitative questionnaire and semi-structured interview covered prognosis, diagnosis, treatment, and return to play of adolescents with OSD. For quantitative data, those who reported likely/very likely considered "for" and unlikely/very unlikely "against" (for specific diagnostic/management strategy). Qualitative data analysis used a phenomenological approach. RESULTS: Two hundred and fifty-one healthcare professionals completed the questionnaire. The most common diagnostic criterion was pain at the tibial tuberosity (97% for). The most common treatments were patient education (99%) and exercise therapy (92%). Other treatment options were more heterogeneous, for example, pain medication (31% for and 34% against). Managing training load (97%), pain intensity (87%), and psychological factors (86%) were considered the most important factors influencing the return to activities. Several themes emerged from the interviews (on N = 20) including imaging, pain management, family, and psychosocial factors influencing prognosis. CONCLUSION: Diagnosis criteria of OSD were relatively well agreed upon, whereas the triangulation of qualitative and quantitative data showed heterogeneity of treatments. Psychosocial factors including family were highlighted as critical in the management of OSD.

Injection therapy for base of thumb osteoarthritis: a systematic review and meta-analysis.

OBJECTIVE: To evaluate the effectiveness of injection-based therapy in base of thumb osteoarthritis. DESIGN: Systematic review and meta-analysis. DATA SOURCES: MEDLINE and EMBASE via OVID, CINAHL and SPORTDiscus via EBSCO were searched from inception to 22 May 2018. STUDY SELECTION: Randomised controlled trials (RCTs) and non-RCTs of adults with base of thumb osteoarthritis investigating an injection-based intervention with any comparator/s. DATA EXTRACTION AND ANALYSIS: Data were extracted and checked for accuracy and completeness by pairs of reviewers. Primary outcomes were pain and function. Comparative treatment effects were analysed by random-effects model for short-term and medium-term follow-up. RESULTS: In total, 9 RCTs involving 504 patients were identified for inclusion. All compared different injection-based therapies with each other, no studies compared an injection-based therapy with a non-injection-based intervention. Twenty injection-based intervention groups were present within these nine trials, consisting of hyaluronic acid (n=9), corticosteroid (n=7), saline placebo (n=3) and dextrose (n=1). Limited meta-analysis was possible due to the heterogeneity in the injections and outcomes used, as well as incomplete outcome data. Meta-analysis of two RCTs (92 patients) demonstrated reduced Visual Analogue Scale pain on activity with corticosteroid versus hyaluronic acid (mean difference (MD) -1.32, 95% CI -2.23 to -0.41) in the medium term, but no differences in other measures of pain or function in the short term and medium term. Overall, the available evidence does not suggest that any of the commonly used injection therapies are superior to placebo, one another or a non-injection-based comparator. CONCLUSION: Current evidence is equivocal regarding the use of injection therapy in base of thumb osteoarthritis, both in terms of which injection-based therapy is the most effective and in terms of whether any injection-based therapy is more effective than other non-injection-based interventions. Given limited understanding of both the short-term and long-term effects, there is a need for a large, methodologically robust RCT investigating the commonly used injection therapies and comparing them with other therapeutic options and placebo. PROSPERO REGISTRATION NUMBER: CRD42018095384.

Therapeutic interventions in children and adolescents with patellar tendon related pain: a systematic review.

OBJECTIVE: Evaluate effectiveness and harms of interventions for patellar tendon related pain in children and adolescents. DESIGN: Systematic review and meta-analysis. DATA SOURCES: Medline via Pubmed, Embase via OVID, CINAHL via Ebsco, SportDiscus up until 24 November 2017 were searched. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Inclusion criteria were (1) controlled or randomised controlled clinical trials (RCTs), (2) participants with diagnosis of patellar tendon related disorder, (3) participants≤18 years of age at enrolment and (4) published in a peer-reviewed English or Scandinavian language journal. RESULTS: Of 530 studies identified, eight were included after screening, with three included in data synthesis. To be included in data synthesis, we required studies to have included (and have data available for) a minimum of 10 participants under 18 years. All studies were rated as being at high risk of bias. For adolescents with patellar tendinopathy, one RCT compared eccentric exercises to usual care and found no difference between groups. In adolescents with Osgood-Schlatter disease (OSD), injection of local anaesthetic with dextrose proved superior to either usual care or local anaesthetic alone (three armed RCTs). In a retrospective case controlled study in adolescents with OSD, surgery provided no benefit over conservative management in terms of persistent symptoms and had a higher complication rate. CONCLUSION: There is weak evidence to support the use of dextrose injection with local anaesthetic and no evidence to support the use of specific types of exercises to treat children/adolescents with OSD/patellar tendinopathy. Until further evidence arises, clinicians should include load modification and advise on a return to sport based on symptoms.

