Baseline Joint Research Articles

Early Rheumatoid Arthritis Patients at Presentation Are Changing: A 24-Year Study of the Early Undifferentiated PolyArthritis (EUPA) Cohort.

To analyze changes in baseline characteristics of very early rheumatoid arthritis (RA) over 24 years in the Early Undifferentiated PolyArthritis (EUPA) cohort. Consecutive recent-onset polyarthritis patients fulfilling RA classification criteria recruited in EUPA were assessed at baseline. Three successive periods were defined: prior to the general availability of biologics (1998-2004; 245 patients), prior to the implantation of the 2010 classification criteria (2005-2010; 266 patients), and the most recent decade (2011-2022; 329 patients). At baseline, demographics, BMI, swollen and tender joint counts, proportion fulfilling 2010 ACR⁄EULAR criteria, Modified Health Assessment Questionnaire, shared epitope status, patient-reported outcomes except pain and Patient Evaluation of Disease Activity remained stable over the 3 periods. Despite a marked decrease in active smoking (22.2 to 12.1%), prevalence of cardiovascular comorbidities and prior cancer increased. While duration of symptoms increased from 2.9 to 4.1 months, seropositivity (53.9 to 42.2%), and CRP began decreasing in the 2005-2010 period. A large decrease in Erosive status (Sharp-van der Heijde erosion score ≥5; 18.3 to 9.4%) was only observed after 2011; this decrease occurred mostly in seronegative patients. DMARD use prior to inclusion remained low and stable (25.7%), but oral corticosteroids increased (18.0 to 33.4%). Baseline characteristics of RA patients evolved since 2005 towards less seropositivity and lower blood inflammation but with more comorbidities. Milder erosive damage at baseline became evident only since 2011, mostly in seronegative patients. These changes at baseline, before any intervention, suggest ongoing secular trends that may favorably impact early RA patients' outcomes.

Small Fiber Neuropathy Associated with Post-COVID-19 and Post-COVID-19 Vaccination Arthritis: A Rare Post-Infective Syndrome or a New-Onset Disease?

Post-COVID-19 (PC) and post-COVID-19 vaccination (PCV) syndromes are considered emergent multidisciplinary disorders. PC/PCV small fiber neuropathy (SFN) was rarely described and its association with undifferentiated arthritis (UA) was never defined. We aimed to evaluate PC/PCV-UA associated with the recent onset of severe lower limb paresthesia, compare SFN positive (+) to negative (-) patients, and evaluate changes in biomarkers in SFN+ during treatments. Nineteen PC/PCV-UA-patients with possible SFN underwent skin biopsy at the Usl Tuscany Center (Florence) early arthritis outpatient clinic from September 2021 to March 2024. Eight selected SFN+ were compared to ten SFN- patients. In SFN+ patients, baseline joint ultrasound (US), electromyography (EMG), optical coherence tomography (OCT), and skin biopsy were repeated at six months. Moreover, SFN+ patients were clinically assessed by a 0-10 numeric rating scale for neurological symptoms and DAS28/ESR up to 12 months follow-up. SFN+ patients showed a lower intraepidermal nerve fiber density at histopathological examination of skin biopsies and a higher frequency of OCT and EMG abnormalities in comparison to SFN- patients. In SFN+ patients, US and DAS28/ESR significantly improved, while intraepidermal nerve fiber density did not significantly change at the six-month follow-up. Fatigue, motor impairment, burning pain, brain fog, and sensitivity disorders decreased at long-term follow-up (12 months).

Multi-scale image compression and reconstruction algorithm for structural health monitoring system

Image data is increasingly common in structural health monitoring systems. However, due to the limitation of hardware resources such as network bandwidth, the data collected by sensors cannot be transmitted efficiently. In order to solve the problem of inefficient data transmission and ensure data recoverability, an end-to-end compression and reconstruction algorithm with an attention-enhanced residual module and a quantization mechanism is proposed. In order to meet the needs of SHM systems for image diversity, multi-scale images of local and global structural damage are used for research. The performance of the proposed algorithm is compared with traditional image compression standards and baseline models. Experimental results show that the peak signal-to-noise ratio of the reconstructed image is greater than 30 dB at different bit rates, effectively reconstructing the original image information; for images with complex textures, the residual block attention module can improve the rate-distortion performance of the proposed algorithm; when the bit rate is less than 0.44 bit per pixel, the peak signal-to-noise ratio and structural similarity of the reconstructed image of the proposed algorithm are better than those of the autoencoder baseline model and Joint Photographic Experts Group compression method. Structural damage detection examples verify the usability of compressed-reconstructed images in engineering applications.

