Mitochondrial mechanisms in the pathogenesis of chronic inflammatory musculoskeletal disorders.

Chronic inflammatory musculoskeletal disorders characterized by prolonged muscle inflammation, resulting in enduring pain and diminished functionality, pose significant challenges for the patients. Emerging scientific evidence points to mitochondrial malfunction as a pivotal factor contributing to these ailments. Mitochondria play a critical role in powering skeletal muscle activity, but in the context of persistent inflammation, disruptions in their quantity, configuration, and performance have been well-documented. Various disturbances, encompassing alterations in mitochondrial dynamics (such as fission and fusion), calcium regulation, oxidative stress, biogenesis, and the process of mitophagy, are believed to play a central role in the progression of these disorders. Additionally, unfolded protein responses and the accumulation of fatty acids within muscle cells may adversely affect the internal milieu, impairing the equilibrium of mitochondrial functioning. The structural discrepancies between different mitochondrial subsets namely, intramyofibrillar and subsarcolemmal mitochondria likely impact their metabolic capabilities and susceptibility to inflammatory influences. The release of signals from damaged mitochondria is known to incite inflammatory responses. Intriguingly, migrasomes and extracellular vesicles serve as vehicles for intercellular transfer of mitochondria, aiding in the removal of impaired mitochondria and regulation of inflammation. Viral infections have been implicated in inducing stress on mitochondria. Prolonged dysfunction of these vital organelles sustains oxidative harm, metabolic irregularities, and heightened cytokine release, impeding the body's ability to repair tissues. This review provides a comprehensive analysis of advancements in understanding changes in the intracellular environment, mitochondrial architecture and distribution, biogenesis, dynamics, autophagy, oxidative stress, cytokines associated with mitochondria, vesicular structures, and associated membranes in the context of chronic inflammatory musculoskeletal disorders. Strategies targeting key elements regulating mitochondrial quality exhibit promise in the restoration of mitochondrial function, alleviation of inflammation, and enhancement of overall outcomes.

Subacromial bursa in patients with rotator cuff tear with or without adhesive capsulitis exhibits a differential transcriptome with potential molecular biomarkers.

Background: Although adhesive capsulitis (AC) is a common condition, the pathological mechanisms remain understudied. The purpose of our research was to evaluate variations in gene expression across the entire genome in the subacromial bursa tissue of individuals with rotator cuff tears (RCT), with or without AC, and to explore the factors that may influence the occurrence and progression of AC. Methods: Transcription profiles of subacromial bursa samples from 12 RCT patients, of whom 6 had also AC, were evaluated. Data were generated using RNA-seq. DESeq2 was utilized to identify the differentially expressed genes (DEGs) in both groups. In order to conduct a more in-depth examination of the DEGs, we performed Gene Ontology (GO) functional enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. A network of interactions between proteins was built, and the central genes were determined using Cytoscape. The hub genes were confirmed through qRT-PCR and immunohistochemistry. Results: 324 of the 16,251 detected genes were identified as DEGs. Analysis of GO functional enrichment showed that the DEGs were enriched in domains of biological process, molecule function and cellular component. Analysis of KEGG pathways revealed enrichment of DEGs in pathways like IL-17 signaling and ECM-receptor interaction. We verified that the association between AC and the increase in expression of the PPI network hub genes. Conclusion: This study investigated the transcriptome differences of subacromial bursa in RCT patients with or without AC. Using bioinformatics technology, we identified the DEGs and screened out the hub genes. The research enhanced the data on gene expression profiles of DEGs in the subacromial bursa tissue of patients with RCT, offering fresh perspectives on the regulation of gene transcription.

Multiple pulmonary sclerosing pneumocytoma, based on a study of 36 cases worldwide.

To analyze the clinical characteristics and to improve clinicians' understanding of multiple pulmonary sclerosing pneumocytoma (PSP) patients. A total of 36 PSP patients with multiple tumor characteristics were identified from the literature search. They were compared with 43 solitary PSP patients diagnosed and treated in our hospital in the past 5 years. Thus, the pathogenesis, clinical symptoms, diagnosis methods, treatment strategies, and prognosis of pulmonary sclerosing pneumocytoma (PSP) patients with multiple tumors were explored. Patients with multiple PSP are mostly distributed in Asia (88.89%) and are females (83.33%). PSP can be located in any one lobe (19.44%), or grow across ipsilateral lobes (44.44%), or even, bilateral lobes (36.11%). It can be accompanied by metastasis (9.09%) and is prone to misdiagnosis (27.78%). Compared with solitary PSP, the occurrence age of multiple PSP was younger (mean ± standard deviation [SD]: 40.36 ± 18.12: 51.28 ± 12.74 years), but there was no significant difference in sex, tumor size (mean ± SD: 43.54 ± 46.18: 30.56 ± 17.62 mm), or symptoms. Individualized surgical resection is required for treatment, including pneumonectomy (17.65%), lobectomy (23.53%), subpulmonary lobectomy (38.24%), or combined lobectomy (5.88%). Multiple PSP is relatively rare. Surgical resection within a limited time should be the main treatment for such patients. The prognosis of patients with multiple PSP is generally good, but inappropriate diagnosis and treatment plans may lead to poor prognosis.

