Acupotomy alleviates knee osteoarthritis in rabbit by regulating chondrocyte mitophagy Pink1-Parkin pathway.

OBJECTIVE: To investigate the effect of acupotomy, on mitophagy and the Pink1-Parkin pathway in chondrocytes from rabbits with knee osteoarthritis (KOA). METHODS: A KOA model was established via the modified Videman method. Rabbits were randomly divided into a control group (CON), KOA group and KOA + acupotomy group (Acu). Rabbits in the acupotomy group were subjected to acupotomy for 4 weeks after model establishment. The behavior of the rabbits before and after intervention was recorded. Cartilage degeneration was evaluated by optical microscopy and fluorescence microscopy. The level of mitophagy was evaluated by transmission electron microscopy, immunofluorescence and enzyme-linked immunosorbent assay (ELISA). The expression of phosphatase and tensin homolog (PTEN)-induced kinase 1 (Pink1)-Parkin mitophagy pathway components was evaluated by immunofluorescence, Western blotting and real-time polymerase chain reaction. RESULTS: In rabbits with KOA, joint pain, mobility disorders and cartilage degeneration were observed, the Mankin score was increased, collagen type Ⅱ (Col-Ⅱ) expression was significantly decreased, mitophagy was inhibited, mitochondrial function was impaired, and factors associated with the Pink1-Parkin pathway were inhibited. Acupotomy regulated the expression of Pink1-Parkin pathway-related proteins, the mitophagy-related protein microtubule-associated protein-1 light chain-3, the translocase of the outer membrane, and the inner mitochondrial membrane 23; increased the colocalization of mitochondria and autophagosomes; promoted the removal of damaged mitochondria; restored mitochondrial adenosine-triphosphate (ATP) production; and alleviated cartilage degeneration in rabbits with KOA. CONCLUSIONS: Acupotomy played a role in alleviating KOA in rabbits by activating mitophagy in chondrocytes via the regulation of proteins that are related to the Pink1-Parkin pathway.

FUNCTIONAL CAPACITY IN PATIENTS WITH KNEE OSTEOARTHRITIS: CROSS-SECTIONAL STUDY.

Knee osteoarthritis (KOA) is a disabling inflammatory disease that makes walking and activities of daily living difficult. This condition can reduce functional capacity and increase the risk for surgery. OBJECTIVE: To know the functional capacity of patients with KOA evaluated by the six-minute walk test (6MWT). METHOD: This cross-sectional study evaluated age, gender, weight, BMI, pain (VAS 90-100), physical disability (WOMAC 0-96), degree of joint damage by radiographic imaging, and 6MWT. RESULTS: A total of 176 patients referred by Orthopedics were evaluated, with the inclusion of 164 participants. The mean age was 61.89 ± 10.62 years, 81% women, 67% with cardiovascular disease, hypertension and/or diabetes, 81% obese, with moderate pain (VAS 47.74 ± 29.27) and according to WOMAC, most had severe or very severe disability. The distance covered in the 6MWT was 354.03 ± 102.03m, 67% of the predicted distance. The maximum heart rate achieved was 107.27 ± 17.71 bpm, which characterizes 68% of the predicted by age. Only 12% of the sample showed a marked drop in oxygenation in the 6MWT and 40% had a recovery heart rate in the 1st minute below 15 bpm. CONCLUSION: Patients with KOA, who were evaluated by the 6MWT, have low functional capacity and physical deconditioning. Level of Clinical Evidence III, Case Control Study.

A osteoartrite de joelho (OAJ) é uma doença inflamatória incapacitante que dificulta as atividades de vida diária do indivíduo. Esta condição pode reduzir a capacidade funcional e aumentar o risco de cirurgia, caso necessária. Objetivo: Conhecer a capacidade funcional de pacientes com OAJ, avaliada pelo teste de caminhada de seis minutos (TC6M). Métodos: Neste estudo transversal, avaliamos idade, sexo, peso, índice de massa corporal (IMC), dor (escala visual analógica ­ EVA 90-100), incapacidade física (Western Ontario and McMaster Universities Osteoarthritis Index ­ WOMAC 0-96), grau de lesão articular por imagem radiográfica e TC6M. Resultados: Foram avaliados 176 pacientes encaminhados pela Ortopedia, com a inclusão de 164 participantes. Na amostra, verificou-se: média de idade de 61,89 ± 10,62 anos; 81% de mulheres; 67% com doença cardiovascular, hipertensão e/ou diabetes; 81% de obesos; com dor moderada (EVA 47,74 ± 29,27); e, segundo WOMAC, maioria com incapacidade intensa ou muito intensa. A distância percorrida no TC6M foi 354,03 ± 102,03 m, sendo esse valor 67% da distância prevista. A frequência cardíaca máxima alcançada foi de 107,27 ± 17,71 bpm, que caracteriza 68% da prevista pela idade. Somente 12% apresentaram acentuada queda de oxigenação no TC6M e 40% apresentaram frequência cardíaca de recuperação no primeiro minuto inferior a 15 bpm. Conclusão: Os pacientes com OAJ, que foram avaliados pelo TC6M, apresentaram baixa capacidade funcional e descondicionamento físico. Nível de Evidência III, Estudo de Caso Controle.

