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Objective: The aim of this study was to characterize the phenotype and genotype of patients with Yao syndrome (YAOS), with focus on comparing to prior cohorts, identifying novel features, and describing treatment observations. Methods: A retrospective medical records review of patients with YAOS seen at Mayo Clinic was conducted to characterize clinical features, NOD2 genotypes, and therapeutic trials and responses. Results: Twenty-two patients diagnosed with YAOS were included. Eighteen patients (81.8%) were female and twenty (90.9%) were White. Mean age at symptom onset was 24.0 ± 14.8 years. Common clinical manifestations included fever (81.8% of patients), rash (95.5%), chronic gastrointestinal symptoms (100%), arthralgia/arthritis (95.5%), and sicca symptoms (68.2%). NOD2 genotypes as single variants included IVS8 + 158 in 14 patients (63.6%), R702W in 8 patients (36.4%), 1007fs in 4 (18.2%), and one patient had only a previously unreported rare variant. Eight patients (36.4%) had compound (two or more) NOD2 variants. Potential comorbidities of YAOS observed in this cohort included gastrointestinal dysmotility, autonomic dysfunction, and mast cell activation-like symptoms. Glucocorticoid responsiveness was observed in 15 of 20 patients exposed (75%). Eleven patients (50.0%) received IL-1 inhibitor therapy, and one patient (4.5%) received IL-6 inhibitor therapy with adequate disease control. Conclusion: Our findings substantiate the occurrence of fevers, arthralgia/ arthritis, rash, chronic gastrointestinal symptoms, and sicca-like symptoms described previously in patients with YAOS. Novel clinical features and one NOD2 variant not previously described were identified. Glucocorticoids, biologic IL-1 inhibitors, and IL-6 receptor inhibitors appeared to be effective for treatment of patients with YAOS. [ABSTRACT FROM AUTHOR]

Hydroxychloroquine, initially used as an antimalarial, is used as an immunomodulatory and anti-inflammatory agent for the management of autoimmune and rheumatic diseases such as systemic lupus erythematosus. Lately, there has been interest in its potential efficacy against severe acute respiratory syndrome coronavirus 2, with several speculated mechanisms. The purpose of this review is to elaborate on the mechanisms surrounding hydroxychloroquine. The review is an in-depth analysis of the antimalarial, immunomodulatory, and antiviral mechanisms of hydroxychloroquine, with detailed and novel pictorial explanations. The mechanisms of hydroxychloroquine are related to potential cardiotoxic manifestations and demonstrate potential adverse effects when used for coronavirus disease 2019 (COVID-19). Finally, current literature associated with hydroxychloroquine and COVID-19 has been analyzed to interrelate the mechanisms, adverse effects, and use of hydroxychloroquine in the current pandemic. Currently, there is insufficient evidence about the efficacy and safety of hydroxychloroquine in COVID-19. HCQ, initially an antimalarial agent, is used as an immunomodulatory agent for managing several autoimmune diseases, for which its efficacy is linked to inhibiting lysosomal antigen processing, MHC-II antigen presentation, and TLR functions. HCQ is generally well-tolerated although severe life-threatening adverse effects including cardiomyopathy and conduction defects have been reported. HCQ use in COVID-19 should be discouraged outside clinical trials under strict medical supervision. [ABSTRACT FROM AUTHOR]

• Morbidities are associated with serious infection risk in rheumatoid arthritis. • Bipolar disorder, dementia, and vitamin D deficiency pose the greatest risk. • Highest risk morbidities are associated with a 3–6-fold risk of serious infection. • Serious infection risk increases by 16 % per morbidity. • The risk of many morbidities is not fully accounted for in 2 common risk models. To assess the association between a comprehensive list of morbidities and serious infection (SI) in patients with rheumatoid arthritis (RA). This study evaluated SI risk associated with 55 comorbidities using a population-based inception cohort including all adult patients with incident RA from 1999 through 2014 with follow up through 2021. Morbidities and SI were ascertained using previously validated international classification of disease (ICD)-9 and ICD-10 codes. Conditional frailty models were utilized to analyze the association between each morbidity and SI: Model 1 adjusted for age, sex, and calendar year; Model 2 adjusted for factors in Model 1 and the Rheumatoid Arthritis Observation of Biologic Therapy (RABBIT) Risk Score of Infections; and Model 3 adjusted for factors in Model 1 and the Mayo SI Risk Score. 911 patients (70 % female, mean age 56 years, 66 % seropositive) were included. There were 293 SI among 155 patients (17 %), corresponding to an incidence of 3.9 SI per 100 person-years. Eighteen SI were fatal. Risk of SI was significantly increased in 27 of 55 morbidities in Model 1, 11 morbidities in Model 2, and 23 morbidities in Model 3. Additionally, several morbidities included in the RABBIT and Mayo risk scores continued to have large effect sizes despite adjustment. Serious infection risk increased by 11–16 % per morbidity in the three models. Several morbidities are associated with an increased risk for SI. Future risk scores may include morbidities identified in this study for improved SI risk assessment. [ABSTRACT FROM AUTHOR]

