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ID PMID Title PublicationDate abstract
32059038 Gut dysbiosis is prevailing in Sjögren's syndrome and is related to dry eye severity. 2020 OBJECTIVE: To investigate gut dysbiosis in patients with Sjögren's syndrome (SS) or dry eye syndrome (DES) compared to normal subjects and to evaluate the association of dysbiosis with dry eye severity. METHODS: 10 subjects with SS, 14 subjects with DES and 12 controls were enrolled. Corneal staining, tear break up time (TBUT) and tear secretion were evaluated. Bacterial genomic 16s rRNA from stool samples were analyzed. Main outcomes were microbiome compositional differences among groups and their correlation to dry eye signs. RESULTS: Gut microbiome analysis revealed significant compositional differences in SS compared to controls and DES. In phylum, Bacteriodetes increased, while Firmicutes/Bacteroidetes ratio and Actinobacteria decreased (p<0.05). In genus, Bifidobacterium was reduced (vs controls; p = 0.025, vs DES; p = 0.026). Beta diversity of SS also showed significant distances from controls and DES (p = 0.007 and 0.019, respectively). SS showed decreased genus of Blautia (p = 0.041), Dorea (p = 0.025) and Agathobacter (p = 0.035) compared to controls and increased genus of Prevotella (p = 0.026), Odoribacter (p = 0.028) and Alistipes (p = 0.46) compared to DES. On the other hand, DES only had increased genus Veillonella (p = 0.045) and reduced Subdoligranulum (p = 0.035) compared to controls. Bacteroidetes, Actinobacteria and Bifidobacterium were significantly related with dry eye signs (p<0.05). After adjustment of age, gender and group classification, multivariate linear regression analysis revealed tear secretion was strongly affected by Prevotella (p = 0.025). With additional adjustment of hydroxychloroquine use, TBUT was markedly affected by Prevotella (p = 0.037) and Actinobacteria (p = 0.001). CONCLUSIONS: Sjögren's syndrome showed significant gut dysbiosis compared to controls and environmental dry eye syndrome, while dry eye patients showed compositional changes of gut microbiome somewhere in between Sjögren's syndrome and controls. Dysbiosis of the gut microbiota was partly correlated to dry eye severity.
31594442 A case report of Sjögren's syndrome associated with protein-losing gastroenteropathy succ 2020 Feb Protein-losing gastroenteropathy (PLGE) is a rare manifestation of primary Sjögren's syndrome that is most commonly reported in Japan. Herein, the case of a 71-year-old Chinese male patient, diagnosed with PLGE and Sjögren's syndrome, is reported. The patient presented with peripheral oedema, and PLGE was diagnosed based on the result of technetium-99m ((99m)Tc)-labelled albumin scintigraphy. In addition to a positive Schirmer's test, the patient had atrophy of the salivary gland with lymphocyte infiltration, impaired parotid-gland secretory and excretory function, and an increased level of anti-SSA antibodies, fulfilling the criteria for Sjögren's syndrome. He was successfully treated with methylprednisolone. Follow-up (99m)Tc-labelled albumin scintigraphy results correlated well with clinical improvement and increased serum albumin levels. The present case study highlights the necessity of considering a diagnosis of protein loss enteropathy associated with primary Sjögren's syndrome when patients have unexplained hypoproteinaemia.
32799896 Lactobacillus sakei suppresses collagen-induced arthritis and modulates the differentiatio 2020 Aug 15 BACKGROUND: To evaluate the immunomodulatory effect of Lactobacillus sakei in a mouse model of rheumatoid arthritis (RA) and in human immune cells. METHODS: We evaluated whether L. sakei reduced the severity of collagen-induced arthritis (CIA) and modulated interleukin (IL)-17 and IL-10 levels, as well as whether it affected the differentiation of CD4(+) T cells and regulatory B cells. We evaluated osteoclastogenesis after culturing bone marrow-derived mononuclear cells with L. sakei. RESULTS: The differentiation of T helper 17 cells and the serum level of IL-17 were suppressed by L. sakei in both human peripheral blood mononuclear cells and mouse splenocytes. The serum level of IL-10 was significantly increased in the L. sakei-treated group, whereas the regulatory T cell population was unchanged. The population of regulatory B cells significantly increased the in L. sakei-treated group. Oral administration of L. sakei reduced the arthritis incidence and score in mice with CIA. Finally, osteoclastogenesis and the mRNA levels of osteoclast-related genes were suppressed in the L. sakei-treated group. CONCLUSION: L. sakei exerted an anti-inflammatory effect in an animal model of RA, regulated Th17 and regulatory B cell differentiation, and suppressed osteoclastogenesis. Our findings suggest that L. sakei has therapeutic potential for RA.
