Comparison of efficacy and safety of complementary and alternative therapies for scapulohumeral periarthritis: A protocol for Bayesian network meta-analysis.

BACKGROUND: Scapulohumeral periarthritis is a disease with high incidence and great pain. The current western treatments with many side effects, poor efficacy cannot fundamentally solve the problem. Complementary and alternative therapies have played an excellent role in the treatment of scapulohumeral periarthritis. However, it is not clear which complementary and alternative therapy is more effective. Therefore, we propose a protocol to compare the efficacy and safety of various complementary and alternative therapies through network meta-analysis (NMA) to provide choice guidance for the therapy. METHODS: A comprehensive search will be conducted for randomized controlled trials of complementary and alternative therapy for scapulohumeral periarthritis as well as ongoing trials. The time limit is from the establishment of the database until January 2021. Literature and data extraction were completed independently by two researchers. Through pairwise comparison and meta-analysis of Bayesian NMA, all the evidences are evaluated comprehensively. STATA16.0 and WinBUGS1.4.3 software will be used for data processing and analysis, and recommendation evaluation will be used to develop and assess grades to classify the quality of NMA evidence. RESULTS: Through the analysis, we will obtain the ranking of the efficacy and safety of different complementary and alternative therapies in the treatment of scapulohumeral periarthritis, in order to provide reference for clinical selection of treatment methods. CONCLUSION: Complementary and alternative therapies of scapulohumeral periarthritis plays a positive role in improving the symptoms of scapulohumeral periarthritis. This study can provide evidence support for clinicians and patients.International Platform of Registered Systematic Review and Meta-Analysis Protocols registration number: INPLASY202140044.

The association between Interleukin-6 rs1800795/rs1800797 polymorphisms and risk of rotator cuff tear in a Chinese population.

Expression of proinflammatory cytokines, such as interleukin (IL)-6 (IL-6) and metalloproteases, are elevated in patients with rotator cuff tear (RCT). In order to investigate the role of IL-6 gene polymorphisms on RCT risk, we genotyped two SNPs on IL-6 gene (rs1800795 and rs1800797) in 138 RCT patients and 137 healthy controls using polymerase chain reaction (PCR) and Sanger sequencing. The IL-6 expression in shoulder joint synovial fluid was determined by using enzyme-linked immunosorbent assay (ELISA) method. The constant score and visual analog scale (VAS) were used to evaluate the clinical outcome of two s (surgicsal vs. conservative) for RCT patients. For rs1800795, individuals with the GG genotype or G allele had significantly higher risk of RCT. Elevated risk of tear size was associated with the GG genotype of the rs1800795 polymorphism. The IL-6 rs1800797 polymorphism was also associated with an increased risk of RCT, especially among female, drinkers, and individuals with B(MI) < 25 kg/m2. The elevated levels of IL-6 gene were observed among the mutant genotype of rs1800795/rs1800797 polymorphism. Surgical group is significantly better than conservative treatment from the perspective of constant score and VAS. Furthermore, CG genotype of rs1800795 polymorphism increased the constant score at 6 months in comparison with CC genotype. In conclusion, our study supports a role of IL-6 rs1800795/rs1800797 polymorphisms on increased RCT risk. The RCT patients with CG genotype of rs1800795 polymorphism have more obvious surgical treatment effects by influencing the IL-6 expression.

Fibroblast activation and inflammation in frozen shoulder.

