Inflamed Knee Research Articles

Macrophage depletion in inflamed rat knees prevents the activation of synovial mesenchymal stem cells by weakening Nampt and Spp1 signaling

BackgroundMacrophages and mesenchymal stem cells (MSCs) engage in crucial interplay during inflammation and have significant roles in tissue regeneration. Synovial MSCs, as key players in joint regeneration, are known to proliferate together with macrophages in synovitis. However, the crosstalk between synovial MSCs and macrophages remains unclear. In this study, we investigated changes in the activation of synovial MSCs in inflamed rat knees following selective depletion of macrophages with clodronate liposomes.MethodsAcute inflammation was induced in rat knee joints by injection of carrageenan (day 0). Clodronate liposomes were administered intra-articularly on days 1 and 4 to deplete macrophages, with empty liposomes as a control. Knee joints were collected on day 7 for evaluation by histology, flow cytometry, and colony-forming assays. Concurrently, synovial MSCs were cultured and subjected to proliferation assays, flow cytometry, and chondrogenesis assessments. We also analyzed their crosstalk using single-cell RNA sequencing (scRNA-seq).ResultsClodronate liposome treatment significantly reduced CD68-positive macrophage numbers and suppressed synovitis. Immunohistochemistry and flow cytometry showed decreased expression of CD68 (a macrophage marker) and CD44 and CD271 (MSC markers) in the clodronate group, while CD73 expression remained unchanged. The number of colony-forming cells per 1000 nucleated cells and per gram of synovium was significantly lower in the clodronate group than in the control group. Cultured synovial MSCs from both groups showed comparable proliferation, surface antigen expression, and chondrogenic capacity. scRNA-seq identified seven distinct synovial fibroblast (SF) subsets, with a notable decrease in the Mki67+ SF subset, corresponding to synovial MSCs, in the clodronate group. Clodronate treatment downregulated genes related to extracellular matrix organization and anabolic pathways in Mki67+ SF. Cell–cell communication analysis revealed diminished Nampt and Spp1 signaling interaction between macrophages and Mki67+ SF and diminished Ccl7, Spp1, and Csf1 signaling interaction between Mki67+ SF and macrophages in the clodronate group. Spp1 and Nampt promoted the proliferation and/or chondrogenesis of synovial MSCs.ConclusionsMacrophage depletion with clodronate liposomes suppressed synovitis and reduced the number and activity of synovial MSCs, highlighting the significance of macrophage-derived Nampt and Spp1 signals in synovial MSC activation. These findings offer potential therapeutic strategies to promote joint tissue regeneration by enhancing beneficial signals between macrophages and synovial MSCs.

Volume and Distribution of Early Knee Effusion After TKA with a PEEK-Based Knee Prosthesis

Background: Early knee effusion is a common phenomenon after total knee arthroplasty (TKA), with potential clinical implications. Unlike traditional alloy knee prostheses, the polyetheretherketone (PEEK) knee system has radiographic transparency on magnetic resonance (MR) scans, which allows analysis of prosthetic knee effusion. We aimed to identify the distribution and volume of knee effusion after TKA with the PEEK prosthesis with use of MR imaging and to analyze whether dynamic changes in effusion were correlated with serum inflammatory marker changes and knee function recovery. Methods: Nine patients with osteoarthritis who were 59 to 74 years old underwent unilateral TKA with the PEEK prosthesis between June 2021 and August 2021. Dynamic early postoperative changes in the volume and distribution of knee effusion were evaluated with use of 3D MR stereoscopic images. Serum inflammatory markers were measured via blood tests, and joint function was evaluated with use of the subjective functional score of the Knee Society Score (KSS) and knee range of motion (ROM). Linear regression analyses were performed to assess for correlations between knee effusion volume and inflammatory markers and between knee effusion volume and joint function. Results: The mean serum inflammatory marker levels increased significantly at 1 week after TKA with the PEEK prosthesis and then gradually decreased with time from 1 to 6 months. The mean total knee effusion volume gradually decreased over time. Concurrently, the mean KSS subjective functional score and mean knee ROM improved with time. Total knee effusion volume was positively correlated with C-reactive protein level (R2 = 0.16; p = 0.007) and negatively correlated with the change in KSS score between the preoperative and postoperative time points (R2 = 0.19; p = 0.003). Using the 1-week total knee effusion volume as a reference, a positive correlation was observed between the reduction in total knee effusion volume and the actual value of the ROM (R2 = 0.36; p = 0.0001) from 3 to 24 months postoperatively. Conclusions: Through 3D MR imaging, the precise distribution and volume of, and dynamic changes in, knee effusion after TKA with the PEEK prosthesis were confirmed and were found to be correlated with inflammation and joint function in the early postoperative period. The results demonstrate the potential clinical benefit of the PEEK-based knee system for future use. Level of Evidence: Diagnostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Direct Effects of the Janus Kinase Inhibitor Baricitinib on Sensory Neurons.