Causal analysis of body composition measurements in osteoarthritis knee: a two-sample mendelian randomization study.

BACKGROUND: To analyse the causal associations of different physical measures with osteoarthritis knee (KOA). METHODS: Exposure factors (weight, body mass index (BMI), body fat percentage, waist circumference, hip circumference, waist-hip ratio (WHR), and basal metabolic rate (BMR)), and outcome factor KOA were analyzed by inverse-variance weighted (IVW) method, along with heterogeneity test, sensitivity and pleiotropy analyses. Meta-analysis was used to combine the effect values of IVW methods in different data sources. RESULTS: Weight, BMI, body fat percentage, waist circumference, hip circumference and BMR analyses showed causal association with increased KOA risk, while WHR analysis indicated a reduction of the incidence of KOA. P-value for all the results was less than 0.05 and F-value large than 20. All results were negative for heterogeneity tests and sensitivity analyses, and there was pleiotropy in weight and BMR. Meta-analysis results showed that the results of Odds Ratios (95% Confidence Intervals) for Weight (1.43(1.35-1.51)), BMI (1.40(1.10-1.78)), body fat percentage (1.56(1.44-1.68)), waist circumference (1.40(1.10-1.78)), hip circumference (1.37(1.30-1.44)), WHR (0.86(0.71-1.04)) and BMR (1.36(1.27-1.46) were consistent with the ones by Mendelian randomization analyses. CONCLUSIONS: Body fat percentage may be a better indicator of KOA than BMI. In addition, weight and BMR may have a causal effect in KOA, but WHR does not have a causal relationship. BMI, body fat percentage, waist circumference, and hip circumference has a causal effect on KOA.

Quadriceps Tendon Autograft ACL Reconstruction With Suture Tape Augmentation: Safe Results Based on Minimum 2-Year Follow-up MRI.

Background: The potential intra-articular effects of ≥1 year after anterior cruciate ligament reconstruction (ACLR) with independent suture tape augmentation (STA) are not fully understood. Purpose: To investigate whether incorporating suture tape in an all-soft tissue quadriceps tendon autograft (QTA) ACLR leads to satisfactory patient outcomes while having no intra-articular side effects as determined by magnetic resonance imaging (MRI). Study Design: Case series; Level of evidence, 4. Methods: Included were 25 patients with a mean age of 19.9 years (95% CI, 17.3-22.5 years) who underwent QTA ACLR with STA between 2016 and 2019. All patients underwent MRI at ≥1 year postoperatively and had at least a 2-year follow-up (mean, 28 months [95% CI, 26.5-29.5 months]) that included physical examination with anterior laxity testing with KT-1000 arthrometer, radiographs, and patient-reported outcome measures (PROMs). At the final follow-up, the minimal clinically important difference (MCID) and the Patient Acceptable Symptom State (PASS) for applicable PROMs were applied to each patient. Postoperative graft and joint integrity were assessed using the Howell classification and the MRI Osteoarthritis Knee Score (MOAKS) joint effusion/synovitis grade. The Mann-Whitney U test for continuous variables and the chi-square or the Fisher exact test for categorical variables were used for statistical analyses. Results: The MRI assessment of the grafts demonstrated intact grafts in all patients. Overall, 96% of patients demonstrated grades 0 or 1 MOAKS for joint effusion/synovitis. All patient outcomes significantly improved from preoperatively to the final follow-up (P < .001), except for the Marx score, which decreased significantly (14.2 [95% CI, 12.7-15.8] vs 9.72 [95% CI, 7.3-12.2]; P = .0014). At least 68% of the patients achieved the MCID threshold, and 92% achieved the PASS threshold for all applicable PROMs. Conclusion: QTA ACLR with STA did not demonstrate adverse intra-articular changes on MRI at ≥1 year postoperatively. In addition, STA did not appear to negatively affect PROMs.

Comparative evaluation of functional outcome and pain relief after pulsed radiofrequency of the saphenous nerve within and distal to the adductor canal in medial compartment knee osteoarthritis: A randomized double-blind trial.

