Public involvement is standard practice to enhance the quality, equity and impact of musculoskeletal pain research. In this review, we aimed to reflect on our own learning journey across multiple musculoskeletal projects and identify lessons learned from meaningful involvement. We then consider the changes needed at the researcher, funder and institutional levels to support involvement as a driver of relevance and impact. This is a narrative position paper drawing on experiential learning from three musculoskeletal pain studies and ongoing community engagement. We reflected on what we have learned from public contributors in our research, focusing on how involvement reshaped study priorities and tools. Lessons were synthesised to highlight recurring themes, supported by reference to reviews, guidance and empirical studies. Across all projects, several key themes emerged: (1) emphasis on purpose rather than process; (2) co-production and partnership rather than review; (3) flexibility and adaptation rather than predetermined steps; (4) relevant public contributors and partners; (5) focus on 'learning' rather than 'doing'; and (6) approaches to diversity and inclusion. Public partnerships should be a collaborative, transformative, relational and learning-based process that reshapes all aspects of research. Realising this potential might require flexible funding for early engagement, training in facilitation and reflexivity, sustained support beyond the research project to promote impact, and taking steps beyond building more infrastructure towards strengthening the systems that enable involvement to work effectively. Working together to improve muscle, joint, and bone pain research through shared learning This paper looks at how public partners (patients, service users, carers and members of the public with relevant lived experience) are involved in research on conditions affecting pain, muscles, bones, and joints. Involving the public in research is now widely expected. Not only does this approach ensures that research genuinely reflects the priorities of the public, but it also shapes the research question and methods to ensure relevance, thereby increasing the likelihood that the findings are meaningful and usable in the real-world. It ensures that research is conducted for the benefit of the public with public input. Involvement is not always meaningful. From our experience, we found that when involvement was genuine and followed the principles of good practice, it not only reshaped the research and tool design but also provided clearer pathways to end-user benefit, underpinned by continuous two-way learning. As we reflect on working with public partners as equals in co-creating our research, it has not only shaped the research to ensure it aligns with our public partners’ priorities, but it has also shaped us as researchers. As researchers, we also face challenges: we must learn to negotiate with public partners as equals and need appropriate support, such as flexible funding, to respond effectively to their knowledge and expertise.
Gamification has shown promising results in pediatric rehabilitation, but there is a lack of research specifically investigating its effects on hip juvenile idiopathic arthritis (JIA) in children. This case study aimed to explore the impact of gamification-based rehabilitation combined with conventional physiotherapy on lower limb function and walking activities in a child with hip JIA. An 11-year-old female was diagnosed with hip JIA and presented with hip joint pain and difficulty in standing and walking. She underwent a 6-month intensive conventional physiotherapy program combined with virtual reality (VR)-based gamification using the Walker View treadmill system and D-Wall digital mirror device. Each treatment session lasted 60 min and was conducted 5 times a week for 6 months. The visual analog scale (VAS), goniometry, Walker View treadmill system score, and Hip Disability and Osteoarthritis Outcome Score (HOOS-12) outcome measures were used during pretest, posttest, and follow-up assessments at 0, 6, 9, and 12 months. The combined approach of VR-based gamification and conventional physiotherapy led to significant improvements in pain, functional range of hip joint movements, and gait in this JIA patient. She also showed significant progress across all outcome measures at different timelines. This case report concludes that combining VR-based gamification with conventional physiotherapy is effective in improving hip joint function and mobility in children with hip JIA. It is recommended to combine VR-based gamification with conventional physiotherapy to enhance lower limb function and walking activities in JIA patients, and more future studies are needed to generalize this effect.
Psoriatic arthritis (PsA) is a chronic immune-mediated inflammatory disease associated with psoriasis that can lead to progressive joint damage and impaired quality of life. Although biologic therapies targeting key inflammatory pathways have advanced rapidly, global research trends and hotspots in PsA treatment have not been systematically characterized. Publications on PsA treatment from 2014 to 2024 were retrieved from the Web of Science Core Collection. Bibliometric and visualization analyses were performed using CiteSpace and VOSviewer to evaluate publication characteristics, collaborative networks, and research trends, including keyword co-occurrence and citation burst analysis. A total of 2704 publications were included. The United States ranked first in both publication output and citations, with extensive international collaboration, particularly with European countries, while contributions from the Asia-Pacific region have increased in recent years. Research focus has shifted over time from tumor necrosis factor inhibitors and clinical validation studies to interleukin-17/23 inhibitors, Janus kinase inhibitors, and personalized treatment strategies. Annals of the Rheumatic Diseases was the most influential journal, and Mease PJ was the most productive author. Keyword and citation analyses indicated that precision medicine, novel therapeutic targets, and combination therapies are emerging research directions. Research on PsA treatment has evolved toward precision and targeted therapy. Future studies should emphasize biomarker-guided treatment and optimization of combination strategies to improve clinical outcomes.
