Browse

Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
35418172 Identification of poor prognostic joint locations in an early rheumatoid arthritis cohort 2022 Apr 14 BACKGROUND: Rheumatoid arthritis (RA) is a heterogeneous disease with established poor prognostic factors such as seropositivity, joint damage, and high disease activity at an early, treatment-naïve stage of disease. However, few studies have examined if specific joint locations are correlated with these factors in such a population. This analysis explored the potential correlation of individual swollen and erosive joints with other disease characteristics at baseline and with remission rates in a post-hoc analysis of the Phase III randomized AGREE study. METHODS: Methotrexate (MTX)-naïve, erosive, RF- and/or ACPA-positive early RA patients (N = 509) were retrospectively evaluated. Baseline joint swelling was analyzed for large and small joints. Baseline erosions were analyzed for wrist, MCP1-5, IP1, PIP2-5 and MTP1-5. Remission rates were assessed after 6 months of treatment with abatacept (ABA) + MTX (N = 256) or MTX (N = 253). The following statistical tests were used: Chi-Square or Fisher's exact test (categorical variables); Student's t-test or Wilcoxon rank-sum test (continuous variables); continuity-corrected Chi-square test (efficacy remission endpoints). RESULTS: Baseline swelling was most frequent in wrist (91.9%) and MCP2 joint (89.1%), while baseline erosion was most frequent in MTP5 joint (43.5%). Swollen shoulder was significantly correlated (p < 0.0001) with swelling of almost all other large or medium joints. Baseline swelling in the knee, temporomandibular joint (TMJ), wrist and elbow was highly correlated (p < 0.001) with higher tender and swollen joint counts, higher DAS28(CRP) and higher SDAI and CDAI. Baseline swelling was not correlated with erosion per joint, except for MCP2. The largest difference in mean Boolean remission rates at 6 months was in patients with baseline swollen wrist favoring ABA + MTX (14.0% vs 4.4%; p < 0.001). CONCLUSIONS: Swelling in the large and medium joints (knee, TMJ, elbow and wrist) was highly correlated with severe disease activity while MCP2 swelling seemed to be correlated with joint damage. The correlation of joint locations at an early, treatment-naïve stage with poor prognostic factors, higher disease activity and joint damage, could establish a rapidly progressing anatomical pattern in early RA. TRIAL REGISTRATION: ClinicalTrials.gov NCT00122382, registered July 2005.
35316991 Pyoderma gangrenosum induced by transcutaneous electrical nerve stimulation: a case report 2022 Mar Pyoderma gangrenosum (PG) is one of the neutrophilic dermatosis, a heterogenous group of rare inflammatory diseases affecting the skin. It is often associated with systemic diseases such as inflammatory bowel disease, rheumatoid arthritis or hematological malignancies. Classical PG is characterized by painful ulcers with violaceous, undermined border, often developing at sites of injury because of the typical pathergy phenomenon. Because of its polymorphic presentation, misdiagnosis and delayed diagnosis are common. We present a case of PG occurring after transcutaneous electrical nerve stimulation (TENS) in a young female patient with ulcerative colitis. Although electric current has previously been incriminated as a trigger for PG, to the best of our knowledge this is the first case precipitated by TENS. We report a typical case of PG occurring after an unusual stimulus and highlight the challenges that the diagnosis of this relatively rare pathology poses to the clinician.
34859834 The Factors Associated with Carpal Tunnel Syndrome Severity. 2022 AIM: To evaluate the effects of factors, which are associated with carpal tunnel syndrome (CTS) prevalence, on disease severity. MATERIAL AND METHODS: This retrospective study included 206 patients who were treated surgically for either moderate or severe CTS. Patients were grouped into moderate and severe CTS then compared regarding to age, gender, BMI, and presence of occupational factors as well as systemic diseases that are associated with CTS. RESULTS: Patients with moderate and severe CTS did not differ in age, gender, occupational risk factors, and most of the systemic diseases, including DM, hypothyroidism, rheumatoid arthritis, cardiovascular disease, renal insufficiency, and folate deficiency. The severe CTS group had a significantly higher BMI than the moderate CTS group. Moreover, vitamin B12 deficiency was significantly more common in the severe CTS group than in the moderate CTS group. CONCLUSION: Patients with severe CTS are more inclined toward surgery than those with moderate CTS. Controlling BMI and preventing vitamin B12 deficiency may help keep alleviate complaints related to CTS with less invasive treatment modalities.
