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Total knee arthroplasty (TKA) is rarely performed in patients under 21 years old, but the frequency of utilization of TKA in this population in the United States is not known. The purpose of this study was to evaluate trends in the use of TKA in patients21 in the United States. Additionally, we aimed to determine the characteristics of these patients and the hospitals in which this procedure is performed.We retrospectively reviewed the Kids' Inpatient Database, a national weighted sample of all inpatient hospital admissions in the United States in patients21 years of age. We used International Classification of Diseases, Ninth Revision (ICD-9) and ICD-10 codes to identify patients undergoing TKA from 2000 to 2019 and determine a primary diagnosis. Descriptive statistics were calculated using the appropriate sample weights.The total weighted number of TKAs performed in patients21 years from 2000 to 2019 was 1,535. There were 70.9% of TKAs performed for a primary diagnosis of tumor, and the use of TKA for malignant tumors has increased. In contrast, the use of TKA for inflammatory arthritis/juvenile idiopathic arthritis decreased significantly over the study period. The majority of TKAs were performed in urban teaching hospitals with a large bed size.Approximately 1,535 TKAs have been performed in patients21 years from 2000 to 2019 in the United States. The majority of these procedures were performed for reconstruction after resection of a malignant tumor. The rate of TKA for inflammatory arthritis/juvenile idiopathic arthritis has decreased over the past two decades.

Background: Patients with inflammatory arthritis are at increased risk of prosthetic joint infections (PJIs), but diagnosis in these patients can be challenging because active inflammatory arthritis produces elevated inflammatory markers that may mimic those seen in PJI. Purpose: In this pilot study, we sought to identify the clinical, microbiologic, and histopathologic features of culture-positive and culture-negative PJI in patients with inflammatory arthritis who underwent total hip arthroplasty (THA) or total knee arthroplasty (TKA). We also sought to obtain preliminary data to support a definitive study of optimal methods for PJI diagnosis in patients with inflammatory arthritis. Methods: We performed a retrospective analysis of TKA and THA patients treated for PJI from 2009 to 2018 at a single tertiary care orthopedic institution. Data were extracted from a longitudinally maintained hospital infection database. We reviewed hematoxylin and eosin slides of osteoarthritis and inflammatory arthritis PJI cases matched 3:1, respectively, by age, sex, and culture status. Clinical characteristics were evaluated using the Fisher exact test, χ2 test, Student t test, and Mann-Whitney U test where appropriate. Results: A total of 807 PJI cases were identified (36 inflammatory arthritis and 771 osteoarthritis cases). Patients with inflammatory arthritis presented younger, had a higher Charlson Comorbidity Index, more frequently used glucocorticoids, were more likely women, and had a higher proportion of culture-negative PJI compared with osteoarthritis patients. Of the 88 inflammatory arthritis cases reviewed for histopathology, a higher proportion of culture-positive than culture-negative PJI cases had >10 polymorphonuclear leucocytes per high-power field and met Musculoskeletal Infection Society criteria but presented with less chronic inflammation. Conclusions: This retrospective prognostic study suggests that culture-negative PJI may be more frequent in patients with inflammatory arthritis than in those with osteoarthritis. Chronic infections, antibiotic use, or misdiagnosis may be contributing factors to unclear PJI diagnoses among culture-negative cases. This preliminary work supports the need for further studies to assess the differences in clinical features between culture-negative and culture-positive PJI in patients with inflammatory arthritis and the ability of biological diagnostic markers to discriminate between them in this population.

Background: Total hip arthroplasty (THA) and total knee arthroplasty (TKA) are cost-effective procedures that decrease pain and improve health-related quality of life for patients with advanced symptomatic arthritis, including rheumatoid arthritis (RA). Patients with RA have a longer length of stay (LOS) after THA or TKA than patients with osteoarthritis, yet the factors contributing to LOS have not been investigated. Purpose: We sought to identify the factors contributing to LOS for patients with RA undergoing THA and TKA at a single tertiary care orthopedic specialty hospital. Methods: We retrospectively reviewed data from a prospectively collected cohort of 252 RA patients undergoing either THA or TKA. Demographics, RA characteristics, medications, serologies, and disease activity were collected preoperatively. Linear regression was performed to explore the relationship between LOS (log-transformed) and possible predictors. A multivariate model was constructed through backward selection using significant predictors from a univariate analysis. Results: Of the 252 patients with RA, 83% were women; they had a median disease duration of 14 years and moderate disease activity at the time of arthroplasty. We had LOS data on 240 (95%) of the cases. The mean LOS was 3.4 ± 1.5 days. The multivariate analysis revealed a longer LOS for RA patients who underwent TKA versus THA, were women versus men, required a blood transfusion, and took preoperative opioids. Conclusion: Our retrospective study found that increased postoperative LOS in RA patients undergoing THA or TKA was associated with factors both non-modifiable (type of surgery, sex) and modifiable (postoperative blood transfusion, preoperative opioid use). These findings suggest that preoperative optimization of the patient with RA might focus on improving anemia and reducing opioid use in efforts to shorten LOS. More rigorous study is warranted.

The immune mechanisms that mediate synovitis and joint destruction in rheumatoid arthritis (RA) remain poorly defined. Although increased levels of CD8+T cells have been described in RA, their role in pathogenesis remains unclear. Here we perform single cell transcriptome and T cell receptor (TCR) sequencing of CD8+T cells derived from anti-citrullinated protein antibodies (ACPA)+ RA blood. We identifyGZMB+CD8+subpopulations containing large clonal lineage expansions that express cytotoxic and tissue homing transcriptional programs, while aGZMK+CD8+memory subpopulation comprises of smaller clonal expansions that express effector T cell transcriptional programs. We demonstrate RA citrullinated autoantigens presented by MHC class I activate RA blood-derivedGZMB+CD8+T cells to expand, express cytotoxic mediators, and mediate killing of target cells. We also demonstrate that these clonally expandedGZMB+CD8+cells are present in RA synovium. These findings suggest that cytotoxic CD8+T cells targeting citrullinated antigens have a role in contributing to synovitis and joint tissue destruction in ACPA+ RA.

