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Although frequently prescribed for frozen shoulder, it is not known if corticosteroid injections improve the course of frozen shoulder. This study aimed to assess the disease-modifying effects of an intra-articular corticosteroid administration at the freezing phase of frozen shoulder. Twenty-four Sprague-Dawley rats were divided into four groups. Their unilateral shoulders were immobilized for the first 3 days in all groups, followed by an intra-articular corticosteroid injection in Group A, an injection and the cessation of immobilization in Group B, no further intervention in Group C, and the cessation of immobilization in Group D. All rats were sacrificed in Week 3 of study, at which point the passive shoulder abduction angles were measured and the axillary recess tissues were retrieved for histological and Western blot analyses. The passive shoulder abduction angles at the time of sacrifice were 138° ± 8° (Group A), 146° ± 5° (Group B), 95° ± 11° (Group C), 132° ± 8° (Group D), and 158° ± 2° (Control). The histological assessments and Western blots showed greater fibrosis and inflammation in the groups that did not receive the corticosteroid injection (Groups C and D) compared to the corticosteroid-injected groups (Groups A and B). These findings demonstrate the anti-inflammatory and disease-modifying effects of corticosteroid injections during the freezing phase of frozen shoulder in an animal model.

Background: Frozen shoulder (FS) is a common progressive disorder that causes restricted motion and refractory pain undermining quality of life. Intra-articular hyaluronic acid (HA) injection is a widely adopted conservative therapy relieving symptomatic FS, whereas the effect of which were contradictory and unclear in current literatures. The aim of the present study is to investigate whether intra-articular HA administration facilitates symptomatic pain relief and functional improvements in patients diagnosed with shoulder FS., Methods: The PubMed, Embase, Cochrane Library electronic databases and Google scholar were searched, from inception to 15th Jan 2022. Randomized controlled trials (RCTs) comparing intra-articular HA administration with any other non-surgical treatment in patients with FS were included. Risk of bias was evaluated using the Cochrane risk-of-bias tool and meta-analyses were undertaken to pool the data of visual analog scale for pain, range of motion (ROM) in external rotation, abduction, and flexion, as well as Shoulder Pain and Disability Index (SPADI), Constant score and American Shoulder and Elbow Surgeons (ASES)., Results: The present study included 7 RCTs involving 504 patients. The results provided no support for superior pain control in patients undergoing HA injection compared with any other treatment (p = 0.75). Furthermore, HA group failed to exert superior improvements to other treatments in ROM concerning abduction (p = 0.69) and flexion (p = 0.33). However, HA injection was observed to facilitate functional recovery in external rotation (p = 0.003). In addition, the pooled data showed a significant higher SPADI score in control group than in HA group (p = 0.01), while no statistical significance between two groups was observed in Constant score (p = 0.36) and ASES (p = 0.76)., Conclusions: The current meta-analysis suggested that HA is a beneficial treatment procedure in improving the ROM of the shoulder for patients with FS, whereas the effect in relieving pain may be equal to the existing therapy. In conclusion, Intra-articular HA injection is recommended for FS patients., (© 2022. The Author(s).)

Classical treatments of shoulder instability are associated with recurrence. To determine whether the modification of the capsule properties may be an alternative procedure, the effect of crosslinking treatment on the structure and mechanical properties of diseased human shoulder capsules was investigated. Joint capsules harvested from patients during shoulder surgery (n = 5) were treated or not with UV and/or riboflavin (0.1%, 1.0% and 2.5%). The structure and the mechanical properties of the capsules were determined by atomic force microscopy. The effect of treatments on cell death was investigated. Collagen fibrils were well-aligned and adjacent to each other with a D-periodicity of 66.9 ± 3.2 nm and a diameter of 71.8 ± 15.4 nm in control untreated capsules. No effect of treatments was observed on the organization of the collagen fibrils nor on their intrinsic characteristics, including D-periodicity or their mean diameter. The treatments also did not induce cell death. In contrast, UV + 2.5% riboflavin induced capsule stiffness, as revealed by the increased Young's modulus values ( p < 0.0001 for each patient). Our results showed that the crosslinking procedure changed the biomechanics of diseased capsules, while keeping their structural organisation unchanged at the single fibril level. The UV/riboflavin crosslinking procedure may be a promising way to preserve the functions of collagen-based tissues and tune their elasticity for clinically relevant treatments.