Low levels of Al stimulate the aboveground growth of Davidia involucrata saplings.

Davidia involucrata is a woody perennial and the only living species in the Genus Davidia. It is native to southern China where it holds cultural and scientific importance. However, D. involucrata is now an endangered species and its natural range includes low pH soils which are increasingly impacted by acid rain, nitrogen deposition and imbalanced nutrient cycling. The combination of these stresses also poses the additional risk of aluminum (Al) toxicity. Since the responses of D. involucrata to low pH and aluminum toxicity have not been investigated previously, a hydroponic experiment was conducted to examine the growth of one year old D. involucrata saplings after 50 d growth in a range of pH and Al conditions. Plant biomass, morphology, antioxidant enzyme activity, mineral concentrations and plant ecological strategy were compared at pH 5.8 and pH 4.0 without added Al (AlCl3) and in 0.1, 0.2 and 0.5 mM Al at pH 4.0. Our results showed that compared with pH 5.8, pH 4.0 (without added Al) not only inhibited root and shoot growth but also limited accumulation of nitrogen (N) and phosphorus (P) in leaves of D. involucrate. However, low Al concentrations (0.1 and 0.2 mM Al) at pH 4.0 partially restored the aboveground growth and leaf N concentrations, suggesting an alleviation of H+ toxicity by low Al concentrations. Compared with low Al concentrations, 0.5 mM Al treatment decreased plant growth and concentrations of N, P, and magnesium (Mg) in the leaves, which demonstrated the toxicity of high Al concentration. The results based on plant ecological strategy showed that D. involucrate decreased the competitiveness and favored its stress tolerance as pH changed from 5.8 to 4.0. Meanwhile, the competitiveness and stress tolerance of D. involucrata increased and decreased at low Al concentrations, respectively, and decreased and increased at high Al concentration, respectively. These trade-offs in ecological strategy were consistent with the responses of growth and antioxidant enzyme activity, reflecting a sensitive adaptation of D. involucrata to acid and Al stresses, which may aid in sustaining population dynamics. These findings are meaningful for understanding the population dynamics of D. involucrata in response to aluminum toxicity in acid soils.

Allogeneic platelet-rich plasma for knee osteoarthritis in patients with primary immune thrombocytopenia: A randomized clinical trial.

The treatment of painful KOA in adult patients with ITP has not been well studied yet. We conducted a prospective, double-blind, randomized, placebo-controlled trial to evaluate the efficacy of intra-articular allogeneic PRP injections on symptoms and joint structure in patients with KOA and ITP. 80 participants were randomly allocated in a 1:1 ratio to allogeneic PRP group or saline group. The primary outcome was the WOMAC total score at 12 months post-injection. The number of patients in each group who achieved MCID of primary outcome showed a statistically significant difference only at 3-month (27/39 vs. 5/39, p = 0.001) and 6-month (15/39 vs. 3/38, p = 0.032). The difference in WOMAC total score exceeded the MCID only at 3 month (mean difference of -15.1 [95% CI -20.7 to -9.5], p < 0.001). Results suggest that allogeneic PRP was superior to placebo only with respect to symptoms at 3-month of follow-up.

Incidence of deep venous thrombosis in patients with hemophilia undergoing bilateral simultaneous total knee arthroplasty: a retrospective cohort study.