Objective Our primary objective was to develop an Outcome Measures in Rheumatology (OMERACT) core domain set to capture the impact of glucocorticoids (GC), both positive and negative, on patients with Rheumatic conditions. Methods The OMERACT Filter 2.1 was used to guide core domain selection. Systematic literature reviews, qualitative studies and quantitative surveys were conducted by the OMERACT GC Impact working group to identify candidate domains for a core domain set. A summary of prior work and Delphi exercise were presented at the OMERACT 2020 virtual GC workshop. A proposed GC Impact core domain set derived from this work was presented for discussion in facilitated breakout groups. Participants voted on the proposed GC Impact core domain set. Results 113 people, including 23 patient research partners, participated in two virtual workshops conducted at different times on the same day. The proposed mandatory domains to be evaluated in clinical trials involving GCs were: infection, bone fragility, hypertension, diabetes, weight, fatigue, mood disturbance and death. In addition, collection of disease specific outcomes was included in the core domain set as “mandatory in specific circumstances”. The proposed core domain set was endorsed by 100% (23/23) of the patient research partners and 92% (83/90) of the remaining participants, including clinicians, researchers and industry stakeholders. Conclusion A GC Impact core domain set was endorsed at the OMERACT 2020 virtual workshop. The OMERACT GC Impact working group will now progress to identify, develop and validate measurement tools to best address these domains in clinical trials.

Resume Objectif Evaluer de quelle maniere les patients atteints de polyarthrite rhumatoide (PR) envisagent l’addition d’un traitement de fond (DMARD) par voie orale ou d’un DMARD biologique (bDMARD) par voie injectable en cas de reponse insuffisante au methotrexate. Methodes Selon la technique du groupe nominal (TGN), les patients atteints de PR ont repondu a la question « Quels criteres vous semblent importants lorsque vous choisissez d’ajouter un traitement par voie orale ou par voie injectable en cas d’inefficacite du methotrexate a controler l’activite de la PR ? » Les patients ont formule, discute et vote pour les reponses. Resultats Quarante-sept patients atteints de PR et issus des centres hospitaliers de Birmingham (n = 6 GN ; 21 patients) et de New-York City (n = 4 GN ; 26 patients) ont ete inclus dans l’etude. La population de patients etait composee d’une majorite de femmes (85 %), 70 % de race blanche, d’âge moyen 64,5 ans et avec une duree de la PR > 10-ans dans 58 % des cas. Les traitements DMARD anterieurs/en cours comprenaient du methotrexate seul chez 6 %, d’autres traitements de fonds conventionnels (csDMARD) chez 15 %, une corticotherapie associee aux csDMARD chez 11 % et des biotherapies et/ou inhibiteurs des JAK chez 68 % des participants. Les domaines ont ete votes dans l’ordre suivant : (1) Efficacite/efficience et delai/mode d’action (78/282 votes) ; (2) Effets secondaires/peur des effets secondaires (84/282 votes) ; (3) Cout incluant les frais a la charge des patients, les co-paiements et la responsabilite financiere du patient (54/282 votes) ; (4) Facilite/frequence d’administration (27/282 votes) ; (5) Avis du medecin (20/282 votes) ; (6) Autres traitements/comorbidites/experiences d’autres patients/effets sur les autres patients (3/282 votes) ; (7) Peur des aiguilles (8/282 votes) ; et (8) Nouveaute du traitement (8/282 votes). Conclusions Nous avons identifie le point de vue des patients concernant le choix entre un DMARD par voie orale et un DMARD injectable en cas de PR refractaire au methotrexate. Ces informations peuvent faciliter la prise de decision partagee quant au choix des DMARD dans le traitement de la PR.

Objective The optimal strategy for perioperative glucocorticoid (GC) management in patients with rheumatoid arthritis (RA) on chronic GCs is unknown. Although there is a concern for hypotension if inadequate doses are used, higher GC exposure may increase perioperative complications. We aimed to investigate the relationships between perioperative GCs with hemodynamic instability and short-term postoperative complications following total hip arthroplasty (THA) and total knee arthroplasty (TKA) in patients with RA. Methods This retrospective study included patients with RA who underwent THA and TKA. GC exposure was assessed by the total cumulative dose (in prednisone equivalents) during hospitalization. Perioperative complications and hypotension were assessed. Results Of 432 patients, 387 (90%) received supraphysiologic perioperative GC. Thirty percent of patients were using chronic GCs (mean daily dose, 7 ± 4 mg). Half (54%) underwent TKA. The median age was 65 years, and 79% were women. The median cumulative GC dose during hospitalization was 37 mg (interquartile range, 27-53.3). A lower cumulative dose of GC did not increase odds of hypotension during hospitalization (unadjusted odds ratio, 1.00 [95% confidence interval, 0.99-1.01]; P = 0.66)]. However, postoperative complications were higher among patients who received higher cumulative doses after adjustment for age, body mass index, home GC use, smoking, and Charlson Comorbidity Index. Risk of short-term complications increased by 8.4% (P = 0.017) for every 10-mg increase in GC dose. Conclusion A lower GC dose was not associated with increased hypotension. However, patients with higher GC exposure were more likely to have hyperglycemia and other complications. These findings suggest that harms may be associated with high perioperative GC doses. Further research is needed to determine the optimal perioperative regimen for patients with RA.

