Is Early Controlled Motion and Weightbearing Recommended for Nonoperatively Treated Acute Achilles Tendon Rupture? A Systematic Review and Meta-analysis.

BACKGROUND: There is disagreement as to whether early controlled motion and weightbearing confer a beneficial effect for nonoperatively treated acute Achilles tendon rupture (ATR) compared with immobilization and late weightbearing. PURPOSE: To conduct a meta-analysis of randomized controlled trials (RCTs) to determine whether early controlled motion and weightbearing results in different outcomes compared with immobilization and late weightbearing for nonoperatively treated patients with acute ATR. STUDY DESIGN: Systematic review; Level of evidence, 1. METHODS: We conducted a search in the PubMed, Web of Science, and EMBASE databases for relevant RCTs in humans from January 1981 to August 2020. The primary outcome was the Achilles Tendon Total Rupture Score (ATRS) at 1-year follow-up. The secondary outcomes were the rerupture rate, return to sports activity and work, and the heel-rise work (limb symmetry index [LSI]). Study quality was assessed using the Cochrane Collaboration risk of bias tool. RESULTS: Included were 7 RCTs involving 424 participants (n = 215 treated with early controlled motion and weightbearing [early group], n = 209 treated with immobilization and late weightbearing [late group]). The quality assessment indicated a low risk of bias in all included RCTs. There was no difference between the early and late groups regarding the ATRS (mean difference [MD], -0.220; 95% CI, -4.489 to 4.049; P = .920). Likewise, we found no difference between the 2 groups in terms of the rerupture rate (odds ratio [OR], 1.107; 95% CI, 0.552 to 2.219; P = .775), the number of patients who returned to sports (OR, 0.766; 95% CI, 0.438 to 1.341; P = .351) and returned to work (OR, 0.706; 95% CI, 0.397 to 1.253; P = .234), the time to return to work (MD, -2.802 days; 95% CI, -6.525 to 0.921 days; P = .140), or the heel-rise work LSI (MD, -0.135; 95% CI, -6.243 to 5.973; P = .965). CONCLUSION: No significant differences were found between early controlled motion and weightbearing compared with immobilization and late weightbearing regarding the ATRS, the rerupture rate, return to sports activity and work, and the heel-rise work in nonoperatively treated patients with acute ATR.

Analysis of the main soft tissue stress associated with flexible flatfoot deformity: a finite element study.

A better understanding of soft tissue stress and its role in supporting the medial longitudinal arch in flexible flatfoot could help to guide the clinical treatment. In this study, a 3-Dimensional finite element (FE) foot model was reconstructed to measure the stress of the soft tissue, and its variation in different scenarios related to flexible flatfoot. All bones, cartilages, ligaments and related tendons around the ankle, and fat pad were included in the finite element model. The equivalent stress on the articular surface of the joints in the medial longitudinal arch and the maximum principal stress of the ligaments around the ankle were obtained. The results show that the plantar fascia (PF) is the main tissue in maintaining the medial longitudinal arch. The equivalent stress of all the joints in the medial longitudinal arch increases when the PF attenuation and the talonavicular joint increases, while other joints decreases when all the three tissue attenuation. Moreover, the maximum principal stress variation of calcaneofibular ligament is largest when the PF attenuation and the tibionavicular ligament and posterior tibiotalar ligament are largest when the posterior tibial tendon (PTT) attenuation. The maximum principal stress variation of tibionavicular ligament and posterior tibiotalar ligament are even larger when all the three tissue attenuation. These findings support that the PF is the main factor in maintaining the medial longitudinal arch. The medial longitudinal arch collapse mainly affects the talonavicular joint and the calcaneofibular ligament, the tibionavicular ligament and the posterior tibiotalar ligament. This approach could help to improve the understanding of adult-acquired flatfoot deformity (AAFD).

Effect of soft inflatable orthosis on the medial longitudinal arch in patients with flexible flatfoot deformity.

