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Purpose: The acetabular labrum plays an important role in joint lubrication, and damage to this structure leads to osteoarthritis. This study aimed to histologically classify the degree of degeneration of the acetabular labrum and to investigate the changes in gene expression induced by mechanical stretching.Methods: We obtained acetabular labrum cells from patients with hip osteoarthritis during total hip arthroplasty (n= 25). The labrum was stained with safranin O, and images were histologically evaluated using a new parameter, the red/blue (R/B) value. The samples were divided into the degenerated group (D group: n= 18) and the healthy group (H group: n= 7) in accordance with the Kellgren-Lawrence (KL) grade. The cultured acetabular labral cells were subjected to loaded uniaxial cyclic tensile strain (CTS). After CTS, changes in gene expression were examined in both groups.Results: Spearman’s correlation analysis revealed that the R/B value was significantly correlated with the KL grade and the Krenn score. The expression levels of genes related to cartilage metabolism, osteogenesis and angiogenesis significantly increased after CTS in the H group, while gene expression in the D group showed weaker changes after CTS than that in the H group compared to the nonstretched control group.Conclusions: The degree of labral degeneration could be classified histologically using the R/B value and the KL grade. Mechanical stretching caused changes in gene expression that support the pathological features of labral degeneration.

Purpose: This study aimed to compare medial meniscus extrusion (MME) in patients with partial medial meniscus posterior root tears (MMPRTs) through magnetic resonance imaging (MRI) conducted at two-time points and to determine whether patient characteristics or MME measurements differ in patients who respond to nonoperative treatment compared with those who require surgical treatment. Methods: Thirty-seven patients with partial MMPRTs underwent two MRI scans during nonoperative management or before pull-out repair. Among these, 17 patients received nonoperative management, and 20 underwent pull-out repair. Partial MMPRTs were diagnosed based on the MRI findings. MME measurements were performed on both MRI scans. Statistical and receiver operating curve (ROC) analyses were performed. Results: The duration between the two MRI scans was significantly shorter in the pull-out repair group than in the nonoperative management group. The increase in MME (ΔMME) on MRI scans was significantly greater in the pull-out repair group than in the nonoperative management group. Linear regression analysis revealed a weak correlation between the MRI interval and ΔMME in the nonoperative management group and a moderate correlation in the pull-out repair group. In the ROC construction, the cut-off value for ΔMME that requires surgical intervention was 0.41 mm, with a sensitivity and specificity of 85.0% and 52.9%, respectively. Conclusion: Patients with partial MMPRTs requiring surgical treatment had greater MME progression in a shorter time and a time-dependent increase in MME. Therefore, a ΔMME of ≥ 0.41 mm may be useful in deciding surgical intervention based on MRI retests. Level of evidence: III.

Introduction: Residual acetabular dysplasia of the hip after open reduction can complicate the treatment of developmental dysplasia of the hip (DDH) due to the potential need for corrective surgery. This retrospective study aimed to determine the predictive factors for acetabular development using postoperative radiographs and magnetic resonance imaging (MRI).Methods: We retrospectively investigated 74 hips of patients with DDH who underwent open reduction after reaching walking age and were followed up radiologically until skeletal maturity. We evaluated the cartilaginous acetabulum and labrum using a new method that measures the cartilaginous and labral landmarks on coronal and axial MR T2*-weighted images in patients aged 5 years. The mean age at the time of surgery was 22 months and that at the final survey was 20 years. Severin classification was determined at the final follow-up. Groups with good (53 hips) and poor (21 hips) outcomes were compared using the postoperative radiographic and MRI parameters recorded at 5 years of age. Factors predicting acetabular development were identified using univariate and multiple logistic analyses.Results: There were no significant differences in the bony-acetabular index (AI) and centre-edge (CE) angle between the good and poor outcome groups. However, the poor outcome group had significantly larger cartilaginous- and labral-AIs but significantly smaller cartilaginous- and labral-CE angles than the good outcome group (both p< 0.05). Multiple logistic regression analysis showed that labral-AI and labral-CE angle were predictors of acetabular development after open reduction for DDH, and their optimal cut-offs were 4° (77% sensitivity, 76% specificity) and 37° (68% sensitivity, 85% specificity), respectively.Discussion: Normal cartilaginous acetabulum development occurs in childhood, and evaluation using only radiographs is difficult. However, labral-AI ⩾4° and labral-CE angle <37° on MRI at 5 years of age offer useful indications for corrective surgery in patients with DDH.