Therapeutically, the Janus kinase (Jak) 1/Jak2 inhibitor baricitinib reduces the pathology of rheumatoid arthritis and may also reduce pain. Here, we investigated whether baricitinib directly affects joint nociceptors. We recorded action potentials from nociceptive C- and A∂-fibers of the normal and inflamed knee joint in anesthetized rats to monitor their responses to innocuous and noxious joint rotation. In isolated and cultured dorsal root ganglion (DRG) neurons, we examined Stat3 activation using Western blots and monitored excitability using patch-clamp recordings. Intra-articular injection of baricitinib did not alter C- and A∂-fiber responses to innocuous and noxious rotations of the normal knee but reduced C-fiber responses to these stimuli in inflamed joints. Baricitinib prevented the increase in C-fiber responses to joint rotation evoked by interleukin (IL)-6 plus soluble interleukin-6 receptor (sIL-6R) but not the increase evoked by TNF. In DRG neurons, baricitinib blocked Stat3 activation by hyper-IL-6, and baricitinib or the Stat3 inhibitor Sta21 prevented induction of hyperexcitability by IL-6 plus sIL-6R. Thus, neuronal Jaks are involved in the generation of C-fiber hyperexcitability induced by inflammation and IL-6. Pain reduction by baricitinib may result, at least in part, from direct effects on joint nociceptors.

Increased Rab1a accelerates osteoarthritis by inhibiting autophagy via activation of the mTORC1-S6K pathway

IntroductionCartilage degradation is a critical alteration in the progression of osteoarthritis (OA) due to the disorder of chondrocyte metabolic homeostasis. Autophagy plays an important role in maintaining intracellular homeostasis. Recent investigations have increasingly underscored the importance of autophagy in modulating the pathological mechanisms underlying OA. Ras-related protein Rab-1a (Rab1a) has been illustrated to regulate autophagy in many diseases but not in OA. ObjectivesThis study aims to elucidate whether Rab1a could regulate the development of OA through modulation of chondrocyte autophagy and apoptosis. MethodsProteomic sequencing, Western blotting, and immunohistochemistry were applied to detect the expression level of Rab1a in vitro and in vivo. Gene Ontology terms and Kyoto Encyclopedia of Genes and Genomes pathways were rigorously identified. The effects of Rab1a and the interaction between Rab1a, mTORC1, autophagy and apoptosis were explored by qPCR, Western blotting, and immunofluorescence. An experimental mouse OA model was also performed to confirm the role of Rab1a in OA pathogenesis in vivo. Histological analysis was employed to demonstrate cartilage damage. ResultsRab1a expression was significantly upregulated in inflamed chondrocytes and knee OA cartilage. Inhibition of Rab1a partially attenuated the degradation of the extracellular matrix and cell apoptosis both in vitro and in vivo, whereas overexpression of Rab1a intensified cartilage matrix degradation and cellular apoptosis. Additionally, elevated Rab1a levels were observed to suppress autophagy and activate the mTORC1-S6K signaling pathway, thereby aggravating OA pathogenesis. ConclusionThe augmentation of Rab1a expression impairs autophagy and promotes apoptosis through the activation of the mTORC1-S6K signaling pathway, further exacerbating OA pathogenesis. This finding suggests that Rab1a serves as a promising and innovative therapeutic target for the prevention and treatment of OA.

Development and validation of a pediatric internationally agreed ultrasound knee synovitis protocol (PIUS-knee) by the PReS imaging working party

