Search Results (197)

Osteoarthritis (OA), the most prevalent form of arthropathy, is characterized by progressive degradation of cartilage, synovial inflammation, and other pathological changes that gradually affect the entire joint. Once regarded as a purely degenerative disease with minimal immune involvement, recent evidence reveals that chronic low-grade inflammation, insidiously fueled by the destructive crosstalk between cartilage and synovium, plays a key role in OA pathophysiology. Among the immune cells involved, eosinophils have emerged as unexpected yet significant contributors, exhibiting both pro-inflammatory and immunoregulatory properties. Traditionally associated with allergic responses and antiparasitic defense, eosinophils can also secrete anti-inflammatory cytokines along with specialized pro-resolving lipid mediators (SPMs) that promote macrophage polarization toward reparative M2 phenotypes. Eosinophils may sustain inflammation or, conversely, act as “silent modulators” that subtly shape the immune microenvironment and support tissue homeostasis. This immunological plasticity positions them at the intersection of joint damage and repair. This article explores emerging evidence on eosinophil activity in OA, emphasizing their dual nature and potential as therapeutic targets to shift the joint milieu from a pro-inflammatory state toward resolution. Understanding eosinophil-mediated pathways may pave the way for novel strategies to reduce synovial inflammation, preserve cartilage integrity, and improve clinical outcomes. Full article

Background/Objectives: The approach to physical activity in people with hemophilia (PwH) is still conditioned by many difficulties. Thus, a prospective observational pilot study has been carried out aiming to evaluate how an adequate and controlled training program can slow down the onset or evolution of arthropathy and improve musculoskeletal health and quality of life. Methods: Performed from April 2022 to April 2023, this study involved nine severe hemophilic A and B patients, aged > 18 years old, on regular prophylaxis with replacement products. Participants, without changing the usual prophylaxis schedule and maintaining a trough level of at least 20% FVIII/FIX before training, were involved in physical activity twice a week. Results: After 12 months, no increase in annual bleeding ratio (ABR) was observed, and baseline joint status (as assessable by HEAD US score, HJHS, and NRS) was maintained. Even if not statistically significant, a trend toward improvement in mean HEAD US score (15.55 vs. 13.11) and HJHS (14.4 vs. 11) from baseline was observed. Some of the physical tests performed showed a significant improvement at 6 months and 12 months from baseline (5 Rep Sit to Stand, Sit and Reach, and 6-minute Walking Test), meaning an improvement in leg strength, dorsal flexibility, and aerobic resistance. Conclusions: This is the first pilot study evaluating at 360 degrees the safety and impact of a controlled physical activity in PwH. No participant experienced bleedings or a worsening in joint status, but they experienced an improvement in articular functionality. Without changing the usual prophylaxis, scheduling training sessions according to individual pharmacokinetics turned out to be a safe and a cost-effective approach. Full article

Background and Objectives: Hemophilic arthropathy, the end result of recurrent hemarthroses in patients with hemophilia, often necessitates total knee arthroplasty (TKA) using constrained implants to address severe deformities and joint destruction. Revision TKA is often required due to aseptic loosening, implant malposition, infection, or periprosthetic fractures. The extended tibial tuberosity osteotomy (ETTO) has emerged as a critical technique for the safe removal of well-fixed tibial stems in such complex cases, demonstrating high union rates and minimal complications. The aim of this study is to evaluate the safety, effectiveness, and clinical outcomes of the ETTO technique during complex revision TKA in patients with hemophilia. Materials and Methods: A retrospective analysis was conducted on seven male hemophilic patients who underwent revision TKA with ETTO between 2015 and 2023. The procedure involved the creation of an extended proximal tibial bone flap, laterally retracted to facilitate tibial stem exposure and removal. Postoperative outcomes included radiological confirmation of osteotomy union, assessment of complications, and evaluation of functional outcomes, including range of motion and extensor mechanism integrity. Results: Osteotomy union was achieved in all patients (mean age 57.5 ± 1.50 years and mean body mass index 26.07 ± 0.67 kg/m²) within four months, confirmed by radiographic evidence of bridging callus. No significant complications, such as nonunion, fragment displacement, or symptomatic hardware, were observed. There was one patient who experienced delayed wound healing, managed successfully with surgical debridement. Postoperative mean knee flexion was 92°, with no extensor lag reported. ETTO enabled safe tibial stem removal and successful revision arthroplasties in all cases. Conclusions: ETTO is a technically demanding but indispensable approach for addressing the challenges of revision TKA in patients with hemophilia. It allows for secure tibial stem removal while maintaining excellent union outcomes and a low rate of complications. Due to its complexity, ETTO should be performed by experienced surgeons in specialized centers. Full article

