Serum vitamin D insufficiency is correlated with quadriceps neuromuscular functions in patients with anterior cruciate ligament injury: A preliminary study.

Background: This study aimed to investigate the correlations of serum vitamin D insufficiency with quadriceps neuromuscular function in patients with anterior cruciate ligament (ACL) injury. Methods: A cross-sectional study was conducted. Eighteen patients with a primary, unilateral ACL injury who had insufficient serum vitamin D concentrations (<30 ng/ml) were recruited for the study. Bilateral quadriceps neuromuscular function, including maximal strength, the speed of rapid contraction, and inhibition, were measured on an isokinetic dynamometer with the hip and the knee joint flexion at 90° and 45°, respectively. Quadriceps strength was measured by maximal voluntary isometric contractions (MVIC); the speed of rapid contraction was quantified by the rate of torque development (RTD), which was divided into the early (RTD0-50) and the late phase (RTD100-200); quadriceps inhibition was quantified by the central activation ratio (CAR). Serum vitamin D concentration was quantitatively determined by serum 25(OH)D concentration measured by the 25(OH)D ELISA kit. The Spearman rank correlation analysis was used to examine the correlation between the vitamin D concentration and bilateral quadriceps MVIC, RTD0-50, RTD100-200, and CAR, respectively. Results: The results of Spearman rank correlation analyses showed that the serum 25(OH)D concentration was significantly correlated with bilateral quadriceps MVIC (injured: r = 0.574, p = 0.013; uninjured: r = 0.650, p = 0.003) and RTD0-50 (r = 0.651, p = 0.003), and CAR (r = 0.662, p = 0.003) on the uninjured limb. However, no significant correlations were found between the serum 25(OH)D concentration and the other outcomes. Conclusions: The serum vitamin D concentration correlates with quadriceps neuromuscular function in patients with ACL injury who had vitamin D insufficiency.

What is the optimal dose of adipose-derived mesenchymal stem cells treatment for knee osteoarthritis? A conventional and network meta-analysis of randomized controlled trials.

BACKGROUND: Despite increasing clinical investigations underscoring the efficacy and safety of adipose-derived mesenchymal stem cells (AD-MSCs) therapy in knee osteoarthritis (KOA), no article has recently reviewed the cell dosage. This study aimed to evaluate the efficacy and safety of varying doses of AD-MSCs in treating KOA using conventional and network meta-analysis. METHODS: A search of databases in in Chinese and English was performed to identify randomized controlled trials (RCT) on MSCs for knee osteoarthritis from the inception date to May 1, 2022. This study mainly analyzed the efficacy of AD-MSCs in the treatment of KOA, and subgroup analysis was performed on the therapeutic effects of MSCs from different tissues at the same dose. We divided the different cell doses into low, moderate, and high groups, with the corresponding cell doses: (0-25)*10^6, (25-50)*10^6, and > 50*10^6 cells, respectively. We further analyzed the improvement of improvement of the Visual Analog Scale (VAS) and the Western Ontario and McMaster Universities Arthritis Index (WOMAC) scores and the incidence of adverse events (AEs) after varied dosage injection. RESULTS: A total of 16 literatures were included in this study, of which 8 literatures were about AD-MSCs. Conventional meta-analysis suggests that AD-MSCs can reduce pain and improve function in KOA patients, regardless of the cell doses, up to 12 months of follow-up. The network meta-analysis showed that intra-articular injection of AD-MSCs significantly improved pain and knee function scores in KOA patients compared with the control group at 3, 6, and 12 months. Among the three groups, the high-dose group had the best treatment effect, and the degree of joint pain and dysfunction indicators improved more significantly in the early stage. For adverse events, there was a dose-response trend that increased with increasing doses. CONCLUSIONS: Both cell doses reduced pain and improved knee function in KOA patients. The effect surpassed in the high-dose group than in the moderate-dose, low-dose and control groups. However, adverse events also increase with the increase in dose, which should be carefully considered in clinical application, and the side effects still need to be paid attention to. Considering the limitations of this meta-analysis, future studies need to further explore the efficacy and safety of different doses of treatment, and carry out large sample, multi-center, randomized controlled trials to ensure the reliability and promotion value of the research results.

Blockage of Osteopontin-Integrin ß3 Signaling in Infrapatellar Fat Pad Attenuates Osteoarthritis in Mice.

