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Abstract Background We previously demonstrated that CD34 + cell transplantation in animals healed intractable fractures via osteogenesis and vasculogenesis; we also demonstrated the safety and efficacy of this cell therapy in an earlier phase I/II clinical trial conducted on seven patients with fracture nonunion. Herein, we present the results of a phase III clinical trial conducted to confirm the results of the previous phase studies using a larger cohort of patients. Methods CD34 + cells were mobilized via administration of granulocyte colony-stimulating factor, harvested using leukapheresis, and isolated using magnetic cell sorting. Autologous CD34 + cells were transplanted in 15 patients with tibia nonunion and 10 patients with femur nonunion, who were followed up for 52 weeks post transplantation. The main outcome was a reduction in time to heal the tibia in nonunion patients compared with that in historical control patients. We calculated the required number of patients as 15 based on the results of the phase I/II study. An independent data monitoring committee performed the radiographic assessments. Adverse events and medical device failures were recorded. Results All fractures healed during the study period. The time to radiological fracture healing was 2.8 times shorter in patients with CD34 + cell transplantation than in the historical control group (hazard ratio: 2.81 and 95% confidence interval 1.16–6.85); moreover, no safety concerns were observed. Conclusions Our findings strongly suggest that autologous CD34 + cell transplantation is a novel treatment option for fracture nonunion. Trial registration UMIN-CTR, UMIN000022814. Registered on 22 June 2016.

Advanced glycation end-products (AGEs) play a critical supportive role during musculoskeletal disorders via glycosylation and oxidative stress. Though apocynin, identified as a potent and selective inhibitor of NADPH oxidase, has been reported to be involved in pathogen-induced reactive oxygen species (ROS), its role in age-related rotator cuff degeneration has not been well clarified. Therefore, this study aims to evaluate the in vitro effects of apocynin on human rotator cuff-derived cells. Twelve patients with rotator cuff tears (RCTs) participated in the study. Supraspinatus tendons from patients with RCTs were collected and cultured. After the preparation of RC-derived cells, they were divided into four groups (control group, control + apocynin group, AGEs group, AGEs + apocynin group), and gene marker expression, cell viability, and intracellular ROS production were evaluated. The gene expression of NOX, IL-6, and the receptor for AGEs (RAGE) was significantly decreased by apocynin. We also examined the effect of apocynin in vitro. The results showed that ROS induction and increasing apoptotic cells after treatment of AGEs were significantly decreased, and cell viability increased considerably. These results suggest that apocynin can effectively reduce AGE-induced oxidative stress by inhibiting NOX activation. Thus, apocynin is a potential prodrug in preventing degenerative changes of the rotor cuff.

Traditionally, angle measurements have been performed using a goniometer, but the complex motion of shoulder movement has made these measurements intricate. The angle of rotation of the shoulder is particularly difficult to measure from an upright position because of the complicated base and moving axes. In this study, we attempted to estimate the shoulder joint internal/external rotation angle using the combination of pose estimation artificial intelligence (AI) and a machine learning model. Videos of the right shoulder of 10 healthy volunteers (10 males, mean age 37.7 years, mean height 168.3 cm, mean weight 72.7 kg, mean BMI 25.6) were recorded and processed into 10,608 images. Parameters were created using the coordinates measured from the posture estimation AI, and these were used to train the machine learning model. The measured values from the smartphone’s angle device were used as the true values to create a machine learning model. When measuring the parameters at each angle, we compared the performance of the machine learning model using both linear regression and Light GBM. When the pose estimation AI was trained using linear regression, a correlation coefficient of 0.971 was achieved, with a mean absolute error (MAE) of 5.778. When trained with Light GBM, the correlation coefficient was 0.999 and the MAE was 0.945. This method enables the estimation of internal and external rotation angles from a direct-facing position. This approach is considered to be valuable for analyzing motor movements during sports and rehabilitation.

Background and Objectives: Androgen deprivation therapy (ADT) for prostate cancer has greatly improved treatment outcomes. As patient survival rates have increased, reports of decreased bone density and increased bone fractures as side effects of ADT have emerged. The prevalence of osteoporosis in Japanese men was 4.6%. The purpose of this study was to evaluate the effect of osteoporosis treatment in prostate cancer patients who underwent ADT in Japan. Materials and Methods: The subjects were 33 male patients who had undergone ADT for prostate cancer, who were noted to have decreased bone density. Mean age was 76.2 ± 7.7 years (64–87). Medications included vitamin D in one case, bisphosphonates (BP) in 27 cases, and denosumab in five cases. The evaluation method examined the rate of change in bone mineral density (BMD) before osteoporosis treatment and 1 year after. For comparison, a group without osteoporosis treatment intervention (n = 33) was selected, and matched for prostate cancer treatment and age. The rate of change in trabecular bone score (TBS) was also calculated. Results: The percentage changes in BMD before and 1 year after treatment were as follows: lumbar spine, 7.1 ± 5.8% in the treatment group versus −3.9 ± 4.1% in the no treatment group; femoral neck, 5.5 ± 6.2% in the treatment group versus −0.9 ± 3.9% in the no treatment group; total femur, 6.6 ± 6.4% in the treatment group versus the no treatment group which was −1.7 ± 3.2%. In all cases, there was a clear significant difference (p < 0.01). The percent change in TBS was further calculated in the same manner. There was no significant difference between the two groups: +1.7 ± 3.8% in the treated group versus +0.3 ± 4.1% in the untreated group. Conclusions: Osteoporosis treatment in Japanese patients with prostate cancer on ADT therapy was found to significantly increase BMD compared to the untreated group. BP and denosumab were found to be very effective in increasing BMD.

Carpal tunnel syndrome (CTS) is caused by subsynovial connective tissue fibrosis, resulting in median nerve (MN) mobility. The standard evaluation method is the measurement of the MN cross-sectional area using static images, and dynamic images are not widely used. In recent years, remarkable progress has been made in the field of deep learning (DL) in medical image processing. The aim of the present study was to evaluate MN dynamics in CTS hands using the YOLOv5 model, which is one of the object detection models of DL. We included 20 normal hands (control group) and 20 CTS hands (CTS group). We obtained ultrasonographic short-axis images of the carpal tunnel and the MN and recorded MN motion during finger flexion–extension, and evaluated MN displacement and velocity. The YOLOv5 model showed a score of 0.953 for precision and 0.956 for recall. The radial–ulnar displacement of the MN was 3.56 mm in the control group and 2.04 mm in the CTS group, and the velocity of the MN was 4.22 mm/s in the control group and 3.14 mm/s in the CTS group. The scores were significantly reduced in the CTS group. This study demonstrates the potential of DL-based dynamic MN analysis as a powerful diagnostic tool for CTS.