Background: Recurrent haemarthrosis leads to progressive and degenerative joint damage in patients with haemophilia from an early age. Haemophilic arthropathy is characterised by chronic pain, restricted range of motion, proprioceptive deficits, and structural alterations. The aim of this study was to evaluate the effectiveness of a manual therapy protocol in patients with haemophilic ankle arthropathy. Methods: A randomised, crossover, double-blind clinical trial was conducted. Thirteen patients with haemophilia were allocated to two sequences: A–B (intervention phase followed by placebo control) and B–A (placebo control followed by intervention). The intervention comprised joint mobilisation techniques, high-velocity low-amplitude manipulations, and myofascial release. In the placebo control condition, a simulated protocol was applied, consisting of intermittent contact and light pressure. Both conditions involved three physiotherapy sessions, delivered once weekly over three consecutive weeks. Outcome measures included functional capacity (2-Minute Walk Test), pain intensity (visual analogue scale), range of motion (goniometer), pressure pain threshold (algometer), joint status (Haemophilia Joint Health Score), kinesiophobia (Tampa Scale of Kinesiophobia), and postural stability (pressure platform). Following a four-week washout period, participants crossed over to the alternate condition. Results: No participants experienced ankle haemarthrosis or other adverse events during the intervention, confirming the safety of the protocol. Significant time*sequence interactions (p < 0.05) with high post hoc power (≥0.80) were observed for functional capacity, range of motion, and joint status. A significant sequence effect was also found for most clinical outcomes, with no evidence of a carry-over effect. Conclusions: This manual therapy protocol might be safe for patients with haemophilia. The physiotherapy intervention demonstrated improvements in functionality, range of motion, and joint status in individuals with haemophilic ankle arthropathy. Full article

Gout and calcium pyrophosphate crystal deposition disease (CPPD) are frequently associated with comorbid disorders, including coronary artery disease and osteoarthritis, in which ectopic calcification with basic calcium phosphate crystals commonly affects arteries and articular cartilage, respectively. Accepting the 2024 G-CAN Gold Medal, I review my research philosophy for translational etiopathogenesis investigation in gout and CPPD, atherosclerosis, responses to arterial injury, and osteoarthritis. Since molecular homeostasis points to pathophysiology and vice versa, I have followed selected molecular players and pathways to phenotypes. Typically, behind each disease target is another target. Illuminating passageways between etiopathogenic pathways is especially productive when using approaches beyond conventional “omics” to reveal the impact of specific post-translational protein modifications, and changes in protein conformation, complex assembly, and interactomes. Highlighting these concepts, I review my past studies on specific molecular pathways, and current perspectives for the following: (i) PP_i, NPP1, ANKH, and transglutaminase 2 (TG2); (ii) relationships between NPP1, ANKH, Vanin-1 Pantetheinase, and ectopic chondrogenesis; (iii) intersections between adenosine, AMPK, CXCL8 and its receptor CXCR2, the receptor for advanced glycation endproducts (RAGE) and chondrocyte hypertrophy; (iv) lubricin homeostasis and proteolysis; (v) receptor for advanced glycation endproducts (RAGE) and TG2-catalyzed post-translational calgranulin modification; (vi) complement activation and C5b-9 assembly, and the nucleotide-bound conformation of TG2. The inescapable conclusion is that these molecular pathways tightly knit crystal arthropathy with both arterial and osteoarthritis comorbidity. Full article