35023421 Persistence of bDMARD therapy in Rheumatoid Arthritis after first-line TNF-inhibitor failu 2022 Jan 13 OBJECTIVE: The optimal choice of a second biological disease-modifying anti-rheumatic drug (bDMARD) after failure with first line tumour necrosis factor inhibitor (TNFi) represents a critical therapeutic challenge. This study aims to evaluate the persistence with treatment using second line bDMARDs with different mechanisms of action in rheumatoid arthritis (RA) patients with inadequate response to first line TNFi. METHOD: A retrospective cohort study on administrative healthcare databases was conducted. We analysed the relationship between different bDMARDs and persistence with treatment in RA patients who started second line bDMARD therapy according to two different strategies: cycling (second TNFi) or switching [change in mechanism of action: abatacept (ABA), tocilizumab (TCZ), and rituximab (RTX)] with or without concomitant conventional synthetic (cs) DMARDs. RESULTS: The cohort comprised 1434 patients. The mean age was 53.8 years and 1142 (79.6%) were women. Among second line bDMARDs, 969 patients (67.6%) started TNFi, 204 (14.2%) ABA, 145 (10.1%) RTX, and 116 (8.1%) TCZ. A bDMARD was prescribed as monotherapy in 359 patients (25.0%). The switching strategy showed a lower overall discontinuation rate [hazard ratio (HR) 0.72], while switching compared to cycling showed significantly better survival for ABA (HR 0.61) and RTX (HR 0.76), but no significant difference for TCZ (HR 0.82). A lower impact of better drug survival in the switching strategy occurred in patients with concurrent methotrexate. CONCLUSIONS: Among RA patients failing a first TNFi, switching is associated with marginally better persistence, in particular for ABA and RTX, with only marginal differences in patients on concurrent csDMARDs.
34962093 Evaluation of an Intervention to Support Patient-Rheumatologist Conversations About Escala 2022 Apr OBJECTIVE: This study's objective was to test whether an online video intervention discussing appropriate treatment escalation improves willingness to change treatment in people living with rheumatoid arthritis (RA). METHODS: We conducted a controlled, randomized trial among patients with RA enrolled in ArthritisPower, a United States patient registry. We recruited participants by email and surveyed their assessment of disease activity (patient global), satisfaction with disease control (patient acceptable symptom state), attitudes about RA medications, decisional conflict (decisional conflict scale), and willingness to modify RA treatment (choice predisposition scale, higher scores are better) if or when recommended by their rheumatologist. Intervention groups watched educational videos relevant to a treat-to-target (T2T) strategy, whereas control groups viewed vaccination-related videos as an "attention control." We compared the between-group difference in patients' willingness to modify RA treatment (primary outcome) and difference in decisional conflict about changing RA treatment (secondary outcome) after watching the videos using t tests. RESULTS: Participants with self-reported RA (n = 208) were 90% White and 90% women, with a mean (standard deviation) age of 50 (11) years, and 52% reported familiarity with the RA T2T strategy. We found a significant improvement in between-group difference in willingness to change RA treatment among intervention versus control participants (0.49 [95% confidence interval 0.09-0.88], P = 0.02). The effect size (Glass's delta) for the intervention was 0.48. Decisional conflict about treatment change decreased, but the between-group difference was not significant. CONCLUSION: This novel educational patient-directed intervention discussing appropriate treatment escalation was associated with improved willingness to change RA treatment if or when recommended by a rheumatologist. Further studies should evaluate whether this change in patients' predisposition translates into actual treatment escalation.
35501149 Male Sex Predicts a Favorable Outcome in Early ACPA-negative Rheumatoid Arthritis: Data Fr 2022 May 2 OBJECTIVE: The aim of the present study was to investigate if the relation between sex and clinical outcomes in early rheumatoid arthritis varies by autoantibody status. METHODS: Two inception cohorts of consecutive patients with early RA (symptom duration ≤12 months) in the Southern Region of Sweden were investigated. Patients were stratified by anti-citrullinated peptide antibody (ACPA) status. The primary outcome was remission (DAS28<2.6) at 12 months. Secondary outcomes were remission at 6 months and EULAR good response compared to baseline at 6 and 12 months. In logistic regression models, adjusted for age, DAS28 and HAQ at baseline, the relation between sex and clinical outcomes, stratified by ACPA status, was investigated. RESULTS: In total 426 patients with early RA were included, 160 ACPA-negative and 266 ACPA-positive. At 12 months, 27% of females and 24% of males with ACPA-positive RA achieved DAS28 remission. In ACPA-negative RA, 16% of females and 49% of males achieved DAS28 remission at 12 months. Males had higher odds of reaching remission at 12 months in the ACPA-negative patient group (pooled adjusted OR 4.79, 95% CI 1.97-11.6), but not in the ACPA-positive group (pooled adjusted OR 1.06, 95 % CI 0.49-2.30). CONCLUSION: Male sex was associated with better clinical outcomes in ACPA-negative early RA, but not in ACPA-positive early RA. The poor outcomes in females with early seronegative RA suggest that this represents a difficult to treat patient group.
