Frozen shoulder. An overview of pathology and biology with hopes to novel drug therapies.

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.

Clinical outcomes and cost-effectiveness of manipulation under brachial plexus block versus physiotherapy for refractory frozen shoulder: a prospective observational study.

Background: Frozen shoulder (FS) is a pathological condition that involves a painful and stiff shoulder joint, most commonly in people aged 40-60 years. Most literature supports treatment with physical therapy (PT), although some studies have demonstrated years of continuing pain and functional deficits. Manipulation under anesthesia is effective at eliminating the contracture of intra-articular lesions for refractory FS. This study aimed to compare whether manipulation under anesthesia or PT is a more effective treatment in refractory FS. Methods: This study was a prospective observational study. A total of 102 patients with refractory FS were enrolled in this study in the medical records, all of whom had severe and multidirectional loss of motion and thickening of the joint capsule and coracohumeral ligament on magnetic resonance imaging. Fifty-one patients were in the manipulation under brachial plexus block (MUB) group (34 females, median age: 57 years), and 51 patients were in the PT group (34 females, median age: 59 years). The MUB procedure consisted of the conventional method with additional adduction manipulation, in which one examiner initially abducted the shoulder joint as much as possible. We recorded the visual analog scale, shoulder range of motion, and American Shoulder and Elbow Surgeons and Constant Scores at the initial baseline visit and at the 1-, 3-, 6-, and 12-month follow-ups. The total cost was calculated from the medical records, and cost-effectiveness was evaluated using quality-adjusted life year and incremental cost-effectiveness ratio. Results: Visual analog scale (P < .001), range of motion (P < .001), and American Shoulder and Elbow Surgeons and Constant Scores (P < .001) in the MUB group were significantly superior to those in the PT group at 1, 3, 6, and 12 months after treatment. The median cost and total quality-adjusted life year in the MUB and PT groups were $1375 versus $2751 and 2.95 versus 2.68, respectively, and the cost-effectiveness ratio between the MUB and PT groups was calculated as -$560. Conclusions: The new MUB procedure provides a shorter treatment period, better clinical outcomes, and higher cost-effectiveness in patients with refractory FS compared to PT.

Adduction Manipulation of the Glenohumeral Joint versus Physiotherapy for Atraumatic Rotator Cuff Tears: A Randomized Controlled Trial.

BACKGROUND: Atraumatic rotator cuff tears (ARCTs) are frequently concomitant with adduction restriction of the glenohumeral joint (GHJ). Adduction manipulation (AM) removes the restriction and relieves pain. The present study aimed to investigate the clinical efficacy of AM versus physiotherapy (PT) in ARCTs. METHODS: Eighty-eight patients with adduction restriction were allocated to the AM and PT groups (n = 44 per group). The glenohumeral adduction angle (GAA) was calculated using X-rays at the first and last follow-up appointments. We recorded pain severity (visual analog scale, VAS), flexion, abduction, external rotation (ER), internal rotation (IR), and American Shoulder and Elbow Society (ASES) and Constant scores at baseline and at 1-, 3-, 6-, and 12- month follow-ups. RESULTS: Forty-three patients (23 males, average age 71.3 years) in the AM group and 41 (16 males, average age 70.7 years) in the PT group were consequently analyzed. At the 1-month follow-up, VAS, shoulder motion except ER, ASES and Constant scores were much better in the AM group than in the PT group, whereas those in the PT group improved gradually up to 12 months. At the final follow-up, flexion, abduction, and Constant score were significantly better in the AM group than in the PT group. The GAA at the initial and final examinations was -21.6° and -3.2°, respectively, in the AM group, and -21.1° and -14.4°, respectively, in the PT group. CONCLUSIONS: The AM procedure, which had better clinical efficacy than PT, is recommended as the first conservative treatment option for ARCTs.

Treatment of acromioclavicular joint separations in Japan: a survey.

