Arthroscopic Bankart repair versus conservative treatment for first-time traumatic anterior shoulder dislocation: a systematic review and meta-analysis.

BACKGROUND: Shoulder is vulnerable to dislocation owing to its anatomical structure and the increasing popularity of contact sports in young population. The management of first-time anterior shoulder dislocation in this group is still controversial and the prognosis are varied. This review aimed to compare the results of arthroscopic Bankart repair and conservative management for first-time traumatic anterior shoulder dislocation in young active patients. METHODS: Databases were searched till November 2021, and comparative studies between arthroscopic Bankart repair and conservative management for first-time traumatic anterior shoulder dislocation in young population were selected. Methodological quality of the studies was assessed according to the Cochrane Back Review Group 12-item scale. Outcome measures included recurrence of instability, return to play, subsequent instability surgery, and shoulder functional scores. RESULTS: The search returned 12 eligible trials with 786 participants. All the trials were of prospective design. After arthroscopic Bankart repair, patients experienced significantly less re-dislocation (7.5% vs. 53.0%, p < 0.00001, I2 = 0%), subluxation (3.1% vs. 24.2%, p < 0.0001, I2 = 0%), positive apprehension test (7.3% vs. 25.8%, p = 0.002, I2 = 11%), and subsequent surgical treatment for instability (5.6% vs. 37.8%, p < 0.00001, I2 = 0%) when compared with those underwent conservative management. And more patients returned to play (83.5% vs. 66.0%, p = 0.03, I2 = 81%) after arthroscopic Bankart repair. Outcomes regarding the functional scores did not reach a significant difference between the two cohorts. CONCLUSIONS: Arthroscopic Bankart repair showed superiority over conservative management in terms of recurrence, return to play, and subsequent instability surgery during the follow-up in young active patients that encountered first episode of dislocation. As long-term prognosis is comparable, an immediate surgical stabilization might not be suitable for everyone.

3D-printed hydrogel particles containing PRP laden with TDSCs promote tendon repair in a rat model of tendinopathy.

Long-term chronic inflammation after Achilles tendon injury is critical for tendinopathy. Platelet-rich plasma (PRP) injection, which is a common method for treating tendinopathy, has positive effects on tendon repair. In addition, tendon-derived stem cells (TDSCs), which are stem cells located in tendons, play a major role in maintaining tissue homeostasis and postinjury repair. In this study, injectable gelatine methacryloyl (GelMA) microparticles containing PRP laden with TDSCs (PRP-TDSC-GM) were prepared by a projection-based 3D bioprinting technique. Our results showed that PRP-TDSC-GM could promote tendon differentiation in TDSCs and reduce the inflammatory response by downregulating the PI3K-AKT pathway, thus promoting the structural and functional repair of tendons in vivo.

GSTP1-mediated S-glutathionylation of Pik3r1 is a redox hub that inhibits osteoclastogenesis through regulating autophagic flux.

Glutathione S-transferase P1(GSTP1) is known for its transferase and detoxification activity. Based on disease-phenotype genetic associations, we found that GSTP1 might be associated with bone mineral density through Mendelian randomization analysis. Therefore, this study was performed both in vitro cellular and in vivo mouse model to determine how GSTP1 affects bone homeostasis. In our research, GSTP1 was revealed to upregulate the S-glutathionylation level of Pik3r1 through Cys498 and Cys670, thereby decreasing its phosphorylation, further controlling the alteration of autophagic flux via the Pik3r1-AKT-mTOR axis, and lastly altering osteoclast formation in vitro. In addition, knockdown and overexpression of GSTP1 in vivo also altered bone loss outcomes in the OVX mice model. In general, this study identified a new mechanism by which GSTP1 regulates osteoclastogenesis, and it is evident that the cell fate of osteoclasts is controlled by GSTP1-mediated S-glutathionylation via a redox-autophagy cascade.

Therapeutic potential and mechanisms of mesenchymal stem cell-derived exosomes as bioactive materials in tendon-bone healing.

