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ID PMID Title PublicationDate abstract
34665707 Sonographic features of lymphoma of the major salivary glands diagnosed with ultrasound-gu 2021 Nov OBJECTIVES: To identify ultrasound (US) features of lymphomas (L) of major salivary glands (SGs) in primary Sjögren's syndrome (pSS) patients and to differentiate US pattern of L and non-L. METHODS: Prospectively, from September 2019 to March 2021, 27 pSS-patients with clinical findings suspicious for L of the SGs underwent US evaluation followed by US-guided core-needle biopsy (CNB). For each patient, we assessed the OMERACT score, dichotomised (0/1 "lower", 2/3 "higher"), and we compared it between L-pSS and nonL-pSS groups. For focal lesions, echogenicity, inner appearance, shape, margins, presence of septa, vascularisation and posterior acoustic features were also assessed and compared between the two groups; we planned to consider as "suspicious" features more frequently associated with L. We expected to compare frequencies at which two or more "suspicious" features were simultaneously present between L-pSS and nonL-pSS. P<0.05 were considered statistically significant. RESULTS: L-pSS showed more inhomogeneous glandular pattern (100% vs. 69.2% higher OMERACT; p=0.0407). For focal lesions, the "suspicious" features identified were: OMERACT grade 3, very hypoechoic, homogenous, oval shape, well-defined margins, presence of septa, colour-Doppler vascularization, posterior acoustic enhancement. 6/8 and 7/8 simultaneous suspicious features were significantly higher among L-pSS patients, compared to nonL-pSS (88.9% vs. 28.6%, p=0.034 for 6/8 features; 77.8% vs. 14.3%, p=0.040 for 7/8 features). CONCLUSIONS: L of the major SGs in pSS was always associated with OMERACT scores 2 or 3 and presented with diffuse or focal patterns. For focal lesions, the association of more "suspicious" features made the diagnosis of L increasingly more likely. This information can help to improve planning of US-guided CNB.
34622984 Stem cells from exfoliated deciduous teeth transplantation ameliorates Sjögren's syndrome 2022 May Mesenchymal stem cell transplantation (MSCT) regulates immune cells, and is a promising therapeutic approach for treating autoimmune diseases. Stem cells from human exfoliated deciduous teeth (SHED) are a unique postnatal stem cell population from the cranial neural crest with high self-renewal, multipotent differentiation, and superior immunomodulatory properties. However, the mechanisms by which SHED can treat autoimmune diseases remain unclear. Sjögren's syndrome (SS) is an autoimmune disease histologically characterized by high lymphocytic infiltration in the salivary and lacrimal glands that results in dryness symptoms. This study explores the potential of systemic transplantation of SHED to ameliorate SS-induced dryness symptoms in mice. Overall, SHED could rescue the balance of regulatory T cell (Treg)/T helper cell 17 (Th17) in the recipient SS mice. Mechanistically, SHED promoted Treg conversion and inhibited Th17 function via paracrine effects, which were related to the secretion of soluble programmed cell death ligand 1 (sPD-L1). Moreover, it directly induced Th17 apoptosis via cell-cell contact, leading to the up-regulation of Treg and down-regulation of Th17 cells. In summary, SHED-mediated rescue of Treg/Th17 balance via the sPD-L1/PD-1 pathway ameliorates the gland inflammation and dryness symptoms in SS mice. These findings suggest that SHED are a promising stem cell source for the treatment of autoimmune diseases in the clinical setting.
