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ID PMID Title PublicationDate abstract
35093832 An increased intake of nutrients, fruits, and green vegetables was negatively related to t 2022 Mar Daily food intake plays an important role in the pathogenesis of arthritis. However, an association between arthritis, food intake, and cardiovascular disease (CVD) risk remains unclear. We hypothesized that higher intakes of nutrients, fruits, and vegetables are associated with a lower risk of arthritis, osteoarthritis (OA), and rheumatoid arthritis (RA) in the Korean population with various comorbidities. This study aims to identify the association between arthritis, OA, RA, food intake, and CVD risk among the elderly population. We conducted a cross-sectional study of 33,966 eligible subjects aged >50 years who completed the 2009-2019 Korea National Health and Nutrition Examination Survey. Logistic regression was used to identify associations between the presence of arthritis, OA, and RA and risk factors and to predict risks of arthritis, OA, and RA based on marginal effects. The prevalence of arthritis (odds ratio [OR] 1.26; 95% confidence interval [CI], 1.15-1.37) and OA (OR 1.24; 95% CI, 1.14-1.36) were significantly higher among individuals with a high risk of CVDs compared with those with low risk. A 2-fold increase in daily vitamin B1, B2, polyunsaturated fatty acids, and n-3 fatty acid consumption is associated with a significantly lower risk of arthritis and OA development. The ORs for high consumption of fruit were 0.72 (0.54-0.95) in arthritis, and 0.70 (0.52-0.94) in OA, in comparison with the low-consumption group. Furthermore, the OR for high consumption of green vegetables was 0.74 (0.55-0.98) in arthritis. Of note, people who have arthritis, or OA, have a significantly increased CVD risk. In conclusion, high consumption of nutrients, fruits, and vegetables was found to be associated with the presence of arthritis and OA. More research is needed to explore whether interactions between intake of nutrients, fruits, and vegetables affect the presence of arthritis, OA, and CVDs.
35326658 Expression of PD-1, PD-L1 and PD-L2 in Lymphomas in Patients with Pre-Existing Rheumatic D 2022 Mar 15 Current research seeks to identify subgroups of non-Hodgkin lymphoma (NHL) patients responsive to PD-1 blocking agents. Whether patients with pre-existing rheumatic diseases might constitute such a subgroup is unknown. We determined intratumoral expression of PD-1 and its ligands in lymphoma patients with pre-existing rheumatic diseases. We included 215 patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) or Sjögren's syndrome with subsequent lymphoma and 74 diffuse large B-cell lymphoma (DLBCL) controls without rheumatic disease. PD-1 and PD-ligand immunohistochemical markers were applied on tumor tissue microarrays. The number of PD-1+ tumor infiltrating leukocytes (TILs) and proportions of PD-L1+ and PD-L2+ tumor cells and TILs were calculated and correlated with clinical data. Expression of PD-L1 in tumor cells and TILs was highest in classical Hodgkin lymphoma and DLBCL. In DLBCLs, expression of PD-1 in TILs and PD-L1 in tumor cells was similar in RA, SLE and controls. In RA-DLBCL, high expression of PD-L1 in tumor cells was significantly more common in patients with the most severe RA disease and was associated with inferior overall survival in multivariable analysis.
35200117 Non-adherence to methotrexate was associated with high disease activity and poor health-re 2022 Feb 17 OBJECTIVES: Although methotrexate (MTX) is the first-line drug for management of rheumatoid arthritis (RA), non-adherence to MTX is highly prevalent and under-recognised. Here, we investigated adherence to MTX and its impact on clinical outcomes during follow-up in patients with RA. METHODS: In total, 367 RA patients were included in this study, with patient visits conducted annually for 4 consecutive years. Adherence was defined by the medication possession ratio during the follow-up period. We divided the patients into two groups; patients who took ≥80% of their prescribed MTX doses and those who did not. In a prospective cohort, the generalised estimating equations were used to identify longitudinal associations between drug adherence and clinical outcomes including disease activity, physical function, and quality of life. RESULTS: Of the 367 RA patients, 8.7% were found to have taken MTX <80% during the period of follow up. After adjustment for confounders, non-adherence to MTX was significantly associated with higher DAS28-ESR during the follow-up period (coefficient β=0.989, 95%; CI: 0.603-1.375; p<0.001). In addition, non-adherence to MTX was a significant predictor of RAPID3 (coefficient β=1.847; 95% CI: 0.221-3.472; p=0.026) and EQ-5D (coefficient β= -0.051; 95% CI: -0.090-0.012; p=0.010) after adjustment for confounding factors. CONCLUSIONS: Non-adherence to MTX was significantly associated with worse clinical outcomes, as evidenced by higher disease activity, poorer physical function, and lower health-related quality of life during a 4-year follow-up of RA patients.