BACKGROUND: Hemophilic arthropathy usually affects the knees bilaterally. In order to reduce costs and improve rehabilitation, bilateral simultaneous total knee arthroplasty (TKA) can be performed. However, pharmacological prophylaxis for deep venous thrombosis (DVT) remains controversial in patients with severe hemophilia. The purpose of this study was to establish the incidence of DVT in severe hemophilia A patients undergoing bilateral simultaneous TKA without pharmacological thromboprophylaxis. METHODS: Consecutive patients with severe hemophilia A undergoing bilateral simultaneous TKA at a single center between January 2015 and December 2020 were retrospectively reviewed. All patients received a modified coagulation factor substitution regimen. Tranexamic acid (TXA) was used for hemostasis in all patients during surgery. All patients followed a standardized postoperative protocol with routine mechanical thromboprophylaxis, and none received anticoagulation. D-dimer was measured preoperatively, on the day of the operation and on postoperative days 1, 7 and 14. Ultrasound (US) of the lower extremities was performed before (within 3 days of hospitalization) and after surgery (days 3 and 14) to detect asymptomatic DVT. Patients were followed up until 2 years after surgery for the development of symptomatic DVT or pulmonary embolism (PE). RESULTS: 38 male patients with severe hemophilia A underwent 76 simultaneous TKAs. Mean (± standard deviation) age at the time of operation was 41.7 (± 17.1) years. Overall, 47.3% of patients had D-dimer concentrations above the threshold 10 µg/mL on day 7 and 39.5% on day 14. However, none of the patients had DVT detected on postoperative US, nor developed symptomatic DVT or PE during the 2-year follow-up. CONCLUSIONS: The risk of DVT in patients with severe hemophilia A after bilateral simultaneous TKA is relatively low, and routine pharmacological thromboprophylaxis may not be needed.

Enhancing Endogenous Hyaluronic Acid in Osteoarthritic Joints with an Anti-Inflammatory Supramolecular Nanofiber Hydrogel Delivering HAS2 Lentivirus.

Osteoarthritis (OA) management remains challenging because of its intricate pathogenesis. Intra-articular injections of drugs, such as glucocorticoids and hyaluronic acid (HA), have certain limitations, including the risk of joint infection, pain, and swelling. Hydrogel-based therapeutic strategies have attracted considerable attention because of their enormous therapeutic potential. Herein, a supramolecular nanofiber hydrogel is developed using dexamethasone sodium phosphate (DexP) as a vector to deliver lentivirus-encoding hyaluronan synthase 2 (HAS2) (HAS2@DexP-Gel). During hydrogel degradation, HAS2 lentivirus and DexP molecules are slowly released. Intra-articular injection of HAS2@DexP-Gel promotes endogenous HA production and suppresses synovial inflammation. Additionally, HAS2@DexP-Gel reduces subchondral bone resorption in the anterior cruciate ligament transection-induced OA mice, attenuates cartilage degeneration, and delays OA progression. HAS2@DexP-Gel exhibited good biocompatibility both in vitro and in vivo. The therapeutic mechanisms of the HAS2@DexP-Gel are investigated using single-cell RNA sequencing. HAS2@DexP-Gel optimizes the microenvironment of the synovial tissue by modulating the proportion of synovial cell subpopulations and regulating the interactions between synovial fibroblasts and macrophages. The innovative nanofiber hydrogel, HAS2@DexP-Gel, effectively enhances endogenous HA production while reducing synovial inflammation. This comprehensive approach holds promise for improving joint function, alleviating pain, and slowing OA progression, thereby providing significant benefits to patients.

M2 macrophage-derived exosomal miR-26b-5p regulates macrophage polarization and chondrocyte hypertrophy by targeting TLR3 and COL10A1 to alleviate osteoarthritis.

Osteoarthritis (OA) is one of the most prevalent chronic musculoskeletal diseases among the elderly population. In this study, macrophage-derived exosomes were isolated and identified. Exosomes were subjected to microRNA (miRNA) sequencing and bioinformatic analysis, and differentially expressed miRNAs were verified. miR-26b-5p target genes were confirmed through target-site mutation combined with a dual-luciferase reporter assay. The effects of miR-26b-5p on macrophage polarization and chondrocyte hypertrophy were assessed in vitro. miR-26b-5p agomir was applied to mice with OA induced by anterior cruciate ligament transection (ACLT). The therapeutic effects of miR-26b-5p were evaluated via pain behavior experiments and histological observations. In vitro, miR-26b-5p repolarized M1 macrophages to an anti-inflammatory M2 type by targeting the TLR3 signaling pathway. miR-26b-5p could target COL10A1, further inhibiting chondrocyte hypertrophy induced by M1 macrophage-conditioned medium (M1-CM). In vivo, miR-26b-5p agomir ameliorated gait abnormalities and mechanical allodynia in OA mice. miR-26b-5p treatment attenuated synovitis and cartilage degeneration, thereby delaying OA progression. In conclusion, M2 macrophage-derived exosomal miR-26b-5p could protect articular cartilage and ameliorate gait abnormalities in OA mice by targeting TLR3 and COL10A1. miR-26b-5p further affected macrophage polarization and chondrocyte hypertrophy. Thus, this exosomal miR-26b-5p-based strategy might be a potential method for OA treatment.

