IL-6 Reduces Spheroid Sizes of Osteophytic Cells Derived from Osteoarthritis Knee Joint via Induction of Apoptosis.

Osteophytes in osteoarthritis (OA) joints contribute to restriction of joint movement, joint pain, and OA progression, but little is known about osteophyte regulators. Examination of gene expression related to cartilage extracellular matrix, endochondral ossification, and growth factor signaling in articular cartilage and osteophytes obtained from OA knee joints showed that several genes such as COL1A1, VCAN, BGLAP, BMP8B, RUNX2, and SOST were overexpressed in osteophytes compared with articular cartilage. Ratios of mesenchymal stem/progenitor cells, which were characterized by co-expression of CD105 and CD166, were significantly higher in osteophytic cells than articular cells. A three-dimensional culture method for cartilage and osteophyte cells was developed by modification of cultures of self-assembled spheroid cell organoids (spheroids). These spheroids cultured in the media for mesenchymal stem cells containing transforming growth factor-ß3 showed characteristic morphologies and gene expression profiles of articular cartilage and osteophytes, respectively. The effects of IL-1ß, tumor necrosis factor-α, and IL-6 on the spheroids of articular and osteophytic cells were studied. To the best of our knowledge, they provide the first evidence that IL-6 suppresses the spheroid size of osteophytic cells by inducing apoptosis and reducing extracellular matrix molecules. These data show that IL-6 is the suppressor of osteophyte growth and suggest that IL-6 expression and/or activity are implicated in the regulation of osteophyte formation in pathologic joints.

Detection of Novel Tyrosine Kinase Fusion Genes as Potential Therapeutic Targets in Bone and Soft Tissue Sarcomas Using DNA/RNA-based Clinical Sequencing.

BACKGROUND: Approximately 1% of clinically treatable tyrosine kinase fusions, including anaplastic lymphoma kinase, neurotrophic tyrosine receptor kinase, RET proto-oncogene, and ROS proto-oncogene 1, have been identified in soft tissue sarcomas via comprehensive genome profiling based on DNA sequencing. Histologic tumor-specific fusion genes have been reported in approximately 20% of soft tissue sarcomas; however, unlike tyrosine kinase fusion genes, these fusions cannot be directly targeted in therapy. Approximately 80% of tumor-specific fusion-negative sarcomas, including myxofibrosarcoma and leiomyosarcoma, that are defined in complex karyotype sarcomas remain genetically uncharacterized; this mutually exclusive pattern of mutations suggests that other mutually exclusive driver oncogenes are yet to be discovered. Tumor-specific, fusion-negative sarcomas may be associated with unique translocations, and oncogenic fusion genes, including tyrosine kinase fusions, may have been overlooked in these sarcomas. QUESTIONS/PURPOSES: (1) Can DNA- or RNA-based analysis reveal any characteristic gene alterations in bone and soft tissue sarcomas? (2) Can useful and potential tyrosine kinase fusions in tumors from tumor-specific, fusion-negative sarcomas be detected using an RNA-based screening system? (3) Do the identified potential fusion tumors, especially in neurotrophic tyrosine receptor kinase gene fusions in bone sarcoma, transform cells and respond to targeted drug treatment in in vitro assays? (4) Can the identified tyrosine kinase fusion genes in sarcomas be useful therapeutic targets? METHODS: Between 2017 and 2020, we treated 100 patients for bone and soft tissue sarcomas at five institutions. Any biopsy or surgery from which a specimen could be obtained was included as potentially eligible. Ninety percent (90 patients) of patients were eligible; a further 8% (8 patients) were excluded because they were either lost to follow-up or their diagnosis was changed, leaving 82% (82 patients) for analysis here. To answer our first and second questions regarding gene alterations and potential tyrosine kinase fusions in eight bone and 74 soft tissue sarcomas, we used the TruSight Tumor 170 assay to detect mutations, copy number variations, and gene fusions in the samples. To answer our third question, we performed functional analyses involving in vitro assays to determine whether the identified tyrosine kinase fusions were associated with oncogenic abilities and drug responses. Finally, to determine usefulness as therapeutic targets, two pediatric patients harboring an NTRK fusion and an ALK fusion were treated with tyrosine kinase inhibitors in clinical trials. RESULTS: DNA/RNA-based analysis demonstrated characteristic alterations in bone and soft tissue sarcomas; DNA-based analyses detected TP53 and copy number alterations of MDM2 and CDK4 . These single-nucleotide variants and copy number variations were enriched in specific fusion-negative sarcomas. RNA-based screening detected fusion genes in 24% (20 of 82) of patients. Useful potential fusions were detected in 19% (11 of 58) of tumor-specific fusion-negative sarcomas, with nine of these patients harboring tyrosine kinase fusion genes; five of these patients had in-frame tyrosine kinase fusion genes ( STRN3-NTRK3, VWC2-EGFR, ICK-KDR, FOXP2-MET , and CEP290-MET ) with unknown pathologic significance. The functional analysis revealed that STRN3-NTRK3 rearrangement that was identified in bone had a strong transforming potential in 3T3 cells, and that STRN3-NTRK3 -positive cells were sensitive to larotrectinib in vitro. To confirm the usefulness of identified tyrosine kinase fusion genes as therapeutic targets, patients with well-characterized LMNA-NTRK1 and CLTC-ALK fusions were treated with tyrosine kinase inhibitors in clinical trials, and a complete response was achieved. CONCLUSION: We identified useful potential therapeutic targets for tyrosine kinase fusions in bone and soft tissue sarcomas using RNA-based analysis. We successfully identified STRN3-NTRK3 fusion in a patient with leiomyosarcoma of bone and determined the malignant potential of this fusion gene via functional analyses and drug effects. In light of these discoveries, comprehensive genome profiling should be considered even if the sarcoma is a bone sarcoma. There seem to be some limitations regarding current DNA-based comprehensive genome profiling tests, and it is important to use RNA testing for proper diagnosis and accurate identification of fusion genes. Studies on more patients, validation of results, and further functional analysis of unknown tyrosine kinase fusion genes are required to establish future treatments. CLINICAL RELEVANCE: DNA- and RNA-based screening systems may be useful for detecting tyrosine kinase fusion genes in specific fusion-negative sarcomas and identifying key therapeutic targets, leading to possible breakthroughs in the treatment of bone and soft tissue sarcomas. Given that current DNA sequencing misses fusion genes, RNA-based screening systems should be widely considered as a worldwide test for sarcoma. If standard treatments such as chemotherapy are not effective, or even if the sarcoma is of bone, RNA sequencing should be considered to identify as many therapeutic targets as possible.