BACKGROUND: Treatment options for acromioclavicular joint (ACJ) separations are highly dependent on severity, as well as the patient's background. Furthermore, some patients can be switched from conservative to surgical treatment. In this study, we conducted a mail-based questionnaire survey of members of the Japan Shoulder Society on the administration of treatments for ACJ separations. METHODS: A questionnaire survey with 5 categories was mailed to all 1655 members of the Japan Shoulder Society (including 59 councilors): initial treatment, whether surgery was performed, indications for surgery based on severity, switching from conservative to surgical treatment, and surgical methods. RESULTS: Altogether, 183 members, including 56 councilors, responded. Regarding the initial treatment, 17 respondents opted for treatment without immobilization or fixation and 166 opted for immobilization or fixation. Of the members, 11 opted for only conservative treatment whereas 172 chose surgery depending on the case; of the latter, 9 considered it for patients with a Rockwood classification of type 2 or higher; 120, for patients with type 3 or higher; and 172, for patients with types 4-6. Furthermore, 75 of 172 members had experience switching to surgical treatment during conservative treatment. For 64 of 172 members, the modified Cadenat method was the most common surgical method. CONCLUSIONS: Only 11 members opted for conservative treatment of ACJ separations, and approximately 95% of physicians chose surgery. Furthermore, >70% of physicians considered surgery for an injury classified as type 3 or higher, and 37% of members performed the modified Cadenat method. However, the popularization of arthroscopic surgery may affect the selection of surgical methods in the future.

Methods used to assess the severity of acromioclavicular joint separations in Japan: a survey.

BACKGROUND: In acromioclavicular joint (ACJ) separations, patient characteristics determine the indications for surgery. However, in Japan, classification methods used to assess the severity of ACJ separations differ between institutions, and even within a classification method, different interpretations can lead to different assessments of severity. Therefore, in this study, we conducted an email survey of Japan Shoulder Society (JSS) members regarding their assessment methods for ACJ separation severity. METHODS: A questionnaire about methods for assessing the severity of ACJ separations was emailed to JSS members (1655) including 59 JSS councilors. The survey focused on diagnostic imaging methods, classifications of severity assessments, and methods of assessing severity. RESULTS: In total, 183 responses were received. All respondents used an anteroposterior view of the ACJ. Severity assessments were classified by the Tossy classification (57 respondents), Rockwood classification (141 respondents), and other classifications (7 respondents) including duplication. Of the 141 respondents using the Rockwood classification, 119 diagnosed type III as ACJ dislocation when the inferior clavicle border translated above the superior acromial border, whereas 56 used the coracoclavicular distance. However, to diagnose type V, 118 respondents used the coracoclavicular distance whereas 38 used palpation. To diagnose type IV, 57 respondents considered all cases in which the clavicle translated posterior to the acromion, even when vertical ACJ dislocation occurred simultaneously. However, 88 respondents did so in the presence of posterior clavicle displacement and ACJ subluxation. CONCLUSION: The Rockwood classification is commonly used for severity assessments in Japan; however, there is some disagreement regarding the assessment for the diagnosis of type IV. Methods to diagnose both superior and posterior translation of the clavicle need further debate.

A new pathophysiology of atraumatic rotator cuff tears: adduction restriction of the glenohumeral joint.

BACKGROUND: The pathophysiology of atraumatic rotator cuff tears (ATTs) has not been fully understood. Adduction restriction of the glenohumeral joint can cause pain and disability in patients with ATTs. We aimed to use our adduction test (pushing the humerus toward the side in the coronal plane with scapular fixation) to fluoroscopically measure the glenohumeral adduction angle (GAA) and to assess the effectiveness of adduction manipulation. MATERIALS AND METHODS: Fifty-five patients with ATTs were included in the study. The GAAs of the patients vs. healthy subjects without ATTs were measured fluoroscopically and compared. During the test, patients showed restriction and expressed pain. The visual analog scale (VAS) score, passive range of motion (ROM), and the American Shoulder and Elbow Surgeons score at the initial visit were compared with those after adduction manipulation. RESULTS: Of the patients, 41 (75%) had positive adduction test results. A higher percentage of positive adduction test results was observed in smaller tears. The average GAA was -21.4° on the affected side, which was smaller than that on the unaffected side, at -2.8° (P < .001), and that in healthy subjects, at 4.8° (P < .001). After manipulation, the GAA was -0.8° (P < .001) and the VAS score, the American Shoulder and Elbow Surgeons score, and all ROM values significantly improved up to the level on the unaffected side. CONCLUSION: Adduction restriction of the glenohumeral joint was identified in 75% of all the patients with ATTs. Adduction manipulation significantly reduces the VAS score and restores the ROM. Adduction restriction is considered a crucial pathophysiology of ATTs.

Receptor Tyrosine Kinases: Principles and Functions in Glioma Invasion.