Previous studies have shown that preoperative factors predict the postoperative Barthel Index score in patients with trochanteric fractures, while there is less evidence on the effects of perioperative factors on the prediction. This study aimed to assess the effects of preoperative and perioperative factors on the early postoperative Barthel Index score in patients with trochanteric fractures. Consecutive 288 patients aged ≥60 years with trochanteric fractures who could independently walk before injury were included. Patients were grouped according to the Barthel Index score measured after 2 weeks of surgery; the cut-off value was 20 points. Two logistic regression models were created to assess the effects of preoperative (model 1: dementia, walking ability before injury, and nutrition status) and perioperative (model 2: independent variables in model 1, reduction quality, and basic mobility function) factors on the Barthel Index score. Sensitivity and specificity were used to assess the predicative accuracy of the models. Poor preoperative (model 1: χ2= 34.626, P< 0.01) and perioperative (model 2: χ2= 43.956, P< 0.01) characteristics were significantly related to lower Barthel Index score. Sensitivity and specificity were similar between the models (model 1: 83.3% and 38.9% and model 2: 82.2% and 42.6%, respectively). Both preoperative and perioperative factors were significantly related to the early postoperative Barthel Index score after trochanteric fracture. However, only minimal increase in predictive accuracy was observed when perioperative predictors were analyzed along with preoperative factors. Both baseline characteristics and basic postoperative mobility should be considered when treating patients with trochanteric fractures.

Purpose: To reveal the outcomes of partial medial meniscus posterior root tears following transtibial pullout repair compared with the outcomes of complete radial meniscus posterior root tears. Materials and methods: We retrospectively evaluated 15 consecutive patients (male/female, 5/10; average age, 64.4 years) who underwent transtibial pullout repair for partial medial meniscus posterior root tears and compared their results with those of 86 consecutive patients who underwent the same surgery for complete medial meniscus posterior root tears. All patients underwent second-look arthroscopy on average 1 year postoperatively, and a semi-quantitative meniscal healing score (anteroposterior width, stability, and synovial coverage, total 10 points) was evaluated. Medial meniscus extrusion was evaluated preoperatively and at second-look arthroscopy. Results: Postoperative clinical scores were not significantly different in the short term. However, second-look arthroscopy revealed a significant difference in repaired meniscal stability (partial tear; 3.3 points, complete tear; 2.3 points, p&lt; 0.001) and total meniscal healing scores (partial tear; 8.3 points, complete tear; 7.1 points, p&lt; 0.001). Medial meniscus extrusion progression was significantly different (partial tear; 0.4 mm, complete tear; 1.0 mm, p&lt; 0.001). Conclusion: Partial medial meniscus posterior root tears showed better meniscal healing and less medial meniscus extrusion progression following pullout repair than complete medial meniscus posterior root tears.

Objective: Precise assessment of spinal instability is critical before and after radiotherapy (RT) for evaluating the effectiveness of RT. Therefore, we retrospectively evaluated the efficacy of RT in spinal instability over a period of 6 months after RT, utilizing the spinal instability neoplastic score (SINS) in patients with painful spinal metastasis. We retrospectively evaluated 108 patients who received RT for painful vertebral metastasis in our institution. Mechanical pain at metastatic vertebrae, radiological responses of irradiated vertebrae, and spinal instability were assessed. Follow-up assessments were done at the start of and at intervals of 1, 2, 3, 4, and 6 months after RT, with the pain disappearing in 67%, 85%, 93%, 97%, and 100% of the patients, respectively. The median SINS were 8, 6, 6, 5, 5, and 4 at the beginning and after 1, 2, 3, 4, and 6 months of RT, respectively. Multivariate analysis revealed that posterolateral involvement of spinal elements (PLISE) was the only risk factor for continuous potentially unstable/unstable spine at 1 month. In conclusion, there was improvement of pain, and recalcification results in regaining spinal stability over time after RT although vertebral body collapse and malalignment occur in some irradiated vertebrae. Clinicians should pay attention to PLISE in predicting continuous potentially unstable/unstable spine.

Background: The accuracies of various navigation systems in total hip arthroplasty (THA) have been described; however, the accuracy of cup orientation with an accelerometer-based navigation system has not been reported. The purpose of this study was to compare the accuracies of computed tomography (CT)- and accelerometer-based navigation systems for cup orientation in THA.Methods: In this prospective study, 30 patients who underwent cementless THA via anterolateral approach in the lateral decubitus position were analysed. A CT-based navigation system (30 hips) and an accelerometer-based navigation system (30 hips) were used simultaneously. The accuracy of cup orientation (absolute difference between intraoperative vs. postoperative measurements) was compared between the navigation systems using postoperative CT.Results: The accuracy of cup inclination was 3.2 ± 2.4° in the CT-based navigation group and 4.1 ± 3.7° in the accelerometer-based navigation group (p= 0.3035). The accuracy of cup anteversion was 3.0° ± 2.5° in the CT-based navigation group and 6.8° ± 4.8° in the accelerometer-based navigation group. Cup anteversion was significantly more accurate with the CT-based navigation system than with accelerometer-based navigation (p= 0.0009). Multiple regression analysis demonstrated that the malposition in cup anteversion was positively correlated with the change in pelvic tilt and loosening of the reference antenna.Conclusions: Although, these results are only true for this specific accelerometer system, cup positioning was significantly more accurate with the CT-based navigation system than an accelerometer-based navigation in the lateral decubitus position. This is because of considerable discrepancies in the sagittal pelvic tilt, resulting in variability in cup anteversion angle with the use of an accelerometer-based navigation system.

This study aimed to investigate whether the initial suture tension when pullout sutures are fixed affects postoperative clinical outcomes following medial meniscus posterior root repair.

