OBJECTIVES: Alkaptonuria is a rare genetic disorder caused by the build-up of homogentisic acid, leading to its deposition in connective tissue. Previous studies have documented histopathological evidence of extracellula...OBJECTIVES: Alkaptonuria is a rare genetic disorder caused by the build-up of homogentisic acid, leading to its deposition in connective tissue. Previous studies have documented histopathological evidence of extracellular matrix and vessel wall deposits and neoangiogenesis in patients with alkaptonuria, as well as the possible role of dermoscopy in characterising macroscopically visible skin deposits. This proof-of-concept study aimed to describe the capillaroscopic changes in patients with alkaptonuria. METHODS: In this cross-sectional single-centre study, alkaptonuria patients were evaluated phenotypically, genetically, and with capillaroscopy. Capillaroscopic findings were compared to three control groups: healthy controls, patients with primary Raynaud's phenomenon and patients with systemic sclerosis. RESULTS: Ten alkaptonuria patients were included (60 % female, mean age 54.4 ± 12.2 years). All patients had skin and/or sclerae pigmentation and the majority (90 %) had musculoskeletal manifestations. One patient had a normal capillaroscopy. Blue-blackish deposits suggestive of homogentisic acid accumulation were observed in six patients, the majority of which were not visible to the naked eye. None of the patients from the three control groups had this capillaroscopic finding. Nine patients with alkaptonuria presented atypical, non-specific capillaroscopic changes. Notably, we observed a significantly higher prevalence of abnormally shaped capillaries compared both to healthy controls (70.0 % vs 20.0 %, p = 0.034) and to patients with primary Raynaud's phenomenon (70.0 % vs 20.0 %, p = 0.034), and of dilated capillaries compared to patients with primary Raynaud's phenomenon (50.0 % vs 13.3 %, p = 0.045). CONCLUSIONS: This study is the first to document capillaroscopic changes in alkaptonuria patients, supporting the hypothesis of microcirculation damage in this disease and raising the question of a possible role of capillaroscopy as a diagnostic, prognostic, and disease monitoring tool in this condition.
OBJECTIVE: To compare the effects of different exercise modalities and doses on pain in patients with knee or hip osteoarthritis (OA). METHODS: A systematic search of six electronic databases was conducted, from database...OBJECTIVE: To compare the effects of different exercise modalities and doses on pain in patients with knee or hip osteoarthritis (OA). METHODS: A systematic search of six electronic databases was conducted, from database inception to December 2024, to identify randomized controlled trials (RCTs) on exercise interventions in patients with knee or hip OA. Bayesian pairwise, network, and dose-response meta-analyses were conducted using a random-effects model to analyze the impact of exercise on pain in knee or hip OA. Two reviewers independently assessed the quality of the literature. RESULTS: A total of 92 RCTs involving 6079 participants were analyzed. Aerobic training was found to have the highest likelihood of ranking first in effectiveness (Surface Under the Cumulative Ranking curve [SUCRA]: 84.7%; Standardized Mean Difference [SMD]: -1.00; 95% CrI: -1.50, -0.62), followed by strength combined with flexibility training (SUCRA: 73.0%; SMD: -0.93; 95% CrI: -1.40, -0.50), yoga (SUCRA: 63.7%; SMD: -0.86; 95% CrI: -1.50, -0.24), and strength training (SUCRA: 55.9%; SMD: -0.78; 95% CrI: -1.00, -0.55); flexibility training (SUCRA: 39.8%; SMD: -0.65; 95% CrI: -1.10, -0.22) ranked the lowest. However, there were no significant differences in effectiveness among the exercise types. When pooling data from all exercise modalities, a 'U-shaped' dose-response relationship was observed between the overall exercise dose and pain. CONCLUSIONS: Exercise effectively reduces pain in patients with knee or hip OA. Although no exercise type was found to be statistically superior to another, based on probabilistic ranking, aerobic training, strength combined with flexibility training, yoga, and strength training had the highest likelihood of being the most effective interventions. The analysis identified that the optimal dose for maximizing pain relief was 620 metabolic equivalent of task (METs)-min/week (SMD: -0.93; 95% CrI: -1.24 to -0.58) (equivalent to, for example, approximately 120 min of moderate-intensity water aerobics per week), while the minimum dose to achieve a clinically important difference was 180 METs-min/week. However, given the methodological limitations of the analysis and the overall low to moderate certainty of the evidence, these findings should be interpreted with caution.