The knowledge of osteoarthritis (OA) has nowadays been extended from a focalized cartilage disorder to a multifactorial disease. Although recent investigations have reported that infrapatellar fat pad (IPFP) can trigger inflammation in the knee joint, the mechanisms behind the role of IPFP on knee OA progression remain to be defined. Here, dysregulated osteopontin (OPN) and integrin ß3 signaling are found in the OA specimens of both human and mice. It is further demonstrated that IPFP-derived OPN participates in OA progression, including activated matrix metallopeptidase 9 in chondrocyte hypertrophy and integrin ß3 in IPFP fibrosis. Motivated by these findings, an injectable nanogel is fabricated to provide sustained release of siRNA Cd61 (RGD- Nanogel/siRNA Cd61) that targets integrins. The RGD- Nanogel possesses excellent biocompatibility and desired targeting abilities both in vitro and in vivo. Local injection of RGD- Nanogel/siRNA Cd61 robustly alleviates the cartilage degeneration, suppresses the advancement of tidemark, and reduces the subchondral trabecular bone mass in OA mice. Taken together, this study provides an avenue for developing RGD- Nanogel/siRNA Cd61 therapy to mitigate OA progression via blocking OPN-integrin ß3 signaling in IPFP.

Comparative short-term effectiveness of non-surgical treatments for insertional Achilles tendinopathy: a systematic review and network meta-analysis.

BACKGROUND: The incidence of Achilles tendinopathy has risen over the past decades. Insertional Achilles tendinopathy is characterised by tissue degeneration of the Achilles tendon from its insertion in the calcaneus to up to 2 cm proximally. This clinical condition is accompanied by pain, loss of function and diminished exercise tolerance. Numerous conservative treatment modalities are available to participants with insertional Achilles tendinopathy, including eccentric exercises, extracorporeal shockwave therapy, laser therapy, cryotherapy, therapeutic ultrasound, and orthotics. Eccentric exercise and extracorporeal shockwave therapy may reduce pain in participants with non-calcified insertional Achilles tendinopathy. However, no specific treatment is recommended over another due to the low methodological quality of trials. Given the lack of standard or preferred non-surgical treatment and the potential risks of surgical treatment, there is an imminent need to reassess different non-surgical treatments based on the newest evidence. Thus, this systematic review aims to evaluate the clinical effectiveness of the various non-surgical treatments for insertional Achilles tendinopathy. METHODS: AMED EBSCOhost, CINAHL, EBSCOhost, EMBASE, PEDro, PubMed, Web of Science, and Clinicaltrials.gov were searched from 1992 to 14th October 2022, randomised controlled trials of adults with insertional Achilles tendinopathy investigating non-surgical treatments compared with each other or no treatment, placebo/sham control. Two reviewers independently screened and extracted the data. Random effects of network meta-analysis immediately after treatments were used to report comparative treatment effects. The surface under the cumulative ranking probabilities was calculated to assess the relative ranking of treatments. RESULTS: Nine trials (total n = 464 participants) were included. This review recommended the combination of eccentric exercise and soft tissue therapy to manage insertional Achilles tendinopathy. With the highest SUCRA values of 84.8, and the best mean rank of 1.9, Eccentric exercise plus soft tissue treatment ranked as the most effective treatment for short-term pain. CONCLUSIONS: This is the first NMA of non-surgical treatment focusing on short-term pain control for IAT which eccentric exercise plus soft-tissue therapy was found to be the most effective treatment combination. However, the overall confidence in non-surgical treatments from all included trials was very low. No recommendation of the best treatment option can be made from this review.

Doxycycline Promotes Graft Healing and Attenuates Posttraumatic Osteoarthritis After Anterior Cruciate Ligament Reconstruction in a Rat Model.