The purposes were to calculate total voxel volume of the entire capsulo-synovial enhanced portion on contrast-enhanced (CE) MRI in adhesive capsulitis, and to investigate its association with glenohumeral joint volume and passive range of motions (ROMs), which are a well-known diagnostic reference standard and clinical hallmark of this condition. Medical records of 169 consecutive patients who underwent ultrasound-guided intraarticular injection with adhesive capsulitis and CE-MRI to exclude other mimicking shoulder diseases were retrospectively reviewed. To calculate total voxel volume of entire capsulo-synovial enhanced portion on CE-MRI, voxel-based 3-dimensional (3D) segmentation was obtained semi-automatically using Fiji, an open-source image processing software. Pearson's correlation coefficients were analyzed. Sixty patients who met eligibility criteria were included. Total voxel volume showed a significant inverse correlation with the glenohumeral joint volume (r = -0.528, P < 0.001), forward elevation, external rotation, and abduction (r = -0.407, P = 0.001; r = -0.342, P = 0.007; r = -0.275, P = 0.034, respectively). Intra-observer and inter-observer reliabilities, measured by intraclass correlation coefficients (ICC), were excellent (ICC = 0.87 and 0.77, respectively). This study's results indicate that voxel-based 3D segmentation of entire capsulo-synovial enhanced portion from CE-MRI can represent the severity of clinical impairments, such as obliterated joint volume and limited passive ROMs in adhesive capsulitis.

Background: Periarthritis of shoulder (PAS) symptom is one of the leading causes prompting many patients to seek treatment. Tuina is a common treatment for PAS in China. But at present, there is no systematic evaluation report on its therapeutic effectiveness and safety. This protocol aims to reveal the efficacy and safety of Tuina for treating PAS., Methods: The following databases will be searched by electronic methods: PubMed, EBASE, WHO International Clinical Trials Registry Platform, Embase, the Chinese Biomedical Literature Database (CBM), Wan-fang Data (WANFANG), the China National Knowledge Infrastructure (CNKI), and other sources from inception to December 2019. Bias risk, subgroup analysis, data synthesis, and meta-analyses will be assessed with RevMan V.5.3 software if the data is met inclusion conditions., Results: This study will present a quality evidence of Tuina for the treatment of PAS patients., Conclusion: The systematic review will present reliable evidence to judge whether or not Tuina is a safe and effective intervention for PAS patients., Prospero Registration Number: CRD42019147445.

Background: Coracohumeral ligament (CHL) thickening, contracture, and fibroplasia have been identified in glenohumeral idiopathic adhesive capsulitis (GHIAC). The CHL is the main structure responsible for the range of motion limitations. Favorable outcomes have been reported with CHL surgical release. Intra-articular glenohumeral joint corticosteroid infiltrations are utilized to disrupt the inflammatory process and reduce pain in GHIAC. The aim of this study was to investigate whether the CHL could be accurately targeted with a periligamentous infiltration., Methods: A convenience sample of 12 unembalmed cadaver shoulders (mean age: 74.5 years, range 66-87 years) without evidence of previous injury or surgery were utilized in this exploratory double factor feasibility cadaveric (unguided and ultrasound (US) guided) case series. Two clinicians trained in musculoskeletal infiltration techniques carried out the infiltrations on each shoulder with colored latex. One clinician infiltrated without guidance, the other with US-guidance. The injecting clinicians were blinded to the others infiltration procedure and the order was randomized. An anatomist blinded to the infiltration order performed a shoulder dissection and recorded the infiltrate location. Percentage calculation for accuracy of infiltration and a chi-square evaluation of the difference between unguided and US-guided infiltrations was applied., Results: An accuracy of 75% was achieved for unguided infiltration and 80% for US-guided infiltration techniques. Chi-squared indicated there was no significant difference (p = 0.82) between the unguided and US-guided techniques., Conclusion: US-guided and unguided infiltrations achieved good accuracy targeting the CHL, suggesting infiltrations can specifically and accurately target the CHL. In vivo investigation using such infiltration techniques are warranted.

Tendon stromal cells isolated from patients with chronic shoulder rotator cuff tendon tears have dysregulated resolution responses. Current therapies do not address the biological processes concerned with persistent tendon inflammation; therefore, new therapeutic approaches that target tendon stromal cells are required. We examined whether two specialized proresolving mediators (SPMs), lipoxin B4 (LXB4) and resolvin E1 (RvE1), modulate the bioactive lipid mediator profiles of IL-1β-stimulated tendon cells derived from patients with shoulder tendon tears and healthy volunteers. We also examined whether LXB4 or RvE1 treatments moderated the proinflammatory phenotype of tendon tear stromal cells. Incubation of IL-1β-treated patient-derived tendon cells in LXB4 or RvE1 up-regulated concentrations of SPMs. RvE1 treatment of diseased tendon stromal cells increased 15-epi-LXB4 and regulated postaglandin F2α. LXB4 or RvE1 also induced expression of the SPM biosynthetic enzymes 12-lipoxygenase and 15-lipoxygenase. RvE1 treatment up-regulated the proresolving receptor human resolvin E1 compared with vehicle-treated cells. Incubation in LXB4 or RvE1 moderated the proinflammatory phenotype of patient-derived tendon tear cells, regulating markers of tendon inflammation, including podoplanin, CD90, phosphorylated signal transducer and activator of transcription 1, and IL-6. LXB4 and RvE1 counterregulate inflammatory processes in tendon stromal cells, supporting the role of these molecules as potential therapeutics to resolve tendon inflammation., (Copyright © 2019 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