OBJECTIVE: To investigate the impact of concomitant inflammatory bowel disease (IBD) on clinical response to biologic therapy in psoriatic arthritis (PsA). The primary aim was to identify predictors of achieving minimal...OBJECTIVE: To investigate the impact of concomitant inflammatory bowel disease (IBD) on clinical response to biologic therapy in psoriatic arthritis (PsA). The primary aim was to identify predictors of achieving minimal disease activity (MDA) and DAPSA remission or low disease activity (LDA) at 6 months. METHODS: We conducted a retrospective, matched cohort study of PsA patients initiating TNF inhibitors or anti-IL-12/23 agents between 2011 and 2023. Patients with (PsA-IBD) and without IBD (Only-PsA) were matched for age, sex, disease duration, and biologic class. Clinical assessments and patient-reported outcomes (PROs) were collected at baseline, 6, and 12 months. Multivariable logistic regression models were used to identify independent predictors of MDA and DAPSA remission/LDA at 6 months. Secondary outcomes included the proportion of patients achieving these targets over time and changes in disease activity scores and PROs. RESULTS: A total of 120 PsA patients (60 PsA-IBD and 60 Only-PsA) were analyzed. At 6 months, MDA and DAPSA remission/LDA were achieved by 32.1 % and 50.0 % of PsA-IBD patients vs. 58.3 % and 78.3 % of Only-PsA patients (p = 0.005 and p = 0.008). IBD independently predicted lower odds of MDA (aOR 0.28, 95 % CI 0.11-0.69; p = 0.006) and showed a borderline association with reduced DAPSA response (aOR 0.39, 95 % CI 0.15-1.02; p = 0.055). At 12 months, PsA-IBD patients reported persistently higher VAS pain, PtGA, and HAQ-DI scores despite objective clinical improvements. CONCLUSION: Concomitant IBD is associated with impaired treatment response and greater residual symptom burden in PsA, underscoring the need for tailored therapeutic strategies in this challenging phenotype.
OBJECTIVES: Given recent projections for shortages in rheumatology workforce, we sought to define trends in the number of applicants, training positions, and unfilled training positions for rheumatology training in the U...OBJECTIVES: Given recent projections for shortages in rheumatology workforce, we sought to define trends in the number of applicants, training positions, and unfilled training positions for rheumatology training in the United States (US). METHODS: This was a retrospective, cross-sectional study of all applicants for US rheumatology training over the past sixteen years (2009-2024). Data were obtained from the National Resident Matching Program and annual trends analyzed with linear regression. RESULTS: The annual number of rheumatology programs (99 to 127, 28.3 % increase, P < 0.001), training positions (181 to 276, 52.5 % increase, P < 0.001), and applicants (243 to 359, 47.7 % increase, P < 0.001) increased over the study period. However, the annual applicant-to-training position ratio did not change (1.3 to 1.3, P = 0.489). The annual rate of unfilled training positions decreased (7.2 % to 1.1 %, P < 0.001) and there were no significant changes in the annual match rate (69.1 % to 76.0 %, P = 0.781). The percentage of applicants that matched at their first-choice fellowship decreased (49.4 % to 33.4 %, P = 0.001) while the percentage of applicants that matched at their ≥ fourth-choice fellowship increased (5.8 % to 18.1 %, P < 0.001). There was no clear trend in the rate of unmatched applicants over the study period (29.6 % to 20.1 %, P = 0.316). CONCLUSIONS: US rheumatology training remains competitive as demonstrated by an annual surplus of applicants relative to available training positions. These results suggest an ability to increase the number of US rheumatologists by increasing the number of training positions. Surveillance of future match outcomes remains critical given projected inadequacies in the US rheumatology workforce.