32961016 Walking Disabilities in Association With Tenosynovitis at the Metatarsophalangeal Joints: 2022 Feb OBJECTIVE: The relationship between functional disability and magnetic resonance imaging (MRI) inflammation has been studied for the hands, but has not been well established for the feet, even though walking difficulties are common. Therefore, our objective was to study whether walking difficulties were associated with MRI inflammation at metatarsophalangeal (MTP) joints in early arthritis patients, at diagnosis and during 24 months of follow-up. METHODS: A total of 532 consecutive patients presenting with early arthritis reported on the presence and severity of walking difficulties (Health Assessment Questionnaire question 4a, scale 0-3), and underwent unilateral contrast-enhanced MRI of MTP joints 1-5 at baseline. In total, 107 patients had clinical and MRI data at follow-up (4, 12, and 24 months). MRI inflammation (synovitis, tenosynovitis, and osteitis) was scored in line with the Rheumatoid Arthritis Magnetic Resonance Imaging Scoring system. At baseline, the association of walking disability with MRI inflammation was assessed using regression. Longitudinally, the association between a change in walking disability with a change in MRI inflammation was studied with linear mixed models. RESULTS: At baseline, 81% of patients with walking disabilities had MRI inflammation at MTP joints, versus 68% without walking disabilities (P < 0.001). Total MRI inflammation (i.e., the sum of tenosynovitis, synovitis, and osteitis) was associated with severity of walking disability (β = 0.023, P < 0.001). Studying the MRI features separately, tenosynovitis, synovitis, and osteitis were all univariably associated with severity of walking disability (P < 0.001, P < 0.001, and P = 0.014, respectively). In multivariable analysis, the association was strongest for tenosynovitis. During follow-up, a decrease in MTP inflammation was associated with a decrease in walking disability (β = 0.029, P = 0.001); in multivariable analyses only, tenosynovitis was independently associated (β = 0.073, P = 0.049). CONCLUSION: Of the different inflamed tissues in MTP joints, predominantly MRI-detected tenosynovitis was associated with walking disabilities. Likewise a reduction in tenosynovitis related to a decrease in walking disabilities. These results increase our understanding of the involvement of tenosynovitis in walking disabilities in early arthritis.
35077491 Impact of delayed type hypersensitivity arthritis on development of heart failure by aorti 2022 AIMS: Patients with rheumatoid arthritis (RA) have increased risk of heart failure (HF). The mechanisms and cardiac prerequisites explaining this association remain unresolved. In this study, we sought to determine the potential cardiac impact of an experimental model of RA in mice subjected to HF by constriction of the ascending aorta. METHODS: Aorta was constricted via thoracotomy and placement of o-rings with inner diameter 0.55 mm or 0.66 mm, or sham operated. RA-like phenotype was instigated by delayed-type hypersensitivity arthritis (DTHA) two weeks after surgery and re-iterated after additional 18 days. Cardiac magnetic resonance imaging (MRI) was performed before surgery and at successive time points throughout the study. Six weeks after surgery the mice were euthanized, blood and tissue were collected, organ weights were documented, and expression levels of cardiac foetal genes were analysed. In a supplemental study, DTHA-mice were euthanized throughout 14 days after induction of arthritis, and blood was analysed for important markers and mediators of RA (SAP, TNF-α and IL-6). In order to put the latter findings into clinical context, the same molecules were analysed in serum from untreated RA patients and compared to healthy controls. RESULTS: Significant elevations of inflammatory markers were found in both patient- and murine blood. Furthermore, the DTHA model appeared clinically relevant when compared to the inflammatory responses observed in three prespecified RA severity disease states. Two distinct trajectories of cardiac dysfunction and HF development were found using the two o-ring sizes. These differences were consistent by both MRI, organ weights and cardiac foetal gene expression levels. Still, no difference within the HF groups, nor within the sham groups, could be found when DTHA was induced. CONCLUSION: DTHA mediated systemic inflammation did not cause, nor modify HF caused by aortic constriction. This indicates other prerequisites for RA-induced cardiac dysfunction.