32870689 Immunoaffinity Targeted Mass Spectrometry Analysis of Human Plasma Samples Reveals an Imba 2020 Oct 2 One of the most important advantages of mass spectrometry is the ability to quantify proteins and their modifications in parallel to obtain a holistic picture of the protein of interest. Here, we present a hybrid immunoaffinity targeted mass spectrometry (MS) method that combines efficient pan-antibody enrichment of a specific protein from plasma with the selectivity of high-resolution targeted MS analysis to quantitate specific proteoforms of interest. We used this approach to quantify plasma levels of the chemokine CXCL10 that has been associated with many immunological disorders such as systemic lupus erythematosus and primary Sjögren's Syndrome (pSS). The hybrid approach enabled sensitive, specific, and simultaneous quantification of total, full-length (active) CXCL10(1-77) and DPP4-truncated (inactive) CXCL10(3-77) in human plasma down to the low pg/mL level, reaching ELISA sensitivities. Samples from 30 control subjects and 34 pSS patients (n = 64) were analyzed. The ratio of CXCL10(1-77) to truncated CXCL10(3-77) was significantly increased in patients with pSS and provided the highest correlation with pSS disease activity. Therefore, this CXCL10 proteoform ratio represents an interesting exploratory disease activity biomarker to further investigate. As this strategy can be readily adapted to other plasma proteins and proteoforms of interest, we are convinced that it will lead to a more detailed understanding of proteoforms in physiology and pathology yielding more relevant biomarkers and drug targets.
32383062 APPA (apocynin and paeonol) modulates pathological aspects of human neutrophil function, w 2020 Oct Neutrophils are key players in the pathophysiological process underlying inflammatory conditions not only by release of tissue-damaging cytotoxic enzymes, reactive oxygen species (ROS) but also by secretion of important immunomodulatory chemokines and cytokines. Here, we report the effects of the novel agent APPA, undergoing formal clinical development for treatment of osteoarthritis, and its constituent components, apocynin (AP) and paeonol (PA) on a number of neutrophil functions, including effects on TNFα- expression and signalling. Neutrophils were treated with APPA (10-1000 µg/mL) prior to the measurement of cell functions, including ROS production, chemotaxis, apoptosis and surface receptor expression. Expression levels of several key genes and proteins were measured after incubation with APPA and the chromatin re-modelling agent, R848. APPA did not significantly affect phagocytosis, bacterial killing or expression of surface receptors, while chemotactic migration was affected only at the highest concentrations. However, APPA down-regulated neutrophil degranulation and ROS levels, and decreased the formation of neutrophil extracellular traps. APPA also decreased cytokine-stimulated gene expression, inhibiting both TNFα- and GM-CSF-induced cell signalling. APPA was as effective as infliximab in down-regulating chemokine and IL-6 expression following incubation with R848. Whilst APPA does not interfere with neutrophil host defence against infections, it does inhibit neutrophil degranulation, and cytokine-driven signalling pathways (e.g. autocrine signalling and NF-κB activation), processes that are associated with inflammation. These observations may explain the mechanisms by which APPA exerts anti-inflammatory effects and suggests a potential therapeutic role in inflammatory diseases in which neutrophils and TNFα signalling are important in pathology, such as rheumatoid arthritis.