OBJECTIVE: To determine the prevalence and specific patterns of antinuclear antibodies (ANAs) and to identify potential risk factors among Chinese pregnant women. METHODS: ANAs were detected by indirect immunofluorescenc...OBJECTIVE: To determine the prevalence and specific patterns of antinuclear antibodies (ANAs) and to identify potential risk factors among Chinese pregnant women. METHODS: ANAs were detected by indirect immunofluorescence (IIF) method using HEp-2 cell antigen. The magnetic bar code immunofluorescent luminescence method was used to detect specific ANAs. Socio-demographic information, lifestyle elements and other data were obtained in the Qingdao Women and Children's Hospital from a questionnaire-based interviews. RESULTS: We analyzed 2159 Chinese pregnant women in their first trimester of pregnancy. The ANAs prevalence was 14.7 %. The most common antibody titer was 1:100 (n=241, 11.2 %), followed by 1:320 (n=55, 2.5 %) and >1:320 (n=22, 1.0 %). The most common staining pattern was nuclear speckled type (n=95, 30.0 %), followed by nuclear dense fine speckled (n=82, 25.8 %), cytoplasmic (n=39, 12.3 %), homogeneous (n=30, 9.4 %) and nucleolar (n=19, 6.0 %).The common specific ANAs included SSA (n=37,11.6 %), Ro52 (n=33,10.3 %), AMA-M2(n=16, 5.0 %),and SSB (n=20, 6.3 %),etc. Passive smoking, age at 30-34 years, multiparity, pre-pregnancy thyroid diseases and hypertension significantly increased the probability of ANA positivity. CONCLUSIONS: ANAs were present in 14.7 % of Chinese women during their first trimester of pregnancy. Passive smoking, multiparity, pre-pregnancy thyroid diseases, and hypertension were significantly associated with ANA positivity.
OBJECTIVE: To illustrate the correlation between the reduction of subchondral bone marrow lesions (BMLs) and the early recovery of trabecular bone mineral density (TBMD) in symptomatic knee osteoarthritis (KOA) patients....OBJECTIVE: To illustrate the correlation between the reduction of subchondral bone marrow lesions (BMLs) and the early recovery of trabecular bone mineral density (TBMD) in symptomatic knee osteoarthritis (KOA) patients. METHODS: A RANKL inhibitor was applied to osteoporosis (OP) patients who also had symptomatic KOA and BMLs and whose knee symptoms were refractory to NSAID therapy. Clinical symptoms, HRQoL, BMLs, knee TBMD, systemic BMD, and bone turnover markers were evaluated within a 6-month follow-up. The correlation between early TBMD recovery and BML reduction was explored. RESULTS: Following a RANKL inhibitor application: (1) At the first-week follow-up, clinical symptoms were relieved and persisted until the final follow-up; HRQoL showed improvement. (2) BMLs and TBMD progressively improved at 4-week and 3-month follow-ups; the bone turnover markers significantly decreased. (3) Systemic BMD improved at the 6-month follow-up. (4) At the 3-month follow-up, the reduction in subchondral BML areas positively correlated with the increase in CT-HU values (r = 0.329; BML areas reduction: 173.09 ± 45.23 mm²; CT-HU values increase: 23.72 ± 3.77). CONCLUSION: In this clinical study, after the application of a RANKL inhibitor for OP treatment, BMLs and knee pain were effectively reduced in OP patients with symptomatic KOA and BMLs. In addition, the correlation between early recovery of TBMD and reduction in BML area was also demonstrated. This study supports the concept of osteoporotic osteoarthritis (OPOA) and highlights the potential of subchondral bone as a target for KOA treatment.