Background: Recently, arthroscopic ankle arthrodesis has been performed for moderate-to-severe varus-deformed ankle osteoarthritis. However, the effect of osteophyte resection in the lateral gutter in arthroscopic ankle arthrodesis has not been clarified. We hypothesized that a varus-deviated ankle with lateral gutter osteophytes can be corrected by osteophyte resection.Methods: Thirty-nine ankles of 38 patients were included. The mean age of patients was 70.0 (45-83) years. The patients were divided into the following groups: group with an osteophyte in the lateral gutter (osteophyte) and group with no osteophytes (nonosteophyte). Preoperative and postoperative tibiotalar angle, tibial plafond angle, and tibiotalar angle under valgus stress, as well as the Japanese Society for Surgery of the Foot (JSSF) ankle/hindfoot scale, were recorded. Twelve ankles underwent lateral gutter osteophyte resection, whereas the other 27 ankles did not require osteophyte resection.Results: Preoperative tibiotalar angle was higher in the osteophyte group than in the nonosteophyte group (21.8 vs 11.2 degrees, P= .01). The tibiotalar angle in the preoperative valgus stress imaging was higher in the osteophyte group (12.9 vs 5.7, P< .01). However, the postoperative tibiotalar angle was similar between the 2 groups (7.1 vs 5.4, P= .183). JSSF ankle/hindfoot scale improved in both groups.Conclusion: Lateral gutter osteophyte resection enabled correction of the varus malalignment in arthroscopic ankle arthrodesis.Level of Evidence: Level III, retrospective comparative series.

Posterior root repair of the medial meniscus (MM) can prevent rapid progression of knee osteoarthritis in patients with a MM posterior root tear (MMPRT). The anatomic reattachment of the MM posterior root is considered to be critical in a transtibial pullout repair. However, tibial tunnel creation at the anatomic attachment is technically difficult. We hypothesized that a newly developed point-contact aiming guide [Unicorn Meniscal Root (UMR) guide] can create the tibial tunnel at a better position rather than a previously designed MMPRT guide. The aim of this study was to compare the position of the created tibial tunnel between the two meniscal root repair guides. Thirty-eight patients underwent transtibial pullout repairs. Tibial tunnel creation was performed using the UMR guide (19 cases) or MMPRT guide (19 cases). Three-dimensional computed tomography images of the tibial surface were evaluated using the Tsukada’s measurement method postoperatively. The expected anatomic center of the MM posterior root attachment was defined as the center of three tangential lines referring to three anatomic bony landmarks (anterior border of the posterior cruciate ligament, lateral margin of the medial tibial plateau, and retro-eminence ridge). The expected anatomic center and tibial tunnel center were evaluated using the percentage-based posterolateral location on the tibial surface. The distance between the anatomic center and tunnel center was calculated. The anatomic center of the MM posterior root footprint was located at a position of 79.2% posterior and 39.5% lateral. The mean of the tunnel center in the UMR guide was similar to that in the MMPRT guide (posterior direction, P= 0.096; lateral direction, P= 0.280). The mean distances between the tunnel center and the anatomic center were 4.06 and 3.99 mm in the UMR and MMPRT guide group, respectively (P= 0.455). The UMR guide, as well as the MMPRT guide, is a useful device to create favorable tibial tunnels at the MM posterior root attachment for pullout repairs in patients with MMPRTs. IV

Background: Patients with partial medial meniscus posterior root tears (MMPRTs) sometimes require arthroscopic pullout repair because of their intolerable/repeated knee pains and continuous disturbance in gait during activities of daily living. However, the predisposing factors for future knee surgery in patients with partial MMPRTs remain unclear. We compared the findings of magnetic resonance imaging (MRI) between patients who underwent pullout repair and nonoperative management following partial MMPRTs. Methods: Twenty-five patients who required arthroscopic repair for partial MMPRTs and 23 patients who were managed nonoperatively were evaluated during a mean follow-up period of 27.1 months. Sex, age, height, body weight, body mass index, duration from onset to initial MRI, MRI findings, and medial meniscus (MM) extrusion were compared between the two groups. Linear regression analysis was used to assess the correlation between MM extrusion and duration from onset to MRI examination. Results: No significant differences were observed between the pullout repair and nonoperative management groups in terms of patient demographics and the positive ratio of MRI-based root tear signs. However, absolute MM extrusion in the pullout repair group (3.49 ± 0.82 mm) was larger than that in the nonoperative management group (2.48 ± 0.60 mm, P&lt; 0.001). Extrusion of the MM (> 3 mm) was detected more frequently in the pullout repair group than in the nonoperative management group (P&lt; 0.001). The odds ratio in the pullout repair and MM extrusion > 3 mm cases was 9.662. Linear regression analysis revealed a fair correlation between the duration from onset to MRI and MM extrusion only in the pullout repair group (0.462 mm/month increase in MM extrusion). Conclusions: This study demonstrated that more severe MM extrusions were observed in the pullout repair group than in the nonoperative management group. Major extrusion (> 3 mm) was also observed more in the pullout repair group than in the nonoperative group. Assessing MM extrusion and its severity can help determine a valid treatment for patients with partial MMPRTs. Level of evidence: IV, Retrospective comparative study.