BACKGROUND: Orthoses can stabilize the foot and restore the medial longitudinal arch for symptomatic flexible flatfoot. However, the effectiveness of orthoses remains controversial. The purpose of this study was to evaluate effectiveness of a customized soft inflatable orthosis on the medial longitudinal arch of flexible flatfoot patients under load. METHODS: We obtained CT scans of the feet of 14 healthy volunteers and 14 patients with flexible flatfoot under non- and simulated weight-bearing conditions. Then CT scans under the same conditions were taken for patients with flexible flatfoot equipped with soft inflatable orthosis. Three-dimensional models of the medial longitudinal arch and hindfoot were constructed from CT images. The three-dimensional mobility of the medial longitudinal arch joints under load was compared between patients with flexible flatfoot equipped with soft inflatable orthosis or not. FINDINGS: From non- to simulated weight-bearing condition, the eversion and dorsiflexion of the talocalcaneal joint, the eversion of the talonavicular joint, the abduction and dorsiflexion of the cuneonavicular joint, and the dorsiflexion of the first tarsometatarsal joint were significantly larger in patients with flexible flatfoot than healthy volunteers. The customized soft inflatable orthosis could reduce the eversion of the talonavicular joint and the eversion and dorsiflexion of the talocalcaneal joint. INTERPRETATION: The soft inflatable orthosis is effective to improve medial longitudinal arch height and reduce excessive mobility of joints for flexible flatfoot deformity. The results of this study could provide evidence for the optimal orthosis design to treat flexible flatfoot in the future.

Magnetically Actuated Manipulation and Its Applications for Cartilage Defects: Characteristics and Advanced Therapeutic Strategies.

For the fact that articular cartilage is a highly organized and avascular tissue, cartilage defects are limited to spontaneously heal, which would subsequently progress to osteoarthritis. Many methods have been developed to enhance the ability for cartilage regeneration, among which magnetically actuated manipulation has attracted interests due to its biocompatibility and non-invasive manipulation. Magnetically actuated manipulation that can be achieved by introducing magnetic nanoparticles and magnetic field. This review summarizes the cutting-edge research on the chondrogenic enhancements via magnetically actuated manipulation, including cell labeling, cell targeting, cell assembly, magnetic seeding and tissue engineering strategies.

Proximal versus distal adductor canal blocks for total knee arthroplasty: A protocol for randomized controlled trial.

BACKGROUND: Currently, there remains a paucity of literature about the efficiency of proximal adductor canal block (PACB) versus distal adductor canal block (DACB) for pain management after total knee arthroplasty (TKA). The purpose of this study is to perform a randomized controlled trial to compare the efficiency of PACB versus DACB for early postoperative pain treatment after TKA. METHODS: This study is a 2-arm, parallel-group, randomized controlled trial that is conducted at a single university hospital in China. Subjects presenting for unilateral TKA are randomized in a 1:1 ratio to either a PACB or DACB group. The primary outcome of this noninferiority study is opioid consumption within the first 24 hours following surgery. Secondary outcomes include quadriceps strength, pain scores, distance ambulated, and patient satisfaction. Continuous variables are compared using Student t test. RESULTS: This clinical trial is expected to provide evidence of whether the PACB and DACB provide similar analgesia after TKA. TRIAL REGISTRATION: This study protocol was registered in Research Registry (researchregistry5440).

Exosomes in osteoarthritis and cartilage injury: advanced development and potential therapeutic strategies.

Articular cartilage injury is a common clinical problem, which can lead to joint dysfunction, significant pain, and secondary osteoarthritis (OA) in which major surgical procedures are mandatory for treatment. Exosomes, as endosome-derived membrane-bound vesicles, participating in intercellular communications in both physiological and pathophysiological conditions, have been attached great importance in many fields. Recently, the significance of exosomes in the development of OA has been gradually concerned, while the therapeutic value of exosomes in cartilage repair and OA treatment has also been gradually revealed. The functional difference of different types and derivations of exosomes are determined by their specific contents. Herein, we provide comprehensive understanding on exosome and OA, including how exosomes participating in OA, the therapeutic value of exosomes for cartilage injury/OA, and related bioengineering strategies for future therapeutic design.

The dual character of exosomes in osteoarthritis: Antagonists and therapeutic agents.

