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ID PMID Title PublicationDate abstract
33095151 Ten years of the ESSDAI: is it fit for purpose? 2020 Jul Primary Sjögren's syndrome (pSS) is a very heterogeneous disease with systemic manifestations such as arthritis, skin, lung and renal involvement. To be able to assess systemic disease activity, the EULAR Sjögren's syndrome disease activity index (ESSDAI) was developed for use in daily clinical practice and in clinical trials. Since its development it has been widely used in cohort studies and clinical trials. The ESSDAI gives a systematic overview of a patient's systemic disease activity, which is very useful in daily clinical practice. However, using the ESSDAI as outcome measure in trials has been more challenging. Several RCTs with the ESSDAI as primary endpoint failed and showed large 'response rates' in placebo-treated patients as well. In this review, we discuss what we learned from using the ESSDAI in cohorts and clinical trials. We recommend to use the ESSDAI only in combination with other important outcome measures, such as patient-reported symptoms and glandular function as part of a composite endpoint in clinical trials in pSS patients.
32370746 Metabolic abnormalities exacerbate Sjögren's syndrome by and is associated with increased 2020 May 5 BACKGROUND: Sjögren's syndrome (SS) is an autoimmune disease mediated by lymphocytic infiltration into exocrine glands, resulting in progressive lacrimal and salivary destruction and dysfunctional glandular secretion. Metabolic syndrome influences the immune system. To investigate its relationship with metabolic abnormalities, we evaluated the pathogenesis of SS and the immune cell populations in non-obese diabetic NOD/ShiLtJ mice with type 1 diabetes (T1D). METHODS: To induce metabolic abnormalities, streptozotocin (STZ)-a glucosamine-nitrosourea compound that destroys pancreatic β cells, resulting in T1D-was injected into NOD/ShiLtJ mice. The blood glucose level was measured to evaluate induction of T1D. The severity of SS was assessed by determining the body weight, salivary flow rate, and histologic parameters. The expression levels of proinflammatory factors in the salivary glands, lacrimal gland, and spleen were quantified by real-time PCR. The populations of various T- and B-cell subtypes in the peripheral blood, spleen, and salivary glands were assessed by flow cytometry. RESULTS: Induction of T1D in NOD/ShiLtJ mice increased both the severity of SS and the levels of proinflammatory cytokines in the salivary glands compared to the controls. Furthermore, the number of interleukin-17-producing immune cells in the peripheral blood, spleen, and salivary glands was increased in STZ- compared to vehicle-treated NOD/ShiLtJ mice. CONCLUSIONS: Metabolic abnormalities play an important role in the development of SS.
31529714 Telomere erosion in Sjögren's syndrome: A multi-tissue comparative analysis. 2020 Jan BACKGROUND: Acinar progenitor cells within salivary glands have decreased regenerative capacity and exhibit shorter telomeres in primary Sjögren's syndrome (pSS) patients. We investigated whether DNA of saliva, PBMCs, and labial salivary gland (LSG) biopsy tissue have shorter telomeres in pSS compared to controls. mRNA expression of genes associated with pSS pathogenesis (ETS1, LEF1, and MMP9), telomere DNA damage response (ATM), senescence (CDKN2A), telomerase inhibition (IFN-y, TGFβ1), and the shelterin complex (TPP1, POT1) were assessed in LSG tissue by qRT-PCR to examine potential defects in telomere maintenance. METHODS: Relative telomere length in DNA of saliva, PBMCs, and LSGs from non-pSS sicca and pSS patients was measured using qPCR. Saliva DNA telomere length was further compared to healthy controls. Expression of genes affecting telomere maintenance was analyzed in LSGs using qRT-PCR. RESULTS: Primary Sjögren's syndrome patients have shorter telomeres in saliva DNA (n = 21) than healthy controls (n = 27) (P = .0035). ATM mRNA expression was higher in pSS LSG tissue (n = 16) vs non-pSS sicca patients (n = 13) (P = .0283) and strongly correlated with LEF1, TPP1, and POT1 (P < .01, r > 0.6). CONCLUSIONS: Patients with pSS exhibited significant telomere erosion in saliva DNA. Overexpression of ATM in LSGs could represent a compensatory response to telomere shortening. The role of LEF1 in telomere erosion remains to be elucidated.