The Combined Suture Bridge With Mason-Allen Technique Is Superior to the Conventional Suture Bridge Technique for Arthroscopic Rotator Cuff Repair.

PURPOSE: To compare clinical results and retear rates between the combined suture bridge with Mason-Allen (SBMA) technique and the conventional suture bridge (SB) technique in patients with full-thickness rotator cuff tears who underwent arthroscopic rotator cuff repair. METHODS: One hundred two patients who underwent arthroscopic rotator cuff repair using the SB technique (n = 50) or SBMA technique (n = 52) for a full-thickness rotator cuff tear and had at least 2 years of follow-up were retrospectively analyzed. Magnetic resonance imaging was performed before surgery and 2 years after to determine preoperative tear size, Goutallier stage, and presence of retear after surgery. Patients were clinically evaluated using the Japanese Orthopaedic Association (JOA) score. RESULTS: The groups did not significantly differ in terms of follow-up period, age, sex, tear size, Goutallier stage, or number of suture anchors. The retear rate was significantly lower in the SBMA group (7.7% vs 28.0%; P < .01). The JOA score was significantly higher at last follow-up than before surgery in both groups (P <.01). The JOA score at last follow-up was significantly higher in the SBMA group (P = .02). CONCLUSIONS: Arthroscopic rotator cuff repair using the SBMA technique may provide better clinical and anatomical outcomes than the conventional SB technique. LEVEL OF EVIDENCE: Level III, retrospective cohort design; treatment study).

Shear wave elastography correlates to degeneration and stiffness of the long head of the biceps tendon in patients undergoing tenodesis with arthroscopic shoulder surgery.

BACKGROUND: Tendinopathy of the long head of the biceps (LHB) tendon causes degeneration and changes its stiffness. However, a reliable means of diagnosis has not been established. Shear wave elastography (SWE) provides quantitative tissue elasticity measurements. In this study, the relationship of preoperative SWE values with biomechanically measured stiffness and degeneration of the LHB tendon tissue was investigated. METHODS: LHB tendons were obtained from 18 patients who underwent arthroscopic tenodesis. SWE values were measured preoperatively at 2 sites, proximal to and within the bicipital groove of the LHB tendon. The LHB tendons were detached immediately proximal to the fixed sites and at their superior labrum insertion. Tissue degeneration was histologically quantified using the modified Bonar score. Tendon stiffness was determined using a tensile testing machine. RESULTS: The SWE values of the LHB tendon were 502.1 ± 113.6 kPa proximal to the groove and 439.4 ± 123.3 kPa within the groove. The stiffness was 39.3 ± 19.2 N/mm. The SWE values displayed a moderate positive correlation with the stiffness proximal to the groove (r = 0.80) and within it (r = 0.72). The SWE value of the LHB tendon within the groove showed a moderate negative correlation with the modified Bonar score (r = -0.74). CONCLUSIONS: These findings suggest that preoperative SWE values of the LHB tendon correlate moderately positively with stiffness and moderately negatively with tissue degeneration. Therefore, SWE may predict LHB tendon tissue degeneration and changes in stiffness caused by tendinopathy.