Exosomes have gained increasing attention as they participate in cell cross-talk in pathological environments and are functional paracrine factors of therapeutic stem cells. Osteoarthritis (OA) is a common age-related degenerative joint disease, leading to a debilitating lifestyle for sufferers. However, currently no drugs on the market promote cartilage repair, and the patients usually have to undergo arthroplasty in the late stage of OA. Although significant progress has been made in the development of stem cells for the treatment of OA and cartilage injury, problems like immune rejection remain. Recently, increasing evidence has demonstrated that exosomes from the joint microenvironment ("negative" exosomes) could play vital and complicated roles in the progression of OA. Moreover, exosomes from therapeutic cells ("therapeutic" exosomes) have also shown enormous potential for OA therapy/cartilage repair. Here, we first discuss the definition and biological background of exosomes. Then, we critically examine the roles of the "negative" exosomes in OA-affected joint. Then, we will cover the potential of the "therapeutic" exosomes for OA therapy/cartilage repair. Next, the recent progress of tissue engineering with exosomes, especially for OA therapy/cartilage repair, will also be discussed. Finally, the limitations and opportunities of exosome-based OA therapy will be outlined. STATEMENT OF SIGNIFICANCE: As natural extracellular vesicles, exosomes participate in the intercellular communication. On the basis of biological characteristics of exosomes, exosomes have their two sides for osteoarthritis (OA). On the one hand, exosomes in the OA microenvironment are involved in pathology of OA. On the other hand, exosomes from therapeutic cells have the potential as advanced strategies for OA therapy. In addition, the development of tissue engineering technology is beneficial to the exosome-based OA therapy. According to the latest research status, exosomes are of great significance and interest for the personalized and precision treatment of OA in the future, despite the limitations and challenges.

Monocyte chemoattractant protein­1 promotes the proliferation, migration and differentiation potential of fibroblast­like synoviocytes via the PI3K/P38 cellular signaling pathway.

Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammation of the joints and joint destruction. Monocyte chemoattractant protein 1 (MCP­1) is highly expressed in the joints of patients suffering from RA. The present study aimed to evaluate the effects of MCP­1 on the phenotype of fibroblast­like synoviocytes (FLSs) and their differentiation potential towards vascular endothelial cells. The expression of MCP­1 in collagen­induced arthritis (CIA) rats was investigated by PCR, ELISA and immunohistology. Cell proliferation induced by MCP­1 was measured using a Cell Counting Kit­8 (CCK­8) and 5­Bromo­2­deoxyuridine ELISA assay. In addition, the effects of MCP­1 on the migration of FLSs was examined using a Transwell assay. Activation of PI3K and P38 were investigated by western blotting following MCP­1 treatment. The vascular endothelial cell markers, tumor necrosis factor alpha (TNF­α) and interleukin­1 beta (IL­ß), were also examined by western blotting. LY294002 [PI3K inhibitor, (LY)] and SB203580 [P38 inhibitor, (SB)] were used to examine the proliferative and pro­differentiation effect of PI3K and P38. The present findings showed that the expression level of MCP­1 in the synovium of CIA rats was significantly higher compared with controls. The present in vitro study suggested that MCP­1 increased the FLSs cell numbers with a maximal effect at 200 ng/ml, and induced the maximal phosphorylation of PI3K at 15 min and P38 at 30 min. In addition, MCP­1 stimulation significantly increased the migration of FLSs. Furthermore, MCP­1­induced the expression of vascular endothelial growth factor and CD31 in FLSs. Suppression of PI3K and P38 was found to reduce MCP­1 induced FLSs proliferation and migration, and decreased the expression levels of angiogenesis markers increased following MCP­1 treatment. MCP­1 was also found to increase the expression levels of both TNF­α and IL­ß. Therefore, MCP­1 could promote the proliferation and migration of FLSs, and was found to increase the expression levels of various angiogenesis markers via PI3K/P38, suggesting a role for this pathway in synovium hyperplasia in RA.

En Bloc lumpectomy of T12 vertebra for progressive hepatocellular carcinoma metastases following liver transplantation: A case report.

RATIONALE: Liver transplantation (LT) is the preferred surgical option for the treatment of early hepatocellular carcinoma (HCC). In contrast, surgical treatment of progressive HCC metastasized to the spine following LT constitutes a considerable challenge. Here, we report the first case of progressive HCC metastasized to the T12 vertebra after local radiotherapy, treated successfully with en bloc lumpectomy following LT for HCC. PATIENT CONCERNS: A 40-year-old man who had undergone LT for the treatment of HCC 2 months prior presented to our clinic with symptoms of progressive back pain. Magnetic resonance imagining (MRI) and positron emission tomography (PET) examinations showed a solitary metastasis at T12 without recurrence in the liver or metastasis to other organs. DIAGNOSES: The patient was diagnosed with HCC metastasized to the T12 vertebra after liver transplantation. INTERVENTIONS: Local radiation therapy of the T12 vertebra was performed; however, the lesion continued to grow one month after irradiation. Accordingly, the patient was treated with en bloc lumpectomy of the T12 vertebra. After surgery, the patient reported significant pain relief. At 11 months post-surgery, a C4 metastasis with spinal cord compression was revealed by MRI. Multiple grafted liver metastases were also detected by ultrasound along with several lung metastases, which were discovered by X-ray. The patient was treated with a pedicle screw system and a mesh cage filled with frozen autografts for C4 metastasis. OUTCOMES: The patient died 15 months after liver transplantation due to recurrence in the liver and metastasis to the lung. LESSONS: En bloc lumpectomy may be a viable therapeutic option for patients with progressive solitary spinal metastases after LT refractory to radiotherapy. Use of immunosuppressive therapy after LT may significantly inhibit immune function, making patients more susceptible to HCC recurrence and bone metastasis.