Stiffness-Based Evaluation of Hinge Joints in Prefabricated Assembled Multi-Girder Bridges under Operational Conditions.

Presently, the prevailing approaches to assessing hinge joint damage predominantly rely on predefined damage indicators or updating finite element models (FEMs). However, these methods possess certain limitations. The damage indicator method requires high-quality monitoring data and demonstrates variable sensitivities of distinct indicators to damage. On the other hand, the FEM approach mandates a convoluted FEM update procedure. Hinge joint damage represents a major kind of defect in prefabricated assembled multi-girder bridges (AMGBs). Therefore, effective damage detection methods are imperative to identify the damage state of hinge joints. To this end, a stiffness-based method for the performance evaluation of hinge joints of AMGBs is proposed in this paper. The proposed method estimates hinge joint stiffness by solving the characteristic equations of the multi-beam system. In addition, this study introduces a method for determining baseline joint stiffness using design data and FEM. Subsequently, a comprehensive evaluation framework for hinge joints is formulated, coupling a finite element model with the baseline stiffness, thereby introducing a damage indicator rooted in stiffness ratios. To verify the effectiveness of the proposed method, strain and displacement correlations are analyzed using actual bridge monitoring data, and articulation joint stiffness is identified. The results underscore the capability of the proposed method to accurately pinpoint the location and extent of hinge joint damage.

The Role of the Hip Capsule in Restoring Stability in the Initial Phase of Hip Distraction: An In Vivo Analysis

Background: The labral suction seal has been shown to provide the majority of resistance in the initial phase of hip distraction. However, the effect of an unrepaired interportal capsulotomy and capsular repair on the initial phase of hip distractive stability in vivo is not well understood. Purpose: To investigate the effect of capsular repair on the initial phase of distractive stability of hip joints in patients with femoroacetabular impingement (FAI) syndrome. Study Design: Controlled laboratory study. Methods: Patients undergoing primary hip arthroscopy for FAI between March and August 2020 were prospectively enrolled. Total joint space was measured on fluoroscopic images at the medial and lateral edges of the sourcil at 12.5-lb (5.7-kg) axial traction intervals (up to 100 lb [45.4 kg]) in 3 capsular states: (1) native capsule, (2) interportal capsulotomy, and (3) capsular repair. Distraction on anteroposterior radiographs was calculated as the difference between total joint space at each traction interval and baseline joint space at 0 lb, normalized to millimeters. The native, capsulotomy, and capsular repair states were compared using Wilcoxon signed-rank and McNemar tests. Results: Included were 36 hips in 35 patients. The median force required to distract ≥3 mm was 75 lb (34.0 kg; 95% CI, 70-80 lb [31.8-36.3 kg]) in both the native and capsular repair states ( P = .629), which was significantly greater than the median force required to distract ≥3 mm in the capsulotomy state (50 lb [22.7 kg]; 95% CI, 45-55 lb [20.4-24.9 kg]) ( P < .001). The most rapid rates of change in joint space were observed at the traction interval at which hips first achieved ≥3 mm of distraction (n = 33 hips; 92%). Conclusion: The traction force at which hips distracted ≥3 mm was 75 lb (34.0 kg) in both the native capsular and capsular repair states. Significantly less traction force (50 lb [22.7 kg]) distracted hips ≥3 mm in the capsulotomy state. Complete capsular closure after interportal capsulotomy resulted in restoration of initial distractive stability relative to the unrepaired capsulotomy state at time zero after primary hip arthroscopy. Clinical Relevance: This study provides surgeons with an improved understanding of the additional stability to the hip joint from capsular repair after hip arthroscopy for FAI syndrome.

3D printed auxetic metal stiffener for lightweight metal–composite T-joints with high strength and toughness

A novel auxetic structure-based stiffener for stainless steel–carbon reinforced polymer (CFRP) T-joints with outstanding strength and toughness improvement is proposed. The stiffener was composed of a bulk web and re-entrant structure flange that was 3D printed using a selective laser melting 3D printer. The stiffener was bonded to a CFRP skin, and a pull-off test was performed to evaluate the pull-off strength, stiffness, and toughness of the joint. The results demonstrated that the proposed structure has specific strength and toughness that were 3.4 and 77 times greater than those of the baseline joint, respectively. The improvement in strength was due to the delayed damage initiation caused by the mismatch between the bending stiffness of the bulk web and the stiffener under the first re-entrant structure. However, the damage initiation in the baseline joint was located at the stiffener edge. Moreover, the negative Poisson's ratio of the re-entrant structure arrested the delamination growth after damage initiation, which enhances the toughness of the joint. By optimizing the structure of the stiffener, a joint with 2.66 and 38.2 times larger specific strengths and toughness compared to the baseline joint with the same specific stiffness was achieved.