BACKGROUND: Doxycycline (Doxy) has been shown to facilitate tendon healing by reducing on-site matrix metalloproteinase (MMP) activity, but its effect on graft healing after anterior cruciate ligament reconstruction (ACLR) has not been investigated, and the therapeutic effect of Doxy in preventing ACLR-induced posttraumatic osteoarthritis (PTOA) is unclear. HYPOTHESIS: Doxy promotes graft healing and alleviates the progression of PTOA after ACLR. STUDY DESIGN: Controlled laboratory study. METHODS: Sprague Dawley rats (n = 74; age, 12-13 weeks; male) that underwent ACLR were divided into untreated control and Doxy treatment (50 mg/kg/d orally until sacrifice) groups. At 2 and 6 weeks after surgery, graft healing was assessed by biomechanical testing, histology, immunohistochemical staining, and micro-computed tomography (µCT). The progression of PTOA was evaluated at 6 weeks by histology, the Mankin score, and immunofluorescence staining of the tibial plateau, and osteophyte formation was evaluated by µCT. Hindlimb weight distribution was evaluated at 6 weeks, and gait patterns were evaluated at 2 and 6 weeks. Intra-articular MMP activity was evaluated at 6 weeks in vivo using an MMP-activatable near-infrared fluorescent probe. RESULTS: Graft healing was enhanced by Doxy treatment, and the ultimate failure load (P = .002) and stiffness of the graft (P = .007) were significantly higher in the Doxy group at week 2. Bone mineral density and bone volume/total volume for both the tibial and the femoral tunnels at week 6 in the Doxy group were significantly higher compared with in the control group (P < .05). The overall graft healing scores were significantly higher in the Doxy group. Doxy treatment enhanced graft integration, intratunnel graft integrity, and collagen birefringence; more collagen types 1 and 10 and less MMP-13 were found at the graft-bone interface. At week 6, the Doxy group had a lower modified Mankin score (P = .033) and showed fewer MMP 13-positive chondrocytes at the articular cartilage surface (P = .002), indicating moderate joint cartilage damage. µCT revealed less osteophyte formation, and gait analysis revealed more symmetric weightbearing and gait patterns, after Doxy treatment at week 6 (P < .05). In vivo imaging with the near-infrared fluorescent probe identified significantly lower intra-articular MMP activity in the Doxy group at week 6 (P = .016). CONCLUSION: The oral administration of Doxy was able to synchronously promote graft healing and attenuate PTOA in an ACLR rat model. CLINICAL RELEVANCE: Our results indicated that Doxy, a widely used drug, is potentially beneficial to patients after ACLR.

Effects of Deficits in the Neuromuscular and Mechanical Properties of the Quadriceps and Hamstrings on Single-Leg Hop Performance and Dynamic Knee Stability in Patients After Anterior Cruciate Ligament Reconstruction.

BACKGROUND: Understanding the role of neuromuscular and mechanical muscle properties in knee functional performance and dynamic knee stability after anterior cruciate ligament reconstruction (ACLR) may help in the development of more focused rehabilitation programs. PURPOSE: To compare the involved and uninvolved limbs of patients after ACLR in terms of muscle strength, passive muscle stiffness, muscle activation of the quadriceps and hamstrings, hop performance, and dynamic knee stability and to investigate the association of neuromuscular and mechanical muscle properties with hop performance and dynamic knee stability. STUDY DESIGN: Cross-sectional study; Level of evidence, 3. METHOD: The authors studied the quadriceps and hamstring muscles in 30 male patients (mean ± SD age, 25.4 ± 4.1 years) who had undergone unilateral ACLR. Muscle strength was measured using isokinetic testing at 60 and 180 deg/s. Passive muscle stiffness was quantified using ultrasound shear wave elastography. Muscle activation was evaluated via electromyographic (EMG) activity. Hop performance was evaluated via a single-leg hop test, and dynamic knee stability was evaluated via 3-dimensional knee movements during the landing phase of the hop test. RESULTS: Compared with the uninvolved limb, the involved limb exhibited decreased peak torque and shear modulus in both the quadriceps and hamstrings as well as delayed activity onset in the quadriceps (P < .05 for all). The involved limb also exhibited a shorter hop distance and decreased peak knee flexion angle during landing (P < .05 for both). Decreased peak quadriceps torque at 180 deg/s, the shear modulus of the semitendinosus, and the reactive EMG activity amplitude of the semimembranosus were all associated with shorter hop distance (R 2 = 0.565; P < .001). Decreased quadriceps peak torque at 60 deg/s and shear modulus of the vastus medialis were both associated with smaller peak knee flexion angle (R 2 = 0.319; P < .001). CONCLUSION: In addition to muscle strength deficits, deficits in passive muscle stiffness and muscle activation of the quadriceps and hamstrings were important contributors to poor single-leg hop performance and dynamic knee stability during landing. Further investigations should include a rehabilitation program that normalizes muscle stiffness and activation patterns during landing, thus improving knee functional performance and dynamic knee stability.

Identification of Osteosarcoma Metastasis-Associated Gene Biomarkers and Potentially Targeted Drugs Based on Bioinformatic and Experimental Analysis.

BACKGROUND: Metastasis is the leading cause of death for patients with osteosarcoma (OS). In the present study, we explore the biomarkers for metastatic OS and provide potential therapeutic approaches. MATERIALS AND METHODS: RNA-Seq data and clinical follow-up information were downloaded from TARGET and GEO databases. A Cox regression model was used to analyze metastatic events. L1000FWD, DGIdb, and CMap databases were used to identify potential drugs related to metastasis. Invasion and migration transwell assays and an adhesion assay were used to identify biological functions of genes. RESULTS: A total of 15 metastasis-related signatures (MRSs) were associated with the prognosis based on the TARGET or GSE21257 cohorts, among which IL10RA and TLR7 genes were especially significant. In the DGIdb drug-gene interaction database, TLR7 and IFNGR1 were found to have potential interactions with drugs. After inhibiting the expression of TLR7, the migration, invasion, and adhesion ability of OS cells were significantly enhanced, which further promoted metastasis. CONCLUSION: We identified a set of MRS that may be related to OS metastases. Among them, TLR7 plays a vital role and may be a potential target for OS metastasis treatment.