OBJECTIVE: To assess the predictive value of nailfold capillaroscopy (NFC) findings for major cardiovascular events (MCEs) and mortality in systemic sclerosis (SSc) patients, in comparison with other clinical variables....OBJECTIVE: To assess the predictive value of nailfold capillaroscopy (NFC) findings for major cardiovascular events (MCEs) and mortality in systemic sclerosis (SSc) patients, in comparison with other clinical variables. METHODS: This retrospective, observational study included 360 SSc patients diagnosed according to the 2013 ACR/EULAR criteria. All patients underwent NFC within one month of diagnosis. RESULTS: At baseline, 88% of patients presented a scleroderma NFC pattern (33.05% early, 32.5% active, and 22.5% late). Giant capillaries were found in 75.28%, microhaemorrhages in 54.17%, and avascular areas in 38.6% of patients. During a median follow-up of 11.7 years, 64 patients (17.8%) experienced a MCE. The overall mortality rate was 21.1% (76 patients), with 30.9% of deaths attributed to SSc-related complications, 29.4% to MCEs, and 39.7% to other causes. In multivariable analyses, independent predictors of MCEs were diabetes mellitus (HR 2.37, p = 0.031), interstitial lung disease (HR 3.16, p < 0.001), avascular areas on baseline NFC (HR 2.24, p = 0.034), and previous MCE (HR 3.89, p < 0.001). Whereas, microhaemorrhages showed protective trend (HR 0.55, p = 0.053). Independent predictors of all-cause mortality were age (HR 1.03, p = 0.039), disease duration (HR 0.81, p < 0.001), and avascular areas (HR 2.09, p = 0.032), while microhaemorrhages were protective (HR 0.35, p = 0.002) For SSc-related mortality rates, avascular areas associated with a poorer survival rate (log-rank p-value <0.001) and microhaemorrhages with a better survival (log rank p-value = 0.01). CONCLUSION: Avascular areas in baseline NFC are strong predictors of MCEs and mortality in SSc, whereas microhaemorrhages have a lower risk. Integrating NFC into clinical practice as a prognostic tool may improve risk stratification.
Enns JP, Wang J, Jiang B
… +16 more, Srivatsan S, Kowalski EN, Wang X, Williams ZK, Qian G, Hanberg J, Johnson C, Negron M, Bade KJ, Saavedra A, Mueller KT, Vanni KMM, Kotton CN, Sparks JA, Wallace ZS, Patel NJ
Semin Arthritis Rheum
· 2025 Dec · PMID 41072235
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BACKGROUND: Respiratory syncytial virus (RSV) is a common respiratory viral illness which can cause severe outcomes in older and immunosuppressed populations. There is little data regarding RSV outcomes among people with...BACKGROUND: Respiratory syncytial virus (RSV) is a common respiratory viral illness which can cause severe outcomes in older and immunosuppressed populations. There is little data regarding RSV outcomes among people with systemic autoimmune rheumatic diseases (SARDs). METHODS: This retrospective cohort study examined risk factors for hospitalization in individuals with SARDs and documented RSV infection between 2015 and 2023 at Mass General Brigham (Boston, MA). Clinical data were collected from electronic health records. Multivariable adjusted logistic regression was used to identify factors associated with hospitalization for RSV infection. RESULTS: Of 188 individuals with SARDs and RSV (mean age 68.5 years, 75.5% female), 96 (51.0%) were hospitalized. Higher Charlson Comorbidity Index (aOR 1.16 per point, 95% CI: 1.04-1.31), Claims-Based Frailty Index (aOR 4.80 vs. robust/pre-frail, 95% CI: 2.32-9.94), and concurrent infection (aOR 2.52 vs. RSV alone, 95% CI: 1.07-5.92) were associated with increased odds of hospitalization. CD20 inhibitor treatment (aOR 3.84 vs. csDMARD, 95% CI: 0.99-15.20) and older age (OR 1.03 per year, 95% CI: 1.01-1.05) were associated with numerically increased odds of RSV hospitalization. Among hospitalized individuals, 56% required oxygen. There were 12 deaths within 90 days (12.5% of those hospitalized; 6% of all with RSV). CONCLUSIONS: This study highlights the increased risk of severe outcomes of RSV infection in individuals with SARDs. Factors associated with RSV hospitalization included frailty, higher comorbidity burden, and concurrent infection at the time of RSV. These findings should inform clinical decisions regarding RSV vaccination and prevention strategies.