32982752 Sigesbeckia orientalis L. Extract Alleviated the Collagen Type II-Induced Arthritis Throug 2020 Excessive proliferation and inflammation of synovial fibroblasts accelerate and decorate the pathological process of rheumatoid arthritis (RA). Sigesbeckia orientalis L. (SO) is one of the main plant sources for Sigesbeckiae Herba (SH) which has been used traditionally in treating various forms of arthritis and rheumatic pain. However, the anti-arthritic mechanisms of SO are still not clearly understood. In this study, we investigated the therapeutic effects and the underlying mechanisms of SO against collagen type II (C II)-induced RA in rats as well as the interleukin (IL)-1β-induced human synovial SW982 and MH7A cells. For the in vivo studies, thirty-six Wistar male rats were randomly arranged to six groups based on the body weight, and then C II-induced to RA model for 15 days, followed by treatment with the 50% ethanolic extract of SO (SOE, 0.16, 0.78, and 1.56 g/kg) for 35 days. The results suggested that SOE significantly inhibited the formation of pannus (synovial hyperplasia to the articular cavity) and attenuated the cartilage damaging and bone erosion in the CIA-induced rats' hind paw joints. Moreover, SOE decreased the production of C-reactive protein (CRP) in the serum and the expression of IL-6 and IL-1β in the joint muscles, as well as recovered the decreased regulatory T lymphocytes. The results obtained from the in vitro studies showed that SOE (50, 100, and 200 µg/ml) not only inhibited the proliferation, migration, and invasion of human synovial SW982 cells but also decreased the IL-1β-induced expression of IL-6 and IL-8 both in SW982 and MH7A cells. Besides, SOE reduced the expression of COX-2, NLRP3, and MMP9, and increased the expression of MMP2 in the IL-1β-induced SW982 cells. Furthermore, SOE blocked the activation of NF-κB and reduced the phosphorylation of MAPKs and the expression of AP-1. In conclusion, SOE attenuated the C II-induced RA through inhibiting of MAPKs/NF-κB/AP-1-mediated synovial hyperplasia and inflammation.
32623648 Systemic immune-inflammation index combined with ferritin can serve as a reliable assessme 2021 Feb OBJECTIVE: The diagnosis of adult-onset Still's disease (AOSD) is based on nonspecific symptoms and laboratory data, and several infectious, autoimmune, and malignant diseases must be ruled out. This study aimed to elucidate the value of various laboratory inflammatory scores, including the systemic immune-inflammation index (SII), C-reactive protein/albumin ratio (CAR), albumin/globulin ratio (AGR), prognostic nutritional index (PNI), and ferritin/erythrocyte sedimentation rate ratio (FER) as assessment factors for diagnosis and evaluation of disease activity in AOSD. METHODS: The medical records of patients suspected of AOSD between January 1999 and June 2019 were examined. The inflammatory scores were compared between AOSD and non-AOSD groups, and receiver operating characteristic (ROC) curve analysis was performed to evaluate diagnostic utility. RESULTS: A total of 164 patients diagnosed with AOSD had higher values of SII, CAR, and FER, as well as lower values of AGR and PNI, than non-AOSD patients (n = 61). For an AOSD diagnosis, the area under the receiver operating characteristic curve (AUC) was 0.859 (95% confidence interval [CI], 0.806-0.911) for the SII, 0.769 (95% CI, 0.702-0.837) for the CAR, 0.749 (95% CI, 0.615-0.782) for the AGR, 0.699 (95% CI, 0.675-0.823) for the PNI, and 0.764 (95% CI, 0.693-0.834) for the FER, with optimal cut-off values of 2195.7, 1.8, 1.38, 48.8, and 17, respectively. The SII had the largest AUC and the highest specificity (91.5%). In further analysis, the AUC for the combination of SII and ferritin was 0.904 (95% CI, 0.863-0.945), with a cut-off value of 2615.4. CONCLUSIONS: Laboratory inflammatory scores can be used as a practical tool for diagnosing AOSD. The SII and ferritin combination proved to be the most powerful assessment tool. Key Points • The systemic immune-inflammation index (SII), C-reactive protein/albumin ratio (CAR), ferritin/erythrocyte sedimentation rate ratio (FER), prognostic nutritional index (PNI), and albumin/globulin ratio (AGR) can be used as initial assessment scores for AOSD. • SII combined with ferritin (AUC = 0.904; 95% CI, 0.863-0.945) appears to be the most effective and valuable assessment score for AOSD.