Dynamic joint stiffness in individuals with femoroacetabular impingement syndrome pre- and post-hip arthroscopy

BackgroundPatients with hip-related pain often fail to return to their desired level of activity following hip arthroscopy. Lasting biomechanics alterations may be one potential explanation. Dynamic joint stiffness assesses the mechanistic controls of the lower limb during high impact movements, and thus, may provide valuable clinical targets to improving movement and optimizing return to activity after surgery. MethodsTwenty-five participants (13 females) with hip-related pain underwent 3D motion capture during a drop jump task before surgery and six months post-operatively. Nineteen healthy controls (9 females) were collected for comparison. Sagittal plane dynamic joint stiffness was calculated during the initial landing phase. Baseline and 6-month dynamic joint stiffness data were compared 1) between males and females with hip-related pain and 2) between individuals with hip-related pain and controls using Wilcoxon Signed-Rank and Mann Whitney U tests. Sexes were analyzed separately. FindingsFrom baseline to 6 months post-operatively, females with hip-related pain demonstrated decreased dynamic ankle stiffness (2.26 Nm/deg. [0.61] to 1.84 Nm/deg. [0.43]) (p = .005) and males with hip-related pain demonstrated increased dynamic hip stiffness (2.73 [0.90] to 3.88 [1.73]) (p = .013). There were no differences in dynamic stiffness at any joint between individuals with hip-related pain at either timepoint when compared to controls (p ≥ .099). InterpretationFemales and males with hip-related pain may demonstrate unique changes in dynamic joint stiffness after surgery, indicating return to activity may follow different trajectories for each sex. Additional work should examine the relationship between hip joint stiffness and treatment outcomes and identify additional movement-related rehabilitation targets.

Neurological intervention transition model for dynamic prediction of good outcome in spontaneous subarachnoid haemorrhage.

Deterioration of neurovascular conditions can be rapid in patients with spontaneous subarachnoid haemorrhage (SAH) and often lead to poor clinical outcomes. Therefore, it is crucial to promptly assess and continually track the progression of the disease. This study incorporated baseline clinical conditions, repeatedly measured neurological grades and haematological biomarkers for dynamic outcome prediction in patients with spontaneous SAH. Neurological intervention, mainly aneurysm clipping and endovascular embolisation, was also incorporated as an intermediate event in developing a neurological intervention transition (NIT) joint model. A retrospective cohort study was performed on 701 patients in spontaneous SAH with a study period of 14days from the MIMIC-IV dataset. A dynamic prognostic model predicting outcome of patients was developed based on combination of Cox model and piecewise linear mixed-effect models to incorporate different types of prognostic information. Clinical baseline covariates, including cerebral oedema, cerebral infarction, respiratory failure, hydrocephalus and vasospasm, as well as repeated measured Glasgow Coma Scale (GCS), glucose and white blood cell (WBC) levels were covariates contributing to the optimal model. Incorporation of neurological intervention as an intermediate event increases the prediction performance compared with baseline joint modelling approach. The average AUC of the optimal model proposed in this study is 0.7783 across different starting points of prediction and prediction intervals. The model proposed in this study can provide dynamic prognosis for spontaneous SAH patients and significant potential benefits in critical care management.

Effects of individual practice on joint musical synchronization.

Successful music-making requires precise sensorimotor synchronization, both in individual (solo) and joint (ensemble) social settings. We investigated how individual practice synchronizing with a temporally regular melody (Solo conditions) influences subsequent synchronization between two partners (Joint conditions). Musically trained adults practiced producing a melody by tapping on a keypad; each tap generated the next tone in the melody. First, the pairs synchronized their melody productions with their partner in a baseline Joint synchronization task. Then each partner separately synchronized their melody with a computer-generated recording of the partner's melody in a Solo intervention condition that presented either Normal (temporally regular) auditory feedback or delayed feedback (by 30-70 ms) in occasional (25%) randomly placed tone positions. Then the pairs synchronized again with their partner in a Joint condition. Next, they performed the second Solo condition (normal or delayed auditory feedback) followed again by the Joint condition. Joint synchronization performance was modeled with a delay-coupled oscillator model to assess the coupling strength between partners. Absolute asynchronies in the Solo Intervention tasks were greater in the Delayed feedback condition than in the Normal feedback condition. Model estimates yielded larger coupling values between partners in Joint conditions that followed the Solo Normal feedback than the Solo Delayed feedback. Notably, the asynchronies were smaller in the Joint conditions than in the Solo conditions. These findings indicate that coupled interactions in settings of two or more performers can be improved by individual synchronization practice.