Background: Adhesive capsulitis is one of the most well-known causes of pain and stiffness of the shoulder. Corticosteroid injections have been used for many years. However, it is still controversial where corticosteroid should be injected, whether subacromial or intra-articular., Objective: The objective of this meta-analysis was to compare the effects of intra-articular (IA) and subacromial (SA) corticosteroid injections for the treatment of adhesive capsulitis., Materials and Methods: Four foreign databases and two Chinese databases were searched for RCTs and quasi-RCTs involving the comparison of IA and SA corticosteroid injection for the treatment of adhesive capsulitis. The Cochrane risk of bias tool and PEDro score were used to evaluate the quality of the studies. The primary clinical outcomes including VAS, Constant score, ASES score, and ROM were collected. The secondary outcome of corticosteroid-related adverse reactions was also compared between the two groups. The results were evaluated and compared at five time points. Subgroup analyses were performed to further explore the differences between groups., Results: Eight RCTs and one quasi-RCT, involving 512 participants, were identified and included in this meta-analysis. All studies were of low risk of bias and medium-high quality with the PEDro score ≥5 points. The pooled effect showed that there was no significant difference in the primary outcomes between IA injection and SA injection, with an exception of VAS at 2-3 weeks ( P =0.02) and ROM of internal rotation at 8-12 weeks ( P =0.02). According to the results of subgroup analyses, the differences of VAS and ROM of internal rotation did not last beyond the 2-3-week time period. Additionally, SA injection had the advantage of avoiding adverse reactions from the corticosteroid, especially in avoiding a large fluctuation of serum blood glucose levels., Conclusions: When corticosteroid injection is used to treat adhesive capsulitis, both injection sites can be selected. However, due to the scarcity of related studies, more rigorous trials are needed to confirm the current findings., Competing Interests: No authors have conflicts of interest to declare., (Copyright © 2019 Xiaoke Shang et al.)

In the past few years, bisphenol A, (BPA) an endocrine-disrupting chemical, has received increasing attention because of its detrimental health effects. There is ample evidence to support that BPA interferes with the reproductive health of humans and animals. In spermatozoa, BPA-induced adverse effects are mostly caused by increased oxidative stress. Using an in vitro experimental model, we examined whether antioxidants (glutathione, vitamin C, and vitamin E) have defensive effects against BPA-induced stress in spermatozoa. The results showed that antioxidants inhibit the overproduction of reactive oxygen species (basically cellular peroxides) and increase intracellular ATP levels, thereby preventing motility loss and abnormal acrosome reaction in BPA-exposed spermatozoa. In particular, glutathione and vitamin E reduced the protein kinase A-dependent tyrosine phosphorylation in spermatozoa and, thus, prevented the precocious acrosome reaction from occurring. Furthermore, we found that the compromised fertilisation and early embryo development mediated by BPA-exposed spermatozoa can be improved following their supplementation with glutathione and vitamin E. Based on these findings, we suggest that antioxidants reduce oxidative stress in BPA-exposed spermatozoa, thus preventing detrimental effects on their function and fertility.

Arthrofibrosis is a prevalent condition affecting greater than 5% of the general population and leads to a painful decrease in joint range of motion (ROM) and loss of independence due to pathologic accumulation of periarticular scar tissue. Current treatment options are limited in effectiveness and do not address the underlying cause of the condition: accumulation of fibrotic collagenous tissue. Herein, the naturally occurring peptide hormone relaxin-2 is administered for the treatment of adhesive capsulitis (frozen shoulder) and to restore glenohumeral ROM in shoulder arthrofibrosis. Recombinant human relaxin-2 down-regulates type I collagen and α smooth muscle actin production and increases intracellular cAMP concentration in human fibroblast-like synoviocytes, consistent with a mechanism of extracellular matrix degradation and remodeling. Pharmacokinetic profiling of a bolus administration into the glenohumeral joint space reveals the brief systemic and intraarticular (IA) half-lives of relaxin-2: 0.96 h and 0.62 h, respectively. Furthermore, using an established, immobilization murine model of shoulder arthrofibrosis, multiple IA injections of human relaxin-2 significantly improve ROM, returning it to baseline measurements collected before limb immobilization. This is in contrast to single IA (sIA) or multiple i.v. (mIV) injections of relaxin-2 with which the ROM remains constrained. The histological hallmarks of contracture (e.g., fibrotic adhesions and reduced joint space) are absent in the animals treated with multiple IA injections of relaxin-2 compared with the untreated control and the sIA- and mIV-treated animals. As these findings show, local delivery of relaxin-2 is an innovative treatment of shoulder arthrofibrosis., Competing Interests: Conflict of interest statement: M.W.G., E.K.R., and A.N. are coinventors on a patent application submitted to the United States Patent and Trademark Office on the application of human relxin-2 as a treatment for arthrofibrosis.