34587995 Olfactory impairment in patients with primary Sjogren's syndrome and its correlation with 2021 Sep 29 OBJECTIVE: Patients with autoimmune diseases often present with olfactory impairment. The aim of the study was to assess the olfactory functions of patients with primary Sjögren's syndrome and to correlate these findings with their disease activity. METHODS: Fifty-two patients with primary SS and 52 sex- and age-matched healthy control subjects were included. All of them underwent clinical and laboratory examination. Olfactory functions were evaluated using olfactory function assessment by computerized testing including the three stages of smell: threshold, identification, and memory of the different odors. RESULTS: All the olfactory scores (olfactory threshold, identification, and memory) in patients with pSS were significantly decreased than the control group (all P < 0.01). Patients had higher proportion of anosmia (13.5% vs 0%) and hyposmia (19.2% vs 11.5%) than controls (χ(2) = 10.526, P < 0.01). Multivariable regression analysis revealed that ESSDAI and the symptoms of dryness, fatigue, and limb pain had negative influence on olfactory function (adjusted R(2) = 0.381, 0.387, 0.513, and 0.614, respectively). ESSPRI showed significantly negative association with olfactory threshold, identification, memory, and total scores. Olfactory identification and memory scores were decreased in pSS patients with thyroid dysfunction or hypocomplementemia (P < 0.05). Smell threshold scores were decreased in pSS patients with anti-SSA antibody or anti-nuclear antibody compared with those without those autoantibodies (P < 0.01). CONCLUSION: Our findings indicate that olfactory functions are impaired in pSS patients. There was a close correlation between olfactory dysfunction and disease severity and immunological abnormalities. Immune and systemic inflammation dysregulation might play a role in the mechanism of this defect.
34523037 Exposure-lag-response associations between extreme environmental conditions and primary Sj 2022 Feb INTRODUCTION: Patients with primary Sjögren's syndrome (pSS) reportedly believe that their symptoms worsen on extreme weather days due to variations in environmental conditions. However, few studies have assessed the acute effects of environmental exposure on the onset of pSS. This study aimed to evaluate the exposure-response relationship between extreme environmental conditions and pSS outpatient visits. METHOD: We obtained data on pSS outpatient visits from two provincial general hospitals in Hefei, China, during 2014-2019. A distributed lag non-linear model was used to estimate the exposure-lag-response relationship between environmental variables and pSS. RESULTS: We detected significant and non-linear associations between extreme environments and pSS. The estimated relative risk (RR) for a lag of 3 days was 1.11 (95% CI: 1.03 to 1.19) for extreme cold and for a lag of 21 days was 1.07 (95% CI: 1.01 to 1.12) for extreme dampness. Long sunshine duration was positively correlated with pSS (lag 11, 1.05, 95% CI: 1.01 to 1.08). Moreover, female patients were more susceptible to these effects. Patients older than 65 years old were more vulnerable to frigid environments (lag 3, RR = 1.30, 95% CI: 1.09 to 1.54), while younger patients were more vulnerable to extreme dampness (lag 21, RR = 1.10, 95% CI: 1.03 to 1.16). Extreme cold and high humidity were negatively correlated with the same-day outpatient visits. CONCLUSIONS: Our findings suggest a potential relationship between exposure to extreme environmental conditions and increased risk of pSS outpatient visits. We therefore suggest that policymakers and doctors aim to further our understanding of environmental effects on pSS and adopt adequate measures to alleviate pSS symptoms. Key Points • Extreme cold, extreme dampness, and long sunshine duration increased the risk of pSS outpatient visits, especially for females. • Young pSS patients are more susceptible to a rise in humidity. • Elderly pSS patients are more sensitive to extreme cold weather.
34349764 Differentially Expressed Gene Pathways in the Conjunctiva of Sjögren Syndrome Keratoconju 2021 Sjögren syndrome (SS) is an autoimmune condition that targets the salivary and lacrimal glands, with cardinal clinical signs of dry eye (keratoconjunctivitis sicca, KCS) and dry mouth. The conjunctiva of SS patients is often infiltrated by immune cells that participate in the induction and maintenance of local inflammation. The purpose of this study was to investigate immune-related molecular pathways activated in the conjunctiva of SS patients. Female SS patients (n=7) and controls (n=19) completed a series of oral, ocular surface exams. Symptom severity scores were evaluated using validated questionnaires (OSDI and SANDE). All patients fulfilled the ACR/EULAR criteria for SS and the criteria for KCS. Fluorescein and lissamine green dye staining evaluated tear-break-up time (TBUT), corneal and conjunctival disease, respectively. Impression cytology of the temporal bulbar conjunctiva was performed to collect cells lysed and subjected to gene expression analysis using the NanoString Immunology Panel. 53/594 differentially expressed genes (DEGs) were observed between SS and healthy controls; 49 DEGs were upregulated, and 4 were downregulated (TRAF5, TGFBI, KLRAP1, and CMKLRI). The top 10 DEGs in descending order were BST2, IFITM1, LAMP3, CXCL1, IL19, CFB, LY96, MX1, IL4R, CDKN1A. Twenty pathways had a global significance score greater or equal to 2. Spearman correlations showed that 29/49 upregulated DEGs correlated with either TBUT (inverse) or OSDI or conjunctival staining score (positive correlations). Venn diagrams identified that 26/29 DEGs correlated with TBUT, 5/26 DEGs correlated with OSDI, and 16/26 correlated with conjunctival staining scores. Five upregulated DEGs (CFB, CFI, IL1R1, IL2RG, IL4R) were uniquely negatively correlated with TBUT. These data indicate that the conjunctiva of SS patients exhibits a phenotype of immune activation, although some genes could be inhibitory. Some of the DEGs and pathways overlap with previous DEGs in salivary gland biopsies, but new DEGs were identified, and some of these correlated with symptoms and signs of dry eye. Our results indicate that gene analysis of conjunctiva imprints is a powerful tool to understand the pathogenesis of SS and develop new therapeutic targets.