Background and Aims: Pulsed radiofrequency (PRF) of the saphenous nerve (SN) has shown effective pain relief in knee pain because of knee osteoarthritis (KOA). The adductor canal (AC) contains other sensory nerves innervating the medial part of the knee joint apart from SN. We compared the PRF of SN within and outside the AC for their quality and duration of pain relief in knee osteoarthritis of the medial compartment (KOA-MC). Material and Methods: We conducted a randomized prospective study in 60 patients with anteromedial knee pain because of KOA-MC. Patients in group A received PRF-SN, and those in group B received PRF-AC. The primary objectives were comparison of pain by Visual Analog Scale (VAS) scores and changes in quality of daily living by Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and OXFORD knee scores. The secondary objectives were comparison of analgesic requirements using Medicine Quantification Scale (MQS) scores and block-related complications. Intra-group comparison was performed by analysis of variance. Inter-group normally distributed data were assessed by Student's t-test, non-normally distributed and ordinal data were assessed by Mann-Whitney U-test, and categorical data were assessed by Chi-square test. A P value of <0.05 was considered significant. Results: VAS scores were significantly lower in Gr-B at 12 weeks. The WOMAC scores and OXFORD scores at 4, 8, 12, and 24 weeks were significantly lower in Gr-B compared to Gr-A. Conclusion: The PRF-AC provides better pain relief and functional outcome than PRF-SN; however, duration of pain relief was not significantly different.

Primary osteoarthritis chondrocyte map of chromatin conformation reveals novel candidate effector genes.

OBJECTIVES: Osteoarthritis is a complex disease with a huge public health burden. Genome-wide association studies (GWAS) have identified hundreds of osteoarthritis-associated sequence variants, but the effector genes underpinning these signals remain largely elusive. Understanding chromosome organisation in three-dimensional (3D) space is essential for identifying long-range contacts between distant genomic features (e.g., between genes and regulatory elements), in a tissue-specific manner. Here, we generate the first whole genome chromosome conformation analysis (Hi-C) map of primary osteoarthritis chondrocytes and identify novel candidate effector genes for the disease. METHODS: Primary chondrocytes collected from 8 patients with knee osteoarthritis underwent Hi-C analysis to link chromosomal structure to genomic sequence. The identified loops were then combined with osteoarthritis GWAS results and epigenomic data from primary knee osteoarthritis chondrocytes to identify variants involved in gene regulation via enhancer-promoter interactions. RESULTS: We identified 345 genetic variants residing within chromatin loop anchors that are associated with 77 osteoarthritis GWAS signals. Ten of these variants reside directly in enhancer regions of 10 newly described active enhancer-promoter loops, identified with multiomics analysis of publicly available chromatin immunoprecipitation sequencing (ChIP-seq) and assay for transposase-accessible chromatin using sequencing (ATAC-seq) data from primary knee chondrocyte cells, pointing to two new candidate effector genes SPRY4 and PAPPA (pregnancy-associated plasma protein A) as well as further support for the gene SLC44A2 known to be involved in osteoarthritis. For example, PAPPA is directly associated with the turnover of insulin-like growth factor 1 (IGF-1) proteins, and IGF-1 is an important factor in the repair of damaged chondrocytes. CONCLUSIONS: We have constructed the first Hi-C map of primary human chondrocytes and have made it available as a resource for the scientific community. By integrating 3D genomics with large-scale genetic association and epigenetic data, we identify novel candidate effector genes for osteoarthritis, which enhance our understanding of disease and can serve as putative high-value novel drug targets.

[Evolving indications for partial knee replacement : New aspects]. / Update Indikation Teilprothese : Neue Aspekte.

BACKGROUND: Partial knee replacement has proven to be an effective therapy for advanced unicompartmental arthrosis of the knee. Despite continuous advancements in implants and surgical techniques over the past decades, the global preference for total knee arthroplasty still persists for historical reasons. OBJECTIVES: This report aims to illuminate advantages and disadvantages of partial knee replacement considering long-term results, the evolution of indication criteria over recent decades and new aspects in patient selection with potential improvements through emerging technologies. MATERIAL AND METHODS: The analysis involves the examination of long-term results from clinical studies and registry data, highlighting the risk factors for potential failures and their influence on the development of indication criteria. RESULTS: Present-day long-term results demonstrate excellent prosthetic survival, aligning with outcomes from total knee arthroplasty. New perspectives for expanding indication criteria are discussed, including the possible application of partial knee replacement in cases of severe varus deformity > 15°, anterior cruciate ligament insufficiency, young active patients, anterior knee pain, and/or patellofemoral arthritis, as well as mild radiographic arthritis with degenerative medial meniscus root tear and meniscal extrusion. DISCUSSION: Indication criteria have consistently expanded in recent years, taking into account modern insights, and the application of advanced technologies can enhance precision and minimize surgical errors. Furthermore, this report emphasizes that revision rates are not the sole criterion for success and underscores the necessity for a comprehensive examination of clinical results.

Efficacy and safety of extracorporeal shock wave therapy combined with sodium hyaluronate in treatment of knee osteoarthritis: a systematic review and Meta-analysis.

