Gene association analysis to determine the causal relationship between immune-mediated inflammatory diseases and frozen shoulder.

Multiple studies have indicated a potential correlation between immune-mediated inflammatory diseases (IMIDs) and Frozen shoulder (FS). To explore the genetic causal relationship between IMIDs and FS using 2-sample Mendelian randomization (MR) analysis. Genome-wide association study (GWAS) summary data for FS were obtained from Green's study, while data for 10 IMIDs were sourced from the FinnGen Consortium. The MR analysis was performed using inverse variance weighting, MR Egger, and weighted median methods. IVW, as the primary MR analysis technique, was complemented with other sensitivity analyses to validate the robustness of the results. Additionally, reverse MR analysis was further conducted to investigate the presence of reverse causal relationships. In the forward MR analysis, genetically determined 4 IMIDs are causally associated with FS: rheumatoid arthritis (odds ratio [OR] (95% confidence interval [95% CI]) = 1.05 [1.02-1.09], P < .01); type 1 diabetes (OR [95% CI] = 1.06 [1.03-1.09], P < .01); hypothyroidism (OR [95% CI] = 1.07 [1.01-1.14], P = .02); and Celiac disease (OR [95% CI] = 1.02 [1.01-1.04], P = .01). However, no causal relationship was found between 6 IMIDs (autoimmune hyperthyroidism, Crohn disease, ulcerative colitis, psoriasis, sicca syndrome and systemic lupus erythematosus) and FS. Sensitivity analyses did not detect any heterogeneity or horizontal pleiotropy. In the reverse MR analysis, no causal relationship was observed between FS and IMIDs. In conclusion, this MR study suggests a potential causal relationship between rheumatoid arthritis, type 1 diabetes, hypothyroidism, and Celiac disease in the onset and development of FS. Nevertheless, more basic and clinical research will be needed in the future to support our findings.

Anti-TNF (adalimumab) injection for the treatment of pain-predominant early-stage frozen shoulder: the Anti-Freaze-Feasibility randomised controlled trial.

OBJECTIVE: 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. DESIGN: Multicentre, randomised feasibility trial, with embedded qualitative study. SETTING: Four UK National Health Service (NHS) musculoskeletal and related physiotherapy services. PARTICIPANTS: Adults ≥18 years with new episode of shoulder pain attributable to early-stage frozen shoulder. INTERVENTIONS: 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. RESULTS: 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%. CONCLUSION: 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. TRIAL REGISTRATION NUMBER: ISRCTN 27075727, EudraCT 2021-03509-23, ClinicalTrials.gov NCT05299242 (REC 21/NE/0214).

Unveiling potential therapeutic targets for diabetes-induced frozen shoulder through Mendelian randomization analysis of the human plasma proteome.

INTRODUCTION: This study aimed to assess the causal relationship between diabetes and frozen shoulder by investigating the target proteins associated with diabetes and frozen shoulder in the human plasma proteome through Mendelian randomization (MR) and to reveal the corresponding pathological mechanisms. RESEARCH DESIGN AND METHODS: We employed the MR approach for the purposes of establishing: (1) the causal link between diabetes and frozen shoulder; (2) the plasma causal proteins associated with frozen shoulder; (3) the plasma target proteins associated with diabetes; and (4) the causal relationship between diabetes target proteins and frozen shoulder causal proteins. The MR results were validated and consolidated through colocalization analysis and protein-protein interaction network. RESULTS: Our MR analysis demonstrated a significant causal relationship between diabetes and frozen shoulder. We found that the plasma levels of four proteins were correlated with frozen shoulder at the Bonferroni significance level (p<3.03E-5). According to colocalization analysis, parathyroid hormone-related protein (PTHLH) was moderately correlated with the genetic variance of frozen shoulder (posterior probability=0.68), while secreted frizzled-related protein 4 was highly correlated with the genetic variance of frozen shoulder (posterior probability=0.97). Additionally, nine plasma proteins were activated during diabetes-associated pathologies. Subsequent MR analysis of nine diabetic target proteins with four frozen shoulder causal proteins indicated that insulin receptor subunit alpha, interleukin-6 receptor subunit alpha, interleukin-1 receptor accessory protein, glutathione peroxidase 7, and PTHLH might contribute to the onset and progression of frozen shoulder induced by diabetes. CONCLUSIONS: Our study identified a causal relationship between diabetes and frozen shoulder, highlighting the pathological pathways through which diabetes influences frozen shoulder.