Background Primary care physicians (PCPs) are often gatekeepers to specialist care. This study assessed the relationship between PCP density and total knee (TKA) and total hip arthroplasty (THA) outcomes. Methods We obtained patient-level data from an institutional registry on patients undergoing elective primary TKA and THA for osteoarthritis, including Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain and function scores at baseline and 2 years. Using geocoding, we identified the number of PCPs in the patient’s census tract (communities). We used Augmented Inverse Probability Weighting and Cross-validated Targeted Minimum Loss-Based Estimation to compare provider density and outcomes adjusting for potential confounders. Results Our sample included 3606 TKA and 4295 THA cases. The median number of PCPs in each community was similar for both procedures: TKA 2 (interquartile range 1, 6) and for THA 2 (interquartile range 1, 7). Baseline and 2-year follow-up WOMAC pain, function, and stiffness scores were not statistically significantly different comparing communities with more than median number of PCPs to those with less than median number of PCPs. In sensitivity analyses, adding 1 PCP to a community with zero PCPs would not have statistically significantly improved baseline or 2-year follow-up WOMAC pain, function, and stiffness scores. Conclusions In this sample of patients who underwent elective TKA or THA for osteoarthritis, we found no statistically significant association between PCP density and pain, function, or stiffness outcomes at baseline or 2 years. Further studies should examine what other provider factors affect access and outcomes in THA and TKA.

Background The impact of social determinants of health on children with polyarticular juvenile idiopathic arthritis (pJIA) is poorly understood. Prompt initiation of treatment for pJIA is important to prevent disease morbidity; however, a potential barrier to early treatment of pJIAs is delayed presentation to a pediatric rheumatologist. We examined the impact of community poverty level, a key social determinant of health, on time from patient reported symptom onset to first pediatric rheumatology visit among pJIA patients enrolled in the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Registry. Methods This is a cohort study of pJIA patients in the CARRA registry who lived in the United States from July 2015–February 2020. The primary exposure was community poverty level derived by geocoding patient addresses. The primary outcome was time to first rheumatology appointment. Kaplan-Meier analysis was performed to analyze time to first rheumatologist visit, stratified by community poverty and family income. Log-rank tests were used to identify differences between groups. Adjusted cox proportional-hazards models were used to determine the relationship between community poverty level and time from onset of disease symptoms to date first seen by rheumatologist. Results A total of 1684 patients with pJIA meeting study inclusion and exclusion criteria were identified. Median age of onset of pJIA was 7 years (IQR 3, 11), 79% were female, 17.6% identified as minority race and/or ethnicity, and 19% were from communities with ≥20% community poverty level. Kaplan-Meier analysis by community poverty level (p = 0.6). The Cox proportional hazards model showed that patients with ≥20% community poverty level were 19% less likely (adjusted HR 0.81, 95% CI 0.67–0.99, p = 0.038) to be seen by a rheumatologist compared to patients with Conclusion In this study of pJIA patients in the CARRA registry, increased community poverty level is associated with longer time to presentation to a pediatric rheumatologist after symptom onset.

Clinical practice guidelines are important documents developed and endorsed by the American College of Rheumatology to support its membership and other clinicians in the care of patients with rheumatic and musculoskeletal diseases. Clinical practice guidelines serve several roles including guiding health care professionals on treatment of a disease, screening, and/or diagnosis. Rigorously developed guidelines are based on the most recent scientific evidence, in consultation with experts, including patients. This article discusses the purpose of clinical practice guidelines, highlighting their strengths and limitations. Policies and procedures of the American College of Rheumatology for the development and endorsement of guidelines are summarized.

Background Over 1 million Americans undergo joint replacement each year, and approximately 1 in 75 will incur a periprosthetic joint infection. Effective treatment necessitates pathogen identification, yet standard-of-care cultures fail to detect organisms in 10% to 20% of cases and require invasive sampling. We hypothesized that cell-free DNA (cfDNA) fragments from microorganisms in a periprosthetic joint infection can be found in the bloodstream and utilized to accurately identify pathogens via next-generation sequencing. Methods In this prospective observational study performed at a musculoskeletal specialty hospital in the U.S., we enrolled 53 adults with validated hip or knee periprosthetic joint infections. Participants had peripheral blood drawn immediately prior to surgical treatment. Microbial cfDNA from plasma was sequenced and aligned to a genome database with >1,000 microbial species. Intraoperative tissue and synovial fluid cultures were performed per the standard of care. The primary outcome was accuracy in organism identification with use of blood cfDNA sequencing, as measured by agreement with tissue-culture results. Results Intraoperative and preoperative joint cultures identified an organism in 46 (87%) of 53 patients. Microbial cfDNA sequencing identified the joint pathogen in 35 cases, including 4 of 7 culture-negative cases (57%). Thus, as an adjunct to cultures, cfDNA sequencing increased pathogen detection from 87% to 94%. The median time to species identification for cases with genus-only culture results was 3 days less than standard-of-care methods. Circulating cfDNA sequencing in 14 cases detected additional microorganisms not grown in cultures. At postoperative encounters, cfDNA sequencing demonstrated no detection or reduced levels of the infectious pathogen. Conclusions Microbial cfDNA from pathogens causing local periprosthetic joint infections can be detected in peripheral blood. These circulating biomarkers can be sequenced from noninvasive venipuncture, providing a novel source for joint pathogen identification. Further development as an adjunct to tissue cultures holds promise to increase the number of cases with accurate pathogen identification and improve time-to-speciation. This test may also offer a novel method to monitor infection clearance during the treatment period. Level of evidence Diagnostic Level II. See Instructions for Authors for a complete description of levels of evidence.