ObjectivesTo identify an optimal pediatric musculoskeletal ultrasound (MSUS) protocol for the detection of knee arthritis in patients with juvenile idiopathic arthritis (JIA) including a comparison with existing protocols. Secondary aims were to correlate MSUS-identified B-Mode (BM) and Power Doppler-Mode (PD) synovitis with clinical findings.MethodsConsecutive JIA patients with confirmed knee arthritis after clinical examination underwent a thorough MSUS study protocol which included views identified and consented by the Pediatric Rheumatology european Society (PReS) Imaging Working Party for the detection of synovitis. In total eight views including measurement of the suprapatellar recess were included. Scoring of synovitis followed the pediatric OMERACT criteria (BM and PD severity grading 0 to 3). Interobserver reliability of BM and PD was tested before study begin. Previously published MSUS protocols for knee synovitis were also identified from the literature and their scan protocols compared to identify differences in sensitivity for synovitis according to the number and specific type of views included. Finally, a clinically applicable MSUS protocol for knee synovitis could be proposed.ResultsIn 114 patients with clinically active knee inflammation, BM positivity (grading ≥ 1) was most frequently detected in the suprapatellar longitudinal and transverse scans performed in any positioning (frequency 97–99% in suprapatellar longitudinal in 30° or neutral respectively). PD positivity was however higher in these views performed in 30° flexion compared to neutral. Intrasynovial PD positivity (grading ≥ 1) was most frequently detected in the lateral parapatellar (69%, sensitivity 0.68, specificity 0.98), medial parapatellar (frequency 67%, sensitivity 0.67, specificity 1.0), the longitudinal lateral (68%, sensitivity 0.67, specificity 0.98) and suprapatellar transverse in 30° (frequency 64%, sensitivity 0.64, specificity 1.0). A combination of five views was the most sensitive for BM and PD synovitis. The suprapatellar recess size was analyzed by age and gender. For each group, the recess was wider in knees with arthritis than without (p < 0.001). Interobserver reliability of BM and PD positivity showed 85% agreement, with kappa 0.74 (very good). Three published studies with knee synovitis MSUS protocols were identified, which included a range of 1–3 views. Evaluation of the sensitivity of positive PD findings of each of these protocols reached a range of 53–83%; the highest sensitivity (91%) was achieved with the 5 views as identified by this study. These five views were therefore combined to form the Pediatric Internationally agreed Ultrasound (PIUS) knee protocol.ConclusionBM and PD positivity reliably correlated with the identification of pathological findings in knees of patients with JIA. From an internationally agreed protocol of eight images, a combination of five showed the greatest sensitivity for synovitis. This protocol, termed ‘PIUS-Knee’ performed well when compared to existing protocols.

METTL3 mediated ferroptosis in chondrocytes and promoted pain in KOA via HMGB1 m6A modification.

Methyltransferase-like 3 (METTL3) plays a role in the development of knee osteoarthritis (KOA). However, the mechanism underlying the role of METTL3 in KOA is unclear. This work investigated the effects of MELLT3 on ferroptosis and pain relief in in vitro and in vivo KOA models. Chondrocytes were treated with 10 ng/mL interleukin-1β (IL-1β) or 5 μM Erastin (ferroptosis inducer). IL-1β or Erastin treatment inhibited cell viability and glutathione levels; increased Fe2+, lipid reactive oxygen species and malondialdehyde production; and decreased glutathione peroxidase 4, ferritin light chain and solute carrier family 7 member 11 levels. The overexpression of METTL3 facilitated the N6-methyladenosine methylation of high mobility group box 1 (HMGB1). HMGB1 overexpression reversed the effect of sh-METTL3 on IL-1β-treated chondrocytes. A KOA rat model was established by the injection of monosodium iodoacetate into the joints and successful model establishment was confirmed by haematoxylin and eosin staining and Safranin O/Fast Green staining. METTL3 depletion alleviated cartilage damage, the inflammatory response, ferroptosis and knee pain in KOA model rats, and these effects were reversed by the addition of HMGB1. In conclusion, METTL3 depletion inhibited ferroptosis and the inflammatory response, and ameliorated cartilage damage and knee pain during KOA progression by regulating HMGB1.

Investigating the anti-inflammatory and immune-modulatory effects of “Gola” guava fruit and leaf extract in alleviating papain-induced knee osteoarthritis

IntroductionThis present research was designed to investigate the anti-inflammatory and immune-modulatory effects of a 50% hydroethanolic extract of “Gola” guava fruit (GF50%) and guava leaf (GL50%) against papain-induced knee osteoarthritis (KOA).MethodsSixty Sprague–Dawley rats were divided into five groups (10 rats/ group): T0 (negative control), T1 (positive control), T2 (200 mg/kg GF50%), T3 (400 mg/kg GF50%), T4 (200 mg/kg GL50%), and T5 (400 mg/kg GL50%). Physical parameters were evaluated throughout the trial, while biochemical, histopathological, and radiographic analyses were performed at 0, 15, and 30 days. The histopathological and radiographic analyses were evaluated using the Osteoarthritis Research Society International (OARSI) score and Kellgren–Lawrence (KL) classification systems, respectively.Results and discussionThe T1 group demonstrated a significant increase in knee diameter, confirming successful OA induction. The T5 group maintained a significantly lower body weight at day 30, and the T3 group exhibited the highest weight gain. The high dose of GL50% (400 mg/ kg) effectively reduced knee inflammation and significantly downregulated myeloperoxidase (MPO), interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α). In contrast, it significantly (p &amp;lt; 0.001) upregulated the serum and knee capsule tissue superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx). In addition, histopathological and X-ray examinations also confirmed the chondroprotective potential of GL50% extract against OA. Consequently, 400 mg/kg GL50% exhibited anti-inflammatory and chondroprotective potential by lowering oxidative stress and pro-inflammatory cytokines and elevating antioxidant status. These findings could provide a theoretical basis for understanding the mechanism and potential medicinal value of guava fruit and leaf in treating KOA.