Acute and chronic traumatic diaphragmatic hernia: 10 years' experience.

Controversy persists regarding many aspects of traumatic diaphragmatic hernia (TDH). We aimed to understand why some traumatic diaphragmatic injuries present with chronic hernia and to evaluate diagnosis and treatment options. Fifty acute and 19 chronic TDH patients were diagnosed and treated at our institution over a 10-year period. Clinical data from these two groups were analyzed statistically and compared. Chronic TDH patients had a significantly lower Injury Severity Score than acute TDH patients (10.26 ± 2.68 vs. 26.92 ± 4.79, P < 0.001). The most common surgical approach for acute and chronic TDH was thoracotomy and laparotomy, respectively. The length of the diaphragmatic rupture was significantly shorter in chronic TDH patients than acute TDH patients (6.00 ± 1.94 cm vs. 10.71 ± 3.30 cm, P < 0.001). The mean length of hospital stay was significantly longer for acute TDH patients than chronic TDH patients (41.18 ± 31.02 days vs. 16.65 ± 9.61 days, P = 0.002). In conclusion, milder trauma and a smaller diaphragmatic rupture were associated with delayed diagnosis. A thoraco-abdominal computed tomography scan is needed for patients with periphrenic injuries to avoid delayed diagnosis of TDH. Improved awareness and understanding of diaphragmatic injuries will increase the rate of early diagnosis and improve prognosis.

Surgical treatment of progressive cauda equina compression caused by spontaneous spinal subdural hematoma: A case report.

RATIONALE: Spontaneous spinal subdural hematoma (SSDH) without an underlying pathology is a very rare condition. The treatment protocol for SSDH is early diagnosis and treatment before irreversible damage to neural tissue. However, there is no agreement on the etiopathogenesis, as well as the need for surgery to treat spontaneous SSDH. Here, we report a rare case of spontaneous SSDH with progressive deterioration and symptoms of cauda equina syndrome after ineffective conservative treatment. PATIENT'S CONCERN: A 38-year-old male patient presented with sudden lower back and bilateral leg pain. DIAGNOSIS: A magnetic resonance imaging (MRI) scan on the third day after the onset of symptoms revealed a subdural hematoma from L1 to S1, presenting as hyperintensities on T1 weighted sequences and hypointensities to isointensities on T2 weighted sequences. INTERVENTION: Laminectomy and subdural evacuation were performed immediately. OUTCOMES: An abnormal ligamentum flavum was observed intraoperatively. A histological examination revealed extravasation of blood in the degenerated ligamentum flavum. Postoperatively, the lower limb pain improved immediately. At the 6-month follow-up, the pain and numbness of the lower limb disappeared, and the muscle strength of both legs recovered completely with normal gait. LESSONS: Spontaneous SSDH with ligamentum flavum hematoma was caused by a sudden increase of intravenous pressure, resulting from a marked surge in the intra-abdominal or intrathoracic pressure. Consecutive MRI scans provided valuable information, leading to a diagnosis of spontaneous SSDH. The treatment protocol for spontaneous SSDH should be determined based on the location and stage of the hematoma, as well as the subject's neurological status.

Neuroprotective effects of rapamycin on spinal cord injury in rats by increasing autophagy and Akt signaling.