Introduction: Adequate initial stability of the acetabular cup is essential for total hip arthroplasty (THA). However, changes in the alignment of the acetabular component caused by screw fixation are concerning in patients with inadequate bone stock. This study aimed to investigate the effects of screw fixation on the alignment of the acetabular component in THA patients with hip dysplasia.Methods: We retrospectively examined 256 hips (range 28–87 years) that underwent THA using a navigation system. Patients were divided into 2 groups based on the presence or absence of changes in the alignment of the intraoperative acetabular cup, and univariate and multivariate analyses were performed to identify factors that were predictive of changes in acetabular component alignment after screw fixation in 2 dimensions: inclination and anteversion.Results: Screw fixation led to a mean change in inclination of 1.6° (range 0–10°) and a mean change in anteversion of 1.4° (range 0–14°). The Crowe classification, the presence of bone cysts, and the use of an inferior quadrant screw were identified as factors that correlated with acetabular cup alignment changes in inclination (odds ratios, 6.01, 5.94 and 0.03, respectively). Only the Crowe classification was identified as a factor that correlated with intraoperative alignment changes in anteversion (odds ratio, 2.08).Conclusions: Screw fixation altered the acetabular cup alignment. The inclination changes were related to the extent of the dysplasia, and the risk was reduced when the inferior quadrant screw was used. Surgeons should use caution during screw fixation in THAs performed on severely dysplastic hips.

Supplemental Digital Content is available in the text.Spinopelvic fixation provides a strong fixation for unstable pelvic ring fractures. However, the technique is usually performed with the patient in the prone position, with the applied weight on the anterior superior iliac crests aggravating fracture displacement. We developed a novel approach for minimally invasive percutaneous spinopelvic fixation that is performed with the patient in a lateral (side lying) position. We describe the application of our technique for the treatment of a bilateral pelvic ring and acetabulum fracture in a 79-year-old woman injured in a traffic accident. Initial posterior fixation was performed with the patient in the left-side lying position, using bilateral pedicle screws at L3 and L4 and a left sacral-alar iliac screw and 2 right iliac screws inserted under navigation. The lateral and cranial displacement of the right pelvic ring was reduced percutaneously. One week after this initial surgery, we proceeded with an open anterior reduction and internal fixation of the left pelvic ring and acetabulum fracture. The postoperative course was uneventful and clinical outcomes were satisfactory. Reduction of a pelvic ring fracture in a lateral position, with subsequent spinopelvic fixation, is a reasonable option for the treatment of an unstable pelvic ring fracture.

Investigational drugs for rare cancers are often approved based solely on a single-arm phase II trial that primarily evaluates response rate in Japan. Such trials typically use a fixed sample size determined on the basis of the frequentist manner. However, since predicting the speed of patient enrollment is challenging because of the disease rarity, the time needed to complete the enrollment of the fixed number of patients is prolonged in some cases. A Bayesian design without fixing the sample size is useful for single-arm phase II trials of rare cancers. However, the arbitrariness of prior distribution specifications and the frequentist operating characteristics are regulatory issues. We recently started a Bayesian single-arm phase II trial of nivolumab in patients with sarcoma for new drug application in Japan and examined the statistical rationale and design consideration. In the Bayesian design, we specify the minimum and maximum numbers of enrolled patients during the enrollment period and the prior distributions of response rates. Considering these parameters, we obtain the minimum number of responders needed for the positive conclusion of the efficacy of nivolumab for each sample size. Simulation studies demonstrated that the operating characteristics of this design would be acceptable from the frequentist view. The Bayesian design provided an adaptive decision rule for efficacy conclusion for the drug without fixing the sample size. We hope our trial’s success will provide a new drug development option for rare cancers in Japan.

Background: We investigated the clinical outcomes of resection and joint-preserving arthroplasty for forefoot deformities in patients with rheumatoid arthritis.Methods: Sixteen feet of 14 women (average age, 67.1 years; range, 53-82) underwent resection arthroplasty of the metatarsal head (resection group), and 18 feet of 15 women (average age, 61.3 years; range, 40-73) underwent a metatarsophalangeal joint-preserving procedure with shortening oblique metatarsal osteotomies of the lesser toes (joint preservation group). The mean disease duration in the resection and joint preservation groups was 23.6 and 19.1 years, and the average follow-up period was 37.3 and 33.5 months, respectively. The classification of Larsen was used to assess the severity of destruction of the metatarsophalangeal (MTP) joint. Preoperative and postoperative clinical evaluation included Japanese Society for Surgery of the Foot (JSSF) score and postoperative complications.Results: The number of preoperative radiographic destruction of the MTP joints (Larsen grade II, III, IV, and V) was 0, 29, 39, and 12 joints in the resection group and 13, 67, 9, and 1 joints in the joint preservation group. The mean JSSF score improved significantly from 61.3 to 83.9 points in the resection group (P< .001) and from 62.2 to 90.8 points in the joint preservation group (P< .001). In the resection group, recurrence of callosities and claw toe deformity was observed in 6 and 3 feet, respectively. In the joint-preserving group, recurrence of callosities and hammer toe deformity was observed in 1 foot each.Conclusion: The resection arthroplasty and joint-preserving procedure showed satisfactory clinical outcomes. However, whether both procedures can maintain the good clinical results without the recurrence of forefoot deformity will require longer follow-up.Level of Evidence: Level III, retrospective comparative series.