Association between smoking and duration of regional anesthesia - A propensity score matching study.

BACKGROUND: Previous studies have shown shorter duration of general anesthesia in smokers but it is unclear in regional anesthesia among smokers. We investigated the association between smoking status and the duration of regional anesthesia. METHODS: A total of 77 patients with a mean age of 47.3 years who underwent lower extremity orthopaedic surgery under regional anesthesia between January 2021 and June 2022 were enrolled. Sixteen patients were smokers and 57 patients were non-smokers. Propensity score matching was performed to balance patient characteristics. Our primary outcome was the time to onset of motor or sensory blockade and the duration required for full recovery of motor or sensory function. RESULTS: The time to sensory loss was 43.4 (SD 35.9) minutes in the smoking group and 39.6 (SD 31.7) minutes in the non-smoking group (p = 0.69), and the time to motor blockade was 37.0 (SD 28.4) minutes in the smoking group and 30.1 (SD 24.1) minutes in the non-smoking group (p = 0.35). The time for recovery of sensory function was 1146.7 (SD 197.8) minutes in the smoking group and 1024.6 (SD 177.9) minutes in the non-smoking group (p = 0.024). The time to recovery of motor function was 978.3 (SD 220.5) minutes in the smoking group and 1090.9 (SD 222.8) minutes in the non-smoking group (p = 0.08). The duration of sensory effect was significantly longer in the smoking group than in the non-smoking group. CONCLUSIONS: We found no significant association in the onset of regional anesthesia, but the duration of sensory blockade was significantly longer in the smoking group than in the non-smoking group. Hence, attention should be paid to the risks of the insensate limb in smokers due to prolonged sensory blockade as compared to non-smokers, rather than be concerned about delays in the onset of anesthesia.

Non-metastatic hip fractures surgery in patients with active cancer: benefit and risk.

PURPOSE: Although rare, non-metastatic proximal femoral fracture (PFF) can develop in patients with active cancer. However, little data are available regarding the risks and benefits of surgical treatment in such patients. The purpose of his study was to investigate the risks and benefits of surgical treatment of PFF in patients with and without cancer. METHODS: We retrospectively examined the medical records of all patients treated for PFF, excluding those with pathological fracture, at our hospital from July 2013 to December 2020. The patients were divided into two groups; The active cancer group and the standard group. We investigated in both groups about surgical and medical complications during the perioperative period, walking ability two weeks postoperatively, and one-year postoperative mortality rate. RESULT: After the inclusion and exclusion criteria, 39 patients in the active cancer group and 331 patients in the standard group were finally investigated. There were no statistically significant differences between the two groups. The complication rate did not appear statistical significance between two groups (16.7% in active cancer group vs 10.7% in standard group: p = 0.272). Walking ability was also similar in two groups. Mortality rate at one year was significantly higher in the active cancer group. (41.2% in active cancer group vs 6.0% in standard group: p < 0.05). CONCLUSION: Although the active cancer group had a higher mortality rate at one year, which was influenced by the prognosis of the cancer, the benefits of surgical intervention, such as regaining walking ability, were the same in patients with and without active cancer.

Characteristics of older patients with postmenopausal osteoporosis who developed loss of muscle mass during the COVID-19 pandemic - a case-control study.

BACKGROUND: Under the restriction of social activities during the coronavirus disease 2019 (COVID-19) pandemic, there was concern about the loss of muscle mass due to a decrease in physical activity for the elderly. The purpose of this study was to investigate the characteristics of older patients with postmenopausal osteoporosis who developed loss of muscle mass during the COVID-19 pandemic in Japan. METHODS: A total of 54 patients with postmenopausal osteoporosis were evaluated in this study. Whole-body dual-energy X-ray absorptiometry was performed pre- and post-COVID-19 pandemic to measure trunk and lower limb muscle mass. At the time of the post-COVID-19 pandemic, we conducted a survey to compare lifestyle before pandemic (the frequency of going out, the frequency of meeting acquaintances or families living apart, regular exercise habits, walking time, family structure), and comorbidities between the muscle mass loss (ML) group and the muscle mass maintenance (MM) group. The ML group consisted of patients with at least a 5% decrease in lower limb muscle mass or trunk muscle mass. RESULTS: A significant difference was found only for the family structure (P = 0.0279); in the ML group, those living alone were the largest group, while in the MM group they were the smallest group. CONCLUSIONS: The ML group was significantly more likely to live alone than the MM group. The current study showed that loss of muscle mass was more common in patients living alone.

Potential of whole-body dual-energy X-ray absorptiometry to predict muscle size of psoas major, gluteus maximus and back muscles.