Total joint arthroplasty (TJA) is one of the most common surgical procedures in the United States; however, racial and ethnic disparities in utilizations and outcomes have been well documented. This systematic review and meta-analysis investigated associations between race/ethnicity and several metrics in total hip arthroplasty (THA) and total knee arthroplasty (TKA).In August 2021, PubMed, Scopus, CINAHL, and SPORTDiscus databases were queried. Sixty three studies investigating racial/ethnic disparities in TJA utilizations, complications, mortalities, lengths of stay (LOS), discharge dispositions, readmissions, and reoperations were included. Study quality was assessed using a modified Newcastle-Ottawa Scale.A majority of studies demonstrated disparities in TJA utilizations and outcomes. Black patients exhibited higher rates of 30-day complications (THA odds ratio [OR] 1.18, 95% confidence interval [CI] 1.08-1.29; TKA OR 1.20, 95% CI 1.10-1.31), 30-day mortality (THA OR 1.27, 95% CI 1.08-1.48), prolonged LOS (THA mean difference [MD] +0.27 days, 95% CI 0.21-0.33; TKA MD +0.30 days, 95% CI 0.20-0.40), nonhome discharges (THA OR 1.47, 95% CI 1.37-1.57; TKA OR 1.65, 95% CI 1.38-1.96), and 30-day readmissions (THA OR 1.13, 95% CI 1.08-1.19; TKA OR 1.19, 95% CI 1.16-1.21) than White patients. Rates of complications (THA 1.18, 95% CI 1.03-1.36), prolonged LOS (TKA MD +0.20 days, 95% CI 0.17-0.23), and nonhome discharges (THA OR 1.26, 95% CI 1.10-1.45; TKA OR 1.37, 95% CI 1.22-1.53) were also increased among Hispanic patients, while Asian patients experienced longer LOS (TKA MD +0.09 days, 95% CI 0.05-0.12) but fewer readmissions. Outcomes among American Indian-Alaska Native and Pacific Islander patients were infrequently reported but similarly inequitable.Racial and ethnic disparities in TJA utilizations and outcomes are apparent, with minority patients often demonstrating lower rates of utilizations and worse postoperative outcomes than White patients. Continued research is needed to evaluate the efficacy of recent efforts dedicated to eliminating inequalities in TJA care.IV.

Four major medical societies involved with hydroxychloroquine (HCQ) therapy concur on the need for common principles and cooperation to minimize the risk of ocular toxicity. At a daily dosage of ≤5 mg/kg/day actual body weight, the risk of retinal toxicity from HCQ is

BACKGROUND: We sought to examine bilateral total knee arthroplasty (BTKA) vs unilateral TKA (UTKA) utilization and in-hospital complications comparing African Americans (AAs) and Whites. METHODS: In this retrospective analysis of patients ≥50 years who underwent elective primary TKA, National Inpatient Sample - Healthcare Cost and Utilization Project database (2007–2016) was used. We computed differences in temporal trends in utilization and major in-hospital complication rates of BTKA vs UTKA comparing AAs and Whites. We performed multivariable logistic regression models to assess racial differences in trends adjusting for individual-, hospital- and community-level variables. Discharge weights were used to enable nationwide estimates. We used multiple imputation procedures to impute values for 12% missing race information. RESULTS: An estimated 276,194 BTKA and 5,528,429 UTKA were performed in the US. The proportion of BTKA amongst all TKAs declined, and AAs were significantly less likely to undergo BTKA compared to Whites throughout the study period (trend P = 0.01). In-hospital complication rates for UTKA were higher in AAs compared to Whites throughout the study period (trend P < .0001). However, for BTKA, the in-hospital complication rates varied between Whites and AAs throughout the study period (trend P = 0.09). CONCLUSION: In this nationwide sample of patients from 2007–2016 who underwent total knee arthroplasty, the utilization of BKTA was higher in Whites compared to AAs. On the other hand, while AAs have consistently higher in-hospital complication rates in UTKA over the time period, this pattern was not consistent for BTKA.

Background Little is known about the relationship between infection and the risk of risk of venous thromboembolism (VTE) following orthopaedic surgery. We assessed the 90-day risk of VTE following revision total knee replacement to measure the association between periprosthetic joint infection and the risk of postoperative VTE. Methods We used New York Statewide Planning and Research Cooperative System data to identify all New York State residents undergoing revision total knee replacement from 1998 to 2014. ICD-9-CM (International Classification of Diseases, Ninth Revision, Clinical Modification) codes were used to identify comorbidities and to classify the indication for revision total knee replacement as aseptic, infection, or fracture. The primary outcome was any diagnosis code for VTE recorded for the revision surgery and/or subsequent admissions within 90 days. A multivariable logistic regression model that included demographic characteristics and comorbidities was used to estimate the risk of VTE after revision for infection or fracture, with aseptic revision as the reference group. Results The present study included 25,441 patients who were managed with revision total knee replacement; the indication for revision was aseptic for 17,563 patients (69%), infection for 7,075 (28%), and fracture for 803 (3%). The mean age (and standard deviation) was 66 ± 12 years, 15,592 (61%) of the patients were female, 3,198 (13%) were Black, 1,192 (5%) were smokers, and 4,222 (17%) were obese. Seven hundred and nineteen patients (2.8%) had VTE within the 90 days after revision total knee replacement, including 387 (1.5%) during the admission for the revision procedure. The 90-day incidence of VTE was 2.1% after aseptic revision, 4.3% after revision for infection, and 5.9% after revision for fracture. The adjusted odds ratio (aOR) for VTE relative to aseptic revision was 2.01 (95% confidence interval [CI], 1.72 to 2.35) for septic revision total knee replacement and 2.62 (95% CI, 1.91 to 3.6) for fracture. A history of VTE was also a strong risk factor for VTE following revision total knee replacement (aOR, 2.01; 95% CI, 1.48 to 2.71). Conclusions We found that the odds of VTE after revision total knee replacement for infection were double those after aseptic revision total knee replacement. Although fracture accounts for a small percentage of revision total knee replacements, the risk of VTE was 2.6-fold higher after these procedures. The indication for revision total knee replacement should be considered when choosing postoperative VTE prophylaxis. Level of evidence Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Patients with rheumatic disease, including those with systemic lupus erythematous, rheumatoid arthritis, and spondyloarthritis, use total hip and knee arthroplasties at high rates. They represent a particularly vulnerable population in the perioperative setting because of their diseases and the immunosuppressant therapies used to treat them. Careful planning among internists, medical specialists, and the surgical team must therefore occur preoperatively to minimize risks in the postoperative period, particularly infection. Management of immunosuppressant medications, such as conventional synthetic disease-modifying antirheumatic drugs and targeted therapies including biologics, is one avenue by which this infectious risk can be mitigated.