Background: Peripheral nerve stimulation (PNS) has been employed as a therapeutic modality for managing chronic pain across diverse etiologies and neural targets. Nevertheless, its application in treating chronic axial neck pain remains markedly underexplored. Accordingly, this study aimed to both review the existing literature and present a retrospective single-center case series of patients who underwent temporary PNS targeting the cervical medial branch nerves (CMBNs) for chronic axial neck pain. Methods: This investigation comprises a narrative literature review alongside a single-center, retrospective case series evaluating percutaneous, temporary PNS for the management of cervical spondylosis facet arthropathy in the absence of myelopathy or radiculopathy. The primary outcomes were pain reduction, as measured by the numeric rating scale, and improvements in functional disability, with assessments conducted at baseline and at 60 days post-intervention. Results: PNS represents a neuromodulatory, nondestructive intervention that targets the CMBN to alleviate chronic axial neck pain, in contrast to the destructive mechanisms inherent in cervical radiofrequency ablation (CRFA). Although PNS has been applied to other neural targets, its use in the cervical region is sparsely documented, with limited case studies available. Notably, this case series is the first to report pain and disability outcomes specifically associated with CMBN PNS. At the 60-day follow-up, 66% of subjects achieved the minimal clinically important difference (MCID) for pain reduction, while 77% met the MCID for disability reduction. Moreover, our analysis uniquely examined the impact of previous CRFA and a history of cervical spine surgery on treatment outcomes, revealing that patients with such interventions experienced more modest improvements compared to their surgery- and CRFA-naive counterparts. Conclusions: The current literature reveals a significant gap regarding the use of CMBN PNS, underscoring an unmet need in the treatment algorithm for chronic axial neck pain beyond conservative modalities. Our findings suggest that CMBN PNS may offer a promising adjunctive therapy for carefully selected patients with refractory chronic axial neck pain who have not improved after medications, physical therapy, or injections. Additionally, the comparative analysis of outcomes in patients with a history of CRFA or cervical surgery underscores potential advantages of PNS prior to destructive therapies. Future research, ideally in the form of prospective studies with larger cohorts and extended follow-up durations, is warranted to further evaluate long-term outcomes and refine the place of PNS in the treatment algorithm. Full article

Background: The management of irreparable posterosuperior rotator cuff tears with an isolated loss of external rotation presents significant challenges. Latissimus dorsi tendon transfer in conjunction with medialized reverse total shoulder arthroplasty has been employed to rectify external rotation deficits; however, lateralized RTSA designs may yield similar outcomes with a reduced incidence of complications. The objective of this study was to compare the clinical outcomes of lateralized reverse total shoulder arthroplasty without latissimus dorsi tendon transfer against medialized RTSA with LDT in patients with ILER and a positive external rotation lag sign. Methods: This retrospective cohort study involved 34 patients diagnosed with CTA and severe external rotation deficiency, characterized by a positive ER lag sign and 0° active ER. The patients were treated with either lateralized reverse total shoulder arthroplasty (n = 21) or medialized RTSA with LDT (n = 13). Outcomes evaluated preoperatively and at the 24-month follow-up comprised range of motion, ER lag sign, Constant–Murley Score, SPADI, and radiographic offset parameters. Statistical analyses were adjusted for age, sex, and baseline values. Results: At follow-up, 70% of patients undergoing lateralized RTSA exhibited resolution of ER lag, compared to 23% in the LDT group (p < 0.05). Active external rotation improvement was more significant in the LDT group (34.6° compared to 18.5°, p < 0.05). However, both groups exhibited comparable final external rotation and functional scores (CMS: 63 ± 9 vs. 63 ± 16; SPADI: 73 ± 20 vs. 74 ± 22). Lateralized RTSA demonstrated superior preservation of internal rotation, as evidenced by a higher percentage of patients achieving a negative Apley scratch test (67% compared to 23%, p < 0.05). A greater glenoidal offset correlated with improved postoperative external rotation and resolution of external rotation lag. The influence of teres minor integrity was more significant in the LDT group. Conclusions: Lateralized reverse total shoulder arthroplasty without latissimus dorsi tendon transfer provides similar functional restoration of external rotation in irreparable posterosuperior rotator cuff tear patients, accompanied by reduced complications, shorter surgical durations, and improved preservation of internal rotation. LDT has the potential to provide enhanced ER gains from a low baseline; however, it is characterized by increased invasiveness and technical complexity. Prosthetic lateralization is a biomechanically effective method for restoring external rotation in patients with rotator cuff arthropathy and external rotation deficits. Full article