33030565 Publication activity in the field of Sjögren's syndrome: a ten-year Web of Science based 2021 Apr Bibliometric analysis is widely utilized to evaluate global research productivity in different research topics. However, to date, there has been no assessment of worldwide research productivity associated with Sjögren's syndrome. Therefore, the aim of this study was to evaluate the global research productivity in the field of Sjögren's syndrome using bibliometric analysis. The Web of Science database was scanned with the search terms 'Sjögren's syndrome' and 'Sjögren syndrome' for publications in the period 2010-2019. Original articles and reviews were selected for analysis. The most active countries were determined, and the number of articles, citations, research productivity adjusted by population and gross domestic product were analyzed. A total of 3856 articles were identified from 65 different countries. A statistically significant trend was observed in the direction of increase (in terms of the number of articles; from 282 to 461) in the 10-year period. A total of 3004 (77.90%) articles were from high-income countries. The five most productive countries were the United States (n = 714, 18.51%), China (n = 428, 11.09%), Japan (n = 308, 7.98%), Italy (n = 299, 7.75%) and France (n = 249, 6.45%). When the number of articles was adjusted according to population, Norway was the most productive country, followed by Greece and the Netherlands. In analysis according to gross domestic product, Greece was the leading country, followed by Norway and the Netherlands. The results of this study demonstrated a remarkable growth in global research productivity on Sjögren's syndrome between 2010 and 2019. More than three quarters of the articles were from high-income countries. When population and gross domestic product were considered, relatively small European countries came to the fore.
32934126 Elevated Granulocyte Colony-stimulating Factor Levels in Patients With Active Phase of Adu 2021 May OBJECTIVE: Neutrophilia is a hallmark of adult-onset Still disease (AOSD). We aimed to investigate the levels of granulocyte colony-stimulating factor (G-CSF), an essential regulator of neutrophil production and function, in the pathogenesis of AOSD. METHODS: Sera were collected from 70 patients with AOSD and 20 healthy controls (HCs). The levels of G-CSF were determined by ELISA. Low-density granulocytes (LDGs) were quantified by flow cytometry. Correlations between G-CSF levels and disease activity, laboratory variables, and LDG levels in patients with AOSD were analyzed by Spearman correlation test. RESULTS: Patients with active AOSD presented significantly higher levels of G-CSF compared to inactive AOSD patients (P < 0.001) and HCs (P < 0.0001). The G-CSF levels were significantly decreased after active AOSD patients achieved disease remission (P = 0.0015). The G-CSF levels were significantly correlated with C-reactive protein, erythrocyte sedimentation rate, ferritin, and systemic score in AOSD (P < 0.0001). Significant correlations between the levels of G-CSF and circulating neutrophils (P < 0.0001), neutrophil-to-lymphocyte ratio (P < 0.0001), percentages of LDGs in the peripheral blood mononuclear cells (P = 0.004), as well as absolute numbers of circulating LDGs (P = 0.018) were identified. Patients with fever, evanescent rash, sore throat, arthralgia, myalgia, lymphadenopathy, or hepatomegaly/elevated liver enzymes displayed significantly higher levels of G-CSF compared to patients without these manifestations (P < 0.05). CONCLUSION: Our findings indicate that G-CSF is implicated in the pathogenesis of AOSD, and targeting G-CSF may have therapeutic potential for AOSD. In addition, introducing circulating G-CSF levels into the clinical assessment system may help to monitor disease activity.
33329615 Corrigendum: Monomeric C-Reactive Protein Binds and Neutralizes Receptor Activator of NF-Î 2020 [This corrects the article DOI: 10.3389/fimmu.2018.00234.].