OBJECTIVE: To assess the efficacy and safety of extracorporeal shockwave therapy (ESWT) combined with sodium hyaluronate (HA) for the treatment of knee osteoarthritis (KOA). METHODS: PubMed, Embase, the Cochrane Library, Web of Science, China National Knowledge Infrastructure, Wanfang database, China Science and Technology Journal Database, and SinoMed were searched from inception to July 2020. The quality of the randomized controlled trials was evaluated independently by two reviewers according to the criteria in the Cochrane Collaboration for Systematic Reviews. The identified articles were then screened individually using EndnoteX9 for eligibility in this Meta-analysis. The heterogeneity among the articles was evaluated using I2. RESULTS: A total of 17 studies, comprising 2000 individuals, were included in this Meta-analysis. The results showed that a significant improvement was observed in knee pain and function based on the clinical efficacy of ESWT combined with HA. Statistical analysis of clinical efficacy showed that [relative risk (RR) = 1.21, 95% confidence interval (CI) (1.12, 1.30), P < 0.01]. Statistical analysis of visual analog scale showed that [standardized mean difference (SMD) = －2.84, 95%CI (－4.01, －1.66), P < 0.01]. Western Ontario and McMaster University osteoarthritis index statistical analysis showed that [SMD = －1.57, 95% CI (－2.52, －0.61), P < 0.01]. Lysholm score statistical analysis showed that [SMD = 1.71, 95% CI (0.98, 2.44), P < 0.01]. In addition, only minor side effects, such as redness and swelling of the skin, were observed. CONCLUSIONS: Medium to low quality evidence showed that ESWT combined with HA offers an inexpensive, well-tolerated, safe, and effective method to improve pain and functionality in patients with KOA. However, tightly controlled, randomized, large multicenter trials are warranted to validate the current findings.

Efficacy and Safety of Cryoablation Compared with Cooled Radiofrequency Ablation of Genicular Nerves in Advanced Osteoarthritis of the Knee: A Study Protocol of Single-Centric, Assessor-Blinded, Randomized, Parallel-Group, Non-inferiority Study.

PURPOSE: In patients with symptomatic osteoarthritis knee (OAK), cryoneurolysis (CRYO) and cooled radiofrequency ablation (C-RFA) are reported to be effective and safe; however, they have not been compared directly. The objective of this study is to compare CRYO and C-RFA of the genicular nerve (GN) in terms of efficacy and safety profile in patients with Kellgren and Lawrence (KL) grade ≥ 3 OAK. METHODS: This single-centric, assessor-blinded, randomized, parallel-group, non-inferiority study will include 80 patients with KL grade ≥ 3 OAK. The patients with ≥ 50% pain relief on diagnostic block of three GNs will be randomized to one of the two groups, i.e., CRYO (n = 40) or C-RFA (n = 40). The three target GNs for the interventions will include: superior medial, superior lateral, and inferior medial. The primary outcome will be efficacy of CRYO or C-RFA at 2, 12, and 24 weeks post-procedure based on the 11-point Numerical Pain Rating Scale. The secondary outcomes will be functional improvement based on 12-item Oxford Knee Score and safety of both the procedures. The study is registered in the Clinical Trials Registry-India. CONCLUSION: CRYO and C-RFA provide pain relief and improve functional outcome by preventing transmission of pain signals, though by distinct mechanisms. While C-RFA is an established treatment modality, recent evidence supports CRYO in patients with OAK. This study intends to demonstrate non-inferiority of CRYO against C-RFA, thereby supporting the use of CRYO as an additional treatment modality in patients with KL grade ≥ 3 OAK.

Comparative Functional and Isokinetic Analysis between Implants with Posterior Stabilization and Rotating Hinge Total Knee Arthroplasty.

Objective : To compare the function and muscle strength of the limb between patients undergoing knee arthroplasties using primary implants with posterior stabilization (control group) and patients with rotating hinge implants (Hinge group). Methods : Function assessment was performed using the Knee Society Score (KSS) and muscle strength using an isokinetic dynamometer using a speed of 60°/s. Results : 43 patients were analyzed, who underwent 51 surgeries, with the Hinge group comprising 25 surgeries and the control group comprising 26 primary surgeries. We did not observe significant differences between the Hinge and control groups in the values of functional KSS (p = 0.54), objective KSS (p = 0.91), peak flexor torque (p = 0.25) and peak extensor torque (p = 0.08). Patients in the Hinge group who underwent primary arthroplasties had a higher peak flexor torque (0.76 Nm/kg) than those who used the implant in revision after septic failure (0.33 Nm/kg) (p < 0.05). The constrained implant was indicated in arthroplasty revision surgeries with severe ligament instability and in cases of complex primary arthroplasties with bone destruction or severe coronal deformity in the coronal plane. Conclusion : The use of constrained implants enables joint function and muscle strength comparable to patients who underwent primary arthroplasty using conventional implants with posterior stabilization. Patients undergoing septic revision with a rotating Hinge prosthesis exhibit lower flexor muscle strength compared to those undergoing primary arthroplasty with a constrained implant.

