The development of frozen shoulder (FS) is primarily characterized by pathological fibrosis, yet clinical treatment options remain limited. Recent studies have identified estrogen depletion during perimenopause as a significant contributor to the onset of FS and fibrosis. This study investigates the role of estradiol (E2) and the estrogen-related receptor (GPER) in fibrotic processes associated with FS to elucidate the underlying mechanisms. The functional relationship between E2, GPER, and FS progression was examined using a rat immobilization model and synovial-derived fibroblasts (SFs) from FS patients. E2's effects on GPER expression, fibroblast activation, and tissue fibrosis were evaluated through Western blotting, immunofluorescence staining, collagen contraction assays, wound healing assays, and histological staining. RNA sequencing identified signaling pathways and key regulators involved in E2 treatment. Both E2 and the GPER activator G1 exhibited antifibrotic effects, improving shoulder mobility, reducing extracellular matrix (ECM) deposition in the periarticular capsule, and decreasing the expression of fibrosis-related genes, including fibronectin, α-SMA, and COL3. In contrast, the GPER inhibitor G15 reversed these effects, suggesting that E2 mediates its antifibrotic action through GPER activation. Mechanistically, KEGG pathway analysis revealed that E2 suppresses the PI3K/AKT signaling pathway by inhibiting PI3K and AKT phosphorylation, thereby preventing fibroblast activation and reversing FS-associated fibrosis. These findings provide mechanistic insights into the previously unrecognized role of GPER in FS progression and may open new avenues for research to optimize future clinical therapies.

The aim of this review is to outline the clinical presentation of patients with shoulder girdle neoplasm to help differentiate it from frozen shoulder contracture syndrome (FSCS) as well as quantify misdiagnosis rates in the literature.

Four electronic databases were searched (Embase, Medline, PUBMED and Scopus) for cohort studies of patients with shoulder girdle neoplasm with or without misdiagnosis as FSCS in line with the PRISMA-ScR guidelines for scoping reviews.

The initial search yielded 2462 studies, 10 of which were included in the final review. The most common symptom of patients with shoulder girdle neoplasm was shoulder pain (62%) followed by swelling/mass/deformity (34%) and local/bony tenderness (13%). In patients with neoplasm initially misdiagnosed as FSCS the main complaints were shoulder pain and subjective stiffness/loss of range of motion (73% each). Misdiagnosis rates ranged from 10% to 50% and resulted in diagnostic delays of up to 30 months.

Key clinical features of bone and soft tissue tumours such as local bony tenderness and careful observation for swelling/mass/deformity should be included in the physical examination to help differentiate between the two pathologies and help guide the choice of initial imaging for the primary contact clinician.

Frozen shoulder (FS) is a complex and multifactorial condition characterized by persistent inflammation, fibrosis, and metabolic dysregulation. Despite extensive research, the underlying drivers of FS remain poorly understood. Recent findings indicate the coexistence of pro-inflammatory and fibrosis-resolving macrophages within affected tissues, suggesting a dysregulated immune response influenced by metabolic and neuroendocrine factors. This review proposes that leptin resistance, a hallmark of metabolic syndrome and chronic inflammation, may play a central role in FS pathogenesis by impairing macrophage polarization, perpetuating inflammation, and disrupting fibrosis resolution. The JAK-STAT signaling pathway, critically modulated by leptin resistance, may further contribute to immune dysregulation by sustaining inflammatory macrophage activation and interfering with tissue remodeling. Additionally, FS shares pathogenic features with fibrotic diseases driven by TGF-β signaling, mitochondrial dysfunction, and circadian disruption, further linking systemic metabolic dysfunction to localized fibrotic pathology. Beyond immune and metabolic regulation, alterations in gut microbiota, bacterial translocation, and chronic psychosocial stress may further exacerbate systemic inflammation and neuroendocrine imbalances, intensifying JAK-STAT dysregulation and leptin resistance. By examining the intricate interplay between metabolism, immune function, and fibrotic remodeling, this review highlights targeting leptin sensitivity, JAK-STAT modulation, and mitochondrial restoration as novel therapeutic strategies for FS treatment. Future research should explore these interconnections to develop integrative interventions that address both the metabolic and immune dysregulation underlying FS, ultimately improving clinical outcomes.

The primary aim of this retrospective study is to compare the short and medium-term outcomes for shoulder hydrodilatation for treatment of shoulder AC between diabetic and non-diabetic patients, to evaluate if there were better outcomes amongst non-diabetic patients.

Patients with clinical or radiological diagnosis of AC and who underwent fluoroscopic guided shoulder hydrodilatation in our local institution from January 2021 to June 2022 were included in this study. Clinical outcomes were measured with visual analog scale (VAS) for pain and passive range of motion consisting of forward flexion (FF) and external rotation (ER) at pre-hydrodilatation, one month and six months post hydrodilatation.

A total of 163 shoulders were included, corresponding to 156 patients consisting of 47 diabetics, 109 non-diabetics and seven bilateral shoulders (3 diabetics and 4 non-diabetics). At the time of presentation, there was no significant difference in VAS, FF or ER between diabetics and non-diabetics. From pre-hydrodilatation to 1-month post-hydrodilatation and one month to six months post-hydrodilatation, there was significant improvement in VAS, FF and ER for both groups. Comparing diabetics vs. non-diabetics, the non-diabetic group had significantly better FF (p < 0.01) at one month post hydrodilatation. At 6 months post-hydrodilatation, non-diabetic group also had significantly better outcomes including VAS score (p = 0.02), FF (p < 0.01) and ER (p = 0.02).

Hydrodilatation is an effective treatment option in the short and medium term in both diabetics and non-diabetics with adhesive capsulitis, with good relief of pain and improvement in shoulder range of motion. Diabetic patients have significantly less improvement in range of motion and pain compared to non-diabetics at six months post hydrodilatation.

This systematic review examines the clinical presentations and prevalence of scapulohumeral periarthritis (SP) by synthesizing the relevant literature from open-access articles from international databases (Medline, Pedro, and EBSCO).

Keywords guiding the review included 'scapulohumeral periarthritis', 'clinical forms', 'incidence', 'impingement syndrome, 'calcifying tendinitis', 'bicipital tendonitis', 'shoulder bursitis', 'adhesive capsulitis or frozen shoulder', 'rotator cuff tears', 'functional assessment', and 'clinical trials'. Eligible studies included randomized controlled trials, nonrandomized controlled trials, cross-sectional studies, and review articles published between 1972 and 2024.

Our screening identified 2481 initial articles, of which 621 were further reviewed for eligibility resulting in 107 articles that met the relevance criteria. The findings highlight six distinct clinical forms of SP, such as partial rotator cuff tears and calcific tendinitis, each characterized by specific pathological features and prevalence patterns. Key factors contributing to SP include injuries, scapular instability, acromion deformities, and degenerative rotator cuff changes. Functional assessments, including the Neer, Hawkins, Pain Arc, and Yocum tests, demonstrated diagnostic value in distinguishing SP from other shoulder conditions.

By comprehensively analyzing the clinical forms, functional assessment methods, and prevalent lesions of SP, functional testing can improve early diagnosis and guide personalized physiotherapy protocols for optimal rehabilitation in the physiotherapist's practice.

To compare clinical outcomes following steroid injections using the anterior and posterior approaches.

Systematic review with meta-analysis.

Embase, Web of Science, and Cochrane Center Register of Controlled Trials were searched for randomized control trials (RCTs) and prospective comparative studies.

Patients with adhesive capsulitis.

Glenohumeral steroid injections using either anterior or posterior approach.

Pain visual analog scale (VAS) and shoulder range of motion (ROM) at 12 weeks, accuracy, and adverse events. Standardized mean difference (SMD) for VAS and weighted mean difference (WMD) for ROMs.

We identified 6 RCTs and one prospective comparative study with a total of 468 patients. While there was no difference in pain VAS at 12 weeks between the 2 approaches (SMD, -0.86; 95% CI, -1.76 to 0.04), the anterior approach resulted in greater improvements in external rotation (WMD, 8.08; 95% CI, 0.79-15.38) and abduction (WMD, 6.76; 95% CI, 3.05-10.48) compared with the posterior approach. Subgroup analysis with RCTs that utilized steroid injection with hydrodilatation for both approaches demonstrated greater reduction in pain VAS at 12 weeks with the anterior approach (SMD, -0.52; 95% CI, -0.98 to -0.07). Overall, procedures were well tolerated without major complications.