35084303 Alcohol consumption and the risk of mortality and myocardial infarction in patients with r 2022 Jan 25 OBJECTIVES: Many studies have found that moderate alcohol consumption is associated with lower risks of mortality and myocardial infarction (MI). Our aim was to examine the potential effects of alcohol on all-cause mortality and MI in rheumatoid arthritis (RA), a risk factor condition. METHODS: A cohort study (1995-2017) was conducted using medical records of RA patients from The Health Improvement Network in the United Kingdom (UK). Alcohol exposure was divided into non-drinkers, mild (1-7 UK units/week), moderate (8-14 UK units/week), moderate-high (15-21 UK units/week), and high (>21 UK units/week) consumption levels. We calculated hazard ratios (HRs) for the relation of alcohol consumption to all-cause mortality and MI, adjusting for covariates. RESULTS: Of 30,320 RA patients, 5,994 deaths and 1,098 MI cases occurred over 236,188 person-years. Mild-to-moderate alcohol use was associated with lower all-cause mortality in RA patients, including those taking methotrexate. The multivariable HRs (95% CI) for mortality by alcohol use category were non-drinkers 1.0, mild 0.80 (0.75-0.85), moderate 0.74 (0.67-0.82), moderate-high 0.84 (0.72-0.98), and high 0.99 (0.86-1.15). Mild, moderate-high, and high levels of alcohol use were associated with lower risk of MI among RA patients. The HRs MI risk by alcohol use category were non-drinkers 1.0, mild 0.81 (0.70-0.94), moderate 0.84 (0.68-1.04), moderate-high 0.51 (0.35-0.74), and high 0.59 (0.42-0.84). CONCLUSIONS: These findings suggest that mild-to-moderate alcohol use is associated with a lower mortality risk and overall alcohol use is associated with a lower MI risk in RA patients, similar to the general population.
34270471 Risk Factors of Carpal Tunnel Syndrome in Taiwan: A Population-Based Cohort Study. 2022 Jan 1 BACKGROUND: Carpal tunnel syndrome (CTS), 1 of the most common peripheral neuropathies of the upper extremity, has been studied for decades regarding its epidemiology and associated medical conditions. We conducted a large-scale, age- and gender-matched study from an Asian population database to investigate the relationship between the incidence and the demographic characteristics. METHODS: A retrospective cohort study using data of National Health Insurance Research Database was conducted. One million enrollees in Taiwan was used to identify 9442 patients with CTS and 37,768 randomly selected controls, in a control-case ratio of 4:1. Diagnoses of CTS were ascertained from January 1, 2003, to December 31, 2012. Sociodemographic and medical characteristics were evaluated to assess the correlation with CTS. RESULTS: Annual incidence of CTS was approximately 0.4% during the 10-year-period in Taiwan, with higher incidence rate in female sex and middle age of group (50-59 years). Among the medical conditions, previous wrist injuries, obesity, gout, and rheumatoid arthritis were associated with CTS most significantly. CONCLUSIONS: Carpal tunnel syndrome has presented a relatively constant incidence in Taiwan. Female gender with middle age seemed to have the highest incident rate during a 10-year period from 2003 to 2012. Among the risk factors of CTS, previous wrist injuries, obesity, gout, and rheumatoid arthritis were demonstrated to be the most significantly correlated comorbidities.