35210510 Local inhibition of TGF-β1 signaling improves Th17/Treg balance but not joint pathology d 2022 Feb 24 TGF-β1 is an important growth factor to promote the differentiation of T helper 17 (Th17) and regulatory T cells (Treg). The potential of TGF-β1 as therapeutic target in T cell-mediated diseases like rheumatoid arthritis (RA) is unclear. We investigated the effect of TGF-β1 inhibition on murine Th17 differentiation in vitro, on human RA synovial explants ex vivo, and on the development of experimental arthritis in vivo. Murine splenocytes were differentiated into Th17 cells, and the effect of the TGF-βRI inhibitor SB-505124 was studied. Synovial biopsies were cultured in the presence or absence of SB-505124. Experimental arthritis was induced in C57Bl6 mice and treated daily with SB-505124. Flow cytometry analysis was performed to measure different T cell subsets. Histological sections were analysed to determine joint inflammation and destruction. SB-505124 potently reduced murine Th17 differentiation by decreasing Il17a and Rorc gene expression and IL-17 protein production. SB-505124 significantly suppressed IL-6 production by synovial explants. In vivo, SB-505124 reduced Th17 numbers, while increased numbers of Tregs were observed. Despite this skewed Th17/Treg balance, SB-505124 treatment did not result in suppression of joint inflammation and destruction. Blocking TGF-β1 signalling suppresses Th17 differentiation and improves the Th17/Treg balance. However, local SB-505124 treatment does not suppress experimental arthritis.
35240430 Measurement of glycosylated ferritin with Concanavalin A: Assay design, optimization and v 2022 Apr 1 INTRODUCTION: Ferritin is the major iron-storage glycoprotein found in all tissues. Ferritin glycosylation can be assessed by the differential affinities of ferritin glycoforms for Concanavalin A (ConA), a lectin. The fraction of serum ferritin bound to ConA is called "glycosylated ferritin" (GF). Low GF reflects macrophagic activation and is an essential biomarker used in adult-onset Still's disease (AOSD), macrophage activation syndrome (MAS) and Gaucher disease diagnosis and therapeutic management. To date, no complete assay description and method validation according to the ISO 15189 standard has been published. This study aimed to describe and validate our method used for GF measurement and describe GF values observed in patients. MATERIALS AND METHODS: Ferritin glycoforms were separated based on their affinities for ConA using commercially available TRIS-barbital buffer, Sepharose and ConA/Sepharose 4B gels. Ferritin concentrations were measured on the Siemens Dimension Vista 1500®. We analysed 16,843 GF values obtained between 2000 and 2021 from our database of patients. RESULTS: Optimal separation of ferritin glycoforms was obtained by 15-min incubation of serum with ConA/Sepharose at pH 8. The optimized volume were 0.4 mL for total serum ferritin (TSF) 30-1000 µg/L and 0.5 mL for TSF 1000-2500 µg/L. Serum with higher TSF should be pre-diluted in the TRIS-barbital buffer. Reproducibility of ferritin measurement in the TRIS-barbital buffer matrix was excellent (intra-assay CV < 1%; inter-assay CV < 4%). Reproducibility of GF assay was good (intra-assay CV < 10% for low and high ferritin samples, respectively; and inter-assay CV < 10%). Inter-operator variability was 21.6% for GF < 20%. Ferritin was stable for up to 3 days in the TRIS-barbital buffer. An inter-laboratory exchange program conducted with another French hospital showed good agreement between results. In our database, <20% GF levels were scarce, compatible with the low prevalence of Still's disease, MAS, and Gaucher disease. The 95% confidence interval for GF was [26-58]%, lower than values described in the literature for healthy individuals. CONCLUSION: Thanks to good performances, this technique can become readily available for laboratories servicing patients with AOSD, MAS (including severe COVID-19 patients) and Gaucher disease patients.
35068221 Hyperinflammation after anti-SARS-CoV-2 mRNA/DNA vaccines successfully treated with anakin 2022 Feb The current SARS-CoV-2 pandemic diffused worldwide has encouraged the rapid development of vaccines to counter the spread of the virus. At present in Italy, 75.01% of the population completed the vaccination course (AIFA.gov.it) and very few adverse events have been recorded by now. Side-effects related to a theoretical over-reaction of the immune system in response to vaccines administration have been described, and the possibility that an autoimmune or a hyperinflammatory condition may occur was recently observed. Herein, we report four cases of hyperinflammatory syndrome with features indicative of Adult-onset Still's disease (AOSD) and macrophage activation syndrome (MAS), occurred after anti-SARS-CoV-2 vaccine injection and seen at our Unit between March and May 2021. Since interleukin (IL)-1 is one of the pivotal cytokines involved in AOSD pathogenesis, the inhibition of IL-1 is crucial in ameliorating the clinical symptoms of those patients. Moreover, it has been highlighted the central role of IL-1 as a hallmark of the hyperinflammatory status elicited by SARS-CoV-2 infection. In this case series, we successfully employed the IL-1 receptor antagonist anakinra to curb the cytokine release likely unleashed by the vaccine stimulation in potentially predisposed subjects. We also made a literature search to detect other patients with hyperinflammation temporally related to vaccines injection who benefited from IL-1 inhibition, while other AOSD/MAS-like described syndromes improved with other immunomodulatory strategies.