While pain reduction is similar, the anterior approach may be more beneficial in restoring shoulder external rotation and abduction compared with the posterior approach at 12 weeks. Steroid injection combined with hydrodilatation may further improve pain control when performed with the anterior approach at 12 weeks.

Frozen shoulder (FS), also known as adhesive capsulitis, is a condition that causes contraction and stiffness of the shoulder joint capsule. The main symptoms are persistent shoulder pain and a limited range of motion in all directions. These symptoms and poor prognosis affect people's physical health and quality of life. Currently, the specific mechanisms of FS remain unclear, and there is variability in treatment methods and their efficacy. Additionally, the early symptoms of FS are difficult to distinguish from those of other shoulder diseases, complicating early diagnosis and treatment. Therefore, it is necessary to develop and utilize animal models to understand the pathogenesis of FS and to explore treatment strategies, providing insights into the prevention and treatment of human FS. This paper reviews the rat models available for FS research, including external immobilization models, surgical internal immobilization models, injection modeling models, and endocrine modeling models. It introduces the basic procedures for these models and compares and analyzes the advantages, disadvantages, and applicability of each modeling method. Finally, our paper summarizes the common methods for evaluating FS rat models.

Elbow trauma can lead to joint contracture and reduced range of motion (ROM). Nonsurgical interventions can improve ROM, but in some cases capsule release surgery is required. Although surgery can improve ROM, it often does not restore full ROM. Thus, alternatives are needed. One approach is to target activated myofibroblasts, which are commonly associated with fibrotic tissue. Mechanical and biochemical cues drive a feedback loop that can result in normal or pathological healing. We hypothesize that this feedback loop exists in joint contracture and can be manipulated so that myofibroblast activity is reduced, normal healing is achieved, and ROM is improved. We previously demonstrated that blebbistatin can inhibit myofibroblast contractile forces and reduce collagen synthesis in vitro. Thus, the purpose of this study was to assess the use of blebbistatin in an animal model of elbow contracture, which was induced in 7 groups of 4 rats each (n = 28). All elbows were mechanically and histologically tested. The uninjured contralateral elbows of each rat were used as a control group. Capsule release surgery significantly improved (p < 0.01) outcomes 1 week after surgery compared to injury alone and was not significantly different from uninjured elbows. Three weeks after surgery, outcomes worsened, indicating joint stiffening consistent with what is observed clinically. The addition of blebbistatin did not significantly improve outcomes. Future work will investigate relationships among treatment, fibrotic tissue deposition, myofibroblast activity, and biomechanics to determine if blebbistatin is a useful adjunctive therapy for treating joint contracture.

The risk of adhesive capsulitis of shoulder in diabetic patients taking metformin has not been evaluated. We aimed for evaluating the relative risk of adhesive capsulitis of shoulder in diabetic patients taking metformin at the level of the whole country population. We conducted a retrospective cohort study using a national health insurance database in Taiwan from 2000 to2015. We used International Classification of Diseases, Ninth Revision, to categorise the medical condition for study group and comparison group. We used Cox proportional hazard regression analyses to determined adjusted hazard ratios (aHRs) of adhesive capsulitis of shoulder between study and comparison group after adjusting for sex, age, and comorbidities.Among 30,412 diabetic patients using metformin, 3020 patients were diagnosis with adhesive capsulitis of shoulder during follow up. Of the 121,648 patients without the use of metformin, 11,375 patients developed adhesive capsulitis of shoulder. Adhesive capsulitis of shoulder risk was elevated in patients taking metformin than in non-metformin group (adjusted hazard ratio [HR] 1.179, 95% confidence interval [95% CI] 1.022 to 1.268; p = 0.039). Risk of adhesive capsulitis of shoulder among the diabetic patients taking metformin was higher than those did not taking metformin.

Adhesive capsulitis is a common pathological condition of the shoulder that affects the general population. The aim of the present study was to explore shoulder ultrasonographic findings in patients with adhesive capsulitis. A cross-sectional descriptive study was conducted on 96 patients with adhesive capsulitis. Abnormal shoulder ultrasonographic findings were found in all participants. The top three abnormal ultrasonographic imaging features were biceps tendon effusion (71.8%), positive dynamic supraspinatus impingement (56.2%) and subdeltoid-subacromial bursitis (47.9%). By assessing the relationship between limited functional shoulder range of motion (ROM) and abnormal shoulder ultrasonographic findings, limited passive ROM (PROM) with shoulder flexion of ≤120 degrees was found to be significantly associated with positive dynamic supraspinatus impingement. Similarly, limited PROM in shoulder abduction of ≤130 degrees was found to be significantly associated with subdeltoid and subacromial bursitis, as well as positive dynamic supraspinatus impingement. In addition, limited PROM with shoulder internal rotation of ≤60 degrees was significantly associated with positive dynamic supraspinatus impingement. Varying abnormal shoulder ultrasonographic findings were obtained in patients with adhesive capsulitis. Therefore, it should be cautioned that relying solely on physical examination may not accurately indicate true shoulder pathology and it is suggested that the final diagnosis should be based on a combination of the patients' clinical and overall ultrasonographic findings.

The pathogenesis of frozen shoulder (FS) remains unclear, and current research primarily focuses on immune responses. Increasing evidence suggests that immune cells play a significant role in FS development. However, the causal relationship between the two remains poorly understood. Therefore, we aimed to investigate this using Mendelian randomization (MR) analysis. Single nucleotide polymorphisms closely associated with 731 immune phenotypes were obtained from publicly available GWAS datasets as instrumental variables. FS was used as the outcome with a sample size of 451,099 cases. Causal effects were analyzed using the inverse variance-weighted method. We conducted sensitivity tests, including the intercept of the MR-Egger and MR-PRESSO analyses. The presence of heterogeneity was evaluated using Cochran Q test. We identified potential causal relationships in terms of increased risk for FS with 5 immune phenotypes: CD25++ CD45RA+ CD4 not regulatory T cell %CD4+ T cells (odds ratio [OR] = 1.0273, 95% confidence interval [CI]: 1.0093-1.0457, P = .0028), CD25++ CD45RA+ CD4 not regulatory T cell %T cell (OR = 1.0240, 95% CI: 1.0057-1.0427, P = .0098), CD127 on CD28+ CD4+ T cells (OR = 1.0398, 95% CI: 1.0121-1.0682, P = .0046), CD4 on human leukocyte antigen DR+ CD4+ T cells (OR = 1.0795, 95% CI: 1.0316-1.2195, P = .0009), and human leukocyte antigen DR on CD14- CD16+ monocytes (OR = 1.0533, 95% CI: 1.0136-1.0945, P = .0081). Few significant heterogeneities or horizontal pleiotropies were observed. Through MR analysis, we identified distinct 5 types of immune cells that were positively correlated with the occurrence and development of FS, providing guidance for clinical intervention in FS.

Acute pain is a major concern after arthroscopic shoulder surgery, supraclavicular brachial plexus blockade has shown favorable postoperative analgesic effects. However, its duration of analgesia does not meet clinical needs. We aimed to explore whether the combination of different local anesthetic adjunct can prolong the analgesic duration of supraclavicular brachial plexus block for arthroscopic shoulder surgery.

In this prospective randomized controlled trial, we allocated 80 patients into four groups: Group DMD (dexamethasone 10 mg + ropivacaine 100 mg + dexmedetomidine 50 µg + magnesium sulfate 250 mg), Group DM (ropivacaine 100 mg + dexmedetomidine 50 µg + magnesium sulfate 250 mg), Group M (ropivacaine 100 mg + magnesium sulfate 250 mg) and Group D (ropivacaine 100 mg + dexmedetomidine 50 µg). The primary outcome was the time to first request for analgesia. Secondary outcome measures included cumulative opioid consumption at 6, 12, 18, 24, and 48 h postoperatively, VAS scores at 6, 12, 18, 24, and 48 h postoperatively and so on.