Background: Reverse total shoulder arthroplasty (RTSA) is increasingly used for managing cuff tear arthropathy, osteoarthritis, complex fractures, and revision procedures. As the demand for surgical precision and reproducibility grows, immersive technologies such as virtual reality (VR), augmented reality (AR), and metaverse-based platforms are being explored for surgical training, intraoperative guidance, and rehabilitation. While early data suggest potential benefits, a focused synthesis specific to RTSA is lacking. Methods: This systematic review was conducted in accordance with PRISMA 2020 guidelines. A comprehensive search of PubMed, Scopus, and Cochrane Library databases was performed through 30 May 2025. Eligible studies included those evaluating immersive technologies in the context of RTSA for skill acquisition or intraoperative guidance. Only peer-reviewed articles published in English were included. Data were synthesized narratively due to heterogeneity in study design and outcome metrics. Results: Out of 628 records screened, 21 studies met the inclusion criteria. Five studies evaluated immersive VR for surgical training: four randomized controlled trials and one retrospective case series. VR training improved procedural efficiency and showed non-inferiority to cadaveric training. Sixteen studies investigated intraoperative navigation or AR guidance. Clinical and cadaveric studies consistently reported improved accuracy in glenoid baseplate positioning with reduced angular and linear deviations in postoperative controls as compared to preoperative planning. Conclusions: Immersive technologies show promise in enhancing training, intraoperative accuracy, and procedural consistency in RTSA. VR and AR platforms may support standardized surgical education and precision-based practice, but their broad clinical impact remains limited by small sample sizes, heterogeneous methodologies, and limited long-term outcomes. Further multicenter trials with standardized endpoints and cost-effectiveness analyses are warranted. Postoperative rehabilitation using immersive technologies in RTSA remains underexplored and presents an opportunity for future research. Full article

Background/Objectives: Sarcopenia is defined by the progressive loss of muscle mass, strength, and/or physical performance associated with aging. Radiofrequency ablation (RFA) of the medial branch nerves is a well-established and effective treatment for lumbar facetogenic pain. While sarcopenia is associated with poor outcomes following epidural steroid injections and lumbar spine surgeries, its impact on clinical outcomes in patients undergoing RFA for facetogenic pain remains unexplored. This study aims to evaluate the influence of sarcopenia on treatment outcomes in this patient cohort. Methods: Patients were classified into sarcopenia (n = 35) and non-sarcopenia groups (n = 67) based on predefined psoas muscle index (PMI) thresholds. The primary outcomes included changes in back pain intensity and the proportion of responders at 1, 3, and 6 months following RFA. The secondary outcome was to identify demographic, clinical, and sarcopenia-related factors predictive of treatment response at each follow-up interval. Results: Both groups demonstrated statistically significant improvements in pain scores compared to baseline at all follow-up points. However, the median pain scores at 3 months post-RFA remained significantly higher in the sarcopenia group. Despite this, the proportion of responders did not differ significantly between the two groups at any time point. At 3 months, the absence of prior spinal surgery was identified as a significant predictor of treatment response. At 6 months, favorable outcomes were significantly associated with the absence of diabetes, no history of spinal surgery, and a higher PMI. Conclusions: Sarcopenia may influence the extent of pain improvement following medial branch nerve RFA. Additionally, patient-specific factors, such as diabetes, prior spinal surgery, and PMI, should be considered when predicting treatment outcomes. Full article