Abstract Background Quercetin, a flavonoid abundantly in vegetables and fruits, exerts antioxidant and anti-inflammatory effects. We investigated the protective effects of quercetin against oxidative stress in the Achilles tendons of diabetic rats. Methods Cells were collected from the Achilles tendons of Sprague–Dawley rats and cultured under four conditions: regular glucose (RG) without quercetin (Quer-), RG with quercetin (Quer +), high-glucose (HG) Quer-, and HG Quer + . The expression of genes related to NADPH oxidase (NOX) and inflammation, reactive oxygen species accumulation, and apoptosis rates was analyzed. Additionally, diabetic rats were divided into two groups and subjected to quercetin (group Q) or no quercetin (group C) treatment. Histological evaluation and expression analysis of relevant genes in the Achilles tendon were performed. Results In rat tendon-derived cells, the expression of Nox1, Nox4, and Il6; reactive oxygen species accumulation; and apoptosis rates were significantly decreased by quercetin treatment in the HG group. The collagen fiber arrangement was significantly disorganized in the diabetic rat Achilles tendons in group C compared with that in group Q. The mRNA and protein expression levels of NOX1 and NOX4 were significantly decreased upon quercetin treatment. Furthermore, the expression of Il6, type III collagen, Mmp2, and Timp2 was significantly decreased, whereas that of type I collagen was significantly increased in group Q compared with that in group C. Conclusions Quercetin treatment decreases NOX expression and thus exerts antioxidant and anti-inflammatory effects in the Achilles tendons of diabetic rats. Quercetin treatment may be effective against diabetic tendinopathy.

Abstract Background A link between tendinopathy and oxidative stress has been recently reported. Nicotinamide mononucleotide (NMN) is a precursor of nicotinamide adenine dinucleotide, which plays an important role in cell redox homeostasis. The aim of this study was to evaluate the antioxidant effect of NMN on tendinopathy in vitro and in vivo. Methods Tenocytes from healthy Sprague-Dawley rats were cultured in regular glucose (RG) and high-glucose (HG) conditions with or without NMN, and were divided into four groups: RG NMN(−), RG NMN(+), HG NMN(−), and HG NMN(+). Cell viability, reactive oxygen species (ROS) accumulation, apoptotic rate, and mRNA expression of nicotinamide adenine dinucleotide phosphate oxidase (NOX)1, NOX4, interleukin (IL)6, sirtuin (SIRT)1, and SIRT6 were investigated. In addition, rats with collagenase-induced tendinopathy were treated with or without NMN. Immunostaining of NOX1 and NOX4; mRNA expression of SIRT1, SIRT6, and IL6; and superoxide dismutase (SOD) activity measurements in the Achilles tendon were performed. Results NMN increased the expression of SIRT1 and SIRT6 in rat tenocytes, but decreased the levels of NOX1, NOX4, IL6, ROS, and apoptosis. In Achilles tendons with collagenase-induced tendinopathy, NMN increased the mRNA expression of SIRT1 and SIRT6, as well as SOD activity; while suppressing protein expression of NOX1 and NOX4, and mRNA expression of IL6. Conclusion The in vitro and in vivo results of this study show that NMN exerts an antioxidant effect on tendinopathy by promoting the expression of SIRT while inhibiting that of NOX.

Abstract Background Most degenerative rotator cuff tears (RCTs) are associated with a limited range of motion (ROM) of the shoulder joint. Additionally, patients with diabetes mellitus (DM) show a higher frequency of limited ROM. Recently, advanced glycation end products (AGEs) of proteins have been observed to cause tissue fibrosis, primarily through abnormal collagen cross-linking and oxidative stress. In this study, we investigated the effect of AGEs on ROM limitation in the shoulder capsule and its relationship with DM in the patients with RCTs. Methods Sixteen patients (eight in the DM and non-DM groups) who underwent arthroscopic surgery for RCT with limited shoulder ROM were included in this study. AGE-related pathologies in both groups were compared, and the relationship between AGE accumulation and shoulder joint ROM was evaluated. Shoulder capsule tissue was harvested and subjected to histological and in vitro evaluation. Results The DM group displayed high levels of AGEs and reactive oxygen species (ROS), and reduced cell viability. There was a significant positive correlation between ROS expression, apoptosis, and preoperative hemoglobin A1c. ROS expression, apoptosis, and ROM of the shoulder joint showed a negative correlation. The NADPH oxidase (NOX) expression and collagen III/I ratio were significantly higher in the DM group than in the non-DM group. Conclusions The DM group showed significant AGEs deposition in the shoulder capsule. Additionally, there was a significant association between AGEs and ROM limitation. Collectively, the findings suggest that the oxidative stress induced by AGEs deposition, which leads to fibrosis and local inflammation, might contribute to the limited ROM of the shoulder joint in patients with RCTs accompanied by DM.

There are no reports investigating the relationship between shoulder range of motion (ROM) and pitching elbow torque in junior high school pitchers. Therefore, we aimed to evaluate the factors associated with medial elbow torque in this population. Sixty-three junior high school baseball pitchers were recruited for this study. The participants completed a questionnaire and passive ROM measurements of shoulder abduction and horizontal adduction. All pitchers pitched three fastballs at maximum effort while wearing a wireless sensor recording pitching mechanics and elbow valgus torque for each pitch. Age (r = 0.65, p < 0.001), height (r = 0.83, p < 0.001), body weight (r = 0.82, p < 0.001), BMI (r = 0.60, p < 0.001), and ball velocity (r = 0.80, p < 0.001) were significantly positively correlated with elbow valgus torque. Participants were divided into two groups based on elbow valgus torque, >30 (high torque [HT]) and

Abstract Tendon rupture and nerve injury cause fatty infiltration of the skeletal muscle, and the adipokines secreted from the infiltrated adipocytes are known to contribute to chronic inflammation. Therefore, in this study, we evaluated the effects of the adipokines on chronic inflammation using a rat sciatic nerve-crushed injury model. In vitro and in vivo experiments showed that the expression of adiponectin was decreased (0.3-fold) and the expression of Il6 (~ 3.8-fold) and Tnf (~ 6.2-fold) was increased in the nerve-crushed group compared to that in the control group. It was also observed that the administration of an adiponectin receptor agonist decreased the levels of Il6 (0.38-fold) and Tnf (0.28-fold) and improved cellular viability (~ 1.9-fold) in vitro. Additionally, in the fatty infiltrated skeletal muscle, low adiponectin levels were found to be associated with chronic inflammation. Therefore, the local administration of adiponectin receptor agonists would prevent chronic inflammation.