The time to first request for analgesia in Group DMD was significantly longer than Group DM (P = 0.011) and Group M (P = 0.003). The cumulative opioid consumption at 18 h postoperatively in Group DMD was significantly lower than in Group DM (P = 0.002) and Group M (P = 0.007). The cumulative opioid consumption at 24 h postoperatively in Group DMD was significantly lower than in Group DM (P = 0.016). The VAS score at 6 h postoperatively in Group DMD was significantly lower than in Group DM and Group M. The VAS score at 12 h postoperatively in Group DMD was significantly lower than in Group M. For American Shoulder and Elbow Surgeons Score, Group DMD had a better score than Group DM and Group D.

The analgesic efficacy of supraclavicular brachial plexus blockade combined with dexamethasone, magnesium sulfate, and dexmedetomidine is significantly superior to the combination of magnesium sulfate and dexmedetomidine, and significantly superior to the use of magnesium sulfate alone.

This trial was registered in Chinese Clinical Trial Registry. (ChiCTR2200061181, Date of registration: June 15, 2022, http://www.chictr.org.cn ).

Background/Objectives: Frozen shoulder is a common shoulder disorder that often places limitations on the range of motion of the shoulder. The disease may induce neck pain due to overuse of the neck muscle in an attempt to compensate for lack of shoulder movement. In clinical practice, swelling and inflammation of the scalene and levator scapulae may be detected via sonography in patients with frozen shoulder. The aim of this study was, therefore, to determine whether the involvement of the scalene complex or levator scapulae could compensate for the limited motion of the shoulder in patients with frozen shoulder. Methods: We retrospectively reviewed the medical records of 362 patients with unilateral frozen shoulder. These patients were divided into four groups depending on the involvement of the scalene complex or levator scapulae muscle. The range of motion of the shoulder-encompassing flexion, abduction, and external rotation-was measured with a goniometer. We also performed an ultrasound scan on each shoulder. The involvement of the scalene complex and levator scapulae muscle was also assessed via musculoskeletal ultrasound. Results: The range of motion of the shoulder in terms of flexion, abduction, external rotation, and total range of motion differed significantly between the four groups (p < 0.05). Patients in whom the scalene complex or levator scapulae muscle was involved demonstrated a significantly wider range of motion in different shoulder directions than patients without the involvement of those muscles (p < 0.05). Conclusions: A greater range of motion in the shoulder can be obtained through the activation of the scalene complex or levator scapulae muscle, which act to compensate for the lack of shoulder movement in patients with frozen shoulder. These two muscles showed thickening and hypoechoic changes upon sonography.

Arthroscopic capsular release is a most well-known technique with favorable outcomes for frozen shoulder. However, considering the surgical trauma and the improvement of multisite injection, we design a study to compare the pain relief and safety of multisite injection (MI) versus arthroscopic capsular release (ACR) for frozen shoulder. A total of 80 patients with unilater al frozen shoulder were enrolled in this study. Group RBT (n = 40) received multisite injection (0.5% lidocaine and triamcinolone acetonide, once a week, no more than 2 injections), while Group ACR received arthroscopic capsular release. The following parameters were employed to compare: visual analog scale (VAS), range of motion (ROM), the Disability of Arm, Hand, and Shoulder (DASH) score and Oxford shoulder score (OSS). Side effects were also recorded. The VAS, ROM, DASH and OSS all improved significantly (P < 0.001). Internal rotation and external rotation at 1 month after operation were better in ACR group (40.35 ± 4.79 Vs 36.58 ± 7.49, 40.55 ± 4.37 Vs 38.63 ± 4.01, P = 0.009,0.043). However, no significance in terms of functional results and ROM was found at 6 months after operation. The OSS, DASH and VAS in patients with diabetes were 44.25 ± 3.05, 2.29 ± 1.12 and 0.50 ± 0.72, compared with 43.89 ± 3.09, 2.34 ± 1.49 and 0.29 ± 0.56 in patients without diabetes (P = 0.636, 0.889, 0.157). Multisite injection and arthroscopic capsular release are both effective treatments in the treatment of frozen shoulder. However, multisite injection is a simple, cost effective and superior alternative.

To compared the arthroscopic capsular release (ACR) with manipulation under anaesthesia (MUA) for the surgical treatment of frozen shoulder (FS) based on postoperative outcomes and complications. PubMed, Cochrane Library, Embase, and Web of Science were searched on October 2, 2023 to retrieve eligible studies that compared ACR with MUA in terms of clinical outcomes (pain visual analogue scale, external rotation, forward flexion and adverse events) for patients with FS. Mean differences (MD) were calculated for continuous outcomes and odds ratios (OR) were calculated for dichotomous outcomes. Six papers, including 5 clinical studies (a total of 690 shoulders), were included in the final meta-analysis. The forward flexion was found to be larger in the ACR group at 3 months (MD, 2.73; 95%CI, 0.42-5.04; I2 = 44%; P = 0.02) and 6 months (MD, 2.36; 95%CI, 1.29-3.44; I2 = 0%; P < 0.0001). Except for this, ACR was comparable with MUA in terms of pain visual analogue scale at 3, 6 and 12 months (p = 0.25, p = 0.11, p = 0.28, respectively), external rotation at 3, 6 and 12 months (p = 0.15, p = 0.52, p = 0.23, respectively), and forward flexion at 12 months (p = 0.08). There were no differences in complication rates between the two groups (OR, 0.82; 95%CI, 0.47-1.44; I2 = 0%; P = 0.50). In comparison with MUA, ACR demonstrated better outcomes for forward flexion at 3 and 6 months, while there were no significant differences between ACR and MUA in terms of pain visual analogue scale, external rotation and adverse events.

Frozen shoulder (FS) manifests as progressively worsening pain and a reduction in shoulder range of motion (ROM). Salvianolic acid B (SaB) is recently expected to be used in the treatment of fibrosis diseases including FS. We firstly demonstrate that SaB can effectively hinder the progression of oxidative stress, inflammation, and pathological fibrosis within the synovial tissue in FS, potentially leading to the reduction or reversal of capsule fibrosis and joint stiffness. For further clinical application, we design and synthesize a novel, superior, antioxidant and antibacterial CSMA-PBA/OD-DA (CPDA) hydrogel for the delivery of SaB. In vitro experiments demonstrate that the CPDA hydrogel exhibits excellent biocompatibility and rheological properties, rendering it suitable for intra-articular injections. Upon injection into the contracted joint cavity of FS model rat, the SaB-CPDA hydrogel accelerate the recovery of ROM and exhibit superior anti-fibrosis effect, presenting the promise for the treatment of FS in vivo.

Background/Objectives: To update the perspectives of the association between diabetes (DM) and adhesive capsulitis (AC). Methods: Our findings were summarized in a narrative review. We searched PubMed, Embase, and Consensus databases, using keywords such as "diabetes", "adhesive capsulitis", and "frozen shoulder", for articles published from January 2015 to June 2024, covering both type 1 and type 2 DM. Results: After compiling relevant articles on DM-related AC published since 2015, we found that most studies show an increased prevalence of AC in DM patients, ranging from 3 to 10 times. A longer duration of DM is a risk factor for AC. Whether T1DM or prolonged insulin use will increase the risk of AC is still controversial. Poor blood sugar control seems to increase the risk of AC. Recent studies also show a correlation between blood sugar levels and the prevalence of AC. Cytokines, such as IL-6, IL-8, TNF-α, VEGF, and AGEs, related to inflammation and fibrosis may contribute to the pathophysiological processes of AC. Conclusions: Recent research findings have revealed new perspectives divergent from past notions, while also presenting some topics worthy of exploration. Due the close relationship between DM and AC, clinicians need to be alert to the presence of AC, especially early stage, in DM cases, and control the blood glucose level to reduce the risk of AC. Further research is still needed to provide better prevention and management for DM patients with AC.

Although existing studies have indicated a connection between chronic low-grade inflammation and the onset of frozen shoulder (FS), the precise causal relationship between distinct circulating inflammatory factors and FS has yet to be thoroughly evaluated. In this study, we employed a bidirectional two-sample Mendelian randomization (MR) analysis to investigate the potential causal relationship between systemic cytokines and FS.

A genome-wide association dataset comprising 41 serum cytokines from 8,293 individuals of Finnish descent was utilized, along with FS data from the UK Biobank included 10,104 FS cases and 451,099 controls. The primary MR method was the inverse variance weighted approach, and four additional MR techniques (MR-Egger, weighted median, simple mode, and weighted mode) were also employed to support and validate the findings. Heterogeneity and horizontal pleiotropy assessments were assessed using Cochrane's Q and MR-Egger intercept tests. Moreover, a series of sensitivity analyses were conducted to strengthen the accuracy and credibility of these findings.