Although there are some reports highlighting the applicability of double plates in distal femoral fractures, there is no standard approach or fixation method for supracondylar fractures combined with posterior coronal shear fractures. We report a case of distal femoral fracture treated with a lateral locking plate and posterior buttress plate using anterolateral and posterolateral approaches from one incision.

Background: There are no recommendations for specific suture materials in transtibial pullout repair of medial meniscus posterior root tears. This study aimed to evaluate the clinical outcomes of transtibial pullout repair of medial meniscus posterior root tears using ultrahigh-molecular-weight polyethylene sutures and suture tape. Methods: We retrospectively reviewed the data of 36 patients (27 women and 9 men, mean age 64.1 years) who had undergone transtibial pullout repair of medial meniscus posterior root tears between November 2018 and December 2019. Two groups of 18 patients each received either two different cord-like sutures or suture tape. Clinical parameters were assessed preoperatively and on second-look arthroscopy (mean postoperative period 12 months). The meniscal healing status was assessed using a previously published scoring system (ranging from 0 to 10), and the incidence rate of suture cut-out was assessed on second-look arthroscopy. Results: All clinical scores significantly improved in both groups, with no significant between-group differences on second-look arthroscopy. The arthroscopic meniscal healing scores significantly differed between sutures (mean 6.7 points) and suture tape (mean 7.4 points; p= 0.044). No significant between-group difference in the suture cut-out rate was observed. Conclusions: This study found no significant differences in the clinical outcomes between ultrahigh-molecular-weight polyethylene sutures and suture tape. Favorable clinical outcomes were obtained using both types of suture; however, the usefulness of suture tape appears to be limited.

Chronic pain coexists with disability, anxiety, depression, and sleep disturbances, which are factors of pain chronicity in the fear-avoidance model. Self-efficacy for managing pain plays a protective role against pain chronicity. For chronic pain sufferers, social support from caregivers is important. However, such caregivers face enormous physical and mental burdens. This study aimed to assess how self-efficacy and factors related to the fear-avoidance model affect caregiver burden. Participants were 135 chronic pain patients and their caregivers who visited our outpatient pain special clinic. In clinical assessments, numeric rating scale (NRS), pain catastrophizing scale (PCS), hospital anxiety and depression scale (HADS), Athens insomnia scale (AIS), pain disability assessment scale (PDAS), pain self-efficacy questionnaire (PSEQ) for the patients and Zarit Burden Interview (ZBI) for their caregivers were evaluated. Participants were divided into 2 groups (L group ZBI < 24 points and H group ZBI ≥ 24 points) and compared. Regression analyses were conducted to identify factors correlated with the ZBI scores. Compared to L group, H group showed significantly higher NRS and HADs depression scores, and lower PSEQ scores. In univariate regression analysis, ZBI scores were significantly correlated with NRS, PCS, HADS anxiety, HADS depression, PDAS and PSEQ. Multiple linear regression analysis revealed that ZBI scores were significantly correlated with PSEQ. The caregivers who perceived high caregiver burden had significantly higher patients’ pain intensity, depression, and lower self-efficacy than those who perceived low caregiver burden. Caregiver burden correlated with the pain intensity, pain catastrophizing, anxiety, depression, disability, and self-efficacy of chronic pain patients. Among these factors, self-efficacy was the most negatively correlated with caregiver burden. Treatments focused on increasing self-efficacy for managing pain have the potential to reduce caregiver burden.

There are currently no reports of implant-related neuropathy associated with humeral proximal fracture surgery. Herein, we report a case of implant-related late-onset neuropathy that developed 3 years after proximal humeral fracture surgery.

The lengths of the anteromedial bundle (AMB) and posterolateral bundle (PLB) change during knee motion during double-bundle anterior cruciate ligament (ACL) reconstruction. However, the actual intra-articular graft length would be affected by the bone tunnel position and tunnel creation angle during ACL reconstruction. The aim of this study was to investigate the intra-articular length change of the AMB and PLB in patients who underwent anatomic double-bundle ACL reconstruction.

How mechanical stress affects physical performance via tendons is not fully understood. Piezo1 is a mechanosensitive ion channel, and E756del PIEZO1was recently found as a gain-of-function variant that is common in individuals of African descent. We generated tendon-specific knock-in mice using R2482H Piezo1, a mouse gain-of-function variant, and found that they had higher jumping abilities and faster running speeds than wild-type or muscle-specific knock-in mice. These phenotypes were associated with enhanced tendon anabolism via an increase in tendon-specific transcription factors, Mohawk and Scleraxis, but there was no evidence of changes in muscle. Biomechanical analysis showed that the tendons of R2482H Piezo1mice were more compliant and stored more elastic energy, consistent with the enhancement of jumping ability. These phenotypes were replicated in mice with tendon-specific R2482H Piezo1replacement after tendon maturation, indicating that PIEZO1 could be a target for promoting physical performance by enhancing function in mature tendon. The frequency of E756del PIEZO1was higher in sprinters than in population-matched nonathletic controls in a small Jamaican cohort, suggesting a similar function in humans. Together, this human and mouse genetic and physiological evidence revealed a critical function of tendons in physical performance, which is tightly and robustly regulated by PIEZO1 in tenocytes.