Background: Primary adhesive capsulitis is mainly characterized by spontaneous chronic shoulder pain and the gradual loss of shoulder motion. The main treatment for adhesive capsulitis is a trial of conservative therapies, including analgesia, exercise, physiotherapy, oral nonsteroidal anti-inflammation drugs, and intra-articular corticosteroid injections. Previously, it was reported that intra-articular corticosteroid lead to fast pain relief and improvement of range of motion (ROM). The objective of this study was to determine whether corticosteroid injections would lead to better pain relief and greater improvement in ROM., Methods: We searched PubMed, Medline, and the Cochrane library. We included 5 articles of the 1166 articles identified. Totally injection group included 115 patients and placebo group included 110 patients. We calculated the weighted mean differences to evaluate the pain relief as the primary outcome. We determined the ROM as the secondary outcome. Study quality was evaluated using the 12-item scale. We also used the criteria of the Grading of Recommendations Assessment, Development and Evaluation to evaluate the quality of evidence., Results: In total, 5 studies were included, 4 of which were randomized clinical trials, with a sample size of 225 patients with adhesive capsulitis of the shoulders. The overall pooled data demonstrated that, compared with placebo as control treatment, intra-articular corticosteroid injections were more effective in reducing the pain score at 0 to 8 weeks, but there was no difference between the injection group and the control group at 9 to 24 weeks. Improvement of ROM in the injection group was greater than that of the control group both at 0 to 8 and 9 to 24 weeks., Conclusions: Intra-articular corticosteroid injections were more effective in pain relief in the short term, but this pain relief did not sustain in the long term. Intra-articular corticosteroid injection resulted in greater improvement in passive ROM both in the short and the long terms.

Background and Objectives: In this study it was aimed to examine the histological and morphometric effects on cartilage structure of intra-articular application of levobupivacaine to the shoulder joint., Methods: In twenty New Zealand adult male rabbits, 35 shoulders were used for the study and prepared in 5 groups of 7. These groups were defined as Groups L1, L2, L3 and L4 which were right shoulders administered with 0.25% and 0.5% levobupivacaine, Group C which were left shoulders as the control group and Groups S1 and S2 which were left shoulders administered with 0.9% saline. On the 2nd and 15th days the animals were killed, the glenohumeral joints were evaluated macroscopically then cartilage samples were taken. These samples were evaluated with Mankin score, and histomorphometrically by measuring the thickness of the cartilage between the superficial cartilage layer and the tidemark and the thickness of calcified cartilage between the tidemark and the subchondral bone., Results: Macroscopically, on the 15th day the joint fluid was seen to have reduced in all the groups. After microscopic evaluation, the highest Mankin score (mean: 3.14±2.1/14) was in the L4 group (15th day 0.5% levobupivacaine) and was found to be statistically significant (p<0.05). No statistically significant difference was determined between the other groups., Conclusions: Histologically, as the highest Mankin score was in the L4 group, this indicates that in a single intra-articular injection of levobupivacaine a low concentration should be selected., Level of Evidence: Level 5, animal study., (Copyright © 2016 Sociedade Brasileira de Anestesiologia. Published by Elsevier Editora Ltda. All rights reserved.)

Background: Conservative and even surgical management of adhesive capsulitis often is prolonged and painful. Management of adhesive capsulitis is lacking evidence-based controlled clinical trials., Questions/purposes: We asked: (1) Does a collagenase clostridium histolyticum (CCH) injection lyse shoulder capsule collagen in adhesive capsulitis and at what dose? (2) Can a shoulder capsule injection be administered extraarticularly? (3) Do CCH injections result in better scores for pain and function than can be achieved with physical therapy among patients with adhesive capsulitis?, Methods: First, 60 patients with adhesive capsulitis were evaluated by clinical examination. To make the diagnosis of adhesive capsulitis, a patient had to have restricted active ROM of at least 60° in total active ROM in the affected shoulder compared with the unaffected contralateral shoulder; with the scapula stabilized, external rotation with the elbow at the side was a very important determinant. Patients were randomized to receive a single injection of 0.5 mL placebo or 0.145, 0.29, or 0.58 mg CCH. All 60 patients were followed up at 30 days. After that, if patients did not attain treatment thresholds they were eligible for up to five open-label 0.58-mg collagenase injections. For the longer-term followup in the open-label phase, 53 patients (83%) were followed to 12 months, 46 (77%) for 24 months, 36 (60%) for 36 months, 37 (62%) for 48 months, and 25 (42%) for 60 months. The extraarticular injection was directed at the anterior shoulder capsule with the patient in the supine position. To prove that these injections could be delivered reliably to the anterior shoulder capsule extraarticularly, the next study involved volunteers without adhesive capsulitis, in which 10 volunteers received a 10-mL injection of normal saline under ultrasound guidance. Finally, to determine the efficacy and dosing of CCH, four cohorts of 10 patients received up to three ultrasound-guided injections separated by 21 days. These injections were administered at one of four dose-volume levels. A fifth cohort of 10 patients was used as a control group and performed standardized home shoulder exercises only. All patients performed standardized home shoulder exercises three times daily. For Study 3, followup was at 22, 43, 64, and 92 days. No patients were lost to followup., Results: In the first study, a single CCH injection did not provide clinically important improvements from baseline in active ROM, passive ROM, and function and pain scores compared with patients who received placebo. Ultrasound guidance confirmed extraarticular injection of the shoulder capsule in Study 2. The CCH injection was more effective than exercise therapy alone at 0.58 mg/1 mL and 0.58 mg/2 mL compared with exercise only in the primary measure of efficacy (active forward flexion) as shown in Study 3. For active forward flexion the mean in degrees in the 0.58 mg/2 mL group was 38° compared with 12° in the exercise-only group (p = 0.03). For active forward flexion the mean in the 0.58 mg/1mL group was 43° compared with 12° in the exercise-only group (p = 0.01)., Conclusions: Extraarticular injections of CCH for treatment of adhesive capsulitis were well tolerated and seem effective compared with exercise therapy. Future FDA-regulated clinical trials must verify CCH injection therapy for adhesive capsulitis., Level of Evidence: Level II, therapeutic study.