Based on the IVW method, genetically predicted increasing levels of growth regulated oncogene alpha (GROa) (OR=1.08, 95 % CI 1.02-1.13, P=0.005), interferon gamma-induced protein 10 (IP-10) (OR=1.09, 95 % CI 1.02-1.17, P=0.010), regulated on activation, C-C Motif Chemokine Ligand 5 (CCL5) (OR=1.11, 95 % CI 1.03-1.20, P=0.007) were suggestively associated with an increased risk of FS. Reverse MR analysis revealed no significant causal effect of FS on the 41 systemic inflammatory factors. No heterogeneity or horizontal pleiotropy was observed in our analysis.

This study established a causal association between 41 systemic inflammatory factors and FS, indicating that elevated levels of GROa, IP-10 and CCL5 were associated with a higher risk of FS. Further research is warranted to explore the potential of these biomarkers as early predictors and therapeutic targets for FS.

Frozen shoulder (FS) is a common disorder causing shoulder pain and limited motion. Magnetic resonance imaging (MRI) is expected to help diagnose FS and realize the disease stage if stage-specific features are present. We aimed to survey stage-related MRI findings of FS in the literature.

MEDLINE, SCOPUS, and Google Scholar databases were searched with search terms "frozen shoulder" or "adhesive capsulitis" combined with "magnetic resonance imaging." Studies that discussed MRI findings in relation to FS stages were retrieved. The course of FS was divided into stages 1 to 4 according to Hannafin and Chiaia.

Two of the noncontrast-enhanced MRI findings were stage-related. T2 signal hyperintensity of the joint capsule was more frequent in stages 1 and 2. The axillary capsule thickness was greater in stages 1 and 2. However, these findings were also seen in the later stages to a lesser degree. Effusion around the long head of biceps, subcoracoid fat obliteration, and coracohumeral ligament thickening were common in FS but their relation to the stages was not evident. Signal enhancement on contrast-enhanced MRI was not consistently linked to stages.

T2 signal hyperintensity and axillary capsule thickening are characteristic of the early stages of FS, although MRI alone cannot completely define the disease stage.

This study aimed to evaluate the severity of adhesion between muscles in the shoulder joint using dynamic ultrasonography and to confirm whether adhesions cause range of motion (ROM) restrictions.

Twenty-four shoulders from 15 frozen shoulder patients and 24 shoulders from 18 rotator cuff disorder patients were enrolled. We obtained ultrasound video sequences of the subscapularis (SSC) and deltoid muscles during shoulder external rotation. The mean stretching velocities of the deltoid and SSC were subsequently analyzed using a personal computer. If adhesions occurred between both muscles, the deltoid was stretched more vigorously, and we calculated mean stretching velocity of the deltoid / SSC as adhesion severity. The coracohumeral ligament thickness was measured using the same images. Shoulder ROM was measured by using a universal goniometer.

The intraclass correlation coefficients (1.1) and (2.1) of the adhesion severity measurements were 0.85 and 0.91, respectively. Multiple linear regression analysis revealed that the adhesion severity is a significant predictor for external rotation ROM in the rotator cuff disorder group (R2 = 0.44, F = 10.1, P < .01, t = -2.9), while coracohumeral ligament thickness predicts ROM in the frozen shoulder group (R2 = 0.28, F = 5.5, P = .01, t = -3.0).

The proposed method is reliable. Muscle adhesion causes ROM restriction of the shoulder joint. The primary cause of shoulder ROM restriction differed between the diagnostic groups.

The Anti-Freaze-F (AFF) trial assessed the feasibility of conducting a definitive trial to determine whether intra-articular injection of adalimumab can reduce pain and improve function in people with pain-predominant early-stage frozen shoulder.

Multicentre, randomised feasibility trial, with embedded qualitative study.

Four UK National Health Service (NHS) musculoskeletal and related physiotherapy services.

Adults ≥18 years with new episode of shoulder pain attributable to early-stage frozen shoulder.

Participants were randomised (centralised computer generated 1:1 allocation) to either ultrasound-guided intra-articular injection of: (1) adalimumab (160 mg) or (2) placebo (saline (0.9% sodium chloride)). Participants and outcome assessors were blinded to treatment allocation. Second injection of allocated treatment (adalimumab 80 mg) or equivalent placebo was administered 2-3 weeks later. PRIMARY FEASIBILITY OBJECTIVES: (1) Ability to screen and identify participants; (2) willingness of eligible participants to consent and be randomised; (3) practicalities of delivering the intervention; (4) SD of the Shoulder Pain and Disability Index (SPADI) score and attrition rate at 3 months.

Between 31 May 2022 and 7 February 2023, 156 patients were screened of whom 39 (25%) were eligible. The main reasons for ineligibility were other shoulder disorder (38.5%; n=45/117) or no longer in pain-predominant frozen shoulder (33.3%; n=39/117). Of the 39 eligible patients, nine (23.1%) consented to be randomised (adalimumab n=4; placebo n=5). The main reason patients declined was because they preferred receiving steroid injection (n=13). All participants received treatment as allocated. The mean time from randomisation to first injection was 12.3 (adalimumab) and 7.2 days (placebo). Completion rates for patient-reported and clinician-assessed outcomes were 100%.

This study demonstrated that current NHS musculoskeletal physiotherapy settings yielded only small numbers of participants, too few to make a trial viable. This was because many patients had passed the early stage of frozen shoulder or had already formulated a preference for treatment.

ISRCTN 27075727, EudraCT 2021-03509-23, ClinicalTrials.gov NCT05299242 (REC 21/NE/0214).

Several risk factors have been identified for the development of postoperative shoulder stiffness, and there has been increasing interest in orthopedic literature regarding patient-reported allergy (PRA) as an identifiable risk factor for adverse outcomes. The purpose of this study is to determine whether PRAs are associated with subsequent rates of diagnosis of adhesive capsulitis (AC) or return to the operating room for postoperative shoulder stiffness within 2 years after arthroscopic rotator cuff repair (ARCR).

Current Procedural Terminology surgical billing codes were used to retrospectively identify patients who underwent ARCR at a single urban academic institution from January 2012 to December 2020 with minimum 2-year follow-up. Lysis of adhesions (LOA), manipulation under anesthesia (MUA), and AC of the shoulder were further queried within 2 years postoperatively for the ipsilateral shoulder. Patients were excluded if they had undergone ipsilateral MUA/LOA or received a diagnosis of AC before the index procedure. Demographic characteristics and medical comorbidities (hypertension, diabetes, hyperlipidemia, and hypothyroidism) were extracted from electronic medical records. Baseline characteristics were compared between patients with and without PRAs. Multivariate logistic regression analyses were performed to determine the association of the presence of PRAs overall, as well as the presence of 1, 2, or 3 or more PRAs, with subsequent MUA/LOA or diagnosis of AC within 2 years postoperatively.

Of 7057 patients identified in the study period, 6583 were eligible for the final analysis. The mean age was 56.6 ± 11.7 years, and the mean body mass index was 29.1 ± 5.6. Overall, 19.3% of patients (n = 1271) reported at least 1 allergy, and 7.1% (n = 469) had >1 PRA. A total of 44 patients (0.7%) underwent subsequent ipsilateral MUA/LOA within 2 years postoperatively, whereas 93 patients (1.4%) received a diagnosis of ipsilateral AC in the same time frame. PRAs were significantly associated with subsequent diagnosis of AC (odds ratio [OR]: 2.39; 95% confidence interval [CI]: 1.45-3.92; P < .001), but not MUA/LOA (OR: 1.97, 95% CI: 1.26-3.61; P = .133). Patients with 2 PRAs had greater odds of being diagnosed with AC than patients with 1 PRA (OR: 2.74; 95% CI: 1.14-5.99; P = .012). Although this association was nonsignificant for MUA/LOA, patients with 2 PRAs (OR: 2.67; 95% CI: 0.96-8.80; P = .059) demonstrated a similar statistical trend.