Tendon-bone insertion (TBI) injuries, such as anterior cruciate ligament injury and rotator cuff injury, are the most common soft tissue injuries. In most situations, surgical tendon/ligament reconstruction is necessary for treating such injuries. However, a significant number of cases failed because healing of the enthesis occurs through scar tissue formation rather than the regeneration of transitional tissue. In recent years, the therapeutic potential of mesenchymal stem cells (MSCs) has been well documented in animal and clinical studies, such as chronic paraplegia, non-ischemic heart failure, and osteoarthritis of the knee. MSCs are multipotent stem cells, which have self-renewability and the ability to differentiate into a wide variety of cells such as chondrocytes, osteoblasts, and adipocytes. Numerous studies have suggested that MSCs could promote angiogenesis and cell proliferation, reduce inflammation, and produce a large number of bioactive molecules involved in the repair. These effects are likely mediated by the paracrine mechanisms of MSCs, particularly through the release of exosomes. Exosomes, nano-sized extracellular vesicles (EVs) with a lipid bilayer and a membrane structure, are naturally released by various cell types. They play an essential role in intercellular communication by transferring bioactive lipids, proteins, and nucleic acids, such as mRNAs and miRNAs, between cells to influence the physiological and pathological processes of recipient cells. Exosomes have been shown to facilitate tissue repair and regeneration. Herein, we discuss the prospective applications of MSC-derived exosomes in TBI injuries. We also review the roles of MSC-EVs and the underlying mechanisms of their effects on promoting tendon-bone healing. At last, we discuss the present challenges and future research directions.

Synergistic Effect of Reverse Drilling and Bone Dust on Femoral Tendon-Bone Healing After Anterior Cruciate Ligament Reconstruction in a Rabbit Model.

BACKGROUND: Anterior cruciate ligament (ACL) injuries and bone tunnel enlargement (BTE) after ACL reconstruction (ACLR) remain frequent issues. Bone dust (BD) produced by tunnel preparation with osteogenic ability and reverse drilling (RD), an easy compaction technique, make it accessible to enhance tendon-bone healing in the clinic. HYPOTHESIS: RD and BD synergistically promote tendon-bone healing by improving peritunnel bone and preventing BTE in femurs. STUDY DESIGN: Controlled laboratory study. METHODS: In total, 96 New Zealand White rabbits underwent ACLR. The semitendinosus tendon was freed before medial parapatellar arthrotomy. After the native ACL was transected, bone tunnels were prepared through the footprint of the native ACL. All animals were randomly assigned to 1 of 4 groups according to different tunnel preparation methods: group 1 (irrigation after extraction drilling [ED]; control group), group 2 (irrigation after RD), group 3 (no irrigation after ED), and group 4 (no irrigation after RD). BD was harvested by irrigating tunnels and was characterized by morphology and size. The specimens underwent microarchitectural, histological, and biomechanical evaluations at 4, 8, and 12 weeks postoperatively. RESULTS: Micro-computed tomography demonstrated more peritunnel bone and less BTE in the femurs of group 4 compared with the other groups. Histologically, BD possessed osteogenic activity in bone tunnels postoperatively. Meanwhile, group 4 regenerated a higher amount of the tendon-bone interface and more peritunnel bone than group 1. Biomechanically, group 4 showed higher failure loads and stiffness than group 1. However, peritunnel bone loss, active osteoclasts, and significant BTE were found in the femurs of group 1 and group 3 at 12 weeks postoperatively, while no strong correlation was found between BTE and inflammatory cytokines. Scanning electron microscopy and particle size analysis suggested that BD produced by ED and RD had no difference in size. CONCLUSION: Tendon-bone healing was facilitated by the synergistic effect of RD and BD in femurs. CLINICAL RELEVANCE: This study provides a more accessible and effective surgical strategy to promote tendon-bone healing after ACLR by increasing peritunnel bone and preventing BTE in femurs.

Smart pH-responsive polyhydralazine/bortezomib nanoparticles for remodeling tumor microenvironment and enhancing chemotherapy.