Protein tyrosine kinases are enzymes that are capable of adding a phosphate group to specific tyrosines on target proteins. A receptor tyrosine kinase (RTK) is a tyrosine kinase located at the cellular membrane and is activated by binding of a ligand via its extracellular domain. Protein phosphorylation by kinases is an important mechanism for communicating signals within a cell and regulating cellular activity; furthermore, this mechanism functions as an "on" or "off" switch in many cellular functions. Ninety unique tyrosine kinase genes, including 58 RTKs, were identified in the human genome; the products of these genes regulate cellular proliferation, survival, differentiation, function, and motility. Tyrosine kinases play a critical role in the development and progression of many types of cancer, in addition to their roles as key regulators of normal cellular processes. Recent studies have revealed that RTKs such as epidermal growth factor receptor (EGFR), platelet-derived growth factor receptor (PDGFR), c-Met, Tie, Axl, discoidin domain receptor 1 (DDR1), and erythropoietin-producing human hepatocellular carcinoma (Eph) play a major role in glioma invasion. Herein, we summarize recent advances in understanding the role of RTKs in glioma pathobiology, especially the invasive phenotype, and present the perspective that RTKs are a potential target of glioma therapy.

Representative survey of frozen shoulder questionnaire responses from the Japan Shoulder Society: What are the appropriate diagnostic terms for primary idiopathic frozen shoulder, stiff shoulder or frozen shoulder?

BACKGROUND: Primary frozen shoulder has unknown etiology and significant restriction of active and passive motion. The distinction between frozen shoulder and stiff shoulder has been unclear. Therefore, the purposes of this study were to perform a survey regarding definition and classification of frozen shoulder proposed by the American Academy of Orthopedic Surgeons (AAOS) among the members of the Japan Shoulder Society (JSS) and to compare the results with those obtained among the members of the American Shoulder and Elbow Surgeons (ASES). METHODS: The Scientific Research Project Committee of the JSS prepared the questionnaire for frozen shoulder and stiff shoulder. Surveys were sent by e-mail on Jan 14, 2016 to JSS registered members and the response dead-line was set on March 13, 2016. RESULTS: The number of respondents was 230, including all directors, councilors, and senior doctors. Agreement with the definition of primary frozen shoulder was 67%, the classification of primary or secondary frozen shoulder was 53%, and the 3 divisions of secondary frozen shoulder was 53%. Diagnostic terms for the cases of shoulder stiffness with unknown etiology were as follows: frozen shoulder (31%), stiff shoulder (22%), periarthritis scapulohumeralis (16%), so called "Gojukata" in Japan, which means shoulder problems in their fifties (16%), idiopathic frozen shoulder (6%), primary frozen shoulder (4%), adhesive capsulitis (3%), others (2%). CONCLUSION: The survey shows lower rates of agreement among the JSS members than the ASES members for the definition of primary frozen shoulder, the classification of primary and secondary frozen shoulder, and the divisions of secondary frozen shoulder. To avoid confusion between stiff shoulder and frozen shoulder, the committee agrees to the ISAKOS recommendation that the term "frozen shoulder" should be used exclusively for primary idiopathic stiff shoulder.

Effects of Arthroscopic Coracohumeral Ligament Release on Range of Motion for Patients with Frozen Shoulder.

BACKGROUND: A thickened coracohumeral ligament is a highly specific manifestation of, and primary restraint against external rotation in frozen shoulders. OBJECTIVE: The purpose of this study was to evaluate the effects of complete arthroscopic coracohumeral ligament release on range of motion in frozen shoulder. METHODS: Fifty-two consecutive shoulders in 52 patients were treated between April 2015 and June 2016. To evaluate solely glenohumeral range of motion, the scapula was fixed by an examiner with one hand (without palpating scapular motion), and range of motion was measured using a goniometer. For the first step, arthroscopic pancapsular release was performed in a beach-chair position with (Group 1) or without (Group 2) complete coracohumeral ligament release. For the final step, the remaining coracohumeral ligaments in Group 2 were released and the ranges of motion were compared to those in Group 1. RESULTS: The average age of the patients was significantly higher in Group 1, but there were no significant differences between the two groups with respect to sex, affected side, preoperative range of motion, or American Shoulder and Elbow Society Score. Abduction, external rotation at adduction, and external and internal rotations at 90° of flexion in Group 1 were significantly greater than those in Group 2. After the additional release of the remaining coracohumeral ligaments in Group 2, all ranges of motion were significantly recovered and there was no significant difference between the groups. CONCLUSION: Complete coracohumeral ligament release is a recommended intraoperative procedure for regaining full range of motion in frozen shoulders.