ObjectiveTo evaluate and quantify the indicators of fetal and maternal morbidity in deliveries for patients with systemic lupus erythematosus (SLE) compared with deliveries in patients without SLE.MethodsWe used retrospective data from the National Inpatient Sample (NIS) to identify all delivery related hospital admissions of patients with and without SLE from 2008 to 2017 using ICD-9/10 codes. Fetal morbidity indicators included pre-term delivery and intrauterine growth restriction (IUGR). 21 indicators of severe maternal morbidity were identified using standard Centers for Disease Control and Prevention (CDC) definitions. Descriptive statistics, including 95% confidence intervals, were calculated using sample weights from the NIS dataset.ResultsAmong the 40 million delivery-related admissions, 51 161 patients were reported to have SLE. Patients with SLE had a higher risk of fetal morbidity, including IUGR (8.0% vs 2.7%) and pre-term delivery (14.5% vs 7.3%), than patients without SLE. During delivery, mothers with SLE were nearly four times as likely to require a blood transfusion or develop a cerebrovascular disorder, and 15 times as likely to develop acute renal failure than those without SLE.ConclusionOur study demonstrates that fetal morbidity and severe maternal morbidity occur at a higher rate in patients with SLE compared with those without. This quantitative work can help inform and counsel patients with SLE during pregnancy and planning.

Resume Objectif Evaluer les raisons pour lesquelles les patients choisissent une biotherapie anti-TNF ou non anti-TNF pour le traitement de la polyarthrite rhumatoide (PR) active apres echec du methotrexate. Methodes Les participants ont repondu a la question : « Quels elements entrent dans le choix d’un patient entre deux types de biotherapie injectable, anti-TNF ou non anti-TNF, pour traiter une polyarthrite rhumatoide dont l’activite n’a pas pu etre controlee par le methotrexate ? ». Ils ont selectionne des reponses, discute, puis vote. Resultats Quarante-quatre patients ont ete repartis dans 10 groupes nominaux (Birmingham n = 6 ; New York City n = 4). La majorite etait des femmes (86 %), 68 % etaient blanches et l’âge moyen etait de 65 ans (ecart-type [ET] 12). Les traitements de fond antirhumatismaux (DMARD) actuels/passes comprenaient le methotrexate dans 88 % des cas, les glucocorticoides dans 12 % et des biotherapies et/ou des inhibiteurs de JAK dans 68 % des cas. La douleur et la fatigue etaient legeres a moderees avec une moyenne de 3,9 (ET 2,5) et de 4,3 (ET 2,5), respectivement, sur une echelle de 0 a 10 ; la duree moyenne de la raideur articulaire matinale etait de 1,3 heure (ET 2,1). Le nombre de groupes ayant selectionne chaque reponse et le nombre total de votes par reponse etaient les suivants : (1) « Effets indesirables/crainte d’effets indesirables » : 10/10, 31 % des votes (82/264) ; (2) « Efficacite/capacite a reduire les degradations articulaires » : 9/10, 30 % des votes (80/264) ; (3) « Avis du medecin » : 6/10, 12 % des votes (32/264) ; (4) « Cout » : 7/10, 9 % des votes (25/264) ; (5) « Autres medicaments/comorbidites » : 4/10, 12 % des votes (31/264) ; (6) « Experience d’autres personnes/recherche d’informations/recherche personnelle » : 2/10, 2 % des votes (5/264) ; (7) « Nouveaute » : 1/10, 2 % des votes (6/264) ; et (8) « Aspect pratique/frequence d’utilisation » : 1/10, 1 % des votes (3/264). Conclusions Nous avons identifie les avis des patients quant au choix entre biotherapie anti-TNF et non anti-TNF pour le traitement d’une PR active, des informations propres a faciliter la decision partagee dans la prise en charge clinique.

To develop updated American College of Rheumatology/American Association of Hip and Knee Surgeons guidelines for the perioperative management of disease-modifying medications for patients with rheumatic diseases, specifically those with inflammatory arthritis (IA) and those with systemic lupus erythematosus (SLE), undergoing elective total hip arthroplasty (THA) or elective total knee arthroplasty (TKA).We convened a panel of rheumatologists, orthopedic surgeons, and infectious disease specialists, updated the systematic literature review, and included currently available medications for the clinically relevant population, intervention, comparator, and outcomes (PICO) questions. We used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology to rate the quality of evidence and the strength of recommendations using a group consensus process.This guideline updates the 2017 recommendations for perioperative use of disease-modifying antirheumatic therapy, including traditional disease-modifying antirheumatic drugs, biologic agents, targeted synthetic small-molecule drugs, and glucocorticoids used for adults with rheumatic diseases, specifically for the treatment of patients with IA, including rheumatoid arthritis and spondyloarthritis, those with juvenile idiopathic arthritis, or those with SLE who are undergoing elective THA or TKA. It updates recommendations regarding when to continue, when to withhold, and when to restart these medications and the optimal perioperative dosing of glucocorticoids.This updated guideline includes recently introduced immunosuppressive medications to help decision-making by clinicians and patients regarding perioperative disease-modifying medication management for patients with IA and SLE at the time of elective THA or TKA.