The clinical translation of nanomedicines has been impeded by the unfavorable tumor microenvironment (TME), particularly the tortuous vasculature networks, which significantly influence the transport and distribution of nanomedicines into tumors. In this work, a smart pH-responsive bortezomib (BTZ)-loaded polyhydralazine nanoparticle (PHDZ/BTZ) is presented, which has a great capacity to augment the accumulation of BTZ in tumors by dilating tumor blood vessels via specific release of vasodilator hydralazine (HDZ). The Lewis acid-base coordination effect between the boronic bond of BTZ and amino of HDZ empowered PHDZ/BTZ nanoparticles with great stability and high drug loading contents. Once triggered by the acidic tumor environment, HDZ could be released quickly to remodel TME through tumor vessel dilation, hypoxia attenuation, and lead to an increased intratumoral BTZ accumulation. Additionally, our investigation revealed that this pH-responsive nanoparticle dramatically suppressed tumor growth, inhibited the occurrence of lung metastasis with fewer side effects and induced immunogenic cell death (ICD), thereby eliciting immune activation including massive cytotoxic T lymphocytes (CTLs) infiltration in tumors and efficient serum proinflammatory cytokine secretion compared with free BTZ treatment. Thus, with efficient drug loading capacity and potent immune activation, PHDZ nanoparticles exhibit great potential in the delivery of boronic acid-containing drugs aimed at a wide range of diseases.

HemoglobinA1c Is a Risk Factor for Changes of Bone Mineral Density: A Mendelian Randomization Study.

Background: As a valuable blood glucose measurement, HemoglobinA1c (HbA1c) is of great clinical value for diabetes. However, in previous observational studies, studies on its effect on bone mineral density (BMD) have different results. This study aimed to use Mendelian randomization (MR) to assess the effect of HbA1c on bone mineral density and fracture risk, and try to further explore whether this association was achieved through glycemic or non-glycemic factors. Methods: Take HbA1c measurement as exposure, and BMD estimated from quantitative heel ultrasounds (eBMD) and bone fractures as outcomes. Two-Sample MR Analysis was conducted to assess the causal effect of HbA1C on heel BMD and risk fracture. Then, we performed the analysis using two subsets of these variants, one related to glycemic measurement and the other to erythrocyte indices. Results: Genetically increased HbA1C was associated with the lower heel eBMD [odds ratio (OR) 0.91 (95% CI 0.87, 0.96) per %-unit, P = 3 × 10-4(IVW)]. Higher HbA1C was associated with lower heel eBMD when using only erythrocytic variants [OR 0.87 (0.82, 0.93), P=2× 10-5(IVW)]; However, when using only glycemic variants, this casual association does not hold. In further MR analysis, we test the association of erythrocytic traits with heel eBMD. Conclusion: Our study revealed the significant causal effect of HbA1c on eBMD, and this causal link might achieve through non-glycemic pathways (erythrocytic indices).

Cepharanthine Ameliorates Chondrocytic Inflammation and Osteoarthritis via Regulating the MAPK/NF-κB-Autophagy Pathway.

Osteoarthritis is a worldwide joint disease caused by abnormal chondrocytic metabolism. However, traditional therapeutic methods aimed at anti-inflammation for early-stage disease are palliative. In the present study, we demonstrated that cepharanthine (CEP), extracted from the plant Stephania cepharantha, exerted protective medicinal efficacy on osteoarthritis for the first time. In our in vitro study, CEP suppressed the elevated expression of matrix metalloproteinases (MMPs), a disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTS5) and inducible nitric oxide synthase (iNOS) stimulated by IL-1ß or TNF-α by inhibiting the activation of MAPK and NF-κB signaling pathways, and upregulated the protein expression of aggrecan, collagen II, and Sox9. Also, CEP could reverse the reduced level of cellular autophagy in IL-1ß or TNF-α-induced chondrocytes, indicating that the protective effect of CEP on osteoarthritis was achieved by restoring MAPK/NF-κB-mediated autophagy. Furthermore, in a murine OA model, CEP mitigated cartilage degradation and prevented osteoarthritis in the CEP-treated groups versus the OA group. Hence, our results revealed the therapeutic prospect of CEP for anti-osteoarthritic treatment.

