Noninterportal capsulotomy of hip arthroscopy showed improved outcomes in borderline hip dysplasia: A retrospective study with minimum 2-year follow-up.

PURPOSE: The present study aimed to evaluate the functional outcomes of hip arthroscopy using a noninterportal capsulotomy technique to address labral tears in patients with borderline hip dysplasia (BHD). Additionally, we also compared these outcomes with those of patients with BHD who underwent the standard repaired interportal capsulotomy (RIPC) arthroscopy. METHODS: Data from patients with BHD were retrieved from a database of patients who underwent arthroscopic hip surgery with noninterportal capsulotomy or RIPC to treat labral tears between January 2014 and December 2020. Data collected included both pre- and postoperative patient-reported outcomes (PROs). RESULTS: A total of 58 patients (noninterportal capsulotomy, n = 37; RIPC, n = 21) with a mean age of 30.9 ± 5.6 and 28.6 ± 5.5 years, respectively, met the inclusion criteria. All of the patients underwent a minimal 2-year follow-up. The mean lateral centre-edge angle was 23.3 ± 1.2° in the noninterportal capsulotomy group and 23.7 ± 1.0° in the RIPC group, with no significant difference. The PROs improved from the preoperative to the latest follow-up, with a p < 0.001. There were no differences between the groups. CONCLUSION: Using strict patient selection criteria, hip arthroscopy with noninterportal capsulotomy demonstrated significant pre- to postoperative improvements in patients with BHD and achieved results comparable to those from hip arthroscopy with RIPC. LEVEL OF EVIDENCE: Level III.

Development of a prognostic nomogram for lymph node positive HR+/HER2- breast cancer patients: a study of SEER database and a Chinese cohort.

Background: The hormone receptor+/human epidermal growth factor receptor 2- (HR+/HER2-) breast cancer (BC) patients account for the largest proportion in all patients and are still at high risk of long-range recurrence. This current study aimed to construct a prognostic nomogram to predict 3-year and 5-year BC-specific survival (BCSS) in HR+/HER2- BC patients with axillary lymph node metastasis. Methods: A total of 25,338 HR+/HER2- patients with axillary lymph node-positive BC were enrolled from the Surveillance, Epidemiology and End Results (SEER) database and randomly divided into the training (n=17,738) and validation (n=7,600) cohorts using a ratio of 7:3. Univariate and multivariable Cox regression hazards were used to build a prognostic nomogram based on the training cohort. The nomogram was validated with two independent cohorts. Receiver operating characteristic (ROC) curves and calibration plots were used to evaluate the performance of the model, and Kaplan-Meier survival analyses were applied to test the clinical utility of the risk stratification system. Results: Twelve factors including age, race, marital status, grade, T stage, N stage, radiotherapy, chemotherapy, and metastasis to the bone, brain, lung and liver were identified and incorporated to construct the nomogram (P<0.001). The area under the ROC curve (AUC) values at 3- and 5-year in the training and internal validation sets were 0.800, 0.800, 0.831 and 0.819, respectively, while those of the external set were 0.765 and 0.735, indicating a satisfactory discrimination with our nomogram. The calibration curves showed highly consistent results for the actual and predicted survival probabilities. Furthermore, patients were divided into three risk groups according to the total scores of the nomogram. The risk stratification system accurately differentiated between patients with different BCSS rates. Conclusions: We constructed the first nomogram and corresponding risk stratification system to predict the 3-year and 5-year BCSS for HR+/HER2- patients with lymph node-positive BC, indicating a satisfactory accuracy and clinical application.

Rspo2 exacerbates rheumatoid arthritis by targeting aggressive phenotype of fibroblast-like synoviocytes and disrupting chondrocyte homeostasis via Wnt/ß-catenin pathway.