[Establishment and evaluation of a rabbit model of frozen shoulder induced by persistent strain injuries and ice compression].

OBJECTIVE: To evaluate the rabbit modle of frozen shoulder induced by persistent strain injuries and ice compression. METHODS: Twelve clean, healthy male New Zealand rabbits with a mass of (2 500±500) g were selected and randomly divided into a blank group and a control group with 6 rabbits in each group. In the control group, the rabbits were modeled with persistent strain injuries and ice compression, the general conditions of the rabbits and the active and passive activities of the shoulder joint were observed and their body weights were recorded. MRI was performed on the affected shoulder joints at 6 d and 29 d after modelling to observe the fluid and soft tissue;HE staining was used to observe the morphology of the rabbit biceps longus tendon and the synovial membrane of the joint capsule;Masson staining was used to observe the fibrous deposits of the rabbit biceps longus tendon and the synovial membrane of the joint capsule, and the fibrous deposits were analysed semi-quantitatively by Image J software. RESULTS: Six days after the end of modeling, the active movement of the shoulder joints in the control group was limited, the passive movement was not significantly limited, and they walked with a limp;29 days after the end of the modeling, the active and passive movements of the shoulder joints in the model group were severely limited. Compared with the blank group (2.50±0.14) kg, the body weight of the model group (2.20±0.17) kg was significantly reduced(P<0.01). MRI showed that 6 days after modelling, the muscles around the shoulder joint were not smooth in shape, the joint capsule structure was narrowed and a large amount of fluid was seen in the joint cavity;29 days after modelling, the muscles around the shoulder joint were rough in shape, structure of the joint capsule was unclear and the fluid in the joint cavity was reduced compared with 6 days after modelling. Pathological staining showed that the long-headed biceps tendon fibres in the control group were disorganised, curled or even broken, and the synovial tissue of the joint capsule was heavily vascularised, with collagen fibre deposits and severe inflammatory cell infiltration. The fiber deposition of the long head of biceps brachii in the model group [(23.58±3.41)%, (27.56±3.70)%] and synovial tissue [(41.78±5.59)%, (62.19±7.54)%] were significantly higher than those in the blank group [(1.79±1.03) %, (1.29±0.63) %] at 7 and 30 days after modeling and synovial tissue fiber deposition [(8.15±3.61) %, (11.29±7.10) %], as shown by the semi-quantitative analysis of Masson staining results by Image J software. And the longer the time, the more severe the fibrosis (P<0.01). CONCLUSION: The behavioral, imaging and pathological findings showed that the rabbit frozen shoulder model with persistent strain injuries and ice compression is consistent with the clinical manifestations and pathogenesis of periarthritis, making it an ideal method for periarthritis research.

[Frozen Shoulder - a short review for the practice].

INTRODUCTION: The Frozen Shoulder is a frequently encountered pathology in clinical practice. This condition often coexists with various comorbidities and is characterized by severe pain and a significantly restricted motion of the affected shoulder. A limited passive external rotation with the arm in adduction, with no signs of any other pathology that could explain the finding, such as shoulder osteoarthritis or an undetected posterior dislocation, is pathognomonic. The course of the disease typically spans over one to two years and is usually self-limiting. In the vast majority of cases, this condition can be managed conservatively. Keywords: shoulder, shoulder stiffness, shoulder pain, conservative therapy.