PRAs are associated with increased odds of receiving a diagnosis of AC within 2 years after ARCR but were not found to be associated with return to the operating room for postoperative stiffness.

Fibroblast activation protein inhibitor (FAPI) targeting PET has been introduced as a novel molecular imaging modality for visualizing cancer-associated fibroblasts. There have also been reports suggesting incidental findings of localized accumulation in the shoulder joints. However, further characterization in a larger patient cohort is still lacking.

77 consecutive patients (28 females; mean age, 63.1 ± 11.6) who underwent Ga-68 FAPI-04 PET/CT for diagnosis of solid tumors were included. The incidence and localization of tracer uptake in shoulder joints were investigated and compared with available F-18 FDG scans serving as reference.

Ga-68 FAPI-04 uptake was evaluated in 77 patients (154 shoulder joints), of whom 54 subjects (108 shoulder joints) also had available F-18 FDG scans for head-to-head comparison. On FAPI-targeted imaging, 67/154 shoulders (43.5%) demonstrated increased radiotracer accumulation in target lesions, which were distributed as follows: acromioclavicular (AC) joints in 25/67 (37.3%), followed by glenohumeral and subacromial (GH + SA) joints in 23/67 (34.3%), or both (AC and GH + SA joints) in the remaining 19/67 (28.4%). Ga-68 FAPI-04 correlated with quantified F-18 FDG uptake (r = 0.69, p < 0.0001). Relative to the latter radiotracer, however, in-vivo FAP expression in the shoulders was significantly increased (Ga-68 FAPI-04, 4.7 ± 3.2 vs F-18 FDG, 3.6 ± 1.3, p < 0.001).

Our study revealed focal accumulation of Ga-68 FAPI-04 in the shoulders, particularly in the AC joints, with higher uptake compared to the inflammatory-directed PET radiotracer F-18 FDG in oncological studies. As a result, further trials are warranted to investigate the potential of FAPI-directed molecular imaging in identifying chronic remodeling in shoulder joints. This could have implications for initiating anti-FAP targeted photodynamic therapy based on PET signal strength.

Frozen shoulder (FS), also known as adhesive capsulitis of the shoulder (FS), is a fibrotic inflammatory process of unknown etiology whose main symptoms are pain, stiffness and the loss of joint mobility. These symptoms may be associated with pathologies such as diabetes, Dupuytren's syndrome and the prevalence of today's sedentary lifestyle. This literature review provides an overview of the epidemiology and pathogenesis of this pathology, as well as the mechanisms of lowgrade chronic inflammation and infection, insulin resistance, and omics-science associated with it. We also propose a new hypothesis related to the possibility that the GABAergic system could play a decisive role in the development of frozen shoulder and that therefore diabetes type 1, endocrinological autoimmune disorders and frozen shoulder are connected by the same pathophysiological mechanisms. If that is true, the combined presence of psycho-emotional stress factors and pathogenic immune challenges could be the main causes of frozen shoulder syndrome. Finally, we propose a series of possible intervention strategies based on a multifactorial etiological and mechanistic concept.

Frozen shoulder (FS) is a common disorder characterized by spontaneous onset of shoulder pain accompanied by progressive loss of range-of-motions. The cause of FS is still unclear, and radical therapy has not been established. With the final aim of preventing or curing FS at an earlier stage, we reviewed the pathological and biological features of this disease. Many studies indicate that the main pathology of FS is inflammation initially and fibrosis later. There are inflammatory cytokines, immune cells, fibrotic growth factors, and type-III collagen in the synovium and the joint capsule. The immune cell landscape switches from the macrophages to T cells. Activated fibroblasts seem to regulate the inflammatory and fibrotic processes. The imbalance between matrix metalloproteinases and tissue inhibitors of metalloproteases might promote fibrosis. Additionally, advanced glycation end-products are noted in the FS synovium. Diabetes mellitus and hypothyroidism are closely related to the development of FS. In terms of nonsurgical treatment, oral or intra-articular glucocorticoids are the only drugs that provide early benefit. Some other anti-inflammatory or antifibrotic drugs may potentially control the FS, but have not been proven effective in the clinical setting. Future studies should be targeted to develop steroid-sparing agents that inhibit biological events in FS.

Is it feasible to conduct a definitive multicentre trial in community settings of corticosteroid injections (CSI) and hydrodilation (HD) compared to CSI for patients with frozen shoulder? An adequately powered definitive randomized controlled trial (RCT) delivered in primary care will inform clinicians and the public whether hydrodilation is a clinically and cost-effective intervention. In this study, prior to a full RCT, we propose a feasibility trial to evaluate recruitment and retention by patient and clinician willingness of randomization; rates of withdrawal, crossover and attrition; and feasibility of outcome data collection from routine primary and secondary care data.

In the UK, the National Institute for Health and Care Excellence (NICE) advises that prompt early management of frozen shoulder is initiated in primary care settings with analgesia, physiotherapy, and joint injections; most people can be managed without an operation. Currently, there is variation in the type of joint injection: 1) CSI, thought to reduce the inflammation of the capsule reducing pain; and 2) HD, where a small volume of fluid is injected into the shoulder joint along with the steroid, aiming to stretch the capsule of the shoulder to improve pain, but also allowing greater movement. The creation of musculoskeletal hubs nationwide provides infrastructure for the early and effective management of frozen shoulder. This potentially reduces costs to individuals and the wider NHS perhaps negating the need for a secondary care referral.

We will conduct a multicentre RCT comparing CSI and HD in combination with CSI alone. Patients aged 18 years and over with a clinical diagnosis of frozen shoulder will be randomized and blinded to receive either CSI and HD in combination, or CSI alone. Feasibility outcomes include the rate of randomization as a proportion of eligible patients and the ability to use routinely collected data for outcome evaluation. This study has involved patients and the public in the trial design, dissemination methods, and how to include groups who are underserved by research.

We will disseminate findings among musculoskeletal clinicians via the British Orthopaedic Association, the Chartered Society of Physiotherapy, the Royal College of Radiologists, and the Royal College of General Practitioners. To ensure wide reach we will communicate findings through our established network of charities and organizations, in addition to preparing dissemination findings in Bangla and Urdu (commonly spoken languages in northeast London). If a full trial is shown to be feasible, we will seek additional National Institute for Health and Care Research funding for a definitive RCT. This definitive study will inform NICE guidelines for the management of frozen shoulder.

Frozen shoulder (FS) is a common cause of shoulder pain and stiffness. Conservative treatment is sufficient for the majority of patients with long-term recovery of shoulder function. Manipulation under anesthesia (MUA) is known as a well-established treatment option if conservative treatment fails. It is unknown whether MUA does indeed shorten the duration of symptoms or leads to a superior outcome compared to conservative treatment. The objective of the current trial is to evaluate the effectiveness of MUA followed by a physiotherapy (PT) program compared to a PT program alone in patients with stage 2 FS.

A prospective, single-center randomized controlled trial was performed. Patients between 18 and 70 years old with stage 2 FS were deemed eligible if an initial course of conservative treatment consisting of PT and intra-articular corticosteroid infiltration was considered unsatisfactory. Patients were randomized, and data was collected with an online data management platform (CASTOR). MUA was performed by a single surgeon under interscalene block, and intensive PT treatment protocol was started within 4 hours after MUA. In the PT group, patients were referred to instructed physiotherapist, and treatment was guided by tissue irritability. The primary outcome was the Shoulder Pain and Disability Index (SPADI) score. Secondary outcomes were pain, range of motion (ROM), Oxford Shoulder Score, quality of life, and ability to work.

In total, 82 patients were included, 42 in the PT group and 40 in the MUA group. There was a significant improvement in SPADI, Oxford Shoulder Score, pain, ROM, and quality of life in both groups at 1-year follow-up. SPADI scores at three months were significantly improved in favor of MUA. MUA showed a significantly bigger increase in anteflexion and abduction compared to PT at all points of follow-up. No significant differences between both groups were found for all other parameters. No fractures, dislocations, or brachial plexus injuries occurred in this trial.

MUA in stage 2 FS can be considered safe and results in a faster recovery of ROM and improved functional outcome, measured with SPADI scores, compared to PT alone in the short term. After 1 year, except for slightly better ROM scores for MUA, the result of MUA is equal to PT.