35522672 Macrophage activation syndrome in rheumatic disease: Clinical characteristics and prognosi 2022 OBJECTIVES: Macrophage activation syndrome (MAS) is a hyperinflammatory condition that is known to be secondary hemophagocytic lymphohistiocytosis (HLH) in patients with rheumatic disease. The aim of study was to evaluate the clinical manifestations and outcomes in patients with MAS with rheumatic disease. MATERIALS AND METHODS: We performed a retrospective study of 20 adult patients who were diagnosed with MAS from 2012 to 2020. MAS was classified according to the HLH-2004 criteria. Patients' information, including clinical features, laboratory findings, and treatment regimens, was collected, and the overall survival rate was estimated by the Kaplan-Meier method. RESULTS: Twenty patients (18 women, 35.6 ± 18.3 years) who met the HLH-2004 criteria also fulfilled the 2016 EULAR/ACR/PRINTO classification criteria for MAS, and HScore was higher than 169 (mean, 241.1). Fourteen patients with systemic lupus erythematosus and 6 patients with adult-onset Still's disease were included. All patients were treated initially with corticosteroids, and 16 patients required additional immunosuppressants. The overall survival at 3 and 6 months was 75.2% and 64.3%. In survivors, renal impairment was less common (7.7% versus 71.4%, p = 0.007), the levels of AST (364.0 versus 81.0 IU/L, p = 0.019) and LDH (1346.0 versus 343.0IU/L, p = 0.014), and platelet count (90.0 versus 43.0 × 109/L, p = 0.02) were higher in compared to non-survivors. Nine patients had opportunistic infections, five of whom died during admission. CONCLUSION: The mortality of patients with MAS associated with rheumatic disease remains high. Renal impairment, levels of AST and LDH, and platelet count might be associated with prognosis.
35563492 Decreased BAFF Receptor Expression and Unaltered B Cell Receptor Signaling in Circulating 2022 May 4 Animal models of autoimmunity and human genetic association studies indicate that the dysregulation of B-cell receptor (BCR) signaling is an important driver of autoimmunity. We previously showed that in circulating B cells from primary Sjögren's syndrome (pSS) patients with high systemic disease activity, protein expression of the BCR signaling molecule Bruton's tyrosine kinase (BTK) was increased and correlated with T-cell infiltration in the target organ. We hypothesized that these alterations could be driven by increased B-cell activating factor (BAFF) levels in pSS. Here, we investigated whether altered BCR signaling was already present at diagnosis and distinguished pSS from non-SS sicca patients. Using (phospho-)flow cytometry, we quantified the phosphorylation of BCR signaling molecules, and investigated BTK and BAFF receptor (BAFFR) expression in circulating B cell subsets in an inception cohort of non-SS sicca and pSS patients, as well as healthy controls (HCs). We found that both BTK protein levels and BCR signaling activity were comparable among groups. Interestingly, BAFFR expression was significantly downregulated in pSS, but not in non-SS sicca patients, compared with HCs, and correlated with pSS-associated alterations in B cell subsets. These data indicate reduced BAFFR expression as a possible sign of early B cell involvement and a diagnostic marker for pSS.
35408851 Salivary and Lacrimal Gland Alterations of the Epidermal Fatty Acid-Binding Protein (E-FAB 2022 Mar 23 The purpose of this study was to investigate the changes in E-FABP in the salivary and lacrimal glands of the Sjögren syndrome (SS) model non-obese diabetic mice (NOD). Cotton thread and ocular vital staining tests were performed on 10-week NOD male mice (n = 24) and age- and sex-matched wild-type (WT) mice (n = 25). Tear and saliva samples were collected at sacrifice for E-FABP ELISA assays. Salivary and lacrimal gland specimens underwent immunohistochemistry stainings for E-FABP. Real-time RT-PCR was also performed for the quantification of mRNA expression levels in the salivary and lacrimal glands. Corneal vital staining scores in the NOD mice were significantly higher compared with those for the wild-type mice (p = 0.0001). The mean tear E-FABP level showed a significantly lower concentration in the NOD mice (p = 0.001). The mean saliva E-FABP level also showed a significantly lower concentration in the NOD mice (p = 0.04). Immunohistochemistry revealed intense E-FABP staining in the LG acinar epithelium and less intense staining in the acinar epitheliae of the SGs in the NOD mice compared to the WT mice. Real-time RT-PCR for the mRNA expression of E-FABP showed a significantly decreased expression in the SG and a significant increase in the LG of the NOD mice compared to the WT mice. In conclusion, the E-FABP showed marked alterations in the tear film, saliva, lacrimal, and salivary glands of the NOD mouse, which may help explain the ocular surface changes in relation to the dry eye disease in this SS model mouse and keratoconjunctivitis sicca in SS patients.