Background: Corticosteroid injection has a wide range of success in adhesive capsulitis but the reason for this has not yet been explained. We hypothesized that this difference might be due to the distribution of the corticosteroids injected into the joint cavity because particulate steroid deposits in the capsule and will not be moved over time by shoulder motion., Objectives: The purpose of this study is to determine whether the therapeutic efficacy of particulate corticosteroid injection into the glenohumeral joint differs according to the dispersion pattern., Study Design: Prospective evaluation., Setting: Outpatient clinics at a tertiary university hospital., Methods: Seventy-two patients diagnosed as having adhesive capsulitis received a corticosteroid injection at the glenohumeral joint. The posterior capsule and the subscapular bursa were selected as dispersion sites and the dispersion of contrast dye was expressed as a ratio (%). Two weeks and 3 months after the injection clinical improvement ("not improved," "slightly improved," "much improved"), numeric rating scale (NRS), and passive range of motions (PROM) were evaluated. The dispersion of the contrast dye was compared according to the clinical improvements by an analysis of variance test. Pearson correlation test was done to find the relationship between PROM and the dispersion and between change of NRS and the dispersion., Results: The distribution in the subscapular area was 30.0% in the "much improved" group, 22.0% in the "slightly improved" group, and 37.1% in the "no improvement" group which was not significantly different (P = 0.179). Correlations between changes of NRS and the dye distribution were not statistically significant (P = 0.429 at 2 weeks and P = 0.629 at 3 months). The change of passive external rotation 3 months after the injection was significantly correlated with the dye distribution (P = 0.035)., Limitations: Because of diverse pathologic findings in adhesive capsulitis, further studies will be needed to address the effect of the dye distribution on the pain improvement according to pathologic findings revealed by magnetic resonance imaging (MRI)., Conclusion: External rotation of the shoulder in adhesive capsulitis has greater improvement as the corticosteroid solutions injected into the glenohumeral joint are increasingly dispersed to the subscapularis area. However, this does not affect the pain improvement after the injection.

Introduction: Adhesive capsulitis (AC) of the shoulder presents with an insidious onset of pain and progressive limitation of shoulder movement., Objectives: To investigate whether intra-articular hyaluronic acid (HA) administration alone is superior to conventional therapies and whether the addition of intra-articular HA administration to conventional therapies improves clinical outcomes in patients with AC., Methods: The PubMed, EMBASE, CINAHL, and Cochrane Library electronic databases were searched without language restrictions in July 2014 with a priori defined inclusion and exclusion criteria., Results: Four randomized controlled trials (273 participants, 278 shoulders) were included in this review. Two trials compared intra-articular HA administration with conventional therapies and 2 trials evaluated intra-articular HA administration as an addition to conventional therapies. Pain and shoulder function/disability outcomes in the HA injection group were not superior to those achieved in the conventional therapy groups. No significant differences in pain or shoulder function/disability outcomes were noted between the groups with and without adjunctive HA administration., Conclusions: Intra-articular HA administration alone is not superior to conventional AC treatments, and the addition of intra-articular HA administration to conventional therapies does not provide significant added benefits. HA administration in AC patients who are receiving conventional therapies should be evaluated to avoid unnecessary medical expenditure.

