A 30-year follow-up study of rotational acetabular osteotomy for pre- and early-stage osteoarthritis secondary to dysplasia of the hip.

Aims: The objective of this study was to present the outcomes of rotational acetabular osteotomy (RAO) over a 30-year period for osteoarthritis (OA) secondary to dysplasia of the hip in pre- or early-stage OA. Methods: Between September 1987 and December 1994, we provided treatment to 47 patients (55 hips) with RAO for the management of pre- or early-stage OA due to developmental hip dysplasia. Of those, eight patients (11 hips) with pre-OA (follow-up rate 79%) and 27 patients (32 hips) with early-stage OA (follow-up rate 78%), totalling 35 patients (43 hips) (follow-up rate 78%), were available at a minimum of 28 years after surgery. Results: In the pre-OA group, the mean Merle d'Aubigné score improved significantly from 14.5 points (SD 0.7) preoperatively to 17.4 points at final follow-up (SD 1.2; p = 0.004) and in the early-stage group, the mean score did not improve significantly from 14.0 (SD 0.3) to 14.6 (SD 2.4; p = 0.280). Radiologically, the centre-edge angle, acetabular roof angle, and head lateralization index were significantly improved postoperatively in both groups. Radiological progression of OA was observed in two patients (two hips) in the pre-OA group and 17 patients (18 hips) in the early-stage group. Kaplan-Meier survival analysis, with radiological progression of OA as the primary outcome, projected a 30-year survival rate of 81.8% (95% confidence interval (CI) 0.59 to 1.00) for the pre-OA group and 42.2% (95% CI 0.244 to 0.600) for the early-stage group. In all cases, the overall survival rate stood at 51.5% (95% CI 0.365 to 0.674) over a 30-year period, and when the endpoint was conversion to total hip arthroplasty, the survival rate was 74.0% (95% CI 0.608 to 0.873). Conclusion: For younger patients with pre-OA, joint preservation of over 30 years can be expected after RAO.

Human Trials on the Prevention of Tunnel Widening by the Emdogain in Anterior Cruciate Ligament Reconstruction.

Background Although anterior cruciate ligament reconstruction (ACLR) is an established procedure, some problems remain, such as bone tunnel widening after ACLR. In animal studies, Emdogain (EMD) prevented tunnel widening by promoting tendon-bone healing. This study aimed to evaluate the effects of EMD on the prevention of tunnel widening after anterior cruciate ligament (ACL) injury in humans. Methods Nineteen patients who underwent ACLR were included. Seven patients in the EMD group were administered EMDs into the femoral tunnel during ACLR, while 12 patients in the control group were not administered EMDs. After surgery, at two and four weeks and three, six, and 12 months, femoral and tibial tunnel widening were evaluated on computed tomography images. Anteroposterior laxity and clinical scores such as the Lysholm score, the International Knee Documentation Committee (IKDC) subjective form, and the Knee Injury and Osteoarthritis Outcome Score (KOOS) were assessed before surgery and 12 months postoperatively. Results Tunnel widening on the femoral side was significantly smaller in the EMD group than in the control group at two weeks. However, there was no significant difference between the two groups at 12 months. There were no significant differences in anteroposterior laxity and clinical scores between the groups before and 12 months after surgery. Conclusion EMD administration into the bone tunnel did not prevent tunnel widening at 12 months after ACLR, although tunnel widening of the femoral tunnel was reduced by EMD administration in the early phase.

A Comparison of Central Anatomic Single-Bundle Reconstruction and Anatomic Double-Bundle Reconstruction in Anteroposterior and Rotational Knee Stability: Intraoperative Biomechanical Evaluation.