BACKGROUND: Measurement of trunk muscle cross-sectional area (CSA) using axial magnetic resonance imaging (MRI) is considered clinically meaningful for understanding several spinal pathologies, such as low back pain and spinal sagittal imbalance. However, it remains unclear whether trunk muscle mass (TMM) measured using dual-energy X-ray absorptiometry (DXA) can predict the trunk muscle CSA. The aim of this study is to determine if DXA-derived TMM is associated and predicts with CSA of paraspinal muscles and gluteus maximus measured using MRI in healthy volunteers. METHODS: A total of 48 healthy volunteers underwent whole-body DXA and MRI of the spinopelvic region. The CSA of the psoas major, back muscles, and gluteus maximus were measured on axial MRI. Correlations and linear regressions between the TMM measured using DXA and the CSA of each musculature were investigated. RESULTS: There was a weak correlation between TMM and CSA of the psoas major in men (r = 0.39, P = 0.0678), and the linear regression was y = 301.74x - 401.24 (R2 = 0.2976, P = 0.0070). A moderate correlation was found in women (r = 0.58, P = 0.0021), and the linear regression was y = 230.21x - 695.29 (R2 = 0.4445, P = 0.0003). Moderate correlations were observed between TMM and CSA of the back muscles in both men (r = 0.63, P = 0.0012) and women (r = 0.63, P = 0.0007), the linear regression was y = 468.52x + 3688.5 (R2 = 0.5505, P < 0.0001) in men and y = 477.39x + 2364.1 (R2 = 0.564, P < 0.0001) in women. There was a strong correlation between TMM and CSA of the gluteus maximus in men (r = 0.72, P < 0.0001), and the linear regression was y = 252.69x - 880.5 (R2 = 0.6906, P < 0.0001). A moderate correlation was found in women (r = 0.69, P < 0.0001), and the linear regression was y = 230.74x - 231.32 (R2 = 0.6542, P < 0.0001). CONCLUSIONS: The DXA-derived TMM was able to predict the CSA of the psoas major, back muscles, and gluteus maximus, and significantly correlated with the CSA of the back muscles and gluteus maximus. It might be a safer and cheaper alternative for evaluating the size of the back muscles and gluteus maximus.

Higher fibular head is a risk for lateral hinge fracture in medial open wedge high tibial osteotomy.

PURPOSE: To examine the association between the hinge position, fibular head position, and type III lateral hinge fracture (LHF) in patients with knee osteoarthritis (OA) who underwent medial open wedge high tibial osteotomy (MOWHTO). METHODS: This retrospective study examined patients who underwent MOWHTO. Radiographically, the Kellgren-Lawrence (K/L) classification, distance between the articular surface and the tip of the fibular head (fibular head position), hinge point (hinge position), type of LHF, and safe zone (within the proximal tibiofibular joint) outlier were evaluated. To determine the cut-off value of the hinge position and fibular head position associated with type III LHF, a receiver operating characteristic (ROC) curve analysis was performed. The odds ratio (OR) was calculated from the obtained cut-off values using logistic regression, which was adjusted by age, gender, body mass index, and opening distance. RESULTS: Among 132 knees in 120 patients, the radiographic severity of knee OA was 19 (14%), 73 (55%), and 40 (30%) of K/L grades 2, 3, and 4, respectively. LHF was observed in 40 knees (30%), including types I, II, and III fractures in 21 (16%), 5 (4%), and 14 (11%) knees, respectively. Hinge and fibular head positions were 16 and 10 mm, respectively, with significant correlation. Safe zone outlier was observed in 38 knees (29%). The hinge and fibular head positions with type III LHF were significantly higher (more cranial) than those with no fracture or other LHF subtypes. The ROC curve revealed that the cut-off value for the hinge and fibular head positions was 13.3 and 8.6 mm, respectively. The OR of the hinge and fibular head positions was 22.42 and 13.86, respectively. CONCLUSIONS: A higher hinge position was a risk factor for type III LHF and was associated with a higher fibular head in patients with knee OA who underwent MOWHTO. The hinge position should be placed at a certain distance from the articular surface to avoid type III LHF, especially in participants with higher fibular head position, even if the hinge position is located in the safe zone. LEVEL OF EVIDENCE: Retrospective cohort study, Level III.

Comparison of anemia, renal function, and nutritional status in older women with femoral neck fracture and older women with osteoarthritis of the hip joint.