INTRODUCTION: Frozen shoulder is a common, fibro-proliferative disease characterised by the insidious onset of pain and progressively restricted range of shoulder movement. Despite the prevalence of this disease, there is limited understanding of the molecular mechanisms underpinning the pathogenesis of this debilitating disease. Previous studies have identified increased myofibroblast differentiation and proliferation, immune cell influx and dysregulated cytokine production. We hypothesised that subpopulations within the fibroblast compartment may take on an activated phenotype, thus initiating the inflammatory processes observed in frozen shoulder. Therefore, we sought to evaluate the presence and possible pathogenic role of known stromal activation proteins in Frozen shoulder. METHODS: Shoulder capsule samples were collected from 10 patients with idiopathic frozen shoulder and 10 patients undergoing shoulder stabilisation surgery. Fibroblast activation marker expression (CD248, CD146, VCAM and PDPN, FAP) was quantified using immunohistochemistry. Control and diseased fibroblasts were cultured for in vitro studies from capsule biopsies from instability and frozen shoulder surgeries, respectively. The inflammatory profile and effects of IL-1ß upon diseased and control fibroblasts was assessed using ELISA, immunohistochemistry and qPCR. RESULTS: Immunohistochemistry demonstrated increased expression of fibroblast activation markers CD248, CD146, VCAM and PDPN in the frozen shoulder group compared with control (p < 0.05). Fibroblasts cultured from diseased capsule produced elevated levels of inflammatory protein (IL-6, IL-8 & CCL-20) in comparison to control fibroblasts. Exposing control fibroblasts to an inflammatory stimuli, (IL-1ß) significantly increased stromal activation marker transcript and protein expression (CD248, PDPN and VCAM). CONCLUSIONS: These results show that fibroblasts have an activated phenotype in frozen shoulder and this is associated with inflammatory cytokine dysregulation. Furthermore, it supports the hypothesis that activated fibroblasts may be involved in regulating the inflammatory and fibrotic processes involved in this disease.

Microdialysis to Quantify Inflammatory Cytokines in the Glenohumeral Joint: A Brief Methods Report.

Microdialysis quantifies in vivo soft-tissue biochemical concentrations via passive diffusion of interstitial molecules through a porous membrane into a dialysate. The purpose of this pilot study was to evaluate a technique to measure inflammatory cytokines associated with rotator cuff tendinopathy by inserting a microdialysis catheter into the posterior glenohumeral joint. The technique was tested in a convenience sample of six pain-free, able-bodied veterans. Complete dialysate samples were collected in two participants. Two participants' sample volumes were smaller than what was required for analysis (30 µl) and thus were diluted. Catheter failures in two participants prevented collection altogether. Three cytokine concentrations were quantified: interleukin-1 receptor antagonist, interleukin 8, and regulated on activation, normal T-cell expressed and secreted. Microdialysis is not recommended for use in the glenohumeral joint, yet quantification of glenohumeral joint cytokines could yield valuable information to better understand pathophysiology of the joint and its surrounding tissues. Another technique, such as joint lavage, may be a more attractive alternative to overcome the limitations of microdialysis in the glenohumeral joint.

Process of neovascularisation compared with pain intensity in tendinopathy of the long head of the biceps brachii tendon associated with concomitant shoulder disorders, after arthroscopic treatment. Microscopic evaluation supported by immunohistochemical.

BACKGROUND: Tendinopathy of the long head of the biceps brachii tendon (LHBT) is one of the most common, painful conditions of the anterior part of the shoulder and often coexists with rotator cuff tears. Multifactorial aetiopathology of tendi-nopathy is poorly understood; however, several studies indicated that it is seen predominantly in areas with decreased vascularity of the tissue; the pathology is also characterised by expansive and abundant neovascular in-growth. The aim of the study was to investigate the relationship between the neovascularisation of proximal part of the LHBT and pain along the bicipital groove. MATERIALS AND METHODS: Tissue material was obtained from 28 patients who underwent a shoulder arthroscopy and experienced pain along the bicipital groove measured using Visual-Analog Scale (VAS) score. CD31 and CD34 molecules were visualised by immunohistochemical method to assess biceps tendon neovascula-risation and quantify it based on a Bonar scoring system. RESULTS: Although all patients reported pain prior to arthroscopy (mean VAS score was 7.5), microscopic examination did not reveal neovascularisation in all cases. Immunohistochemical staining for CD31 and CD34 allowed for very precise visualisation and quantification of neovascularisation; however there was also no correlation between vessels in-growth scores and pain. CONCLUSIONS: The obtained data suggest that neovascularisation process in tendino-pathy is not directly related to pain; however, further studies are needed to explain its significance in the LHBT tendinopathy. (Folia Morphol 2018; 77, 2: 378-385).

Shoulder pain and intra-articular interleukin-8 levels in patients with rotator cuff tears.