Postoperative anterior and rotational stability are still controversial when compared with single-bundle (SB) and double-bundle (DB) anterior cruciate ligament (ACL) reconstruction. This study aimed to compare the central anatomical SB and anatomical DB ACL reconstruction in intraoperative knee kinematics during continuous knee flexion-extension. A total of 34 patients who underwent ACL reconstruction using the hamstring tendon were evaluated intraoperatively before and immediately after ACL reconstruction using OrthoPilot ACL Navigation System Version 3.0. The patients were prospectively randomized into the central anatomical SB (17 knees) and the anatomical DB reconstruction (17 knees) groups. The tibial translation and rotation were continuously measured during knee flexion-extension under conventional knee motion, anterior tibial load (100N), and internal-external torque (3 N·m). The anterior tibial translation and total range of tibial rotation were calculated from the measurement values from 20 to 50 degrees at each 5-degree point. The anterior tibial translation (p = 0.59; two-factor repeated measures analysis of variance; η 2G = 0.0077) and total range of tibial rotation (p = 0.95; η 2G = 0.0001) at each knee flexion angle showed no significant difference between the central anatomical SB and anatomical DB reconstruction groups. It is suggested that the central anatomical SB reconstruction is comparable with the anatomical DB reconstruction in biomechanical anteroposterior and rotational knee stability at time 0.

Clinical outcomes of knee joint distraction combined with marrow stimulation procedures for patients with advanced knee osteoarthritis.

BACKGROUND: Knee joint distraction (KJD) has received much attention as a joint preserving surgery, especially in young patients with advanced knee osteoarthritis (OA). METHODS: This study included 16 patients with advanced knee OA who underwent KJD combined with marrow stimulating techniques and were followed up for more than 2 years. The patients' clinical scores, including the Japanese Orthopaedic Association (JOA) score, Knee Injury and Osteoarthritis Outcome Score (KOOS) subscales, ROM, joint space width, and semiquantitative MRI were evaluated. The factors affecting clinical outcomes were analyzed. RESULTS: Postoperatively, the JOA score and the individual scores of the KOOS subscales improved significantly (JOA score: P = 0.0028, KOOS-symptoms: P = 0.0016, -pain: P = 0.0011, -ADL: P = 0.0009, -sports/recreation: P = 0.0144, and -QOL: P = 0.0034). Although the extension of the knee joint did not change throughout the follow-up period, flexion of the joint deteriorated at the time of device removal but recovered to the preoperative level at the final follow-up. Preoperative joint space width was 2.4 ± 2.0 mm and at the final follow-up, it increased to 3.3 ± 1.5 mm, showing statistically significant improvement (P = 0.034). The postoperative semiquantitative MRI score also improved significantly (from 6.0 ± 3.0 to 42.1 ± 28.7, P = 0.0001). A high BMI was associated with a poor clinical outcome. CONCLUSION: Although the effect of marrow stimulating techniques for cartilage repair was not well clarified and the complication rate was high, the clinical and radiographic outcomes showed significant improvement after KJD combined with marrow stimulating techniques in patients with advanced knee OA. However, we should be careful about suggesting this procedure in obese patients.

Treatment of Intra-Articular Distal Phalanx Fractures in Baseball Players by Joint Distraction and Early Mobilization Using a New Dynamic External Finger Fixator.

In baseball players, a high degree of functional recovery is required for the treatment of fractures in the distal interphalangeal (DIP) joint, especially on the throwing side. While dynamic external fixation is a useful treatment option to restore the joint function, existing external fixators are too large for use on DIP joints. Three cases of DIP joint intra-articular comminuted fractures in baseball players treated using the new dynamic external finger fixator which we developed are reported. The external fixator was kept attached for four weeks. The patients returned to play baseball 7-8 weeks after surgery. The total arc of the DIP joint was 90-100% of the contralateral side. Follow-up radiographs demonstrated that joint congruity had been reacquired. This technique was adaptive in the treatment of comminuted intra-articular fractures of the DIP joint and resulted in a near-normal range of joint motion and remodeling of the joint surface.

Evaluation of the intraoperative kinematics during double-bundle anterior cruciate ligament reconstruction using a navigation system.