Abstract Background While the precise measurement of the range of motion (ROM) of the elbow joint is important for clinical assessment and rehabilitation, problems include low accuracy and reproducibility in goniometer measurements due to the influence of soft tissue. The purpose of this study was to validate elbow joint motion analysis using a three-dimensional electromagnetic sensor system (EMS). Methods The accuracy and reproducibility of the EMS system were evaluated at four angles (0°, 45°, 90°, and 135°) using a model bone of the humerus and forearm. In addition, the maximum extension and maximum flexion of six elbows of six healthy volunteers were assessed by radiographic and EMS measurements. Accuracy was assessed by calculating the mean value of the measurement angle, standard deviation, Pearson’s correlation coefficient, and the Bland–Altman method. Reproducibility was assessed by calculating the intra-rater and inter-rater reliabilities using intraclass correlation coefficients. Results In the model bone evaluation, the mean angles of the EMS measurement were 1.2° ± 2.0°, 45.4° ± 2.1°, 91.7° ± 2.4°, and 134.6° ± 2.7° at 0°, 45°, 90°, and 135°, respectively. In the in vivo evaluation, the elbow angles at the maximum extension with the EMS and radiographic angles were 4.7° ± 3.0° and 2.7° ± 2.0°, respectively, and the angles at maximum flexion were 131.8° ± 13.0° and 130.8° ± 4.5°, respectively. There were statistically significant correlations between the EMS and radiographic measurements; the Bland–Altman plots indicated that the two methods were almost in agreement for both extension and flexion. Conclusions This method of measuring ROM of the elbow joint using EMS showed high accuracy, reliability, and reproducibility. The current results demonstrated the possibility of using the electromagnetic system to provide an accurate evaluation of the elbow joint in clinical settings.

Abstract Introduction Excellent outcomes of arthroscopic rotator cuff repair for small and medium tears have been recently reported. However, re-tears after surgery have been a common complication after surgical repair of large and massive rotator cuff tears and often occur in early postoperative phase. It was previously reported that basic fibroblast growth factor and platelet-rich plasma enhanced rotator cuff tear healing. We hypothesized that this combined therapy could enhance rotator cuff healing after rotator cuff repair in a rat model. This study aimed to evaluate the efficacy of combined therapy of platelet-rich plasma and basic fibroblast growth factor with gelatin-hydrogel sheet. Methods To create a rotator cuff defect, the infraspinatus tendon of Sprague Dawley rat was resected from the greater tuberosity. The infraspinatus tendons were repaired and covered with gelatin-hydrogel sheet impregnated with PBS (control group), basic fibroblast growth factor (bFGF group), platelet-rich plasma (PRP group), or both basic fibroblast growth factor and platelet-rich plasma (combined group). Histological examinations were conducted using hematoxylin and eosin, safranin O, and immunofluorescence staining, such as Isolectin B4, type II collagen at 2 weeks postoperatively. For mechanical analysis, ultimate failure load of the tendon-humeral head complex was evaluated at 6 weeks postoperatively. Results In the hematoxylin and eosin staining, the tendon maturing score of the combined group was higher than that of the control group at postoperative 2 weeks. In the safranin O staining, stronger proteoglycan staining was observed in the combined group compared with the other groups at postoperative 2 weeks. Vascular staining with isolectin B4 in 3 treatment groups was significantly higher than that in the control group. Type II collagen expression in the combined group was significantly higher than those in the other groups. The ultimate failure load of the combined group was significantly higher than that of the control group. Conclusion Combined therapy of basic fibroblast growth factor and platelet-rich plasma promoted angiogenesis, tendon maturing and fibrocartilage regeneration at the enthesis, which could enhance the mechanical strength. It was suggested that combined basic fibroblast growth factor and platelet-rich plasma might enhance both tendon and bone–tendon junction healing, and basic fibroblast growth factor and platelet-rich plasma might be synergistic.

Substantial advancements in markerless motion capture accuracy exist, but discrepancies persist when measuring joint angles compared to those taken with a goniometer. This study integrates machine learning techniques with markerless motion capture, with an aim to enhance this accuracy. Two artificial intelligence-based libraries—MediaPipe and LightGBM—were employed in executing markerless motion capture and shoulder abduction angle estimation. The motion of ten healthy volunteers was captured using smartphone cameras with right shoulder abduction angles ranging from 10° to 160°. The cameras were set diagonally at 45°, 30°, 15°, 0°, −15°, or −30° relative to the participant situated at a distance of 3 m. To estimate the abduction angle, machine learning models were developed considering the angle data from the goniometer as the ground truth. The model performance was evaluated using the coefficient of determination R2 and mean absolute percentage error, which were 0.988 and 1.539%, respectively, for the trained model. This approach could estimate the shoulder abduction angle, even if the camera was positioned diagonally with respect to the object. Thus, the proposed models can be utilized for the real-time estimation of shoulder motion during rehabilitation or sports motion.

Background: Screening for elbow osteochondritis dissecans (OCD) using ultrasound (US) is essential for early detection and successful conservative treatment. The aim of the study is to determine the diagnostic accuracy of YOLOv8, a deep-learning-based artificial intelligence model, for US images of OCD or normal elbow-joint images. Methods: A total of 2430 images were used. Using the YOLOv8 model, image classification and object detection were performed to recognize OCD lesions or standard views of normal elbow joints. Results: In the binary classification of normal and OCD lesions, the values from the confusion matrix were the following: Accuracy = 0.998, Recall = 0.9975, Precision = 1.000, and F-measure = 0.9987. The mean average precision (mAP) comparing the bounding box detected by the trained model with the true-label bounding box was 0.994 in the YOLOv8n model and 0.995 in the YOLOv8m model. Conclusions: The YOLOv8 model was trained for image classification and object detection of standard views of elbow joints and OCD lesions. Both tasks were able to be achieved with high accuracy and may be useful for mass screening at medical check-ups for baseball elbow.

Abstract Background The accurate assessment of distal radioulnar joint (DRUJ) instability is still challenging as there is no established objective evaluation method. This study aimed to develop a noninvasive measurement method using a three-dimensional electromagnetic sensor system (EMS) to quantitatively assess and characterize the normal DRUJ movement in healthy volunteers. Methods The DRUJ movement was mimicked using both a block model and saw bone. Movement of the models was measured by EMS, and the accuracy and reproducibility of the measurements were assessed. In vivo measurement was performed in a sitting position with the elbow flexed and the forearm pronated. One sensor each was attached to the distal radial shaft and the ulnar head. The examiners fixed the distal radius and the carpal bones, moved the ulnar head from the dorsal to the volar side and measured the dorsovolar translation. The volar translation was measured by EMS and ultrasonography, and the correlation coefficient was calculated. The dorsovolar translation was evaluated in 14 healthy volunteers (7 men and 7 women) by three hand surgeons. The intraclass and inter-rater correlation coefficients (ICCs), the differences between the dominant and non-dominant sides and between men and women were assessed. Results The accuracy and reproducibility assessment results of the EMS showed high accuracy and reproducibility. In the comparison between EMS and ultrasonography, the correlation coefficient was 0.920 (p = 0.16 × 10-3). The ICC (1,5) for the intra-rater reliability was 0.856, and the ICC (2,5) for inter-rater reliability was 0.868. The mean ulnar head translation and difference between dominant and non-dominant sides were 6.00 ± 1.16 mm (mean ± SD) and − 0.12 ± 0.40 mm, respectively. There were no significant differences between any of the parameters. Conclusions A new measurement method using EMS could evaluate DRUJ movement with high accuracy, reproducibility, and intra- and inter-rater reliability. In healthy volunteers, the dorsovolar ulnar head translation was 6.00 mm. The difference between the dominant and non-dominant sides was < 1.0 mm with no significant difference. EMS provided an objective, non-invasive, real-time assessment of dynamic changes in the DRUJ. These findings could be useful in the treatment of patients with DRUJ instability.