Do expanded seven-day NHS services improve clinical outcomes? Analysis of comparative institutional performance from the "NHS Services, Seven Days a Week" project 2013-2016.

BACKGROUND: The cause of adverse weekend clinical outcomes remains unknown. In 2013, the "NHS Services, Seven Days a Week" project was initiated to improve access to services across the seven-day week. Three years on, we sought to analyse the impact of such changes across the English NHS. METHODS: Aggregated trust-level data on crude mortality rates, Summary Hospital-Level Mortality Indicator (SHMI), mean length of stay (LOS), A&E admission and four-hour breach rates were obtained from national Hospital Episode Statistics and A&E datasets across the English NHS, excluding mental and community health trusts. Trust annual reports were analysed to determine the presence of any seven-day service reorganisation in 2013-2014. Funnel plots were generated to compare institutional performance and a difference in differences analysis was performed to determine the impact of seven-day changes on clinical outcomes between 2013 and 2014, 2014-2015 and 2015-2016. Data was summarised as mean (SD). RESULTS: Of 159 NHS trusts, 79 (49.7%) instituted seven-day changes in 2013-2014. Crude mortality rates, A&E admission rates and mean LOS remained relatively stable between 2013 and 2016, whilst A&E four-hour breach rates nearly doubled from 5.3 to 9.7%. From 2013 to 2014 to 2014-2015 and 2015-2016, there were no significant differences in the change in crude mortality (2014-2015 p = 0.8, 2015-2016 p = 0.9), SHMI (2014-2015 p = 0.5, 2015-2016 p = 0.5), mean LOS (2014-2015 p = 0.5, 2015-2016 p = 0.4), A&E admission (2014-2015 p = 0.6, 2015-2016 p = 1.0) or four-hour breach rates (2014-2015 p = 0.06, 2015-2016 p = 0.6) between trusts that had implemented seven-day changes compared to those which had not. CONCLUSIONS: Adverse weekend clinical outcomes may not be ameliorated by large scale reorganisations aimed at improving access to health services across the week. Such changes may negatively impact care quality without additional financial investment, as demonstrated by worsening of some outcomes. Detailed prospective research is required to determine whether such reallocation of finite resources is clinically effective.

The Effects of Glucocorticoid on Tendon and Tendon Derived Cells.

Glucocorticoids are generally used to relieve pain and/or inflammation in a wide variety of musculoskeletal disorders including osteoarthritis, inflammatory arthritis, tendinopathy and degenerative spine disease. Glucocorticoids reduce tendon derived cell proliferation in vitro and reduce extracellular matrix synthesis both in vitro and in vivo, in particular type I collagen synthesis. Glucocorticoids also appear to result in acute deleterious changes in healthy in vivo tendon including collagen necrosis, collagen disorganisation and inflammatory cell infiltration; while the overall effect of glucocorticoid administration on the mechanical properties of healthy in vivo tendon are generally negative. Overall the existing in vitro and in vivo evidence suggests that glucocorticoids should be used with caution in treating painful tendinopathy. Certainly a real need exists to follow up the long term clinical effects of glucocorticoid in treating tendinopathy, as there is currently a paucity of evidence in this area. However in this context while the short term benefits are clear, glucocorticoids remain a useful treatment option provided they are used in the right patients in sensible moderation.

Are inflammatory cells increased in painful human tendinopathy? A systematic review.