31820705 Total Ankle Replacement in Hemophilia. 2020 INTRODUCTION: Severe ankle hemophilic arthropathy can be a calamitous sign of severe hemophilia with important inferences for activities of daily living. AIMS: To summarize the contemporary, accessible information on Total Ankle Replacement (TAR) for ankle hemophilic arthropathy. METHODS: A search of Cochrane Library and PubMed (MEDLINE) regarding the role of TAR in ankle hemophilic arthropathy. RESULTS: The insufficient information regarding the results of TAR for hemophilic arthropathy is confined to scanty case series and case reports. An evaluation of the accessible literature reveals encouraging but inconstant outcomes. The reported rate of adverse events is 33%. The reported anticipated survival of TAR is 94% at 5 years, 85% at 10 years and 70% at 15 years. CONCLUSION: Whereas people with advanced hemophilic arthropathy of the ankle are prone to ameliorate pain and range of motion following TAR, there is deficient knowledge to regularly recommend its use. Adverse events and infection percentages are disturbing. Moreover, the lack of survival analysis knowledge makes it difficult to assess the benefit to people with hemophilia. TAR is a demanding surgical procedure and its survival is not comparable to that after hip or knee replacement.
32905192 Impact of tumor necrosis factor inhibitors and methotrexate on diabetes mellitus among pat 2020 BACKGROUND: To determine whether initiation of a tumor necrosis factor inhibitor (TNFi) or methotrexate improves hemoglobin A1c in patients with psoriatic arthritis (PsA), rheumatoid arthritis (RA), or ankylosing spondylitis (AS) who also have diabetes mellitus (DM). METHODS: A retrospective cohort study was conducted in Optum's de-identified Clinformatics® Data Mart Database, an administrative claims database, using data from 2000 to 2014. Patients with PsA, RA, or AS, with DM (defined by ICD-9-CM codes) and/or HbA1c ≥7%, who newly initiated either a TNFi, MTX, or metformin (positive control) were identified. The change in HbA1c after drug initiation was calculated. Statistical differences in the change in HbA1c between drugs were assessed using the Wilcoxon rank sum test and linear regression models adjusting for potential confounders. RESULTS: Among 10,389 drug initiations in 9541 patients with PsA, RA, or AS, and available HbA1c values, HbA1c was ≥7 at baseline in 254 (35%) TNFi initiations, 361(37%) MTX initiations, and 2144 (50%) metformin initiations. Median HbA1c change was - 0.35 (IQR -1.10, 0.30) after TNFi initiation, - 0.40 (IQR -1.20, 0.30) after MTX initiation, and - 0.80 (IQR -1.60, - 0.10) after metformin initiation. In adjusted analyses, TNFi initiators had less of a decrease in HbA1c compared to MTX initiators (β 0.22, 95% CI: 0.004, 0.43), p = 0.046. Metformin initiators had a significantly greater decrease in HbA1c than MTX, β - 0.38 (95% CI: - 0.52, - 0.23), p < 0.001. Glucocorticoid use was not accounted for in the models. CONCLUSION: HbA1c decreased with TNFi initiation or MTX initiation. Reductions in HbA1c after initiation of a TNFi or MTX are about half (~ 0.4 units) the decrease observed after initiation of metformin.
31599078 The therapeutic effects of edaravone on collagen-induced arthritis in rats. 2020 Feb Current research suggests that synovial phagocytic cells remove excessive amounts of free oxygen radicals (reactive oxygen species [ROS]), thereby preventing damage to synovial tissues. Moreover, ROS may affect the expression of growth arrest and DNA damage inducible α (GADD45A), thus further promoting the activation of synovial fibroblasts. Male adult rats were assessed for progression of collagen-induced arthritis (CIA) using a macroscopic arthritis scoring system of the hind paws and by measuring the changes in the rat's body weight, and activity level before and after diagnosis of CIA. Rats were intraperitoneally injected twice daily with edaravone at doses of 3, 6, and 9 mL/kg. Samples were taken at 2, 4, and 6 weeks, respectively. Edaravone was found to significantly reduce macroscopic arthritis and microscopic pathology scores in CIA rats. The concentration of endothelial nitric oxide synthase-6, glutathione, and heme oxygenase-1 in the serum of rats decreased, as was the production of ROS around the synovium and inflammatory factors. Moreover, ROS-1 increased the expression of the nuclear factor-κB (NF-κB) p65 protein by altering the expression level of GADD45A, causing aggravation of tissue damage. Edaravone also significantly improved the physiological condition of CIA rats, including appetite, weight changes, and loss of fur, as well as limb mobility. We believe that edaravone acts to reduce the expression of NF-ĸB p65 by clearing ROS, which causes reduced expression of GADD45A, and subsequently reduces the level of apoptosis and inflammatory response proteins, thereby reducing the symptoms of CIA. We, therefore, propose that edaravone is an effective option for clinical treatment of rheumatic arthritis.