Anti-Peptidylarginine Deiminase 4 Autoantibodies and Disease Duration as Predictors of Treatment Response in Rheumatoid Arthritis.

Given that autoantibodies to peptidylarginine deiminase 4 (PAD4) are associated with erosive disease in established rheumatoid arthritis (RA), this study was conducted to compare the clinical and prognostic use of anti-PAD4 antibodies in patients with early and established RA. Sera from patients with early (duration <2 years; n=422) or established (duration ≥2 years; n=359) RA from two randomized clinical trials of tofacitinib ± methotrexate compared with adalimumab + MTX or MTX alone were evaluated for the presence of anti-PAD4 and anti-PAD3/4 antibodies at baseline and posttreatment time points. Summary statistics were calculated for demographic, clinical, and serological characteristics, and generalized estimating equations were used to model clinical outcomes by disease duration according to anti-PAD4 status. Anti-PAD4 antibodies were present in 22% and 40% of patients with early and established RA, respectively, stable following treatment, and associated with baseline joint damage only in established RA. In early RA, baseline anti-PAD4 antibodies were associated with a greater improvement in disease activity score 28-joint count using C-reactive protein levels after treatment compared with individuals with negative anti-PAD4 (P = 0.049). Tofacitinib ± MTX was more broadly efficacious than MTX alone at improving clinical outcomes in early and established RA, irrespective of anti-PAD4 status (P < 0.05 for all), whereas adalimumab + MTX exhibited differential benefits in achieving disease activity score remission in early RA (P = 0.036) and American College of Rheumatology 20 responses in established RA (P = 0.002). Differences in prevalence, clinical associations, and treatment-response outcomes according to anti-PAD4 antibody status in early and established RA suggests the existence of a therapeutic window to prevent the accumulation of irreversible joint damage in early patients with RA with anti-PAD4 antibodies.

Sex-specific cardiovascular protein levels and their link with clinical outcome in heart failure.

This study aims to provide insight into sex-specific cardiovascular protein profiles and their associations with adverse outcomes, which may contribute to a better understanding of heart failure (HF) pathophysiology and the optimal use of circulating proteins for prognostication in women and men. In 250 stable patients with HF with reduced ejection fraction (HFrEF), we performed trimonthly blood sampling (median follow-up: 26 [17-30] months). We selected all baseline samples and two samples closest to the primary endpoint (PEP; composite of cardiovascular death, heart transplantation, left ventricular assist device implantation, and HF hospitalization) or one sample closest to censoring and applied the Olink Cardiovascular III panel. We used linear regression to study sex-based differences in baseline levels and joint models to study differences in the prognostic value of serially measured proteins. In 66 women and 184 men (mean age of 66 and 67years, respectively), 21% and 28% reached the PEP, respectively. Mean baseline levels of fatty acid-binding protein 4, secretoglobin family 3A member 2, paraoxonase 3, and trefoil factor 3 were higher in women (Pinteraction : 0.001, 0.007, 0.018, and 0.049, respectively), while matrix metalloproteinase-3, interleukin 1 receptor-like 1, and myoglobin were higher in men (Pinteraction : <0.001, 0.001, and 0.049, respectively), independent of clinical characteristics. No significant differences between sexes were observed in the longitudinal associations of proteins with the PEP. Only peptidoglycan recognition protein 1 showed a suggestive interaction with sex for the primary outcome (Pinteraction =0.028), without multiple testing correction, and was more strongly associated with adverse outcome in women {hazard ratio [HR] 3.03 [95% confidence interval (CI), 1.42 to 6.68], P=0.008} compared with men [HR 1.18 (95% CI, 0.84 to 1.66), P=0.347]. Although multiple cardiovascular-related proteins show sex differences at baseline, temporal associations with the adverse outcome do not differ between women and men with HFrEF.