Although prior observational studies indicate an association between cardiovascular diseases (CVDs) and frozen shoulder (FS), the potential causal relationship between them remains uncertain. This study aims to explore the genetic causal relationship between CVDs and FS using Mendelian randomization (MR).

Genetic variations closely associated with FS were obtained from the FinnGen Consortium. Summary data for CVD, including atrial fibrillation (AF), coronary artery disease (CAD), heart failure (HF), myocardial infarction (MI), stroke, and ischemic stroke (IS), were sourced from several large-scale genome-wide association studies (GWAS). MR analysis was performed using inverse variance weighting (IVW), MR Egger, and weighted median methods. IVW, as the primary MR analysis method, complemented by other sensitivity analyses, was utilized to validate the robustness of the results. Further reverse MR analysis was conducted to explore the presence of reverse causal relationships.

In the forward MR analysis, genetically determined risk of stroke and IS was positively associated with FS (OR [95% CI] = 1.58 (1.23-2.03), P < 0.01; OR [95% CI] = 1.46 (1.16-1.85), P < 0.01, respectively). There was no strong evidence of an effect of genetically predicted other CVDs on FS risk. Sensitivity analyses confirmed the robustness of the results. In the reverse MR analysis, no causal relationships were observed between FS and various CVDs.

The study suggests that stroke increases the risk of developing FS. However, further basic and clinical research is needed to substantiate our findings.

Observational studies have suggested an association between frozen shoulder (FS) and carpal tunnel syndrome (CTS). However, due to challenges in establishing a temporal sequence, the causal relationship between these two conditions remains elusive. This study, based on aggregated data from large-scale population-wide genome-wide association studies (GWAS), investigates the genetic causality between FS and CTS.

Initially, a series of quality control measures were employed to select single nucleotide polymorphisms (SNPs) closely associated with the exposure factors. Two-sample Mendelian randomization (MR) was utilized to examine the genetic causality between FS and CTS, employing methods including Inverse-Variance Weighted (IVW), MR-Egger, Weighted Median, Simple Mode, and Weighted Mode approaches. Subsequently, sensitivity analyses were conducted to assess the robustness of the MR analysis results.

IVW analysis results indicate a positive causal relationship between CTS and FS (p < 0.05, OR > 1), while a negative causal relationship between the two conditions was not observed. Heterogeneity tests suggest minimal heterogeneity in our IVW analysis results (p > 0.05). Multivariable MR testing also indicates no pleiotropy in our IVW analysis (p > 0.05), and stepwise exclusion tests demonstrate the reliability and stability of the MR analysis results. Gene Ontology (GO) pathway analysis reveals enrichment of genes regulated by the associated SNPs in the TGFβ-related pathways.

This study provides evidence of the genetic causal association between frozen shoulder and carpal tunnel syndrome and provides new insights into the genetics of fibrotic disorders.

Frozen shoulder (FS) is a common disorder often treated with Tuina, but the mechanisms involved remain unclear. We employed proteomics and phosphoproteomics to investigate the mechanisms associated with the treatment of capsule fibrosis in FS rats. We used a method composed of three weeks of cast immobilization to establish a model of FS. We then administered Tuina once daily for 14 days, evaluated glenohumeral range of motion (ROM), assessed histological changes, and identified differentially expressed proteins (DEPs) using proteomics and phosphoproteomics. This study demonstrated that Tuina could improve glenohumeral ROM and reserve capsule fibrosis in FS rats. Proteomics revealed proteins regulated by Tuina belonging to the PI3K-AKT and ECM receptor interaction signaling pathways. Phosphoproteomics detected differentially phosphorylated proteins regulated by Tuina to be enriched in the MAPK signaling pathway. The combination of proteomics and phosphoproteomics for Protein-Protein Interaction (PPI) network analysis revealed that the phosphorylation of Myh3 and Srsf1 with a node degree larger than the average degree were considered the central regulatory protein modulated by Tuina to reverse capsule fibrosis. Thbs1, Vtn, and Tenascin-W were significantly enriched in PI3K-AKT and ECM receptor interaction signaling pathways and highly expressed in model rats. Tuina resulted in reduced expression of these proteins. Our findings demonstrated some of mechanisms behind the reversal of FS capsule fibrosis following Tuina, a scientific medical therapy for FS patients.

To evaluate posterior glenohumeral capsule edema compared to other MRI findings in adhesive capsulitis (AC).

This study was approved by the local Institutional Review Board and it is HIPAA compliant. A retrospective search identified subjects who received fluoroscopically guided intra-articular corticosteroid injections for AC and had an MRI within 6 months prior to injection. The study group was compared with an age-, sex-, and side-matched control group who underwent the same procedures but did not have AC. MRIs were evaluated for edema of posterior capsule, anterior capsule, axillary pouch, coracohumeral ligament (CHL) and rotator interval (RI), thickness of axillary pouch and CHL, thickness of anterior capsule, RI and subcoracoid fat replacement, and teres minor atrophy and edema. Multivariable analysis was performed.

A total of 57 subjects with AC and 57 matched controls were studied: mean age 52 ± 7 (range 31-71) years, 37 female and 20 male, 22 right and 35 left. Posterior capsule edema was more common in the AC group vs. control group (66.7 vs 17.5%, p < 0.001). Multivariable analysis showed posterior capsule edema, CHL edema, and axillary pouch (glenoid) thickness (optimum cutoff = 4 mm) were significant independent predictors of AC. Simplified analysis using these three variables had an area under the curve of 0.860 (95%CI: 0.792-0.928). With all three variables present, the sensitivity and specificity for AC were 32% and 98%, respectively.

Posterior joint capsule edema may be helpful to confirm AC. Posterior capsule edema, CHL edema, and axillary pouch (glenoid) thickness produce a strong model for distinguishing AC from controls.

Edema involving the posterior shoulder joint capsule is an imaging marker of capsulitis and is useful in differentiating patients with adhesive capsulitis from those without in conjunction with other proven MRI findings.

• Posterior capsule edema has a sensitivity of 66.7% and a specificity of 82.5% for the detection of adhesive capsulitis. • Posterior capsule edema, coracohumeral ligament (CHL) edema, and axillary pouch (glenoid) thickness were significant independent predictors of adhesive capsulitis, and combining these variables together produces a very strong model for distinguishing cases from controls (AUC = 0.860). • Optimal cutoff values for CHL, axillary pouch (humeral), axillary pouch (glenoid), and axillary pouch (total) thickness were 2.5, 2.6, 4, and 6.3 mm, respectively.

Background and objective The shoulder is the most flexible ball- and socket-type joint in the human body. The pathological condition that can commonly affect this joint is the frozen shoulder. This condition is marked by pain and stiffness in the area surrounding the shoulder complex. This leads to difficulty in doing the daily activities of living. Exercise and physical therapy are mostly recommended to decrease pain and improve and maintain the range of motion (ROM). Mainly traditional techniques such as Mulligans, Maitland, and Kaltenborn are used, along with electrotherapy and exercises, for the treatment of this condition. The effect of the Spencer technique is seen in baseball players' shoulder function. Thus, the purpose of this study is to determine how the Spencer approach affects patients with frozen shoulders in terms of pain, ROM, and functional impairment. Methodology This study included 20 patients aged between 40 and 60 years with stage 2 and 3 diagnosed frozen shoulder. This is a single-group pilot study that received the Spencer technique along with a moist heat pack and Codman's exercises on the affected shoulder for three weeks. Outcome measures used for assessment before and after treatment were the visual analog scale (VAS), shoulder ROM, and shoulder pain and disability index (SPADI). After the second, third, and sixth months, a follow-up was conducted. Two patients were lost to follow-up; consequently, statistical analysis was performed on the data from 18 patients. Results The current study's results suggested that there was an improvement in the mean values of VAS, ROM, and SPADI at post-three weeks, and a sustained effect was observed at the second, third, and sixth months. A statistically significant difference (P < 0.05) was found. Conclusions The study's conclusions demonstrated improved pain, ROM, and SPADI scores post-intervention. Treatment effects persisted, as seen by follow-up at the two, three, and six-month marks. As a result, the Spencer technique utilized in this pilot study on frozen shoulder patients proved effective. Also, the outcome effects were sustained, which suggests its utility in frozen shoulder rehabilitation.