Prediction of Bedridden Duration of Hospitalized Patients by Machine Learning Based on EMRs at Admission.

Being bedridden is a frequent comorbid condition that leads to a series of complications in clinical practice. The present study aimed to predict bedridden duration of hospitalized patients based on EMR at admission by machine learning. The medical data of 4345 hospitalized patients who were bedridden for at least 24 hours after admission were retrospectively collected. After preprocessing of the data, features for modeling were selected by support vector machine recursive feature elimination. Thereafter, logistic regression, support vector machine, and extreme gradient boosting algorithms were adopted to predict the bedridden duration. The feasibility and efficacy of above models were evaluated by performance indicators. Our results demonstrated that the most important features related to bedridden duration were Charlson Comorbidity Index, age, bedridden duration before admission, mobility capability, and perceptual ability. The extreme gradient boosting algorithm showed the best performance (accuracy, 0.797; area under the curve, 0.841) when compared with support vector machine (accuracy, 0.771; area under the curve, 0.803) and logistic regression (accuracy, 0.765; area under the curve, 0.809) algorithms. Meanwhile, the extreme gradient boosting algorithm had a higher sensitivity (0.856), specificity (0.650), and F1 score (0.858) than that of support vector machine algorithm (0.843, 0.589, and 0.841) and logistic regression (0.852, 0.545, and 0.839), respectively. These findings indicate that machine learning based on EMRs at admission is a feasible avenue to predict the bedridden duration. The extreme gradient boosting algorithm shows great potential for further clinical application.

Genetic Associations Between IL-6 and the Development of Autoimmune Arthritis Are Gender-Specific.

Objectives: To find out the genetic association between IL6 and autoimmune arthritis. Methods: We performed a two-sample Mendelian randomization (MR) study using multiple genome-wide association studies (GWAS) datasets. Furthermore, a sex-stratified MR study was performed to identify sexual dimorphism in the association between IL6 and autoimmune arthritis. Then, LocusZoom plots were displayed based on the IL6R gene region to present evidence of genetic colocalization between diseases. Results: The MR result denoted a genetic association between the increased level of IL-6 signaling and risk of RA (ß=0.325, 95%CI 0.088, 0.561, p=7.08E-03) and AS (ß=1.240, 95%CI 0.495, 1.980, p=1.1E-03). Accordingly, sIL6R was found to have negatively correlation with the onset of RA (ß=-0.020, 95%CI -0.0320, -0.008, p=1.18E-03) and AS (ß=-0.125, 95%CI -0.177, -0.073, p=2.29E-06). However, no genetic association between IL6/sIL6R and PsA was detected. The gender-stratified MR analysis showed that IL6 was associated with AS in the male population, with RA in the female population, and with PsA in the male population. Additionally, ADAR, a gene identified by a sensitive test, could be the reason for the nonsignificant association between IL6 and PsA in a pooled population. Conclusion: Our findings showed that the overactive IL6 signal pathway led to autoimmune arthritis, especially in RA and AS. Sexual difference was also observed in IL6-intermediate susceptibility to autoimmune arthritis.

Virtual screening identified natural Keap1-Nrf2 PPI inhibitor alleviates inflammatory osteoporosis through Nrf2-mir214-Traf3 axis.