BACKGROUND: The role of inflammation in tendinopathy has historically been a subject of significant controversy. Our primary aim was to determine whether inflammatory cell numbers were increased in painful human tendinopathy versus healthy control tendons. Our secondary aim was to assess whether the inflammatory cells had been linked with symptoms or disease stage. METHODS: We conducted a systematic review of the scientific literature using the PRISMA and Cochrane guidelines of the Medline database using specific search criteria. Only studies measuring inflammatory cells using specific markers in tissue from human patients with the clinical diagnosis of tendinopathy were included. Inclusion was agreed on by 2 independent researchers on review of abstracts or full-text using specific predetermined criteria. The search yielded 5 articles in total. RESULTS: There were increased numbers of macrophages (4 studies) and mast cells (3 studies) in tendinopathic versus healthy control tissues. One study demonstrated increased numbers of T cells in tendinopathic tissue versus healthy control tendons. There were reduced numbers of T cells (1 study), macrophages (2 studies) and mast cells (2 studies) in torn tendon versus intact tendinopathic tissue. CONCLUSIONS: The existing evidence supports the hypothesis that increased numbers of inflammatory cells are present in pathological tendons. The lack of high-quality quantitative studies in this area demonstrates a clear need for future research to better understand the role of inflammation in tendinopathy.

Differences in glutamate receptors and inflammatory cell numbers are associated with the resolution of pain in human rotator cuff tendinopathy.

INTRODUCTION: The relationship between peripheral tissue characteristics and pain symptoms in soft tissue inflammation is poorly understood. The primary aim of this study was to determine immunohistochemical differences in tissue obtained from patients with persistent pain and patients who had become pain-free after surgical treatment for rotator cuff tendinopathy. The secondary aim was to investigate whether there would be differences in glutaminergic and inflammatory gene expression between disease-derived and healthy control cells in vitro. METHODS: Supraspinatus tendon biopsies were obtained from nine patients with tendon pain before shoulder surgery and from nine further patients whose pain had resolved completely following shoulder surgery. Histological markers relating to the basic tendon characteristics, inflammation and glutaminergic signalling were quantified by immunohistochemical analysis. Gene expression of glutaminergic and inflammatory markers was determined in tenocyte explants derived from painful rotator cuff tendon tears in a separate cohort of patients and compared to that of explants from healthy control tendons. Dual labelling was performed to identify cell types expressing nociceptive neuromodulators. RESULTS: Tendon samples from patients with persistent pain demonstrated increased levels of metabotropic glutamate receptor 2 (mGluR2), kainate receptor 1 (KA1), protein gene product 9.5 (PGP9.5), CD206 (macrophage marker) and CD45 (pan-leucocyte marker) versus pain-free controls (p <0.05). NMDAR1 co-localised with CD206-positive cells, whereas PGP9.5 and glutamate were predominantly expressed by resident tendon cells. These results were validated by in vitro increases in the expression of mGluR2, N-methyl-D-aspartate receptor (NMDAR1), KA1, CD45, CD206 and tumour necrosis factor alpha (TNF-α) genes (p <0.05) in disease-derived versus control cells. CONCLUSIONS: We conclude that differences in glutamate receptors and inflammatory cell numbers are associated with the resolution of shoulder pain in rotator cuff tendinopathy, and that disease-derived cells exhibit a distinctly different neuro-inflammatory gene expression profile to healthy control cells.

In vitro effects of glutamate and N-methyl-D-aspartate receptor (NMDAR) antagonism on human tendon derived cells.

It is known that extracellular glutamate concentrations are increased in tendinopathy but the effects of glutamate upon human tendon derived cells are unknown. The primary purpose was to investigate the effect of glutamate exposure on human tendon-derived cells in terms of viability, protein, and gene expression. The second purpose was to assess whether NMDAR antagonism would affect the response of tendon-derived cells to glutamate exposure. Human tendon-derived cells were obtained from supraspinatus tendon tissue obtained during rotator cuff repair (tendon tear derived cells) and from healthy hamstring tendon tissue (control cells). The in vitro impact of glutamate exposure and NMDAR antagonism (MK-801) was measured using the Alamar blue cell viability assay, immunocytochemistry, and quantitative real-time PCR. Glutamate reduced cell viability at 24 h in tendon tear derived cells but not in control cells at concentrations of 7.5 mM and above. Cell viability was significantly reduced after 72 h of 1.875 mM glutamate in both cell groups; this deleterious effect was attenuated by NMDAR antagonism with 10 µM MK-801. Both 24 and 72 h of 1.875 mM glutamate exposure reduced Type 1 alpha 1 collagen (COL1A1) and Type 3 alpha 1 collagen (COL3A1) gene expression, but increased Aggrecan gene expression. We propose that these effects of glutamate on tendon derived cells including reduced cell viability and altered matrix gene expression contribute to the pathogenesis of tendinopathy.