Inflammation of non-barrier immunologically quiescent tissues is associated with a massive influx of blood-borne innate and adaptive immune cells. Cues from the latter are likely to alter and expand the spectrum of states observed in cells that are constitutively resident. However, local communications between immigrant and resident cell types in human inflammatory disease remain poorly understood. Here, we explored heterogeneity of synovial fibroblasts (FLS) in inflamed joints of rheumatoid arthritis (RA) patients using paired single cell RNA and ATAC sequencing (scRNA/ATAC-seq), multiplexed imaging, and spatial transcriptomics along with in vitro modeling of cell extrinsic factor signaling. These analyses suggest that local exposures to myeloid and T cell derived cytokines, TNFα, IFNγ, IL-1β, or lack thereof, drive six distinct FLS states some of which closely resemble fibroblast states in other disease-affected tissues including skin and colon. Our results highlight a role for concurrent, spatially distributed cytokine signaling within the inflamed synovium.

Background Patients with rheumatoid arthritis (RA) receive transfusions more often than patients with osteoarthritis following lower extremity total joint arthroplasty (TJA), but mitigating factors are not described. Tranexamic acid (TXA) is widely used to reduce blood loss in patients undergoing TJA, but its effect on transfusion rates in patients with RA has not been studied. Methods We retrospectively reviewed data from a prospectively collected cohort of patients with RA undergoing TJA. Disease activity measured by Clinical Disease Activity Index, patient-reported outcome measures, and serologies was obtained. Baseline characteristics were summarized and compared. Transfusion requirements and TXA usage were obtained from chart review. Logistic regression was used to determine factors associated with transfusion in RA patients undergoing TJA. Results The cohort included 252 patients, mostly women with longstanding RA and end-stage arthritis requiring TJA. In multivariate analysis, 1 g/dL decrease in baseline hemoglobin (odds ratio [OR] = 0.394, 95% confidence interval [CI] [0.232, 0.669], P = .001), 1-minute increase in surgical duration (OR = 1.022, 95% CI [1.008, 1.037], P = .003), and 1-point increase in Clinical Disease Activity Index (OR = 1.079, 95% CI [1.001, 1.162]) were associated with increased risk of transfusion. TXA use was not associated with decreased risk of postoperative transfusion. Conclusions Preoperative health optimization should include assessment and treatment of anemia in RA patients before TJA, as preoperative hemoglobin level is the main risk factor for postoperative transfusion. Increased disease activity and increased surgical time were independent risk factors for postoperative transfusion but are less modifiable. While TXA did not decrease transfusion risk in this population, a prospective trial is needed to confirm this. Level of Evidence IV.

OBJECTIVE: With hydroxychloroquine (HCQ) and chloroquine (CQ) emerging as potential therapies for coronavirus disease 2019 (COVID-19), shortages have been reported. We aimed to understand how rheumatologists, one of the most common prescribers of HCQ/CQ, prescribed these medications to manage COVID-19 and to understand if their patients are affected by shortages. METHODS: Between April 8 and April 27, 2020, an online survey was distributed to a convenience sample of rheumatologists who practice medicine in a diverse range of settings globally, resulting in 506 responses. Adjusted Poisson regression models were calculated. RESULTS: Only 6% of respondents prescribed HCQ/CQ for COVID-19 prophylaxis, and only 12% for outpatient treatment of COVID-19. Compared to the United States, the likelihood of prescribing HCQ/CQ for prophylaxis was higher in India (adjusted risk ratio [aRR], 6.7; 95% confidence interval [CI], 2.7-16.8; p < 0.001). Further, compared to the United States and those with 1 to 5 years of experience, rheumatologists in Europe (aRR, 2.9; 95% CI, 1.6-5.3; p < 0.001) and those with 10+ years of experience (11-20 years: aRR, 2.5; 95% CI, 1.2-5.3; p = 0.015; 21+ years: aRR = 3.3; 95% CI, 1.4-7.4; p = 0.004) had a higher likelihood of prescribing HCQ/CQ for outpatient treatment. Of note, 71% of all rheumatologists reported that their patients were directly affected by HCQ/CQ shortages. CONCLUSION: The results suggest that only a small percentage of rheumatologists are prescribing HCQ/CQ for prophylaxis or outpatient treatment of COVID-19. Medication shortages experienced by large numbers of autoimmune disease patients are concerning and should play a role in decisions, especially given poor efficacy data for HCQ/CQ in COVID-19.

Background Despite high risk for cardiovascular disease (CVD) mortality, screening and treatment of hyperlipidemia in patients with rheumatoid arthritis (RA) is suboptimal. We asked primary care physicians (PCPs) and rheumatologists to identify barriers to screening and treatment for hyperlipidemia among patients with RA. Methods We recruited rheumatologists and PCPs nationally to participate in separate moderated structured group teleconference discussions using the nominal group technique. Participants in each group generated lists of barriers to screening and treatment for hyperlipidemia in patients with RA, then each selected the three most important barriers from this list. The resulting barriers were organized into physician-, patient- and system-level barriers, informed by the socioecological framework. Results Twenty-seven rheumatologists participated in a total of 3 groups (group size ranged from 7 to 11) and twenty PCPs participated in a total of 3 groups (group size ranged from 4 to 9). Rheumatologists prioritized physician level barriers (e.g. ‘ownership’ of hyperlipidemia screening and treatment), whereas PCPs prioritized patient-level barriers (e.g. complexity of RA and its treatments). Conclusion Rheumatologists were conflicted about whether treatment of CVD risk among patients with RA should fall within the role of the rheumatologist or the PCP. All participating PCPs agreed that CVD risk reduction was within their role. Factors that influenced PCPs’ decisions for screening and treatment for CVD risk in patients with RA were mainly related to their concern about how treatment for CVD risk could influence RA symptomatology (myalgia from statins) or how inflammation from RA and RA medications influences lipid profiles.