34301381 Validation and adaptation to Spanish of the EULAR Sjögren's Syndrome Patient Reported Ind 2021 Aug INTRODUCTION AND OBJECTIVES: Sjögren's Syndrome (SS) is an autoimmune disease with a wide spectrum of clinical manifestations that can have an important impact on the patient's quality of life. To make an objective evaluation of the components of the disease, clinimetric tools such as the ESSPRI have been designed. The objective of this study is to adapt this scale to the Spanish language. MATERIALS AND METHODS: This is a cross-sectional study to validate clinimetric scales, carried out in Cali, Colombia. A translation of the original English version of ESSPRI into Spanish was made and applied to patients with SS, as well as PROFAD and ESSDAI, as an activity marker. The reliability index of the questionnaire in Spanish with Cronbach's alpha coefficient and Spearman's correlation coefficient were calculated to compare the scales. Demographic, clinical and laboratory characteristics were also evaluated. RESULTS: ESSPRI, PROFAD and ESSDAI were applied to 42 patients with SS, 97.62% were women. The average result of the ESSPRI was 5.8 (± 4.6), with a reliability coefficient of .8034 and a correlation with PROFAD of .5800 (p=.0001), and of -.0848 (p=.593) with ESSDAI. DISCUSSION AND CONCLUSIONS: Reliability with the applied version of ESSPRI in Spanish was adequate. A discrepancy was found between this scale and ESSDAI, which highlights the importance of applying both tools to ensure objective monitoring of disease control and its impact on the quality of life of patients with SS.
33980205 Corneal nerve structure in patients with primary Sjögren's syndrome in China. 2021 May 12 BACKGROUND: The aim of this study was to evaluate the in vivo confocal microscopic morphology of corneal subbasal nerves and its relationship with clinical parameters in patients with primary Sjögren's syndrome in China. METHODS: This was a case control study of 22 dry eye disease (DED) patients with primary Sjögren's syndrome (pSS) and 20 control subjects with non-Sjögren dry eye disease (NSDE). Each patient underwent an evaluation of ocular surface disease using the tear film break-up time (TBUT), noninvasive tear film break-up time (NIKBUT), noninvasive tear meniscus height (NIKTMH), corneal staining (National Eye Institute scale, NEI), Schirmer I test, meibography, and corneal subbasal nerve analysis with in vivo confocal microscopy (IVCM). The right eye of each subject was included in this study. RESULTS: SS patients showed a shorter TBUT (P = 0.009) and Schirmer I test results (P = 0.028) than the NSDE group. However, there was no significant difference in NIKBUT between the two groups (P = 0.393). The nerve density of subbasal nerves, number of nerves and tortuosity of the SS group were significantly lower than those of the NSDE group (P = 0.001, P < 0.001 and P = 0.039, respectively). In the SS group, the mean nerve length was correlated with age and the Schirmer I test (r = - 0.519, P = 0.013 and r = 0.463, P = 0.035, respectively). Corneal staining was correlated with nerve density and the number of nerves (r = - 0.534, P = 0.013 and r = - 0.487, P = 0.025, respectively). CONCLUSIONS: Sjögren syndrome dry eye (SSDE) patients have more severe clinical dry eye parameters than non-Sjögren dry eye disease (NSDE) patients. Compared with NSDE patients, we found that SSDE patients showed decreased corneal subbasal nerve density and numbers.