Evidence-based practice guidelines recommend combining the long-term use of opioids for chronic noncancer pain (CNCP) with suitable nonpharmacologic treatments. Whether long-term opioid therapy (LTOT) in Germany aligns with these recommendations is unknown so far. Therefore, our objective was to determine the use of nonpharmacologic treatments among patients receiving LTOT for CNCP. The retrospective observational analysis was based on administrative claims data of the German statutory health insurance fund DAK-Gesundheit. Patients with LTOT and no cancer diagnosis were selected between January 2018 and June 2019. The utilization of nonpharmacologic treatments, including physical therapy, psychotherapy, lifestyle modification, and other inpatient and outpatient treatments, was examined over a two-year period. Subgroup analyses were conducted by age, preindex opioid prescriptions (≥ 1 year vs < 1 year), and the presence of ICD-10 diagnoses, including osteoarthritis, chronic back pain, inflammatory rheumatic diseases (excluding rheumatoid arthritis), neuropathy/polyneuropathy, radiculopathy, and chronic pain disease. Additionally, regression analyses were performed to examine the association between diagnostic groups and the utilization of treatments. A total of 113,476 patients met the inclusion criteria, of whom 25,945 (23%) did not utilize any of the defined nonpharmacologic treatments during the two-year observation period. The most frequently utilized treatment was physical therapy (62%). Psychotherapy was used by 7% of patients, outpatient special pain therapy by 16%, whereas lifestyle modification (relaxation exercises and nutrition therapy) was used by fewer than 30 patients. Patients with ≥ 1 year of opioid prescriptions prior to inclusion and elderly patients utilized most treatments less frequently. Over the 2-year period, treatment provision remained largely constant, except for a steady decline in physical therapy for patients who had initiated opioid therapy more recently. Except for chronic pain disease, certain diagnoses were only weakly associated with treatment utilization. Contrary to guideline recommendations, a notable proportion of LTOT patients may not receive pain management combining opioid therapy with nonpharmacologic treatments, particularly elderly patients and those with longer treatment duration. Future research should examine reasons for the low use of nonpharmacologic treatments. German Clinical Trials Register: DRKS00024854.
Conventional therapies for rheumatoid arthritis (RA) are limited by poor selectivity, insufficient modulation of the oxidative inflammatory microenvironment, and systemic side effects. Oxidative stress and macrophage-driven immune dysregulation represent critical therapeutic targets. Cinnamaldehyde (CA) and arginine (Arg) possess antioxidant, anti-inflammatory, and anti-osteoclastogenic activities, but their poor solubility, instability, and lack of targeting restrict clinical application. Here, we report a pH-responsive cinnamaldehyde-arginine nanoprodrug (Arg-CA NPs), synthesized via Schiff base reaction, that spontaneously self-assembles into uniform nanoparticles capable of acid-triggered dual-drug release. Arg-CA NPs enhanced the solubility and stability of CA, exhibited excellent dispersibility and circulatory stability, and demonstrated intrinsic antioxidant and anti-inflammatory properties. Mechanistically, Arg-CA NPs attenuated intracellular ROS accumulation, preserved mitochondrial function, and reprogrammed macrophages toward an anti-inflammatory M2 phenotype by suppressing hypoxia-inducible factor-1α (HIF-1α), cyclooxygenase-2 (COX-2), and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling. In an adjuvant-induced arthritis (AIA) rat model, Arg-CA NPs selectively accumulated in inflamed joints and significantly alleviated joint swelling, synovial inflammation, cartilage erosion, and bone destruction. These findings identify Arg-CA NPs as a promising redox-active nanoplatform for RA therapy by targeting oxidative stress and immune dysregulation.