Haemophilic arthropathy is caused by repeated joint bleeding episodes, primarily affecting knees, ankles and elbows. Conservative options should be considered prior to surgery, as well as postural evaluation, since any functional overload promotes the development of new bleeding. The aim of this study is to verify the use of foot orthoses in combination with postural rehabilitation, assessing the incidence of spontaneous haemarthroses and haematomas. In total, 15 patients were enrolled and randomly divided into two groups: 8 in group A, composed of patients who were prescribed foot orthoses and a 20-session rehabilitation program, and 7 in group B, composed of patients who were instructed to use foot orthoses only. All patients were evaluated at baseline (T0), at 3 months (T1—end of the rehabilitation program), and at 12 months (T2), using the following scales: Functional Independence Score in Haemophilia (FISH), Haemophilia Joint Health Score (HJHS) and Numerical Rating Scale (NRS). During the 12 months between the first and the last assessment, no patient in group A developed hemarthroses or hematomas, while one case of hemarthrosis was recorded in group B. The HJHS improved significantly (≤0.05) in group A at both T1 and T2, while in group B it improved significantly only in T2. As for FISH, it showed significant improvements in both groups at T1 and T2. NRS showed a significant reduction only at T2 in both groups (p-value T0–T1 0.3 in group A e 0.8 in group B). No patient reported any adverse effects from the use of orthotic insoles. The combination of postural rehabilitation, the use of foot orthoses and pharmacological prophylaxis could improve functioning and joint status in patients affected by haemophilic arthopathy, delaying or preventing new hemarthroses by improving the distribution of joint loads and the modification of musculoskeletal system’s characteristics. Full article

Background: Immune checkpoint inhibitors (ICIs) transformed cancer treatment, producing significant survival benefits. However, ICIs can trigger toxicities called immune-related adverse events (irAEs), including inflammatory arthritis (IA) and polymyalgia rheumatica (PMR)-like syndromes. Our study aimed to systematically further characterize musculoskeletal ultrasound (MSKUS) findings in patients with ICI-IA and ICI-PMR, collectively referred to as “MSK-irAEs”, and explore the role of US in guiding treatment. Methods: The authors conducted a comprehensive chart review for patients receiving ICIs undergoing MSKUS at our center’s rheumatology clinics. US examinations were performed and reviewed by two MSKUS-certified rheumatologists. Descriptive statistics were performed to summarize demographic, clinical, and treatment-related variables. US findings were categorized with a novel scoring system: 0—no signs of inflammatory arthropathy or tendinopathy, 1—potential signs of inflammation (grayscale ≥ 2, effusion without power Doppler, synovial hypertrophy in the joint), and 2—active inflammation in joints and/or tendons (characterized by power Doppler) and signs of inflammation. Results: Twenty-three patients were included. The median age was 63 years, 52% were male, and 87% were White. Melanoma was the most common cancer (48%). MSK-irAEs were diagnosed in nineteen (83%), with MSKUS showing inflammation in seventeen (74%). Sixteen (70%) received escalation in MSK-irAE treatment after MSKUS. Four (17%) had erosive disease due to MSK-irAEs, while one had erosive osteoarthritis. Individuals with inflammatory erosive changes experienced prolonged intervals between symptom onset and MSKUS, ranging from 17 to 82 months, suggesting that erosions may reflect chronic, under-recognized inflammation. On MSK-irAE therapy, nine (47%) experienced symptomatic improvement, five (26%) achieved resolution, and in four (21%) cases, it was too early to assess the response. MSKUS detected other causes of MSK symptoms besides MSK-irAEs in several patients, allowing ICI resumption in one. Conclusions: Our study highlights the clinical utility of MSKUS not only as a diagnostic tool but also to guide therapeutic decision-making. Full article

Osteoarthritis (OA) is the most common chronic arthropathy worldwide. OA synovitis is a common feature that predicts the development and progression of symptoms and joint damage. Although the OA synovium is a target for novel therapies, the development of ex vivo models remains an area requiring further research. We aim to develop a 3D tissue explant culture model of human OA synovium that preserves the architecture and cellular heterogeneity of the original tissue in vitro. We derived tissue explant models from seven patients with OA and followed the culture for up to 10 days, assessing their morphology and cellular composition by immunohistochemistry (IHC) and flow cytometry, respectively. IHC analysis of explant cultures showed that tissue integrity and viability were maintained in our in vitro system. Furthermore, cellular heterogeneity was essentially unchanged when considering CD4⁺ T cells, CD8⁺ T cells, and myeloid fractions in our model. No significant variation was observed in the CD90⁺ and CD90^-CD55⁺ fractions, which also maintained an activated state as indicated by high levels of FAP expression. An ex vivo OA synovial tissue explant model can maintain pathological tissue integrity for 10 days in culture. This simple and reliable culture system may be useful for analyzing the pathogenesis of OA disease and for the development and testing of therapeutic drugs. Full article