Comparative Study between Ultrasound Guided Intraarticular Injection of Corticosteroids and Ultrasound Guided Genicular Nerve Block in Patients with Chronic Knee Pain

Abstract Background Chronic knee pain represents a major cause of disability and a burden on healthcare systems worldwide, being more prevalent in middle-aged and elderly patients. It can take a toll on patients’ daily life, keeps them from their favorite activities, saps of productivity, and diminishes overall quality of life. It can be caused by degenerative conditions, such as osteoarthritis (the most common cause), rheumatoid arthritis, crystalline arthritis and gout. lifestyle modification, pharmacologic management, and injections are the mainstay of therapy for elderly patients having chronic symptomatic knee pain with multiple medical comorbidities who do not wish/fit for surgical options. Intra-articular corticosteroid injection (IACSI) was commonly adopted to alleviate chronic knee pain and was traditionally performed blindly depending only on anatomical land marks. Recently, Genicular nerve block (GNB) has recently emerged as a novel alternative treatment for chronic knee pain. Both Intra-articular corticosteroid injection (IACSI) and Genicular nerve block (GNB) can be carried out under Ultrasound guidance as a safer, cheaper and more feasible imaging modality for guidance as it provides real-time imaging for the knee structures in a dynamic manner giving the ability to do interventional procedures and providing more effective clinical results when compared to blind injections. Aim of the Work Illustrate the technical aspects, the indications and the methodology of local therapies for chronic knee pain performed by interventional radiologists and provide current evidence. Assess the efficacy of Ultrasound (US) guided intraarticular corticosteroids injection and Genicular nerve block to control moderate and advanced chronic knee pain. Compare the immediate and short-term symptomatic and functional improvement obtained after both techniques. Patients and Methods The study was carried out on 30 patients of symptomatic chronic knee pain with radiologically proven knee joint arthritis (26 of them had osteoarthritis, 3 had gout arthritis and one patient had rheumatoid arthritis), all of them were not responding to medical treatment. They were divided into two groups (intraarticular corticosteroids injection group and Genicular nerve block one) both procedures were performed under ultrasound guidance to identify target points for injection. GNB target points for injection where close to the superior lateral, superior medial and inferior medial genicular arteries while target point for the IACSI group was the suprapatellar bursa. All procedures were performed with a spinal needle (22 G) introduced under ultrasound guidance till reaching the desired target points at both groups. Then injection of a mixture of Lidocaine, Bupivacaine hydrochloride and Triamcinolone Acetonide was done. Results In our study, in IACSI group the mean of initial VAS was 80.7±10.3 compared to 81.3±7.7 in GNB group. The mean VAS significantly dropped to be 20.7±5.3 in IACSI group compared to 18.3±5.9 in GNB group. After 2 weeks, it was 34.3±8.4 and 27.7±8.2 respectively. After 4 weeks, it increased to 40±8.7 and 33.7±9.3 respectively. At 8 weeks, it was obviously increased to 75.3±10.3 and 66.7±11.4 respectively and the effect returned gradually till nearly the baseline at 8 weeks. In our study, in IACSI group the mean of initial OKS was 48.6±7.4 compared to 50.1±7.6 in GNB group. After 2 weeks, it was markedly decreased to 25.5±3.9 and 22.7±6.8 respectively. After 4 weeks, it increased to 31.1±3.5 and 27.±6.9 respectively. At 8 weeks, it was obviously increased to 44.1±7.1 and 39.3±6.1 respectively and the effect returned gradually till nearly the baseline at 8 weeks. Conclusion Ultrasound guided genicular nerve block with a mixture of corticosteroid and local anesthetic is an effective, radiation free method to alleviate chronic knee pain and improve knee joint function. US guided intra-articular corticosteroid injection through suprapatellar approach is also an effective method to relive chronic knee pain and inflammation and to improve knee joint functional capacity. Both procedures are effective in alleviation of chronic knee pain for up to 4 weeks with marked decrease in VAS score after 2 weeks and slight increasing trend towards 4 weeks. The favorable effect returned gradually till nearly the baseline at 8 weeks. Genicular nerve block is more effective than intra-articular corticosteroid injection in both pain alleviation and improving knee joint function. The earlier the Kellgren- Lawrence score is, the more reduction in chronic knee pain and the more improvement of joint function is achieved after both procedures.

A Standardized Boswellia serrata Gum Extract Promotes Chondroprotection and Improves Knee Pain, Function, and Inflammation in Adults With Mild to Moderate Osteoarthritis

A Standardized Boswellia serrata Gum Extract Promotes Chondroprotection and Improves Knee Pain, Function, and Inflammation in Adults With Mild to Moderate Osteoarthritis

Exploring causal correlations between inflammatory cytokines and knee osteoarthritis: a two-sample Mendelian randomization.