34734580 Olfactory dysfunction in primary Sjogren's syndrome and its correlation with dry eye. 2021 Oct OBJECTIVE: To evaluate the olfactory function in primary Sjögren's syndrome (pSS) patients and investigate its correlation with dry eye parameters. METHODS: Thirty-eight pSS patients (49.47 ± 10.06 years) and 20 healthy volunteers (47.40 ± 8.92 years) were enrolled in the study. All participants underwent ENT and eye examinations including a modified Connecticut Chemosensory Clinical Research Center (CCCRC) test, tear break-up time (TBUT), ocular surface staining (OSS) and Schirmer test. The parameters were compared between the two groups using Student-t test, and Pearson test was used to evaluate the correlations. RESULTS: Mean Schirmer and TBUT values were 2.39 ± 1.48 mm/5 min and 3.66 ± 1.5 sec in pSS and 18.30 ± 6.16 mm/5 min and 14.60 ± 3.64 sec in healthy subjects (p < 0.001, both). There was a significant decrease in mean odour threshold, odour identification, CCCRC and VAS scores in the pSS group (p < 0.001). Dry eye parameters showed moderate correlations with CCCRC parameters (r = 0.4-0.6, p < 0.001) and olfaction VAS score (r = 0.4-0.75, p < 0.05). CONCLUSIONS: There is a mild clinical impairment in smell sense in patients with pSS which seems to be correlated with dry eye parameters. Therefore, smell complaints should be queried in pSS patients suffering from severe dry eye.
33785060 Total metabolic lesion volume of lymph nodes measured by (18)F-FDG PET/CT: a new predictor 2021 Mar 30 BACKGROUND: To investigate the potential utility of quantitative parameters obtained by (18)F-fluorodeoxyglucose positron emission tomography/computed tomography ((18)F-FDG PET/CT) in the assessment of disease severity and the occurrence of macrophage activation syndrome (MAS) in adult-onset Still's disease (AOSD). METHODS: Fifty-seven patients with AOSD who underwent pre-treatment (18)F-FDG PET/CT were recruited in this study and compared with 60 age- and sex-matched healthy controls. Clinical features and laboratory data were recorded. The systemic score was assessed to determine the disease severity. The maximal standardized uptake value (SUV(max)), metabolic lesion volume (MLV), and total lesion glycolysis (TLG) were used to evaluate the involved organs and tissues that abnormally accumulated (18)F-FDG. Multivariate analysis was performed to identify the PET/CT-derived risk factors contributing to the AOSD-related MAS, and their diagnostic efficiency was evaluated. RESULTS: High (18)F-FDG accumulation was observed in the bone marrow (SUV(max) median, 5.10), spleen (SUV(max) median, 3.70), and lymph nodes (LNs, SUV(max) median, 5.55). The SUV(max) of the bone marrow (rho = 0.376, p = 0.004), SUV(max) of the spleen (rho = 0.450, p < 0.001), TLG(total) of LNs (rho = 0.386, p = 0.017), and MLV(total) of LNs (rho = 0.391, p = 0.015) were correlated with the systemic score. The SUV(max) of the spleen (p = 0.017), TLG(total) of LNs (p = 0.045), and MLV(total) of LNs (p = 0.012) were higher in patients with MAS than in those without MAS. A MLV(total) of LNs > 62.2 (OR 27.375, p = 0.042) was an independent predictive factor for MAS with a sensitivity of 80.0% and a specificity of 93.9%. CONCLUSIONS: The glucose metabolic level of the spleen could be an effective and easy-to-use imaging indicator of disease severity, and MLV(total) of LNs > 62.2 was a strong predictor of MAS occurrence in patients with AOSD.