35439369 Cost-effectiveness of the early arthritis clinic organizational model: the ELECTRA study. 2022 Apr 19 OBJECTIVE: Early diagnosis and tight control improve outcomes of rheumatoid arthritis (RA). However, it is not known whether establishing an Early Arthritis Clinic (EAC) is sustainable for national health systems. This analysis aims to compare effectiveness and costs of an EAC compared to patients followed as for standards of care. METHODS: A retrospective study on administrative health databases of patients with a new diagnosis of RA was conducted: 430 patients followed in an EAC were enrolled, and 4 non-EAC controls were randomly matched for each of them. During two years of follow up, the mean healthcare costs (outpatient, inpatient, pharmaceutical and global) and 3 effectiveness measures (number and length of hospitalization and quality of care) of EAC and non-EAC were estimated. The incremental cost-effectiveness ratio was calculated as well as the cost-effectiveness acceptability curve. RESULTS: The cohorts included patients with a mean age of 55.4 years and 1506 (70%) females. Mean pharmaceutical (2602 versus 1945 €) and outpatient (2447 versus 1778 €) costs were higher in the EAC cohort. Conversely, a higher rate of non-EAC patients had a low adherence to quality-of-care indicators. The expected number of hospitalizations and the length of stay were statistically significant higher in non-EAC versus EAC. CONCLUSION: Despite an expected increase in outpatient costs (visits and diagnostic tests) and pharmaceutical costs, the reduction in terms of number and length of hospitalizations and the higher adherence to international quality of care guidelines support the effectiveness of the EAC model.
35211629 Pharmacological Inhibition of Glutaminase 1 Normalized the Metabolic State and CD4+ T Cell 2022 Previous studies have shown that abnormal metabolic reprogramming in CD4+ T cells could explain the occurrence of several autoimmune disorders, including Sjogren's syndrome (SS). However, therapeutic targets of the abnormal metabolism of CD4+ T cells remain to be explored. Here, we report that glutaminase 1 (Gls1), a pivotal factor in glutaminolysis, might be involved in the pathogenesis of SS. The expression of Gls1 was upregulated in infiltrated labial CD4+ T cells and circulating CD4+ T cells of SS patients. Inhibiting Gls1 with BPTES significantly abolished the proliferation rate, as indicated by EdU, CFSE, and Western blot analyses. Additionally, BPTES downregulated the extracellular acidification rate (ECAR) and oxygen consumption rate (OCR) values of activated CD4+ T cells from SS mice. In vivo, we injected different doses of BPTES into SS-like NOD/Ltj mice and found that 10 mg/kg BPTES significantly restored the salivary flow rate. Histological and qRT-PCR analyses showed that this concentration of BPTES attenuated lymphocytic infiltration and the numbers of PCNA-positive cells and CD4+ T cells. The proportions of IFNγ-producing cells and IL-17A-producing cells and the expression of several proinflammatory cytokines, including IFNγ and IL-17A, were also affected in the salivary glands of SS-like mice. Cytokine production in circulating serum was analyzed and showed that BPTES downregulated the effector functions of Th17 cells and Th1 cells. Collectively, these results indicate a positive relationship between Gls1 and SS development. Pharmacological inhibition of Gls1 with BPTES could normalize the effector functions of CD4+ T cells and effectively attenuate the symptoms of SS.
35649554 Correlation of fibromyalgia survey questionnaire and quantitative sensory testing among pa 2022 Jun 1 OBJECTIVE: Patients with rheumatoid arthritis (RA) commonly demonstrate disordered pain processing, associated with high pain sensitization. Pain sensitization is often assessed using quantitative sensory testing (QST), which is burdensome to patients. The self-administered fibromyalgia survey questionnaire (FSQ) has been proposed as a low-burden, surrogate measure of central pain sensitization. We examined the correlation between FSQ and QST in patients with active RA. METHODS: Participants in the Central Pain in Rheumatoid Arthritis (CPIRA) cohort underwent FSQ and QST evaluation at enrollment. QST measures included pressure pain threshold (PPT) at the thumb, trapezius, wrist and knee; temporal summation (TS) at the wrist and arm; and conditioned pain modulation (CPM). Partial Spearman correlation between FSQ and each QST measure was assessed, adjusted for demographic factors, study site, disease characteristics, and pain catastrophizing. Sensitivity analyses included a) stratified analysis by sex and b) evaluation of how each component of FSQ associates with the QST measures. RESULTS: Among 285 participants with active RA, FSQ was weakly but statistically significantly correlated with PPT ( r = -0.21 to -0.31), and TS ( r = 0.13 to 0.15) at all sites in unadjusted analyses. After adjustment, statistically significant correlations persisted for PPT at all sites except the thumb, and for TS at the wrist. Sensitivity analyses did not identify differences in association based on sex or with individual FSQ components. CONCLUSION: FSQ and QST were correlated among participants with active RA, but the strength of association was weak. QST and FSQ are not interchangeable measures of pain sensitization.