Background/objective The objective of this prospective cohort study was to understand the positive and negative effects of glucocorticoids (GCs) in patients with systemic lupus erythematosus and myositis from the patients' perspective with the aim of developing a patient-reported outcome measure. Methods Included patients were asked to participate in 1 of 5 nominal groups where demographic information and a quality-of-life questionnaire were collected. Patients were asked 2 open-ended questions on (1) benefits and (2) harms related to GC use. We used the Nominal Group Technique, a highly structured consensus method in which responses are generated, shared, and ranked. Descriptive statistics were used to summarize the results. Nominal group sessions took place from April to May 2019. Results Of 206 patients who were approached, 21 patients participated, 17 with systemic lupus erythematosus and 4 with myositis, predominantly women with more than 10 years of steroid use. The domains ranked highest for GC benefits were disease control (55 votes), fast onset of action (30 votes), increased energy (10 votes), and pain relief (10 votes). The highest-ranked negative effects were bone loss (38 votes) and weight gain (16 votes); psychological effects and damaged internal organs each received 12 votes. Conclusions The top-ranked GC effects-both benefits and harms-among patients with systemic rheumatic disease are consistent with the top domains associated with GC use reported with other inflammatory diseases. This study informs the development of a comprehensive patient-reported outcome measure that can be used across inflammatory diseases.

Immune checkpoint inhibitor (ICI) therapies that promote T cell activation have improved outcomes for advanced malignancies yet also elicit harmful autoimmune reactions. The T cell mechanisms mediating these iatrogenic autoimmune events remain unclear. Here we assayed T cells from joints of patients affected by ICI-induced inflammatory arthritis (ICI-arthritis), which can present clinically indistinguishable from rheumatoid arthritis (RA). Compared to the autoimmune arthritides RA and psoriatic arthritis (PsA), ICI-arthritis joints contained an expanded CD38hi CD127− CD8+ T cell subset that displays cytotoxic, effector, and interferon (IFN) response signatures. The abundance of CD38hi CD8 T cells in ICI-arthritis resulted from a limited number of clones that could be found proliferating in the joint. Exposure of synovial T cells to Type I IFN, more so than IFN-γ, induces the CD38hi cytotoxic phenotype. Relative to other CD8+ T cell subsets in the joints, the CD38hi population is distinct from a dysfunctional population and clonally most related to TCF7+ memory populations. Examination of synovial tissue from bilateral knee arthroplasty demonstrated considerable sharing of TCR clonotypes in the CD38hi CD8 T cell fraction from both knees. These results define a distinct CD8 T cell subset that may be directly activated by ICI therapy and mediate a tissue-specific autoimmune cellular reaction in patient joints.

Background Patient satisfaction, with both process of care and outcome of care, is critical for measuring the quality and value of elective procedures such as arthroplasty. The purpose of this study was to evaluate the correlation between early postoperative satisfaction with the process of care and 2-year satisfaction with the outcome of care after total hip arthroplasty (THA) and total knee arthroplasty (TKA). Methods We retrospectively analyzed data from institutional arthroplasty registries. Satisfaction with the outcome of care was measured on a scale of 0-100 by a previously-validated questionnaire administered 2-years post-operatively. Patient satisfaction with the process of care was measured by the Press Ganey (PG) inpatient survey, also scored 0-100. We examined the correlation between these two measures of satisfaction in patients who underwent primary THA or TKA. Results 721 TKA patients and 760 THA patients underwent surgery and completed both the PG survey and 2-year satisfaction questionnaire. The mean age was 65.1 years with a mean BMI of 28.8 and 56% were female. The mean PG survey score for the entire cohort was 95.6. The mean 2-year satisfaction score was 90.3. The Spearman correlation coefficient between the PG survey and the 2-year satisfaction survey was 0.23 for TKA patients (p Conclusion We found a weak correlation between the measurement of satisfaction with the process of care surrounding hip and knee arthroplasty using the PG survey and measurement of satisfaction with the outcome of care after arthroplasty using a validated 2-year satisfaction instrument.

Ectopic lymphoid structures (ELS) can develop in rheumatoid arthritis (RA) synovial tissue, but the precise pathways of B cell activation and selection are not well understood. Here, we identified a unique B cell population in the synovium characterized by co-expression of a family of orphan nuclear receptors, NR4A1 (also known as NUR77), NR4A2 (NURR1) and NR4A3 (NOR1), that is highly enriched at both early and late stages of RA. NR4A B cells are rare in healthy peripheral blood, RA blood, and SLE kidney, but share markers with blood transcriptomic signatures that peak during RA disease flare. Using combined single cell transcriptomics and B cell receptor (BCR) sequencing, we demonstrate that NR4A synovial B cells have an activated transcriptomic profile that significantly overlaps with germinal center (GC) light zone (LZ) B cells and an accrual of somatic hypermutation that correlates with loss of naïve B cell status. NR4A B cells uniquely co-express lymphotoxin β and IL6, supporting important functions in ELS promotion and pro-inflammatory cytokine production. Further, the presence of shared clones in this activated B cell state and NR4A expressing synovial plasma cells (PC) and the rapid up-regulation with BCR stimulation points to in situ differentiation. Taken together, we identified a dynamic progression of B cell activation in RA synovial ELS, with NR4A transcription factors having an important role in antigen activation and local adaptive immune responses.One sentence summaryB cells in the rheumatoid arthritis synovium undergo a spectrum of in situ activation, with the NR4A family of transcription factors having an important role in antigen stimulation, local adaptive immunity, and pathological B cell responses.