Short-term Clinical Results of Manipulation Under Ultrasound-Guided Brachial Plexus Block in Patients with Idiopathic Frozen Shoulder and Diabetic Secondary Frozen Shoulder.

PURPOSE: This study examined the effectiveness of manipulation under ultrasound-guided brachial plexus block in patients with recalcitrant idiopathic frozen shoulder and diabetic secondary frozen shoulder (diabetic frozen shoulder). METHODS: Forty-four idiopathic frozen shoulders and 10 diabetic frozen shoulders with failed conservative treatment for at least 3 months were included in this study. The manipulation was performed under ultrasound-guided brachial plexus block and visual analogue scale, range of motion, and Constant scores were measured before manipulation and at the last follow-up examination. RESULTS: No major complications were observed during the procedure. Sufficient improvement was not obtained in two patients during the procedure and to avoid complications, the procedure was discontinued and subsequently arthroscopic capsular release was performed. Visual analogue scale, range of motion towards all directions, and Constant scores were significantly improved after the manipulation in both the idiopathic frozen shoulder and diabetic frozen shoulder groups, however the diabetic group showed inferior results compared with those of the idiopathic group. CONCLUSION: This manipulation was effective and shortened the duration of symptoms in most of the idiopathic and diabetic frozen shoulders without major complications during the procedure. Diabetic frozen shoulder showed inferior clinical results and difficulty in recovery in range of motion, which indicated that diabetic frozen shoulder should be discussed as a different entity.

Arthroscopic Coracohumeral Ligament Release for Patients With Frozen Shoulder.

Arthroscopic pancapsular release has been recommended for recalcitrant frozen shoulder, but regaining range of motion has not been sufficient compared with the unaffected side. There is no consensus about the reasons for these remaining restrictions in range of motion, but residual capsular or connective tissue must be considered a candidate. A thickened coracohumeral ligament at the rotator interval has been reported as one of the most specific manifestations of frozen shoulder. It covers wider portions of the subscapularis tendon, supraspinatus tendon, and infraspinatus tendon than previously reported. We describe an arthroscopic surgical technique for the release of the entire coracohumeral ligament including the subscapularis and supraspinatus portions and the release of the inferior and posterior parts of the glenohumeral ligament using the 7-o'clock portal. These procedures are essential and reliable methods to release the entire joint capsule to regain full range of motion for frozen shoulder.

Anatomic study and electromyographic analysis of the teres minor muscle.

BACKGROUND: The teres minor muscle is a focused topic on the treatment of massive rotator cuff tears and reverse total shoulder arthroplasty. Its precise anatomy and function have not been completely investigated. The purposes of this study were to anatomically investigate the muscle and analyze electromyographic (EMG) activities during shoulder motion. METHODS: This anatomic study used 20 shoulders from deceased donors (mean age, 75.0 years). EMG data were recorded from 10 healthy volunteers (mean age, 21.7 years) during flexion, abduction, and external rotations at 0° of abduction, at 90° of abduction, and at 90° of flexion in their dominant arms synchronized with a computerized 3-dimensional motion analysis system. RESULTS: The muscle in all specimens consisted of 2 distinct muscular bundles: the upper and lower portions. The upper portion attached to the round area of the greater tuberosity, and the lower portion inserted into the linear shaped area. Both portions were independent in their origins, insertions, and innervation. The muscle engaged force during each shoulder motion. EMG activities of abduction and the 3 forms of external rotation were similar. Maximal voluntary contraction in the 3 forms of external rotation was 32% in maximum external rotation in the neutral position, 25% in flexion, and 40% in abduction. CONCLUSIONS: The teres minor consists of independent upper and lower portions. The muscle engages force in all ranges of 5 shoulder motions, and maximum external rotation in abduction is a reliable method to evaluate potential activity of the muscle.

Quadrilateral Space Syndrome With Involvement of the Tendon of the Latissimus Dorsi.

