The information required by people with inflammatory arthritis when taking Methotrexate: a mixed-methods systematic review.

OBJECTIVES: This mixed-methods systematic review aimed to identify and synthesize knowledge of the characteristics, content, and preferred format of information to support people with inflammatory arthritis (IA) to take MTX. METHODS: A literature search using MEDLINE, The Cochrane Library, EMBASE, CINAHL, PsychInfo, GreyEU, Web of Science and Open Dissertation was conducted to identify all studies published from 2000 to December 2022. Included studies detailed factors related to MTX information needs of people aged ≥18 years with IA published in English. The Joanna Briggs Institute Guidelines (JBI) for convergent integrated mixed-methods systematic reviews were followed using validated tools for data extraction and quality. The data was analysed using reflexive thematic analysis. RESULTS: Thirteen studies (seven quantitative, two mixed-methods and four qualitative) were included, involving 3425 adults, mainly female n = 2434 (71%), age 20-84 years. An overarching theme of a requirement for person-centred care was developed, with three interlinking themes: (1) accepting the need for treatment with MTX, (2) concerns about taking MTX, and (3) a need for tailored information and support. Limitations of the evidence included the use of heterogeneous outcome measures and instruments for measuring information needs. CONCLUSION: People with IA have individual, multifaceted information and support needs about MTX that are often unresolved when a one-size-fits-all approach is used. The findings of this review can inform rheumatology training to support a person-centred approach to identifying and addressing the specific needs and concerns and development of consistent easy-to-understand accessible MTX information.

Pneumococcal vaccine uptake in patients with inflammatory arthritis: a single centre cohort study.

INTRODUCTION: Current guidelines recommend pneumococcal vaccination in individuals who are over the age of 65 or are immunosuppressed due to a disease or treatment. The objective of this study was to assess vaccine uptake rates in people with inflammatory arthritis for the pneumococcal, influenza and Covid-19 vaccines and factors determining uptake. METHODS: We conducted a retrospective single centre cohort study in the UK of individuals with rheumatoid arthritis, psoriatic arthritis and axial spondylarthritis between October and December 2023. Data were collected for age, gender, co-morbidities, immunosuppressive therapies, and dates of vaccines. Logistic regression was used to evaluate predictors of vaccine uptake, with adjustments for demographic and clinical factors. RESULTS: 906 individuals were identified. 46% were receiving treatment with csDMARD, 26% on biologic monotherapy, and 23% were on both biologic and csDMARDs. 316 individuals (35%) received a pneumococcal vaccine, lower than uptake for influenza (63%) and Covid-19 (87%) vaccines. Predictors of pneumococcal vaccine uptake included age, with older patients more likely to be vaccinated (odds ratio [OR] for age ≥ 65 years: 1.67, 95% CI 1.21-2.29). Those on biological therapy demonstrated higher likelihood of vaccination (OR for biologic therapy: 1.81, 95% CI 1.33-2.47). Additional Joint committee for immunisation and vaccination (JCVI) Green Book indicators also positively influenced vaccine uptake (OR: 1.67, 95% CI 1.19-2.33). CONCLUSION: Pneumococcal vaccine uptake in inflammatory rheumatic diseases is low, especially in younger patients and those not on biological therapy. The study highlights the need for a focused approach, distinct from strategies for other vaccines, to address this public health challenge.

The course of cytokine and chemokine gene expression in clinically suspect arthralgia patients during progression to inflammatory arthritis.