Unveiling inflammatory and prehypertrophic cell populations as key contributors to knee cartilage degeneration in osteoarthritis using multi-omics data integration.

OBJECTIVES: Single-cell and spatial transcriptomics analysis of human knee articular cartilage tissue to present a comprehensive transcriptome landscape and osteoarthritis (OA)-critical cell populations. METHODS: Single-cell RNA sequencing and spatially resolved transcriptomic technology have been applied to characterise the cellular heterogeneity of human knee articular cartilage which were collected from 8 OA donors, and 3 non-OA control donors, and a total of 19 samples. The novel chondrocyte population and marker genes of interest were validated by immunohistochemistry staining, quantitative real-time PCR, etc. The OA-critical cell populations were validated through integrative analyses of publicly available bulk RNA sequencing data and large-scale genome-wide association studies. RESULTS: We identified 33 cell population-specific marker genes that define 11 chondrocyte populations, including 9 known populations and 2 new populations, that is, pre-inflammatory chondrocyte population (preInfC) and inflammatory chondrocyte population (InfC). The novel findings that make this an important addition to the literature include: (1) the novel InfC activates the mediator MIF-CD74; (2) the prehypertrophic chondrocyte (preHTC) and hypertrophic chondrocyte (HTC) are potentially OA-critical cell populations; (3) most OA-associated differentially expressed genes reside in the articular surface and superficial zone; (4) the prefibrocartilage chondrocyte (preFC) population is a major contributor to the stratification of patients with OA, resulting in both an inflammatory-related subtype and a non-inflammatory-related subtype. CONCLUSIONS: Our results highlight InfC, preHTC, preFC and HTC as potential cell populations to target for therapy. Also, we conclude that profiling of those cell populations in patients might be used to stratify patient populations for defining cohorts for clinical trials and precision medicine.

A Quantum-Enhanced Precision Medicine Application to Support Data-Driven Clinical Decisions for the Personalized Treatment of Advanced Knee Osteoarthritis: The Development and Preliminary Validation of precisionKNEE_QNN.

Background Quantum computing and quantum machine learning (QML) are promising experimental technologies that can improve precision medicine applications by reducing the computational complexity of algorithms driven by big, unstructured, real-world data. The clinical problem of knee osteoarthritis is that, although some novel therapies are safe and effective, the response is variable, and defining the characteristics of an individual who will respond remains a challenge. In this study, we tested a quantum neural network (QNN) application to support precision data-driven clinical decisions to select personalized treatments for advanced knee osteoarthritis. Methodology After obtaining patients' consent and Research Ethics Committee approval, we collected the clinicodemographic data before and after the treatment from 170 patients eligible for knee arthroplasty (Kellgren-Lawrence grade ≥3, Oxford Knee Score (OKS) ≤27, age ≥64 years, and idiopathic aetiology of arthritis) treated over a two-year period with a single injection of microfragmented fat. Gender classes were balanced (76 males and 94 females) to mitigate gender bias. A patient with an improvement ≥7 OKS was considered a responder. We trained our QNN classifier on a randomly selected training subset of 113 patients to classify responders from non-responders (73 responders and 40 non-responders) in pain and function at one year. Outliers were hidden from the training dataset but not from the validation set. Results We tested our QNN classifier on a randomly selected test subset of 57 patients (34 responders, 23 non-responders) including outliers. The no information rate was 0.59. Our application correctly classified 28 responders out of 34 and 6 non-responders out of 23 (sensitivity = 0.82, specificity = 0.26, F1 Statistic = 0.71). The positive and negative likelihood ratios were 1.11 and 0.68, respectively. The diagnostic odds ratio was 2. Conclusions Preliminary results on a small validation dataset showed that QML applied to data-driven clinical decisions for the personalized treatment of advanced knee osteoarthritis is a promising technology to reduce computational complexity and improve prognostic performance. Our results need further research validation with larger, real-world unstructured datasets, as well as clinical validation with an artificial intelligence clinical trial to test model efficacy, safety, clinical significance, and relevance at a public health level.

EULAR recommendations for the non-pharmacological core management of hip and knee osteoarthritis: 2023 update.