Efficacy of a high-intensity home stretching device and traditional physical therapy in non-operative management of adhesive capsulitis - a prospective, randomized control trial.

BACKGROUND: Historically, in-person physical therapy serves as a foundational component of nonoperative treatment of adhesive capsulitis (AC). This study compares the effectiveness of an at-home high-intensity stretch (HIS) device to traditional physical therapy (PT) and to PT in combination with the HIS device. We hypothesize that the HIS device will be as effective as PT alone or as combination therapy in the first-line treatment of AC and use of the HIS device will exhibit improvement at higher rate. METHODS: Thirty-four patients with idiopathic adhesive capsulitis and a minimum of 12 months follow-up were included in this study. Patients were randomized into one of the three groups: HIS device, PT alone, or HIS device + PT. Passive range of motion (ROM), American Shoulder and Elbow Surgeons (ASES), and Simple Shoulder Test (SST) scores were measured. Additionally, patient satisfaction, compliance and complications were recorded. Paired t-test, ANOVA and Chi-squared tests were used in analysis. RESULTS: Final ROM in all planes improved for all groups compared to baseline (p < 0.001), with only HIS device group able to restore > 95% of contralateral ROM in all planes at final follow-up. Patients with PT alone were on average slowest to improve ROM from baseline, at 3 months, 6 months, and 1 year in all planes except internal rotation. ASES and SST scores improved for all groups when compared to baseline (p < 0.001). Use of HIS-device resulted in greater improvement in SST and ASES Total scores compared to PT alone (p = 0.045, and p = 0.048, respectively). CONCLUSIONS: Use of an at-home high-intensity stretching device for conservative treatment of idiopathic adhesive capsulitis improves outcomes in ROM and in ASES and SST scores both when used as an adjunct to physical therapy and when used alone. TRIAL REGISTRATION: The study protocol was registered at www. CLINICALTRIALS: gov (20/05/2022, NCT05384093).

Advanced osteoarthritis of the hip as reason for extensive asymmetric leg edema: a rare case report and review of the literature.

An enlarged iliopectineal bursa (IB) can cause pressure on iliofemoral veins. Clinical presentation can manifest as asymmetrical lower extremity edema. This case report demonstrates extensive asymmetrical leg edema caused by femoral vein compression based on iliopectineal bursitis (IB-itis) associated with advanced osteoarthritis (OA) of the left hip joint with an outline of relevant current literature. A female patient presented with left hip pain and edema in the leg. X-ray showed severe OA of the left hip. Computed Tomography (CT) concluded a cystic abnormality at the left iliopsoas muscle associated with the joint consistent with IB-itis, associated with a degenerative left hip joint. Hybrid total hip replacement was performed. At three-month follow-up her left leg showed no longer signs of extensive edema and she walked without the use of walking aids. IB-itis is mostly associated with rheumatoid arthritis (RA). There are no reports which only describe OA as cause of IB-itis. Extensive asymmetrical leg edema can be caused by venous compression of the femoral vein by an IB-itis. If the latter is the consequence of advanced hip OA, a total hip replacement can yield excellent clinical outcomes both functionally and with regard to the edema.

Agomir-122-loaded nanoparticles coated with cell membrane of activated fibroblasts to treat frozen shoulder based on homologous targeting.