Knee osteoarthritis (KOA) and certain inflammatory cytokines (such as interleukin 1 [IL-1] and tumor necrosis factor alpha [TNF-a]) are related; however, the causal relationship remains unclear. Here, we aimed to assess the causal relationship between 41 inflammatory cytokines and KOA using Mendelian randomization (MR). Two-sample bidirectional MR was performed using genetic variation data for 41 inflammatory cytokines that were obtained from European Genome-Wide Association Study (GWAS) data (n=8293). KOA-related genetic association data were also obtained from European GWAS data (n=40,3124). Inverse variance weighting (IVW), MR, heterogeneity, sensitivity, and multiple validation analyses were performed. Granulocyte colony-stimulating factor (G-CSF) or colony-stimulating factor 3 (CSF-3) levels were negatively associated with the risk of developing KOA (OR: 0.93, 95%CI:0.89-0.99, P=0.015). Additionally, macrophage inflammatory protein-1 alpha (MIP-1A/CCL3) was a consequence of KOA (OR: 0.72, 95%CI:0.54-0.97, P=0.032). No causal relationship was evident between other inflammatory cytokines and KOA development. This study suggests that certain inflammatory cytokines may be associated with KOA etiology. G-CSF exerts an upstream influence on KOA development, whereas MIP-1A (CCL-3) acts as a downstream factor.

Higher Synovial Immunohistochemistry Reactivity of IL-17A, Dkk1, and TGF-β1 in Patients with Early Psoriatic Arthritis and Rheumatoid Arthritis Could Predict the Use of Biologics.

Delay in diagnosis and therapy in patients with arthritis commonly leads to progressive articular damage. The study aimed to investigate the immunohistochemical reactivity of synovial cytokines associated with inflammation and the bone erosives/neoformatives processes among individuals diagnosed with psoriatic arthritis (PsA), rheumatoid arthritis (RA), osteoarthritis (OA), and radiographic axial spondyloarthritis (r-axSpA), with the intention of identifying potential biomarkers. Specimens were collected from the inflamed knee joints of patients referred for arthroscopic procedures, and the synovial tissue (ST) was prepared for quantifying protein expression through immunohistochemical analysis (% expressed in Ratio_Area-Intensity) for TGF-β1, IL-17A, Dkk1, BMP2, BMP4, and Wnt5b. The collected data underwent thorough analysis and examination of their predictive capabilities utilising receiver operating characteristic (ROC) curves. Valid synovial tissue samples were acquired from 40 patients for IHC quantification analysis. Initially, these patients had not undergone treatment with biologics. However, after 5 years, 4 out of 13 patients diagnosed with PsA and two out of nine patients diagnosed with RA had commenced biologic treatments. Individuals with early PsA who received subsequent biologic treatment exhibited significantly elevated IHC reactivity in ST for TGF-β1 (p = 0.015). Additionally, patients with both PsA and RA who underwent biologic therapy displayed increased IHC reactivity for IL-17A (p = 0.016), TGF-β1 (p = 0.009), and Dkk1 (p = 0.042). ROC curve analysis of IHC reactivity for TGF-β1, Dkk1, and IL-17A in the synovial seems to predict future treatment with biologics in the next 5 years with the area under the curve (AUC) of a combined sum of the three values: AUC: 0.828 (95% CI: 0.689-0.968; p 0.005) S 75% E 84.4%. Higher synovial immunohistochemistry reactivity of IL-17A, Dkk1, and TGF-β1 in patients with early psoriatic arthritis and rheumatoid arthritis may serve as potential indicators for predicting the necessity of utilising biologic treatments.

Optimizing the Maastricht Work-Related Support intervention in clinical patient care: the value of integrating action research into intervention mapping

BackgroundHealthcare professionals (HCPs) are increasingly recommended to play an important role in supporting people with chronic disease in work participation. An intervention for HCPs to provide work-related support to their patients in clinical care was developed with intervention mapping (Maastricht Work-Related Support; Maastricht WRS). Action research proposes ‘combining research and practice’, which allows us to incorporate experiences of HCPs while implementing and to realize intervention’s full potential. Therefore, the aim of this study is to explore, by integrating action research into an intervention mapping approach, how experiences of HCPs with early implementation can be used to optimize the Maastricht WRS in clinical care.MethodsSemi-structured interviews were held with nine HCPs (response rate 82%), involved in care for people with inflammatory arthritis, knee problems or inflammatory bowel disease. Some of them were not yet trained in the Maastricht WRS while others had received the training and were providing the Maastricht WRS.ResultsAll participants regarded WRS an important part of clinical care. Untrained HCPs indicated a lack of knowledge and skills in providing the Maastricht WRS, and a need for tools. Trained HCPs were satisfied with the training and tools, but stressed that practical limitations hindered providing the Maastricht WRS. Action research showed that the intervention meets the needs of HCPs, but need some optimizations: (1) organizing ‘intervision’ for HCPs, (2) inform and activate patients to discuss work with their HCP, (3) update initial tools and (4) including patients’ work status in the electronic patient system.ConclusionsAction research integrated into intervention mapping proved to improve the Maastricht WRS intervention. By involving HCPs, the intervention could be optimized to provide to support people with chronic diseases in clinical care in healthy and sustainable work participation.