34571920 Inhibition of Cellular and Animal Inflammatory Disease Models by NF-κB Inhibitor DHMEQ. 2021 Sep 1 General inflammatory diseases include skin inflammation, rheumatoid arthritis, inflammatory bowel diseases, sepsis, arteriosclerosis, and asthma. Although these diseases have been extensively studied, most of them are still difficult to treat. Meanwhile, NF-κB is a transcription factor promoting the expression of many inflammatory mediators. NF-κB is likely to be involved in the mechanism of most inflammatory diseases. We discovered a specific NF-κB inhibitor, dehydroxymethylepoxyquinomicin (DHMEQ), about 20 years ago by molecular design from a natural product. It directly binds to and inactivates NF-κB components. It has been widely used to suppress cellular and animal inflammatory disease models and was shown to be potent in vivo anti-inflammatory activity without any toxicity. We have prepared ointment of DHMEQ for the treatment of severe skin inflammation. It inhibited inflammatory cytokine expressions and lowered the clinical score in mouse models of atopic dermatitis. Intraperitoneal (IP) administration of DHMEQ ameliorated various disease models of inflammation, such as rheumatoid arthritis, sepsis, and also graft rejection. It has been suggested that inflammatory cells in the peritoneal cavity would be important for most peripheral inflammation. In the present review, we describe the synthesis, mechanism of action, and cellular and in vivo anti-inflammatory activities and discuss the clinical use of DHMEQ for inflammatory diseases.
34452007 Impact of Low-Dose Methotrexate-Adalimumab Combination Therapy on the Antibody Response In 2021 Aug 9 Patients with rheumatoid arthritis (RA) are treated with drugs that may impact their immune responses to SARS-CoV-2 vaccines. We describe here the anti-Spike (anti-S) IgG and neutralizing antibody responses induced by the mRNA-1273 SARS-CoV-2 vaccine in a 78-years-old patient with RA, who received a low-dose combination therapy of methotrexate and adalimumab, shortly before vaccine administration. Both near-normal and impaired immune responses to vaccines have been reported previously in patients treated with these drugs. Our case report shows that, even at low doses, combined methotrexate-adalimumab therapy can be associated with a weak immune response to the mRNA1273 vaccine in elderly patients.
34441297 Precision Medicine for Rheumatoid Arthritis: The Right Drug for the Right Patient-Companio 2021 Jul 29 Despite the growing number of biologic and JAK inhibitor therapeutic agents available to treat various systemic autoimmune illnesses, the lack of a validated companion diagnostic (CDx) to accurately predict drug responsiveness for an individual results in many patients being treated for years with expensive, ineffective, or toxic drugs. This review will focus primarily on rheumatoid arthritis (RA) therapeutics where the need is greatest due to poor patient outcomes if the optimum drug is delayed. We will review current FDA-approved biologic and small molecule drugs and why RA patients switch these medications. We will discuss the sampling of various tissues for potential CDx and review early results from studies investigating drug responsiveness utilizing advanced technologies including; multiplex testing of cytokines and proteins, autoantibody profiling, genomic analysis, proteomics, miRNA analysis, and metabolomics. By using these new technologies for CDx the goal is to improve RA patient outcomes and achieve similar successes like those seen in oncology using precision medicine guided therapeutics.
34417735 Incidence of Infusion Reactions and Clinical Effectiveness of Intravenous Golimumab Versus 2021 Dec OBJECTIVE: Evaluate tolerability and effectiveness of golimumab-IV versus infliximab in patients with rheumatoid arthritis (RA) in a real-world setting. METHODS: AWARE, a prospective, real-world, pragmatic, observational, multicenter, phase 4 study, enrolled RA patients when initiating golimumab-IV or infliximab. Treatment decisions were made by the treating rheumatologist. The approved doses for RA are 2 mg/kg at weeks 0, 4, then Q8W for golimumab-IV and 3 mg/kg at weeks 0, 2, 6, then Q8W (dose escalation permitted) for infliximab. A prespecified formal interim analysis was conducted. The primary endpoint was the incidence of infusion reactions (any adverse event that occurred during or within 1 h of infusion) through week 52. Major secondary endpoints were mean change from baseline in CDAI at months 6 and 12 in biologic-naïve patients (non-inferiority margin in the CDAI = 6). Baseline characteristics were adjusted using propensity scores with inverse probability of treatment weights (IPTW). RESULTS: In the formal interim analysis (golimumab-IV, n = 479; infliximab, n = 354), the incidence of infusion reactions was significantly lower with golimumab-IV vs. infliximab (3.6 vs. 17.6%, p < 0.001, IPTW-adjusted). Among biologic-naïve patients, mean changes from baseline in CDAI at month 6 (- 9.5 golimumab-IV vs. - 10.1 infliximab) and at month 12 (- 9.4 golimumab-IV vs. - 10.1 infliximab) demonstrated non-inferiority. CONCLUSIONS: The proportion of patients with an infusion reaction was significantly lower with golimumab-IV vs. infliximab. Among biologic-naïve patients, mean change from baseline in CDAI at months 6 and 12 was non-inferior for golimumab-IV vs. infliximab. Compared with fixed-dose golimumab-IV, infliximab dose escalation did not provide any greater improvements in CDAI for patients with RA. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT02728934.