OBJECTIVES: Autoantibody responses increase years before the onset of inflammatory arthritis (IA) and are stable during transitioning from clinically suspect arthralgia (CSA) to IA. Cytokine and chemokine levels also increase years before IA onset. However, the course in the at-risk stage of CSA during progression to disease or non-progression is unknown. To increase the understanding of processes mediating disease development, we studied the course of cytokine, chemokine and related receptors gene expression in CSA patients during progression to IA and in CSA patients who ultimately did not develop IA. METHODS: Whole-blood RNA expression of 37 inflammatory cytokines, chemokines and related receptors was determined by dual-colour reverse transcription multiplex ligation-dependent probe amplification in paired samples of CSA patients at CSA onset and either at IA development or after 24 months without IA development. ACPA-positive and ACPA-negative CSA patients developing IA were compared at CSA onset and during progression to IA. Generalised estimating equations tested changes over time. A false discovery rate approach was applied. RESULTS: None of the cytokine/chemokine genes significantly changed in expression between CSA onset and IA development. In CSA patients without IA development, G-CSF expression decreased (P = 0.001), whereas CCR6 and TNIP1 expression increased (P < 0.001 and P = 0.002, respectively) over a 2 year period. Expression levels in ACPA-positive and ACPA-negative CSA patients who developed IA were similar. CONCLUSION: Whole-blood gene expression of assessed cytokines, chemokines and related receptors did not change significantly from CSA to IA development. This suggests that changes in expression of these molecules may not be related to the final process of developing chronicity and may have occurred preceding CSA onset. Changes in gene expression in CSA patients without IA development may provide clues for processes related to resolution.

Revision to the musculoskeletal domain of the BILAG-2004 index to incorporate ultrasound findings.

OBJECTIVES: To improve the definitions of inflammatory arthritis within the musculoskeletal (MSK) domain of the BILAG-2004 index by incorporating imaging findings and clinical features predictive of response to treatment. METHODS: The BILAG MSK Subcommittee proposed revisions to the BILAG-2004 index definitions of inflammatory arthritis, based on review of evidence in two recent studies. Data from these studies were pooled and analysed to determine the impact of the proposed changes on the severity grading of inflammatory arthritis. RESULTS: The revised definition for severe inflammatory arthritis includes definition of 'basic activities of daily living'. For moderate inflammatory arthritis, it now includes synovitis, defined by either observed joint swelling or MSK US evidence of inflammation in joints and surrounding structures. For mild inflammatory arthritis, the definition now includes reference to symmetrical distribution of affected joints and guidance on how US may help re-classify patients as moderate or no inflammatory arthritis. Data from two recent SLE trials were analysed (219 patients). A total of 119 (54.3%) were graded as having mild inflammatory arthritis (BILAG-2004 Grade C). Of these, 53 (44.5%) had evidence of joint inflammation (synovitis or tenosynovitis) on US. Applying the new definition increased the number of patients classified as moderate inflammatory arthritis from 72 (32.9%) to 125 (57.1%), while patients with normal US (n = 66/119) could be recategorized as BILAG-2004 Grade D (inactive disease). CONCLUSIONS: Proposed changes to the definitions of inflammatory arthritis in the BILAG-2004 index will result in more accurate classification of patients who are more or less likely to respond to treatment.

Psychological distress over 12 months post-diagnosis in an early inflammatory arthritis cohort.

OBJECTIVES: People with inflammatory arthritis (IA) experience worsened mental wellbeing alongside disease progression. Using the National Early Inflammatory Arthritis Audit (NEIAA), we assessed trends in psychological distress during 12-months following IA diagnosis, mapping these against clinical outcomes to identify associations. METHODS: This is a prospective study of people recruited to NEIAA receiving an IA diagnosis and completing the baseline patient survey. Patient reported outcomes (PROs) at baseline, 3-months and 12-months were collected, including psychological distress (assessed using Patient Health Questionnaire Anxiety and Depression Screener (PHQ4ADS)). Mixed effects linear regression models estimated associations between predictor variables with psychological distress at baseline and over time. RESULTS: Of 6,873 eligible patients, 3,451 (50.2%) showed psychological distress at baseline. Of those completing follow-ups, 30.0% and 24.1% were distressed at 3-months and 12-months, respectively. Higher psychological distress at diagnosis was more commonly reported by younger, female, and non-white patients. Clinical factors, including higher counts of comorbidities, prior depression, and higher disease activity at diagnosis were associated with higher distress. Higher distress at baseline was associated with poorer outcomes over time in quality of life, disability, work performance, disease activity, as well as reduced likelihood of achieving good treatment response by EULAR criteria. CONCLUSION: Half of patients with IA show significant mental health comorbidity at presentation, which associated with worse disease outcomes and quality of life. Screening for anxiety and depression should be a universal standard, and access to effective mood therapies alongside arthritis treatments is essential. Strategies should be culturally valid and consider multi-morbidities.