Abstract Background Dehydroepiandrosterone (DHEA), an adrenal steroid, has a protective role against diabetes. This study aimed to investigate the in vitro and in vivo protective effects of DHEA against high glucose-induced oxidative stress in tenocytes and tendons. Methods Tenocytes from normal Sprague-Dawley rats were cultured in low-glucose (LG) or high-glucose (HG) medium with or without DHEA. The experimental groups were: control group (LG without DHEA), LG with DHEA, HG without DHEA, and HG with DHEA. Reactive oxygen species (ROS) production, apoptosis, and messenger RNA (mRNA) expression of NADPH oxidase (NOX) 1 and 4, and interleukin-6 (IL-6) were determined. Further, diabetic rats were divided into a control group and a DHEA-injected group (DHEA group). NOX1 and NOX4 protein expression and mRNA expression of NOX1, NOX4, IL-6, matrix metalloproteinase (MMP)-2, tissue inhibitors of matrix metalloproteinase (TIMP)-2, and type I and III collagens in the Achilles tendon were determined. Results In rat tenocytes, DHEA decreased the expression of NOX1 and IL-6, ROS accumulation, and apoptotic cells. In the diabetic rat Achilles tendon, NOX1 protein expression and mRNA expression of NOX1, IL-6, MMP-2, TIMP-2, and type III collagen were significantly lower while type I collagen expression was significantly higher in the DHEA group than in the control group. Conclusions DHEA showed antioxidant and anti-inflammatory effects both in vitro and in vivo. Moreover, DHEA improved tendon matrix synthesis and turnover, which are affected by hyperglycemic conditions. DHEA is a potential preventive drug for diabetic tendinopathy.

Background: Coronal shear fractures of the distal humerus are rare injuries, and fragmentation of the capitellum and trochlea with posterior comminution is challenging for surgeons. We retrospectively evaluated the functional outcomes of patients with coronal shear fractures managed with open reduction and internal fixation, focusing on the number of trochlea fragments in Dubberley type 3B fractures. Materials and methods: The functional outcomes of 25 patients, including 8 patients with type 3B fractures, with a mean age (and standard deviation) of 57 ± 20 years, were evaluated at a mean follow-up duration of 15 ± 9 months. Type 3B fractures were classified into two groups: those with two trochlea fragments or less group (group A) and those with three or more fragments (group B). Patient outcomes were assessed with clinical and radiographic examination, range of motion, and the Mayo Elbow Performance scale (MEPS). Results: Two patients with type 3B in group B experienced nonunion, and two patients with type 3B in group A and 1 patient with type 1B demonstrated avascular necrosis on radiographs. The average MEPS score was 96.3 points (range, 70-100), with 18 excellent, 5 good, and 1 fair results. The average range of motion was 10 ± 8 to 130 ± 12. The MEPS score worsened as Dubberley classification progressed from type 1 to type 3 (98.3 vs. 96.7 vs. 88, P = .014, respectively) and subtypes A to B (97.9 vs. 90, P = .014, respectively). In comparing groups A and B, the MEPS score was significantly worse in group B (93.8 vs. 76.3, P = .006). Conclusion: Our open reduction and internal fixation results were largely good, although functional outcomes were diminished as Dubberley classification progressed from type 1 to type 3 and subtype A to B. Type 3B fractures with three trochlea fragments or more in the elderly were the most difficult to treat with open reduction and internal fixation and possibly 1-term total elbow arthroplasty.

The coracohumeral ligament (CHL) is related to the range of motion of the shoulder joint. The evaluation of the CHL using ultrasonography (US) has been reported on the elastic modulus and thickness of the CHL, but no dynamic evaluation method has been established. We aimed to quantify the movement of the CHL by applying Particle Image Velocimetry (PIV), a technique used in the field of fluid engineering, to cases of shoulder contracture using the US. The subjects were eight patients, with 16 shoulders. The coracoid process was identified from the body surface, and a long-axis US image of the CHL parallel to the subscapularis tendon was drawn. The shoulder joint was moved from 0 degrees of internal/external rotation to 60 degrees of internal rotation at a rhythm of one reciprocation every 2 s. The velocity of the CHL movement was quantified by the PIV method. The mean magnitude velocity of CHL was significantly faster on the healthy side. The maximum magnitude velocity was significantly faster on the healthy side. The results suggest that the PIV method is helpful as a dynamic evaluation method, and in patients with shoulder contracture, the CHL velocity was significantly decreased.

The diagnosis of osteoporosis is made by measuring bone mineral density (BMD) using dual-energy X-ray absorptiometry (DXA). Machine learning, one of the artificial intelligence methods, was used to predict low BMD without using DXA in elderly women. Medical records from 2541 females who visited the osteoporosis clinic were used in this study. As hyperparameters for machine learning, patient age, body mass index (BMI), and blood test data were used. As machine learning models, logistic regression, decision tree, random forest, gradient boosting trees, and lightGBM were used. Each model was trained to classify and predict low-BMD patients. The model performance was compared using a confusion matrix. The accuracy of each trained model was 0.772 in logistic regression, 0.739 in the decision tree, 0.775 in the random forest, 0.800 in gradient boosting, and 0.834 in lightGBM. The area under the curve (AUC) was 0.595 in the decision tree, 0.673 in logistic regression, 0.699 in the random forest, 0.840 in gradient boosting, and 0.961, which was the highest, in the lightGBM model. Important features were BMI, age, and the number of platelets. Shapley additive explanation scores in the lightGBM model showed that BMI, age, and ALT were ranked as important features. Among several machine learning models, the lightGBM model showed the best performance in the present research.

Abstract Background Rad is the prototypic member of a subfamily of Ras-related small G-proteins and is highly expressed in the skeletal muscle of patients with type II diabetes. Our previous microarray analysis suggested that Rad may mediate fracture nonunion development. Thus, the present study used rat experimental models to investigate and compare the gene and protein expression patterns of both Rad and Rem1, another RGK subfamily member, in nonunions and standard healing fractures. Methods Standard healing fractures and nonunions (produced via periosteal cauterization at the fracture site) were created in the femurs of 3-month-old male Sprague-Dawley rats. At post-fracture days 7, 14, 21, and 28, the fracture callus and fibrous tissue from the standard healing fractures and nonunions, respectively, were harvested and screened (via real-time PCR) for Rad and Rem1 expression. The immunolocalization of both encoded proteins was analyzed at post-fracture days 14 and 21. At the same time points, hematoxylin and eosin staining was performed to identify the detailed tissue structures. Results Results of real-time PCR analysis showed that Rad expression increased significantly in the nonunions, compared to that in the standard healing fractures, at post-fracture days 14, 21, and 28. Conversely, immunohistochemical analysis revealed the immunolocalization of Rad to be similar to that of Rem1 in both fracture types at post-fracture days 14 and 21. Conclusions Rad may mediate nonunion development, and thus, may be a promising therapeutic target to treat these injuries.