35222675 Tetrandrine Ameliorates Rheumatoid Arthritis in Mice by Alleviating Neutrophil Activities. 2022 Rheumatoid arthritis (RA) is a common autoimmune disease worldwide. Neutrophils play critical roles in the onset and development of RA and are the promising target for RA treatment. Tetrandrine is a bis-benzyl isoquinoline alkaloid derived from the traditional Chinese herbal Stephania tetrandra S. Moore. Tetrandrine is effective in alleviating RA by inhibiting macrophage inflammatory response, fibroblast overproliferation, and pannus formation. However, whether tetrandrine regulates the activities of neutrophils in RA is largely unknown. In this study, we adopted adjuvant-induced arthritis (AA) murine model to explore the effect of tetrandrine on RA and neutrophils. Twenty-eight mice were divided into four groups. The control group was injected with PBS in the limbs and treated with PBS by intraperitoneal injection (i.p.) from Day 10 to Day 37. The arthritis murine model was induced by injecting FCA into the ankle joints of hind limbs. The AA group, the AA + TET group, and the AA + DEX group mice were treated with PBS, tetrandrine (6 mg/kg), or dexamethasone (1 mg/kg) i.p. daily, respectively. Arthritic scores were evaluated, and the joint diameter was measured every three days. A cytometric bead assay was performed to measure the concentrations of IFN-γ, TNF-α, and IL-6 in the serum. H&E staining and Safranin O-fast staining were adopted to monitor the tissue changes in the joint. Immunohistochemistry assays were applied to detect the MPO, NE, CitH3, and PAD4 expression levels. To assess the effect of tetrandrine on neutrophil activities in vitro, CCK8 tests were applied to determine cell viability. The qPCR and ELISA were performed to determine IL-1β and IL-6 expression levels. Immunofluorescence assays were performed to measure the formation of NETs. The results indicated that tetrandrine significantly alleviated the symptoms of RA in terms of the ankle diameter (from 4.629 ± 2.729 to 3.957 ± 0.257; P < 0.01) and ankle score (from 4.000 ± 0.000 to 3.286 ± 0.756; P < 0.05). Tetrandrine treatment significantly increased the cartilage areas and decreased serum IL-6 significantly (from 5.954 ± 2.127 to 2.882 ± 2.013; P < 0.01). The immunohistochemistry assays also showed decreased expression levels of NE, MPO, PAD4, and CitH3 induced by tetrandrine in comparison with the AA group (P < 0.01). The qPCR assays and ELISAs showed that tetrandrine had an anti-inflammatory effect in vitro by significantly inhibiting IL-6 (P < 0.01). The immunofluorescence assays showed that NET formation induced by PMA could be reduced by tetrandrine (P < 0.01). In conclusion, tetrandrine has good efficacy in treating RA by regulating neutrophil-involved inflammation and NET formation.
35463097 The Impact of Traditional Chinese Medicine QingreHuoxue Treatment and the Combination of M 2022 Traditional Chinese medicine (TCM) has been used successfully to treat rheumatoid arthritis (RA). QingreHuoxue treatment (QingreHuoxue decoction [QRHXD]/QingreHuoxue external preparation [QRHXEP]) is a Chinese medicine treatment for RA. To date, very few studies have compared the long-term effects of QRHXD with those of conventional disease-modifying antirheumatic drugs on RA disease activity and radiological progression. QRHXD delayed the radiological progression and showed long-term clinical efficacy of RA. In clinical experiments, the clinical evidence of delaying the radiological progression of RA patients was obtained. A portion of the patients who participated in the "Traditional Chinese Medicine QingreHuoxue Treatment vs. the Combination of Methotrexate and Hydroxychloroquine for Active Rheumatoid Arthritis" study were followed up for 52 weeks, and intention-to-treat (ITT) and compliance protocol (PP) analyses were used to collect and compare the clinical indicators and imaging data between baseline and week 52. Two radiologists who were blind to treatment scored the images independently. Of the 468 subjects, 141 completed the 52-week follow-up. There were no significant differences among the three groups: the traditional Chinese medicine comprehensive treatment group, the Western medicine treatment group, and the integrated traditional Chinese and Western medicine treatment group. There were no differences in the total Sharp score, joint space stenosis score, and joint erosion score at baseline or 52 weeks. In the comparison of the estimated annual radiographic progression (EARP) and the actual annual Sharp total score changes among the three groups, the actual changes were much lower than the EARP at baseline. The radiological progress in all three groups was well controlled. Results of the ITT and PP data sets showed that the disease activity score 28 level of the three groups at 52 weeks was significantly lower than that at baseline. During the 52-week treatment period, the clearance of heat and promotion of blood circulation controlled disease activity and delayed the radiological progress of active RA.