Prospective Assessment of Glucocorticoid Toxicity in Rheumatology Practice: A Focus on the Glucocorticoid Toxicity Index.

OBJECTIVE: The glucocorticoid toxicity index (GTI) is developed to measure glucocorticoid (GC)-related morbidity over time. This study aimed to assess GC-toxicity in patients at a rheumatology outpatient clinic by using the GTI and to identify the factors that interfere with the GTI. METHODS: This prospective study included patients with inflammatory arthritis (IA), connective tissue disease, and vasculitis who were newly prescribed GC-treatment (GC-naive) or have been still on GC-treatment for ≤2 years (GC-experienced). Patient demographics and disease characteristics, aggregate improvement score (GTI-AIS), cumulative worsening score (GTI-CWS), and cumulative GC-doses were recorded at baseline, 3rd month, and 6th month. Generalized estimating equations (GEE) were used to evaluate the GTI scores and associated factors including cumulative GC-doses. RESULTS: The study included 156 (48.7% GC-naive) patients with a mean age of 49.1 ± 17.1 years. More than half of the patients in both groups had a diagnosis of vasculitis. A higher cumulative GC-dose was found to be associated with higher GTI-scores in both groups (p< 0.001). In the GC-naive group, patients with vasculitis showed higher GTI-scores than IA patients (p< 0.001); there was also a significant increase in the GTI-CWS at the 6th month compared with the 3rd month. In the GC-experienced group, GTI-AIS and GTI-CWS were significantly different at 3rd and 6th month (p< 0.05). CONCLUSION: It was shown that GTI scores were associated with cumulative GC-doses and vasculitis patients in the GC-naive patients had higher GTI scores than inflammatory arthritis. The GTI allows individualized assessment and management of adverse effects experienced by patients as a result of GC treatment.

Neuropsychiatric symptoms in Systemic Lupus Erythematosus: mixed methods analysis of patient-derived attributional evidence in the international INSPIRE project.

OBJECTIVE: Attribution of neuropsychiatric symptoms in systemic lupus erythematosus (SLE) relies heavily on clinician assessment. Limited clinic time, variable knowledge, and symptom under-reporting contributes to discordance between clinician assessments and patient symptoms. We obtained attributional data directly from patients and clinicians in order to estimate and compare potential levels of direct attribution to SLE of multiple neuropsychiatric symptoms using different patient-derived measures. METHODS: Quantitative and qualitative data analysed included: prevalence and frequency of neuropsychiatric symptoms, response to corticosteroids, and concurrence of neuropsychiatric symptoms with non-neuropsychiatric SLE disease activity. SLE patients were also compared with controls and inflammatory arthritis (IA) patients to explore attributability of neuropsychiatric symptoms to the direct disease effects on the brain/nervous system. RESULTS: We recruited 2,817 participants, including 400 clinicians. SLE patients (n = 609) reported significantly higher prevalences of neuropsychiatric symptoms than controls (n = 463) and IA patients (n = 489). SLE and IA patients' quantitative data demonstrated multiple neuropsychiatric symptoms relapsing/remitting with other disease symptoms such as joint pain. Over 45% of SLE patients reported resolution/improvement of fatigue, positive sensory symptoms, severe headache, and cognitive dysfunction with corticosteroids. Evidence of direct attributability in SLE was highest for hallucinations and severe headache. SLE patients had greater reported improvement from corticosteroids (p= 0.008), and greater relapsing-remitting with disease activity (p< 0.001) in the comparisons with IA patients for severe headache. Clinician and patients reported insufficient time to discuss patient-reported attributional evidence. Symptoms viewed as indirectly related/non-attributable were often less prioritised for discussion and treatment. CONCLUSION: We found evidence indicating varying levels of direct attributability of both common and previously unexplored neuropsychiatric symptoms in SLE patients, with hallucinations and severe headache assessed as the most directly attributable. There may also be-currently under-estimated-direct effects on the nervous system in IA and other systemic rheumatological diseases.

Exploring the causal relationship between inflammatory cytokines and inflammatory arthritis: A Mendelian randomization study.