Rapamycin treatment has been shown to increase autophagy activity and activate Akt phosphorylation, suppressing apoptosis in several models of ischemia reperfusion injury. However, little has been studied on the neuroprotective effects on spinal cord injury by activating Akt phosphorylation. We hypothesized that both effects of rapamycin, the increased autophagy activity and Akt signaling, would contribute to its neuroprotective properties. In this study, a compressive spinal cord injury model of rat was created by an aneurysm clip with a 30 g closing force. Rat models were intraperitoneally injected with rapamycin 1 mg/kg, followed by autophagy inhibitor 3-methyladenine 2.5 mg/kg and Akt inhibitor IV 1 µg/kg. Western blot assay, immunofluorescence staining and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay were used to observe the expression of neuronal autophagy molecule Beclin 1, apoptosis-related molecules Bcl-2, Bax, cytochrome c, caspase-3 and Akt signaling. Our results demonstrated that rapamycin inhibited the expression of mTOR in injured spinal cord tissue and up-regulated the expression of Beclin 1 and phosphorylated-Akt. Rapamycin prevented the decrease of bcl-2 expression in injured spinal cord tissue, reduced Bax, cytochrome c and caspase-3 expression levels and reduced the number of apoptotic neurons in injured spinal cord tissue 24 hours after spinal cord injury. 3-Methyladenine and Akt inhibitor IV intervention suppressed the expression of Beclin-1 and phosphorylated-Akt in injured spinal cord tissue and reduced the protective effect of rapamycin on apoptotic neurons. The above results indicate that the neuroprotective effect of rapamycin on spinal cord injury rats can be achieved by activating autophagy and the Akt signaling pathway.

Correlation between three-dimensional medial longitudinal arch joint complex mobility and medial arch angle in stage II posterior tibial tendon dysfunction.

BACKGROUND: The purpose of this study was to evaluate correlation between three-dimensional medial longitudinal arch joint complex mobility and medial arch angle in stage II posterior tibial tendon dysfunction flatfoot under loading. METHODS: CT scans of 15 healthy feet and 15 feet with stage II posterior tibial tendon dysfunction flatfoot were taken both in non- and simulated weight-bearing condition. The CT images of the hindfoot and medial longitudinal arch bones were reconstructed into three-dimensional models with Mimics and Geomagic reverse engineering software. The three-dimensional complex mobility of each joint in the medial longitudinal arch and their correlation with the medial arch angle change were calculated. RESULTS: From non- to simulated weight-bearing condition, the medial arch angle change and the medial longitudinal arch joints mobility were significant larger in stage II posterior tibial tendon dysfunction flatfoot (p<0.05). The eversion of the talocalcaneal joint, the proximal translation of the calcaneus relative to the talus, the dorsiflexion of the talonavicular joint, the dorsiflexion and abduction of the medial cuneonavicular joint, and the lateral translation of the medial cuneiform relative to the navicular, and the dorsiflexion of the first tarsometatarsal joint were all significantly correlated to the medial arch angle change in stage II posterior tibial tendon dysfunction flatfoot (all r>0.5, p<0.05). CONCLUSIONS: There is increased mobility in the medial longitudinal arch joints in stage II posterior tibial tendon dysfunction flatfoot and the medial arch angle change under loading causes displacement not only at hindfoot joints but also involve midfoot and forefoot joint.

P65-mediated miR-590 inhibition modulates the chemoresistance of osteosarcoma to doxorubicin through targeting wild-type p53-induced phosphatase 1.

Osteosarcoma (OS) is a primary malignant bone tumor with high morbidity. Developing new therapeutic approaches with neoadjuvant is of great interest in OS treatment. Reportedly, ataxia telangiectasia mutated (ATM)/ataxia telangiectasia and radiation resistance gene 3 related (ATR)-p53 signaling is considered as a critical DNA damage signaling pathway sensitizing cancer cells to chemotherapies; while wild-type p53-induced phosphatase 1 (WIP1), an oncogene overexpressed in diverse cancers, has been regarded as a critical inhibitor in the ATM/ATR-p53 DNA damage signaling pathway. Herein, the expression of WIP1 in OS tissues and cell lines was examined; to investigate the mechanism of WIP1 abnormal upregulation, online tools were used to predict the upstream regulatory microRNAs (miRNAs) targeting WIP1. Among the candidate miRNAs, the expression and detailed function of miR-590 were validated. Through binding to the 3'-untranslated region of WIP1, miR-590 inhibited WIP1 expression and, therefore, enhanced the effect of Dox on OS cell proliferation and apoptosis through downstream ATM-p53 signaling. Moreover, RELA could bind to the promoter region of miR-590 to inhibit its expression, thereby affecting downstream WIP1 and ATM-p53 signaling. The expression of p65 was upregulated in OS tissues, indicating that the effect of p65 inhibition on cell viability, apoptosis, and related mechanisms could be partially restored by miR-590 inhibition. Taken together, these results showed that p65-mediated miR-590/WIP1/ATM-p53 modulation might be a novel target to enhance the cellular effect of Dox on OS cell lines.