Recent advances of exosomes in soft tissue injuries in sports medicine: A critical review on biological and biomaterial applications.

Sports medicine is generally associated with soft tissue injuries including muscle injuries, meniscus and ligament injuries, tendon ruptures, tendinopathy, rotator cuff tears, and tendon-bone healing during injuries. Tendon and ligament injuries are the most common sport injuries accounting for 30-40% of all injuries. Therapies for tendon injuries can be divided into surgical and non-surgical methods. Surgical methods mainly depend on the operative procedures, the surgeons and postoperative interventions. In non-surgical methods, cell therapy with stem cells and cell-free therapy with secretome of stem cell origin are current directions. Exosomes are the main paracrine factors of mesenchymal stem cells (MSCs) containing biological components such as proteins, nucleic acids and lipids. Compared with MSCs, MSC-exosomes (MSC-exos) possess the capacity to escape phagocytosis and achieve long-term circulation. In addition, the functions of exosomes from various cell sources in soft tissue injuries in sports medicine have been gradually revealed in recent years. Along with the biological and biomaterial advances in exosomes, exosomes can be designed as drug carriers with biomaterials and exosome research is providing promising contributions in cell biology. Exosomes with biomaterial have the potential of becoming one of the novel therapeutic modalities in regenerative researches. This review summarizes the derives of exosomes in soft tissue regeneration and focuses on the biological and biomaterial mechanism and advances in exosomal therapy in soft tissue injuries.

Tranexamic acid is safe with respect to the risk of deep venous thrombosis in patients with hemophilic arthritis undergoing total knee arthroplasty without chemoprophylaxis: A prospective study.

BACKGROUND: Pharmacologic thromboprophylaxis is controversial for hemophiliacs who undergo total joint replacements. The purpose of this study was to assess the safety of tranexamic acid (TXA) utilization with respect to the incidence of deep venous thrombosis (DVT) in hemophiliacs undergoing total knee arthroplasty (TKA). METHODS: A total of 104 patients with hemophilic arthritis were included in the study. The patients were randomly divided into two groups of 52 subjects. All patients received a modified coagulation factor substitution regimen. In the TXA group, 1 g of TXA was injected intravenously 15 min before incision and 2 g of TXA was intra-articularly injected in the surgical area. A routine mechanical prophylaxis was administered to all patients under a standardized postoperative protocol. Thromboembolic complications in both groups were followed up for 2 years. RESULTS: All patients were male and underwent 146 arthroplasties. There was a mean age of 33.2 ± 8.8 years and a mean body mass index of 22.2 ± 5.1 kg/m2. A 100% compliance rate was observed with mechanical prophylaxis. No asymptomatic DVT was detected on postoperative ultrasound in all patients. We also failed to find any proof of clinical venous thromboembolism in our patients during a 2-year follow up. Only two cases in the TXA group underwent blood transfusions (4.0%), while 29.2% of the patients in the non-TXA group needed transfusion. CONCLUSIONS: This prospective study showed that TXA could be safely utilized in patients with hemophilic arthritis who underwent TKA without increasing the incidence of DVT and routine chemoprophylaxis may not be necessary.

Predictive value of atherogenic index of plasma and atherogenic index of plasma combined with low-density lipoprotein cholesterol for the risk of acute myocardial infarction.

Background and aims: Acute myocardial infarction (AMI) is a prevalent medical condition associated with significant morbidity and mortality rates. The principal underlying factor leading to myocardial infarction is atherosclerosis, with dyslipidemia being a key risk factor. Nonetheless, relying solely on a single lipid level is insufficient for accurately predicting the onset and progression of AMI. The present investigation aims to assess established clinical indicators in China, to identify practical, precise, and effective tools for predicting AMI. Methods: The study enrolled 267 patients diagnosed with acute myocardial infarction as the experimental group, while the control group consisted of 73 hospitalized patients with normal coronary angiography. The investigators collected general clinical data and relevant laboratory test results and computed the Atherogenic Index of Plasma (AIP) for each participant. Using acute myocardial infarction status as the dependent variable and controlling for confounding factors such as smoking history, fasting plasma glucose (FPG), low-density lipoprotein cholesterol (LDL-C), blood pressure at admission, and diabetes history, the researchers conducted multivariate logistic regression analysis with AIP as an independent variable. Receiver operating characteristic (ROC) curves were employed to determine the predictive value of AIP and AIP combined with LDL-C for acute myocardial infarction. Result: The results of the multivariate logistic regression analysis indicated that the AIP was an independent predictor of acute myocardial infarction. The optimal cut-off value for AIP to predict AMI was -0.06142, with a sensitivity of 81.3%, a specificity of 65.8%, and an area under the curve (AUC) of 0.801 (95% confidence interval [CI]: 0.743-0.859, P < 0.001). When AIP was combined with LDL-C, the best cut-off value for predicting acute myocardial infarction was 0.756107, with a sensitivity of 79%, a specificity of 74%, and an AUC of 0.819 (95% CI: 0.759-0.879, P < 0.001). Conclusions: The AIP is considered an autonomous determinant of risk for AMI. Utilizing the AIP index alone, as well as in conjunction with LDL-C, can serve as effective predictors of AMI.