32683611 Real-World Analysis of Therapeutic Patterns in Patients Affected by Rheumatoid Arthritis i 2020 Sep INTRODUCTION: The objective of this study was to evaluate treatment patterns in patients with rheumatoid arthritis (RA), with a focus on the utilization of baricitinib, an oral highly selective Janus kinase 1 and 2 inhibitor, in an Italian real-world setting. METHODS: This observational retrospective analysis was based on data collected in selected Italian administrative databases. Patients aged ≥ 18 years with a diagnosis of RA defined by hospitalization discharge diagnosis (International Classification of Diseases, Ninth Revision, Clinical Modification code 714.0) or by disease exemption code 006 for RA in 2018 were included. The index date (ID) was defined as the date of first prescription for a drug indicated for RA during the inclusion period. Patients without a prescription for biologic/targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) before the ID were considered to be b/tsDMARD naïve. A further analysis was performed on patients only receiving baricitinib. RESULTS: A total of 41,290 RA patients were enrolled, of whom 55.6% were not treated with conventional synthetic DMARDs (csDMARDs) or b/tsDMARDs, 39.4% were receiving therapy with csDMARDs, and 5.0% were using b/tsDMARDs. In the latter group, 2.7% (n = 56) were receiving therapy with baricitinib. In 2018, 13.2% of csDMARD-treated patients switched to b/tsDMARDs, of whom 4.3% (n = 93) of these switched to baricitinib. In total, 149 patients (mean age ± standard deviation 57.6 ± 12.1; 12.8% male) had a baricitinib prescription, of whom 51% were b/tsDMARD naïve. At baseline, 61.7% of baricitinib users were receiving combination therapy with csDMARDs plus corticosteroids, 26.2% were receiving combination therapy with corticosteroids, and 8.1% were receiving combination therapy with csDMARDs; 4% were receiving baricitinib monotherapy. During follow-up, the proportion of patients receiving baricitinib monotherapy increased to 38.9%, while 26.9, 18.8, and 15.4% of baricitinib users received combination therapy with corticosteroids, csDMARDs plus corticosteroids, and csDMARDs, respectively. CONCLUSION: This study provides a current view of the treatment patterns in Italian patients with RA in a real-world setting of daily clinical practice, with a focus on baricitinib utilization.
32641449 Strategies for the assessment of competences during rheumatology training across Europe: r 2020 Jul OBJECTIVES: To gain insight into current methods and practices for the assessment of competences during rheumatology training, and to explore the underlying priorities and rationales for competence assessment. METHODS: We used a qualitative approach through online focus groups (FGs) of rheumatology trainers and trainees, separately. The study included five countries-Denmark, the Netherlands, Slovenia, Spain and the United Kingdom. A summary of current practices of assessment of competences was developed, modified and validated by the FGs based on an independent response to a questionnaire. A prioritising method (9 Diamond technique) was then used to identify and justify key assessment priorities. RESULTS: Overall, 26 participants (12 trainers, 14 trainees) participated in nine online FGs (2 per country, Slovenia 1 joint), totalling 12 hours of online discussion. Strong nationally (the Netherlands, UK) or institutionally (Spain, Slovenia, Denmark) standardised approaches were described. Most groups identified providing frequent formative feedback to trainees for developmental purposes as the highest priority. Most discussions identified a need for improvement, particularly in developing streamlined approaches to portfolios that remain close to clinical practice, protecting time for quality observation and feedback, and adopting systematic approaches to incorporating teamwork and professionalism into assessment systems. CONCLUSION: This paper presents a clearer picture of the current practice on the assessment of competences in rheumatology in five European countries and the underlying rationale of trainers' and trainees' priorities. This work will inform EULAR Points-to-Consider for the assessment of competences in rheumatology training across Europe.