OBJECTIVES: Previous studies have reported an association between inflammatory cytokines and inflammatory arthritis, including Ankylosing spondylitis (AS), rheumatoid arthritis (RA), and psoriatic arthritis (PsA). This study aims to explore the causal relationship between inflammatory cytokines and AS, RA, and PsA using Mendelian randomization (MR). METHODS: We conducted a bidirectional two-sample MR analysis using genetic summary data from a publicly available genome-wide association study (GWAS) that included 41 genetic variations of inflammatory cytokines, as well as genetic variant data for AS, RA, and PsA from the FinnGen consortium. The main analysis method used was Inverse variance weighted (IVW) to investigate the causal relationship between exposure and outcome. Additionally, other methods such as MR Egger, weighted median (WM), simple mode, and weighted mode were employed to strengthen the final results. Sensitivity analysis was also performed to ensure the reliability of the findings. RESULTS: The results showed that macrophage colony-stimulating factor (MCSF) was associated with an increased risk of AS (OR = 1.163, 95 % CI = 1.016-1.33, p = 0.028). Conversely, high levels of TRAIL and beta nerve growth factor (ß-NGF) were associated with a decreased risk of AS (OR = 0.892, 95 % CI = 0.81-0.982, p = 0.002; OR = 0.829, 95 % CI = 0.696-0.988, p = 0.036). Four inflammatory cytokines were found to be associated with an increased risk of PsA: vascular endothelial growth factor (VEGF) (OR = 1.161, 95 % CI = 1.057-1.275, p = 0.002); Interleukin 12p70 (IL12p70) (OR = 1.189, 95 % CI = 1.049-1.346, p = 0.007); IL10 (OR = 1.216, 95 % CI = 1.024-1.444, p = 0.026); IL13 (OR = 1.159, 95 % CI = 1.05-1.28, p = 0.004). Interleukin 1 receptor antagonist (IL-1rα) was associated with an increased risk of seropositive RA (OR = 1.181, 95 % CI = 1.044-1.336, p = 0.008). Similarly, genetic susceptibility to inflammatory arthritis was found to be causally associated with multiple inflammatory cytokines. Lastly, the sensitivity analysis supported the robustness of these findings. CONCLUSIONS: This study provides additional insights into the relationship between inflammatory cytokines and inflammatory arthritis, and may offer new clues for the etiology, diagnosis, and treatment of inflammatory arthritis.

Clinical profile, treatment and quality of life of patients with psoriatic arthritis in Malaysia: A population-based cross-sectional study.

Psoriatic arthritis (PsA) is a major comorbidity of psoriasis and may lead to irreversible joint damage and disability. This study aims to describe the clinical profile, treatment and quality of life (QoL) of patients with PsA in Malaysia. This is a multicentre retrospective cross-sectional study of psoriasis patients who were notified to the Malaysian Psoriasis Registry (MPR) from January 2007 to December 2018. Of 21 735 psoriasis patients, 2756 (12.7%) had PsA. The male to female ratio was 1:1. The mean age of psoriasis onset for PsA patients was 34.73 ± 14.44 years. They had a higher rate of family history of psoriasis (26% vs. 22.4%, p < 0.001), scalp (82.7% vs. 81.0%, p = 0.04) and nail involvement (73.3% vs. 53.3%, p < 0.001), obesity (62.6% vs. 54.4%, p < 0.001), dyslipidaemia (23.8% vs. 15.4%, p < 0.001), hypertension (31.1% vs. 22.7%, p < 0.001) and diabetes mellitus (20.9% vs. 15.2%, p < 0.001) compared to non-PsA patients. More than half (54.3%) had severe psoriasis [(body surface area >10% and/or Dermatology Life Quality Index (DLQI) >10)]. Most had oligo-/monoarthropathy (40.3%), followed by distal interphalangeal arthropathy (31.3%), symmetrical polyarthropathy (28.3%), spondylitis/sacroiliitis (8.2%) and arthritis mutilans (3.2%). Nearly 40% of PsA patients received systemic treatment, but only 1.6% received biologic agents. QoL was more significantly affected in PsA than in non-PsA patients (mean DLQI 10.12 ± 7.16 vs. 9.52 ± 6.67, p < 0.001). One in eight patients with psoriasis in Malaysia had PsA. They had a higher incidence of comorbidities, severe disease, impaired QoL and were more likely to receive systemic and biological treatment compared to non PsA patients.