BACKGROUND: Several studies in older patients with femoral neck fracture found that preoperative anemia and malnutrition were associated with higher mortality and poorer physical function. Therefore, we compared nutritional status, Hb level, and renal function in women with femoral neck fracture and women of the same age with osteoarthritis of the hip joint. METHODS: We enrolled 257 women aged 70 years and older who suffered femoral neck fracture (F group) or who were scheduled to undergo total hip arthroplasty for osteoarthritis of the hip joint (OA group). The F and OA groups were further divided into 2 groups on the basis of age, ie, 74 years old and younger (F70 and OA70) and 75 years old and older (F75 and OA75). To assess whether patients had undernutrition, mortality risk, anemia, and renal dysfunction, we assessed Geriatric Nutritional Risk Index (GNRI), Hb, and eGFR. RESULTS: We found a significant difference in the mean Hb levels and GNRI scores between the F75 and OA75 and F70 and OA70. Moreover, we found a moderate correlation between Hb level and GNRI score in the F75 and OA75. With respect to the GNRI category, the percentage of patients at moderate or major risk was 42.1% in the F70 group and 57.6% in the F75 group but only 1.9% in the OA70 group and 4.3% in the OA75 group. CONCLUSION: We found that women with femoral neck fracture had significantly lower Hb levels and lower GNRI scores than women with hip OA in the same age and that anemia and undernutrition were closely linked in women aged 75 and above. Moreover, we found that more than 40% of patients with a femoral neck fracture had a moderate to major risk on the basis of their GNRI scores.

Effect of pre-operative HbA1c and blood glucose level on the surgical site infection after lumbar instrumentation surgery.

BACKGROUND: This study aims to investigate the effect of pre-operative hemoglobin A1c (HbA1c) and pre-operative blood glucose control on the rate of surgical site infection (SSI) after posterior lumbar instrumentation surgery in diabetes mellitus (DM) patients. METHODS: A total of 1046 patients who had undergone posterior lumbar instrumentation surgery were reviewed. Based on pre-operative HbA1c, patients were divided into three groups: non-DM group, low HbA1c group (HbA1c < 7.0 % in DM) and high HbA1c group (≥7.0). As well, based on the status of blood glucose control in DM patients immediately before surgery, patients were divided into two groups: good control group (post-prandial blood glucose [PBG] < 200 mg/dl) and poor control group (≥200). The rate of SSI was compared among these groups. RESULTS: SSI occurred in 1.9 % in non-DM group, 2.4 % in low HbA1c group, and 9.3 % in high HbA1c group. Compared with non-DM group, high HbA1c group had significantly higher rate of SSI (p = 0.001). There was not statistically different between non-DM and low HbA1c groups (p = 0.550). SSI occurred in 2.2 % in good control group, and 10.2 % in poor control group. The rate of SSI was significantly lower in good control group (p = 0.013). CONCLUSION: This study showed that the rate of SSI after posterior lumbar instrumentation surgery tend to be higher in DM patients with high HbA1c. However, the rate might be reduced to the same level as that of non-DM group by lowering PBG to <200 mg/dl immediately before surgery.

Highly accurate acoustical prediction using support vector machine algorithm for post-operative subsidence after cementless total hip arthroplasty.

PURPOSE: Acoustic analysis has recently been applied to cementless total hip arthroplasty (THA). The aim of this study was to develop a machine learning algorithm to predict post-operative subsidence with high accuracy. METHODS: The acoustic parameters of the hammering sounds during a broaching procedure for 62 hips in 55 patients who underwent THAs with cementless taper-wedged stem were analysed. The patient's basic background such as age, sex, height, weight and body mass index, the femoral morphological parameters and the hammering sound characteristics of 24 features of normalised sound pressure (nSP) in 24 frequency ranges were applied to binary classification using a support vector machine using the following models with different features: model A, nSP only; model B, nSP + patients' basic background features; model C, nSP + patients' basic background features + femoral morphological parameters. RESULTS: In 62 hips with 310 hammering sounds, 12 hips (19.4%) showed ≥ 3 mm of post-operative subsidence; hence, 60 hammering sounds were set as positive examples and 250 hammering sounds were set as negative examples. The AUC was very high in all models. The accuracy (AUC/sensitivity/specificity/positive predictive value/negative predictive value/accuracy rate) of each model was as follows: model A, 0.963/0.656/0.996/0.980/0.925/0.934; model B, 0.9866/0.675/1.000/1.000/0.928/0.937 and model C, 0.998/0.750/1.000/1.000/0.950/0.957. CONCLUSION: In this study, we developed a high-accuracy machine learning algorithm for post-operative subsidence using acoustic parameters and additional pre-operative features. Our results represent a step toward the realisation of acoustic monitoring to avoid the complication in cementless THA.

Elimination of Lumbar Plexus Injury by Changing the Entry Point and Traction Direction of the Psoas Major Muscle in Transpsoas Lateral Lumbar Spine Surgery.