Background: The early management of orthopaedic outpatients by physiotherapists may be useful in reducing public hospital waiting lists. Physiotherapists in Australia are prevented by legislation and funding models from investigating, prescribing, injecting and referring autonomously. This gap in service is particularly noticeable in the management of shoulder pain in early-access physiotherapy services, as patients needing corticosteroid injection face delays or transfer to other services for this procedure. This trial will investigate the clinical (decision making and outcomes) and economic feasibility of a physiotherapist prescribing and delivering corticosteroid and local anaesthetic injections for shoulder pain in an Australian public hospital setting., Methods/design: A double-blinded (patient and assessor) non-inferiority randomised controlled trial will compare an orthopaedic surgeon and a physiotherapist prescribing and delivering corticosteroid injections to the shoulder. Agreement in decision making between the two clinicians will be investigated, and economic information will be obtained for estimating disease burden and an economic evaluation. The surgeon and the physiotherapist will independently assess patients, and 64 eligible participants will be randomised to receive subacromial injection of corticosteroid and local anaesthetic from either the surgeon or the physiotherapist. Post-injection, all participants will receive physiotherapy. The primary outcome measure will be the Shoulder Pain and Disability Index measured at baseline, and at 6 and 12 weeks post-injection. Analysis will be conducted on an intention-to-treat basis and compared to a per-protocol analysis. A cost-utility analysis will be undertaken from the perspective of the health funder., Discussion: Findings will assist policy makers and services in improving access for orthopaedic patients., Trial Registration: Australia and New Zealand Clinical Trials Registry: 12612000532808 First registered: 21 May 2012. First participant randomized: 16 January 2013.

Objectives: To investigate the prevalence of ultrasonographic (US) shoulder abnormalities in patients with rheumatoid arthritis (RA) and to investigate the relationship between US findings and demographic and clinical features., Methods: Consecutive patients attending the rheumatology units involved in this study were enrolled. Clinical and demographical data were recorded. US of bilateral shoulders was performed at the same time, examining tendons, bursae, gleno-humeral and acromion-clavicular joints. The presence of signs of inflammation, bone erosions or rotator cuff pathology was evaluated., Results: A total of one hundred patients were enrolled, mean age (SD) 59.6 (14.7) years, median disease duration (IQR) 56.5 (34.7, 96.5) months, 98% of them were on DMARDs and 22% on biologics. Shoulder tenderness was reported by 44% of patients. 34% of patients showed at least one sign of inflammatory involvement, and 25% of them presented with humeral head erosions. Signs of rotator cuff pathology were seen in 49% of patients. Agreement between the presence of spontaneous pain and US inflammatory abnormalities was moderate (kappa 0.501). Patients with inflammatory involvement of the shoulders had significantly higher DAS28, HAQ, VAS pain, acute phase reactants and disease duration compared to patient with no inflammatory signs, they were more frequently RF positive and reported more frequently spontaneous pain., Conclusions: US assessment of the shoulder in RA patients can be considered of value, especially in patients with relevant indicators of disease activity and severity.

Objective: To compare the clinical and functional outcomes of US-guided (USG) vs landmark-guided (LMG) injection for the treatment of adults with shoulder pathology., Method: MEDLINE, AMED and Embase in addition to unpublished literature databases were searched from 1950 to August 2011. Studies were included if they were randomized or non-randomized controlled trials comparing USG vs LSG injections for the treatment of adults with shoulder pathology. Two reviewers independently performed data extraction and appraisal of the studies. Meta-analyses were performed where possible and when inappropriate a narrative review of the data was presented., Results: Six papers including 307 patients were reviewed; 142 received LMG injections and 165 received USG injections. There was a statistically significant difference in favour of USG for pain at 6 weeks (standardized mean difference 1.03; 95% CI 0.12, 1.93; P = 0.03). There was no statistically significant difference between the injection methods with respect to shoulder function (standardized mean difference 0.33; 95% CI -0.59, 1.25; P = 0.48). There was a significant difference between interventions for shoulder abduction at 6 weeks in favour of the USG method (mean difference 2.81; 95% CI 0.67, 4.95; P = 0.01). No other movements showed a statistically significant difference., Conclusion: There is a statistically significant difference in pain and abduction between LMG and USG steroid injections for adults with shoulder pathology. However, these differences are small and may not represent clinically useful differences. The current evidence base is limited by a number of important methodological weaknesses, which should be considered when interpreting these findings. The cost-effectiveness of the intervention should be considered in the design of future studies.

Purpose: The aim of this study was to compare shoulder manipulation and arthroscopic arthrolysis with glenohumeral steroid injections in patients affected by idiopathic adhesive shoulder capsulitis., Methods: In this prospective study we randomly assigned patients to enter group A (23 patients, shoulder manipulation and arthroscopic arthrolysis) and group B (21 patients, glenohumeral steroid injections). Patients were followed-up at three, six and 12 weeks, and at six and 12 months with the Constant and Murley, ASES, UCLA and SST evaluation scales. Moreover, passive forward flexion, abduction, and internal and external rotations were recorded., Results: Range of motion showed satisfactory results in both groups at final follow-up: in group A the mean ABD increased from 60° to 154°, ER from 20° to 40°, and FF from 75° to 174°; in group B, ABD raised from 76° to 145°, ER from 20° to 35°, and FF from 115° to 164°. All the evaluation scales performed increased significantly at final follow-up in both groups. However, while patients of group A had already reached significant improvement at the six-week follow-up (p <0.03), in group B this happened only at the 12 week follow-up (p <0.03)., Conclusions: Both types of treatment were effective in improving final range of motion; however, while patients of group A accomplished their goal by the six-week follow-up, in group B the same result was obtained at the 12-week follow-up.