Precision Medicine in Rheumatology: The Promise of Ultrasound-Guided Synovial Biopsy, Barriers to Its Implementation in the United States, and Proposed Solutions.

PURPOSE OF REVIEW: In the clinical evaluation of inflammatory arthritis and the research into its pathogenesis, there is a growing role for the direct analysis of synovial tissue. Over the years, various biopsy techniques have been used to obtain human synovial tissue samples, and there have been progressive improvements in the safety, tolerability, and utility of the procedure. RECENT FINDINGS: The latest advancement in synovial tissue biopsy techniques is the use of ultrasound imaging to guide the biopsy device, along with evolution in the characteristics of the device itself. While ultrasound guided synovial biopsy (UGSB) has taken a strong foothold in Europe, the procedure is still relatively new to the United States of America (USA). In this paper, we describe the expansion of UGSB in the USA, elucidate the challenges faced by rheumatologists developing UGSB programs in the USA, and describe several strategies for overcoming these challenges.

Recent advances in the treatment of gout with NLRP3 inflammasome inhibitors.

Gout is an autoinflammatory disorder characterized by the accumulation of monosodium urate crystals in joints and other tissues, representing the predominant type of inflammatory arthritis with a notable prevalence and propensity for severe outcomes. The NLRP3 inflammasome, a member of the pyrin domain-containing NOD-like receptor family, exerts a substantial impact on both innate and adaptive immune responses and serves as a pivotal factor in the pathogenesis of gout. In recent years, there has been significant academic and industrial interest in the development of NLRP3-targeted small molecule inhibitors as a promising therapeutic approach for gout. To assess the advancements in NLRP3 inflammasome inhibitors for gout treatment, this review offers a comprehensive analysis and evaluation of current clinical candidates and other inhibitors targeting NLRP3 inflammasome from a chemical structure standpoint, with the goal of identifying more efficacious options for clinical management of gout.

Dietary omega-3 fatty acids modulate the production of platelet-derived microvesicles in an in vivo inflammatory arthritis model.

PURPOSE: The aim of this study was to investigate the effects of different ω-3 polyunsaturated fatty acid (PUFA) enriched diets, including a novel renewable plant source of ω-3 fatty acids (Buglossoides arvensis), on the development and progression of rheumatoid arthritis (RA). METHODS: RA was induced in mice consuming experimental diets using the K/BxN model. The experimental diets consisted of either a western control diet (control), diets containing B. arvensis oil or fish oil. The effects of the diets on platelets, platelet microvesicles (PMVs), and inflammatory markers such as clinical index, ankle thickness and cytokine/chemokine release were measured. RESULTS: While ω-3 PUFA-enriched diets did not prevent the development of arthritis in the K/BxN model, a significant decrease in ankle swelling was observed compared to the control group. Platelets isolated from mice consuming either low content of B. arvensis oil or fish oil diets exhibited significantly decreased PMVs production compared to mice consuming the control diet. CONCLUSION: Our study provides insight into the contribution of ω-3 PUFA supplementation in modulating the pro-inflammatory phenotype of platelets in RA pathology. Furthermore, our study suggests that low concentrations of dietary B. arvensis oil may have similar anti-inflammatory potential seen with dietary fish oil supplementation.

Ongoing shielding behavior one year post COVID-19: results from a longitudinal study of patients with inflammatory arthritis.

Many patients with inflammatory arthritis (IA) were instructed to shield during the COVID-19 pandemic. Despite the ending of lockdowns and vaccination, large proportions of IA patients were continuing to shield when it is no longer needed. Given the detrimental effects of shielding on mental and physical health, understanding the rates and reasons for shielding is needed to help clinicians advise patients accordingly. This study was a 12-month prospective study following participants with IA during the COVID-19 pandemic. The proportions of IA patients shielding at each time point were calculated. Additionally, regressions and odds ratios for shielding were determined to assess medication type, mental health, and risk perception. While the extent of shielding fluctuated over the year of lockdowns, nearly all IA patients (93.5%) were still engaging in some shielding in 2021, with nearly half (43%) still shielding most or all of the time. Medications that were previously considered higher risk were not significantly associated with higher rates of shielding (OR = 1.60, p = 0.29), but greater symptoms of depression in June 2020 (OR = 1.07, p = 0.03) was both associated with increased the odds of shielding in June 2021. The high rates of IA patients continuing to shield in 2021 put more strain on patients and professionals as social isolation is linked with worsening mental and physical health, as well as greater difficulty with self-management. It is important for clinicians to be aware of this trend to ease the stress on patients.