The subsheath of the extensor carpi ulnaris (ECU) tendon, a component of the triangular fibrocartilage complex (TFCC), is particularly important as it dynamically stabilizes the distal radioulnar joint. However, the relationship between TFCC injury and ECU dynamics remains unclear. This study aimed to analyze ECU movement and morphology using ultrasonography (US) images. Twenty wrists of patients with TFCC injury, who underwent TFCC repair, were included in the injury group, and 20 wrists of healthy volunteers were in the control group. For static image analysis, curvature and linearity ratios of the ECU in US long-axis images captured during radioulnar deviation were analyzed. For dynamic analysis of the ECU, the wrist was moved from radial deviation to ulnar deviation at a constant speed, and the velocity of the tendon was analyzed using particle image velocimetry. The static analysis showed that the ECU tendon was more curved in ulnar deviation in the injury group than in the control group, and the dynamic analysis showed that only vertical velocity toward the deep side during ulnar deviation was higher in the injury group. These results suggest that TFCC injury caused ECU curvature during ulnar deviation and increased the vertical velocity of the ECU during wrist deviation.

Abstract Background Aging impairs tendon healing and is a potential risk factor for chronic tendinitis. During normal aging, tendons undergo structural and biomechanical degenerative changes, accompanied by a reduction in the number of tenocytes and changes to their properties. However, molecular changes in aged tendons under inflammatory conditions are not well understood. The present study analyzed the molecular changes in collagenase induced acute tendon injury using a senescence-accelerated mouse (SAM) model. Methods SAMP6 mice were used as an aging animal model and SAMR1 mice were used as a control to represent a senescence-resistant inbred strain. All the mice used in the study were 40 weeks old. Collagenase I from Clostridium histolyticum (20 μL) was injected percutaneously to the tendon-bone junction of the Achilles tendon. Two weeks after treatment, the Achilles tendons were harvested and stained using Picrosirius Red to determine collagen expression. Real-time PCR was performed to analyze gene expression of IL-6, tenomodulin, type I and type II collagen, MMP-9, TIMP-1, and TIMP-2. Results Collagenase injection resulted in significantly higher gene expression of IL-6 but significantly lower tenomodulin expression compared with the control in SAMP6 and SAMR1 mice. In SAMP6 mice, gene expression of type III collagen and MMP-9 was significantly higher in the collagenase-injected group compared with the control group. SAMP6 mice also showed lower expression of type I collagen, TIMP-1, and TIMP-2 in the collagenase-injected group compared with the control group. Picrosirius Red staining showed the highest expression of type III collagen in the collagenase-injected SAMP6 group compared with the other groups. Conclusions The collagenase-injected SAMP6 group showed higher expression of IL-6, MMP-9, and type III collagen and lower expression of type I collagen, TIMP-1, and TIMP-2, which are known to suppress metalloproteinases. The results indicate that aging may lead to dysfunction of the tendon healing process after acute tendon injury.

Introduction. Although the recommended treatment for humeral shaft nonunion is compression plating with autologous bone grafting, we treated a case of humeral shaft nonunion with an intramedullary nail (IMN) without bone grafting. Presentation of Case. Osteosynthesis with IMN was performed on a 24-year-old man with a humeral shaft fracture at another hospital. However, bony union was not obtained 1 year after the first surgery, and he was referred to our institution. We treated the nonunion with exchange nailing without autologous bone grafting using compression function of the nail, leading to bony union at 7 months postoperatively. At the final follow-up 2 years and 4 months postoperatively, the patient had full range of motion in the left shoulder and elbow joints. Discussion. Compression plating with autologous bone grafting is reported to be the gold standard for the treatment of humeral shaft nonunion. IMN is advantageous for minimal invasion; however, the conventional type of IMN cannot apply compression force between fragments and does not have sufficient stability against rotational force. In this case, we used an IMN that could apply compression between the fragments and which had rotational stability via many screws. We did not perform bone grafting because the current nonunion was adjudged to be biologically active, and we achieved good functional results. Conclusion. We treated humeral shaft nonunion using IMN with compression, but without bone grafting, leading to successful clinical outcomes. This strategy might be an appropriate choice for the treatment of humeral shaft nonunion with biological activity.

Introduction Diabetes mellitus (DM) negatively affects fracture repair by inhibiting endochondral ossification, chondrogenesis, callus formation, and angiogenesis. We previously reported that transcutaneous CO2 application accelerates fracture repair by promoting endochondral ossification and angiogenesis. The present study aimed to determine whether CO2 treatment would promote fracture repair in cases with type I DM.Research design and methods A closed femoral shaft fracture was induced in female rats with streptozotocin-induced type I DM. CO2 treatment was performed five times a week for the CO2 group. Sham treatment, where CO2 was replaced with air, was performed for the control group. Radiographic, histologic, genetic, and biomechanical measurements were taken at several time points.Results Radiographic assessment demonstrated that fracture repair was induced in the CO2 group. Histologically, accelerated endochondral ossification and capillary formation were observed in the CO2 group. Immunohistochemical assessment indicated that early postfracture proliferation of chondrocytes in callus was enhanced in the CO2 group. Genetic assessment results suggested that cartilage and bone formation, angiogenesis, and vasodilation were upregulated in the CO2 group. Biomechanical assessment revealed enhanced mechanical strength in the CO2 group.Conclusions Our findings suggest that CO2 treatment accelerates fracture repair in type I DM rats. CO2 treatment could be an effective strategy for delayed fracture repair due to DM.

Most shoulder rotator cuff tears (RCTs) are caused by non-traumatic age-related rotator cuff degeneration, of which hyperglycemia is a risk factor due to its glycation reaction and oxidative stress. We aimed to identify the influence of diabetes-induced glycation and oxidative stress in patients with non-traumatic shoulder RCTs. Twenty patients, aged over 50 years, with non-traumatic shoulder RCTs participated in this study. Patients with a history of diabetes mellitus or preoperative HbA1c ≥ 6.5% were assigned to the diabetic group (n = 10), and the rest to the non-diabetic group (n = 10). Cell proliferation; expression of genes related to oxidative stress, glycation reaction, inflammation, and collagen; intracellular reactive oxygen species (ROS) levels; and apoptosis rates were analyzed. The diabetic group had significantly lower cell proliferation than the non-diabetic group. In the diabetic group, the mRNA expression levels of NOX1, NOX4, IL6, RAGE, type III collagen, MMP2, TIMP1, and TIMP2 were significantly higher; type I collagen expression was significantly lower; and the rate of ROS-positive cells and apoptotic cells, as well as the expression of advanced glycation end-products (AGEs) and the receptor for AGEs (RAGE), was significantly higher. In conclusion, hyperglycemia caused by diabetes mellitus increased AGE and RAGE expression, and led to increased NOX expression, ROS production, and apoptosis in the human rotator cuff. This provides scope to find a preventive treatment for non-traumatic RCTs by inhibiting glycation and oxidative stress.