OBJECTIVES: The Decisional Conflict Scale is a candidate instrument for the Core Outcome Measurement Set of the OMERACT Shared Decision-Making working group. However, its validity among chronic non-cancer pain population...OBJECTIVES: The Decisional Conflict Scale is a candidate instrument for the Core Outcome Measurement Set of the OMERACT Shared Decision-Making working group. However, its validity among chronic non-cancer pain populations is lacking. We explored measurement properties of the English version of the 16-item Decisional Conflict Scale in this population. METHODS: Informed by the COnsensus-based Standards for the selection of health status Measurement INstruments guidelines, we conducted a secondary analysis of a panCanadian cross-sectional survey. We assessed the distribution of score including ceiling and floor effects, readability, internal consistency, structural validity of an hypothesized five-factor model, and convergent and discriminant validities. We tested measurement invariances regarding age, sex, health literacy, and education. RESULTS: We collected data from 1103 respondents. We found ceiling effect at the item-level, while no ceiling and floor effects at the subscale and total score levels. Readability scores were below the sixth-grade reading level. All results of internal consistency were above the a priori threshold. The confirmatory factorial analysis resulted in a good model fit. We found good convergent, but poor discriminant validities. We confirmed measurement invariances for age, sex, health literacy, and education. CONCLUSION: This secondary analysis of a panCanadian survey provides evidence of the measurement properties of the Decisional Conflict Scale in people living with chronic non-cancer pain. We propose that this instrument should be analyzed using its total score rather than its subscales due to a lack of discriminant validity. Further research is necessary to enhance its validity, possibly by re-examining its factor structure.
Allen HM, Holena MM, Allen LE
… +16 more, Zhao S, Castillo RC, Cohen SP, Hurley RW, Scharfstein DO, Haythornthwaite JA, Raja SN, Wegener ST, Rini CM, Keefe FJ, Bridges J, Reeder R, Thompson RE, Hanley D, Campbell CM, SKOAP Consortium
Semin Arthritis Rheum
· 2025 Dec · PMID 41061328
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BACKGROUND: Treatment guidelines for knee osteoarthritis (KOA) vary across organizations, partly due to the lack of high-quality evidence. Experts disagree on the role of psychological management, pharmacologic treatment...BACKGROUND: Treatment guidelines for knee osteoarthritis (KOA) vary across organizations, partly due to the lack of high-quality evidence. Experts disagree on the role of psychological management, pharmacologic treatments including opioids, and interventional therapies. METHODS/DESIGN: The Sequenced strategy for Knee OsteoArthritis Pain (SKOAP) trial is a multi-site, randomized, pragmatic clinical trial that uses a two-phase sequential design to evaluate the effectiveness of several interventions in individuals reporting KOA pain. Described here is the protocol for Phase 1 of the trial sequence which focuses on conservative treatments. All participants receive Best Practices (BP), a guideline-based approach to care that includes physical therapies, alternative treatments, and over-the-counter medications. Participants are then randomized to one of three groups: (1) BP alone, (2) BP plus duloxetine (30-120 mg/day), or (3) BP plus duloxetine and painTRAINER, a web-based, Cognitive Behavioral Therapy (CBT)-informed pain coping skills training. Phase 1 aims to determine whether the combination of duloxetine and BP improves pain compared to BP alone, and whether the combination of painTRAINER, duloxetine and BP provides additional benefit compared to duloxetine combined with BP. The analysis will include a modified Intention to Treat (mITT) approach and two Per-Protocol (PP) analyses; Receipt of Prescription (PP-ROP) and Minimum Effective Dose (PP-MinED). A third aim of Phase 1 is to identify clinical characteristics, patient-level factors, and psychosocial phenotypes that predict short- and long-term outcomes. DISCUSSION: Findings from Phase 1 of the SKOAP trial will provide evidence on the effectiveness of non-opioid pharmacologic and psychological interventions for the treatment of painful KOA beyond established best practices. It may also help refine personalized treatment strategies.