Relationship between spinal imbalance and knee osteoarthritis by using full-body EOS.

BACKGROUND: Orthostatic state is maintained by harmonizing the spine, pelvis and lower extremities. In the past few decades, several studies have demonstrated the associations between spinal imbalance and generalized osteoarthritis. The compensatory mechanisms of pelvis translation and knee flexion, however, have not been fully assessed. METHODS: A total of 213 volunteers, over 40 years of age, were recruited. Radiological measurements were performed by EOS imaging system. Pelvic tilt (PT), pelvic incidence (PI), lumbar lordosis (LL), sagittal vertical axis (SVA), global tilt (GT), hip-knee-angle (HKA), knee flexion angle (KFA), lateral distal femoral angle (LDFA), and medial proximal tibial angle (MPTA) were measured. On the basis of SRS-Schwab, the subjects were classified into decompensated group (PI-LL > 20°), compensated group(10° ≤ PI-LL ≤ 20°), and normal group (PI-LL < 10°). Differences in radiographic parameters among groups were evaluated. Data of Knee Society Score (KSS) and Oswestry Disability Index (ODI) score were collected via questionnaires. RESULTS: Decompensated group showed larger pelvic parameters (PT) and low extremity parameters (LDFA, MPTA, HKA and KFA) than normal group (P < 0.05). Pelvic parameter was larger in the compensated group (median = 31°) compared to the normal group (median = 17°) (P < 0.05). There was no difference in low extremity parameters between the compensated and normal groups. At the sagittal plane, the radiological parameters of spine were greater in subjects with patellofemoral joint pain (PFP) than without PFP (P = 0.058). Higher PI-LL values were observed in women (P < 0.05). CONCLUSIONS: A correlation between sagittal spinal imbalance and knee joint angles was recognized. The progression of knee and low back pain was associated with the severity of sagittal spinal imbalance. Pelvic retroversion was considered to be the probable compensatory mechanism.

Efficacy of intra-articular injection of allogeneic platelet-rich plasma for knee osteoarthritis combined with hematologic blood dyscrasias with platelet dysfunction: protocol of a randomized, double-blind, placebo-controlled trial.

BACKGROUND: Autologous platelet-rich plasma (PRP) has been shown to alleviate the symptoms of patients suffering from knee osteoarthritis (KOA), but for certain patients with hematologic diseases with platelet dysfunction and patients receiving anti-platelet medications, autologous PRP is not an optimum solution. Allogeneic PRP has been proven to be safe and effective in the treatment of osteoarthritis, rotator cuff disease, refractory wounds and other medical fields. However, a well-designed and long-term follow-up prospective randomized controlled trial (RCT) to evaluate the effect of allogeneic PRP intra-articular injections for KOA combined with hematologic blood dyscrasias has not yet been performed. METHODS/ DESIGN: We will conduct an allogeneic PRP injection for KOA combined with hematologic blood dyscrasias with platelet dysfunction study: a prospective, randomized, double-blind, placebo-controlled trial. One hundred participants with KOA combined with hematologic blood dyscrasias with platelet dysfunction will be randomly allocated to receive either one allogeneic PRP injection or one saline injection into the knee joint. The primary outcome will be a 12-month change in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score. Secondary outcomes will be the 36-Item Short-Form General Health Survey (SF-36) score, Lysholm score, overall knee pain score and MRI assessment at 1-, 3-, 6- and 12-month. DISCUSSION: The results of this study will help determine whether allogeneic PRP could be used as a non-surgical intervention to treat patients with knee OA combined with hematologic blood dyscrasias with platelet dysfunction. TRIAL REGISTRATION: Chinese Clinical Trials Registry reference: ChiCTR2100048624. Prospectively registered 11th of July 2021.

Arthroscopic Rotator Cuff Repair In Patients With Parkinson's Disease: A Propensity Score Matching Study With Minimum 2-Year Follow-up.