As a common musculoskeletal disorder, frozen shoulder is characterized by thickened joint capsule and limited range of motion, affecting 2-5% of the general population and more than 20% of patients with diabetes mellitus. Pathologically, joint capsule fibrosis resulting from fibroblast activation is the key event. The activated fibroblasts are proliferative and contractive, producing excessive collagen. Albeit high prevalence, effective anti-fibrosis modalities, especially fibroblast-targeting therapies, are still lacking. In this study, microRNA-122 was first identified from sequencing data as a potential therapeutic agent to antagonize fibroblast activation. Then, Agomir-122, an analog of microRNA-122, was loaded into poly(lactic-co-glycolic acid) (PLGA) nanoparticles (Agomir-122@NP), a carrier with excellent biocompatibility for the agent delivery. Moreover, relying on the homologous targeting effect, we coated Agomir-122@NP with the cell membrane derived from activated fibroblasts (Agomir-122@MNP), with an attempt to inhibit the proliferation, contraction, and collagen production of abnormally activated fibroblasts. After confirming the targeting effect of Agomir-122@MNP on activated fibroblasts in vitro, we proved that Agomir-122@MNP effectively curtailed fibroblasts activation, ameliorated joint capsule fibrosis, and restored range of motion in mouse models both prophylactically and therapeutically. Overall, an effective targeted delivery method was developed with promising translational value against frozen shoulder.

[OLECRANON BURSITIS].

INTRODUCTION: The olecranon bursa is a pocket-like structure located at the posterior aspect of the elbow that is responsible for the smooth movement of the surrounding tissues. Frequently, it is the source of elbow pain due to an inflammation which may be caused by local injury or penetration of bacteria through the skin. This can lead to an initial acute and possibly a late chronic inflammation. Chronic inflammation may originate from systemic diseases such as gout and rheumatoid arthritis as well. The treatment of olecranon bursitis may be conservative (non-surgical) or surgical. Recently, there is more supporting evidence for the use of conservative management over surgical intervention in treating olecranon bursitis.

Psychometric properties of the Disability of Arm Shoulder and Hand (DASH) in subjects with frozen shoulder: a reliability and validity study.

BACKGROUND: Frozen Shoulder (FS) is a painful condition characterized by severe pain and progressive restriction of shoulder movement, leading to functional impairment and reduced quality of life. While different Patient Reported Outcome Measurements (PROMs) tools exist for assessing shoulder diseases, few specific PROMs are validated for FS patients. PURPOSE: This study aims to assess the psychometric properties of the Disability of Arm, Shoulder, and Hand (DASH) questionnaire in FS patients. METHODS: One hundred and twenty-four subjects (mean ± SD age = 55.4 ± 7.9 years; 55.6% female) diagnosed with FS were included and completed the DASH questionnaire, the Numerical Pain Rating Scale (NPRS), the Shoulder Pain and Disability Index (SPADI), and the Short-Form Health Survey 36 (SF-36). Floor or ceiling effects were investigated. Structural validity was analysed through a unidimensional Confirmatory Factor Analysis (CFA), internal consistency through Cronbach's alpha, test-retest reliability through the Intraclass Correlation coefficient (ICC), measurement error through the Standard Error of Measurement (SEM), and the Minimum Detectable Change (MDC), and construct validity through the hypothesis testing with the correlation with the other outcome measures used. RESULTS: No floor or ceiling effects were observed. CFA confirmed a one-factor structure after addressing local item dependency (Root Mean Square Error of Approximation = 0.055; Standardized Root Mean Square Residual = 0.077; Comparative Fit Index = 0.970; Tucker-Lewis Index = 0.968). Cronbach's alpha was high (= 0.951), and test-retest reliability was excellent (ICC = 0.999; 95% CI: 0.998-1.000). SEM was equal to 0.5 points, and MDC to 1.5 points. Construct validity was considered satisfactory as 80% of the a-priori hypotheses were met. CONCLUSION: The DASH questionnaire demonstrated good psychometric properties in FS patients, supporting its use as a valuable tool for assessing the impact of FS in clinical and research settings.

Ketorolac Injections for Musculoskeletal Conditions: A Narrative Review.

Musculoskeletal conditions of the upper and lower extremities are commonly treated with corticosteroid injections. Ketorolac, a parenteral nonsteroidal anti-inflammatory drug, represents an alternative injectant for common shoulder, hip, and knee conditions. A review of the current literature was conducted on the efficacy of ketorolac injection in musculoskeletal diseases. Several studies support the use and efficacy of ketorolac injection in subacromial bursitis, adhesive capsulitis, and hip and knee osteoarthritis. Given the systemic effects of glucocorticoid injections, ketorolac may be a safe and effective alternative in patients with musculoskeletal disease. However, more evidence is required to better understand the effects ketorolac has on the human body during inflammatory processes.