BACKGROUND/OBJECTIVE: There is controversy regarding the biomechanical function of the anteromedial (AM) and posterolateral (PL) bundles in isolated tibiofemoral rotation during double-bundle anterior cruciate ligament (ACL) reconstruction. This study aimed to evaluate the biomechanical function of the AM and PL bundles of the ACL using a computer navigation system. METHODS: This study involved 15 patients who underwent double-bundle ACL reconstruction. Anteroposterior and isolated rotational knee laxity were measured with a navigation system. The measurements were performed four times, namely, before fixation, after temporary PL bundle fixation, after AM bundle fixation, and after double-bundle reconstruction. With knee flexion ranging from 20° to 60°, we continuously measured the anterior tibial displacement under an anterior drawer stress (100 N using a spring balance). The total range of tibial rotation was also measured under an external and internal rotational torque of 3 Nm. RESULTS: Fixation of either the AM or the PL bundle significantly reduced the anteroposterior displacement at all knee flexion angles. Although the anteroposterior displacement after AM bundle fixation was relatively similar throughout the range of motion (2.4-3.2 mm), the anteroposterior displacement after PL bundle fixation increased continuously with knee flexion (2.2-4.6 mm). With respect to the total range of tibial rotation under external and internal rotational torque, there was no significant difference between AM and PL bundle fixation throughout the range of motion. The total range of tibial rotation was significantly reduced only on double-bundle reconstruction at 20° and 25° knee flexion compared to the pre-reconstruction range (P = 0.015 and 0.036, respectively). CONCLUSION: The AM and PL bundles function differently for controlling anterior knee laxity throughout the range of motion. The function of the AM and PL bundles was similar for controlling isolated tibiofemoral rotation. Isolated tibiofemoral rotation was significantly controlled only on double-bundle reconstruction at knee flexion angles of 20° and 25°.

Transplantation of autologous bone marrow-derived mesenchymal stem cells under arthroscopic surgery with microfracture versus microfracture alone for articular cartilage lesions in the knee: A multicenter prospective randomized control clinical trial.

INTRODUCTION: To investigate the efficacy of the transplantation of autologous bone marrow-derived mesenchymal stem cells (BMSCs) under arthroscopy with microfracture (MFX) compared with microfracture alone. METHODS: Eleven patients with a symptomatic articular cartilage defect of the knee were included in the study. They were randomized to receive BMSCs with MFX (cell-T group, n=7) or MFX alone (control group, n=4). Clinical results were evaluated using International Knee Documentation committee (IKDC) knee evaluation questionnaires and the Knee Injury and Osteoarthritis Outcome Score (KOOS) before and 48 weeks after surgery. Quantitative and qualitative assessments of repair tissue were carried out at 48 weeks by T2 mapping of magnetic resonance images (MRIs) and the magnetic resonance observation of cartilage repair tissue (MOCART) scoring system with follow-up MRI. RESULTS: No significant differences between preoperative and postoperative IKDC and KOOS were observed in the cell-T or control group. However, forty-eight weeks after surgery, the cell-T group showed a trend for a greater KOOS QOL score compared with the control group (79.4 vs. 39.1, respectively; P=0.07). The T2 value did not differ significantly between the two groups, but the mean MOCART score was significantly higher in the cell-T group than in the control group (P=0.02). CONCLUSIONS: Compared with MFX alone, BMSC transplantation with MFX resulted in better postoperative healing of the cartilage and subchondral bone as determined by the MOCART score. Clinically, BMSC transplantation with MFX gave a higher KOOS QOL score after 48 weeks.

Factors associated with pain in nonsurgically treated rotator cuff tears -A study with magnetic resonance imaging.