Purpose We investigated objective and patient-reported outcomes after resection arthroplasty or shortening oblique osteotomy (SOO) of the lesser metatarsals combined with arthrodesis of the first metatarsophalangeal (MTP) joint for severe rheumatoid forefoot deformities.Methods 17 feet from 14 women (mean age, 67.8 years) underwent resection arthroplasty of the lesser metatarsal heads (MTH resection group), while 13 feet from nine women and two men (mean age, 68.7 years) underwent SOO of the lesser metatarsals (MTH preservation group). Arthrodesis of the first MTP joint was performed in all cases. Mean follow-up in the MTH resection and preservation groups was 25.0 and 21.3 months, respectively. Preoperative and postoperative clinical evaluation included Japanese Society for Surgery of the Foot (JSSF) scale and self-administered foot evaluation questionnaire (SAFE-Q) scores.Results Mean total JSSF scale significantly improved from 53.4 to 76.4 in the MTH resection group (p< .001) and from 50.1 to 74.2 in the MTH preservation group (p= .002). Pain and pain-related and shoe-related SAFE-Q subscale scores significantly improved after surgery in both groups. In the MTH resection group, recurrence of painful callosities and claw toe deformity was observed in four and three feet, respectively. In the MTH preservation group, one patient experienced recurrence of painful callosities and one underwent revision surgery for IP joint dislocation.Conclusion Resection arthroplasty or SOO of the lesser metatarsals combined with arthrodesis of the first MTP joint achieved significant improvement with respect to pain relief, deformity correction, and footwear comfort.

Novel strategies against treatment‐resistant tumor cells remain a challenging but promising therapeutic approach. Despite accumulated evidence suggesting the presence of highly malignant cell populations within tumors, the unsolved issues such as in vivotargeting and clinical relevance remain. Here, we report a preclinical trial based on the identified molecular mechanisms underlying osteosarcoma‐initiating cells and their clinical relevance. We identified key microRNAs (miRNAs) that were deregulated in a highly malignant CD133highpopulation and found that miR‐133a regulated the cell invasion that characterizes a lethal tumor phenotype. Silencing of miR‐133a with locked nucleic acid (LNA) reduced cell invasion of this cell population, and systemic administration of LNA along with chemotherapy suppressed lung metastasis and prolonged the survival of osteosarcoma‐bearing mice. Furthermore, in a clinical study, high expression levels of CD133 and miR‐133a were significantly correlated with poor prognosis, whereas high expression levels of the four miR‐133a target genes were correlated with good prognosis. Overall, silencing of miR‐133a with concurrent chemotherapy would represent a novel strategy that targets multiple regulatory pathways associated with metastasis of the malignant cell population within osteosarcoma. StemCells2014;32:959–973

Induced pluripotent stem (iPS) cells are a type of undifferentiated cell that can be obtained from differentiated cells and have the pluripotent potential to differentiate into the musculoskeletal system, the myocardium, vascular endothelial cells, neurons, and hepatocytes. We therefore cultured mouse iPS cells in a DMEM containing 15% FBS, 10−7M dexamethasone, 10 mM β-glycerophosphate, and 50 μg/ml ascorbic acid for 3 weeks, in order to induce bone differentiation, and studied the expression of the bone differentiation markers Runx2 and osteocalcin using RT-PCR in a time-dependent manner. Osteocalcin, a bone differentiation marker in bone formation, exhibited the highest expression in the third week. In addition, the deposition of calcium nodules was observed using Alizarin red S staining. iPS cells cultured for bone differentiation were transplanted into severe combined immunodeficiency (SCID) mice, and the osteogenic potential exhibited after 4 weeks was studied. When bone differentiation-induced iPS cells were transplanted into SCID mice, bone formation was confirmed in soft X-ray images and tissue specimens. However, teratoma formation was confirmed in 20% of the transplanted models. When mouse iPS cells were treated with irradiation of 2 Gray (Gy) prior to transplantation, teratoma formation was inhibited. When mouse iPS cells treated in a likewise manner were xenotransplanted into rats, bone formation was confirmed but teratoma formation was not observed. It is believed that irradiation before transplantation is an effective way to inhibit teratoma formation.

Osteofibrous dysplasia occurs most frequently in the tibia and may result in deformity and pathological fracture. We report one such case in a 6-year-old girl who underwent minimally invasive plate osteosynthesis using a locking compression plate. The varus deformity of the tibia was manually corrected, and the plate was inserted without extensive surgical exposure. At 20-week follow-up, the fracture had healed completely, and she had returned to normal daily living. At 3-year follow-up, radiographs showed no progression of the varus deformity. Minimally invasive plate osteosynthesis is useful for treatment of pathological fractures caused by osteofibrous dysplasia. It preserves blood flow at the fracture site, leading to good bone healing and stability to prevent further deformity and an early return to daily activity.