Comparative effectiveness of low-level laser therapy versus muscle energy technique among diabetic patients with frozen shoulder: a study protocol for a parallel group randomised controlled trial.

BACKGROUND: Diabetes mellitus is one of the fastest-growing health challenges of the twenty-first century with multifactorial impact including high rates of morbidity and mortality as well as increased healthcare costs. It is associated with musculoskeletal complications, with frozen shoulder being commonly reported. While low-level laser therapy (LLLT) and muscle energy technique (MET) are commonly used to manage  this condition, there remains a lack of agreement on the most effective approach, with limited research available on their comparative efficacy. OBJECTIVES: To evaluate the comparative effectiveness of LLLT versus MET among diabetic patients with frozen shoulder. METHODS: This is a single-centre, prospective, single-blind, randomised controlled trial with three parallel groups to be conducted at Ahmadu Bello University Teaching Hospital, Zaria, Kaduna State, Nigeria. Sixty diabetic patients with frozen shoulder will be randomly assigned into LLLT group, MET group, or control group in a 1:1:1 ratio. All the groups will receive treatment three times weekly for 8 weeks. The primary outcome will be shoulder function and the secondary outcomes will include pain intensity, shoulder ROM, interleukin-6 (IL-6), depression, anxiety, and quality of life (QoL). All outcomes will be assessed at baseline, at post 8-week intervention, and at 3 months follow-up. DISCUSSION: This will be the first randomised controlled trial to evaluate the comparative effectiveness of LLLT versus MET on both clinical and psychological parameters among diabetic patients with frozen shoulder. The findings of the study may provide evidence on the efficacy of these interventions and most likely, the optimal treatment approach for frozen shoulder related to diabetes, which may guide clinical practice. TRIAL REGISTRATION: Pan African Clinical Trials Registry (PACTR202208562111554). Registered on August 10, 2022.

A review of the injuries caused by occupational footwear.

BACKGROUND: Occupational footwear is intended to provide protection against the risks associated with work activities. The choice of footwear is complex due to the welfare, health and safety conditions of workers. AIMS: To identify the injuries and problems caused by occupational footwear through a systematic review of the existing literature. METHODS: A literature search was carried out in the Cumulative Index to Nursing and Allied Health Literature, Dialnet Plus, Pubmed, Scientific Electronic Library Online, Medline, Scopus and Web of Science databases over the period 2000-23, following the PRISMA Declaration guidelines. RESULTS: A total of 27 studies were included in the review. The results indicated that there is a wide variety of injuries caused by occupational footwear: from dermal injuries (e.g. calluses) and injuries to the nail apparatus to inflammatory pathologies such as plantar fasciitis or bursitis. In addition, inappropriate footwear can cause pain in the ankle and foot, knees, hips and lower back. Other results include the discomfort derived from the footwear itself. CONCLUSIONS: Inappropriate footwear can cause injuries to the foot and other related bone structures. Further studies are needed on the detection of foot injuries caused by occupational footwear and the levels of action at this level to improve the worker's health, the adaptability of the footwear to the wearer, and the worker's comfort and adherence to the footwear.

Impact of open bursectomy and biceps tendon release with closed manipulation in frozen shoulder.