Digging deeper into pain: an ethological behavior assay correlating well-being in mice with human pain experience.

The pressing need for safer, more efficacious analgesics is felt worldwide. Preclinical tests in animal models of painful conditions represent one of the earliest checkpoints novel therapeutics must negotiate before consideration for human use. Traditionally, the pain status of laboratory animals has been inferred from evoked nociceptive assays that measure their responses to noxious stimuli. The disconnect between how pain is tested in laboratory animals and how it is experienced by humans may in part explain the shortcomings of current pain medications and highlights a need for refinement. Here, we survey human patients with chronic pain who assert that everyday aspects of life, such as cleaning and leaving the house, are affected by their ongoing level of pain. Accordingly, we test the impact of painful conditions on an ethological behavior of mice, digging. Stable digging behavior was observed over time in naive mice of both sexes. By contrast, deficits in digging were seen after acute knee inflammation. The analgesia conferred by meloxicam and gabapentin was compared in the monosodium iodoacetate knee osteoarthritis model, with meloxicam more effectively ameliorating digging deficits, in line with human patients finding meloxicam more effective. Finally, in a visceral pain model, the decrease in digging behavior correlated with the extent of disease. Ultimately, we make a case for adopting ethological assays, such as digging, in studies of pain in laboratory animals, which we believe to be more representative of the human experience of pain and thus valuable in assessing clinical potential of novel analgesics in animals.

Inflammatory Knee Synovitis: Evaluation of an Accelerated FLAIR Sequence Compared With Standard Contrast-Enhanced Imaging.

The aim of this study was to assess the diagnostic value and accuracy of a deep learning (DL)-accelerated fluid attenuated inversion recovery (FLAIR) sequence with fat saturation (FS) in patients with inflammatory synovitis of the knee. Patients with suspected knee synovitis were retrospectively included between January and September 2023. All patients underwent a 3 T knee magnetic resonance imaging including a DL-accelerated noncontrast FLAIR FS sequence (acquisition time: 1 minute 38 seconds) and a contrast-enhanced (CE) T1-weighted FS sequence (acquisition time: 4 minutes 50 seconds), which served as reference standard. All knees were scored by 2 radiologists using the semiquantitative modified knee synovitis score, effusion synovitis score, and Hoffa inflammation score. Diagnostic confidence, image quality, and image artifacts were rated on separate Likert scales. Wilcoxon signed rank test was used to compare the semiquantitative scores. Interreader and intrareader reproducibility were calculated using Cohen κ. Fifty-five patients (mean age, 52 ± 17 years; 28 females) were included in the study. Twenty-seven patients (49%) had mild to moderate synovitis (synovitis score 6-13), and 17 patients (31%) had severe synovitis (synovitis score >14). No signs of synovitis were detected in 11 patients (20%) (synovitis score <5). Semiquantitative assessment of the whole knee synovitis score showed no significant difference between the DL-accelerated FLAIR sequence and the CE T1-weighted sequence (mean FLAIR score: 10.69 ± 8.83, T1 turbo spin-echo FS: 10.74 ± 10.32; P = 0.521). Both interreader and intrareader reproducibility were excellent (range Cohen κ [0.82-0.96]). Assessment of inflammatory knee synovitis using a DL-accelerated noncontrast FLAIR FS sequence was feasible and equivalent to CE T1-weighted FS imaging.

The Effects of Extracellular Matrix Allograft Administration on Knee Inflammation Following an Anterior Cruciate Ligament Injury in Mice

Background and Hypothesis:A human placental-derived extracellular matrix (ECM) allograft has previously been developed and is indicated by the manufacturer for reducing tissue inflammation and accelerated repair. To evaluate the efficacy of this product for reducing post-anterior cruciate ligament (ACL) injury inflammation, we used a novel murine in vivo ACL injury model. This model has previously been shown to induce significant synovitis, infrapatellar fat pad (IFP) fibrosis, and articular cartilage (AC) degradation within 2 weeks following an ACL injury. We hypothesized that intra-articular injections of the allograft would correspond with a decrease in synovitis, fibrosis, and articular cartilage degradation.&#x0D; Experimental Design or Project Methods:Ten-week-old C57BL/6J mice were randomly placed into 4 groups (n=10/group). For all mice, the right ACL was ruptured. One group served as sham controls, with a single intra-articular saline injection 24-hours following injury. The remaining three groups received 1, 2, and 6 allograft injections respectively beginning 24-hours after injury. Mice were euthanized 14 days after injury. Following euthanasia, the degree of IFP fibrosis, knee synovitis, and AC degradation were histopathologically evaluated.&#x0D; Results:Thus far, 5 mice per group have been analyzed. Within this subset of mice, those that received 6 injections demonstrated a significantly higher synovitis score (p &lt; 0.01) than the sham group. The 1-injection (p &lt; 0.01), 2-injection (p = 0.16), and 6-injection (p = 0.03) groups each displayed greater IFP fibrosis, relative to sham. No significant differences were found in AC degeneration across groups.&#x0D; Conclusion and Potential Impact:If the current results hold, following the analyses of the remaining mice, then this particular orthobiologic may not be suitable for reducing the post-ACL injury inflammatory response in mice. However, there are several limitations to this pilot study that will first need to be accounted for to confirm the lack of efficacy found.