Increased prevalence of inflammatory arthritis, systemic lupus erythematosus and systemic sclerosis, during 2020-2023 versus 2016-2019 in a Nation-Wide Cohort Study.

Although several studies have explored the geoepidemiology of autoimmune rheumatic diseases (ARD), trends of their frequency overtime are under-investigated. Herein, in a nation-wide study, we examine trends in the prevalence of various ARD over-time, taking also into account the Covid-19 pandemic. In this retrospective study in the entire Greek adult population (approximately 10.000.000 people), we searched the electronic prescription database of the e-Government Centre for Social Security Services using prespecified ICD-10 codes to capture all adult patients with Psoriatic Arthritis (PsA), Rheumatoid Arthritis (RA), Ankylosing Spondylitis (AS), Systemic Lupus Erythematosus (SLE), Systemic Sclerosis (SSc) and Polymyalgia Rheumatica or Giant Cell Arteritis (PMR/GCA). Two sequential 4-year periods, namely 2016-2019 and 2020-2023 were compared. Prevalence of RA, PsA, AxSpA, SLE and SSc increased significantly during 2020-2023 compared to 2016-2019. This applies to both genders and to all age groups for RA, PsA and AxSpA, to female patients in SLE and SSc and to patients 18-39 years in SLE and ≥ 60 years in SSc. Overall, there was 47% increase in prevalence for AxSpA (0.100% in 2016-19 vs 0.147% in 2020-23), 36.5% for PsA (0.148% vs 0.202%), 20.6% for RA (0.467% vs 0.563%), 19% for SLE (0.137% vs 0.163%) and 13% for SSc (0.023% vs 0.026%). A 16.3% decrease was evident in GCA/PMR, limited to those ≥ 40 years old. In a nation-wide study we confirm that ARD prevalence increases over-time, whereas a contribution of Covid-19 pandemic to our results during 2020-2023, cannot be excluded. Additional human, medical and financial resources will be needed to cover the increased needs of ARD patients.

The real experience of reporting electronic patient-reported outcomes in patients with inflammatory arthritis and factors influencing participation: a scoping review.

Inflammatory arthritis can result in pain, stiffness, fatigue, and reduce quality of life. Frequent monitoring of disease activity is necessary for patients with inflammatory arthritis, and electronic patient-reported outcomes (ePROs) play a crucial role in this process. This study aimed to investigate the real experience of reporting ePROs in patients with inflammatory arthritis, as well as to identify factors influencing participation. The ultimate goal was to inform targeted strategies and develop interventions to enhance the utilization of ePROs in clinical settings. A scoping review was performed using PubMed, Web of science, Embase, and the Cochrane library from 2000 to the present and the literature search focused on the experience of reporting ePROs in inflammatory arthritis and the factors that influence participation. Screening articles based on inclusion and exclusion criteria. A total of 1478 studies were identified, out of which 26 were included in the review. The top experience of applications/platforms in patients was that they were easy to use and that the applications were clear, logical and intuitive. A summary of 18 potential influencing factors were identified and there was inconsistent evidence for five of these factors. The participation of reporting ePROs is influenced by various factors, and the experience is a crucial aspect in patients with inflammatory arthritis. Analyzing patients' experience and influencing factors provides a theoretical basis for future interventions to facilitate the clinical application of ePRO. However, further research is needed to fully understand the association between influencing factors and intervention outcomes.

14-3-3ζ: A suppressor of inflammatory arthritis.