Overactive osteoclastogenesis is involved in the inflammatory bone loss and could be target for therapy. Here, we applied transcription factor enrichment analysis using public inflammatory osteolysis datasets and identified Nrf2 as the potential therapeutic target. Additionally, in-silico screening was performed to dig out Nrf2-Keap1 PPI inhibitor and Forsythoside-ß was found to be the best-performing PHG compound. We firstly tested the effect of Forsythoside-ß in inflammatory osteoporosis models and found it was able to attenuate the bone loss by inhibiting osteoclastogenesis and activating Nrf2-signaling in vivo. Forsythoside-ß was capable to suppress the differentiation of osteoclast in time and dose-dependent manners in vitro. Further, Forsythoside-ß could inhibit the production of reactive oxygen species and induce Nrf2 nuclear-translocation by interrupting Nrf2-Keap1 PPI. Recently, Nrf2 was identified as the epigenetic regulator modulating levels of miRNA in various diseases. We discovered that Forsythoside-ß could suppress the expression of mir-214-3p, one of most variable miRNAs during osteoclastogenesis. To clarify the undermining mechanism, by utilizing chip-seq dataset, we found that Nrf2 could bind to promoter of mir-214-3p and further regulate this miRNA. Collectively, Forsythoside-ß was able to prevent bone loss through Nrf2-mir-214-3p-Traf3 axis, which could be a promising candidate for treating inflammatory bone loss in the future.

A 3D-printed PRP-GelMA hydrogel promotes osteochondral regeneration through M2 macrophage polarization in a rabbit model.

Osteochondral regeneration is an orchestrated process of inflammatory immunity, host cell response, and implant degradation in tissue engineering. Here, the effects of a platelet-rich plasma (PRP)-gelatin methacryloyl (GelMA) hydrogel scaffold fabricated using the digital micro-mirror device (DMD) technique for osteochondral repair were investigated in a rabbit model. GelMA hydrogels with different PRP concentrations were fabricated, and their roles in bone marrow mesenchymal stem cells (BMSCs) and macrophage polarization in vitro were investigated. The incorporation of 20% PRP into the hydrogel showed optimal effects on the proliferation, migration, and osteogenic and chondrogenic differentiation of BMSCs. The 20% PRP-GelMA (v/v) hydrogel also promoted M2 polarization with high expression of Arg1 and CD206. Compared to the 20% PRP group, the 50% PRP group showed similar biological roles in BMSCs but less extent of osteogenesis. In the vivo study, the 20% PRP-GelMA composite was used for osteochondral reconstruction and showed more cartilage and subchondral bone regeneration than that observed using the pure GelMA hydrogel. The PRP-GelMA group exhibited more M2 macrophage infiltration and less M1 macrophage presentation at three time points as compared to the nontreatment group. The expression of Arg1 in the PRP-GelMA group increased significantly at 6 weeks but decreased to a lower level at 12 weeks, while CD163 showed sustained high expression until 18 weeks. Our findings demonstrated that the 3D-printed PRP-GelMA composite could promote osteochondral repair through immune regulation by M2 polarization and could be a potential candidate for osteochondral tissue engineering. STATEMENT OF SIGNIFICANCE: PRP-GelMA hydrogels promoted the migration and osteogenic and chondrogenic differentiation of BMSCs. PRP-GelMA hydrogels participated in immune regulation and M1-to-M2 transition of macrophages. PRP-GelMA hydrogels coordinated and promoted several overlapping osteochondral repair events, including dynamic immune regulation, chemotaxis of MSCs, and osteochondral differentiation. PRP-GelMA hydrogels showed superior cartilage and subchondral bone repair properties.

Relationship between Serum Nutritional Factors and Bone Mineral Density: A Mendelian Randomization Study.

PURPOSE: Multiple risk factors have been implicated in the development of osteoporosis. This study examined potential associations between serum nutritional factors and bone mineral density (BMD). METHODS: Six nutritional factors were selected as exposures. Outcomes included total body BMD (n = 66 945); BMD at the forearm (FA), femoral neck (FN) and lumbar spine (LS) (n = 8143, n = 32 735, and n = 28 498, respectively); estimated heel BMD (HL eBMD) (n = 394 929); and HL eBMD stratified by sex (n = 206 496). A 2-sample Mendelian randomization approach was adopted to estimate the association between serum nutritional factors and BMD. The threshold for adjusted P value was 1.39 × 10-3. RESULTS: Serum calcium levels were inversely associated with LS BMD (effect = -0.55; 95% CI, -0.86 to -0.24; P = 0.001), whereas serum selenium levels were positively correlated with HL eBMD (effect = 0.22; 95% CI, 0.10 to 0.33; P = 1.70 × 10-4). Regarding nominal significance, there was a positive association between serum selenium levels and FA BMD. Nominally significant results were also obtained for serum retinol as well as vitamin E levels and HL eBMD. Moreover, sex-specific effects of serum retinol and vitamin E levels on BMD were observed in men. CONCLUSION: Serum calcium and selenium levels influence BMD at specific skeletal sites. This implies that these nutritional factors play crucial roles in bone metabolism.