32426102 Are gene polymorphisms related to adverse events of methotrexate in patients with rheumato 2020 AIMS: We performed an updated meta-analysis to verify correlations between gene polymorphisms and adverse events in methotrexate (MTX)-treated rheumatoid arthritis (RA) patients. Then, we conducted a retrospective cohort study of Han Chinese in China. METHODS: Relevant studies were collected from the PubMed database and the EMBASE database until December 2017. Pre-allele, dominant, recessive, codominant, and homozygotic models were applied. In addition, a retrospective cohort study enrolling 162 RA patients treated with MTX was conducted. Single nucleotide polymorphism (SNP) genotyping was analyzed by PCR and product sequencing. RESULTS: A total of 39 studies were included in 20 meta-analyses; meta-analysis showed a significant association between MTX-related toxicity and 5,10-methylenetetrahydrofolate reductase (MTHFR) 677C>T(rs1801133) polymorphism in East Asian RA patients, and significant associations were observed between MTX-related toxicity and 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase/IMP cyclohydrolase (ATIC) 347C>G (rs2372536), reduced folate carrier 1 (RFC-1) 80G>A (rs1051266), and adenosine triphosphate-binding cassette B1 (ABCB1) 3435C>T(rs1045642) polymorphisms in European RA patients but not in East Asian RA patients. Moreover, in our retrospective cohort study, ATIC 347C>G(rs2372536) and ABCB1 3435C>T(rs1045642) polymorphisms were not associated with MTX-related toxicity. However, a significant association was observed between MTX-related toxicity and RFC-1 80G>A (rs1051266) polymorphism in Chinese Han RA patients. CONCLUSION: Evidence-based results suggest that the MTHFR 677C>T(rs1801133), ATIC 347C>G(rs2372536), RFC-1 80G>A (rs1051266), ABCB1 3435C>T(rs1045642) polymorphisms are associated with MTX-related toxicity. Larger and more stringent study designs may provide more accurate findings for the effects of these SNPs on MTX-related toxicity, and larger sample-size studies of the Chinese Han population should be conducted for further validation.
33088533 Mixed connective tissue disease: Not always an obvious diagnosis. 2020 Oct Mixed connective tissue disease (MCTD) is characterized by a mixture of clinical features. The initial presentation is often incomplete, and the features of MCTD usually develop as the disease evolves. We present a 37-year-old female patient with overlapping symptoms. The most plausible diagnosis was MCTD.
32666164 [Periprosthetic and interprothetic fractures in patients with rheumatism : Characteristics 2020 Aug BACKGROUND: Periprosthetic fractures in patients with underlying rheumatic diseases can be a special challenge depending on the extent, bone quality and septic complications. OBJECTIVES: Does the underlying rheumatic disease influence the treatment strategy for periprosthetic fractures? What effect do the many extra-articular and local joint-specific rheumatic involvement patterns have on the surgical strategy? How should the potential immunosuppressive side effects of continuously new biologicals be perioperatively taken into account? How can less conspicuous infections under immunosuppression be recognized clinically and using laboratory parameters? MATERIAL AND METHODS: Rheumatic disease manifestations that must be perioperatively considered are presented based on the literature. The results are supplemented by many years of experience in a hospital with more than 1500 operations on patients with an underlying rheumatic disease. RESULTS: The treatment of periprosthetic fractures with underlying rheumatic diseases necessitates the specific consideration of the multiple accompanying conditions. In general, extra-articular manifestations, average younger age, increased susceptibility to infections, multiple joint involvement and the basic medication must be taken into consideration. The local poorer bone quality can require an adaptation of the surgical technique. These factors are summarized in a treatment algorithm for periprosthetic fractures in patients with rheumatism taking the stability of the prosthesis, the infection status, the etiology, the localization and extent of the fracture into consideration.