34085401 What Is the Persistence to Methotrexate in Rheumatoid Arthritis, and Does Machine Learning 2021 Jul OBJECTIVE: The objectives of this study were to assess the 1-year persistence to methotrexate (MTX) initiated as the first ever conventional synthetic disease-modifying antirheumatic drug in new-onset rheumatoid arthritis (RA) and to investigate the marginal gains and robustness of the results by increasing the number and nature of covariates and by using data-driven, instead of hypothesis-based, methods to predict this persistence. METHODS: Through the Swedish Rheumatology Quality Register, linked to other data sources, we identified a cohort of 5475 patients with new-onset RA in 2006-2016 who were starting MTX monotherapy as their first disease-modifying antirheumatic drug. Data on phenotype at diagnosis and demographics were combined with increasingly detailed data on medical disease history and medication use in four increasingly complex data sets (48-4162 covariates). We performed manual model building using logistic regression. We also performed five different machine learning (ML) methods and combined the ML results into an ensemble model. We calculated the area under the receiver operating characteristic curve (AUROC) and made calibration plots. We trained on 90% of the data, and tested the models on a holdout data set. RESULTS: Of the 5475 patients, 3834 (70%) remained on MTX monotherapy 1 year after treatment start. Clinical RA disease activity and baseline characteristics were most strongly associated with the outcome. The best manual model had an AUROC of 0.66 (95% confidence interval [CI] 0.60-0.71). For the ML methods, Lasso regression performed best (AUROC = 0.67; 95% CI 0.62-0.71). CONCLUSION: Approximately two thirds of patients with early RA who start MTX remain on this therapy 1 year later. Predicting this persistence remains a challenge, whether using hypothesis-based or ML models, and may yet require additional types of data.
33418089 Long-term outcomes of total elbow arthroplasty: a systematic review of studies at 10-year 2021 Jun BACKGROUND: The purpose of this study was to systematically review the literature to evaluate the functional outcomes, dislocation, and revision rates following total elbow arthroplasty (TEA) at a minimum 10 years' mean follow-up. MATERIALS AND METHODS: Two independent reviewers performed a literature search using the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines using PubMed, Embase, and Cochrane Library databases. Studies were only included if they focused on outcomes post-TEA at a minimum 10 years' mean follow-up. RESULTS: Our search found 23 studies including 1429 elbows (60.4% linked TEA) that met our inclusion criteria. There were 1276 patients (79.0% female), with an average age of 64.7 years (19-93) and a mean follow-up of 137.2 months (120-216). At final follow-up, the mean Mayo Elbow Performance Score, Oxford Elbow Score, and Quick Disabilities of the Arm, Shoulder, and Hand scores were 89.1 (35-100), 64.4 (16-48), and 39.2 (3-93), respectively, and 63.3% of patients reported having no pain. The rates of aseptic loosening, infection, implant dislocation, and nerve injury were 12.9%, 3.3%, 4.2%, and 2.1%, respectively. The overall complication and revision rates were 16.3% and 14.6%, respectively. DISCUSSION AND CONCLUSION: Our systematic review established that TEA offers patients satisfactory clinical outcomes at long-term follow-up, with relatively stable revision and complication rates compared to short and medium term.