BACKGROUND: Although the effectiveness of arthroscopic rotator cuff repair (ARCR) for structural and functional outcomes has been widespread proven, few researchers investigated the impact of ARCR on patients with Parkinson's Disease (PD), which may have previously been viewed as a relative contraindication to ARCR. METHODS: Data were collected retrospectively for all patients who underwent ARCR for small- to large-sized rotator cuff tears between September 2014 and May 2019. Patients were eligible for the study if they indicated that they diagnosed with rotator cuff repair and had minimum 2-year postoperative outcome scores for the range of motion (ROM), the Western Ontario Rotator Cuff Index (WORC), the Constant-Murley Score (CMS), the University of California, Los Angeles (UCLA), Pittsburgh Sleep Quality Index (PSQI), Hospital Anxiety and Depression Scale (HADS), and the visual analog scale (VAS) for pain. Propensity score matching (PSM), a statistical method, was used to screen a control group without PD matched 1:1 with similar age, sex, tear size, preoperative stiffness, and fatty infiltration, which have previously been identified as important factors influencing success rates. RESULTS: Three hundred and eighty-nine patients met all study criteria including required follow-up, of whom 31 and 358 with PD and without PD, respectively. After adjusting for confounders, the propensity score matched indicators were compared, patients with PD experienced significantly more pain (4.45 ± 2.43 vs. 0.52 ± 1.18; P<.001) and had lower WORC (49.10 ± 21.22 vs. 78.90 ± 17.54; P<.001), CMS (46.77 ± 22.24 vs. 79.45 ± 14.74; P<.001) and UCLA (21.11 ± 8.54 vs. 28.16 ± 6.16; P<.001) scores respectively than the matched control group. They also exhibited higher sleep disturbance (10.04 ± 5.36 vs. 5.19 ± 3.28; P<.001), as well as higher anxiety and depression psychological status at 24 months (P<.001; P<.001). Overall clinical outcomes from preoperatively to postoperatively were not improved significantly for patients with PD vs. without PD. CONCLUSION: Patients with PD experienced significantly more pain, resulted in worse shoulder functional outcomes, and reported persistently diminished mental and physical health status. Shoulder surgeons should be cognizant of PD as an outcome-modifying variable when treating patients with rotator cuff tears. This finding suggested that the need for ARCR in patients with PD should be carefully considered in the light of personalized needs and physical conditions.

Short-term clinical effectiveness of 5% lidocaine patch after arthroscopic rotator cuff repair: study protocol for a randomized, double-blinded, placebo-controlled clinical trial.

BACKGROUND: Arthroscopic rotator cuff repair (ARCR) often causes unbearable postoperative pain, even more severe than before surgery. Opioids are the drugs of choice for temporary postoperative analgesia. However, this conventional approach also has some side effects and potential for drug abuse. The aims of this study are expected to verify the effect of 5% lidocaine patch (LP5) on the intensity of early postoperative pain, functional recovery and quality of life in patients undergoing ARCR. METHODS: In this randomized, double-blind, and placebo-controlled clinical trial, a total of 102 postoperative patients undergoing ARCR will be randomly assigned to either the LP5 group, receiving topical lidocaine analgesia, or the placebo control group. The primary outcome measure will be the change in the American Shoulder Elbow Surgeons score from pre-operation to 90 days post-operation. Secondary outcomes will include pain scores, range of motion, opioid use, safety indicators, blinding assessment and several shoulder function score questionnaires. The effect of the allocated treatment will be assessed at preoperative baseline and at 7-, 14-, 30- and 90-day postoperatively. DISCUSSION: In this study, the efficacy and safety of the 5% lidocaine patch will be evaluated in terms of short-term clinical symptoms in patients undergoing ARCR. The results of this study will help determine whether LP5 is effective in early functional recovery in ARCR and whether it relieves pain and reduces opioid consumption. TRIAL REGISTRATION: Chinese Clinical Trial Registry ( http://www.chictr.org.cn ) ChiCTR2200060108. Registered on 19 May 2022.

Antioxidant PDA-PEG nanoparticles alleviate early osteoarthritis by inhibiting osteoclastogenesis and angiogenesis in subchondral bone.