33376379 Methotrexate (MTX) Plus Hydroxychloroquine versus MTX Plus Leflunomide in Patients with MT 2020 PURPOSE: To compare the efficacy, safety, and cost-effectiveness of methotrexate (MTX) plus hydroxychloroquine (HCQ) vs MTX plus leflunomide (LEF) in established rheumatoid arthritis (RA) with inadequate response to MTX monotherapy in a real-world Chinese cohort. PATIENTS AND METHODS: A prospective RA cohort (n=549) was screened with eligible patients who had inadequate response (disease activity score in 28 joints using erythrocyte sedimentation rate, DAS28-ESR>3.2) to initial MTX monotherapy and subsequently received either MTX+HCQ or MTX+LEF. Propensity score matching (PSM) was applied to adjust the possible baseline confounders between two groups. The primary outcome was the proportion of patients achieving first remission (DAS28-ESR<2.6) during follow-up by log rank test. Secondary outcomes were changes of DAS28, glucocorticoids (GCs) exposure, safety, cost-effectiveness, sustained remission, and low disease activity (LDA) rate after 24-month follow-up. RESULTS: Overall, 222 eligible patients were subjected to the aforementioned two treatment protocols (MTX+HCQ, n=102; MTX+LEF, n=120). After PSM adjustment, 97 patients in each group were analyzed. A higher remission rate was observed in the MTX+HCQ group than in the MTX+LEF group (70.1% vs 56.7%, P=0.048). The median time to remission was 11 and 16 months in the two groups, respectively. At the endpoint, more patients achieved remission (46.8% vs 32.5%, P=0.063) and maintained sustained LDA in the HCQ group (53.2% vs 38.6%, P=0.062) and also more patients withdrew GCs in this group (32% vs 16.7%, P=0.053) than those in the LEF group. Safety profiles were non-alarming, with no significant difference between the two groups. The incremental cost-effectiveness ratio yielded by MTX+HCQ over MTX+LEF was $1,111.8 per quality-adjusted life-year (QALY), within the cost-effective threshold set as the per capita gross domestic product (GDP) of China. CONCLUSION: The MTX+HCQ combination was seemingly superior to MTX+LEF in a real-world cohort of Chinese RA patients with inadequate response to methotrexate monotherapy in respect of the efficacy and cost-effectiveness.
33327594 HLA-DRB1*07:01 and *08:02 Alleles Confer a Protective Effect Against ACPA-Positive Rheumat 2020 Dec 14 HLA-DRB1 shared epitope (SE) alleles are important genetic contributors for the risk of developing anti-citrullinated protein antibodies (ACPA)-positive rheumatoid arthritis (RA), particularly in Caucasians. We aimed to analyze the contribution of HLA-DRB1 alleles and single nucleotide polymorphisms (SNPs) within the major histocompatibility complex (MHC) region to the susceptibility to develop ACPA-positive RA in a Latin American (LA) population with admixed ancestry. A total of 289 ACPA-positive RA patients and 510 controls were enrolled in this study. The presence of HLA-DRB1*04:01, *09:01 and *10:01 was increased in ACPA-positive RA patients compared with healthy controls (p < 0.0001, p < 0.001 and p < 0.01, respectively), whereas DRB1*07:01 and *08:02 was associated with a decreased risk of ACPA-positive RA (p < 0.001 and p < 0.01, respectively). These results showed a strong correlation with estimates from studies in Asians but not in Caucasian populations. The present study describes the protective effects of the HLA-DRB1*07:01 and *08:02 alleles in ACPA-positive RA patients in a LA population for the first time. Identifying relationships between HLA-DRB1 alleles and RA is important for identifying disease associations in different ethnic groups in order to reach a better understanding of RA worldwide.