BACKGROUND: In rotator cuff tears, some cases become asymptomatic with nonsurgical treatment, others remain symptomatic. The purpose of this study was to identify factors associated with pain in nonsurgically treated rotator cuff tears using magnetic resonance imaging (MRI). METHODS: In total, 108 shoulders diagnosed with supraspinatus (SSP) tendon tears using MRI were nonsurgically treated, and MRI was repeated after more than a year. The patients were divided into pain or improvement group according to whether the pain persisted or disappeared. Bursal fluid accumulation; SSP tendon retraction; subscapularis (SSC) tendon tears; infraspinatus (ISP) tendon tears; and Goutallier classification into SSC, SSP, and ISP were included as evaluation factors. Predictive factors for persistent pain on initial MRI and factors associated with persisting pain after nonsurgical treatment on repeat MRI were statistically analyzed using multivariate logistic regression analysis. RESULTS: The improvement group showed a significant decrease in bursal fluid accumulation compared with the pain group (p < 0.01). SSC tendon tears (OR, 4.42; 95% CI, 1.16-16.9; P = 0.03) on initial MRI were significantly associated with persistent pain. Bursal fluid accumulation (OR, 2.44; 95% CI, 1.18-5.07; P = 0.02) and SSC tendon tears (OR, 2.25; 95% CI, 1.15-4.39; P = 0.02) on repeat MRI were significantly associated with persistent pain. CONCLUSIONS: Bursal fluid accumulation decreased when pain improved. The involvement of SSC tendon tears can serve as a predictive factor for persistent pain. Pain may persist although patients with rotator cuff tears including SSC tendon tears are nonsurgically treated. LEVEL OF EVIDENCE: Level IV case-control study.

In Vitro Safety and Quality of Magnetically Labeled Human Mesenchymal Stem Cells Preparation for Cartilage Repair.

IMPACT STATEMENT: This study is very important for a preclinical assessment of the safety and quality of magnetically labeled mesenchymal stem cells (MSCs) for use in cartilage repair. The findings of this study show that magnetic labeling with an appropriate density of magnetic particles has no harmful effects on the safety and quality of MSCs.

Coculturing of mesenchymal stem cells of different sources improved regenerative capability of osteochondral defect in the mature rabbit: An in vivo study.

PURPOSE: Choosing a therapeutic cell source for osteochondral repair remains a challenge. The present study investigated coculturing mesenchymal stem cells (MSCs) from different sources to provide an improved therapeutic cell option for osteochondral repair. METHODS: Dutch and Japanese white rabbits were used in this study, the first for isolating MSCs and the second for creating an osteochondral model in the medial femoral condyle. The 26 rabbit knees were divided randomly into four groups: control ( n = 6), bone marrow-derived MSCs (BMSCs) ( n = 7), synovial tissue MSCs (SMSCs) ( n = 7), and cocultured MSCs ( n = 6). Tissue repair was assessed using the Fortier scale, and colony-forming assay was performed. RESULTS: At different cell densities, cocultured and SMSCs formed larger colonies than BMSCs, indicating their high proliferative potential. After 2 months, complete filling of the defect with smooth surface regularity was detected in the cocultured MSC group, although there was no significant difference among the therapeutic groups macroscopically. Also, tissue repair was histologically better in the cocultured MSC group than in the control and SMSC groups, due to repair of the subchondral bone and coverage with hyaline cartilage. Additionally, toluidine blue and collagen-II staining intensity in the repaired tissue was better in the cocultured MSC group than in the remaining groups. CONCLUSION: Our results suggest that cocultured MSCs are a suitable option for the regeneration capability of osteochondral defects due to their enhanced osteochondrogenic potential.

Novel Near-Infrared Fluorescence-Guided Surgery With Vesicular Stomatitis Virus for Complete Surgical Resection of Osteosarcomas in Mice.

Attempts have been made to visualize tumor cells intraoperatively with fluorescence guidance. However, the clear demarcation and complete tumor resection have always been a challenging task. To address this, we have developed a novel fluorescence bioimaging system with vesicular stomatitis virus (VSV) incorporating Katushka, near-infrared fluorescent protein. VSV is tumor-specific owing to the deficiency of antiviral interferon signaling pathways in tumor cells. We aimed to evaluate the tumor specificity of the recombinant VSV-Katushka (rVSV-K) in osteosarcoma cells and to assess the feasibility of complete tumor resection by the rVSV-K fluorescence guidance. In in vitro experiments, mouse and human osteosarcoma cell lines and normal human mesenchymal stem cells were infected with rVSV-K and observed by fluorescence microscopy. Near-infrared fluorescence was observed only in osteosarcoma cells, even at a low-concentration of virus infections. In in vivo experiments, mouse osteosarcoma (LM8) cells were transplanted subcutaneously into the back of immune-competent mice to produce an osteosarcoma, which was then injected with rVSV-K. The areas emitting fluorescence were resected using a bioimaging system. The distance between the surgical and tumor margins of the fluorescence-guided resection with rVSV-K group was significantly larger than that of the non-guided resection groups. The local recurrence rate was significantly lower in the fluorescence-guided resection with rVSV-K group than in the non-guided resection groups. The distant metastasis rate and average survival rate were not significantly different between all groups. These results suggest that the rVSV-K is specific to osteosarcoma cells and enables complete tumor resection of osteosarcomas in mice. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res.