Inflammatory arthritis (IA) is a common disease that affects millions of individuals worldwide. Proinflammatory events during IA pathogenesis are well studied; however, loss of protective immunity remains underexplored. Earlier, we reported that 14-3-3zeta (ζ) has a role in T-cell polarization and interleukin (IL)-17A signal transduction. Here, we demonstrate that 14-3-3ζ knockout (KO) rats develop early-onset severe arthritis in two independent models of IA, pristane-induced arthritis and collagen-induced arthritis. Arthritic 14-3-3ζ KO animals showed an increase in bone loss and immune cell infiltration in synovial joints. Induction of arthritis coincided with the loss of anti-14-3-3ζ antibodies; however, rescue experiments to supplement the 14-3-3ζ antibody by passive immunization did not suppress arthritis. Instead, 14-3-3ζ immunization during the presymptomatic phase resulted in significant suppression of arthritis in both wild-type and 14-3-3ζ KO animals. Mechanistically, 14-3-3ζ KO rats exhibited elevated inflammatory gene signatures at the messenger RNA and protein levels, particularly for IL-1ß. Furthermore, the immunization with recombinant 14-3-3ζ protein suppressed IL-1ß levels, significantly increased anti-14-3-3ζ antibody levels and collagen production, and preserved bone quality. The 14-3-3ζ protein increased collagen expression in primary rat mesenchymal cells. Together, our findings indicate that 14-3-3ζ causes immune suppression and extracellular remodeling, which lead to a previously unrecognized IA-suppressive function.

Whole-body MRI for the investigation of joint involvement in inflammatory arthritis.

OBJECTIVES: This study aimed to develop a novel whole-body MRI protocol capable of assessing inflammatory arthritis at an early stage in multiple joints in one examination. MATERIALS AND METHODS: Forty-six patients with inflammatory joint symptoms and 9 healthy volunteers underwent whole-body MR imaging on a 3.0 T MRI scanner in this prospective study. Image quality and pathology in each joint, bursae, entheses and tendons were scored by two of three radiologists and compared to clinical joint scores. Participants were divided into three groups based on diagnosis at 1-year follow-up (healthy volunteers, rheumatoid arthritis and all other types of arthritis). Radiology scores were compared between the three groups using a Kruskal-Wallis test. The clinical utility of radiology scoring was compared to clinical scoring using ROC analysis. RESULTS: A protocol capable of whole-body MR imaging of the joints with an image acquisition time under 20 min was developed with excellent image quality. Synovitis scores were significantly higher in patients who were diagnosed with rheumatoid arthritis at 12 months (p < 0.05). Radiology scoring of bursitis showed statistically significant differences between each of the three groups-healthy control, rheumatoid arthritis and non-rheumatoid arthritis (p < 0.05). There was no statistically significant difference in ROC analysis between MRI and clinical scores. CONCLUSION: This study has developed a whole-body MRI joint imaging protocol that is clinically feasible and shows good differentiation of joint pathology between healthy controls, patients with rheumatoid arthritis and patients with other forms of arthritis.

Shoulder arthroplasty for inflammatory arthritis is associated with higher rates of medical and surgical complications: a nationwide matched cohort analysis from 2016-2020.

BACKGROUND: Inflammatory arthritis (IA) represents a less common indication for anatomic and reverse total shoulder arthroplasty (TSA) than osteoarthritis (OA). The safety and efficacy of anatomic and reverse TSA in this population has not been as well studied compared to OA. We analyzed the differences in outcomes between IA and OA patients undergoing TSA. METHODS: Patients who underwent primary anatomic total shoulder arthroplasty (aTSA) and reverse total shoulder arthroplasty (rTSA) from 2016-2020 were identified in the Premier Healthcare Database. Inflammatory arthritis (IA) patients were identified using International Classification of Diseases, Tenth Revision, diagnosis codes and compared to osteoarthritis controls. Patients were matched in a 1:8 fashion by age (±3 years), sex, race, and presence of pertinent comorbidities. Patient demographics, hospital factors, and patient comorbidities were compared. Multivariate regression was performed following matching to account for any residual confounding and 90-day complications were compared between the 2 cohorts. Descriptive statistics and regression analysis were employed with significance set at P < .05. RESULTS: Prior to matching, 5685 IA cases and 93,539 OA controls were identified. Patients with IA were more likely to be female, have prolonged length of stay and increased total costs (P < .0001). After matching and multivariate analysis, 4082 IA cases and 32,656 controls remained. IA patients were at increased risk of deep wound infection (OR 3.14, 95% CI 1.38-7.16, P = .006), implant loosening (OR 4.11, 95% CI 1.17-14.40, P = .027), and mechanical complications (OR 6.34, 95% CI 1.05-38.20, P = .044), as well as a decreased risk of postoperative stiffness (OR 0.36, 95% CI 0.16-0.83, P = .002). Medically, IA patients were at increased risk of PE (OR 2.97, 95% CI 1.52-5.77, P = .001) and acute blood loss anemia (OR 1.27, 95% CI 1.12-1.44, P < .0001). DISCUSSION AND CONCLUSION: Inflammatory arthritis represents a distinctly morbid risk profile compared to osteoarthritis patients with multiple increased surgical and postoperative medical complications in patients undergoing aTSA and rTSA. Surgeons should consider these potential complications and employ a multidisciplinary approach in preoperative risk stratification of IA undergoing shoulder replacement.