Although electromyography is the routine diagnostic method for cubital tunnel syndrome (CuTS), imaging diagnosis by measuring cross-sectional area (CSA) with ultrasonography (US) has also been attempted in recent years. In this study, deep learning (DL), an artificial intelligence (AI) method, was used on US images, and its diagnostic performance for detecting CuTS was investigated. Elbow images of 30 healthy volunteers and 30 patients diagnosed with CuTS were used. Three thousand US images were prepared per each group to visualize the short axis of the ulnar nerve. Transfer learning was performed on 5000 randomly selected training images using three pre-trained models, and the remaining images were used for testing. The model was evaluated by analyzing a confusion matrix and the area under the receiver operating characteristic curve. Occlusion sensitivity and locally interpretable model-agnostic explanations were used to visualize the features deemed important by the AI. The highest score had an accuracy of 0.90, a precision of 0.86, a recall of 1.00, and an F-measure of 0.92. Visualization results show that the DL models focused on the epineurium of the ulnar nerve and the surrounding soft tissue. The proposed technique enables the accurate prediction of CuTS without the need to measure CSA.

The triangular fibrocartilage complex (TFCC) is a significant stabilizer of the distal radioulnar joint. Diagnosing TFCC injury is currently difficult, but ultrasonography (US) has emerged as a low-cost, minimally invasive diagnostic tool. We aimed to quantitatively analyze TFCC by performing motion analysis by using US. Twelve healthy volunteers, comprising 24 wrists (control group), and 15 patients with TFCC Palmer type 1B injuries (injury group) participated. The US transducer was positioned between the ulnar styloid process and triquetrum and was tilted ulnarly 30° from the vertical line. The wrist was then actively moved from 10° of radial deviation to 20° of ulnar deviation in a 60-rounds-per-minute rhythm that was paced by a metronome. The articular disc displacement velocity magnitude was analyzed by using particle image velocimetry fluid measurement software. The mean area of the articular discs was larger on ulnar deviation in the control group. The mean articular disc area on radial deviation was larger in the injury group. The average articular disc velocity magnitude for the injury group was significantly higher than that for the control group. The results suggest that patients with TFCC injury lose articular disc cushioning and static stability, and subsequent abnormal motion can be analyzed by using US.

Abstract Background Fascia lata augmentation of massive rotator cuff tears has shown good clinical results. However, its biological effect during the early healing process is not clearly understood. The purpose of the study was to evaluate the biological efficacy of fascia lata augmentation during the early healing process of rotator cuff tears using a rabbit rotator cuff defect model. Methods The infraspinatus tendon was resected from the greater tuberosity of a rabbit to create a rotator cuff tear. The tendon edge was directly sutured to the humeral head. The rotator cuff repaired site was augmented with a fascia lata autograft (augmentation group, group A). The rotator cuff defect in the contralateral shoulder was repaired without augmentation (reattachment group, group R). A group with intact rotator cuff was set as the control group. Histological examinations and mechanical analysis were conducted 4 and 8 weeks postoperatively. Results In the HE staining, the tendon maturing score of group A was higher than that of group R at 4 weeks postoperatively. In the safranin O staining, proteoglycan staining at the repaired enthesis in group A at 4 weeks postoperatively was stronger than that in group R. Picrosirius red staining showed that type III and type I collagen in group A was more strongly expressed than that in group R at 4 weeks postoperatively. The ultimate failure load of the infraspinatus tendon–humeral head complex in group A was statistically higher than that in group R at 4 weeks postoperatively. The ultimate failure load of group A was similar to that of the control group. Conclusion The biological and mechanical contribution of fascia lata augmentation for massive rotator cuff tears was analyzed in this study. Type III collagen was reported to be expressed during the tendon healing process. Although the biological action similar to natural ligament healing occurred around the fascia lata grafts, type III collagen was gradually replaced by type I collagen as the tissue matured. Our results suggest that fascia lata augmentation could stimulate biological healing and provide initial fixation strength of the repaired rotator cuff.

Abstract Background Advanced glycation end products are associated with aging, hyperglycemia, and oxidative stress. Accumulation of advanced glycation end products can cause various pathological conditions; however, the association of Dupuytren’s disease with advanced glycation end products has not been demonstrated yet. The aim of this study is to investigate the association of Dupuytren’s disease with advanced glycation end products. Methods Normal palmar fascia from five patients with carpal tunnel syndrome (control group) and Dupuytren’s cords from five patients (Dupuytren’s disease group) were harvested. The tissues were stained using an anti-advanced glycation end products antibody, anti-receptor for advanced glycation end products antibody, and an anti-reactive oxygen species modulator 1 antibody. The expression of nicotinamide adenine dinucleotide phosphate oxidase-1 and nicotinamide adenine dinucleotide phosphate oxidase-4 genes was also assessed using real-time PCR. For in vitro analysis, the cells harvested from the control and Dupuytren’s disease groups were used. After 3 days of exposure to four types of media (control group, control + advanced glycation end products group, Dupuytren’s disease group, Dupuytren’s disease + advanced glycation end products group), superoxide detection reagent was detected using a total reactive oxygen species/superoxide detection kit. Results Immunostaining of the palmar fasciae of the Dupuytren’s disease group showed higher expressions of advanced glycation end products and receptor for advanced glycation end products than that in the control group. The expression of nicotinamide adenine dinucleotide phosphate oxidase oxidase-1 and nicotinamide adenine dinucleotide phosphate oxidase-4 as well as reactive oxygen species modulator 1, an oxidatively damaged protein, was also higher in the Dupuytren’s disease group than in the control group. In an in vitro cell culture, the addition of advanced glycation end products to the Dupuytren’s disease-derived cells produced more superoxide free radicals. Conclusions These data suggest that the advanced glycation end products receptor for advanced glycation end products interaction produced free radicals via nicotinamide adenine dinucleotide phosphate oxidase activation in Dupuytren’s disease patients. Further studies are required to confirm these results.

Dorsal extension block pinning is a commonly performed surgical technique for acute bony mallet fingers. However, the treatment of chronic bony mallet finger remains controversial. We investigated the use of dorsal extension block pinning with percutaneous curettage for chronic bony mallet fingers. Seven patients with chronic bony mallet fingers were treated by dorsal extension block pinning with percutaneous curettage. The average age was 17 (range, 12–23) years, and the average time from injury to surgery was 20 (range, 7–49) weeks. Bone union was achieved in all patients. None of the patients experienced pain after bone union. The average loss of distal interphalangeal joint extension was 6 (range, 5–20) degrees, and the average flexion was 59 (range, 40–80) degrees. The Crawford functional score was excellent in three patients, good in two, and fair in two. Dorsal extension block pinning with percutaneous curettage could be a useful treatment for chronic bony mallet fingers.

Excellent clinical results of arthroscopic repair of rotator cuff tears have been reported. However, retears after surgical repair of large and massive rotator cuff tears are one of the most common complications. We present single-row repair with graft augmentation of the fascia lata for large and massive rotator cuff tears to reduce tension at the tendon-bone repair site, and this technique may prevent retears of the repaired rotator cuff. A candidate for this technique is a patient who has a large or massive rotator cuff tear in which the torn edge cannot reach the footprint after mobilization of the torn rotator cuff. This technique could provide an excellent option for irreparable large and massive rotator cuff tears.