BACKGROUND: The aggressive phenotype of fibroblast-like synoviocytes (FLS) has been identified as a contributing factor to the exacerbation of rheumatoid arthritis (RA) through the promotion of synovitis and cartilage damage. Regrettably, there is currently no effective therapeutic intervention available to address this issue. Recent research has shed light on the crucial regulatory role of R-spondin-2 (Rspo2) in cellular proliferation, cartilage degradation, and tumorigenesis. However, the specific impact of Rspo2 on RA remains poorly understood. We aim to investigate the function and mechanism of Rspo2 in regulating the aggressive phenotype of FLS and maintaining chondrocyte homeostasis in the context of RA. METHODS: The expression of Rspo2 in knee joint synovium and cartilage were detected in RA mice with antigen-induced arthritis (AIA) and RA patients. Recombinant mouse Rspo2 (rmRspo2), Rspo2 neutralizing antibody (Rspo2-NAb), and recombinant mouse DKK1 (rmDKK1, a potent inhibitor of Wnt signaling pathway) were used to explore the role and mechanism of Rspo2 in the progression of RA, specifically in relation to the aggressive phenotype of FLS and chondrocyte homeostasis, both in vivo and in vitro. RESULTS: We indicated that Rspo2 expression was upregulated both in synovium and articular cartilage as RA progressed in RA mice and RA patients. Increased Rspo2 upregulated the expression of leucine-rich repeat-containing G-protein-coupled receptor 5 (LGR5), as the ligand for Rspo2, and ß-catenin in FLS and chondrocytes. Subsequent investigations revealed that intra-articular administration of rmRspo2 caused striking progressive synovitis and articular cartilage destruction to exacerbate RA progress in mice. Conversely, neutralization of Rspo2 or inhibition of the Wnt/ß-catenin pathway effectively alleviated experimental RA development. Moreover, Rspo2 facilitated FLS aggressive phenotype and disrupted chondrocyte homeostasis primarily through activating Wnt/ß-catenin pathway, which were effectively alleviated by Rspo2-NAb or rmDKK1. CONCLUSIONS: Our data confirmed a critical role of Rspo2 in enhancing the aggressive phenotype of FLS and disrupting chondrocyte homeostasis through the Wnt/ß-catenin pathway in the context of RA. Furthermore, the results indicated that intra-articular administration of Rspo2 neutralizing antibody or recombinant DKK1 might represent a promising therapeutic strategy for the treatment of RA.

Metabolic regulation by biomaterials in osteoblast.

The repair of bone defects resulting from high-energy trauma, infection, or pathological fracture remains a challenge in the field of medicine. The development of biomaterials involved in the metabolic regulation provides a promising solution to this problem and has emerged as a prominent research area in regenerative engineering. While recent research on cell metabolism has advanced our knowledge of metabolic regulation in bone regeneration, the extent to which materials affect intracellular metabolic remains unclear. This review provides a detailed discussion of the mechanisms of bone regeneration, an overview of metabolic regulation in bone regeneration in osteoblasts and biomaterials involved in the metabolic regulation for bone regeneration. Furthermore, it introduces how materials, such as promoting favorable physicochemical characteristics (e.g., bioactivity, appropriate porosity, and superior mechanical properties), incorporating external stimuli (e.g., photothermal, electrical, and magnetic stimulation), and delivering metabolic regulators (e.g., metal ions, bioactive molecules like drugs and peptides, and regulatory metabolites such as alpha ketoglutarate), can affect cell metabolism and lead to changes of cell state. Considering the growing interests in cell metabolic regulation, advanced materials have the potential to help a larger population in overcoming bone defects.

Relaxin in fibrotic ligament diseases: Its regulatory role and mechanism.