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Current treatments for rheumatoid arthritis (RA) and psoriatic arthritis (PsA) reduce disease activity but often fail to achieve sustained remission. The Decision on Optimal Combinatorial Therapies in Immune-mediated inflammatory diseases using Systems approaches (DocTIS) program has shown that additive anti-inflammatory effects in patients with arthritis can be achieved by combining tumour necrosis factor (TNF) and interleukin (IL)-6 inhibitor therapies. The goal was to provide proof-of-principle evaluation of whether combining TNF and IL-6 inhibitors shows a signal of activity on remission outcomes in RA and PsA. This is a single-arm, multicentre, adaptive basket trial recruiting 20 patients with RA and 20 with PsA and including 24 weeks of treatment and 10 weeks of safety follow-up. Eligible participants on TNF for ≥6 weeks will proceed with the addition of IL-6 inhibitor (tocilizumab) at 162 mg every 2 weeks for 8 weeks, increasing to weekly dosing in weeks 9-24 if well tolerated. The primary outcome is remission at 24 weeks (Clinical Disease Activity Index score ≤2.8 in RA and Disease Activity in PsA score <4). Secondary outcomes include safety, tolerability and disease activity assessments. Using Simon's two-stage design (80% power, one-sided α = 0.10), the trial aims to detect an increase in remission (10% to 30%). An interim futility analysis will occur after seven participants per basket reach 24 weeks. Findings from this proof-of-principle study will inform the feasibility and design of future randomised trials evaluating combination biologic therapy in inflammatory arthritis. www.isrctn.com; ISRCTN50666516.
Atrial fibrillation (AF) affects up to 6 million adults, approximately 1 million of whom receive care through the Veterans Health Administration (VA). Considering advanced rhythm control interventions like catheter ablation are often limited to higher-resourced urban care settings, disparities may disproportionately affect the VA patient population given the 4.6 million Veterans who live in rural communities. To assess differences in use of or time to rhythm control therapy based on rurality. This was a retrospective study of 21,600 Veterans with AF and no preceding heart failure (HF) in the VA Mid-Atlantic Health Care Network. Utilization of diagnostic testing and therapeutic interventions were assessed by total use and time from AF diagnosis. Mean age at AF diagnosis was 72 years, 97.9% were male, 79.8% self-identified as White, and 24.9% lived in rural communities. No differences were observed in the use of rhythm control therapies based on rurality (antiarrhythmic prescriptions 20.1%, 20.9%, and 20.6% and catheter ablation 2.2%, 1.6%, and 2.1% for urban, large rural, and isolated rural settings, respectively; p>0.05 for both comparisons). However, low utilization rates and delays in time to rhythm control therapy, including catheter ablation (median time 2.6 years), were appreciated across the rural-urban spectrum. No major clinical differences were revealed in use of or time to rhythm control therapy based on rurality in the VA. However, low utilization rates and delays to therapy across the rural-urban spectrum warrants additional investigation to identify systemic drivers that may disproportionately affect the VA patient population.
Tumor necrosis factor inhibitors (TNFi) have transformed the management of rheumatoid arthritis (RA); however, up to 40% of patients fail to achieve an adequate clinical response. Current clinical predictors remain insufficient, highlighting the need for pharmacogenetic biomarkers to guide biologic therapy selection. In this study, we investigated genetic variants associated with TNFi treatment response, with a particular focus on body mass index (BMI)-dependent effects, using a large real-world cohort. A total of 519 patients with RA were identified from the Taiwan Precision Medicine Initiative (TPMI), an electronic health record-linked biobank. Eligible patients had received TNFi therapy for at least 6 months and had available genotyping data. Ninety-seven candidate single nucleotide polymorphisms (SNPs) previously reported to be associated with TNFi response were identified through a systematic literature search. Five variants located in immune-metabolic genes (FTO, ZNF618, RANK, CD84, and LOC105375523) were further analyzed using univariable and multivariable logistic regression models. Subgroup analyses stratified by BMI were performed to explore potential effect modification. Three variants-FTO rs7195994, ZNF618 rs16911006, and LOC105375523 rs834811-were significantly associated with TNFi response in initial analyses. In multivariable models, only FTO rs7195994 remained an independent predictor of non-response (odds ratio [OR] 0.44, 95% confidence interval [CI] 0.22-0.87; p = 0.019). Among patients with BMI < 27 kg/m², carriers of the rs7195994 risk allele had a 49% lower likelihood of achieving treatment response (OR 0.51, 95% CI 0.28-0.92; p = 0.0249), whereas no significant association was observed in patients with higher BMI. These findings identify FTO rs7195994 as a novel, BMI-modulated pharmacogenetic marker of TNFi non-response in RA. Incorporating BMI-stratified genetic profiling into clinical decision-making may facilitate early identification of patients unlikely to benefit from TNFi therapy, thereby supporting precision treatment strategies. Further validation in multiethnic populations and functional studies is warranted.