Background and Objectives: The lateral approach is commonly used for anterior column reconstruction, indirect decompression, and fusion in patients with lumbar degenerative diseases and spinal deformities. However, intraoperative lumbar plexus injury may occur. This is a retrospective comparative study to investigate and compare neurological complications between the conventional lateral approach and a modified lateral approach at L4/5. Materials and Methods: Patients with a lumbar degenerative disease requiring single-level intervertebral fusion at L4/5 were included and categorized into group X and group A. Patients in group X underwent conventional extreme lateral interbody fusion, while those in group A underwent a modified surgical procedure that included splitting of the anterior third of the psoas muscle, which was dilated by the retractor on the anterior third of the intervertebral disc. The incidence of lumbar plexus injury, defined as a decrease of ≥1 grade on manual muscle testing of hip flexors and knee extensors and sensory impairment of the thigh for ≥3 weeks, on the approach side, was investigated. Results: Each group comprised 50 patients. No significant between-group differences in age, sex, body mass index, and approach side were observed. There was a significant between-group difference in intraoperative neuromonitoring stimulation value (13.1 ± 5.4 mA in group X vs. 18.5 ± 2.3 mA in group A, p < 0.001). The incidence of neurological complications was significantly higher in group X than in group A (10.0% vs. 0.0%, respectively, p < 0.05). Conclusions: In our modified procedure, the anterior third of the psoas muscle was entered and split, and the intervertebral disc could be reached without damaging the lumbar plexus. When performing lumbar surgery using the lateral approach, lumbar plexus injury can be avoided by following surgical indication criteria based on the location of the lumbar plexus with respect to the psoas muscle and changing the transpsoas approach to the intervertebral disc.

Posterior shoulder stiffness was associated with shoulder pain during throwing in college baseball players: assessment of shear wave elastography.

PURPOSE: To investigate shoulder stiffness on the throwing and non-throwing sides in college baseball players using ultrasound shear wave elastography (SWE), and investigate the relationship between stiffness and shoulder pain during throwing. METHODS: Forty-nine college baseball players (98 shoulders) were recruited. Shoulder range of motion was evaluated. SWE was used to measure stiffness of the bilateral supraspinatus tendons, infraspinatus tendons, subscapularis tendons, supraspinatus muscles, infraspinatus muscles (ISPM), and posterior capsules. Participants were divided into pain and no pain groups based on the presence or absence of shoulder pain during throwing within 1 month before measurements on the throwing side. Items were compared between the throwing and non-throwing sides, and between the pain and no pain groups. Factors affecting shoulder pain during throwing were also investigated via multiple logistic regression analysis. RESULTS: Compared with the non-throwing side, the throwing side had significantly greater external rotation at 90° abduction, significantly lesser internal rotation at 0° abduction and internal rotation at 90° abduction (AbdIR), significantly higher SWE values of the infraspinatus tendon, ISPM, and posterior capsule, and significantly lower SWE values of the subscapularis tendon. Compared with the no pain group, the pain group had a significantly higher SWE value of the ISPM, and significantly lesser AbdIR. Increased ISPM SWE values and decreased AbdIR were significantly correlated with shoulder pain during throwing. CONCLUSIONS: The posterior tissue was stiffer than the anterior tissue on the throwing side. Decreased AbdIR and increased ISPM stiffness may be correlated with shoulder pain during throwing.

Synergistic upregulation of ADAMTS4 (aggrecanase-1) by cytokines and its suppression in knee osteoarthritic synovial fibroblasts.

The ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) family includes nine members with aggrecan-degrading activity, i.e., ADAMTS1, 4, 5, 8, 9, 15, 16, 18, and 20. However, their systematic expression profile in knee osteoarthritis (OA) synovium and effects of cytokines and growth factors on the expression in OA synovial fibroblasts remain elusive. In this study, expression of all nine aggrecanolytic ADAMTS species was assessed by quantitative real-time PCR in OA and control normal synovial tissues. OA synovial fibroblasts were treated with interleukin-1α (IL-1α), IL-1ß, tumor necrosis factor-α (TNF-α), transforming growth factor-ß (TGF-ß), vascular endothelial growth factor165, and heparin-binding epidermal growth factor, and analyzed for the expression of the ADAMTS species. The signaling pathways and inhibition of ADAMTS4 expression by high-molecular-weight hyaluronan, adalimumab, tocilizumab, and signaling molecule inhibitors were studied. ADAMTS1, 4, 5, 9, and 16 were expressed in OA synovium, but only ADAMTS4 expression was significantly higher in OA as compared to normal synovium. IL-1α, TNF-α, and TGF-ß markedly increased ADAMTS4 expression, while their effects were minimal for the other ADAMTS species. ADAMTS4 was synergistically upregulated by treatment with IL-1α and TNF-α, IL-1α and TGF-ß, or IL-1α, TNF-α and TGF-ß. The signaling molecules' inhibitors demonstrated that IL-1α-induced ADAMTS4 expression is predominantly through TGF-ß-associated kinase 1 (TAK1), and the TNF-α-stimulated expression is via TAK1 and nuclear factor-κB (NF-κB). The TGF-ß-promoted expression was through the activin receptor-like kinase 5 (ALK5)/Smad2/3, TAK1, and non-TAK1 pathways. Adalimumab blocked TNF-α-stimulated expression. ADAMTS4 expression co-stimulated with IL-1α, TNF-α and TGF-ß was abolished by treatment with adalimumab, TAK1 inhibitor, and ALK5/Smad2/3 inhibitor. These data demonstrate marked and synergistic upregulation of ADAMTS4 by IL-1α, TNF-α and TGF-ß in OA synovial fibroblasts, and suggest that concurrent therapy with an anti-TNF-α drug and inhibitor(s) may be useful for prevention against aggrecan degradation in OA.