AIM: Rotator cuff disease (RCD) is one of the most common disorders in the shoulder joint and causes joint pain and functional disability. In this study, we investigated the associations among cytokine levels and clinical symptoms in patients with RCD. METHOD: Joint fluid specimens of the shoulder joint were obtained from 38 patients with RCD before arthroscopic surgery. The levels of inflammatory cytokines, including interleukin (IL)-1ß, IL-6 and IL-8, were evaluated using enzyme-linked immunosorbent assay kits, and the associations between these cytokine levels and the clinical symptoms were determined. A multiple linear regression analysis was performed to identify the parameters accounting for the visual analogue scale (VAS) score at rest. RESULTS: IL-8 level was correlated with IL-6 (r = 0.434, P = 0.006) and IL-1ß (r = 0.575, P < 0.001) levels. The cuff tear size was inversely correlated with the VAS score at rest. A multiple stepwise linear regression analysis revealed that the VAS score at rest could be explained by the VAS score at night, the VAS score during movement and the intra-articular IL-8 level (adjusted R² = 0.544, P < 0.001). The intra-articular IL-8 level is associated with resting pain in rotator cuff tear patients. CONCLUSION: These results suggest that an increased concentration of IL-8 is associated with resting pain in rotator cuff tear patients.

Ultrasound imaging for the rheumatologist XLVIII. Ultrasound of the shoulders of patients with rheumatoid arthritis.

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.

Increased interleukin 1ß levels in the subacromial fluid in diabetic patients with rotator cuff lesions compared with nondiabetic patients.

BACKGROUND: Diabetic patients have a high prevalence of shoulder pain and stiffness. Interleukin (IL) 1ß was reportedly correlated with shoulder stiffness and decreased shoulder function. We retrospectively compared the expression of IL-1ß in the subacromial synovial fluid between diabetic and nondiabetic patients with rotator cuff tearing. MATERIALS AND METHODS: We enrolled 68 patients with rotator cuff tearing (23 diabetic patients and 45 nondiabetic patients). The preoperative sum of range-of-motion deficit (SROMD), Constant score, and visual analog scale (VAS) score were obtained. Intraoperatively, subacromial synovial fluid was collected for the IL-1ß level measurement. Comparisons of IL-1ß levels, Constant scores, SROMD, and VAS scores between diabetic and nondiabetic patients were analyzed with the Mann-Whitney U test. RESULT: Diabetic patients with rotator cuff tearing had significantly increased subacromial IL-1ß levels (P = .048), SROMD (P < .001) and VAS scores (P = .022) and lower Constant scores (P < .001) than nondiabetic patients. The IL-1ß levels in the subacromial fluid were significantly correlated with the Constant score (r = -0.477, P < .001), VAS score (r = 0.698, P < .001), and SROMD (r = 0.293, P = .015) in all patients. CONCLUSION: The elevated IL-1ß levels in the subacromial fluid of patients with diabetes may explain the likelihood of pain and shoulder stiffness developing in these patients. We suggest more aggressive treatment for rotator cuff lesions in diabetic patients.

Comparison between NSAID and intra-articular corticosteroid injection in frozen shoulder of diabetic patients; a randomized clinical trial.