Periploca forrestii Schltr. (PF), traditionally used by the Miao ethnic group in China, has been reported to exert a therapeutic effect on rheumatoid arthritis (RA), potentially through regulating of the TNF-α signaling pathway. This study aimed to identify PF-derived TNF-α-targeting compounds and elucidate their anti-RA mechanisms. TNF-α-binding constituents in PF were screened using affinity ultrafiltration plus liquid chromatography-mass spectrometry (AU-LC/MS). Initial screening for TNF-α antagonistic activity was performed in L929 cells. Binding interactions were verified by biolayer interferometry (BLI), surface plasmon resonance (SPR), cellular thermal shift assay (CETSA), and drug affinity responsive target stability (DARTS). LPS-induced RAW264.7 cells were used to evaluate anti-inflammatory activity, while MH7A cells were employed to assess the effects of active compounds on inflammation and TNF-α-mediated NF-κB signaling. The underlying mechanisms were further investigated using molecular docking and competitive binding assays. The anti-RA efficacy of selected compounds was evaluated in a collagen-induced arthritis (CIA) rat model. Nine TNF-α-binding compounds were identified, among which isochlorogenic acid B, daucosterol, and vitamin E exhibited strong TNF-α binding affinity and effectively protected L929 cells from TNF-α-induced cytotoxicity. These compounds directly interacted with TNF-α as confirmed by BLI, SPR, CETSA, and DARTS, and interfered with TNF-α/TNFR1 interaction. Consequently, they suppressed NF-κB activation, decreased phosphorylation of IκBα and p65, and reduced the levels of NO and proinflammatory cytokine (such as TNF-α, IL-6, and IL-1β). Further analyses, including molecular dynamics simulations and molecular docking, demonstrated stable binding of these compounds to TNF-α, consistent with experimental findings. In CIA rats, all three compounds markedly alleviated joint swelling, histopathological damage, and inflammatory cytokine levels. Isochlorogenic acid B, daucosterol, and vitamin E are key TNF-α-targeting constituents of Periploca forrestii that exert anti-RA effects by blocking TNF-α/TNFR1 interaction and inhibiting NF-κB-mediated inflammatory responses. These findings suggest that PF may serve as a source of natural small-molecule TNF-α inhibitors for RA therapy.
Although there has been growing interest in better understanding risk factors for progression from psoriasis (PsO) to psoriatic arthritis (PsA), research on the role of ambient temperature in potentiating PsA risk has been limited. We sought to evaluate the association of average-annual ambient temperature exposure with prevalent PsA diagnosis among a large cohort of US adults with PsO. We studied electronic health record-data from participants with PsO, with and without an associated PsA diagnosis, who enrolled in the National Institutes of Health's All of Us Research Program between May 31, 2017, and July 1, 2022. Average-annual ambient temperature exposure data was obtained from the National Oceanic and Atmospheric Administration. Multivariable logistic regression analysis was utilized to assess the association between three-digit Zone Improvement Plan (ZIP) code-level ambient temperatures and prevalent PsA diagnosis, controlling for patient age, sex, body mass index, smoking history, race and ethnicity, income, urbanicity, and community deprivation. In this cohort of 5466 patients with PsO (mean age [SD], 61.86 years [15.45 years]; 3153 females [57.7%]) and 1080 patients with both PsO and PsA (mean age [SD], 60.76 years [13.48 years]; 665 females [61.6%]), each 1°F increase in average-annual ambient temperature was associated with 2% increased odds of prevalent PsA diagnosis (adjusted odds ratio [aOR], 1.02; 95% CI, 1.01-1.03). Our study provides data to support further investigation of long-term, warmer ambient temperature exposure as a potential risk factor for PsA among those with PsO.