INTRODUCTION: Hip and knee osteoarthritis (OA) are increasingly common with a significant impact on individuals and society. Non-pharmacological treatments are considered essential to reduce pain and improve function and quality of life. EULAR recommendations for the non-pharmacological core management of hip and knee OA were published in 2013. Given the large number of subsequent studies, an update is needed. METHODS: The Standardised Operating Procedures for EULAR recommendations were followed. A multidisciplinary Task Force with 25 members representing 14 European countries was established. The Task Force agreed on an updated search strategy of 11 research questions. The systematic literature review encompassed dates from 1 January 2012 to 27 May 2022. Retrieved evidence was discussed, updated recommendations were formulated, and research and educational agendas were developed. RESULTS: The revised recommendations include two overarching principles and eight evidence-based recommendations including (1) an individualised, multicomponent management plan; (2) information, education and self-management; (3) exercise with adequate tailoring of dosage and progression; (4) mode of exercise delivery; (5) maintenance of healthy weight and weight loss; (6) footwear, walking aids and assistive devices; (7) work-related advice and (8) behaviour change techniques to improve lifestyle. The mean level of agreement on the recommendations ranged between 9.2 and 9.8 (0-10 scale, 10=total agreement). The research agenda highlighted areas related to these interventions including adherence, uptake and impact on work. CONCLUSIONS: The 2023 updated recommendations were formulated based on research evidence and expert opinion to guide the optimal management of hip and knee OA.

Telerehabilitation is as effective as outpatient visits in the management of early osteoarthritis knee and mechanical low backache.

PURPOSE: Teleconsultation services can be used to overcome the barriers imposed by the Covid-19 pandemic in providing basic orthopaedic rehabilitation services. Aim of the study is to compare the effectiveness of rehabilitation provided via outpatient and teleconsultation in patients with mechanical low backache (LBA) and early osteoarthritis (OA) of the knee joint utilizing Patient-Reported Outcome Measures. The satisfaction level of patients receiving teleconsultation will also be assessed. METHODOLOGY: This study was a hospital-based prospective observational study. The study's participants were divided into two groups (Outpatient and Teleconsultation, respectively), and each group was further divided into two subgroups of 100 participants each (Knee-pain subgroup 1; LBA subgroup 2). SF-12 questionnaire, visual analogue scale (VAS) score for pain, and functional outcome scores (KOOS score for knee pain and the modified Oswestry Disability Index-MODI for LBA) were assessed at initial presentation and 6 months follow-up. Participants' satisfaction for teleconsultation service was assessed at final follow-up by 5 points Likert scale (5, very satisfied; 1, very dissatisfied). RESULTS: Mean consultation time was significantly longer in the outpatient group (p < 0.001). No statistically significant difference in the VAS score, KOOS score (58.0 ± 7.6 vs. 57.8 ± 9.2; p = 0.893), and MODI Score (24.7 ± 13.3 vs. 27.4 ± 12.4; p = 0.128) between the corresponding subgroups of the two groups at final follow-up. Eighty-seven percentage of the participants were satisfied (Likert score ≥ 4) with the teleconsultation services. CONCLUSION: Teleconsultation is equally effective to that as face-to-face outpatient consultation in the rehabilitation of patients with early OA knee and mechanical LBA. LEVEL OF STUDY: Level 2, Prospective comparative study.

OA susceptibility in mice is partially mediated by the gut microbiome, is transferrable via microbiome transplantation and is associated with immunophenotype changes.

OBJECTIVES: The Murphy Roths Large (MRL)/MpJ 'superhealer' mouse strain is protected from post-traumatic osteoarthritis (OA), although no studies have evaluated the microbiome in the context of this protection. This study characterised microbiome differences between MRL and wild-type mice, evaluated microbiome transplantation and OA and investigated microbiome-associated immunophenotypes. METHODS: Cecal material from mixed sex C57BL6/J (B6) or female MRL/MpJ (MRL) was transplanted into B6 and MRL mice, then OA was induced by disruption of the medial meniscus surgery (DMM). In other experiments, transplantation was performed after DMM and transplantation was performed into germ-free mice. Transplanted mice were bred through F2. OARSI, synovitis and osteophyte scores were determined blindly 8 weeks after DMM. 16S microbiome sequencing was performed and metagenomic function was imputed. Immunophenotypes were determined using mass cytometry. RESULTS: MRL-into-B6 transplant prior to DMM showed reduced OA histopathology (OARSI score 70% lower transplant vs B6 control), synovitis (60% reduction) and osteophyte scores (30% reduction) 8 weeks after DMM. When performed 48 hours after DMM, MRL-into-B6 transplant improved OA outcomes but not when performed 1-2 weeks after DMM. Protection was seen in F1 (60% reduction) and F2 progeny (30% reduction). Several cecal microbiome clades were correlated with either better (eg, Lactobacillus, R=-0.32, p=0.02) or worse (eg, Rikenellaceae, R=0.43, p=0.001) OA outcomes. Baseline immunophenotypes associated with MRL-into-B6 transplants and MRL included reduced double-negative T cells and increased CD25+CD4+ T cells. CONCLUSION: The gut microbiome is responsible in part for OA protection in MRL mice and is transferrable by microbiome transplantation. Transplantation induces resting systemic immunophenotyping changes that correlate with OA protection.