Deletion of Hyaluronan-Binding Protein Involved in Hyaluronan Depolymerization (HYBID) Results in Attenuation of Osteoarthritis in Mice.

Hyaluronan (HA)-binding protein involved in HA depolymerization (HYBID) is involved in cartilage destruction via HA depolymerization in human knee osteoarthritis. However, the role of HYBID in the progression of osteoarthritis remain elusive. This study sought to examine whether genetic depletion of Hybid could suppress surgically induced osteoarthritis of mouse knee joints. In osteoarthritis induced by medial collateral ligament transection with meniscus removal, articular cartilage destruction and osteophyte formation at the medial femoral-tibial joint were significantly inhibited in Hybid-deficient (Hybid-/-) mice compared with wild-type mice. Hybid was highly produced by synovial cells and articular chondrocytes in the osteoarthritis joints of wild-type mice. IL-1ß, IL-6, and tumor necrosis factor-α were up-regulated in the osteoarthritis joint tissues of both wild-type and Hybid-/- mice. Vascular density at the synovial and periosteal junction was significantly reduced in Hybid-/- mice compared with wild-type mice. High-molecular-weight HA accumulated in osteoarthritis joint tissues of Hybid-/- mice. Injections of high-molecular-weight HA to knee joints attenuated the cartilage destruction and osteophyte formation in wild-type mouse osteoarthritis group. Inhibition of cartilage destruction and osteophyte formation in Hybid-/- mice was also observed in destabilization of the medial meniscus model. These data are the first to demonstrate that cartilage destruction and osteophyte formation are suppressed in Hybid-/- mice and suggest that Hybid-mediated HA depolymerization is implicated for the progression of mechanically-induced knee osteoarthritis.

Three-dimensional morphological analysis of the thoracic pedicle and related radiographic factors in adolescent idiopathic scoliosis.

BACKGROUND: This study aimed to investigate the laterality of the pedicle morphology at the apical vertebra (AV) level and identify the radiographic factors associated with the laterality ratio of the pedicle morphology at the AV level in patients with adolescent idiopathic scoliosis (AIS). METHODS: Overall, 684 pedicles in 57 AIS patients aged 10-20 years, who underwent preoperative computed tomography (CT) and had Lenke type 1 or 2 with right convex main thoracic curves (MTC), were evaluated. Pedicle diameters of the MTC were assessed. We defined and compared the region containing two vertebrae adjacent to the AV (APEX±1) and the region containing two vertebrae adjacent to the neutral vertebra. We analyzed the pedicle diameter and laterality ratio of APEX±1 and performed multiple linear regression analysis to identify the radiographic factors associated with the laterality of the pedicle diameter. RESULTS: On the concave side of APEX±1, the pedicles of 15 patients (26.3%) did not accept a 4-mm-diameter pedicle screw (PS), even with 25% cortical bone width expansion. Laterality ratio differences in the pedicle diameters of the cortical bone width in APEX±1 were large in patients with more proximal AV level (p < 0.001) and smaller apical vertebral rotation (AVR) (p = 0.029). CONCLUSIONS: Preoperative planning to accurately select and insert the PS in AIS should be based on the anatomical limitations in APEX±1, AV level, and AVR degree. In APEX±1, the correlation between AVR and the laterality ratio of the pedicle diameter may be useful for pathoetiological interpretation of the AIS deformity.

A bone bruise at the lateral and medial tibial plateau with an anterior cruciate ligament injury is associated with a meniscus tear.