People with rheumatoid arthritis (RA) are at increased risk of serious infection, but less is known about nonserious infections. Our prospective cohort study evaluated associations between medications for RA and the risk of nonserious infections. We remotely recruited adults with RA in a community rheumatology practice-based research network. Participants joined the ArthritisPower Registry (now PatientSpot) and completed a baseline and up to six monthly follow-up surveys. Using data from consecutive monthly surveys, we assessed associations between medication use at the prior survey and infection report at the subsequent survey, adjusting for confounders. We recruited 351 people with RA (mean age 60, 84% female) who reported 439 infections (330 infections per 100 patient-years). Associations between medication use and infection were assessed among 1,075 qualifying observations with 289 (27%) total infections and 146 (14%) infections with health care encounters or antibiotic use. Compared to those receiving conventional synthetic disease-modifying antirheumatic drugs who were biologic or JAK inhibitor (JAKi) naïve, current biologic or JAKi use was not associated with either infection outcome. Infections were numerically more common with glucocorticoids ≥10 mg/day (odds ratio 1.94, 95% confidence interval 0.89-4.24). Season, previous infection, poorer function, and rural residence were significantly associated with one or both infection outcomes. Biologics and JAKi were not associated with greater risk for nonserious infections compared to conventional therapies. Given that nonserious infection risk may be due more to exposures and general health status, future studies should assess whether the common practice of interrupting medications in people with infection improves or worsens outcomes.
Background/Objectives: Rheumatoid arthritis (RA) is a chronic, inflammatory, autoimmune disease that primarily affects the joints. Current treatments aim to relieve pain and limit joint damage; however, many are associated with significant side effects or high costs. Neutrophils play a critical role in RA development and progression by driving synovial inflammation and tissue damage, yet no approved therapies directly target neutrophil-mediated pathogenic mechanisms. Cannabinoids have demonstrated anti-inflammatory potential. Although cannabinoids have been studied in RA, the direct modulation of neutrophil-driven mechanisms by purified CBG has not been systematically addressed. To harness the cannabinoid potential, we investigated the effects of the purified cannabinoid Cannabigerol (CBG) on neutrophil-mediated immune responses in RA. Methods: We assessed the effects of CBG on human blood isolated neutrophil cytokine secretion, signal transduction and migration as ex vivo models. In addition, collagen antibody-induced arthritis (CAIA) was applied in C57BL/6 wt mice, and immune-cell recruitment and cytokine secretion were examined after CBG treatment. Results: Ex vivo experiments demonstrated that CBG hampered the secretion of pro-inflammatory cytokines from human neutrophils in a dose-dependent manner (TNF-α and IL-6 by 68% and 72%, respectively). Furthermore, CBG downregulated inflammatory signal transduction, such as P38-MAPK, ERK1/2 and Akt phosphorylationpost neutrophil activation by 41%, 54% and 78%, respectively. Importantly, 60% of the CBG downregulation of IL-6 was consistent with the CB2 receptor axis in a selective way. In addition, CBG attenuated neutrophil migration toward IL-8 by 67%. To further evaluate CBG therapeutic capacity, we used CAIA as an in vivo model. CBG treatment resulted in improving mice arthritis clinical scores and body weight in comparison to RA-diseased mice. Moreover, CBG reduced leukocyte recruitment to the inflamed joints by 48%, primarily through the inhibition of neutrophil and monocyte cells to 27% and 49%, respectively. Additionally, CBG showed its anti-inflammatory effect by decreasing inflammatory cytokines like IL-6 and IL-1β by 98% and 60% in the blood. Also, CBG reduced MCP-1 and IL-1β cytokines in the joints by 22% and 38%, respectively. Conclusions: These results show that CBG has anti-inflammatory capacity and therapeutic potential in regulating neutrophil-mediated immunity in RA. These findings are preclinical and require further validation before therapeutic positioning.
Rheumatoid arthritis (RA) is a chronic autoimmune disease with inflammation-mediated joint damage. Its pathogenesis involves synergistic impairment of multiple physiological balances, including immune cell subset dysregulation, abnormal inflammation, oxidative stress, pathological angiogenesis, bone homeostasis disorder and gut microbiota dysbiosis. Conventional therapies have high costs and adverse effects. Traditional Chinese medicine (TCM) follows a holistic balance-restoring concept and is a promising alternative, with Tripterygium wilfordii, Wutou Decoction and Toddalia asiatica extract as evidence-based representatives. This review summarizes 2020-2025 in vitro and in vivo studies on anti-RA TCM. Its core therapeutic mechanism is multi-target, network-based regulation. It rectifies various pathological imbalances simultaneously: modulating immune cell polarization, rebalancing inflammatory factors, scavenging ROS, inhibiting abnormal angiogenesis, regulating osteoblast-osteoclast crosstalk and reshaping gut microbiota. Single TCM agents act on multiple balance networks, showing complex pharmacological properties. TCM's unique advantage for RA is reestablishing the body's dynamic homeostasis by targeting interconnected pathological balances. Further research is needed to clarify TCM components' synergistic regulatory mechanisms and promote their clinical translation.