Causal relationship of serum nutritional factors with osteoarthritis: a Mendelian randomization study.

OBJECTIVES: OA is the most common form of arthritis worldwide and has a major impact on the quality of life among the older population. This study aimed at determining the potential causal effects of several serum nutritional factors on OA. METHODS: A total of seven serum nutritional factors were identified from genome-wide association studies. Summary statistics for OA were obtained from UK Biobank (194 153 for women and 166 988 for men) and a large genome-wide association studies meta-analysis based on the European population (455 221, 393 873 and 403 124 for overall, hip and knee OA, respectively). Two-sample Mendelian randomization approach was used to estimate the causal association between the selected nutritional factors and the risk of OA. RESULTS: The Mendelian randomization analyses suggested that serum calcium levels were inversely associated with overall OA (95% CI, 0.595, 0.850), hip OA (95% CI, 0.352, 0.799) and knee OA (95% CI, 0.461, 0.901). Serum retinol levels were also inversely associated with hip OA (95% CI, 0.257, 0.778). Moreover, sex-specific associations were observed between serum calcium levels (95% CI, 0.936, 0.998), iron levels (95% CI, 1.000, 1.012), selenium levels (95% CI, 0.923, 0.999) and OA in women. CONCLUSION: In this study, an inverse causal association between serum calcium levels and OA was established. Serum retinol levels were inversely associated with hip OA. In addition, we provide evidence for the causal effect of serum calcium, iron and selenium on the risk of OA in women.

Carnosol attenuates RANKL-induced osteoclastogenesis in vitro and LPS-induced bone loss.

Osteolysis is characterized by the imbalance of bone remodeling triggered by excessive activation of osteoclasts, which ultimately leads to pathological bone destruction. Diseases caused by overactive osteoclasts, such as osteolysis around the prosthesis, periodontitis and osteoporosis, are clinically common but lack effective treatment. Therefore, exploring regimens that could specifically impair the formation and function of osteoclasts has become a breakthrough in the treatment of these diseases. Carnosol is a natural phenolic diterpene with anti-inflammatory, antibacterial, anti-tumor and antioxidant properties. In this study, we found that carnosol can impede RANKL-induced osteoclastogenesis via modulating the activation of NF-κb and JNK signaling pathways in vitro. Additionally, we confirmed that carnosol could alleviate bone loss in amurine model of LPS-induced inflammatory bone erosion in vivo. Thence, these findings demonstrate that carnosol may be a potentially effective regent for the treatment of osteoclast-related disorders.

Parathyroid Hormone and Bone Mineral Density: A Mendelian Randomization Study.