Glucocorticoids induce specific ion-channel-mediated toxicity in human rotator cuff tendon: a mechanism underpinning the ultimately deleterious effect of steroid injection in tendinopathy?

BACKGROUND: Glucocorticoid injection (GCI) and surgical rotator cuff repair are two widely used treatments for rotator cuff tendinopathy. Little is known about the way in which medical and surgical treatments affect the human rotator cuff tendon in vivo. We assessed the histological and immunohistochemical effects of these common treatments on the rotator cuff tendon. STUDY DESIGN: Controlled laboratory study. METHODS: Supraspinatus tendon biopsies were taken before and after treatment from 12 patients undergoing GCI and 8 patients undergoing surgical rotator cuff repair. All patients were symptomatic and none of the patients undergoing local GCI had full thickness tears of the rotator cuff. The tendon tissue was then analysed using histological techniques and immunohistochemistry. RESULTS: There was a significant increase in nuclei count and vascularity after rotator cuff repair and not after GCI (both p=0.008). Hypoxia inducible factor 1α (HIF-1α) and cell proliferation were only increased after rotator cuff repair (both p=0.03) and not GCI. The ionotropic N-methyl-d-aspartate receptor 1 (NMDAR1) glutamate receptor was only increased after GCI and not rotator cuff repair (p=0.016). An increase in glutamate was seen in both groups following treatment (both p=0.04), while an increase in the receptor metabotropic glutamate receptor 7 (mGluR7) was only seen after rotator cuff repair (p=0.016). CONCLUSIONS: The increases in cell proliferation, vascularity and HIF-1α after surgical rotator cuff repair appear consistent with a proliferative healing response, and these features are not seen after GCI. The increase in the glutamate receptor NMDAR1 after GCI raises concerns about the potential excitotoxic tendon damage that may result from this common treatment.

The risks and benefits of glucocorticoid treatment for tendinopathy: a systematic review of the effects of local glucocorticoid on tendon.

OBJECTIVE: Our primary objective was to summarise the known effects of locally administered glucocorticoid on tendon tissue and tendon cells. METHODS: We conducted a systematic review of the scientific literature using the PRISMA and Cochrane guidelines of the Medline database using specific search criteria. The search yielded 50 articles, which consisted of 13 human studies, 36 animal studies and one combined human/animal study. RESULTS: Histologically, there was a loss of collagen organisation (6 studies) and an increase in collagen necrosis (3 studies). The proliferation (8 studies) and viability (9 studies) of fibroblasts was reduced. Collagen synthesis was decreased in 17 studies. An increased inflammatory cell infiltrate was shown in 4 studies. Increased cellular toxicity was demonstrated by 3 studies. The mechanical properties of tendon were investigated by 18 studies. Descriptively, 6 of these studies showed a decrease in mechanical properties, 3 showed an increase, while the remaining 9 showed no significant change. A meta-analysis of the mechanical data revealed a significant deterioration in mechanical properties, with an overall effect size of -0.67 (95% CI = 0.01 to -1.33) (data from 9 studies). CONCLUSIONS: Overall it is clear that the local administration of glucocorticoid has significant negative effects on tendon cells in vitro, including reduced cell viability, cell proliferation and collagen synthesis. There is increased collagen disorganisation and necrosis as shown by in vivo studies. The mechanical properties of tendon are also significantly reduced. This review supports the emerging clinical evidence that shows significant long-term harms to tendon tissue and cells associated with glucocorticoid injections.

The peripheral neuronal phenotype is important in the pathogenesis of painful human tendinopathy: a systematic review.