To evaluate the impact of continuing versus stopping biologic disease-modifying anti-rheumatic drugs (bDMARDs) during the perioperative period on surgical site infections (SSIs), delayed wound healing, and disease flares in patients with inflammatory arthritis (IA) undergoing elective non-orthopaedic surgery. We conducted a systematic review of observational studies assessing the perioperative management of bDMARDs in IA patients undergoing elective non-orthopaedic surgery. Searches were conducted across seven databases and trial registries from the year 2000 onwards. Eligible studies compared outcomes in patients who continued versus stopped biologic therapy. Risk of bias was assessed using the ROBINS-I tool and due to heterogeneity data were synthesised narratively. Eight observational studies met the inclusion criteria. All studies were at moderate or serious risk of bias. Four studies compared infections with two suggesting higher infection rates in the stop biologic group. Two studies assessed delayed wound healing, both suggesting higher rates in the stop group. Disease flares were more common in patients who stopped biologics in all three of the studies reporting this outcome. No studies assessed health-related quality of life. The available observational evidence does not demonstrate a consistent increase in postoperative infection or wound complications related to biologic continuation, however, confidence in these findings is limited by serious risk of bias and outcome heterogeneity. High-quality randomised controlled trials are needed to inform the perioperative management guidelines for IA patients undergoing elective non-orthopaedic procedures.
Rheumatoid arthritis (RA) is a chronic, progressive autoimmune disorder characterized by persistent synovial inflammation, pannus formation, bone erosion, and eventual joint destruction. Murraya exotica L. (ME), a botanical source of Murrayae Folium et Cacumen (MFC), has not been previously investigated for its anti-arthritic potential, which motivated this study. The chemical composition of ME was characterized using ultra-performance liquid chromatography (UPLC), and its anti-arthritic effects were evaluated in collagen-induced arthritis (CIA) rats and interleukin (IL)-1β-stimulated SW982 cells. The contents of meranzin hydrate, hainanmurpanin, murrayone, and 3',4',5,5',6,7-hexamethoxyflavone in the ME extract were quantified as 2.86% ± 0.01%, 1.88% ± 0.01%, 0.07% ± 0.00%, and 0.01% ± 0.00%, respectively. In CIA rats, ME treatment alleviated clinical symptoms, attenuated histopathological joint damage, including synovial hyperplasia, cartilage degeneration, and bone erosion, ameliorated inflammation, and reduced oxidative stress. In IL-1β-stimulated SW982 cells, ME inhibited proliferation and migration, suppressed the inflammatory response, and mitigated oxidative stress. Network pharmacology and molecular docking analyses predicted strong interactions between ME-derived compounds (e.g., murrayone) and nuclear factor-kappa B (NF-κB) p65, which were further validated by cellular thermal shift assay (CETSA) and drug affinity responsive target stability (DARTS) assay. Mechanistically, ME blocked NF-κB activation by inhibiting phosphorylation and degradation of inhibitor of NF-κB-α (IκBα) and preventing p65 nuclear translocation, while simultaneously suppressing activator protein-1 (AP-1) activation through downregulation of c-Fos and c-Jun. The involvement of the NF-κB and AP-1 pathways in ME-mediated anti-inflammatory, anti-proliferative, and anti-oxidative effects in RA was further confirmed using specific pharmacological inhibitors: pyrrolidinedithiocarbamate (PDTC) for NF-κB and SR11302 for AP-1.