• Our study showed that approximately 49 % of ankylosing spondylitis (AS) patients had multimorbidity and identified five distinct multimorbidity phenotypes, highlighting the importance of the type of morbidity in addition to the number of morbidities for longitudinal outcomes in AS. • The depression cluster was associated with worse disease activity and function, thus emphasizing the importance of outlining optimal screening and management strategies for depression in AS. • Identifying AS multimorbidity clusters or phenotypes in clinical practice could help delineate individuals at the greatest risk of worse outcomes earlier and enable more comprehensive and effective care. To examine the association of multimorbidity phenotypes at baseline with disease activity and functional status over time in ankylosing spondylitis (AS). Patient-reported AS morbidities (comorbidities, N = 28 and extra-musculoskeletal manifestations, EMMs, N = 3) within 3 years of enrollment with a prevalence ≥1 %, were included from the Prospective Study of Outcomes in Ankylosing Spondylitis (PSOAS) cohort. We defined multimorbidity as ≥2 morbidities (MM2+) and substantial multimorbidity as ≥5 morbidities (MM5+). Multimorbidity clusters or phenotypes were identified using K-median clustering. Disease activity (ASDAS-CRP) and functional status (BASFI) measures were collected every 6 months. Generalized estimating equation method was used to examine the associations of multimorbidity counts and multimorbidity clusters with measures of disease activity and functional status over time. Among 1,270 AS patients (9,885 visits) with a median follow-up of 2.9 years (IQ range: 1.0–6.8 years), the prevalence of MM2+ and MM5+ was 49 % and 9 % respectively. We identified five multimorbidity clusters: depression (n = 321, 25 %), hypertension (n = 284, 22 %), uveitis (n = 274, 22 %), no morbidities (n = 238, 19 %), and miscellaneous (n = 153, 12 %). Patients in the depression cluster were more likely to be female and had significantly more morbidities and worse disease activity and functional status compared to those with no morbidities. Approximately 49 % of AS patients in the PSOAS cohort had multimorbidity and five distinct multimorbidity phenotypes were identified. In addition to the number of morbidities, the type of morbidity appears to be important to longitudinal outcomes in AS. The depression cluster was associated with worse disease activity and function. [ABSTRACT FROM AUTHOR]

To examine time trends in glucocorticoid (GC) use among patients diagnosed with rheumatoid arthritis (RA) during the biologic era. A population-based inception cohort of RA patients diagnosed during 1999 – 2018 was followed longitudinally through their medical records until death, migration or 12/31/2020. All patients fulfilled 1987 American College of Rheumatology classification criteria for RA. GC start and stop dates were collected along with dosages in prednisone equivalents. The cumulative incidence of GC initiation and discontinuation adjusted for the competing risk of death was estimated. Cox models adjusted for age and sex were used to compare trends between time periods. The study population included 399 patients (71% female) diagnosed in 1999 – 2008 and 430 patients (67% female) diagnosed in 2009 – 2018. GC use was initiated within 6 months of meeting RA criteria in 67% of patients in 1999-2008 and 71% of patients in 2009-2018, corresponding to a 29% increase in hazard for initiation of GC in 2009-2018 (adjusted hazard ratio [HR]: 1.29; 95% confidence interval [CI]: 1.09-1.53). Among GC users, similar rates of GC discontinuation within 6 months after GC initiation were observed in patients with RA incidence in 1999 – 2008 and 2009 – 2018 (39.1% versus 42.9%, respectively), with no significant association in adjusted Cox models (HR: 1.11; 95% CI: 0.93-1.31). More patients are initiating GCs early in their disease course now compared to previously. The rates of GC discontinuation were similar, despite the availability of biologics. [ABSTRACT FROM AUTHOR]

To assess transition probability between different levels of functional disability (FD) and time spent with FD in patients with versus without rheumatoid arthritis (RA) after RA incidence/index date. This retrospective population-based cohort study included Olmsted County, Minnesota residents (1987 ACR criteria met in 1999–2013) and comparators without RA from the same area with similar age, sex and RA incidence/index date. Activities of Daily Living (ADL) were obtained by self-report questionnaires annually since 1999. FD was defined as having difficulty with ≥1 ADL. Multistate modeling was used to estimate the probability of transitioning between FD states. Five hundred fifty-eight patients with RA and 457 comparators completed ≥2 questionnaires and were included. Patients with RA had increased risk of transitioning from no FD to FD: Hazard Ratio (HR) 2.4; 95%CI:1.9–3.0. Each additional FD at RA onset reduced the probability of returning to no FD by 14%. However, the probability of having ≥1 FD was stable between RA incidence and 10-year follow-up. In the first 15 years of disease, patients with RA spent on average 10.1 years without FD and 3.4 years with ≥1 FD versus 11.6 years and 2.0 years (p <0.001) in comparators. Patients with RA remain functionally disadvantaged compared to individuals without RA. The likelihood of returning to no FD in RA decreases with each additional preexisting FD. However, the probability of FD does not increase within 10 years of RA onset, potentially reflective of the benefits of disease-modifying treatments in RA. [ABSTRACT FROM AUTHOR]