Quadrilateral space syndrome (QSS) is the term used to describe axillary nerve palsy due to compression of the axillary nerve and posterior circumflex artery in the quadrilateral space. The precise pathophysiology of QSS is still unclear; hence, a consensus of diagnosis and treatment for QSS has not yet been achieved. The authors present the case of a 17-year-old male baseball player with symptoms of QSS, including right elbow and shoulder joint pain and upper limb numbness while throwing. The symptoms had worsened during baseball. Conservative management for 3 months failed to resolve the symptoms, so surgery was performed. Axillary nerve decompression resulted in functional improvement. The cause of QSS has been previously reported to be fibrous bands, the long head of the triceps, and Bennett lesions. However, the cause of QSS in this case was compression of the axillary nerve between the proximal humerus and the tendinous attachment of the latissimus dorsi. The authors incised a 10- to 15-mm segment of the medial edge of the tendinous insertion of the latissimus dorsi, which resulted in resolution of QSS symptoms. [Orthopedics. 2017; 40(4):e714-e716.].

Does Scapular Motion Regress with Aging and is It Restricted in Patients with Idiopathic Frozen Shoulder?

PURPOSES: It has been reported that the amount of posterior tilt and upward rotation in scapular motions decreases with aging. The purposes of the current study were to investigate age related scapular motion regression and scapular restriction in patients with idiopathic frozen shoulder (IFS). METHODS: The groups were recruited as follows: two groups of 50 asymptomatic subjects aged in their twenties and fifties, and 56 patients with IFS. We passively moved the scapula toward 8 directions: elevation/depression; upward/downward rotation; external/internal rotation; and anterior/posterior tilt. The grading of scapular motion was ranged from 0 to 3 (3, normal; and 0, severe restriction) and the score for each direction and the total aggregated score for all directions were calculated. RESULTS: Scapular restriction was present in 3 subjects (6%) in the normal 20s group, 10 (14%) in the 50s group, and 51 (91%) in the IFS group. The total score between the normal 20s and 50s groups did not show statistical difference; however, greater significance was present between the normal 50s group and the IFS group (p < 0.01). There was statistical significance in depression (p < 0.01), downward rotation (p < 0.01), and posterior tilt (p < 0.01) among the 3 groups. CONCLUSION: Depression, downward rotation, and posterior tilt substantially regress with aging. Scapular motions towards depression, downward rotation, external rotation, and posterior tilt are severely restricted in the IFS group.

A Thickened Coracohumeral Ligament and Superomedial Capsule Limit Internal Rotation of the Shoulder Joint: Report of Three Cases.

Adhesive capsulitis of the shoulder (also known as frozen shoulder) is a painful and disabling disorder with an estimated prevalence ranging from 2% to 5% in the general population. Although the precise pathogenesis of frozen shoulder is unclear, thickened capsule and coracohumeral ligament (CHL) have been documented to be one of the most specific manifestations. The thickened CHL has been understood to limit external rotation of the shoulder, and restriction of internal rotation of the shoulder has been believed to be related to posterior capsular tightness. In this paper, three cases of refractory frozen shoulder treated through arthroscopic release of a contracted capsule including CHL were reported. Two cases in which there is recalcitrant severe restriction of internal rotation after manipulation under anesthesia (MUA) were finally treated with arthroscopic surgery. Although MUA could release the posterior capsule, internal rotation did not improve in our cases. After release of the thickened CHL, range of motion of internal rotation was significantly improved. This report demonstrates the role of the thickened CHL in limiting the internal rotation of the shoulder. We highlight the importance of release of thickened CHL in addition to the pancapsular release, in case of severe limitation of internal rotation of shoulder.

Massive Hemorrhage from the Posterior Ethmoidal Artery during Transsphenoidal Surgery: Report of 2 Cases.

Nasal bleeding is a major complication that can occur during and after transsphenoidal surgery (TSS) for intra- and suprasellar tumors. In most cases, the cause of this bleeding can be attributed to a branch of the maxillary artery called the sphenopalatine artery, injury to which can lead to life-threatening situations. Upon exposure of the suprasellar region and planum sphenoidale during surgery, it is also important to avoid damaging the posterior ethmoidal artery (PEA), a branch of the ophthalmic artery. While recent advancement in endoscopic techniques enables the performance of extended TSS, the chances of PEA injury seem to be increasing. In the current report, we present two cases that showed massive PEA bleeding during regular (not extended) TSS. The total blood loss was 2280 ml and 2150 ml, and endoscopic views disturbed by the massive hemorrhages remarkably delayed accurate stanching of the responsive artery. Therefore, anatomical recognition of the PEA is required to avoid fatal hemorrhaging during even regular TSS, especially for the beginners of this surgery.

Symptomatic foramen of Magendie arachnoid cyst in an elderly patient.