Role of Mesenchymal Stem Cells Densities When Injected as Suspension in Joints with Osteochondral Defects.

OBJECTIVE: The aim of this study was to evaluate an intraarticular injection of different doses of autologous mesenchymal stem cells (MSCs) for improving repair of midterm osteochondral defect. DESIGN: At 4 weeks postoperative marrow stimulation model bilaterally (3 mm diameter; 4 mm depth) in the medial femoral condyle, autologous MSCs were injected into knee joint. Twenty-four Japanese rabbits aged 6 months were divided randomly into 4 groups ( n = 6 per group): the control group and and MSC groups including 0.125, 1.25, and 6.25 million MSCs. Repaired tissue was assessed macroscopically and histologically at 4 and 12 weeks after intraarticular injection of MSCs. RESULTS: At 12 weeks, there was no repair tissue in the control group. The gross appearance of the 1.25 and 6.25 million MSC groups revealed complete repair of the defect with white to pink tissue at 12 weeks. An osteochondral repair was histologically significantly better in the 1.25 and 6.25 million MSC groups than in the control and 0.125 million MSC groups at 4 and 12 weeks, due to presence of hyaline-like tissue in the deep layer at 4 weeks, and at 12 weeks hyaline cartilage formation at the periphery and fibrous tissue containing some chondrocytes in the deep layer of the center of the defect. Subchondral bone was restructured in the 1.25 and 6.25 million MSC groups, although it did not resemble the normal bone. CONCLUSION: An intraarticular injection of 1.25 or 6.25 million MSCs could promote the repair of subchondral bone, even in the case of midterm osteochondral defect.

Outcomes of arthroscopic rotator cuff repair with muscle advancement for massive rotator cuff tears.

BACKGROUND: We performed arthroscopic rotator cuff repair (ARCR) combined with miniopen supraspinatus and infraspinatus muscle advancement for massive rotator cuff tears (RCTs) to decrease tension at the repair site with the goal of reduction of the failure rate. We evaluated the clinical outcomes and failure rate after this procedure. METHODS: This study included 47 patients diagnosed with chronic massive RCTs between October 2010 and March 2015. Of these patients, 21 underwent transosseous equivalent (TOE) ARCR only (control group), and 26 underwent TOE ARCR with muscle advancement (study group). We evaluated shoulder clinical outcomes at preoperative and postoperative assessments and also measured muscle strength and the acromiohumeral interval (AHI) at the same time in both groups. Failure rates were calculated in both groups by evaluating the cuff integrity with postoperative magnetic resonance imaging. RESULTS: Although there was statistically significant improvement for the mean clinical scores in the both groups, there were no significant differences between the 2 groups. The postoperative abduction muscle strength and AHI were significantly higher in the study group (46.3 ± 20.6 N and 9.4 ± 2.9 mm; P = .04) than in the control group (34.6 ± 20.0 N and 7.7 ± 3.0 mm; P = .04). The failure rates were significantly lower in the study group than in the control group (23.1% and 52.4%; P = .03). CONCLUSION: The TOE ARCR with muscle advancement can achieve significantly better abduction muscle strength, wider AHI, and lower failure rates for massive RCTs than the normal TOE ARCR.

Conventional 99mTc-(hydroxy) methylene diphosphate remains useful to predict osteosarcoma response to neoadjuvant chemotherapy: Individual patient data and aggregate data meta-analyses.