Although pregnancy in systemic lupus erythematosus (SLE) carries a high risk for mother and fetus, outcomes may be improving.To assess nationwide trends and disparities in maternal and fetal complications among pregnant women with SLE.Retrospective cohort study.United States, 1998 to 2015.Adult pregnant women with and without SLE who had hospitalizations recorded in the National Inpatient Sample (NIS) database.Outcome measures were in-hospital maternal mortality, fetal mortality, preeclampsia or eclampsia, caesarean sections, non-delivery-related admissions, and length of stay. To assess whether trends in outcomes over time differed between patients with SLE and those without SLE, logistic or linear regression with an interaction term between year and SLE (yes or no) was used. Nationwide population estimates incorporating sampling and poststratification weights were obtained.An estimated 93 820 pregnant women with SLE and 78 045 054 without SLE were hospitalized in the United States from 1998 through 2015. Outcomes improved during those 18 years. In-hospital maternal deaths (per 100 000 admissions) declined among patients with as well as those without SLE (442 vs. 13 for 1998 to 2000 and50 vs. 10 for 2013 to 2015), although the decrease was greater in women with SLE (difference in trends, P0.002). The percentage of patients with SLE in all pregnancy-related, as well as delivery-related, admissions increased significantly.The sample for this analysis was identified by using diagnostic codes; detailed information on hospital-specific trends, SLE disease activity, and medications was not available. Race trends could not be analyzed. Given that NIS uses weighted estimates, the incidence of outcomes reported may not be exact.In this large study examining SLE and non-SLE pregnancies over 18 years, in-hospital maternal mortality and overall outcomes improved markedly, particularly among women with SLE. However, improvement is still needed, because SLE pregnancy risks remain high.None.

INTRODUCTION Socioeconomic factors such as poverty may mediate racial disparities in health outcomes after total hip arthroplasty (THA) and confound analyses of differences between blacks and whites. METHODS Using a large institutional THA registry, we built models incorporating individual and census tract data and analyzed interactions between race and percent of population with Medicaid coverage and its association with 2-year patient-reported outcomes. RESULTS Black patients undergoing THA had worse baseline and 2-year pain and function scores compared with whites. We observed strong positive correlations between census tract Medicaid coverage and percent living below poverty (rho = 0.69; P < 0.001). Disparities in 2-year Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain and function were magnified in communities with high census tract Medicaid coverage. For blacks in these communities, 2-year WOMAC function scores were predicted to be -5.54 points lower (80.42 versus 85.96) compared with blacks in less deprived communities, a difference not observed among whites. CONCLUSION WOMAC pain and function 2 years after THA are similar among blacks and whites in communities with little deprivation (low percent census tract Medicaid coverage). WOMAC function at 2 years is worse among blacks in areas of higher deprivation but is not seen among whites. LEVEL OF EVIDENCE Level II - Cohort Study.

Hydroxychloroquine (HCQ) and chloroquine (CQ) are well-established medications used in treating systemic lupus erythematosus and rheumatoid arthritis, as well as skin conditions such as cutaneous lupus erythematosus. In rare cases, arrhythmias and conduction system abnormalities, as well as cardiomyopathy, have been reported in association with HCQ/CQ use. Recently, however, the corrected QT interval (QTc)-prolonging potential of these medications, and risk of torsade de pointes (TdP) in particular, have been highlighted in the setting of their experimental use for COVID-19 infection. This report was undertaken to summarize the current understanding of HCQ/CQ cardiac toxicity, describe QTc prolongation and TdP risks, and discuss areas of priority for future research. A working group of experts across rheumatology, cardiology, and dermatology performed a nonsystematic literature review and offered a consensus-based expert opinion. Current data clearly indicate that HCQ and CQ are invaluable medications in the management of rheumatic and dermatologic diseases, but they are associated with QTc prolongation by directly affecting cardiac repolarization. Prescribing clinicians should be cognizant of this small effect, especially in patients taking additional medications that prolong the QTc interval. Long-term use of HCQ/CQ may lead to a cardiomyopathy associated with arrhythmias and heart failure. Risk and benefit assessment should be considered prior to initiation of any medication, and both initial and ongoing risk-benefit assessments are important with regard to prescription of HCQ/CQ. While cardiac toxicity related to HCQ/CQ treatment of rheumatic diseases is rarely reported, it can be fatal. Awareness of the potential adverse cardiac effects of HCQ and CQ can increase the safe use of these medications. There is a clear need for additional research to allow better understanding of the cardiovascular risk and safety profile of these therapies used in the management of rheumatic and cutaneous diseases.

Background: Inflammatory arthritis (IA) patients are at increased risk for prosthetic joint infections (PJI); however, diagnosis is challenging because active IA patients have elevated inflammatory markers that may mimic joint infection and definitive microbiologic diagnosis may be delayed. The objective of this pilot study was to identify the clinical, microbiologic, and histopathologic features of culture positive (CP) and culture negative (CN) total hip (THA) and total knee arthroplasty (TKA) PJI in IA patients and obtain preliminary data to support a definitive study to determine the optimal method for PJI diagnosis in patients with inflammatory arthritis. Methods: A retrospective cohort of THA/TKA PJIs, from 2009 to 2016, were identified using an institutional PJI registry. H&E slides of OA and IA PJI cases matched by age, sex, and culture status were histologically reviewed. Clinical characteristics were evaluated using Fisher’s exact, Chi-Square tests, Students’ t test, and Mann Whitney U test where appropriate.Results: 807 PJI cases were identified including 36 IA and 771 OA. A higher proportion of IA PJI were CN (N=10, 27%) vs. OA PJI (N=109, 14%, p=0.02). IA PJI patients compared to OA patients presented younger (p10 PMN per HPF (p= 0.003) and met MSIS criteria (p=0.009) but presented with less chronic inflammation (p=0.017).Conclusions: This hypothesis-generating study suggests that culture negative PJI is more frequent in patients with IA than OA. Higher rates of prior PJI, differences in histopathology, and better clinical outcomes suggest biologic differences between CN and CP PJI that should be explored further in a prospective study.