34398226 Comparison of salivary gland MRI and ultrasonography findings among patients with Sjögren 2022 May 5 OBJECTIVES: This retrospective study compared MRI and US findings among patients with SS over a wide age range. METHODS: Ninety patients with SS aged 8-84 years who had undergone both MRI and US examinations were divided into four groups according to age, as follows: <18 years (juvenile SS, JSS), 9 patients; 18-39 years, 12 patients; 40-69 years, 53 patients; >69 years, 16 patients. Imaging findings of parotid glands (PGs) and submandibular glands (SMGs) were compared among the four groups. Furthermore, the relationships within and between imaging findings and various clinical findings were examined. RESULTS: On MRI, patients with JSS commonly exhibited multiple high-intensity spots in the PGs on MR sialography and fat-suppressed T2-weighted imaging. With increasing SS group age, the frequencies and numbers of the high-intensity spots were lower. Fat areas on MRI and hyperechoic bands on US were rarely observed in the PGs and SMGs of patients with JSS, whereas they were more common in patients with adult SS. In addition, the presence of hyperechoic bands on US, the presence of fat areas on MRI, and decreased salivary flow were associated with one another. CONCLUSION: Salivary gland imaging findings in patients with JSS were characterized by punctate sialectasis, whereas those findings in patients with adult SS were characterized by fatty degeneration. Distinct findings in patients with JSS and adult SS are likely to reflect differences in glandular lesion stage. MRI and US are presumably useful for evaluation of glandular lesion severity during follow-up.
35356004 The Shared Mechanism and Candidate Drugs of Multiple Sclerosis and Sjögren's Syndrome Ana 2022 OBJECTIVE: This study aimed to explore the shared mechanism and candidate drugs of multiple sclerosis (MS) and Sjögren's syndrome (SS). METHODS: MS- and SS-related susceptibility genes and differentially expressed genes (DEGs) were identified by bioinformatics analysis based on genome-wide association studies (GWAS) and transcriptome data from GWAS catalog and Gene Expression Omnibus (GEO) database. Pathway enrichment, Gene Ontology (GO) analysis, and protein-protein interaction analysis for susceptibility genes and DEGs were performed. The drugs targeting common pathways/genes were obtained through Comparative Toxicogenomics Database (CTD), DrugBank database, and Drug-Gene Interaction (DGI) Database. The target genes of approved/investigational drugs for MS and SS were obtained through DrugBank and compared with the common susceptibility genes. RESULTS: Based on GWAS data, we found 14 hub common susceptibility genes (HLA-DRB1, HLA-DRA, STAT3, JAK1, HLA-B, HLA-DQA1, HLA-DQA2, HLA-DQB1, HLA-DRB5, HLA-DPA1, HLA-DPB1, TYK2, IL2RA, and MAPK1), with 8 drugs targeting two or more than two genes, and 28 common susceptibility pathways, with 15 drugs targeting three or more than three pathways. Based on transcriptome data, we found 3 hub common DEGs (STAT1, GATA3, PIK3CA) with 3 drugs and 10 common risk pathways with 435 drugs. "JAK-STAT signaling pathway" was included in common susceptibility pathways and common risk pathways at the same time. There were 133 overlaps including JAK-STAT inhibitors between agents from GWAS and transcriptome data. Besides, we found that IL2RA and HLA-DRB1, identified as hub common susceptibility genes, were the targets of daclizumab and glatiramer that were used for MS, indicating that daclizumab and glatiramer may be therapeutic for SS. CONCLUSION: We observed the shared mechanism of MS and SS, in which JAK-STAT signaling pathway played a vital role, which may be the genetic and molecular bases of comorbidity of MS with SS. Moreover, JAK-STAT inhibitors were potential therapies for MS and SS, especially for their comorbidity.