Background: Little is known about the rate and factors of progression of shoulder osteonecrosis (ON) related to corticosteroids., Purpose: We retrospectively evaluated 125 patients (215 shoulders) with humeral head ON diagnosed by MRI to determine the delay between corticosteroid treatment and the different stages and factors influencing the progression of the disease., Methods: Seventy-four of the shoulders had asymptomatic Stage I ON, 58 had asymptomatic Stage II ON, 46 had symptomatic Stage I ON, and 37 had symptomatic Stage II ON. The minimum followup was 10 years (average, 14 years; range, 10-20 years). The delay between the beginning of the corticosteroid treatment and the diagnosis of ON of the humeral head averaged 15 months (range, 6-24 months)., Results: We observed partial or total regression on MRI only in patients with asymptomatic Stage I ON. At last followup, pain had developed in 98 (74%) and collapse had occurred in 71 (54%) of the 132 previously asymptomatic shoulders. Of the 83 symptomatic shoulders, 68 (82%) had collapsed at the final followup. The time between diagnosis and collapse averaged 10 years for patients with symptomatic Stage I ON and 3 years for patients with symptomatic Stage II ON., Conclusions: Stage at initial visit, occurrence of pain, and continuation of peak doses of corticosteroids predicted progression of disease in asymptomatic shoulders, whereas in the symptomatic shoulders, extent and location of the lesion were the main risk factors for progression., Level of Evidence: Level II, prognostic study. See Guidelines for Authors for a complete description of levels.

Patients commonly present to primary care physicians with musculoskeletal symptoms. Clinicians certified in internal medicine must be knowledgeable about the diagnosis and management of musculoskeletal diseases, yet they often receive inadequate postgraduate training on this topic. The musculoskeletal problems most frequently encountered in our busy injection practice involve, in decreasing order, the knees, trochanteric bursae, and glenohumeral joints. This article reviews the clinical presentations of these problems. It also discusses musculoskeletal injections for these problems in terms of medications, indications, injection technique, and supporting evidence from the literature. Experience with joint injection and the pharmacological principles described in this article should allow primary care physicians to become comfortable and proficient with musculoskeletal injections.

Objective: To describe an outbreak of invasive methicillin-resistant Staphylococcus aureus (MRSA) infection after percutaneous needle procedures (acupuncture and joint injection) performed by a single medical practitioner., Setting: A medical practitioner's office and 4 hospitals in Perth, Western Australia., Patients: Eight individuals who developed invasive MRSA infection after acupuncture or joint injection performed by the medical practitioner., Methods: We performed a prospective and retrospective outbreak investigation, including MRSA colonization surveillance, environmental sampling for MRSA, and detailed molecular typing of MRSA isolates. We performed an infection control audit of the medical practitioner's premises and practices and administered MRSA decolonization therapy to the medical practitioner., Results: Eight cases of invasive MRSA infection were identified. Seven cases occurred as a cluster in May 2004; another case (identified retrospectively) occurred approximately 15 months earlier in February 2003. The primary sites of infection were the neck, shoulder, lower back, and hip: 5 patients had septic arthritis and bursitis, and 3 had pyomyositis; 3 patients had bacteremia, including 1 patient with possible endocarditis. The medical practitioner was found to be colonized with the same MRSA clone [ST22-MRSA-IV (EMRSA-15)] at 2 time points: shortly after the first case of infection in March 2003 and again in May 2004. After the medical practitioner's premises and practices were audited and he himself received MRSA decolonization therapy, no further cases were identified., Conclusions: This outbreak most likely resulted from a breakdown in sterile technique during percutaneous needle procedures, resulting in the transmission of MRSA from the medical practitioner to the patients. This report demonstrates the importance of surveillance and molecular typing in the identification and control of outbreaks of MRSA infection.

Background: Recent reports have noted the appearance of postarthroscopic glenohumeral chondrolysis. Although this devastating process has been identified, no cause has been directly identified., Hypothesis: A cause of postarthroscopic glenohumeral chondrolysis will be associated with a specific factor (ie, implanted device, surgical technique, etc), and this factor can be identified by a review and comparison of cases seen in the senior author's office., Study Design: Case series; Level of evidence, 4., Methods: Analyze possible etiologic factors with imaging studies, demographics, history, and physical examinations of 10 patients (12 shoulders) with postarthroscopic glenohumeral chondrolysis, and then compare perisurgical information with a focused chart review and comparison with the rest of the 177 arthroscopic shoulder surgeries in the same period of time., Results: There were 12 cases of postarthroscopic glenohumeral chondrolysis (all were the senior author's patients). Four common factors were identified, and only high-flow intra-articular pain pump catheters filled with bupivacaine and epinephrine were a new addition to years of shoulder surgery by the senior author; 177 shoulders underwent arthroscopy in the identified time frame, and only 19 shoulders, of 30 with capsular procedures, had intra-articular pain pump catheters filled with bupivacaine and epinephrine. Of these, 12 have been identified with chondrolysis., Conclusion: Use of intra-articular pain pump catheters eluting bupivacaine with epinephrine appear highly associated with postarthroscopic glenohumeral chondrolysis., Clinical Relevance: Intra-articular pain pump catheters, especially those eluting bupivacaine with epinephrine, should be avoided until further investigation.