PURPOSE: Accumulating evidence implicates parathyroid hormone (PTH) in the development of osteoporosis. However, the causal effect of PTH on bone mineral density (BMD) remains unclear. Thus, this study is aimed at exploring the association between the concentrations of serum PTH and BMD. METHODS: The instrumental variables for PTH were selected from a large-scale genome-wide association study (GWAS; n = 29 155). Outcomes included BMD of the forearm (FA; n = 8143), femoral neck (FN; n = 33 297), lumbar spine (LS; n = 32 735), heel (HL; n = 394 929), and risk of fractures in these bones (n = 361 194). Furthermore, the BMD of 5 different age groups: 15 years or younger (n = 11 807), 15-30 (n = 4180), 30-45 (n = 10 062), 45-60 (n = 18 805), and 60 years or older (n = 22 504) were extracted from a GWAS meta-analysis study. The analyses were performed using the 2-sample Mendelian randomization method. RESULTS: Mendelian randomization analysis revealed that the level of serum PTH was inversely associated with BMD of FA (95% CI: -0.763 to -0.016), FN (95% CI: -0.669 to -0.304), and LS (95% CI: -0.667 to -0.243). A causal relationship between serum PTH levels and BMD was observed in individuals aged 30-45 (95% CI: -0.888 to -0.166), 45-60 (95% CI: -0.758 to -0.232), and over 60 years (95% CI: -0.649 to -0.163). MAIN CONCLUSIONS: This study demonstrated that the concentrations of serum PTH is inversely associated with BMD of several bones. Further analysis revealed site- and age-specific correlations between serum PTH levels and BMD, which implies that the levels of serum PTH contribute to the development of osteoporosis.

Sex hormone-binding globulin and arthritis: a Mendelian randomization study.

BACKGROUND: Sex hormone-binding globulin (SHBG) has been reported to be a risk factor associated with the development of arthritis by previous observational studies more so of three common forms of arthritis: osteoarthritis (OA), rheumatoid arthritis (RA), and ankylosing spondylitis (AS). This study aimed to determine whether the concentrations of circulating SHBG are causally associated with the risk of OA, RA, and AS. METHODS: The two-sample Mendelian randomization (MR) approach was used for this study. The inverse-variance-weighted (IVW) method was used for the main analysis. Single-nucleotide polymorphisms (SNPs) associated with SHBG were selected from a large genome-wide association study (GWAS) of 28,837 European individuals. The summary statistics for OA, RA, and AS were extracted from the UK Biobank Resource (n = 361,141) and a GWAS dataset (n = 455,221). RESULTS: Positive causal associations were found between circulating SHBG concentrations and OA (effect = 1.086; 95% CI, 1.009 to 1.168; P = 0.027) and RA (effect = 1.003; 95% CI, 1.000 to 1.007; P = 0.047) in overall analyses. However, there was no evidence of association between SHBG levels and AS. Based on the stratification of skeletal sites, SHBG levels were found to be significantly associated with hip OA (effect = 1.423; 95% CI, 1.219 to 1.660; P = 7.753 × 10-6). However, this was not the case with knee OA. CONCLUSIONS: There were positive causal effects of circulating SHBG on the development of OA and RA. Moreover, there was a site-specific association between SHBG and hip OA. Evidently, measurement of SHBG in serum could be valuable in the clinical assessment of arthritis especially in early screening and prevention of OA and RA. However, the mechanisms by which SHBG plays causal roles in the development of arthritis require further investigations.

Comparison of Leukocyte-Rich Platelet-Rich Plasma and Leukocyte-Poor Platelet-Rich Plasma on Achilles Tendinopathy at an Early Stage in a Rabbit Model.