Transcutaneous Electrical Nerve Stimulation Provides Early Recovery from Arthrogenic Muscle Inhibition Post-Anterior Cruciate Ligament Reconstruction

Abstract Background: Quadriceps weakness that ensues anterior cruciate ligament (ACL) reconstruction, a common procedure done in sportspersons, is a hindrance in the active rehabilitation and delays return to sport. This weakness of quadriceps muscle is a complex neural phenomenon ascribed to arthrogenic muscle inhibition (AMI). Purpose: The purpose of the study was to assess the effectiveness of transcutaneous electrical nerve stimulation (TENS) in AMI post-ACL reconstruction (ACLR). Methods: A prospective randomized study involving 60 patients with isolated ACL injury above 18 years of age were included. Patients with osteoarthritis knee, multiligament injury, previous knee surgery, and inflammatory knee pathology were excluded from the study. Patients were divided into Groups A and B (n = 30, each). Group A received TENS therapy with exercises and ice packs, whereas Group B received only exercise and ice packs post-ACLR. All patients were assessed subjectively using Visual Analog Scale score for pain, Lysholm, and IKDC score for functional outcome pre and postoperatively on day 2, 1 month, 3 months, 6 months, and 1 year. Objective assessment was done by measuring thigh girth (10 cm above knee joint line) and isometric quadriceps strength (using David Biofeedback Strength Evaluation Machine) pre and postoperatively at day 2, 1 week, 2 weeks, 1 month, 3 months, 6 months, and 1 year. Results: Pain decreased in both groups at 1 month, 3 months, and 6 months, but there was significantly lower pain in Group A in comparison to Group B at 1 month (P = 0.003), 3 months (P = 0.001), and 6 months (P ≤ 0.0001). There was no pain at 1 year in both the groups. Lysholm score improved in both groups, but there was statistically significantly better Lysholm score in Group A in comparison to Group B at each follow-up. IKDC score improved in both groups, but the improvement in Group A was significantly higher than Group B at each follow-up. No significant difference in mean thigh girth was observed. Mean quadriceps strength was similar in both groups except at 6 months where Group A was better than Group B (&lt;0.001). Conclusion: Addition of TENS in ACLR rehabilitation decreases pain and provides better clinical outcome.

An Inquiry into the Role of Muscle Atrophy in Rheumatoid Arthritis and Current Treatment Scenario

Around the world, 0.5 to 1% of adults suffer from rheumatoid arthritis. It is a chronic autoimmune inflammatory illness distinguished by inflammation of hands, knees, wrists, and feet, causing bone and cartilage degradation, joint deformity, and muscle atrophy and thus movement limitations. Inflammatory mediators like necrosis factor and interleukins along with other inflammatory cytokines, execute a vital role in the initiation and advancement of rheumatoid arthritis (RA) as well as muscle atrophy. Existing literature discusses extensively the RA condition. However, the muscle atrophy related to this condition has received little attention, despite the substantial role of muscle atrophy in morbidity caused by RA. The review aims to highlight the relationship between muscle atrophy and RA, the mechanisms of muscle atrophy in RA and the association between oxidative stress and muscle atrophy in RA. This review will be useful for getting insights into the etiopathogenesis of muscle atrophy brought on by rheumatoid arthritis and available treatment alternatives for RA and muscle atrophy caused by RA. Discussion on the potential therapeutic targets and agents to treat skeletal muscle atrophy will help advance the knowledge to improve the condition of muscle atrophy associated with RA.