Accumulating evidence suggests that osteoclastogenesis and angiogenesis in subchondral bone are critical destructive factors in the initiation and progression of osteoarthritis (OA). Herein, methoxypolyethylene glycol amine (mPEG-NH2) modified polydopamine nanoparticles (PDA-PEG NPs) were synthesized for treating early OA. The cytotoxicity and reactive oxygen species (ROS) scavenging ability of PDA-PEG NPs were evaluated. The effects of PDA-PEG NPs on osteoclast differentiation and vessel formation were then evaluated. Further, PDA-PEG NPs were administrated to anterior cruciate ligament transection (ACLT)-induced OA mice. Results demonstrated that PDA-PEG NPs had low toxicity both in vitro and in vivo. PDA-PEG NPs could inhibit osteoclastogenesis via regulating nuclear factor kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways. Moreover, PDA-PEG NPs suppressed osteoclast-related angiogenesis via down-regulating platelet-derived growth factor-BB (PDGF-BB). In vivo, PDA-PEG NPs inhibited subchondral bone resorption and angiogenesis, further rescuing cartilage degradation in OA mice. In conclusion, we demonstrated that PDA-PEG NPs deployment could be a potential therapy for OA.

Comparative outcomes of patient-specific instrumentation, the conventional method and navigation assistance in open-wedge high tibial osteotomy: A prospective comparative study with a two-year follow up.

BACKGROUND: To compare and analyze the correction precision, clinical outcomes and complications among the three methods of performing open-wedge high tibial osteotomy (HTO), including patient-specific instrumentation (PSI), conventional method and navigation assistance. METHODS: In this prospective, single-center study, we randomly assigned patients with knee osteoarthritis in a 1:1:1 ratio to undergo Open-wedge high tibial osteotomy (OWHTO) with conventional method, navigation assistance or PSI. The primary outcome was the target/observed hip-knee-ankle (HKA) angle difference at 1 month postoperatively. Secondary outcomes were changes in the postoperative posterior tibial slope (PTS) at 1 month and clinical outcomes including knee pain on a visual analogue scale (ranging from 0 to 100, with higher scores indicating more severe pain), Lysholm and Western Ontario and McMaster Universities Osteoarthritis Index (ranging from 0 to 240) scores at 1 month, 6 months, 12 months, and 24 months. RESULTS: From 2017 through 2019, a total of 608 patients were screened; of those patients, 144 were enrolled, with 48 in each group. The primary outcome of the HKA difference was 2.6 ± 2.0° in the conventional group, 2.3 ± 1.5° in the navigation group and 0.6 ± 1.0° in the PSI group (P < 0.001). Secondary outcomes including changes in the postoperative PTS and clinical outcomes at 1 month, 6 months, and 12 months were in the same direction as the primary outcome. There were no significant differences in the complications among the three groups. CONCLUSIONS: In the present study, none of the three methods showed superiority in objective correction precision and clinical outcomes at 2 years.

No Benefit to Platelet-rich Plasma Over Placebo Injections in Terms of Pain or Function in Patients with Hemophilic Knee Arthritis: A Randomized Trial.

BACKGROUND: Hemophilic knee arthritis is one of the most common presenting symptoms of hemophilia, and its management continues to be challenging to practitioners. Preliminary research has suggested that platelet-rich plasma (PRP) may have short-term efficacy in the treatment of hemophilic knee arthritis, but evidence for this treatment is limited. QUESTIONS/PURPOSES: What is the effectiveness of PRP compared with placebo in (1) reducing pain and improving knee joint function (as measured by WOMAC, VAS, and Hemophilia Joint Health Score [HJHS]) and (2) improving quality of life (as measured by SF-36 scores) in patients with hemophilic knee arthritis through 24 months of follow-up? METHODS: This was a prospective, parallel-group, double-blinded, single-center, placebo-controlled randomized clinical trial that included participants from a tertiary care center starting January 1, 2019, with follow-up completed on November 30, 2021. Participants were older than 18 years and had hemophilic knee arthritis confirmed by MRI, and they were randomly allocated to interventions in a 1:1 ratio. The investigators were not informed of the randomization sequence generated by the computer. Patient groups were comparable with respect to age, gender, BMI, hemophilia type, and disease severity at baseline. Physicians delivered three sessions (one per week) of a standard intraarticular injection of PRP (n = 95) or placebo (n = 95). The rate of successful blinding was balanced across the groups, which was assessed by asking participants which injection they thought they had received. The primary outcome was the WOMAC score (range 0 to 96; higher scores indicate more pain and worse function; minimum clinically important difference, 6.4 points) over 24 months. Among the 190 patients assigned to PRP or saline injections (mean age 31 ± 7 years), 100% (190) of patients were men). There was no between-group difference in the proportion of patients who completed the trial; 97% (92 of 95) of patients in the PRP group and 94% (89 of 95) of patients in the placebo group completed the trial. The most common adverse events were injection site discomfort 8% (8 of 95) in the PRP group and 4% (4 of 95) in the placebo group. An intention-to-treat analysis was planned, but there was no crossover between groups. All patients were included in the analyses. With 95 patients in each group, the study was powered a priori at 90% to detect a difference in WOMAC score of 6.4 points, which was considered a clinically important difference. RESULTS: There were no clinically important differences in the mean WOMAC, VAS pain, HJHS, SF-36, and MRI scores between groups at any timepoint. Intraarticular PRP did not ameliorate function, symptoms, and quality of life in patients with hemophilic knee arthritis. At 24 months of follow-up, the mean difference between the PRP and placebo groups in the WOMAC score was -1 (95% CI -5 to 2; p = 0.42). The mean difference in the VAS pain score was -0.3 (95% CI -0.8 to 0.2; p = 0.19), in the HJHS was -0.6 (95% CI -1.4 to 0.1; p = 0.10), in the SF-36 physical component summary was 0 (95% CI -2 to 3; p = 0.87), and in the SF-36 mental component summary was -1 (95% CI -3 to 2; p = 0.64). The mean differences in the MRI scores of soft tissue and osteochondral subscore were 0.1 (95% CI -0.3 to 0.5; p = 0.59) and -0.3 (95% CI -0.7 to 0.1; p = 0.19), respectively. CONCLUSION: Among patients with hemophilic knee arthritis, three intraarticular PRP injections, compared with placebo injections, did not improve hemophilic knee symptoms, function, and quality of life over 24 months. The results of this study do not support the use of PRP injections in patients who have hemophilic knee arthritis. LEVEL OF EVIDENCE: Level I, therapeutic study.