35128866 [Effects of moxibustion on p53， SLC7A11， and GPX4 expression in synovial tissues of ra 2022 Jan 25 OBJECTIVE: To observe the effects of moxibustion on p53, cystine/glutamate antiporter solute carrier family 7 member 11 (SLC7A11), and glutathione peroxidase 4 (GPX4) in synovial tissues of rats with adjuvant arthritis (AA), so as to explore the mechanism of moxibustion in alleviating rheumatoid arthritis. METHODS: Eighty rats were randomly divided into normal, model, moxibustion, and medication groups (n=20 in each group). The AA model was established by exposure to wind, cold, and damp environmental factors combined with injection of complete Freund's adjuvant. Rats in the moxibustion group received suspended moxibustion at "Shenshu" (BL23) and "Zusanli" (ST36) alternately, while those in the medication group were treated with tripterygium glycoside tablet suspension (8 mg/kg) by gavage, once a day, for 15 successive days. The pathological change in synovial tissue of rat right knee joint was observed by HE staining. The protein and mRNA expression levels of p53, SLC7A11, and GPX4 in the synovial tissue were detected by Western blot and quantitative real-time PCR, respectively. The se-rum glutathione (GSH) and reactive oxygen species (ROS) contents were measured by colorimetry and fluorescence probe me-thod. RESULTS: Compared with the normal group, the model group exhibited synovial hyperplasia of the right knee joint, massive inflammatory cell infiltration, up-regulated mRNA and protein expression of p53 in synovial tissue, elevated serum ROS content (P<0.01), down-regulated mRNA and protein expression of SLC7A11 and GPX4 in synovial tissue, and lowered serum GSH content (P<0.01). Comparison with the model group showed that the synovial injuries in the moxibustion and medication groups were obviously alleviated. The mRNA and protein expression levels of p53 in the synovial tissues and the serum ROS content declined significantly (P<0.01), while the mRNA and protein expression of SLC7A11 and GPX4 in the synovial tissues and the se-rum GSH content increased (P<0.01). There was no significant difference in histopathological change of synovial tissue between the moxibustion group and medication group. However, the p53 protein expression in the synovial tissue and the level of serum ROS were significantly higher in the medication group than in the moxibustion group (P<0.05), while the GPX4 protein expression and serum GSH content were down-regulated (P<0.05). CONCLUSION: Moxibustion improves the inflammatory response in synovial tissue of AA model rats, which may be closely related to its regulation of the expression of ferroptosis-related factors.
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.
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.
35084306 CXCL-13 serum levels in patients with rheumatoid arthritis treated with abatacept. 2022 Jan 27 OBJECTIVES: C-X-C motif chemokine 13 (CXCL-13), which is expressed by synovial follicular dendritic cells and activated mature antigen-experienced T-helper cells, has been described as a surrogate marker of lymphoid phenotype of synovitis in rheumatoid arthritis (RA). A preferential response to anti-interleukin-6 receptor (IL-6R) as compared to anti-tumour necrosis factor alpha (TNFα) monotherapy has been described in patients with increased levels of CXCL-13. We hypothesised that serum levels of CXCL-13 could be used as a biomarker of response to treatment with abatacept (ABA), a T-cell co-stimulation blocker. METHODS: Serum levels of CXCL-13 and of soluble intracellular adhesion molecule 1 (sICAM-1) (a putative marker of the myeloid subtype of synovitis) were measured by indirect solid-phase enzyme immunoassays, before (T0) and after 6 months of therapy with ABA (T6) in 63 patients with RA. Circulating T follicular helper cells and B cell subpopulations were identified by flow-cytometry. RESULTS: At T0, CXCL-13 serum levels were higher in RA patients than in healthy controls (p=0.0001) and correlated with disease activity, while no difference between the two groups was observed as far as sICAM-1 levels. Serum levels of CXCL-13 levels decreased after therapy with ABA both in patients who achieved a clinical response (p<0.01) and in non-responders (p=0.01), whereas sICAM-1 levels did not significantly change. When comparing RA patients who responded to ABA with non-responders no significant difference of baseline serum levels of CXCL-13 was observed. CONCLUSIONS: CXCL-13 serum levels are raised in RA patients and decrease after therapy with ABA. We were not able to demonstrate that serum CXCL-13 levels predict the clinical response to ABA in RA patients.