BACKGROUND: The current standard of chemotherapy response evaluation holds the most important prognostic factor to be the histological assessment of the tumor necrosis of the excised lesion, but the major challenge is to find an early prognostic factor that will allow the adjuvant treatment regimen to be adjusted. The objective of this systematic review is to provide an up-to-date and unprecedented summary of the value of Technetium-methylene diphosphate or -hydroxymethylene diphosphate (Tc-MDP/HMDP) scintigraphy for the preoperative evaluation of osteosarcoma response to chemotherapy. METHODS: Studies evaluating the alteration ratio (percentage change of the Tc-99m -MDP/HMDP uptake between before and after neoadjuvant chemotherapy) to predict the histological response of osteosarcoma to chemotherapy were searched for in MEDLINE, EMBASE, and Web of Science. A meta-analysis of individual patient data (IPD) was performed to determine the optimal cut-off point from the receiver operating characteristic (ROC) curve. Additionally, aggregate data (AD) meta-analysis was performed to compare the value of Tc-MDP/HMDP scintigraphy with that of other quantitative modalities, such as dynamic magnetic resonance imaging (MRI), Tl scintigraphy, and F-FDG PET-CT. RESULTS: Seven studies with 154 patients were included for the IPD meta-analysis. The optimal cut-off point of the alteration ratio was 31.0%. Five studies with 123 patients were considered for the AD meta-analysis. The pooled sensitivity and specificity were 0.76 (95% CI, 0.63-0.86) and 0.89 (95% CI, 0.79-0.95), respectively. There was a significant difference between the good and poor responders in terms of the diagnostic odds ratio. The summary ROC curve demonstrated that the area under curve (AUC) was 0.892, indicating excellent diagnostic accuracy. CONCLUSION: Our findings have suggested that conventional Tc-MDP/HMDP scintigraphy remains as useful as recent quantitative modalities to predict the histological response of osteosarcoma to neoadjuvant chemotherapy.

Magnetic cell delivery for the regeneration of musculoskeletal and neural tissues.

Magnetic targeting is a cell delivery system using the magnetic labeling of cells and the magnetic field; it has been developed for minimally invasive cell transplantation. Cell transplantation with both minimal invasiveness and high efficacy on tissue repair can be achieved by this system. Magnetic targeting has been applied for the transplantation of bone marrow mesenchymal stem cells, blood CD133-positive cells, neural progenitor cells, and induced pluripotent stem cells, and for the regeneration of bone, cartilage, skeletal muscles, and the spinal cord. It enhances the accumulation and adhesion of locally injected cells, resulting in the improvement of tissue regeneration. It is a promising technique for minimally invasive and effective cell transplantation therapy.

Magnetic Resonance Imaging Evaluation of Cartilage Repair and Iron Particle Kinetics After Magnetic Delivery of Stem Cells.

IMPACT STATEMENT: This study is very important as a preclinical study of magnetic resonance imaging (MRI) assessment after magnetic targeting of mesenchymal stem cells. The findings of this study show that MRI is useful for evaluating the regenerative process of cartilage with magnetic targeting and kinetics of iron particles, and is less invasive without any complications.

The endoplasmic reticulum stress transducer old astrocyte specifically induced substance positively regulates glial scar formation in spinal cord injury.

To investigate the relationship between endoplasmic reticulum (ER) stress mediated by old astrocyte specifically induced substance (OASIS) and astrogliosis in spinal cord injury (SCI). SCI models were established using adult male mice deficient for OASIS and C57BL/6 (wild-type mice) mice. After SCI, recovery and astrogliosis were examined in the mice at specific time points using functional and histological methods. After SCI, functional recovery was better in the OASIS-deficient mice than in the wild-type mice. OASIS deletion did not inhibit astrocyte migration but reduced the excessive accumulation of N-cadherin-expressing reactive astrocytes that formed the glial scar around the injury site. In addition, OASIS deletion increased the number of serotonin-positive axons in spinal cord regions caudal to the injury site. These findings suggested that the OASIS-mediated ER stress response inhibits the repair of the injured spinal cord by promoting the development of N-cadherin-expressing reactive astrocytes that form glial scars following injury. OASIS deletion inhibited the development of N-cadherin-positive reactive astrocytes that form glial scars and promoted axon growth and functional recovery after SCI. These results suggest that the ER stress response mediated by OASIS could be a new target in the treatment of SCI.