Background: While hylan G-F 20 is an approved therapy for the treatment of knee osteoarthritis, there are few reports of its use in shoulder osteoarthritis., Hypothesis: Hylan G-F 20 can reduce pain and improve function in patients with glenohumeral osteoarthritis., Study Design: Case series; Level of evidence, 4., Methods: Thirty consecutive patients with idiopathic glenohumeral osteoarthritis who failed to respond to standard conservative measures were enrolled. Patients received 3 weekly intra-articular hylan G-F 20 injections in their affected shoulder and completed a visual analog scale for pain, the UCLA score, and the Simple Shoulder Test at baseline and at 1, 3, and 6 months after the third injection., Results: Of the 30 patients, 3 withdrew during the washout period before treatment; the remaining patients (17 men and 10 women) had an average age of 62 years. The mean baseline visual analog scale score was 54, UCLA score was 15.7, and Simple Shoulder Test score was 5.7 (of 12 possible "yes" responses). At the 6-month follow-up, hylan G-F 20 significantly improved visual analog scale (mean 30, P < .001), UCLA (mean 24, P < .001), and Simple Shoulder Test (7.6 "yes" responses, P < .001) scores. More patients slept comfortably after treatment (56%) versus before treatment (15%). Nine patients had a visual analog scale improvement >40 points after 6 months. No device-related adverse events were observed., Conclusion: Hylan G-F 20 may have a beneficial therapeutic effect on some symptomatic patients with glenohumeral osteoarthritis.

Muscle symptoms are known as adverse effects of HMG-CoA reductase inhibitors but their incidence is reported to be low. We treated a case of shoulder stiffness related to such a drug, which prompted us to preliminarily survey its incidence. We found that nearly one-tenth of women (6/66) taking such drugs reported drug-related shoulder stiffness. Shoulder stiffness is a very common symptom, while drug-induced shoulder stiffness is generally unknown. Many cases involving such an adverse effect may thus be overlooked. We present 2 typical cases here.

In order to clarify the later sequelae of sarin poisoning that occurred in Matsumoto City, Japan, on June 27, 1994, a cohort study was conducted on all persons (2052 Japanese people) inhabiting an area 1050 meters from north to south and 850 meters from east to west with the sarin release site in the center. Respondents numbered 1237 and 836 people when surveys were conducted at one and three years after the sarin incident, respectively. Numbers of persons with symptoms of sarin toxicity were compared between sarin victims and non-victims. Of the respondents, 58 and 46 people had symptoms associated with sarin such as fatigue, asthenia, shoulder stiffness, asthenopia and blurred vision at both points of the survey, respectively. The prevalences were low; some complained of insomnia, had bad dreams, difficulty in smoking, husky voice, slight fever and palpitation. The victims who had symptoms one year after the incident had a lower erythrocyte cholinesterase activity than did those who did not have symptoms at the early stage; such persons lived in an area with a 500 meter long axis north east from the sarin release site. The three-year cohort study clearly showed that the odds ratios of almost all of the symptoms were high in the sarin-exposed group, suggesting a positive relationship between symptoms and grades of exposure to sarin. These results suggest that symptoms reported by many victims of the sarin incident are thought to be sequelae related to sarin exposure.

Elevated serum levels of keratan sulfate (KS) and hyaluronate (HA) in patients with osteoarthritis (OA) have been reported. We measured KS and HA in dogs to determine if there was an elevation of these serum glycosaminoglycans in a canine model of OA. A single intraarticular injection of 1 mg of chymopapain into a shoulder joint increased serum KS by tenfold, and HA by less than twofold, in 24 hours. Serum KS and HA levels were 3-5-fold higher in dogs younger than 2 months of age than in older dogs. Serum KS and HA concentrations and synovial fluid KS concentrations were unrelated to spontaneous cartilage degeneration in 1-year-old dogs. Higher KS levels in synovial fluid correlated with higher KS levels in serum (r = 0.54, P less than 0.025). The mean KS concentration in sera of older dogs (greater than 3 years old) with OA was 37% higher than that in disease-free controls, but the difference between the groups was not statistically significant. Thus, elevated levels of serum KS and HA do not appear to have clinical significance in this model of OA.