BACKGROUND: The pathogenesis of tendinopathy is complex and incompletely understood. Although significant advances have been made in terms of understanding the pathological changes in both the extracellular matrix and the cells involved, relatively little is known about the role of neuronal regulation in tendinopathy. The frequent mismatch between tendon pathology and pain may be explained, in part, by differences in the peripheral neuronal phenotype of patients. QUESTIONS/PURPOSES: The primary purpose of this review was to determine whether evidence exists of changes in the peripheral neuronal phenotype in painful human tendinopathy and, if so, to identify the associated histological and molecular changes. The secondary purpose was to determine if any changes in the peripheral neuronal phenotype reported correlate with pain symptoms. METHODS: We conducted a systematic review of the scientific literature using the PRISMA and Cochrane guidelines. The Medline and Embase databases were searched using specific search criteria. Only studies analyzing the peripheral tissue of patients with the clinical diagnosis of tendinopathy were included. Inclusion was agreed on by two independent researchers on review of abstracts or full text. RESULTS: Overall in the 27 included studies, there was clear evidence of changes in the peripheral neuronal phenotype in painful human tendinopathy. The excitatory glutaminergic system was significantly upregulated in seven studies, there was a significant increase in sensory neuropeptide expression in four studies, and there were significant changes in the molecular morphology of tenocytes, blood vessels, and nerves. In rotator cuff tendinopathy, substance P has been shown to correlate with pain and the neural density in the subacromial bursa has been shown to correlate with rest pain. CONCLUSIONS: The peripheral neuronal phenotype is an important factor in the pathogenesis of painful human tendinopathy. Further research in this area specifically correlating tissue changes to clinical scores has great potential in further developing our understanding of the disease process.

Why does my shoulder hurt? A review of the neuroanatomical and biochemical basis of shoulder pain.

If a patient asks 'why does my shoulder hurt?' the conversation will quickly turn to scientific theory and sometimes unsubstantiated conjecture. Frequently, the clinician becomes aware of the limits of the scientific basis of their explanation, demonstrating the incompleteness of our understanding of the nature of shoulder pain. This review takes a systematic approach to help answer fundamental questions relating to shoulder pain, with a view to providing insights into future research and novel methods for treating shoulder pain. We shall explore the roles of (1) the peripheral receptors, (2) peripheral pain processing or 'nociception', (3) the spinal cord, (4) the brain, (5) the location of receptors in the shoulder and (6) the neural anatomy of the shoulder. We also consider how these factors might contribute to the variability in the clinical presentation, the diagnosis and the treatment of shoulder pain. In this way we aim to provide an overview of the component parts of the peripheral pain detection system and central pain processing mechanisms in shoulder pain that interact to produce clinical pain.

The jones fracture classification, management, outcome, and complications: a systematic review.

BACKGROUND: The Jones fracture has been a topic of controversy ever since being first described by Sir Robert Jones himself in 1902. The aim of this review is to summarize the classification, management, outcome, and complications of this particular injury. METHODS: The authors conducted a systematic review of the scientific literature regarding the Jones fracture. RESULTS: There was no consistent approach to the Jones fracture classification. The rate of nonunion with nonoperative treatment is high in both acute and chronic cases. Surgical intervention reduces the incidence of nonunion, but the complication rate of surgery is high. CONCLUSIONS: Surgical intervention for the acute Jones fracture should be reserved for the athletic individual because there is a clear advantage in terms of time to return to sporting activity. Nonoperative treatment remains a viable alternative to surgery in all acute and delayed cases, providing there is no established nonunion and the patient is aware of the implications.

Modular endoprosthetic replacement for failed internal fixation of the proximal femur following trauma.

PURPOSE: Although originally designed for reconstruction after primary malignant bone tumour resection, modular endoprosthetic replacement (EPR) can be used in salvage surgery for complex periprosthetic fracture and failed internal fixation. The purpose of this study was to assess the functional outcome following EPR for failed internal fixation of the proximal femur. METHODS: We assessed clinical and functional outcomes of using a modular tumour endoprosthesis to reconstruct the proximal femur following failed internal fixation in eight consecutive patients between 2001 and 2008. RESULTS: There were four men and four women, with a mean age of 67.5 (range 50-79) years and a mean follow-up of 16.5 (6-36) months. All patients had failed internal fixation for traumatic proximal femoral fractures--four 31.A2.3, two 31.A3.1, two 31.A3.3 using the Arbeitsgemeinshaft für Osteosynthesefragen (AO) fracture classification. Mean time from the first attempted internal fixation to definitive EPR was 34 (6-102) months, and the median number of previous surgical procedures was two (1-11). Histology revealed infection (two cases), uninfected nonunion (five cases) and plasmocytoma (one case). The EPR was carried out as a one-stage procedure in six cases and a two-stage procedure in two cases. Mean postoperative Harris Hip Score was 71.4 (range 64-85). There were no surgical complications. One patient died as a result of systemic complications of myeloma several years following EPR. CONCLUSIONS: EPR is an effective salvage procedure for failed fixation of traumatic proximal femoral fractures. Immediate weightbearing and a good functional outcome can be expected in this difficult group of patients.