33875975 Failure of chronic hydroxychloroquine in preventing severe complications of COVID-19 in pa 2021 OBJECTIVE: To compare baseline characteristics, clinical presentations and outcomes of patients with rheumatic conditions requiring hospitalization for coronavirus disease 2019 (COVID-19) who received chronic HCQ with those who did not receive chronic HCQ. METHODS: We identified all patients with a rheumatologic disease who were admitted with COVID-19 to two hospitals in New York City between 3 March 3 and 30 April 2020. Patients who received chronic HCQ prior to admission were matched 1:2 (±10 years of age) with patients who did not receive chronic HCQ. We compared demographics, comorbidities, HCQ dosages, concurrent medications, presentations and outcomes between the groups. RESULTS: There were 14 patients receiving HCQ and 28 matched control subjects. The median age of cases was 63 years [interquartile range (IQR) 43-73) and 60 years (IQR 41-75) for controls. Control subjects had a higher prevalence of pulmonary diseases (42.8%), diabetes (35.7%) and obesity (35.7%) than their case counterparts (28.6%, 14.3% and 7.1%, respectively). A higher proportion of cases than control subjects (50% vs 25%) reported the use of prednisone for their rheumatic conditions prior to admission. Despite these differences in baseline characteristics, univariate logistic regression revealed no statistically significant differences in the need for mechanical ventilation [OR 1.5 (95% CI 0.34, 6.38)] or in-hospital mortality [OR 0.77 (95% CI 0.13, 4.56)]. CONCLUSION: HCQ therapy in individuals with rheumatic conditions was not associated with less severe presentations of COVID-19 among hospitalized patients compared with individuals with rheumatic conditions not receiving HCQ.
33816107 Discrepant histological diagnoses: A cause of early low FJS-12 score and if untreated, unh 2021 Jun PURPOSE: Total Knee Arthroplasty (TKA) is one of the most successful operations in orthopedics. Still, a sizable percentage of patients (20%) remain dissatisfied after a well-executed TKA. The study aims to examine the excised synovium from the suprapatellar region in osteoarthritic knees during TKA and evaluate the histopathology (HP) report to know whether discrepant diagnoses affect the Forgotten Joint Score-12 at various time intervals. METHODS: This is a prospective cohort study. Two hundred (160 female; 40 male) end-stage osteoarthritis patients who underwent primary TKA were studied. An inclusion criterion was patient with end-stage osteoarthritis. Clinically and serologically proven rheumatoid arthritis patients were excluded from the study. The synovium excised during the TKA procedure was sent for the HP examination. The statistical significance was measured with the Chi-square test and two-sample t-test. RESULTS: A total of 184 out of the 200 patients (92%) knee synovium showed HP features of osteoarthritis. The discordant diagnoses and discrepant diagnosis rate was 8% and 7%, respectively, which is statistically significant by Chi-square test (p value < 0.0001 and p value = 0.0001). 14 of the patients (12 F:2 M) showed histological features of inflammatory/rheumatoid arthritis who were treated, two patients (all female) showed HP features of villonodular synovitis. The mean (SD) improvement in FJS-12 at six weeks in the concordant group (25.3 [17.6]) is significantly more than the discrepant group (15.3 [12.5]), p-value 0.0385. CONCLUSION: 8% of our patients exhibited unexpected results. The study showed a 7% rate of discrepant diagnosis. This discrepant diagnosis if missed and untreated, would have affected the function and long-term survival of the implanted TKA.
33573628 Bone mineral density assessment by DXA in rheumatic patients with end-stage osteoarthritis 2021 Feb 11 BACKGROUND: Patients with rheumatic diseases have a high risk for joint destruction and secondary osteoarthritis (OA) as well as low bone mineral density (BMD, i.e., osteoporosis). While several factors may lead to low BMD in these patients, the value of BMD measurements in rheumatic patients with end-stage OA scheduled for total joint arthroplasty is unknown. METHODS: In this retrospective cross-sectional study of 50 adults with secondary OA due to rheumatic diseases, we evaluated dual energy X-ray absorptiometry (DXA) measurements of both hips and the spine performed within 3 months prior to arthroplasty (n = 25 total hip arthroplasty, THA; n = 25 total knee arthroplasty, TKA). We analyzed various demographic and disease-specific characteristics and their effect on DXA results by using group comparisons and multivariate linear regression models. RESULTS: Although patients undergoing TKA were younger (63.2 ± 14.2 vs. 71.0 ± 10.8 yr., p = 0.035), osteoporosis was observed more frequently in patients scheduled for TKA than THA (32% vs. 12%). Osteopenia was detected in 13/25 patients (52%) in both the THA and TKA cohort. In the THA cohort, female sex, lower BMI and prednisolone use were associated with lower T-score in the hip. In TKA patients, higher OA grade determined by Kellgren-Lawrence score was associated with lower T-score in the hip of the affected side. CONCLUSIONS: Osteoporosis is present in a considerable frequency of rheumatic patients with end-stage OA, and THA and TKA patients show distinct frequencies and risk factors of low BMD. Our findings point to a potential value of DXA regarding preoperative evaluation of bone status.