Impact of Counseling on Patient Education and Dietary in Quality of Lifestyle and Nutritional Anemia in Diabetes Mellitus Patient: A Case-Control Study

The study’s goal was to see how w education and dietary guidance improved the quality of lifestyle and nutritional anemia in people with diabetes type 2. This 6 month prospective study was conducted in a hospital in Jaipur, Rajasthan. The demographic information (age, gender, social position, and economic status) was gathered using a form HRQoL after gaining the patient’s assent. In the intervention group n is 21 and also in the control group n is 21 so the total; patient was chosen 42. The baseline Hb and health-related quality score were taken in consideration in 1, 2 and baseline visits in a month-long study as a part of the design. Each visit concluded with the measurement of the hemoglobin level and health-related quality of life scores for both the intervention and control groups. The intervention group’s Hblevel changed significantly more than the control group’s after the nutrition education intervention finished [0.56–0.40 vs. 0.16–0.82 gm/dl, p = 0.002]. In contrast to the control group, where the mean increase in general health from baseline to second follow-up was statistically insignificant, the intervention group’s mean increase in general health from baseline to second follow-up was found to be significant as from the result obtained. Thus, nutrition education was found to be substantially linked to higher Hb levels, better dietary consumption, and improved health-related quality.mmune inflammatory illness distinguished by inflammation of hands, knees, wrists, and feet, causing bone and cartilage degradation, joint deformity, and muscle atrophy and thus movement limitations. Inflammatory mediators like necrosis factor and interleukins along with other inflammatory cytokines, execute a vital role in the initiation and advancement of rheumatoid arthritis (RA) as well as muscle atrophy. Existing literature discusses extensively the RA condition. However, the muscle atrophy related to this condition has received little attention, despite the substantial role of muscle atrophy in morbidity caused by RA. The review aims to highlight the relationship between muscle atrophy and RA, the mechanisms of muscle atrophy in RA and the association between oxidative stress and muscle atrophy in RA. This review will be useful for getting insights into the etiopathogenesis of muscle atrophy brought on by rheumatoid arthritis and available treatment alternatives for RA and muscle atrophy caused by RA. Discussion on the potential therapeutic targets and agents to treat skeletal muscle atrophy will help advance the knowledge to improve the condition of muscle atrophy associated with RA.

Low-intensity pulsed ultrasound phonophoresis with diclofenac alleviated inflammation and pain via downregulation of M1 macrophages in rats with carrageenan-induced knee joint arthritis

ObjectiveThis study aimed to investigate the effects of low-intensity pulsed ultrasound (LIPUS) phonophoresis with diclofenac on inflammation and pain in the acute phase of carrageenan-induced arthritis in rats. Design60 male Wistar rats were randomly divided into the arthritis, diclofenac, LIPUS, phonophoresis, and sham-arthritis control groups. LIPUS and transdermal diclofenac gel were applied to the lateral side of the inflamed knee for 7 days, initiated postinjection day 1. In the phonophoresis group, diclofenac gel was rubbed onto the skin, followed by LIPUS application over the medication. Knee joint transverse diameters, pressure pain thresholds (PPTs), and paw withdrawal thresholds (PWT) were evaluated. The number of CD68-, CD11c-, and CD206-positive cells, and IL-1β and COX-2 mRNA expression were analyzed 8 days after injection. ResultsIn the phonophoresis group, the transverse diameter, PPT, PWT significantly recovered at the day 8 compared to those in the LIPUS and diclofenac groups. The number of CD68- and CD11c-positive cells in the phonophoresis group was significantly lower than that in the LIPUS and diclofenac groups, but no significant differences were observed among three groups in CD206-positive cells. IL-1β and COX-2 mRNA levels were lower in the phonophoresis group than in the arthritis group, although there were no differences among the LIPUS, diclofenac, and phonophoresis groups. ConclusionLIPUS phonophoresis with diclofenac is more effective to ameliorate inflammation and pain compared to diclofenac or LIPUS alone, and the mechanism involves the decrease of M1 macrophages.

Effectiveness of Hydrolyzed Collagen Peptide Injection for the Treatment of Collateral Ligament Pain: A Randomized Controlled Trial

Purpose: Collateral ligament pain is a musculoskeletal condition causing knee inflammation, often affecting athletes. Despite various treatments being available, there is failure in addressing the pathophysiologic collagen degradation. Hydrolyzed collagen peptides may help damage tissues in the repairment process, but until now no data is available on local injection of collagen peptides, with data available only on oral supplementation. Methods: A randomized controlled trial assessed the efficacy of hydrolyzed collagen peptide injections (Tiss’You, Republic of San Marino) for persistent collateral ligament pain. Sixty-two patients with ultrasound-confirmed inflammation were divided into two groups. The study group (31 patients) received oral painkillers and a collagen peptide injection, while the control group (31 patients) received oral painkillers and a depo-medrol injection. Results: The study group showed significant improvement in pain relief, functional status, and quality of life, measured by the Visual Analogue Scale and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) after six months. Ultrasound confirmed ligament healing in both groups with no observed differences. The study group reported higher satisfaction and no adverse effects. Conclusion: Hydrolyzed collagen peptide injections may effectively and safely treat collateral ligament pain. This study offers insights into this novel emerging treatment option, exploiting the ability of collagen peptides in helping tissue repair. Further research with larger samples and longer follow-up is necessary to validate these findings.