Intra-Articular AAV9 α-l-Iduronidase Gene Replacement in the Canine Model of Mucopolysaccharidosis Type I

Mucopolysaccharidosis type I (MPS I), an inherited lysosomal storage disorder characterized by deficiency of α-l-iduronidase (IDUA) activity, causes multisystemic pathology due to sequelae of accumulated heparan and dermatan sulfates (HS and DS), the substrates of IDUA. Current treatments, though life-prolonging, inadequately address skeletal dysplasia and do not forestall progressive and painful degenerative joint disease. Previous studies demonstrated that intra-articular enzyme replacement cleared cellular lysosomal storage and reduced joint inflammation. Three nontolerized MPS I canines were studied to assess safety, efficacy, and durability of IDUA gene replacement therapy delivered via intra-articular injection. After baseline joint tissue biopsies, the right shoulder and stifle of each animal were injected in the intra-articular space with AAV9-IDUA and contralateral joints with AAV9-eGFP. Animals received either 5E11 or 5E12 vector genomes/joint. Necropsy was performed at 2- or 52-week postinjection. All animals tolerated injections without adverse effects. At two weeks, supraphysiologic IDUA enzyme activity was measured in AAV9-IDUA-treated but not AAV9-eGFP-treated synovium, with corresponding normalization of HS content and synoviocyte morphology. The AAV9-IDUA-treated cartilage had normal physiologic levels of IDUA enzyme, reduced but not normalized HS and DS levels compared to untreated MPS I cartilage, and healthy chondrocyte morphology. Liver IDUA transgene and IDUA enzyme activity were identified, as was serum IDUA activity which was 40% of wild-type serum enzyme activity. At 52-week postinjection, AAV9-IDUA-treated synovium and cartilage IDUA enzyme activity declined in both animals, corresponding to high tissue HS and DS levels and severe lysosomal storage. Liver and serum IDUA activity levels were undetectable. A dose-dependent serum anti-IDUA antibody response was observed which, together with loss of transgene with age, likely contributed to decline in tissue enzyme activity and treatment efficacy. Our study demonstrates successful proof-of-concept for intra-articular gene replacement therapy as a treatment for MPS-related joint dysplasia. Our observations suggest the possibility of multimodal gene replacement therapy to address multiple refractory manifestations of MPS I. Subsequent studies, in conjunction with immune tolerization and functional assessments of joint pathology, will investigate this possibility.

Moving from assessments to implementation: promising practices for strengthening multisectoral antimicrobial resistance containment capacity

BackgroundAntimicrobial resistance (AMR) poses a global threat to human, animal, and environmental health. AMR is a technical area in the Global Health Security Agenda initiative which uses the Joint External Evaluation tool to evaluate national AMR containment capacity. This paper describes four promising practices for strengthening national antimicrobial resistance containment capacity based on the experiences of the US Agency for International Development’s Medicines, Technologies, and Pharmaceutical Services Program work with 13 countries to implement their national action plans on AMR in the areas of multisectoral coordination, infection prevention and control, and antimicrobial stewardship.MethodsWe use the World Health Organization (WHO) Benchmarks on International Health Regulations Capacities (2019) to guide national, subnational, and facility actions that advance Joint External Evaluation capacity levels from 1 (no capacity) to 5 (sustainable capacity). Our technical approach is based on scoping visits, baseline Joint External Evaluation scores, benchmarks tool guidance, and country resources and priorities.ResultsWe gleaned four promising practices to achieve AMR containment objectives: (1) implement appropriate actions using the WHO benchmarks tool, which prioritizes actions, making it easier for countries to incrementally increase their Joint External Evaluation capacity from level 1 to 5; (2) integrate AMR into national and global agendas. Ongoing agendas and programs at international, regional, and national levels provide opportunities to mainstream and interlink AMR containment efforts; (3) improve governance through multisectoral coordination on AMR. Strengthening multisectoral bodies’ and their technical working groups’ governance improved functioning, which led to better engagement with animal/agricultural sectors and a more coordinated COVID-19 pandemic response; and (4) mobilize and diversify funding for AMR containment. Long-term funding from diversified funding streams is vital for advancing and sustaining countries’ Joint External Evaluation capacities.ConclusionsThe Global Health Security Agenda work has provided practical support to countries to frame and conduct AMR containment actions in terms of pandemic preparedness and health security. The WHO benchmarks tool that Global Health Security Agenda uses serves as a standardized organizing framework to prioritize capacity-appropriate AMR containment actions and transfer skills to help operationalize national action plans on AMR.

Patterns of clinical joint inflammation in juvenile idiopathic arthritis

ObjectivesWe studied patterns of joint inflammation in juvenile idiopathic arthritis (JIA) to assess whether joint activity recurs locally in the same joints.MethodsJoints of 91 patients of the BeSt for Kids...