Autograft or Allograft? Irradiated or Not? A Contrast Between Autograft and Allograft in Anterior Cruciate Ligament Reconstruction: A Meta-analysis.

PURPOSE: To compare the clinical outcomes and adverse events associated with irradiated and nonirradiated allografts in anterior cruciate ligament (ACL) reconstruction. METHODS: PubMed, Web of Science, and EMBASE were searched for randomized controlled trials from January 1990 to March 2018 to compare autograft with allograft in ACL reconstruction. Both objective and subjective outcomes of the function and adverse events were meta-analyzed. Two comparisons were summarized: (1) autograft and nonirradiated allograft and (2) autograft and irradiated allograft. The bias risk was based on the Cochrane Handbook for Systematic Reviews of Interventions. The overall risk ratio or weighted mean difference was calculated using a fixed- or random-effects model. Heterogeneity between studies was evaluated by the Q and the I2 statistics. RESULTS: Eleven trials were included in this review for meta-analysis. A total of 1,172 patients were involved (465 autograft and 461 nonirradiated allograft; 141 autograft and 138 irradiated allograft patients). The average follow-up varied from 2 to >10 years. The mean patient age varied from 22 to 32.8 years. The total failure rate was 2.5%. Our analyses demonstrated better clinical outcomes in autograft than irradiated allograft, which could be observed clearly through the International Knee Documentation Committee score (3.84; 95% confidence interval [CI], 1.93-5.76; P < .0001; I2 = 0%), Lysholm score (2.94; 95% CI, 0.66-5.22; P = .01; I2 = 0%), and Tegner score (0.14; 95% CI, -0.08 to 0.36; P = .22; I2 = 0%) with fewer adverse events 0.20 (95% CI, 0.11-0.39; P < .00001; I2 = 0%). There were no significant differences in autograft and nonirradiated allograft groups (P = .47, P = .27, P = .24, and P = .24, respectively). CONCLUSIONS: Autograft offered greater advantages in functional outcomes and adverse events than irradiated allograft in ACL reconstruction; however, there were no significant differences between autograft and nonirradiated allograft in ACL reconstruction. LEVEL OF EVIDENCE: Level II, meta-analysis of Level I and Level II studies.

Modic Changes in the Lumbar Spine are Common Aging-related Degenerative Findings that Parallel With Disk Degeneration.

STUDY DESIGN: This is a cross-sectional study. OBJECTIVE: To determine the prevalence and distribution patterns of Modic changes (MCs) in the lumbar spine and their associations with disk degeneration in mainland Chinese using a sample of general population. SUMMARY OF BACKGROUND DATA: Previous studies reported that the prevalence of MCs in Hong Kong Chinese was much lower than in other populations. Moreover, their associations with disk degeneration need further study. MATERIALS AND METHODS: The study sample consisted of 442 subjects (53.6±14.9 y; range, 20-88 y) randomly selected from a typical Chinese community. Lumbar spines were imaged using a 3.0 T magnetic resonance scanner. Eleven endplates (L1-S1) in the lumbar spine were evaluated for the presence of MCs, type, location, and size to determine MCs prevalence and distribution patterns. Disk degeneration was graded using a Pfirrmann scale. RESULTS: MCs were present in 209 (47.3%) subjects and 593 (12.2%) endplates. Among these endplates, 84.1% (499) were type II, 9.1% (54) were type I, and 6.4% (38) were mixed MCs. Approximately 2/3 MCs were present in the lower lumbar spine and 44.9% of MCs were at the L5/S1 disk level. Most MCs (73.9%) involved both endplates of a disk. Greater age [odds ratio (OR)=2.44 for each 10-year increase, P<0.001] and body mass index (OR=1.07, P=0.016) were associated with the presence of MCs, as was adjacent disk degeneration (OR=6.00, P<0.001), controlling for age and other covariates. Greater age, body mass index, and adjacent disk degeneration were also associated with greater MCs size. CONCLUSIONS: MCs are common in mainland Chinese, with type II predominating. MCs mainly present in the lower lumbar region and tend to occur in pairs. MCs were strongly associated with age and disk degeneration, suggesting MCs may be aging-related degenerative findings that parallel disk degeneration. LEVEL OF EVIDENCE: Level II.

Injection of synthetic mesenchymal stem cell mitigates osteoporosis in rats after ovariectomy.