Frozen shoulder (FS) is a common condition that can cause severe pain and limited range of motion in the shoulder joint. While intra-articular steroid injection has been shown to be an effective treatment for FS, manipulation under anesthesia (MUA) is an alternative treatment that has gained popularity in recent years. However, there is a lack of evidence regarding the effectiveness of MUA on FS patients with concomitant rotator cuff injury or tear. Though a few studies have shown that MUA is not associated with rotator cuff tears, and will not exacerbate the injury, more high-quality studies with bigger sample sizes are needed. Therefore, the aim of this multi-center, single-blinded, randomized, parallel-group, superiority study is to compare the efficacy of MUA versus intra-articular steroid injection in the treatment of FS patients with a diagnosis of rotator cuff injury or tear by MRI.

A parallel, single-blinded, multi-center randomized controlled trial of 320 patients will be conducted at three hospitals of China. Eligible patients with frozen shoulder and rotator cuff injury or tear diagnosed by MRI will be randomly assigned to, in equal proportions, the manipulation under anesthesia group and the intra-articular steroid injection group via a central randomization system, undergoing a corresponding operation on day one and a sequent physical exercise for 14 days. The primary outcome is the comprehensive efficacy evaluation (total effective rate) and the change of Constant-Murley Score. Outcome assessors and data analysts will be blinded, and participants will be asked not to reveal their allocation to assessors.

This study aims to explore the superiority of manipulation under anesthesia in reducing pain and improving shoulder function in frozen shoulder patients accompanied with rotator cuff injury. To provide a scientific basis for the dissemination and application of manipulation under anesthesia, and a better knowledge for the role of MUA in the treatment of frozen shoulder accompanied with rotator cuff injury.

Chictr.org.cn ChiCTR2200067122 . Registered on 27 December 2022. ChiCTR is a primary registry of the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP) network and includes all items from the WHO Trial Registration data set in Trial registration.

Intra-articular corticosteroid or hyaluronic acid (HA) is commonly prescribed for frozen shoulder. However, few studies have investigated histological and molecular changes after injection.

To compare the effectiveness of intra-articular injections of triamcinolone and HA in a frozen shoulder rat model and verify a greater effect of triamcinolone in passive shoulder abduction compared with HA.

Controlled laboratory study.

Twenty male Sprague-Dawley rats were randomly allocated into 4 groups (n = 5 in each): control group, which did not receive cast immobilization or injection, and 3 experimental groups, which received 3 weeks of unilateral shoulder immobilization followed by intra-articular injections (normal saline, triamcinolone, or HA) at the immobilized shoulder. Passive shoulder abduction angle, histological and immunohistochemical staining, and Western blotting results were assessed 2 weeks after injection. The intensity and extent of staining were converted to semiquantitative scores for further analysis.

Shoulder abduction angles before sacrifice were 153.0°± 2.7° (control group), 107.0°± 5.7° (saline group), 139.0°± 9.6° (triamcinoline group), and 110.0°± 10.6° (HA group), showing significant differences between control and saline groups, control and HA groups, saline and triamcinoline groups, and triamcinoline and HA groups (P < .001) but not between control and triamcinoline groups (P = .053). Histologic evaluation revealed an increase in synovial folds and thickening of the capsular membrane in the saline and HA groups; this change was not evident in the triamcinolone group. A comparison of semiquantitative scores revealed greater expression levels of proteins involved in fibrosis and angiogenesis in the saline and HA groups compared with the control and triamcinolone groups. In Western blotting, the expression of inflammatory cytokines and the receptor for advanced glycation end products was significantly lower in the triamcinolone and HA groups than in the saline group.

Triamcinolone injection was more effective than normal saline or HA injection in improving range of motion and reversing fibrotic and angiogenic features of frozen shoulder. Both triamcinolone and HA injections elicited anti-inflammatory effects.

The antifibrotic and antiangiogenic properties of triamcinolone and the anti-inflammatory properties of both triamcinolone and HA should be considered when performing injections in clinical settings.

The exact pathogenesis of idiopathic adhesive capsulitis (IAC) is not fully understood, but an inflammatory profibrotic cascade, largely mediated by transforming growth factor-beta 1 (TGF- β1) has been implicated. Angiotensin II receptor blockers (ARBs) and angiotensin-converting enzyme inhibitors (ACE-Is) both decrease the activity of TGF-β1. The aim of this study was to determine the impact of ACE-Is or ARBs use on the need for operative intervention in IAC.

This was a retrospective cohort study of patients from a single institutional database with IAC, divided into two cohorts, with and without ACE-I and/or ARB use as the primary exposure and a minimum 2-year follow-up. The primary outcome measured was the incidence of operative intervention including manipulation under anesthesia (MUA) and arthroscopic capsular release (ACR). Additional multivariable logistic regression analysis was performed to evaluate associations between ACE-I/ARB use and likelihood of undergoing an operative procedure.

A total of 17,645 patients met inclusion criteria, with 5424 patients in the ACE-I/ARB cohort and 12,221 in the non-ACE-I/ARB cohort. Overall, 422 (2.4%) patients underwent surgical treatment, 378 (2.1%) ACR, and 74 (0.4%) MUA. There was no significant difference between cohorts in the frequency of surgical procedures or time to procedure since diagnosis. There were no significant differences between individual ACE-Is or ARBs, although Losartan was found to have a trend of decreased rate of intervention (31.7% vs. 36.8%, P = .209) when compared to patients not on losartan that did not reach statistical significance. Patient factors predictive of undergoing MUA/ACR were diabetes (P = .013), obesity (P < .001), and male sex (P < .001). Increasing patient age reduces the likelihood of undergoing operative intervention, with patients aged 50-70 years (P = .022) and age >70 years (P < .001) demonstrating reduced odds as compared to patients aged <30 years.

Patients with IAC have an overall low (2.4%) rate of requiring surgical intervention. While the antifibrotic mechanism of ACE inhibitors and ARBs did not significantly affect the rate of requiring surgical intervention, male gender, obesity, younger age, and diabetes, all increased the risk for operative intervention. Losartan, specifically, may have a disease modifying effect on IAC that should be investigated with larger controlled trials.

The thickened coracohumeral ligament (CHL) is an important part of the typical manifestations and magnetic resonance imaging of frozen shoulder. However, only a few clinical studies with limited cases on arthroscopic extra-articular entire CHL release exist in the literature. This study was to evaluate the effect of arthroscopic extra-articular entire CHL release for patients with recalcitrant frozen shoulder.

From February 2014 to February 2020, 81 cases of recalcitrant frozen shoulder patients treated with surgery in a single-center shoulder department and followed for more than 2 years were analyzed. Arthroscopic 360° capsular release was performed with intra-articular partial release (IPR group) or additional extra-articular entire release (IPR + EER group) of CHL. The same rehabilitation program was performed after surgery in both groups. Visual analogue scale (VAS) for pain, range of motion (ROM), and the Constant-Murley scoring system was evaluated before operation, at 3 months after operation, 6 months after operation, and the final follow-up. T-test, Mann-Whitney U-test and chi-squared test were used to compared data.

There were 39 patients in the IPR group, with an average follow-up of 29.2 months. A total of Forty-two patients in the IPR + EER group completed a mean follow-up of 25.7 months. All incisions healed in stages. There were significant differences in Constant-Murley shoulder score, VAS score, and ROM before operation and at the final follow-up in both groups (both P < 0.001). The VAS score of the IPR + EER group was lower than that of the IPR group at 3 months after surgery (P < 0.05), and 6 months after operation (P < 0.05). External rotation, internal rotation, and abduction of ROMs and Constant-Murley shoulder score were significantly greater in the IPR + EER group at 3 months (P < 0.001, P < 0.05, P < 0.001, P < 0.05, respectively) and 6 months after operation (P < 0.001, P < 0.05, P < 0.001, P < 0.05, respectively). At the last follow-up, there was no significant difference in forward flexion, internal rotation, and abduction of ROMs, VAS, and the Constant-Murley shoulder score between the IPR and IPR + EER groups. The external rotation of the IPR + EER group was still greater than that of the IPR group at the last follow-up (P < 0.001).

Arthroscopic extra-articular entire coracohumeral ligament release could solve early pain of shoulder joint, recover shoulder joint functions effectively, and achieve a satisfactory efficacy in the treatment of recalcitrant frozen shoulder.