The effect of guselkumab on inhibiting radiographic progression in patients with active psoriatic arthritis: study protocol for APEX, a Phase 3b, multicenter, randomized, double-blind, placebo-controlled trial

BackgroundGuselkumab, a fully human monoclonal antibody targeting the interleukin (IL)-23p19 subunit, is approved to treat adults with active psoriatic arthritis (PsA). In the Phase 3 DISCOVER-2 trial of 739 bilogico-naïve patients with active PsA, guselkumab 100 mg resulted in less radiographic progression, assessed via change from baseline in PsA-modified van der Heijde-Sharp (vdH-S) score, compared with placebo at week (W) 24 when given at W0, W4, and then every 4 weeks (Q4W) or Q8W. The least squares mean differences from placebo were -0.66 for guselkumab Q4W (p=0.011) and -0.43 for guselkumab Q8W (p=0.072). Reports suggest baseline C-reactive protein (CRP) and joint erosions are strongly prognostic of poor outcomes, especially radiographic progression, in PsA patients. We designed a trial (APEX) to further assess the effect of guselkumab on radiographic progression in patients with active PsA and risk factors for radiographic progression.MethodsPatients are eligible for APEX if they have had PsA for ≥6 months and active disease (≥3 swollen and ≥3 tender joints, CRP ≥0.3 mg/dL) despite prior therapy with conventional synthetic disease-modifying antirheumatic drugs, apremilast, and/or nonsteroidal anti-inflammatory drugs, with ≥2 joints with erosions on baseline radiographs (hands and feet). The primary and major secondary endpoints are the proportion of patients achieving ≥20% improvement in American College of Rheumatology response criteria (ACR20) response at W24 and change from baseline at W24 in PsA-modified vdH-S score, respectively. Sample sizes of 350/250/350 for guselkumab Q8W/guselkumab Q4W/placebo are expected to provide >99% power to detect significant differences in W24 ACR20 response rates for each guselkumab group vs placebo, as well as ≥90% (Q4W vs placebo) and ≥80% (Q8W vs placebo) power to detect a significant difference in PsA-modified vdH-S score change at W24. A Cochran-Mantel-Haenszel test and analysis of covariance will compare treatment efficacy for the primary and major secondary endpoints, respectively.DiscussionDISCOVER-2 findings informed the design of APEX, a Phase 3b study intended to further evaluate the impact of guselkumab in patients with active PsA and known risk factors for radiographic progression.Trial registrationThis trial was registered at ClinicalTrials.gov, NCT04882098. Registered on 11 May 2021.

Quantification of pre-existing radiographic damage and its relationship with joint activity and long-term clinical outcomes with secukinumab therapy in patients with psoriatic arthritis

BackgroundPsoriatic arthritis (PsA) patient data from two phase 3 secukinumab trials (FUTURE 1, 5) were analysed to quantify the prevalence and extent of pre-existing radiographic damage (RD) at baseline; investigate the association of RD with swollen/tender joint counts (SJC/TJC) at baseline; and investigate the extent to which RD at baseline correlated with response to secukinumab.MethodsPooled data (N = 1554) provided baseline radiographic bone erosion and joint space narrowing (JSN) scores at pre-specified locations per the van der Heijde-modified total Sharp score (vdH-mTSS) for PsA and swollen and tender joint scores in the same joints at multiple visits. Overall patient RD and individual joints RD bone erosion and JSN scores were assessed. The association between joint activity (tenderness, swelling) and vdH-mTSS was assessed at the overall patient-level and individual joint tender, swollen scores (yes/no) and RD joint JSN and bone erosion scores at the individual joint-level. Treatment response was assessed using SJC/TJC at weeks 16 and 52 and the proportion of patients achieving minimal disease activity (MDA) over all assessments within 1 year from FUTURE 5 alone.ResultsA substantial prevalence of pre-existing RD with higher prevalence of erosion than JSN was observed (86% and 60% of patients had positive erosion and JSN scores, respectively); higher RD prevalence was associated with longer time since PsA diagnosis. Joint activity was weakly associated with RD at baseline at the patient-level (Pearson’s coefficients: range 0.12–0.18), but strongly associated at the individual joint-level, with a higher probability of tender/swollen joints to associate with higher JSN/erosion scores: all 42 analysed joints showed statistical significance at the 0.05 level (unadjusted) for the relationship between joint tenderness (yes/no) and its JSN score, all but one for tenderness and bone erosion scores, and all but 2 for swollen and JSN scores and for swollen and bone erosion score. Secukinumab (150/300 mg), reduced TJC and SJC across all values of baseline erosion and JSN scores at weeks 16 and 52. Patients with higher levels of RD were less likely to achieve zero tender/zero swollen joint status and had lower chance of achieving MDA.ConclusionsPsA patients showed substantial prevalence of RD at baseline that correlated with time since diagnosis, but patient’s individual joint activity was strongly associated with pre-existing RD at those joints. Patients with the highest RD at baseline had a reduced likelihood of achieving zero joint count status.