Functional capacity in patients with knee osteoarthritis: cross-sectional study / Capacidade funcional em pacientes com osteoartrite de joelho: estudo transversal

ABSTRACT Knee osteoarthritis (KOA) is a disabling inflammatory disease that makes walking and activities of daily living difficult. This condition can reduce functional capacity and increase the risk for surgery. Objective: To know the functional capacity of patients with KOA evaluated by the six-minute walk test (6MWT). Method: This cross-sectional study evaluated age, gender, weight, BMI, pain (VAS 90-100), physical disability (WOMAC 0-96), degree of joint damage by radiographic imaging, and 6MWT. Results: A total of 176 patients referred by Orthopedics were evaluated, with the inclusion of 164 participants. The mean age was 61.89 ± 10.62 years, 81% women, 67% with cardiovascular disease, hypertension and/or diabetes, 81% obese, with moderate pain (VAS 47.74 ± 29.27) and according to WOMAC, most had severe or very severe disability. The distance covered in the 6MWT was 354.03 ± 102.03m, 67% of the predicted distance. The maximum heart rate achieved was 107.27 ± 17.71 bpm, which characterizes 68% of the predicted by age. Only 12% of the sample showed a marked drop in oxygenation in the 6MWT and 40% had a recovery heart rate in the 1st minute below 15 bpm. Conclusion: Patients with KOA, who were evaluated by the 6MWT, have low functional capacity and physical deconditioning. Level of Clinical Evidence III, Case Control Study.

RESUMO A osteoartrite de joelho (OAJ) é uma doença inflamatória incapacitante que dificulta as atividades de vida diária do indivíduo. Esta condição pode reduzir a capacidade funcional e aumentar o risco de cirurgia, caso necessária. Objetivo: Conhecer a capacidade funcional de pacientes com OAJ, avaliada pelo teste de caminhada de seis minutos (TC6M). Métodos: Neste estudo transversal, avaliamos idade, sexo, peso, índice de massa corporal (IMC), dor (escala visual analógica - EVA 90-100), incapacidade física (Western Ontario and McMaster Universities Osteoarthritis Index - WOMAC 0-96), grau de lesão articular por imagem radiográfica e TC6M. Resultados: Foram avaliados 176 pacientes encaminhados pela Ortopedia, com a inclusão de 164 participantes. Na amostra, verificou-se: média de idade de 61,89 ± 10,62 anos; 81% de mulheres; 67% com doença cardiovascular, hipertensão e/ou diabetes; 81% de obesos; com dor moderada (EVA 47,74 ± 29,27); e, segundo WOMAC, maioria com incapacidade intensa ou muito intensa. A distância percorrida no TC6M foi 354,03 ± 102,03 m, sendo esse valor 67% da distância prevista. A frequência cardíaca máxima alcançada foi de 107,27 ± 17,71 bpm, que caracteriza 68% da prevista pela idade. Somente 12% apresentaram acentuada queda de oxigenação no TC6M e 40% apresentaram frequência cardíaca de recuperação no primeiro minuto inferior a 15 bpm. Conclusão: Os pacientes com OAJ, que foram avaliados pelo TC6M, apresentaram baixa capacidade funcional e descondicionamento físico. Nível de Evidência III, Estudo de Caso Controle.

Comparative Functional and Isokinetic Analysis between Implants with Posterior Stabilization and Rotating Hinge Total Knee Arthroplasty / Análise funcional e isocinética comparativa entre implantes com estabilização posterior e rotatórios constritos (hinge) em artroplastias do joelho

Abstract Objective: To compare the function and muscle strength of the limb between patients undergoing knee arthroplasties using primary implants with posterior stabilization (control group) and patients with rotating hinge implants (Hinge group). Methods: Function assessment was performed using the Knee Society Score (KSS) and muscle strength using an isokinetic dynamometer using a speed of 60°/s. Results: 43 patients were analyzed, who underwent 51 surgeries, with the Hinge group comprising 25 surgeries and the control group comprising 26 primary surgeries. We did not observe significant differences between the Hinge and control groups in the values of functional KSS (p = 0.54), objective KSS (p = 0.91), peak flexor torque (p = 0.25) and peak extensor torque (p = 0.08). Patients in the Hinge group who underwent primary arthroplasties had a higher peak flexor torque (0.76 Nm/kg) than those who used the implant in revision after septic failure (0.33 Nm/kg) (p <0.05). The constrained implant was indicated in arthroplasty revision surgeries with severe ligament instability and in cases of complex primary arthroplasties with bone destruction or severe coronal deformity in the coronal plane. Conclusion: The use of constrained implants enables joint function and muscle strength comparable to patients who underwent primary arthroplasty using conventional implants with posterior stabilization. Patients undergoing septic revision with a rotating Hinge prosthesis exhibit lower flexor muscle strength compared to those undergoing primary arthroplasty with a constrained implant.