35453601 Angiogenic T Cells: Potential Biomarkers for the Early Diagnosis of Interstitial Lung Dise 2022 Apr 5 (1) Background: We explored, for the first time, the contribution of angiogenic T cells (TAng) in interstitial lung disease associated to autoimmune disease (AD-ILD(+)) as potential biomarkers of the disease, evaluating their role in the underlying vasculopathy and lung fibrosis. Additionally, the relationship of TAng with clinical manifestations and cellular and molecular endothelial dysfunction-related biomarkers was assessed. (2) Methods: We included 57 AD-ILD(+) patients (21 with rheumatoid arthritis (RA)-ILD(+), 21 with systemic sclerosis (SSc)-ILD(+) and 15 with other AD-ILD(+)) and three comparative groups: 45 AD-ILD(-) patients (25 RA-ILD(-) and 20 SSc-ILD(-)); 21 idiopathic pulmonary fibrosis (IPF) patients; 21 healthy controls (HC). TAng were considered as CD3(+)CD184(+)CD31(+) by flow cytometry. (3) Results: A similar TAng frequency was found between AD-ILD(+) and IPF, being in both cases lower than that observed in AD-ILD(-) and HC. A lower TAng frequency was associated with negative Scl-70 status and lower FEV1/FVC ratio in SSc-ILD(+), as well as with men in RA-ILD(+) and non-specific interstitial pneumonia radiological pattern in other AD-ILD(+). No relationship between TAng and endothelial progenitor cells, endothelial cells and vascular endothelial growth factor gene expression and protein levels was disclosed. (4) Conclusions: Our findings suggest TAng as potential biomarkers for the early diagnosis of ILD in AD.
28613704 Sweet Syndrome. 2022 Jan Sweet syndrome, first described in 1964 by Robert Douglas Sweet, is an acute febrile neutrophilic dermatosis. Neutrophilic dermatoses consist of a group of non-infectious disorders that are characterized by neutrophilic infiltration of the skin (epidermis, dermis, or hypodermis) with or without true vasculitis. Neutrophilic dermatoses can be idiopathic or secondary to an underlying disorder, localized or generalized, and may or may not have extracutaneous manifestations. Sweet syndrome belongs to the non-vasculitic group of neutrophilic dermatoses disorders, with others including pyoderma gangrenosum, pustular psoriasis, reactive arthritis (Keratoderma blennorrhagicum), Bowed-associated dermatosis-arthritis syndrome (BADAS), rheumatoid neutrophilic dermatosis, Behcet's disease, acne fulminans, Familial Mediterranean Fever, SAPHO syndrome, etc. Sweet syndrome characteristically demonstrates the sudden onset of well defined tender plaques or nodules accompanied by fever, arthralgias, ocular inflammation, headaches, and, rarely, oral or genital lesions. It may also be associated with other extracutaneous systemic manifestations, which are, however, rare. The goal of pharmacotherapy in acute febrile neutrophilic dermatosis (Sweet syndrome) is to reduce morbidity and complications. The best first-line option is systemic or topical corticosteroids if the lesions are limited. If corticosteroids are contraindicated, anti-inflammatory medications such as colchicine or dapsone are available options.