Mallet fingers with an avulsion fracture of the distal phalanx or rupture of the terminal tendon of the extensor mechanism is known as a common injury, while mallet thumb is very rare. In this paper, the case of a 19-year-old woman with a sprained left thumb sustained while playing basketball is presented. Plain radiographs and computed tomography revealed an avulsion fracture involving more than half of the articular surface at the base of the distal phalanx. Closed reduction and percutaneous fixation were performed using the two extension block Kirschner wires’ technique under digital block anesthesia. At 4 months postoperatively, the patient had achieved excellent results according to Crawford’s evaluation criteria and had no difficulties in working or playing basketball. Various conservative and operative treatment strategies have been reported for management of mallet thumb. We chose the two extension block Kirschner wires’ technique to minimize invasion of the extensor mechanism and nail bed and to stabilize the large fracture fragment.

We recently demonstrated that the local transplantation of human peripheral blood (PB) CD34 + cells, an endothelial/hematopoietic progenitor cell-rich population, contributes to fracture repair via vasculogenesis/angiogenesis and osteogenesis. Human PB mononuclear cells (MNCs) are also considered a potential cell fraction for neovascularization. We have previously shown the feasibility of human PB MNCs to enhance fracture healing. However, there is no report directly comparing the efficacy for fracture repair between CD34 + cells and MNCs. In addition, an unhealing fracture model, which does not accurately resemble a clinical setting, was used in our previous studies. To overcome these issues, we compared the capacity of human granulocyte colony-stimulating factor-mobilized PB (GM-PB) CD34 + cells and human GM-PB MNCs in a nonunion model, which more closely resembles a clinical setting. First, the effect of local transplantation of 1 × 10 5 GM-PB CD34 + cells (CD34 + group), 1 × 10 7 GM-PB MNCs (containing approximately 1 × 10 5 GM-PB CD34 + cells) (MNC group), and phosphate-buffered saline (PBS) (PBS group) on nonunion healing was compared. Similar augmentation of blood flow recovery at perinonunion sites was observed in the CD34 + and MNC groups. Meanwhile, a superior effect on nonunion repair was revealed by radiological, histological, and functional assessment in the CD34 + group compared with the other groups. Moreover, through in vivo and in vitro experiments, excessive inflammation induced by GM-PB MNCs was confirmed and believed to be one of the mechanisms underlying this potency difference. These results strongly suggest that local transplantation of GM-PB CD34 + cells is a practical and effective strategy for treatment of nonunion after fracture.

We present a case of carpal tunnel syndrome caused by systemic tumoral calcinosis. A 54-year-old woman experienced hand numbness that persisted for nine months. She had no family history or medical problem. A plain radiograph of her right wrist showed a calcified mass on the volar side of the wrist joint. The patient also experienced pain in her contralateral wrist joint and both right and left shoulders, which had calcification on radiography around the joint. Her condition was diagnosed as carpal tunnel syndrome caused by systemic tumoral calcinosis and a resection biopsy was performed. Histopathological analysis of the biopsied specimen showed basophile deposition inside the fibrous connective tissue. At 14 months after the treatment, she no longer had pain or numbness in her fingers and there was no recurrence of the mass. This patient’s condition is considered as a case of nonfamilial, systemic primary tumoral calcinosis. Since incomplete resection leads to a recurrence of the lesion, a follow-up radiography examination is needed to monitor symptom recurrence.

Introduction. Some patients showed unusual responses to the immobilization without any objective findings with casts in upper extremities. We hypothesized their that intolerance with excessive anxiety to casts is due to claustrophobia triggered by cast immobilization. The aim of this study is to analyze the relevance of cast immobilization to the feeling of claustrophobia and discover how to handle them. Methods. There were nine patients who showed the caustrophobic symptoms with their casts. They were assesed whether they were aware of their claustrophobis themselves. Further we investigated the alternative immobilization to casts. Results. Seven out of nine cases that were aware of their claustrophobic tendencies either were given removable splints initially or had the casts converted to removable splints when they exhibited symptoms. The two patients who were unaware of their latent claustrophobic tendencies were identified when they showed similar claustrophobic symptoms to the previous patients soon after short arm cast application. We replaced the casts with removable splints. This resolved the issue in all cases. Conclusions. We should be aware of the claustrophobia if patients showed unusual responses to the immobilization without any objective findings with casts in upper extremities, where removal splint is practical alternative to cast to continue the treatment successfully.

We present a case of concurrent rotator cuff tear and axillary nerve palsy resulting from anterior dislocation of the shoulder and a large glenoid rim fracture—a “terrible tetrad.” A 61-year-old woman fell on her right shoulder. Radiographs showed anterior dislocation of the shoulder with a glenoid rim fracture, and an MRI two months after injury revealed a rotator cuff tear. Upon referral to our hospital, physical and electrophysiological examinations revealed axillary nerve palsy. The axillary nerve palsy was incomplete and recovering, and displacement of the glenoid rim fracture was minimal and already united; therefore, we surgically repaired only the rotator cuff tear three months after injury. The patient recovered satisfactorily following the operation. In patients whose axillary nerve palsy is recovering, surgeons should consider operating on rotator cuff tears in an attempt to prevent rotator cuff degeneration.

Recent reports indicated that human isolated CD271 + bone marrow mesenchymal stromal cells (BM-MSCs) have a greater expansion and potential for multipotent differentiation including chondrogenesis than classical plastic adherent (PA) BM-MSCs in vitro. Therefore, we set up a hypothesis that CD271 + MSCs may have a greater chondrogenic potential than PA-MSCs in vitro and in vivo. We investigated the superiority of CD271 + MSCs on chondrogenesis using in vitro expansion and pellet culture system and in vivo rat model of cartilage defect when compared to PA-MSCs. In the in vitro study, CD271 + MSCs showed higher expansion potential and produced larger pellets with higher expressions of chondrogenic genes when compared to the control groups. During the culture, CD271 expression decreased, which resulted in decreased chondrogenesis. In the in vivo study, immunohistochemical staining demonstrated differentiated human chondrocytes identified as double-stained cells with human-specific collagen type 2 and human leukocyte antigen-ABC in CD271 + and PA groups. The number of double-stained cells was significantly higher in the CD271 + group than PA group. Real-time RT-PCR analysis of tissue RNA isolated from the chondral defect site for human-specific chondrogenic markers demonstrated a significantly higher expression in CD271 + group than PA group. Macroscopic examination of chondral defect sites at week 8 revealed glossy white and well-integrated repaired tissues in the CD271 + and PA groups, but not in the PBS group. The average histological score in the CD271 + group was significantly greater than in the other groups. Apoptosis analysis at the cell transplanted site with TUNEL staining showed that the CD271 + group had significantly fewer apoptotic chondrocytes compared with the PA group. These results indicate that CD271 + MSCs have a greater chondrogenic potential than PA-MSCs in both in vitro and in vivo conditions.