BACKGROUND: Arachnoid cysts (ACs) are congenital anomalies of the central nervous system and arise in virtually all locations where the arachnoid membrane exists. Posterior fossa ACs are considered to develop in the posterior aspect of the rhombencephalic roof plate and do not communicate freely with the fourth ventricle or perimedullary subarachnoid space. Although posterior fossa ACs have been reported a number of times, ACs arising from the foramen of Magendie are very rare. CASE DESCRIPTION: We report here on a 76-year-old female who presented with progressive gait disturbance. Magnetic resonance imaging of the head showed a large AC in the foramen of Magendie that was compressing the inferior vermis and medial aspects of the cerebellar hemisphere without causing hydrocephalus. Neurological examination revealed cerebellar ataxia without Romberg's sign. A nearly total excision of the cyst was safely performed via a median suboccipital approach. The patient's postoperative course was excellent and her neurological recovery was remarkable. CONCLUSION: Most cases of ACs located in the foramen of Magendie are reported in children, and it is extremely rare to observe such ACs in the elderly. In fact, to our knowledge, a symptomatic foramen Magendie AC has never been reported previously in an elderly person. Our results indicate that proper surgical intervention can yield highly positive outcomes in such cases.

Strong therapeutic potential of γ-secretase inhibitor MRK003 for CD44-high and CD133-low glioblastoma initiating cells.

The Notch signal regulates both cell viability and apoptosis, and maintains stemness of various cancers including glioblastoma (GBM). Although Notch signal inhibition may be an effective strategy in treating GBM initiating cells (GICs), its applicability to the different subtypes of GBM remains unclear. Here, we analyzed the effectiveness of MRK003, a preclinical γ-secretase inhibitor, on GICs. Nine patient-derived GICs were treated by MRK003, and its efficacy on cell viability, apoptosis, sphere forming ability and Akt expression level which might be related to Notch downstream and be greatly important signals in GBM was evaluated. MRK003 suppressed viability and sphere-formation ability, and induced apoptosis in all GICs in varying doses of MRK003. Based on their sensitivities to MRK003, the nine GICs were divided into "relatively sensitive" and "relatively resistant" GICs. Sensitivity to MRK003 was associated with its inhibitory effect on Akt pathway. Transgenic expression of the myristoylated Akt vector in relatively sensitive GICs partially rescued the effect of MRK003, suggesting that the effect of MRK003 was, at least in part, mediated through inhibition of the Akt pathway. These GICs were differentiated by the expression of CD44 and CD133 with flow cytometric analysis. The relatively sensitive GICs are CD44-high and CD133-low. The IC50 of MRK003 in a set of GICs exhibited a negative correlation with CD44 and positive correlation with CD133. Collectively, MRK003 is partially mediated by the Akt pathway and has strong therapeutic potential for CD44-high and CD133-low GICs.

Effects of intra-articular steroid injection before pan-capsular release in patients with refractory frozen shoulder.

PURPOSE: The purpose of the study was to retrospectively determine the effects of intra-articular steroid injection on the clinical outcome of patients who underwent arthroscopic pan-capsular release for refractory frozen shoulder. METHODS: Between 2000 and 2010, 34 patients (20 males, 14 females) who underwent an arthroscopic pan-capsular release for frozen shoulder were included. Intra-articular steroid injections were administered from April 2006, and just before surgery and at the final follow-up, ranges of motion (ROM) and scores of the Shoulder Rating Scale of the University of California, Los Angeles (UCLA) scoring system were evaluated. RESULTS: Intra-articular steroid injection significantly improved the UCLA scores of pain just before surgery and at the final follow-up (1.7 ± 0.5 vs. 6 ± 2, p < 0.0001). We subdivided the patients into those with and without diabetes mellitus. Steroid injection had a significant effect on the ROM in forward flexion (166.6 ± 8.6 vs. 140 ± 36.1, p = 0.026) and the scores of pain (10 vs. 9.3 ± 1.2, p = 0.046) at the final follow-up in the group without diabetes mellitus compared with those with it. CONCLUSION: Intra-articular steroid injection improves pain just before an arthroscopic pan-capsular release and at the final follow-up in all the patients with refractory frozen shoulder. However, it improves the ROM in forward flexion and the UCLA scores of pain at the final follow-up only in those without diabetes mellitus. LEVEL OF EVIDENCE: Therapeutic studies, Level IV.