BACKGROUND: Tendinopathy is still a great challenge in clinical practice, and the role of platelet-rich plasma (PRP) is controversial. The influence of leukocytes on tendinopathy at an early stage has not been defined so far. PURPOSE: To compare the effects of leukocyte-rich PRP (Lr-PRP) and leukocyte-poor PRP (Lp-PRP) on Achilles tendinopathy when applied at an early stage. STUDY DESIGN: Controlled laboratory study. METHODS: A rabbit Achilles tendinopathy model was induced by a collagenase injection. A week later, treatments were applied randomly on local Achilles tendon lesions: (1) 200 µL of Lr-PRP (16 legs), (2) 200 µL of Lp-PRP (16 legs), and (3) 200 µL of saline (16 legs). At 3 and 6 weeks after the collagenase injection, outcomes were evaluated by histology, magnetic resonance imaging (MRI), real-time polymerase chain reaction analysis, immunohistochemistry, and transmission electron microscopy (TEM). RESULTS: The Lr-PRP group had a lower T2 signal intensity (P = .0377) and smaller diameter (P = .0193) and cross-sectional area (P = .0194) than the Lp-PRP group on MRI. Histologically, the Lr-PRP group had better scores than the Lp-PRP group (P = .0284 and P = .0188, respectively). Compared with the Lp-PRP group, higher gene expression and more protein synthesis of collagen I (P = .0160 and P = .0309, respectively) and CD163 (P < .0001 and P = .0411, respectively) were found in the Lr-PRP group. Considering TEM and biomechanical testing, the Lr-PRP group demonstrated more mature collagen fibers (P < .0001), a larger fiber diameter (P = .0005), a higher failure load (P = .00417), and higher tensile stress (P < .0001) than the Lp-PRP group. CONCLUSION: Lr-PRP had more beneficial effects than Lp-PRP when delivered at an early stage during tendon repair. CLINICAL RELEVANCE: Here, we showed that tendinopathy influenced the curative effects of PRP in vivo. An early-stage application of Lr-PRP had more benefits for the repair of tendinopathy than Lp-PRP in a rabbit model, which will supplement guidelines of PRP treatment on tendinopathy clinically.

Detection of extremity chronic traumatic osteomyelitis by machine learning based on computed-tomography images: A retrospective study.

Despite the availability of a series of tests, detection of chronic traumatic osteomyelitis is still exhausting in clinical practice. We hypothesized that machine learning based on computed-tomography (CT) images would provide better diagnostic performance for extremity traumatic chronic osteomyelitis than the serological biomarker alone. A retrospective study was carried out to collect medical data from patients with extremity traumatic osteomyelitis according to the criteria of musculoskeletal infection society. In each patient, serum levels of C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and D-dimer were measured and CT scan of the extremity was conducted 7 days after admission preoperatively. A deep residual network (ResNet) machine learning model was established for recognition of bone lesion on the CT image. A total of 28,718 CT images from 163 adult patients were included. Then, we randomly extracted 80% of all CT images from each patient for training, 10% for validation, and 10% for testing. Our results showed that machine learning (83.4%) outperformed CRP (53.2%), ESR (68.8%), and D-dimer (68.1%) separately in accuracy. Meanwhile, machine learning (88.0%) demonstrated highest sensitivity when compared with CRP (50.6%), ESR (73.0%), and D-dimer (51.7%). Considering the specificity, machine learning (77.0%) is better than CRP (59.4%) and ESR (62.2%), but not D-dimer (83.8%). Our findings indicated that machine learning based on CT images is an effective and promising avenue for detection of chronic traumatic osteomyelitis in the extremity.

Malignant fibrous neoplasms of long bones: analysis of the surveillance, epidemiology, and end results database from 1973 to 2015.

BACKGROUND: Malignant fibrous neoplasms (MFN) of long bones are rare lesions. Moreover, the prognostic determinants of MFN of long bones have not been reported. This study aimed to present epidemiological data and analyse the prognostic factors for survival in patients with MFN. MATERIALS AND METHODS: The Surveillance, Epidemiology, and End Results (SEER) programme database was used to screen patients with malignant fibrous neoplasms (MFN) of long bones from 1973 to 2015, with attention to fibrosarcoma, fibromyxosarcoma, periosteal fibrosarcoma and malignant fibrous histiocytoma. The prognostic values of overall survival (OS) and cancer-specific survival (CSS) were assessed using the Cox proportional hazards regression model with univariate and multivariate analyses. The Kaplan-Meier method was used to obtain OS and CSS curves. RESULTS: A total of 237 cases were selected from the SEER database. Malignant fibrous histiocytoma was the most common form of lesion in long bones. Multivariate analysis revealed that independent predictors of OS included age, stage, tumour size and surgery. Age, stage, tumour size and surgery were also independent predictors of CSS. Additionally, the most significant prognostic factor was whether metastasis had occurred at the time of initial diagnosis. CONCLUSION: Among patients with MFN of long bones, age (> 60 years), tumour size (> 10 cm), distant stage, and non-surgical treatment are factors for poor survival.