Intra-articular injections of platelet-rich plasma decrease pain and improve functional outcomes than sham saline in patients with knee osteoarthritis.

PURPOSE: To compare the long-term clinical efficacy provided by intra-articular injections of either Pure Platelet-rich Plasma (P-PRP) or sham saline to treat knee osteoarthritis (KOA). METHODS: This prospective, parallel-group, double-blind, multi-center, sham-controlled randomized clinical trial recruited participants with KOA from orthopedic departments at nine public hospitals (five tertiary medical centers, four secondary medical units) starting January 1, 2014, with follow-up completed on February 28, 2021. Participants were randomly allocated to interventions in a 1:1 ratio. Data were analyzed from March 1, 2021, to July 15, 2021. Three sessions (1 every week) of P-PRP or sham saline injected by physicians. The primary outcome was the Western Ontario and McMaster Universities Arthritis Index (WOMAC) at 3, 6, 12, 24, 60 months of follow-up. Secondary outcomes included the International Knee Documentation Committee (IKDC) subjective score, visual analogue scale (VAS) score, intra-articular biochemical marker concentrations, cartilage volume, and adverse events. Laboratory of each hospital analyzed the content and quality of P-PRP. RESULTS: 610 participants (59% women) with KOA who received three sessions of P-PRP (n = 308, mean age 53.91 years) or sham saline (n = 302, mean age 54.51 years) injections completed the trial. The mean platelet concentration in PRP is 4.3-fold (95% confidence interval 3.6-4.5) greater than that of whole blood. Both groups showed significant improvements in IKDC, WOMAC, and VAS scores at 1 month of follow-up. However, only the P-PRP group showed a sustained improvement in clinical outcome measurements at month 24 (P < 0.001). There were statistically significant differences between the P-PRP and sham saline groups in all clinical outcome measurements at each follow-up time point (P < 0.001). The benefit of P-PRP was clinically better in terms of WOMAC-pain, WOMAC-physical function and WOMAC-total at 6, 12, 24, and 60 months of follow-up. No clinically significant differences between treatments were documented in terms of WOMAC-stiffness at any follow-up. A clinically significant difference favoring P-PRP group against saline in terms of IKDC and VAS scores was documented at 6, 12, 24 and 60 months of follow-up. At 6 months after injection, TNF-α and IL-1ß levels in synovial fluid were lower in the P-PRP group (P < 0.001). Tibiofemoral cartilage volume decreased by a mean value of 1171 mm3 in the P-PRP group and 2311 mm3 in the saline group over 60 months and the difference between the group was statistically significant (intergroup difference, 1140 mm3, 95% CI - 79 to 1320 mm3; P < 0.001). CONCLUSIONS: In this randomized clinical trial of patients with KOA, P-PRP was superior to sham saline in treating KOA. P-PRP was effective for achieving at least 24 months of symptom relief and slowing the progress of KOA, with both P-PRP and saline being comparable in safety profiles.