31872367 Challenges in Treatment of Primary Sjögren's Syndrome and Opportunities for Chinese Medic 2020 Jul Primary Sjögren's syndrome is a chronic autoimmune disease that can lead to systemic manifestations. At present, immunomodulatory agents have not shown good efficacy, many patients in China seek Chinese medicine treatment. Chinese medicine can comprehensively improve the symptoms of patients through Chinese pattern diagnosis and individualized treatment. Fundamental researches are providing scientific bases for the therapeutic effect of Chinese medicine. Professional Chinese medicine treatment can be integrated into the conventional management of primary Sjögren's syndrome.
32517782 Correction to: Upadacitinib improves patient-reported outcomes in patients with rheumatoid 2020 Jun 9 An amendment to this paper has been published and can be accessed via the original article.
33344817 Preclinical Evaluation of a Novel (99m)Tc-Labeled CB86 for Rheumatoid Arthritis Imaging. 2020 Dec 15 Early diagnosis and therapy are crucial to control disease progression optimally and achieve a good prognosis in rheumatoid arthritis (RA). Previous study showed that a technetium-99m ((99m)Tc)-labeled TSPO ligand ((99m)Tc-CB256 [2-(8-(2-(bis(pyridin-2-yl)methyl)amino)acetamido)-2-(4-chlorophenyl)H-imidazo[1,2-a]pyridin-3-yl)-N,N-dipropylacetamide] composed of a translocator protein (TSPO) ligand CB86 [[2-(4-chlorophenyl)-8-amino-imidazo[1,2-a]-pyridin-3-yl]-N,N-di-n-propylacetamide] and di-(2-picolyl)amine, a bifunctional chelate agent, was used to image a TSPO-rich cancer cell in vitro; however, few (99m)Tc-CB256 in vivo evaluation has been reported so far probably due to the cytotoxicity of CB256 (ca. 75 times more than analogous CB86). Herein, we describe a novel TSPO targeting radiopharmaceutical consisting of CB86 and diethylenetriaminepentaacetic acid (DTPA), a conventional bifunctional chelating ligand in clinical trials used to prepare (99m)Tc-labeled CB86, and its evaluation as a (99m)Tc-single-photon emission computed tomography (SPECT) probe. The radiosynthesis and characterization of (99m)Tc-DPTA-CB86 including hydrophilicity and stability tests were determined. Additionally, the binding affinity and specificity of (99m)Tc-DTPA-CB86 to TSPO were evaluated using RAW264.7 macrophage cells. Biodistribution and (99m)Tc-SPECT studies were conducted on rheumatoid arthritis (RA) rat models after the injection of (99m)Tc-DTPA-CB86 with or without co-injection of unlabeled DTPA-CB86. The radiosynthesis of (99m)Tc-DTPA-CB86 was completed successfully with the labeling yields and radiochemical purity of 95.86 ± 2.45 and 97.45 ± 0.69%, respectively. The probe displayed good stability in vitro and binding specificity to RAW264.7 macrophage cells. In the biodistribution studies, (99m)Tc-DTPA-CB86 exhibited rapid inflammatory ankle accumulation. At 180 min after administration, (99m)Tc-DTPA-CB86 uptakes of the left inflammatory ankle were 2.35 ± 0.10 percentage of the injected radioactivity per gram of tissue (% ID/g), significantly higher than those of the normal tissues. (99m)Tc-SPECT imaging studies revealed that (99m)Tc-DTPA-CB86 could clearly identify the left inflammatory ankle with good contrast at 30-180 min after injection. Therefore, (99m)Tc-DTPA-CB86 may be a promising probe for arthritis (99m)Tc-SPECT imaging.
33225741 Sauve-Kapandji Remains a Viable Option for Distal Radioulnar Joint Dysfunction. 2020 Nov 22 INTRODUCTION: Dysfunction of the distal radioulnar joint (DRUJ) can be significantly debilitating. The Sauve-Kapandji (S-K) procedure can be indicated to address multiple etiologies of DRUJ dysfunction. The purpose of this study was to review our institution's results performing the S-K procedure for DRUJ dysfunction in terms of clinical and radiographic outcomes, as well as complications and reoperations. METHODS: A retrospective review of S-K procedures performed at 2 institutions between 1998 and 2017 with a minimum of 1-year follow-up was performed. Preoperative and postoperative visual analog scale (VAS) pain, grip strength, and wrist range of motion were reviewed. Radiographs were reviewed for DRUJ healing, carpal translation, and radiocarpal degenerative changes. RESULTS: The cohort included 35 patients. The mean age was 51 years. The mean follow-up was 49.5 months. The postoperative range of motion was unchanged in regard to pronation, supination, and wrist extension. There was a decrease in wrist flexion from 43 degrees to 34 degrees. Successful union was noted in 100% of the wrists. There was 1 case (2.8%) of progressive ulnar translation and 4 major complications (11.3%). CONCLUSION: The S-K procedure has several theoretical benefits compared to other procedures for DRUJ dysfunction with results of this study demonstrating excellent pain relief, improved postoperative grip strength, retained wrist pronation, supination, and extension, high rate of successful arthrodesis and low rate of major complications. LEVEL OF EVIDENCE: Level IV.