35477339 Porphyromonas gingivalis amount in the tongue biofilm is associated with erosive arthritis 2022 Apr 28 BACKGROUND: Several data have demonstrated the occurrence of erosive arthritis in Systemic Lupus Erythematosus (SLE) patients. However, a few studies have focused on the pathogenic mechanisms involved in this feature. The implication of oral pathogens has been proved in Rheumatoid Arthritis: in particular, Porphyromonas gingivalis (Pg), by inducing citrullination, could trigger autoimmune response. Here, we evaluated amount of Pg on the tongue in a cohort of SLE patients with arthritis, focusing on the association with the erosive phenotype. METHODS: SLE patients with arthritis were enrolled. DAS28 was applied to assess activity. Erosive damage was evaluated by ultrasound at level of MCP (metacarpophalangeal) and PIP (proximal interphalangeals) joints. All subjects underwent a tongue cytologic swab in order to quantify the amount of Pg (real-time PCR). The bacterium expression was obtained from the ratio between the patient's DNA amount and that obtained from healthy subjects. RESULTS: 33 patients were enrolled (M/F 3/30; median age 47 years, IQR 17; median disease duration 216 months, IQR 180): 12 of them (36.4%) showed erosive damage, significantly associated with ACPA positivity (p = 0.03) and higher values of DAS28 (p = 0.01). A mean ratio of 19.7 ± 31.1 was found for Pg amount. Therefore, we used Pg mean values as threshold, identifying two groups of patients, namely, (high)Pg and (low)Pg. Erosive damage was significantly more frequent in (high)Pg patients in comparison with (low)Pg (60.0% vs 26.0%, p = 0.001). Furthermore, (high)Pg patients showed higher prevalence of skin manifestations, serositis, and neurological involvement (p = 0.005, p = 0.03, p = 0.0001, respectively). CONCLUSION: The possible contribution of oral microbiota in SLE erosive arthritis was here evaluated for the first time, finding a significant association between erosive damage and higher expression of Pg at tongue level.
35238767 Whole-body cryotherapy for the treatment of rheumatoid arthritis: a monocentric, single-bl 2022 Mar 1 OBJECTIVES: To evaluate effects of whole-body cryotherapy (WBC) in rheumatoid arthritis (RA). METHODS: Patients with active RA undergoing a 16-day multimodal rheumatologic complex treatment were randomly assigned to either WBC (6 applications in 14 days at -130°C for 3 min) or no treatment. The primary outcome was the difference between groups in pain on a numerical rating scale after intervention. Secondary outcomes assessed effects on i) disease activity, ii) functional capacity, iii) cytokine levels, and iv) use of analgesics. RESULTS: A total of 56 RA patients completed the trial (intervention group [IG]: 31 patients, control group [CG]: 25 patients). The mean change (± standard error) in pain after intervention was -2 in the IG (95% confidence interval [CI] -2.75 to -1.31, p<0.001) and -0.88 (95% CI -1.43 to -0.33, p=0.003) in the CG, with a baseline-adjusted between-group difference of -1.31 ± 0.4 (95% CI -2.1 to -0.53; p=0.002). Pain at the 12-week follow-up visit remained significantly below baseline values in the IG. Disease activity and functional capacity showed statistically and clinically meaningful improvement after intervention but were not significant at the 12-week follow up. TNF and IL-6 levels changed significantly in the IG. Eighteen of 31 (58%) patients of the IG reduced or discontinued analgesics at the 12-week follow-up. No WBC-related side effects were reported. CONCLUSIONS: WBC in RA reduces pain and disease activity significantly and in a clinically meaningful manner, resulting in a reduction of analgesics. These effects are potentially based on a change in cytokine levels.
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.
35649573 Risk of out-of-hospital cardiac arrest in patients with rheumatoid arthritis: a nationwide 2022 Jun AIM: Inflammatory cytokines in patients with rheumatoid arthritis (RA) directly affect cardiac electrophysiology by inhibiting cardiac potassium currents, leading to delay of cardiac repolarisation and QT-prolongation. This may result in lethal arrhythmias. We studied whether RA increases the rate of out-of-hospital cardiac arrest (OHCA) in the general population. METHODS: We conducted a nested case-control in a cohort of individuals between 1 June 2001 and 31 December 2015. Cases were OHCA patients from presumed cardiac causes, and were matched with non-OHCA-controls based on age, sex and OHCA date. Cox-regression with time-dependent covariates was conducted to assess the association between RA and OHCA by calculating the HR and 95% CI. Stratified analyses were performed according to sex and presence of cardiovascular diseases. Also, the association between OHCA and use of non-steroidal anti-inflammatory drugs (NSAIDs) in patients with RA was studied. RESULTS: We included 35 195 OHCA cases of whom 512 (1.45%) had RA, and 351 950 non-OHCA controls of whom 3867 (1.10%) had RA. We found that RA was associated with increased rate of OHCA after adjustment for cardiovascular comorbidities and use of QT-prolonging drugs (HR: 1.22, 95% CI: 1.11 to 1.34). Stratification by sex revealed that increased OHCA rate occurred in women (HR: 1.32, 95% CI: 1.16 to 1.50) but not in men (HR: 1.12, 95% CI: 0.97 to 1.28; P value interaction=0.046). OHCA rate of RA was not further increased in patients with cardiovascular disease. Finally, in patients with RA, use of NSAIDs was not associated with OHCA. CONCLUSION: In the general population, RA is associated with increased rate of OHCA in women but not in men.