Osteoporosis is a severe skeletal disorder. Patients have a low bone mineral density and bone structural deterioration. Mounting lines of evidence suggest that inappropriate apoptosis of osteoblasts/osteocytes leads to maladaptive bone remodelling in osteoporosis. It has been suggested that transplantation of stem cells, including mesenchymal stem cells, may alter the trajectory of bone remoulding and mitigate osteoporosis in animal models. However, stem cells needed to be carefully stored and characterized before usage. In addition, there is great batch-to-batch variation in stem cell production. Here, we fabricated therapeutic polymer microparticles from the secretome and membranes of mesenchymal stem cells (MSCs). These synthetic MSCs contain growth factors secreted by MSCs. In addition, these particles display MSC surface molecules. In vitro, co-culture with synthetic MSCs increases the viability of osteoblast cells. In a rat model of ovariectomy-induced osteoporosis, injection of synthetic MSCs mitigated osteoporosis by reducing cell apoptosis and systemic inflammation, but increasing osteoblast numbers. Synthetic MSC offers a promising therapy to manage osteoporosis.

The Effect of Cartilage Fragments on Femoral Tunnel Widening After Anterior Cruciate Ligament Reconstruction: A Prospective Randomized Controlled Study.

PURPOSE: To analyze the effect of cartilage fragments on tunnel widening and tendon-bone integration at 2 years' follow-up after anterior cruciate ligament reconstruction (ACLR). METHODS: A prospective randomized controlled study was performed in 116 patients who underwent ACLR with autologous hamstring tendons augmented with cartilage fragments (study group, n = 56) or without any augmentation (control group, n = 60). All patients were followed up for 25.6 months (range, 24-28 months), and the International Knee Documentation Committee score, Lysholm score, and visual analog scale score were determined. Computed tomography scans of all patients were obtained 2 years after surgery to evaluate the diameter of the femoral tunnel and thereby assess the amount of tunnel widening. Magnetic resonance imaging evaluation was performed 2 years postoperatively to evaluate the status of the graft in the femoral tunnel. In addition, 5 patients underwent biopsy of the tendon-bone interface at 24 months postoperatively with histologic assessment and transmission electron microscopy. RESULTS: A total of 107 patients completed the follow-up. There were no significant differences between the 2 groups in terms of International Knee Documentation Committee score (P = .07), Lysholm score (P = .10), and visual analog scale score (P = .57) at 24 months' follow-up. The femoral tunnel diameter and the tunnel widening percentage in the study group were significantly smaller than those in the control group (P < .001). The signal-noise quotient value of the graft in the femoral tunnel was 10.4 ± 7.0 in the study group, which was significantly lower than that in the control group (19.5 ± 9.2, P < .001). Histologic studies of the tendon-bone interface showed that there were more bone formations containing chondroid cells with aligned connective tissue in the study group compared with the control group; in addition, the diameter of the collagen fibrils in the study group was considerably thicker than that in the control group (P < .05). CONCLUSIONS: The use of cartilage fragments was effective in preventing femoral tunnel widening and seemed to promote the tendon-bone integration process after ACLR. LEVEL OF EVIDENCE: Level II, prospective randomized controlled study.

Arthroscopic Rotator Cuff Repair With Graft Augmentation of 3-Dimensional Biological Collagen for Moderate to Large Tears: A Randomized Controlled Study.