This retrospective observational study evaluated the efficacy of 2 different surgical approaches for the treatment of frozen shoulder (adhesive capsulitis). This study aimed to compare the efficacy, safety, and recovery times of the 2 treatment modalities. Fifty patients diagnosed with frozen shoulder and treated at Seyhan State Hospital were included in the study. The patients were retrospectively divided into 2 groups based on the treatment received. Group 1 consisted of 25 patients who underwent standard closed manipulation under anesthesia, a technique involving passive movements of the shoulder joint to tear the tight capsule and expand the range of motion (ROM). Group 2, which included 25 patients, underwent closed manipulation in addition to open bursectomy and biceps tendon capsule release. Open bursectomy involves surgical removal of the bursa to alleviate inflammation, while biceps tendon capsule release addresses chronic biceps tendonitis by partially removing the capsule of the tendon. Data on demographic information, operative details, preoperative and postoperative conditions, and patient-reported outcomes were collected and analyzed. Data analysis revealed that the combination of closed manipulation with open bursectomy and biceps tendon capsule release was more effective in reducing pain, increasing ROM, and improving quality of life than closed manipulation alone. The discussion would typically elaborate on how the results compare with existing literature, the clinical implications, and any potential limitations of the study. The results showed that the method that combined closed manipulation with open bursectomy and biceps tendon capsule release was better than closed manipulation alone in terms of reducing pain, increasing ROM, and improving quality of life.

Dynamics of disability and pain indicators under the influence of physical therapy for adhesives capsulitis and myofascial pain syndrome.

OBJECTIVE: Aim: To compare the effectiveness of end-range mobilization and therapeutic exercises, used in combination with ischemic compression, on disability and pain indicators among patients with adhesive capsulitis of the shoulder joint and thoracic myofascial pain syndrome. PATIENTS AND METHODS: Materials and Methods: The study involved 68 patients. Goniometry of the shoulder joint, assessment of pain in myofascial trigger points, and the Shoulder Pain and Disability Index questionnaire were used before and after physical therapy. The duration of physical therapy comprised 3 weeks. Physical therapy of the first group of patients consisted of end-range mobilization and ischemic compression. Patients of the second group performed therapeutic exercises and ischemic compression. RESULTS: Results: Both groups demonstrated positive dynamics of shoulder joint mobility, Shoulder Pain and Disability Index and pain in trigger points. However, the final results of the studied indicators were better in the first group of patients. CONCLUSION: Conclusions: Physical therapy based on the combination of end-range mobilization and ischemic compression had a more positive impact on disability and pain indicators for adhesive capsulitis of the shoulder joint and myofascial pain syndrome as compared to the combination of therapeutic exercises and ischemic compression.

The comparative effectiveness of combined hydrodilatation/corticosteroid procedure with two different quantities for adhesive capsulitis.

OBJECTIVE: To assess the efficacy of injecting various amounts of fluid into the shoulder joints for capsule distension in patients with adhesive capsulitis. DESIGN: A randomized controlled trial. SETTING: Outpatient clinic of a tertiary care centre. PARTICIPANTS: Eighty-four patients with adhesive capsulitis underwent a baseline (time0), 6 weeks (time1), and 12 weeks (time2) follow-up after hydrodilitation. INTERVENTION: Group 1 (n = 42) received 20 ml of lidocaine, steroid, and saline hydrodilatation via posterior glenohumeral recess, while Group 2 (n = 42) received 10 ml of lidocaine, steroid, and saline hydrodilitation. MAIN MEASURES: The primary outcome was the visual analogue scale for pain. The secondary outcomes were shoulder pain and disability index (SPADI) and ROM of the shoulder. RESULTS: There was a significant reduce in VAS scores for pain, SPADI scores, and increased shoulder ROM in both groups over time; however, the group-by-time interactions for any of the outcomes between groups were not significant except VAS pain in motion. Post-hoc pairwise analysis of the marginal effect of time and group showed that the significant difference of VAS in motion is due to time effect: time1 vs time0 (95% CI -4.09 to -2.68), time2 vs time0 (-4.21 to -2.77), and time2 vs time1 (-0.83 to 0.63), without between-group difference: group 1 vs group 2 (-0.38 to 0.59). CONCLUSION: Our study suggests hydrodilatation achieved an optimal effect at time1 for patients with adhesive capsulitis in both groups, and adding more saline offers additional benefits in flexion and external roatation until time2.