INTRODUCTION: Frozen shoulder or adhesive capsulitis is a relatively common encountered musculo-skeletal disease in which arouses following soft tissue involvement of glenohumeral joint and presents with pain and limitation of shoulder' active and passive motions. The incidence of frozen shoulder among diabetic patients is about 10-20%, stiffness in such patients is more severe and should be managed actively. Local Glucocorticoid injection, NSAIDs and physiotherapy each can relief the symptoms. The aim of this study was to compare the efficacy of glenohumeral injection of Glucocorticoid with NSAIDs in frozen shoulder of diabetic patients. METHOD: The randomized clinical trial study conducted during Feb 2009-Aug 2010 on diabetic patients with frozen shoulder that were referred to rheumatology and endocrinology clinics, Yazd, Iran. Diagnostic criteria of capsulitis were pain of shoulder and range of motion limitation in all directions. The patients were divided into 2 groups, patients of first group received NSAID while the latter group were undergone intra-articular corticosteroid injection. After 1 week, home exercise was done for both group and evaluation of the patients after first visit was done likewise 2nd, 6th, 12th and 24th weeks. All registered data were transformed into SPSS-15 software and analyzed. RESULTS: Totally 57 patients (19 males (33.3%) and 38 females (66.7%) were included in the analysis. There was no significant difference between sex (P=0.4) and age (P=0.19) of patients. No significant relation was detected between 2 groups after 24 weeks according to range of motion in flexion (P=0.51), abduction (P=0.76), external rotation (0.12) and internal rotation (P=0.91). Also any significant difference in pain score was not detected (P=0.91). CONCLUSION: Based on our study, both intra-articular corticosteroid and NSAID are effective in treatment of adhesive capsulitis and there is no significant difference between efficacies of these 2 treatment modalities in diabetic patients.

Functional staging and surgical intervention of the elbow and shoulder joints in a patient with rheumatoid arthritis.

BACKGROUND: A 46-year-old, nonsmoking, nulliparous woman with a 23-year history of rheumatoid arthritis presented with severely destructed right shoulder, right elbow, and right wrist joints, which resulted in a complete loss of working ability. INVESTIGATIONS: Physical examination, X-ray, MRI, ultrasound, functional staging using the Shoulder Pain and Disability Index, the Patient Rated Elbow Evaluation, the Disabilities of the Arm, Shoulder and Hand, and the health-related quality-of-life Short Form 36 questionnaire, determination of the c-reactive protein level, erythrocyte sedimentation rate, Disease Activity Score 28 and the metalloproteinase profile, and histology of removed synovial tissue. DIAGNOSIS: Severe destruction of the right shoulder and elbow (Larsen grade IV) resulting from late-stage seropositive rheumatoid arthritis. MANAGEMENT: Reconstruction of the elbow and ipsilateral shoulder in a two-step procedure: replacement of the elbow joint with a semiconstrained Gschwend-Scheier-Bahler III (GSB III) elbow prosthesis (Zimmer, Inc., Warsaw, IN) followed by replacement of the shoulder with the Promos Modular Shoulder System (Plus Orthopedics AG, Rotkreuz, Switzerland) 1 month later. The patient received 4 weeks of inpatient rehabilitation.

Assessment of shoulder involvement and disability in patients with ankylosing spondylitis.

The purpose of the study was to evaluate the parameters which have an important role in shoulder involvement and disability in ankylosing spondylitis (AS). Ninety patients with AS were divided into two groups according to the presence of shoulder involvement. Bath AS metrology index (BASMI), ankylosing spondylitis quality of life (ASQoL) and shoulder pain and disability index (SPADI) were used. Ranges of movements of limited shoulders were measured. Mean disease duration, age, BASMI, and ASQoL were higher and hip involvement was more frequent in the shoulder-involved group. Disease duration was found to be the most significant factor in shoulder involvement. A significant relationship was found between all SPADI scores and ASQoL. The SPADI disability score was affected by flexion limitation. Patients with hip involvement and longer disease duration should be evaluated for shoulder involvement. Flexion limitation of shoulder affected shoulder disability and shoulder disability impaired quality of life.

Interleukin-1-induced glenohumeral synovitis and shoulder pain in rotator cuff diseases.