Self-assembling peptide scaffold (SAPS) is well known to have very good bone conduction properties. However, the intensity of SAPS is too weak to actually use it for a clinical bone regeneration. Therefore, we have produced a hybrid scaffold system that involves fabricating a cage from polyetheretherketone (PEEK) that has high intensity, filling the interior of this cage with SAPS, and then transplanted this hybrid scaffold to bone defects in rat femurs. After 28 days, soft X-ray radiographs and histological assessment revealed that good new bone formation was clearly observed in the defects transplanted the PEEK cage with SAPS, but not in the PEEK cage only. The PEEK cage maintained a form and osteoconduction ability of internal SAPS, and SAPS promoted bone formation inside the PEEK; therefore, each was in charge of intensity and bone regeneration separately. The present study suggests that hybrid scaffolds made from PEEK cages and SAPS can be useful tools for the regeneration of load-bearing bones, based on the idea that it should be possible to develop ideal bone filler materials by combining the strength of artificial bone with the bone regeneration and bone conduction properties of SAPS.

Human mesenchymal stem cells (hMSCs) are multipotent stem cells found in the adult bone marrow that have the capacity to differentiate into various mesenchymal cell types. The hMSCs may provide a potential therapy to restore damaged tissues or organs of mesenchymal origin; however, a drawback is their limited life span in vitro.

The purpose of this study was to examine the correlation between the changes in the lateral pillar grades and the factors influencing such changes. We reviewed 102 patients with Perthes' disease. Changes were observed in 32 (31) hips. The percentage of the changes in each treatment group showed significant differences. Patients with extensive involvement showed significantly more changes. There was no difference in the age at the onset. We recommend that treatment methods be used that more effectively relieve the mechanical force on the capital femoral epiphysis for patients with extensive involvement regardless of the age at the onset.

Purpose: Medial meniscus (MM) posterior root (PR) tear leads to severe MM posterior extrusion (PE), resulting in rapid knee cartilage degeneration. MMPR repairs are recommended to reduce MMPE, especially during knee flexion. However, the difference in MMPE between different repair techniques remains unknown. This study aimed to investigate preoperative and postoperative MMPE following several pullout repair techniques. We hypothesized that a technique using two simple stitches (TSS) would be more useful than FasT-Fix-dependent modified Mason-Allen suture (F-MMA) to prevent the progression of MMPE in knee extension. Methods: This retrospective study included 35 patients who underwent MMPR repair. To compare MMPE, patients were divided into two groups according to the use of F-MMA while grasping the posterior capsule and TSS without grasping it. Open magnetic resonance imaging was performed at 10° and 90° knee flexion preoperatively, and at 3 and 12 months postoperatively, and the MMPE of both groups was evaluated. Results: A significant difference was observed between preoperative and 3-month postoperative MMPE at 90° knee flexion in both groups (p< .01). A significant difference was observed in 3- and 12-month postoperative MMPE at 10° knee flexion between both groups (p= .04/.02), whereas no significant difference in the preoperative MMPE at 10° knee flexion was observed between them (p= .45). Conclusions: Both repairs were found to be useful to reduce MMPE in knee flexion. Further, F-MMA repair increased MMPE in knee extension, unlike TSS repair. These findings suggest that TSS might have more advantages for load distribution when standing or walking.

Background: Diagnosing partial tears of the medial meniscus (MM) posterior root is difficult. The aim of this study was to evaluate diagnostic values involved in conventional magnetic resonance imaging (MRI) features of MM posterior root tears (MMPRTs) and find other MRI-based findings in patients with partial MMPRTs. Methods: Eighteen patients who had arthroscopically confirmed partial MMPRTs were included. As a control, 18 patients who underwent partial meniscectomy for other types of MM tears were evaluated. Isolated partial MMPRTs were classified into the following three types: type A, accurate partial stable tear (cleavage &lt; 1/2 of root width); type B, bridged unstable root tear (cleavage ≥ 1/2 of root width); type C, complex horn tear expanded to the root. Conventional MRI-based findings of MMPRTs were evaluated between two groups (n= 23). Posterior root irregularity, bone marrow spot, and ocarina-like appearance showing several condensed circles in triangular meniscal horn (ocarina sign) were also evaluated. Results: Posterior root irregularity and bone marrow spot were frequently observed in the partial MMPRTs (47.8%), compared with the other MM tears (P= 0.007 and 0.023, respectively). The ocarina sign was detected in 69.6% of patients with partial MMPRTs. A significant difference between two groups was observed in a positive ratio of ocarina sign (P&lt; 0.001). Types A, B, and C of the partial tear/damage were observed in three, eight, and seven patients, respectively. The ocarina sign was the most common MRI finding in each type of partial MMPRT. Conclusions: This study demonstrated that a characteristic MRI finding, “ocarina sign,” was frequently observed in patients with partial tear/damage of the MM posterior root. The ocarina sign was the most common MRI finding in several types of partial MMPRTs. Our results suggest that the ocarina sign may be useful to diagnose unnoticed partial MMPRTs.