A succinct technique for the extraction of the proximal femoral nail anti-rotation (PFNA) after unlocking failure: a case report.

INTRODUCTION: Proximal femoral nail anti-rotation (PFNA) is a routine method to deal with intertrochanteric fractures in the elder population. It is challenging to remove PFNA in some cases as a result of stripping of blade heads. In this case presentation, we describe a novel technique using commonly available instruments that can be used to remove stripped, even broken anti-rotation blade where conventional methods have failed. METHODS: The subject underwent a PFNA removal surgery 15 months after the previous fixation. We encountered difficulties using the regular instrument to remove the anti-rotation blade. A 5-mm tungsten carbide bur was used to drill a single cortical hole at the end of the blade. Then double-strand steel wire was threaded through the hole, and the distal part was shaped into a circle which could tie to the extraction screw. Slide Hammer was applied to gently knock out the blade along the anatomical direction of the femoral neck. RESULTS: The technique helped us successfully remove the anti-rotation blade and provided the patient with a satisfactory result. CONCLUSION: The use of a tungsten reamer and steel wire loop to remove the proximal femoral anti-rotation blade may provide a cost-effective and straightforward method of dealing with extraction failure.

The OLIF working corridor based on magnetic resonance imaging: a retrospective research.

OBJECTIVE: To provide an anatomical basis for the development of oblique lumbar interbody fusion (OLIF) in Chinese patients. METHODS: Between November 2018 and June 2019, 300 patients' lumbar MRI data were reviewed. According to the Moro system and zone method described by us, the axial view was vertically divided into 6 zones (A, I II, III, IV, P) and was horizontally divided into 4 zones (R, a, b, c, L). The locations of left psoas muscle and the major artery at L2/3, L3/4, and L4/5 levels were evaluated by the grid system. The aortic bifurcation segments will also be evaluated at the level of the vertebral body or the disc. RESULTS: At the L2/3 level, left psoas muscle and the major artery in zone Ib were found in 28.0% of subjects, in zone IIb in 20.3%, and in zone Ic in 20.0%; at the L3/4 level, in zone Ab in 20.7% of subjects, in zone Ac in 26.0%, and in zone Ic in 11.0%; and at the L4/5 level, areas in zone Ab in 31.0% of subjects, in zone Ac in 26.0%, and in zone Ib in 11.7%. The aortic bifurcation segments were mainly at the L4 level. The zone of the left psoas muscle at all levels, the zone of the major artery at L4/5 level, and the zone of the aortic bifurcation segments had significant correlation with gender difference (P < 0.05). CONCLUSION: The left-sided OLIF at L2-L5 disc levels can be a feasible type of surgery for lumbar interbody fusion in the majority of Chinese patients. Before the operation, in order to screen out the appropriate surgical approach, routine lumbar magnetic resonance imaging is recommended to analyze the patient's local anatomical features.

Identification and Development of a Novel 4-Gene Immune-Related Signature to Predict Osteosarcoma Prognosis.

Osteosarcoma (OS) is a malignant disease that develops rapidly and is associated with poor prognosis. Immunotherapy may provide new insights into clinical treatment strategies for OS. The purpose of this study was to identify immune-related genes that could predict OS prognosis. The gene expression profiles and clinical data of 84 OS patients were obtained from the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) database. According to non-negative matrix factorization, two molecular subtypes of immune-related genes, C1 and C2, were acquired, and 597 differentially expressed genes between C1 and C2 were identified. Univariate Cox analysis was performed to get 14 genes associated with survival, and 4 genes (GJA5, APBB1IP, NPC2, and FKBP11) obtained through least absolute shrinkage and selection operator (LASSO)-Cox regression were used to construct a 4-gene signature as a prognostic risk model. The results showed that high FKBP11 expression was correlated with high risk (a risk factor), and that high GJA5, APBB1IP, or NPC2 expression was associated with low risk (protective factors). The testing cohort and entire TARGET cohort were used for internal verification, and the independent GSE21257 cohort was used for external validation. The study suggested that the model we constructed was reliable and performed well in predicting OS risk. The functional enrichment of the signature was studied through gene set enrichment analysis, and it was found that the risk score was related to the immune pathway. In summary, our comprehensive study found that the 4-gene signature could be used to predict OS prognosis, and new biomarkers of great significance for understanding the therapeutic targets of OS were identified.