Synovitis of the subacromial bursa has been identified as a main source of shoulder pain in rotator cuff diseases. Little interest, however, has been paid into the synovitis of glenohumeral joint. The mRNA expression levels of interleukin-1beta (IL-1beta) and interleukin-1 receptor antagonists produced in the synovitis reflect the magnitude of inflammation. The present study was undertaken to determine the relationship between mRNA expression levels of IL-1beta and its receptor antagonists (secreted interleukin-1 receptor antagonist (IL-1ra) and intracellular IL-1ra) in the synovium of the glenohumeral joint and shoulder pain in rotator cuff diseases, analyzing the synovial specimens by reverse transcriptase polymerase chain reaction. Thirty-five patients with rotator cuff diseases were candidates. Based on the presence of cuff perforation, they were divided into two categories: 16 with non-perforating tears and 19 with perforating tears. The degree of shoulder pain was evaluated by use of a visual analogue scale. The pain degree of non-perforating tears was significantly greater than that of perforating tears (P < 0.01). In contrast, the expression levels of the cytokine-mRNAs were constitutively greater in perforating tears than in non-perforating tears (P < 0.01, respectively). The expression levels of the cytokine-mRNAs were inversely correlated with the degree of pain (IL-1beta: r = 0.930; secreted IL-1ra: r = 0.861; intracellular IL-1ra: r = 0.932, P < 0.001 respectively). These results suggest that the expression levels of the cytokine-mRNAs in the synovium of the glenohumeral joint contribute less to the generation of shoulder pain in rotator cuff diseases.

Inflamed shoulder structures in polymyalgia rheumatica with normal erythrocyte sedimentation rate.

OBJECTIVE: To investigate the inflammatory involvement of shoulder articular and extraarticular structures in polymyalgia rheumatica (PMR) patients with a normal erythrocyte sedimentation rate (ESR) at diagnosis. METHODS: This was a case-control study. All consecutive, untreated new outpatients diagnosed as having PMR with a normal ESR (<40 mm/hour) during a 6-month period were included in the study (case patients). Controls were 12 consecutive, untreated PMR outpatients with an ESR of >40 mm/hour who were observed after the case patients. Before starting corticosteroid therapy, all case patients and controls underwent bilateral shoulder ultrasonography (US) and magnetic resonance imaging (MRI). US and MRI scans were evaluated independently by two radiologists who were blinded to the reciprocal results. RESULTS: Six case patients (4 men and 2 women) and 12 controls (4 men and 8 women) were studied. Both US and MRI demonstrated bilateral subacromial/subdeltoid bursitis in all 6 case patients and in 11 of the 12 (92%) controls (P not significant [NS]). One control had unilateral bursitis. Glenohumeral joint synovitis was found in 4 of 6 case patients (67%) by MRI and in 3 of 6 case patients (50%) by US (P NS), as well as in 8 of 12 controls (67%) by MRI and in 7 of 12 controls (58%) by US (P NS). Both MRI and US detected biceps tenosynovitis in 5 of 6 case patients (83%) and in 8 of 12 controls (67%) (P NS). The severity of bursitis did not differ significantly between the groups. US was as effective as MRI in detecting inflammatory changes of the shoulder. CONCLUSION: MRI and US studies showed that PMR patients with normal or high ESRs have similar inflammatory shoulder lesions. Moreover, bilateral subacromial/subdeltoid bursitis represents the imaging hallmark in PMR patients with a high or normal ESR. MRI or US of the shoulder may facilitate the proper diagnosis in patients with the typical proximal symptoms of PMR who also have normal ESRs.

Incidence of glenohumeral joint involvement in seropositive rheumatoid arthritis. A 15 year endpoint study.

OBJECTIVE: To evaluate the incidence of involvement and nature of destruction of glenohumeral (GH) joints in a prospectively followed cohort of 74 patients with seropositive and erosive rheumatoid arthritis (RA). METHODS: At the 15 year followup radiographs of 148 GH joints were evaluated, and the grade of destruction was assessed by the Larsen method. RESULTS: Erosive involvement (Larsen grade 2) was observed in 71/148 (48%) GH joints in 41/74 (55%) patients; 30 patients had bilateral and 11 unilateral involvement. The incidence of mild erosions (Larsen grade 2) was 401148 (27%), and of severe (Larsen 3-5) 31/148 (21%). The 11 most severely involved (Larsen grade 5) joints were seen in 6 (8%) patients. Erosions were most often (61/71 joints) observed on the superolateral articular surface of the humerus. Glenoidal involvement was less common (28/71 joints). The Larsen score (0-100) for peripheral joints correlated significantly with the GH joint Larsen grade on both sides (p < 0.001). CONCLUSION: After 15 years more than half the patients with RA showed definite involvement and 1 in 4 had severe destruction of the GH joint. The greatest destruction was almost always bilateral.