Fibrotic ligament diseases (FLDs) are diseases caused by the pathological accumulation of periarticular fibrotic tissue, leading to functional disability around joint and poor life quality. Relaxin (RLX) has been reported to be involved in the development of fibrotic lung and liver diseases. Previous studies have shown that RLX can block pro-fibrotic process by reducing the excess extracellular matrix (ECM) formation and accelerating collagen degradation in vitro and in vivo. Recent studies have shown that RLX can attenuate connective tissue fibrosis by suppressing TGF-ß/Smads signaling pathways to inhibit the activation of myofibroblasts. However, the specific roles and mechanisms of RLX in FLDs remain unclear. Therefore, in this review, we confirmed the protective effect of RLX in FLDs and summarized its mechanism including cells, key cytokines and signaling pathways involved. In this article, we outline the potential therapeutic role of RLX and look forward to the application of RLX in the clinical translation of FLDs.

[Modified Latarjet splitting subscapularis muscle under arthroscopy: an anatomical study based on axillary nerve, glenoid, and subscapularis muscle].

Objective: To testify the spatial relationship between the subscapularis muscle splitting window and the axillary nerve in modified arthroscopic Latarjet procedure, which could provide anatomical basis for the modification of the subscapularis muscle splitting. Methods: A total of 29 adult cadaveric shoulder specimens were dissected layer by layer, and the axillary nerve was finally confirmed to walk on the front surface of the subscapularis muscle. Keeping the shoulder joint in a neutral position, the Kirschner wire was passed through the subscapularis muscle from back to front at the 4 : 00 position of the right glenoid circle (7 : 00 position of the left glenoid circle), and the anterior exit point (point A, the point of splitting subscapularis muscle during Latarjet procedure) was recorded. The vertical and horizontal distances between point A and the axillary nerve were measured respectively. Results: In the neutral position of the shoulder joint, the distance between the point A and the axillary nerve was 27.37 (19.80, 34.55) mm in the horizontal plane and 16.67 (12.85, 20.35) mm in the vertical plane. Conclusion: In the neutral position of the shoulder joint, the possibility of axillary nerve injury will be relatively reduced when radiofrequency is taken from the 4 : 00 position of the right glenoid (7 : 00 position of the left glenoid circle), passing through the subscapularis muscle posteriorly and anteriorly and splitting outward.

Aerobic exercise-induced circulating extracellular vesicle combined decellularized dermal matrix hydrogel facilitates diabetic wound healing by promoting angiogenesis.

Background: Insufficient blood supply results in unsatisfactory wound healing, especially for challenging wound repair such as diabetic wound defects. Regular exercise training brings a lot of benefits to cardiovascular fitness and metabolic health including attenuation of T2DM progression. Circulating extracellular vesicles (EVs) are postulated to carry a variety of signals involved in tissue crosstalk by their modified cargoes, representing novel mechanisms for the effects of exercise. Prominently, both acute and chronic aerobic exercise training can promote the release of exercise-induced cytokines and enhance the angiogenic function of circulating angiogenic cell-derived EVs. Methods: We investigated the possible angiogenesis potential of aerobic exercise-induced circulating EVs (EXE-EVs) on diabetic wound healing. Circulating EVs were isolated from the plasma of rats subjected to 4 weeks of moderate aerobic exercise or sedentariness 24 h after the last training session. The therapeutic effect of circulating EVs was evaluated in vitro by proliferation, migration, and tube formation assays of human umbilical vein endothelial cells (HUVECs), as well as in vivo by quantification of angiogenesis and cutaneous wound healing in diabetic rats. Results: The number of circulating EVs did not change significantly in exercised rats 24 h post-exercise in comparison with the sedentary rats. Nevertheless, EXE-EVs showed remarkable pro-angiogenic effect by augmenting proliferation, migration, and tube formation of HUVECs. Furthermore, the findings of animal experiments revealed that the EXE-EVs delivered by decellularized dermal matrix hydrogel (DDMH) could significantly promote the repair of skin defects through stimulating the regeneration of vascularized skin. Discussion: The present study is the first attempt to demonstrate that aerobic exercise-induced circulating EVs could be utilized as a cell-free therapy to activate angiogenesis and promote diabetic wound healing. Our findings suggest that EXE-EVs may stand for a potential strategy for diabetic soft tissue wound repair.