Resumo Objetivo: Comparar a função e a força muscular do membro entre pacientes submetidos a artroplastias do joelho que utilizaram implantes primários com estabilização posterior (grupo controle) e pacientes com implantes constritos rotatórios (grupo Hinge). Métodos: A avaliação da função foi feita por meio do Knee Society Score (KSS) e da força muscular por um dinamômetro isocinético utilizando a velocidade de 60°/s. Resultados: Foram analisados 43 pacientes, que realizaram 51 cirurgias, sendo o grupo Hinge composto por 25 cirurgias e o grupo controle por 26 cirurgias primárias. Não observamos diferenças significativas entre os grupos Hinge e controle nos valores do KSS funcional (p = 0,54), KSS objetivo (p = 0,91), pico de torque flexor (p = 0,25) e pico de torque extensor (p =0,08). Os pacientes do grupo Hinge que realizaram artro-plastias primárias apresentaram um pico de torque flexor maior (0,76 Nm/kg) que aqueles que utilizaram o implante em revisão após falha séptica (0,33 Nm/kg) (p < 0,05). O implante constrito foi indicado em cirurgias de revisão de artroplastia com instabilidade ligamentar grave e em casos de artroplastias primárias complexas com destruição óssea ou deformidade coronal grave no plano coronal. Conclusão: O uso de implantes bloqueados possibilita função articular e força muscular comparáveis a dos pacientes que realizaram artroplastia primária utilizando implantes convencionais com estabilização posterior. Pacientes submetidos à revisão séptica com prótese Hinge rotatória apresentam menor força da musculatura flexora em relação àqueles submetidos a artroplastia primária com implante constrito.

Evaluation of an Unloading Concept for Knee Osteoarthritis: A Pilot Study in a Small Patient Group.

Joint compressive forces have been identified as a risk factor for osteoarthritis disease progression. Therefore, unloader braces are a common treatment with the aim of relieving pain, but their effects are not clearly documented in the literature. A knee brace concept was tested with the aim of reducing joint loads and pain in knee osteoarthritis patients by applying an extension moment exclusively during the stance phase. The ideal effects were evaluated during gait based on musculoskeletal modeling of six patients, and experimental tests with a prototype brace were conducted on one patient. The effects were evaluated using electromyography measurements and musculoskeletal models to evaluate the muscle activation and knee compressive forces, respectively. The ideal brace simulations revealed a varying reduction of the first peak knee force between 3.5% and 33.8% across six patients whereas the second peak was unaffected. The prototype reduced the peak vasti muscle activation with 7.9% and musculoskeletal models showed a reduction of the first peak knee compressive force of up to 26.3%. However, the prototype brace increased the knee joint force impulse of up to 17.1% and no immediate pain reduction was observed. The reduction of the first peak knee compressive force, using a prototype on a single patient, indicates a promising effect from an applied knee extension moment for reducing knee joint loads during normal gait. However, further clinical experiments with this brace method are required to evaluate the long-term effects on both pain and disease progression in knee osteoarthritis patients.

Gut-joint axis in knee synovitis: gut fungal dysbiosis and altered fungi-bacteria correlation network identified in a community-based study.

OBJECTIVES: Knee synovitis is a highly prevalent and potentially curable condition for knee pain; however, its pathogenesis remains unclear. We sought to assess the associations of the gut fungal microbiota and the fungi-bacteria correlation network with knee synovitis. METHODS: Participants were derived from a community-based cross-sectional study. We performed an ultrasound examination of both knees. A knee was defined as having synovitis if its synovium was ≥4 mm and/or Power Doppler (PD) signal was within the knee synovium area (PD synovitis). We collected faecal specimens from each participant and assessed gut fungal and bacterial microbiota using internal transcribed spacer 2 and shotgun metagenomic sequencing. We examined the relation of α-diversity, ß-diversity, the relative abundance of taxa and the interkingdom correlations to knee synovitis. RESULTS: Among 977 participants (mean age: 63.2 years; women: 58.8%), 191 (19.5%) had knee synovitis. ß-diversity of the gut fungal microbiota, but not α-diversity, was significantly associated with prevalent knee synovitis. The fungal genus Schizophyllum was inversely correlated with the prevalence and activity (ie, control, synovitis without PD signal and PD synovitis) of knee synovitis. Compared with those without synovitis, the fungi-bacteria correlation network in patients with knee synovitis was smaller (nodes: 93 vs 153; edges: 107 vs 244), and the average number of neighbours was fewer (2.3 vs 3.2). CONCLUSION: Alterations of gut fungal microbiota and the fungi-bacteria correlation network are associated with knee synovitis. These novel findings may help understand the mechanisms of the gut-joint axis in knee synovitis and suggest potential targets for future treatment.