Joint Status and Bleeding Phenotype Characterization in Severe and Non-Severe Hemophilia a and B

Introduction: Persons with hemophilia (PwH) A and B are known to have variable bleeding phenotypes and may have joint bleeding that is less clinically apparent. In recent years, musculoskeletal ultrasound (MSKUS) has become an established modality useful for evaluating joint status. Further, determination of individual bleeding phenotype can be challenging, but clinical tools including the International Society on Thrombosis and Haemostasis Bleeding Assessment Tool (ISTH-BAT), self-BAT, and the Beighton Hypermobility Score (BHS) have been developed. Methods: We hypothesize that presence and degree of joint disease, evaluated with MSKUS and physical assessment scoring, will correlate with severity of bleeding phenotype as characterized through clinical history, BAT assessment, and presence of joint hypermobility in PwH A and B. This will be accomplished through assessing baseline joint status and disease progression over time with MSKUS, as well as through use of the ISTH-BAT, self-BAT, and assessment of hypermobility with the BHS. Up to 100 individual subjects with severe, moderate, or mild hemophilia A or B will be enrolled and assessed at baseline and annually during the study period at our institution. Correlation of joint status with BHS and BAT scores will be analyzed with the generalized estimating equation (GEE) and other statistical methods. Results: Thus far, 15 male patients have been enrolled (Table 1). All moderate and severe hemophilia patients are on prophylactic therapies for bleed prevention, and 3 patients have history of inhibitors. Target joints were reported only in severe PwH. MSKUS measurements were completed using the JADE protocol1. Patient enrollment remains ongoing. Discussion: Knowledge pertaining to joint status and bleeding phenotype is PwH A and B is limited. This pilot study will assess the presence and degree of joint disease, evaluated with MSKUS and physical assessment scoring, and its correlation with severity of bleeding phenotype as characterized through clinical history, BAT assessment, and presence of joint hypermobility in PwH hemophilia A and B. The results will be used to justify a larger, multicenter study to expand understanding of joint status and bleeding phenotype in PwH.

Effects of veterans’ mental health service-connections on patient-reported outcomes following total joint arthroplasty

BackgroundStudies report poor outcomes of elective orthopaedic surgeries among civilian patients receiving Workers’ Compensation (WC). However, little is known about surgical outcomes in veterans receiving similar benefits through the Veterans Affairs (VA) service-connected (SC) disability compensation program. MethodsVeterans undergoing primary total hip arthroplasty (THA) or total knee arthroplasty (TKA) at a VA Medical Center between 07/2019–12/2021 were analyzed by SC status. Outcomes were evaluated using Hip disability and Osteoarthritis Outcome Score for Joint Replacement (HOOS-JR) and Knee injury and Osteoarthritis Outcome Score for Joint Replacement (KOOS-JR) scores collected preoperatively and at 2- and 12-months postoperatively. Repeated measures mixed models were used to test for the effect of SC on HOOS-JR/KOOS-JR scores, controlling for baseline age, sex, and Charlson Comorbidity Index (CCI). SC and baseline joint function (stratified into quartiles using baseline HOOS-JR/KOOS-JR scores) were analyzed for effects on achieving substantial clinical benefit (SCB) at 12-month follow-up. ResultsThe analysis included 67 hips and 142 knees. SC and non-SC (NSC) veterans had similar baseline HOOS-JR/KOOS-JR and CCI. HOOS-JR remained similar between groups through 12 months (79.9 ± 19.2 vs. 82.7 ± 18.8) as did KOOS-JR (70.4 ± 15.6 vs. 74.6 ± 15.3). The designation of any SC and mental health SC reached significance for KOOS-JR (P = 0.034 and P = 0.032, respectively). For HOOS-JR and KOOS-JR, baseline function score quartile significantly influenced final score (P < 0.001), with patients in the lowest quartiles (i.e., worst baseline function) exhibiting significantly greater improvements than patients in higher quartiles. ConclusionsMental health SC and high preoperative functional status are variables that may have unfavorable influences on self-reported outcomes of TKA in veteran patients. SC status does not appear to influence the outcomes of THA or the likelihood of achieving SCB after either THA or TKA. Regardless of SC status, most veterans can expect significant clinical improvements after total joint arthroplasty.