Frozen shoulder (FS) is characterized by pain and limited range of motion (ROM). Inflammation and fibrosis are accepted as main pathologic processes associated with the development of FS. However, the intrinsic mechanisms underlying pathologic fibrosis remain unclear. We aimed to elucidate the key molecules involved in pathologic fibrosis and explore new therapeutic targets for FS. Synovial fibroblasts isolated from patient biopsies were identified using immunofluorescence. Western blotting, RT-qPCR, cell adhesion tests, and would-healing assays were used to evaluate the fibrosis-related functions of synovial fibroblasts. Elevated cluster of differentiation 36 (CD36) expression was detected in FS using Western blotting and immunohistochemistry. Salvianolic acid b (SaB) inhibited CD36, blocking synovial fibroblast-induced inflammation and fibrosis. Our RNA-seq data showed that knocking down CD36 dramatically impaired the capacity of synovial fibroblasts for cell adhesion and that the PI3K-Akt signaling pathway may be crucial to the fibrotic process of FS. By up-regulating CD36 and inhibiting the phosphorylation of Akt, we demonstrated that CD36 promotes pathologic fibrosis by activating the PI3k-Akt pathway. Finally, rats treated with SaB had improved ROM and less collagen fiber deposition than the FS model group. Conclusion: SaB attenuates inflammation and inhibited the CD36-mediated activation of the PI3K-Akt signaling pathway to block pathologic fibrosis of FS in vitro and in vivo models.

To determine the effect of perioperative angiotensin II receptor blocker (ARB) or angiotensin-converting enzyme inhibitors (ACEi) on postoperative arthrofibrosis, as defined by requiring manipulation under anesthesia (MUA) or new diagnosis of adhesive capsulitis (AC) following arthroscopic shoulder procedures.

Patients were retrospectively identified using Current Procedural Terminology surgical billing codes to identify patients who underwent any shoulder arthroscopic procedure at a single urban academic institution from 2012 to 2020 with a minimum 2-year follow-up. Patients were excluded if <30 years old at time of surgery, as these patients rarely use ARB and ACEi medications, or if they had pre-existing AC. Demographics, active medication prescriptions at the time of surgery, and medical comorbidities were recorded. Multivariable logistic regression was performed to determine the effect of ARB/ACEi on subsequent MUA or AC by 90 days, 1 year, and 2 years.

In total, 5,559 patients were included in the final analysis. A majority of the cohort (53.4%) underwent arthroscopic surgery between the ages of 50 to 69 years. Most patients were male (61.8%) and without obesity (67.3%). In total, 18.9% and 15.0% were taking an ARB or ACEi medication perioperatively, respectively. Within 2 years' postoperatively, 51 patients (0.9%) underwent subsequent ipsilateral MUA, and 174 patients (3.1%) developed AC. Patients taking ARBs had a 17.5% rate of postoperative arthrofibrosis within 2-years compared with 19.1% in those not on ARBs, although this difference was not significant (P = .58). Likewise, no significant difference was found between those taking ACEi versus not (15.0% vs 15.0%, P = .99). Individual generic ARB/ACEi subgroup analysis did not demonstrate any significant associations with rate of postoperative arthrofibrosis (P > .05).

ARBs or ACEi did not significantly affect the rate of postoperative arthrofibrosis following shoulder arthroscopy, however female sex, diabetes mellitus, and Black/African American race were associated with an increased rate of necessitating MUA or developing AC within 2 years postoperatively.

Level III, retrospective cohort study.

Frozen shoulder is a common, painful, and movement-restricting condition. Although primary frozen shoulder is idiopathic, secondary frozen shoulder can occur after trauma or surgery. Prophylactic and therapeutic options are often unsatisfactory. Vitamin C (ascorbic acid) is a potent physiological antioxidant and likely inhibits the activation of nuclear factor κB, which plays a decisive role in inflammatory reactions.

Because of its anti-inflammatory effects, vitamin C may be valuable in the prevention of secondary frozen shoulder.

Controlled laboratory study.

An in vivo shoulder contracture model was conducted by fixation of the right proximal limb of Sprague-Dawley rats. A treatment group (n = 8) receiving vitamin C orally was compared with a control group (n = 9) without vitamin C. The primary outcome was capsular thickness at the shoulder joint measured on magnetic resonance imaging (MRI) examination. Further histological examination was performed but was not statistically analyzed because of variability of the cutting plane through the glenoid.

Vitamin C treatment resulted in less thickening of the axillary fold of the operated shoulder at 2 of the 3 locations measured on MRI compared with untreated controls (insertion to the glenoid, P = .074; insertion to the humerus, P = .006; middle of the axillary recess, P = .008). The observed structural changes in histological examination corroborated the significant changes obtained from the MRI measurements.

Prophylactic vitamin C seemed to reduce the thickening of the axillary recess in secondary frozen shoulder in this preclinical study.

Vitamin C may be helpful as a noninvasive therapeutic measure to prevent secondary frozen shoulder (eg, within the context of surgery in the shoulder region or immobilization) or to treat primary frozen shoulder at an early stage. Further studies are required to evaluate the effect of this treatment in humans and the necessary dosage in humans.

The effect of diabetes on adhesive capsulitis (AC) and its impact on the outcomes of ultrasound (US)-guided hydrodistension of the glenohumeral joint are still unclear. We aimed to identify predictors of US-guided hydrodistension outcomes, while assessing the performance of the method in diabetic compared to non-diabetic patients.

A total of 135 patients with AC who underwent US-guided hydrodistension were prospectively included. Demographics and factors linked to chronic inflammation and diabetes were recorded and patients were followed-up for 6 months. Functionality and pain were evaluated with the Disabilities of the Arm, Shoulder and Hand (DASH) and the Visual Analogue Scale (VAS) score. Statistical analysis was performed with Mann-Whitney U test, linear, and binary logistic regression.

Diabetes was identified in 25/135 patients (18.5%). Diabetic patients had worse DASH and VAS score at presentation (P < 0.0001) and presented with a higher grade of AC (P < 0.0001) and lower range of motion (P < 0.01) compared to non-diabetics. Higher DASH (P = 0.025) and VAS scores (P = 0.039) at presentation were linked to worse functionality at 6 months. Presence and duration of diabetes, and the number of hydrodistension repeats, correlated with worse VAS and DASH scores at 6 months. The number of procedure repeats was the only independent predictor of complete pain resolution at 6 months (OR 0.418, P = 003).

Diabetes is linked to more severe AC at presentation and worse outcomes in patients undergoing US-guided hydrodistension. In resistant cases, repeating the intervention is independently linked to worse outcomes for at least 6 months post-intervention.

The Anti-Freaze-F trial will assess the feasibility of conducting a large randomised controlled trial to assess whether intra-articular injection of anti-TNF (adalimumab) can reduce pain and improve function in people with pain predominant early stage frozen shoulder.

We are conducting a multi-centre, randomised feasibility study, with an embedded qualitative sub-study. We will recruit adults ≥18 years with a new episode of shoulder pain attributable to early stage frozen shoulder, recruited from at least five UK NHS musculoskeletal and related physiotherapy services. Participants (n=84) will be randomised (centralised computer generated 1:1 allocation) to receive either: 1) intra-articular injection of anti-TNF (adalimumab 160mg) or 2) placebo injection (saline [0.9% sodium chloride]), both under ultrasound guidance. A second injection of the allocated treatment (adalimumab 80mg) or equivalent volume of placebo will be administered 2-3 weeks later. All participants will receive a physiotherapy advice leaflet providing education and advice about frozen shoulder and pain management. The primary feasibility objectives are: 1) the ability to screen and identify potential participants with pain predominant early stage frozen shoulder; 2) willingness of eligible participants to consent and be randomised to intervention; 3) practicalities of delivering the intervention, including time to first injection and number of participants receiving second injection; 4) standard deviation of the Shoulder Pain and Disability Index (SPADI) score and attrition rate at 3 months (i.e. 12 weeks) post-randomisation in order to estimate the sample size for a definitive trial. We will also assess follow up rates and viability of patient-reported outcome measures and range of shoulder motion for a definitive trial. Research Ethics Committee approval (REC 21/NE/0214).

ISRCTN 27075727; EudraCT number: 2021-003509-23; ClinicalTrials.gov NCT05299242.