BACKGROUND: Due to the highly organized tissue and avascular nature of the rotator cuff, rotator cuff tears have limited ability to heal after the tendon is reinserted directly on the greater tubercle of the humerus. Consequently, retears are among the most common complications after rotator cuff repair. Augmentation of rotator cuff repairs with patches has been an active area of research in recent years to reduce retear rate. HYPOTHESIS: Graft augmentation with 3D collagen could prevent retears of the repaired tendon and improve tendon-bone healing in moderate to large rotator cuff tears. STUDY DESIGN: Randomized controlled study; Level of evidence, 2. METHODS: A prospective, randomized controlled study was performed in a consecutive series of 112 patients age 50 to 85 years who underwent rotator cuff repair with the suture-bridge technique (58 patients, control group) or the suture-bridge technique augmented with 3-dimensional (3D) collagen (54 patients, study group). All patients were followed for 28.2 months (range, 24-36 months). Visual analog scale score for pain, University of California Los Angeles (UCLA) shoulder score, and Constant score were determined. Magnetic resonance imaging was performed pre- and postoperatively (at a minimum of 24 months) to evaluate the integrity of the rotator cuff and the retear rate of the repaired tendon. Three patients in each group had biopsies at nearly 24 months after surgery with histological assessment and transmission electron microscopy. RESULTS: A total of 104 patients completed the final follow-up. At the 12-month follow-up, the UCLA shoulder score was 28.1 ± 1.9 in the study group, which was significantly better than that in the control group (26.9 ± 2.1, P = .002). The Constant score was also significantly better in the study group (87.1 ± 3.2) than in the control group (84.9 ± 4.2, P = .003). However, at the final follow-up, no significant differences were found in the UCLA shoulder scores (29.4 ± 1.9 in the control group and 30.0 ± 1.6 in the study group, P = .052) or Constant scores (89.9 ± 3.2 in the control group and 90.8 ± 3.5 in the study group, P = .18). In terms of structural integrity, more patients in the study group had a favorable type I retear grade (18/51) than in the control group (10/53) ( P = .06). The postoperative retear rate was 34.0% in the control group and 13.7% in the study group, thus indicating a significantly lower retear rate in the study group ( P = .02). Biopsy specimens of the tendon-bone interface in 6 patients revealed more bone formation and more aligned fibers with larger diameters in the study group than in the control group. No intraoperative or postoperative complications were noted in either group. CONCLUSION: 3D collagen augmentation could provide effective treatment of moderate to large rotator cuff tears, providing substantial functional improvement, and could reduce the retear rate. This technique could also promote new tendon-bone formation, thus exerting a prominent effect on tendon-bone healing.

Is Platelet-rich Plasma Injection Effective for Chronic Achilles Tendinopathy? A Meta-analysis.

BACKGROUND: Chronic Achilles tendinopathy is common in the general population, and platelet-rich plasma (PRP) is seeing increased use to treat this problem. However, studies disagree as to whether PRP confers a beneficial effect for chronic Achilles tendinopathy, and no one to our knowledge has pooled the available randomized trials in a formal meta-analysis to try to reconcile those differences. QUESTIONS/PURPOSES: In the setting of a systematic review and meta-analysis of randomized controlled trials (RCTs), we asked: Does PRP plus eccentric strength training result in (1) greater improvements in Victorian Institute of Sports Assessment-Achilles (VISA-A) scores; (2) differences in tendon thickness; or (3) differences in color Doppler activity compared with placebo (saline) injections plus eccentric strength training in patients with chronic Achilles tendinopathy? METHODS: A search of peer-reviewed articles was conducted to identify all RCTs using PRP injection with eccentric training for chronic Achilles tendinopathy in the electronic databases of PubMed, Web of Science (SCI-E/SSCI/A&HCI), and EMBASE from January 1981 to August 2017. Results were limited to human RCTs and published in all languages. Two reviewers assessed study quality using the Cochrane Collaboration risk-of-bias tool. All the included studies had low risk of bias. The primary endpoint was improvement in the VISA-A score, which ranges from 0 to 100 points, with higher scores representing increased activity and less pain; we considered the minimum clinically important difference on the VISA-A to be 12 points. Secondary outcomes were tendon thickness change (with a thicker tendon representing more severe disease), color Doppler activity (with more activity representing a poorer result), and other functional measures (such as pain and return to sports activity). Four RCTs involving 170 participants were eligible and included 85 participants treated with PRP injection and eccentric training and 85 treated with saline injection and eccentric training. The patients in both PRP and placebo (saline) groups seemed comparable at baseline. We assessed for publication bias using a funnel plot and saw no evidence of publication bias. Based on previous studies, we had 80% power to detect a 12-point difference on the VISA-A score with the available sample size in each group. RESULTS: With the numbers available, there was no difference between the PRP and saline groups regarding the primary outcome (VISA-A score: mean difference [MD], 5.3; 95% confidence interval [CI], -0.7 to 11.3; p = 0.085). Likewise, we found no difference between the PRP and saline groups in terms of our secondary outcomes of tendon thickness change (MD, 0.2 mm; 95% CI, 0.6-1.0 mm; p = 0.663) and color Doppler activity (MD, 0.1; 95% CI, -0.7 to 0.4; p = 0.695). CONCLUSIONS: PRP injection with eccentric training did not improve VISA-A scores, reduce tendon thickness, or reduce color Doppler activity in patients with chronic Achilles tendinopathy compared with saline injection. Larger randomized trials are needed to confirm these results, but until or unless a clear benefit has been demonstrated in favor of the new treatment, we cannot recommend it for general use. LEVEL OF EVIDENCE: Level I, therapeutic study.