[Radiographic study of effect of lateral placement of bone graft on shoulder joint degeneration after modified arthroscopic Latarjet surgery with elastic fixation].

OBJECTIVE: To investigate the mid-term effect of lateral placement of bone graft on shoulder joint degeneration after modified arthroscopic Latarjet surgery with elastic fixation for recurrent anterior shoulder dislocation with an anterior glenoid bone defect. METHODS: According to the inclusion and exclusion criteria, 18 patients with recurrent anterior shoulder dislocation and anterior glenoid bone defect who received the modified arthroscopic Latarjet surgery with elastic fixation between January 2015 and November 2016 were enrolled in this study. There were 12 males and 6 females with an average age of 26.2 years (range, 19-37 years). The number of shoulder dislocation ranged from 4 to 30 times (mean, 8.8 times). The disease duration was 8-49 months (mean, 23.8 months). The mean anterior glenoid bone defect was 25.2% of the glenoid surface (range, 20%-29%). The mean preoperative Instability Severity Index Score (ISIS) was 7.6 (range, 7-10). According to Samilson-Prieto classification, the shoulder joint degeneration was rated as grade 0 in 13 cases, grade Ⅰ in 3 cases, and grade Ⅱ in 2 cases. Before and after operation, the visual analogue scale (VAS) score, American Society of Shoulder and Elbow Surgery (ASES) score, Walch-Duplay score, Rowe score, and shoulder mobility were used to evaluate the effectiveness. Imaging examination was performed to observe the shoulder joint degeneration, the position of the bone graft, and the postoperative shaping of the scapular glenoid. RESULTS: All patients were followed up 55-62 months, with an average of 59.6 months. There was no neurovascular injuries, infections, fixation-related and bone graft-related complications. No re-dislocation and revision occurred. All patients returned to normal life, 17 of whom returned to sport. The VAS score was significantly decreased and ASES, Walch-Duplay, and Rowe scores were significantly improved at last follow-up ( P<0.05). No significant difference was found in range of motion of forward flexion, abduction, lateral rotation at 90° abduction, internal rotation at 90° abduction, or lateral rotation at 0° between pre- and post-operation ( P>0.05). Three-dimensional CT showed that the centers of all bone grafts were between 3∶30 and 4∶30 (right shoulder) or between 7∶40 and 8∶20 (left shoulder) and no bone grafts were positioned superiorly or inferiorly in the glenoid En-face view. All bone grafts were positioned lateral to the scapular glenoid with an average distance of 3.5 mm (range, 2.3-4.6 mm) in cross-sectional imaging by CT. Compared with the preoperative Samilson-Prieto classification results, all cases showed no progression of shoulder joint degeneration at 36, 48 months and last follow-up. All bone grafts remodeled to a steady state within 24 months after operation. The bone graft and glenoid finally remodeled analogous to the shape of the intact glenoid in the En-face view and became flush with the glenoid rim, remodeling to a curved shape congruent to the humeral head in cross-sectional imaging by CT. The shape of the remodeled glenoid at last follow-up was not significantly different from that at 24 months after operation. CONCLUSION: The lateral placement of the bone graft during modified arthroscopic Latarjet surgery with elastic fixation do not accelerate the imaging changes of shoulder joint degeneration.

Interbundle Impingement Pressure in Individualized and Nonindividualized Double-Bundle Anterior Cruciate Ligament Reconstruction: A Cadaveric Study.