Transplantation of bone marrow (BM) CD34 + cells, an endothelial/hematopoietic progenitor-enriched cell population, has shown therapeutic efficiency in the treatment of ischemic diseases enhancing neovascularization. However, the number of CD34 + cells obtained from bone marrow is not sufficient for routine clinical application. To overcome this issue, we developed a more efficient and clinically applicable CD34 + cell expansion method. Seven-day ex vivo expansion culture of BM CD34 + cells with a cocktail of five growth factors containing VEGF, SCF, IL-6, Flt-3 ligand, and TPO resulted in reproducible more than 20-fold increase in cell number. The favorable effect of the local transplantation of culture expanded (cEx)-BM CD34 + cells on rat unhealing fractures was equivalent or higher than that of nonexpanded (fresh) BM CD34 + cells exhibiting sufficient therapeutic outcome with frequent vasculogenic/osteogenic differentiation of transplanted cEx-BM CD34 + cells and fresh BM CD34 + cells as well as intrinsic enhancement of angiogenesis/osteogenesis at the treated fracture sites. Specifically, cEx-BM CD34 + cell treatment demonstrated the best blood flow recovery at fracture sites compared with the nonexpanded BM CD34 + cells. In vitro, cEx-BM CD34 + cells showed higher colony/tube-forming capacity than nonexpanded BM CD34 + cells. Both cells demonstrated differentiation potential into osteoblasts. Since fresh BM CD34 + cells can be easily collected from fracture sites at the time of primary operation and stored for future use, autologous cEx-BM CD34 + cell transplantation would be not only a simple but also a promising therapeutic strategy for unhealing fractures in the field of orthopedic trauma surgery.

We recently reported that the ruptured regions of the human anterior cruciate ligament (ACL) contained vascular-derived stem cells, which showed the potential for high expansion and multilineage differentiation. In this study, we performed experiments to test the hypothesis that ACL-derived CD34 + cells could contribute to tendon–bone healing. ACL-derived cells were isolated from the rupture site of human ACL by fluorescence-activated cell sorting. Following ACL reconstruction, immunodeficient rats received intracapsular administration of either ACL-derived CD34 + cells, nonsorted (NS) cells, CD34 - cells, or phosphate-buffered saline (PBS). We also performed in vitro cell proliferation assays and enzyme-linked immunosorbent assays for vascular endothelial growth factor (VEGF) secretion. We confirmed the recruitment of the transplanted cells into the perigraft site after intracapuslar injection by immunohistochemical staining at week 1. Histological evaluation showed a greater area of collagen fiber formation and more collagen type II expression in the CD34 + group than the other groups at the week 2 time point. Immunostaining with isolectin B4 and rat osteocalcin demonstrated enhanced angiogenesis and osteogenesis in the CD34 + group at week 2. Moreover, double immunohistochemical staining for human-specific endothelial cell (EC) and osteoblast (OB) markers at week 2 demonstrated a greater ability of differentiation into ECs and OBs in the CD34 + group. Microcomputerized tomography showed the greatest healing of perigraft bone at week 4 in the CD34 + cell group, and the failure load of tensile test at week 8 demonstrated the greatest biomechanical strength in the CD34 + group. Furthermore, the in vitro studies indicated that the CD34 + group was superior to the other groups in their cell proliferation and VEGF secretion capacities. We demonstrated that ACL-derived CD34 + cells contributed to the tendon–bone healing after ACL reconstruction via the enhancement of angiogenesis and osteogenesis, which also contributed to an increase in biomechanical strength.

We previously reported the therapeutic potential of human peripheral blood (hPB) CD34 + cells for bone fracture healing via vasculogenesis/angiogenesis and osteogenesis. Transplantation of not only hPB CD34 + cells but also hPB total mononuclear cells (MNCs) has shown their therapeutic efficiency for enhancing ischemic neovascularization. Compared with transplantation of purified hPB CD34 + cells, transplantation of hPB MNCs is more attractive due to its simple method of cell isolation and inexpensive cost performance in the clinical setting. Thus, in this report, we attempted to test a hypothesis that granulocyte colony-stimulating factor-mobilized (GM) hPB MNC transplantation could also contribute to fracture healing via vasculogenesis/angiogenesis and osteogenesis. Nude rats with unhealing fractures received local administration of the following materials with atelocollagen: 1 × 10 7 GM hPB MNCs (Hi group), 1 × 10 6 GM hPB MNCs (Lo group), or PBS (PBS group). Immunohistochemistry and real-time reverse transcriptase-polymerase chain reaction (RT-PCR) demonstrated human cell-derived vasculogenesis and osteogenesis in the Hi and Lo groups, but not in the PBS group at week 1. Intrinsic angiogenesis and osteogenesis assessed by rat capillary, osteoblast density, and real-time RT-PCR analysis was significantly enhanced in the Hi group compared to the other groups. Blood flow assessment by laser doppler perfusion imaging showed a significantly higher blood flow ratio at week 1 in the Hi group compared with the other groups. Morphological fracture healing was radiographically and histologically confirmed in about 30% of animals in the Hi group at week 8, whereas all animals in the other groups resulted in nonunion. Local transplantation of GM hPB MNCs contributes to fracture healing via vasculogenesis/angiogenesis and osteogenesis.

We present a case of arthroscopic fixation for bony Bankart lesion using a double-threaded cannulated screw. A 39-year-old man sustained a left shoulder injury from a motorcycle accident. Radiographs showed bony Bankart lesion and CT revealed 40% defect of glenoid articular surface. Arthroscopic fixation was performed using double-threaded cannulated screw after the bony fragment was reduced by suturing the labrum at the edge with a suture anchor. Arthroscopic bony Bankart repair using double-threaded cannulated screw fixation is effective because compression force could be applied between bony fragments and the screw head is not exposed in the glenohumeral joint.

A 74-year-old man developed a severe low back pain and a fever. In the initial examinations, a collapse of the L5 anterosuperior vertebral body and narrowing of the L4/5 disc space were identified on radiographs, and the laboratory data showed inflammatory results. A computed tomography (CT) and a magnetic resonance imaging showed collapse of L5. A needle biopsy was performed to make a diagnosis; however, an abdominal pain and a hypotension appeared after the biopsy. An abdominal CT showed a hematoma in the retroperitoneal space, and an angiography revealed a left fourth lumbar artery pseudoaneurysm. The pseudoaneurysm was treated with transcatheter placement of microcoils. Although haemorrhagic complications following needle biopsy are very rare, patients with large amounts of vertebral destruction may have unusual anatomical positions of the lumber artery. Therefore, surgeons should be aware of the possibility of lumbar artery injury during a needle biopsy and take care of prebiopsy plans.

Although implantation of crude bone marrow cells has been applied in a small number of patients for fracture healing, transplantation of peripheral blood CD34 + cells, the hematopoietic/endothelial progenitor cell-enriched population, in patients with fracture has never been reported. Here, we report the first case of tibial nonunion receiving autologous, granulocyte colony stimulating factor mobilized CD34 + cells accompanied with autologous bone grafting. No serious adverse event occurred, and the novel therapy performed 9 months after the primary operation resulted in bone union 3 months later without any symptoms including pain and gait disturbance.