33544432 Distinct DNA Methylation Patterns of Rheumatoid Arthritis Peripheral Blood and Synovial Ti 2021 Mar OBJECTIVE: To study epigenetic patterns in T lymphocytes that accumulate in the rheumatoid arthritis (RA) synovium, we characterized DNA methylation of CD3(+) T cells in peripheral blood and synovial tissue in patients with RA and osteoarthritis (OA). METHODS: Genomic DNA of CD3(+) T cells was isolated from patients with RA (n = 8) and OA (n = 5) from blood or the synovium at the time of an arthroplasty using antibodies and magnetic beads. Methylation was measured by using the Illumina Infinium MethylationEPIC Kit. Differentially methylated loci (DML) and differentially methylated genes (DMGs) were identified by using Welch's t-test. Principal component analysis, hierarchical clustering, and pathway analysis were used to determine relationships among groups. RESULTS: When we compared DNA methylation of CD3(+) T cells between peripheral blood and synovial tissue within each disease, 4615 and 164 DML were identified in RA and OA samples, respectively, resulting in 832 and 36 DMGs. A principal component analysis showed that methylation differences in T cells were greater on the basis of on location (blood vs synovium) rather than disease (RA vs OA). Differentially modified pathways were significantly enriched between RA blood and synovial T cells, especially in genes related to complement, integrin cell surface interactions, and the P53 pathway. The limited number of DMGs identified between OA blood and synovial T cells did not conform to biologic pathways. CONCLUSION: The patterns of DNA methylation in RA show location-specific differences related to immune pathways, whereas methylation differences in OA are limited. The RA joint-specific signatures could be due to selective accumulation of T-cell populations or expansion of differentially marked adaptive immune cells. Understanding epigenetic patterns could provide clues to the types of T cells that accumulate in the RA joint and identify potential therapeutic targets.
34913611 Pain Reduction in Rheumatoid Arthritis Patients Who Use Opioids: A Post Hoc Analysis of Ph 2022 Mar OBJECTIVE: Pain reduction with baricitinib was assessed in patients with rheumatoid arthritis (RA) who either used opioids or did not use opioids during three randomized, double-blind phase 3 trials. METHODS: Analysis populations were as follows: i) baricitinib 4 mg once daily versus placebo groups integrated from RA-BEAM (NCT01710358) for patients with inadequate response (IR) to methotrexate, RA-BUILD (NCT01721057) with IR to conventional disease-modifying antirheumatic drugs, and RA-BEACON (NCT01721044) with IR to at least one tumor necrosis factor inhibitors; ii) baricitinib 2 mg versus placebo from RA-BUILD and RA-BEACON; and iii) adalimumab 40 mg every other week versus placebo from RA-BEAM. Pain was measured by the Patient Assessment of Pain Visual Analog Scale. Analysis of covariance modeling assessed differences in pain reduction between treatments at each time point through Week 24, with an interaction term to test heterogeneous treatment effects across opioid users and nonusers. RESULTS: Baricitinib 4 mg had greater pain reduction versus placebo in opioid users and nonusers (P < 0.05) at all time points starting from Week 1; the pain reduction was similar between opioid users and nonusers. Baricitinib 2 mg had greater pain reduction versus placebo in opioid users and nonusers starting at Week 4. A significant difference in pain reduction was not observed for adalimumab versus placebo in the opioid users but was observed in nonusers at all time points. CONCLUSION: Pain reduction was observed and was similar between opioid users and nonusers with baricitinib 2 mg and 4 mg but not adalimumab in this post hoc analysis.