Rheumatoid Arthritis Is Not a Contraindication to Unicompartmental Knee Arthroplasty.

BACKGROUND: Rheumatoid arthritis (RA) has historically been considered a contraindication for unicompartmental knee arthroplasty (UKA). However, the widespread use of disease-modifying antirheumatic drugs has substantially improved the management of RA and prevented disease progression. The objective of this study was to ascertain whether RA impacts UKA revision-free survivorship. METHODS: Patients undergoing UKA from 2010 to 2021 were identified in an administrative claims database (n = 105,937) using Current Procedural Terminology code 27446. All patients who underwent UKA who had a diagnosis of RA with a minimum of 2-year follow-up (n = 1,422) were propensity score matched based on age, sex, and Elixhauser Comorbidity Index to those who did not have RA (n = 1,422). Laterality was identified using the 10th Revision of International Classification of Diseases codes. The primary outcome was ipsilateral revision to total knee arthroplasty (TKA) within 2 years, and the secondary outcome was ipsilateral revision at any time. RESULTS: Among the 1,422 patients who had a UKA and a diagnosis of RA, 37 patients (2.6%) underwent conversion to TKA within 2 years, and 48 patients (3.4%) underwent conversion to TKA at any point. In comparison, 28 patients (2.0%) in the propensity-matched control group underwent conversion to TKA within 2 years, and 40 patients (2.8%) underwent conversion to TKA at any point. Statistical analysis revealed no significant difference in conversion to TKA between patients who had and did not have RA, either within 2 years (P = .31) or anytime (P = .45). CONCLUSIONS: Patients who had RA and underwent UKA did not have an increased risk of revision to TKA compared to those who did not have RA. This may indicate that modern management of RA could allow for expanded UKA indications for RA patients.

Anatomic versus reverse total shoulder arthroplasty outcomes after prior contralateral anatomic total shoulder arthroplasty in patients with bilateral primary osteoarthritis with an intact rotator cuff.

PURPOSE: We aimed to compare outcomes in patients that underwent bilateral anatomic total shoulder arthroplasty (aTSA) vs. aTSA/ reverse total shoulder arthroplasty (rTSA) for rotator cuff-intact glenohumeral osteoarthritis (RCI-GHOA) to further elucidate the role of rTSA in this patient population. METHODS: A single-institution prospectively collected shoulder arthroplasty database was reviewed for patients undergoing bilateral total shoulder arthroplasty (TSA) for RCI-GHOA with a primary aTSA and subsequent contralateral aTSA or rTSA. Outcome scores (SPADI, SST, ASES, UCLA, Constant) and active range of motion (abduction, forward elevation [FE], external and internal rotation [ER and IR]) were evaluated. Clinically relevant benchmarks (minimal clinically important difference [MCID], substantial clinical benefit [SCB], and patient acceptable symptomatic state [PASS]) were evaluated against values in prior literature. Incidence of surgical complications and revision rates were examined in qualifying patients as well as those without .05). The 2nd TSAs between groups were similar preoperatively, but aTSA/rTSA had superior outcome scores, overhead motion, and active abduction compared to patients that underwent aTSA/aTSA. There were no differences in active ER and IR scores or complication rates between groups. CONCLUSION: Patients with RCI-GHOA have excellent clinical outcomes after either aTSA/aTSA or aTSA/rTSA.