Artificial intelligence analysis of ECG signals to predict arrhythmia recurrence after cryoballoon ablation of atrial fibrillation

Abstract Introduction Cryoballoon-based pulmonary vein isolation (CB) is an effective option for rhythm control in atrial fibrillation (AF). There have been multiple attempts to predict arrhythmia recurrence, but with moderate success. Purpose To use artificial intelligence (AI) deep electrocardiogram (ECG) analysis to predict arrythmia recurrence after CB. Methods In a single-center study of 250 consecutive pts (58.2±12.6 years, 30% female) treated with CB for AF (05.2017–04.2019), 60% had paroxysmal AF (PAF), 66.5% had hypertension, and 27.2% had a redo CB. Analyses included left atrial volume (LA vol: indexed for BSA and assed by angio-MSCT in 76% and the rest with echo), left ventricle ejection fraction (LVEF) and hypertrophy (LVH: septal/posterior wall thickness ≥11mm in ♂ and ≥10mm in ♀) along with 30s arrhythmia recurrence at 2-yr follow-up. Baseline 500Hz raw 12-lead digital ECG signals were analyzed by means of convolutional neural network (CNN) architecture that was taught to process the 12-channel ECG signal (XML). The transfer learning method of CNN parameters learned on a very large number of coded consecutive training ECG samples (n=1,000) was adopted to analyze current sample of ECG signals. Results Arrhythmia recurrence at 2-yrs was 46.0% (n=115). There was gradual increase in predictive performance being the lowest if only baseline clinical data were analyzed and the highest combing all baseline clinical data plus anatomical and functional parameters (Table 1: #1–#3). AI baseline ECG analysis alone offered predictive performance similar to that made upon analysis of all baseline clinical data or joint analysis of LA vol, LVH, and LVEF (Table 1: #4). AI results added substantially to predictive performance of models using baseline clinical data alone (#1 vs #5, p&amp;lt;0.001) and joint analysis of baseline clinical plus LA vol, LVH and LVEF (#3 vs #6, p=0.0130) (Fig. 1). Conclusions Prediction of recurrence after CB using raw ECG data with deep AI analysis is feasible. Joint analysis of results of AI of baseline ECG and basic clinical data offers predictive performance similar to that made upon analysis of clinical data including advanced information on LA volume and LVH and function. AI analysis of baseline ECG adds significantly to models aimed at recurrent AF prediction. Funding Acknowledgement Type of funding sources: Public hospital(s). Main funding source(s): National Institute of Cardiology, Warsaw, Poland

Heavy Chain Constant Region Usage in Antibodies to Peptidylarginine Deiminase 4 as a Marker of Disease Subsets in Rheumatoid Arthritis.

The study of autoantibody isotypes in autoimmune diseases is useful for identifying clinically relevant endotypes. This study was undertaken to study the prevalence and clinical significance of different isotypes and IgG subclasses of anti-peptidylarginine deiminase 4 (anti-PAD4) autoantibodies in individuals with rheumatoid arthritis (RA). In 196 RA subjects and 64 healthy controls, anti-PAD4 antibody types were determined using enzyme-linked immunosorbent assay. We investigated associations between anti-PAD4 antibodies and clinical outcomes, and relevant features were confirmed in an independent RA cohort. Anti-PAD4 IgG1, anti-PAD4 IgG2, anti-PAD4 IgG3, anti-PAD4 IgG4, anti-PAD4 IgA, and anti-PAD4 IgE antibodies were more frequent in RA patients than healthy controls (P < 0.001). Anti-PAD4 IgG1, anti-PAD4 IgG3, and anti-PAD4 IgE were associated with distinct clinical features. Anti-PAD4 IgG1 was predictive of progressive radiographic joint damage (odds ratio [OR] 4.88, P=0.005), especially in RA patients without baseline joint damage (40% versus 0%, P=0.003) or in those negative for anti-cyclic citrullinated peptide and/or rheumatoid factor (OR 32; P=0.009). IgG1 was also associated with higher levels of C-reactive protein (P=0.006) and interleukin-6 (P=0.021). RA patients with anti-PAD4 IgG3 had higher baseline joint damage scores (median Sharp/van der Heijde score 13 versus 7, P=0.046), while those with anti-PAD4 IgE had higher Disease Activity Score in 28 joints (median 4.0 versus 3.5, P=0.025), more frequent rheumatoid nodules (31% versus 16%, P=0.025), and more frequent interstitial lung disease (ground-glass opacification) (24% versus 9%, P=0.014). Anti-PAD4 IgG1 antibody associations with joint damage were corroborated in an independent RA cohort. Anti-PAD4 IgG1, anti-PAD4 IgG3, and anti-PAD4 IgE antibodies identify discrete disease subsets in RA, suggesting that heavy chain usage drives distinct effector mechanisms of anti-PAD4 antibodies in RA.