35644944 Increased levels of sirtuin-1 in systemic lupus erythematosus. 2022 May 29 AIM: We investigated plasma sirtuin-1 (SIRT1) levels in systemic lupus erythematosus (SLE) patients, and discussed potential of plasma SIRT1 as a biomarker for SLE. METHODS: A total of 359 subjects, including 299 patients (89 SLE, 50 rheumatoid arthritis, 30 osteoarthritis, 30 gout, 38 Sjögren's syndrome, 20 ankylosing spondylitis, 30 mixed connective tissue disease, 12 systemic sclerosis) and 60 healthy controls were recruited. SIRT1 in plasma of SLE patients was detected by enzyme-linked immunosorbent assay. Relationship between SIRT1 levels, clinical, laboratory characteristics in SLE patients was discussed. Plasma SIRT1 to discriminate SLE from different rheumatic patients and healthy controls was assessed by receiver operating characteristic (ROC) curve analysis. RESULTS: SIRT1 levels were elevated in SLE patients compared with healthy controls (6.28 [5.89-6.68] vs 2.42 [2.10-2.74] ng/mL, P < .001). SIRT1 concentration in plasma was significantly associated with disease activity (r(s)  = .317, P < .001). Area under the ROC curve (AUC) analysis showed that compared to healthy controls, SIRT1 had a good ability for diagnosis of SLE (AUC = 0.986, P < .001). Compared with rheumatoid arthritis, osteoarthritis, Sjögren's syndrome, ankylosing spondylitis, mixed connective tissue disease and systemic sclerosis patients, the AUC of plasma SIRT1 in SLE patients was 0.982, 0.881, 0.810, 0.860, 0.781, 0.889, 0.736, respectively. When evaluating the discriminative power of SIRT1, the sensitivity and specificity for distinguishing SLE from non-SLE patients were 95.51%, 61.43%, respectively, at the optimal cut-off value of 4.323 ng/mL. CONCLUSION: Circulating SIRT1 was elevated in SLE, and might be a promising SLE diagnostic marker.
35405530 Binary acronym disambiguation in clinical notes from electronic health records with an app 2022 Apr 1 OBJECTIVE: The use of electronic health records (EHR) systems has grown over the past decade, and with it, the need to extract information from unstructured clinical narratives. Clinical notes, however, frequently contain acronyms with several potential senses (meanings) and traditional natural language processing (NLP) techniques cannot differentiate between these senses. In this study we introduce a semi-supervised method for binary acronym disambiguation, the task of classifying a target sense for acronyms in the clinical EHR notes. METHODS: We developed a semi-supervised ensemble machine learning (CASEml) algorithm to automatically identify when an acronym means a target sense by leveraging semantic embeddings, visit-level text and billing information. The algorithm was validated using note data from the Veterans Affairs hospital system to classify the meaning of three acronyms: RA, MS, and MI. We compared the performance of CASEml against another standard semi-supervised method and a baseline metric selecting the most frequent acronym sense. Along with evaluating the performance of these methods for specific instances of acronyms, we evaluated the impact of acronym disambiguation on NLP-driven phenotyping of rheumatoid arthritis. RESULTS: CASEml achieved accuracies of 0.947, 0.911, and 0.706 for RA, MS, and MI, respectively, higher than a standard baseline metric and (on average) higher than a state-of-the-art semi-supervised method. As well, we demonstrated that applying CASEml to medical notes improves the AUC of a phenotype algorithm for rheumatoid arthritis. CONCLUSION: CASEml is a novel method that accurately disambiguates acronyms in clinical notes and has advantages over commonly used supervised and semi-supervised machine learning approaches. In addition, CASEml improves the performance of NLP tasks that rely on ambiguous acronyms, such as phenotyping.