CCN family protein 2/connective tissue growth factor (CCN2/CTGF) is a unique molecule that promotes the entire endochondral ossification process and regeneration of damaged articular cartilage. Also, CCN2 has been shown to enhance the adhesion and migration of bone marrow stromal cells as well as the growth and differentiation of osteoblasts; hence, its utility in bone regeneration has been suggested. Here, we evaluated the effect of CCN2 on the regeneration of an intractable bone defect in a rat model. First, we prepared two recombinant CCN2s of different origins, and the one showing the stronger effect on osteoblasts in vitrowas selected for further evaluation, based on the result of an in vitrobioassay. Next, to obtain a sustained effect, the recombinant CCN2 was incorporated into gelatin hydrogel that enabled the gradual release of the factor. Evaluation in vivoindicated that CCN2 continued to be released at least for up to 14 days after its incorporation. Application of the gelatin hydrogel–CCN2 complex, together with a collagen scaffold to the bone defect prepared in a rat femur resulted in remarkable induction of osteoblastic mineralization markers within 2 weeks. Finally, distinct enhancement of bone regeneration was observed 3 weeks after the application of the complex. These results confirm the utility of CCN2 in the regeneration of intractable bone defects in vivowhen the factor is incorporated into gelatin hydrogel.

A human cadaveric biomechanical study of fixation strength of an improved novel pedicle screw (NPS) with cement and a conventional screw.

Artificial bones have often used for bone regeneration due to their strength, but they cannot provide an adequate environment for cell penetration and settlement. We therefore attempted to explore various materials that may allow the cells to penetrate and engraft in bone defects. PuraMatrix™ is a self-assembling peptide scaffold that produces a nanoscale environment allowing both cellular penetration and engraftment. The objective of this study was to investigate the effect of PuraMatrix™ on bone regeneration in a mouse bone defect model of the calvaria. Matrigel™ was used as a control. The expression of bone-related genes (alkaline phosphatase, Runx2, and Osterix) in the PuraMatrix™-injected bone defects was stronger than that in the Matrigel™-injected defects. Soft X-ray radiographs revealed that bony bridges were clearly observed in the defects treated with PuraMatrix™, but not in the Matrigel™-treated defects. Notably, PuraMatrix™ treatment induced mature bone tissue while showing cortical bone medullary cavities. The area of newly formed bones at the site of the bone defects was 1.38-fold larger for PuraMatrix™ than Matrigel™. The strength of the regenerated bone was 1.72-fold higher for PuraMatrix™ (146.0 g) than for Matrigel™ (84.7 g). The present study demonstrated that PuraMatrix™ injection favorably induced functional bone regeneration.

Abstract: Background: We compared investigative methods to study the diagnostic capability of ultrasonography. Subjects were 75 patients with proximal femur fractures who underwent surgery from March 2002 to December 2003. Methods: Biochemical assays were carried out on days 3 and 7, and D-dimer levels were investigated as a time series. Ascending lower limb venography and ultrasonography were carried out nearly simultaneously in all cases on day 7. Results: The incidence of deep vein thrombosis (DVT)-positive findings on venography was 61.3% (46/75). Venography results demonstrated a diagnostic sensitivity of 95.5% and specificity of 91.4% using a D-dimer cutoff of 1µg/ml on postoperative day 7. By ultrasonography, diagnostic sensitivity for DVT was 78.3%, and specificity was 96.5%. Among all proximal area cases, there were 18 limbs with DVT seen on venography among which were 17 limbs in cases demonstrating DVT at the same site on ultrasonography, a correct diagnosis rate of 94.4%. Conclusions: For the diagnosis of a thrombus more proximal than the popliteal area, a location at high risk for occurrence of pulmonary embolism, ultrasonography provided results nearly on par with those obtained by venography. Thus, we believe that ultrasonography allowed a more noninvasive, accurate diagnosis and more rapid treatment in cases where D-dimer values were 1µg/ml or more on postoperative day 7.

Doxorubicin and ifosfamide are the two most active agents used to treat soft tissue sarcomas. However, because of their overlapping side effects, concurrent administration to achieve optimal doses of each agent is difficult. We therefore conducted a Phase II trial to investigate the efficacy and feasibility of a novel alternating sequential chemotherapy regimen consisting of high dose ifosfamide and doxorubicin/cyclophosphamide in advanced adult non-small round cell soft tissue sarcomas. Adult patients with non-small round cell soft tissue sarcomas were enrolled. The treatment consisted of four sequential courses of chemotherapy that was planned for every 3weeks. Cycles 1 and 3 consisted of ifosfamide (14g/m2), and cycles 2 and 4 consisted of doxorubicin (60mg/m2) and cyclophosphamide (1200mg/m2). Forty-two patients (median age 47years) were enrolled. Of the 36 assessable patients, 1 complete response and 16 partial responses were observed, for a response rate of 47.2%. Responses were observed in 57% of patients who had received no previous chemotherapy and 13% of those who had previously undergone chemotherapy. Grade 3-4 neutropenia was observed during 70% of all cycles. Sequential administration of high-dose ifosfamide and doxorubicin/cyclophosphamide has promising activity with manageable side effects in patients with advanced adult nonsmall round cell soft tissue sarcomas.