PURPOSE: Bone bruises with anterior cruciate ligament (ACL) injury are well studied, but the association between bone bruises and multiple factors is unclear. The main objective of this study was to investigate the association between bone bruising and ACL injury and concomitant injury as well as clinical and functional scores. The second objective was to investigate the presence and distribution patterns of bone bruises. METHOD: A total of 176 patients who underwent ACL reconstruction for primary ACL injury were included. The demographic characteristics and responses to clinical and functional assessments (the Visual Analog Scale for activities of daily living and sports, the Cincinnati Knee Rating System, the Lysholm score, the Knee Osteoarthritis Outcome Score and side-to-side difference in anterior laxity) were recorded at the initial visit. Concomitant injuries were evaluated by intraoperative assessment. RESULTS: Bone bruises were detected in 141 patients (80.1%). The lateral femoral condyle (LFC) was the most common site in 116 patients (65.9%), followed by the lateral tibial plateau (LTP) in 82 patients (46.6%), medial tibial plateau (MTP) in 47 patients (26.7%) and medial femoral condyle (MFC) in 29 patients (16.5%). Regarding the distribution patterns, bone bruising at only the LFC, which was the most common pattern, was detected in 38 patients (27.0%). Bone bruising at the LTP or MTP was significantly associated with lateral (LM) and medial meniscus (MM) tears (odds ratios 4.0, 3.0, 4.3 and 40.5, 95% confidence intervals 1.5-11.6, 1.2-15.1, 1.2-17.3 and 8.6-283.0, respectively). No marked differences in the functional or clinical scores were noted. The severity of bone bruising at the MTP was significantly associated with MM tears and that at the LTP was significantly associated with LM tears. (p < 0.01). CONCLUSION: This study showed association between bone bruising at LTP and LM tears or at MTP and MM tears. Additionally, it provided detailed information on the presence and distribution patterns of bone bruises at each anatomic site. These findings are clinically relevant and will aid in preoperatively diagnosing meniscus tears in cases of ACL injury. LEVEL OF EVIDENCE: Level III.

Arthroscopic Bankart repair with additional footprint fixation using the double-row technique at the 4 o'clock position anatomically restored the capsulolabral complex and showed good clinical results.

PURPOSE: To investigate the clinical outcome and magnetic resonance imaging (MRI) findings after arthroscopic Bankart repair with additional double anchor footprint fixation (DAFF) at the 4 o'clock position, where the native footprint is widest anatomically, for recurrent anterior shoulder instability. METHODS: Forty-two patients (mean age 27.0 years) with recurrent anterior shoulder instability and without severe glenoid bone defects underwent arthroscopic Bankart repair with additional DAFF at the 4 o'clock position. Using three standard portals, single-row repair was performed at the 2, 3, and 5 o'clock positions, and DAFF with the suture bridging technique was conducted at the 4 o'clock position. MRI was performed preoperatively and at 6 months postoperatively. Patients with follow-up periods of ≥1 year were included in the present study and clinically evaluated at the final follow-up. The morphology at the 2 and 4 o'clock positions on radial MRI slices was compared between the preoperative and 6-month postoperative scans, and the footprint of the repaired capsulolabral complex at 6 months postoperatively was compared between the 2 and 4 o'clock positions. RESULTS: The average follow-up period was 19.5 ± 6.2 months. The rates of dislocation recurrence and positive apprehension test results were 2.4 and 4.8%, respectively. External rotation was restricted by 3.5°. The University of California at Los Angeles and Rowe scores at the final follow-up were 34.5 ± 1.0 points and 97.2 ± 5.7 points, respectively, representing significant improvements over the preoperative scores (p < 0.01). Although the capsulolabral complex at 6 months postoperatively was firmly repaired at both the 2 and 4 o'clock positions compared to its preoperative state, the footprint of the restored capsulolabral complex was wider at the 4 o'clock position than at the 2 o'clock position (p < 0.01). CONCLUSIONS: Additional DAFF at the 4 o'clock position improved the glenohumeral stability and function of the shoulder joint. This study suggests that this technique is a reliable and useful treatment for shoulder instability. LEVEL OF EVIDENCE: IV.

Blood cobalt ion level in patients with different sizes of cobalt/chrome femoral head with the Accolade TMZF stem.

BACKGROUND: Corrosion of stem-cobalt/chromium (Co/Cr) head interface and subsequent systemic Co ion complication have been a clinical concern after total hip arthroplasty (THA). The aim of this study is to investigate correlation between type of femoral head and blood Co ion level. METHODS: One hundred four patients with THA using accolade TMZF and Co/Cr femoral head (32-mm; 55 cases, 36-mm; 20 cases, dual mobility system (DM) with 22.2 or 28-mm inner head; 29 cases) participated in this study, and blood Co ion concentration test was performed in patients a minimum of four years after THA. RESULTS: DM group was significantly older than 32-mm and 36-mm group (DM: 73.9 ± 4.6, 32-mm: 63.3 ± 8.5, 36-mm: 66.8 ± 10.5). The median (interquartile range) blood Co concentration of each group was 32-mm group 0.26 µg/L (0.69), 36-mm group; 0.21 µg/L (0.30); and DM group 0.21 µg/L (0.13). There was a significant difference of Co concentration between DM and 32-mm group (p = 0.023). Abnormal values of the blood Co concentration (> 1 µg/L) were observed in the 32-mm group; 12 cases (21.8%), 36-mm group; 2 cases (10.0%); and DM group; 0 case (0%) (p = 0.018). CONCLUSIONS: Co blood concentration differed among the different sizes of Co/Cr femoral head. THA using DM is a safe option with low risk of complication from cobalt ion if it is used for elderly patients.