35499771 Challenges of caring for homeless patients with inflammatory arthritis: 12-month follow-up 2022 Jun Homelessness is a public health crisis and there is a paucity of information about patients with rheumatic disease experiencing homelessness. We sought to develop approaches to improve care for this unique patient population. We previously reported observations on 17 homeless patients with inflammatory arthritis (15 rheumatoid arthritis (RA), 2 psoriatic arthritis (PsA)). We obtained follow-up information from our original 17 patients and compared this to data summarized and published about them from 12 months previously. We also created and administered a 100-question needs assessment survey. Follow-up 12-month clinical information was available from 13/17 homeless and 13/17 non-homeless controls. Homeless patients remained less well with more disease than non-homeless patients-poorer access to clinic appointments (80% vs 91%, p < 0.05), more emergency services use (20 vs 5 ED visits), less DMARDs use (43% vs 100%, p < 0.01), and more steroid use (29% vs 0%, p < 0.01). Homeless patients also had higher inflammatory markers than non-homeless patients (ESR 32 vs 26 mm/h and CRP 17 vs 5 mg/L), although these findings were not statistically significantly different. Seventy-eight percent of homeless patients were stable, 14% improved, and 7% worse; 21% had stable controlled and 57% stable active disease vs 62% and 0% of non-homeless (p < 0.01). Among the homeless, 6 (4 RA, 2 PsA) completed the survey, 2 declined, and 9 could not be reached. All 6 had found housing although all still had housing insecurity; 4 (67%) were homeless in the past. Three out of six (50%) obtained housing from social assistance during hospitalization following disease exacerbation while homeless. The average monthly income was $873. 5/6 (83.3%), were unable to work due to health, and were in considerable pain that adversely impacted their physical and mental health and ability to perform ADLs. Their perceived "greatest need" included dental care, physical therapy, knee surgery, employment, socialization secondary to isolation, and stable housing. Our understanding of the unique challenges of patients with rheumatic disease experiencing homelessness is improved, but not complete. Strengthened collaboration between street medicine providers and rheumatologists is necessary to improve care for homeless patients, especially given poorer outcomes compared with non-homeless counterparts. Key Points • We report 12-month follow-up information from our original 17 homeless patients with inflammatory arthritis (related in this journal in 2021) and their responses to an extensive needs assessment survey designed to identify barriers to care. • Homeless patients with inflammatory arthritis continued to have worse disease outcomes, use more corticosteroids and less DMARDs, and be seen less often in rheumatology clinics and more frequently in emergency departments than their non-homeless counterparts. • Survey data indicated that social assistance during hospitalization was a key area where healthcare providers could intervene to provide housing security for homeless patients and improve outcomes. Patients perceived "greatest needs" went beyond housing and rheumatological care and critically included access to social/specialty services. • Street medicine is the direct delivery of healthcare to people experiencing homelessness wherever they reside. Our observations, obtained in collaboration with street medicine colleagues, suggest important and salutary opportunities for this partnership to improve care for these particular patients.
35371265 Efficacy and Safety of Mesenchymal Stem Cell Transplantation in the Treatment of Autoimmun 2022 OBJECTIVE: To evaluate the efficacy and safety of mesenchymal stem cell (MSC) transplantation in the treatment of autoimmune diseases. METHODS: The Chinese and English databases were searched for clinical research on the treatment of autoimmune diseases with mesenchymal stem cells. The search time range is from a self-built database to October 1, 2021. Two reviewers independently screened the literature according to the inclusion and exclusion criteria, extracted data, and evaluated the bias of the included studies. RevMan 5.3 analysis software was used for meta-analysis. RESULTS: A total of 18 RCTs involving 5 autoimmune diseases were included. The 5 autoimmune disease were rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), inflammatory bowel disease, ankylosing spondylitis, and multiple sclerosis. For RA, the current randomized controlled trials (RCTs) still believe that stem cell transplantation may reduce disease activity, improve the clinical symptoms (such as DAS28), and the percentage of CD4+CD 25+Foxp3+Tregs in the response group increased and the percentage of CD4+IL-17A+Th17 cells decreased. The total clinical effective rate of RA is 54%. For SLE, the results showed that mesenchymal stem cell transplantation may improve SLEDAI [-2.18 (-3.62, -0.75), P = 0.003], urine protein [-0.93 (-1.04, -0.81), P < 0.00001], and complement C3 [0.31 (0.19, 0.42), P < 0.00001]. For inflammatory bowel disease, the results showed that mesenchymal stem cell transplantation may improve clinical efficacy [2.50 (1.07, 5.84), P = 0.03]. For ankylosing spondylitis, MSC treatment for 6 months may increase the total effective rate; reduce erythrocyte sedimentation rate, intercellular adhesion molecules, and serum TNF-α; and improve pain and activity. For multiple sclerosis, the current research results are still controversial, so more RCTs are needed to amend or confirm the conclusions. No obvious adverse events of mesenchymal stem cell transplantation were found in all RCTs. CONCLUSION: MSCs have a certain effect on different autoimmune diseases, but more RCTs are needed to further modify or confirm the conclusion.