BACKGROUND Ankle arthritis is a chronic degenerative disease; its typical symptom is pain in the ankle joint. This retrospective study of 65 patients with mid-stage ankle osteoarthritis aimed to compare clinical outcomes from supramalleolar osteotomy (SMOT) and supramalleolar osteotomy combined with fibular osteotomy (SMOT+FO). MATERIAL AND METHODS Based on whether fibular osteotomy was performed during the procedure, the patients were categorized into the SMOT group (n=34) or the SMOT+FO group (n=31). Surgical outcomes were systematically assessed using the Visual Analogue Scale (VAS) for pain, American Orthopaedic Foot and Ankle Society (AOFAS) score, range of motion (ROM), and complication rates. Radiographic parameters were compared between the 2 groups, including the distal tibial articular surface angle, talar tilt angle, tibiocrural angle, and tibial lateral surface angle. RESULTS The AOFAS scores, VAS scores, and imaging indicators in both patient groups showed significant improvement compared with preoperative levels (P<0.001). However, no statistically significant improvement was observed in the ROM. Compared to SMOT, the addition of fibular osteotomy demonstrated superior outcomes in terms of AOFAS scores and greater improvement in both the talar tilt and tibiocrural angles (P<0.001). The overall incidence of postoperative complications in the SMOT group was lower than that in the SMOT+FO group (2.9% vs 6.4%; OR, 0.44; 95% CI, 0.04 to 5.10). However, the difference did not reach statistical significance (P=0.500). CONCLUSIONS Combining fibular osteotomy with SMOT not only significantly enhances ankle joint function but also exhibits notable advantages in improving radiological parameters, so as to provide long-term clinical benefits for patients.
Psoriatic arthritis (PsA) is a chronic inflammatory disease with a heterogeneous presentation including peripheral joint arthritis, axial inflammation, enthesitis, dactylitis, and psoriatic skin and nail changes. A substantial proportion of patients develop structural joint damage that can be monitored using standard radiographs. In patients with PsA, structural damage progression has been associated with significant impairment of physical function, health-related quality of life, and work productivity. Tumor necrosis factor inhibitors were the first biologic therapies approved for patients with PsA and have demonstrated efficacy in reducing the rate of structural damage progression in these patients. More recently, biologics targeting the interleukin (IL)-23p19 subunit (guselkumab and risankizumab) and IL-17 (secukinumab, ixekizumab, and bimekizumab) have been approved to treat patients with active PsA and are the subject of this review, with a focus on guselkumab. In separate phase 3, randomized, controlled studies, participants with active PsA treated with guselkumab, secukinumab, ixekizumab, and bimekizumab exhibited less structural damage progression in comparison with placebo. Both guselkumab and risankizumab inhibit the IL-23p19 subunit; however, to date, only guselkumab has demonstrated statistically significant efficacy in inhibiting structural damage progression in this patient population.
Carbonic anhydrase inhibitors (CAIs) have long been used as diuretics, topically acting antiglaucoma agents, anticonvulsants, and for the treatment of altitude sickness. Lately, they have shown promising results as anti-obesity, antimicrobial, and mainly antitumor agents. Recent studies have reported the efficacy of CAIs in treating inflammatory conditions such as arthritis and neuropathic pain. Moreover, a polypharmacological profile has been demonstrated for sulfonamide COX-2 inhibitors such as celecoxib, which also effectively inhibit CAs. Additionally, emerging research showed the effectiveness of CAIs in cerebral ischemia, where they help protect brain tissue by modulating pH levels and reducing acidosis-induced neuronal damage.
Juvenile idiopathic arthritis (JIA) comprises a heterogeneous group of childhood-onset inflammatory arthritides that remain challenging to treat. An expanding range of biologic and targeted synthetic disease-modifying antirheumatic drugs has improved outcomes, yet major unmet needs persist including predicting treatment response and identifying optimal drug sequences. Traditional frequentist randomised controlled trials (RCTs) are often infeasible in JIA because of small sample sizes and ethical concerns about placebo use in children. Modified RCTs - including randomised withdrawal, placebo-phase, and escape designs - have reduced placebo exposure but have inherent limitations. Here we discuss how innovative trial methodologies may enhance our capacity to generate evidence that can improve outcomes for children and young people with JIA. Adaptive designs, Bayesian methods, sequential multiple assignment randomized trials, and two-stage stop-go designs offer greater flexibility within trials, allowing for study protocols to be adapted based on preliminary data. Insights from multiomic analysis of JIA synovial tissue mean that biologically defined endotypes may fundamentally reshape trial stratification and support biomarker-led precision medicine. Master protocols (basket, umbrella and platform trials) provide opportunities to streamline research by combining data into a single trial. The incorporation of external data can increase statistical power and circumvent challenges in recruiting paediatric controls. Integrating these methodological and biological innovations will be critical for delivering targeted, effective, and age-inclusive therapeutic strategies, ultimately improving outcomes for children and young people living with JIA.