Background/Objectives: The variety of magnetic resonance imaging (MRI) scales available to measure soft tissue and osteochondral changes in joints of persons with hemophilia poses challenges in evaluating published clinical/research studies. To evaluate the value of four MRI scales [(i) the 17-point International Prophylaxis Study Group [IPSG] additive scale; (ii) and (iii) the compatible IPSG progressive (P) and additive (A) scales; and (iv) the Denver progressive scale] to assess joint change in boys with hemophilia participating in a prospective two-year prophylaxis study. Methods: Boys with severe hemophilia A (ages, 7–16 years) followed at the Hospital for Sick Children, Toronto, Canada had MRI evaluations of six index joints (ankles, knees, elbows) at study entry and exit. Musculoskeletal (MSK) outcomes included in the study were the Colorado Child Physical Examination (PE) scale; the Pettersson (X-ray) scale; and the aforementioned 4 MRI scales. Results: Very strong (r ≥ 0.80) correlations were observed between the IPSG 17-point, the IPSG progressive (P) and the Denver MRI scales, and moderate (r = 0.40–0.59) to strong (r = 0.60–0.79) correlations for the IPSG 17 point and the IPSG additive (A) MRI scales. Very weak (r = 0.20–0.39) or no correlations were observed between soft tissue MRI scores and the swelling item of the Child PE scale. Conclusions: All four MRI scales demonstrated relative comparability of their construct validities for assessing mild/moderate hemophilic arthropathy. The 17-point IPSG additive scale is recommended as a reference standard in future long-term studies of young boys with hemophilia receiving factor and non-factor-based preventive therapies. Full article

Objectives: (1) To compare cytokine levels in participants with serum urate (SU) < 360 µmol/L, SU ≥ 360 µmol/L with and without monosodium urate (MSU) crystal deposition, respectively, and inter-critical gout. (2) To explore the association of IL-1β, IL-6 and high-sensitivity (hs) CRP with disease duration and the frequency of self-reported gout flares. Methods: Samples and data from 184 participants from studies conducted at Academic Rheumatology, Nottingham City Hospital, were included. Serum high-sensitivity CRP and cytokines involved in the pathogenesis of gouty inflammation were measured. MANCOVA and multivariate linear regression were used, as appropriate, and were adjusted for age, sex, body mass index and self-reported comorbidities. p values were adjusted for multiple testing using a 5% false-discovery rate. Results: Participants with inter-critical gout had greater levels of IL-1β (p_corr = 0.009), IL-18 (p_corr = 0.02), IL-6 (p_corr < 0.0001), IP-10 (p_corr < 0.0001), TNF-α (p_corr < 0.0001), GRO-α (p_corr = 0.0006) and hsCRP (p_corr = 0.009) compared to other groups in multivariate analyses and after correcting for multiple testing. There were no differences in cytokine and hsCRP levels in participants with SU < 360 µmol/L and in participants with SU ≥ 360 µmol/L with or without MSU crystal deposition. There was a statistically non-significant trend for association between IL-6 levels and number of self-reported gout flares. Conclusions: Our findings suggest that gout is a chronic inflammatory condition. The pre-clinical phases of gout were not associated with systemic inflammation, potentially due to the modest sample size. Further research is required to understand whether treating gout by targeting the complete dissolution of MSU crystals would reduce systemic inflammation in inter-critical gout. Full article

Calcium pyrophosphate deposition disease (CPPD) is a common crystal arthropathy characterized by the deposition of calcium pyrophosphate crystals in joints and soft tissues. Ultrasonography (US) has emerged as a valuable imaging modality for diagnosing CPPD, offering real-time visualization of crystal deposits and joint inflammation. In the context of personalized medicine, US plays a critical role in enabling individualized patient assessment, facilitating early and accurate diagnosis, and supporting tailored therapeutic decisions based on specific imaging findings. This article reviews the ultrasonographic features of CPPD, their diagnostic utility, and clinical applications, emphasizing the relevance of US in stratifying patients and guiding personalized management approaches. Full article