BACKGROUND: Graft impingement is one of the main concerns in double-bundle anterior cruciate ligament reconstruction (DB-ACLR). Impingement between the anteromedial (AM) and posterolateral (PL) bundles has been postulated to cause graft deterioration or rerupture, but this has not been thoroughly investigated, and the interbundle impingement pressure (IIP) has not been well researched. PURPOSE: To determine the IIP between the AM and PL bundles in the native anterior cruciate ligament (ACL) and in DB-ACLR with individualized and nonindividualized double-tunnel placement. STUDY DESIGN: Controlled laboratory study. METHODS: A total of 30 fresh-frozen, nonpaired, human cadaveric knees were randomly divided into 3 groups of 10 knees: native intact ACL (NI group), DB-ACLR tunnel placement using the preserved remnant procedure (individualized reconstruction) (PR group), and DB-ACLR tunnel placement using the bony landmark procedure (nonindividualized reconstruction) (BL group). Pressure sensors were inserted between the AM and PL bundles. The knee was moved passively from full extension to full flexion, and the IIP between the 2 ACL bundles was measured every 15°. Similarly, the impingement pressure was measured between the ACL and intercondylar roof and between the ACL and posterior cruciate ligament (PCL). RESULTS: No significant differences were found in the maximum, mean, or minimum ACL-roof and ACL-PCL impingement pressures among the 3 groups. The IIP significantly increased when the knee joint was flexed >120° in all 3 groups (P < .001). Compared with the other 2 groups, the BL group had significantly higher maximum and mean IIP throughout the range of knee movement (P < .001) and from maximum extension to 120° of flexion (P < .001). The BL group also had significantly higher minimum IIP than the other 2 groups when knee flexion was >120° (P < .001). No significant differences were seen in maximum, minimum, or mean IIP between the NI and PR groups. CONCLUSION: The PR procedure (individualized DB-ACLR) was more consistent with the interbundle biomechanical conditions of the native ACL, whereas the BL procedure (nonindividualized DB-ACLR) had higher maximum and mean IIP. The IIP was higher than the ACL-intercondylar roof or ACL-PCL pressures, and it increased significantly when knee flexion was >120°. CLINICAL RELEVANCE: These data suggest that surgeons can perform individualized DB-ACLR using preserved remnants for tunnel placement as impingement-free DB-ACLR.

Effect of Modified Arthroscopic Latarjet on Acromiohumeral Distance at 5-Year Follow-up.

BACKGROUND: It is unclear whether coracoacromial ligament release during the Latarjet procedure will increase superior translation of the shoulder joint. PURPOSE: To evaluate whether a modified suture button Latarjet procedure can decrease the acromiohumeral distance (AHD). STUDY DESIGN: Case series; Level of evidence, 4. METHODS: A retrospective analysis was conducted among 155 patients who underwent a modified suture button Latarjet procedure between 2013 and 2015. AHD was measured on bilateral computed tomography scans taken preoperatively and on scans of the affected shoulder taken on postoperative day 1 and postoperative month (POM) 6, POM 36, and POM 60. At each time point, we recorded pain on a visual analog scale (VAS) and objective shoulder function using the American Shoulder and Elbow Surgeons, Rowe, and Walch-Duplay scores. Preoperative and final follow-up VAS and functional scores were compared using the paired t test. Pairwise comparison of AHD values at each follow-up time point were compared with the preoperative intact side using the paired t test. Intra- and interobserver reproducibility of the AHD measurements was evaluated using the intraclass correlation coefficient. RESULTS: A total of 104 patients who met the criteria completed the final follow-up, which occurred at 62.6 ± 2.4 months (mean ± SD). When compared with presurgery, the VAS and all functional scores improved significantly at the last follow-up (P < .001 for all). Intra- and interobserver intraclass correlation coefficients indicated good reliability for the ADH measurements. Preoperatively, there were no differences in AHD values between the intact and affected shoulders (7.8 ± 0.8 mm for both; P = .851). The AHD values at postoperative day 1 and POM 6, POM 36, and POM 60 were 9.6 ± 0.7 mm, 8.6 ± 0.9 mm, 8.0 ± 0.8 mm, and 7.9 ± 0.8 mm, respectively, all of which were larger than those of the preoperative intact side (P < .001 for all). CONCLUSION: The modified suture button Latarjet procedure not only offered satisfactory therapeutic effects but also did not decrease the AHD at 5-year follow-up.