33197425 Analysis on the expression and value of CCL2 and CCL3 in patients with osteoarthritis. 2021 Feb In this study, we investigated the clinical value of CC chemokine ligand 2 (CCL2) and CC chemokine ligand 3 (CCL3) in osteoarthritis (OA). A prospective analysis was performed on 126 patients with rheumatoid arthritis of the knee (observation group (OG)) who admitted to Qilu hospital from August 2016 to August 2018 and 135 healthy controls (control group (CG)) who underwent physical examinations during the same period. The concentrations of CCL2 and CCL3 in peripheral blood were compared between the two groups, and the predictive value of the two on the occurrence, efficacy and prognosis of recurrence of OA were analyzed. In addition, an OA rat model was established to detect the relative protein levels of CCL2 and CCL3 in rat knee joint tissues. There were no statistically significant differences between the two groups in baseline data such as age, body mass index (BMI), gender, smoking, drinking, educational level, family medical history and living environment (P > 0.05). CCL2 and CCL3 increased in peripheral blood of patients in the OG (P < 0.05), both of which were positively correlated with rheumatoid factor (RF) (P < 0.001). CCL2 and CCL3 were of good predictive value for the occurrence, efficacy and prognosis of recurrence of OA (P < 0.001). The relative protein levels of CCL2 and CCL3 in bone and joint tissues of OA rats were significantly higher than those of normal rats (P < 0.001). CCL2 and CCL3 are elevated in peripheral blood of OA patients, which have good predictive value for the occurrence, efficacy and prognosis of recurrence of OA, indicating their potential roles as excellent markers for diagnosis and treatment of OA in the future.
32517574 An updated review of infliximab biosimilar, CT-P13, in the treatment of immune-mediated in 2020 Jun The introduction of anti-TNFs, such as infliximab (IFX), has revolutionized the treatment of immune-mediated inflammatory diseases. Anti-TNF agents have shown outstanding efficacy and long-term improvement of clinical outcomes, but the cost has been relatively high. Out of this concern, several 'biosimilar' drugs of anti-TNF agents have been developed. CT-P13, the first biosimilar of reference IFX, was approved by the European Medicines Agency and licensed by the US FDA for use in all indications of IFX. This updated review summarizes all aspects of CT-P13, including pharmacology and pharmacokinetics, and evaluates its efficacy, safety and immunogenicity for all indications based on the results of the latest clinical trials as well as on real-world experiences.
33551802 Artocarpus tonkinensis Extract Inhibits LPS-Triggered Inflammation Markers and Suppresses 2020 Artocarpus tonkinensis (At) leaf decoction, a traditional remedy prepared in North Vietnam by the Hmong ethnic group, is a tea extract rich in bioactive compounds that may have therapeutic effects in arthritis and backache. Indeed, it has been demonstrated that At is able to inhibit Th17 lymphocytes development and to protect mice in an experimental model of collagen-induced arthritis. By resorting to macrophage in vitro models of inflammation and osteoclastogenesis, we showed that At extract significantly reduced nitric oxide synthase 2 (NOS2) activity and IL-6 production by RAW 264.7 murine cells. Moreover, At demonstrated an anti-osteoclastogenic effect, as revealed by complete inhibition of TRAP-positive osteoclast formation and decreased expression of key osteoclast-related genes. This At activity likely relies on the inhibition of RANK downstream signaling pathway, as the activation of non-receptor tyrosine kinase Src is reduced upon RANKL-At exposure. Protective effect of At against bone loss was also enlightened in vivo by collagen-induced arthritis (CIA) experiment demonstrating that, although paw edema was only weakly opposed by drinking At decoction, bone and cartilage were well preserved in CIA+At mice and joint tissue expressed decreased levels of osteoclast marker genes respect to CIA control group. Maesopsin 4-O-β-D-glucoside (i.e., TAT-2, one of the main decoction bioactive components) was capable to contrast NOS2 activity, IL-6 expression and osteoclast formation, too, albeit to a lesser extent when compared to At decoction. Overall, this study enlightens another At cell target, macrophages, beside Th17 lymphocytes, and suggests that the anti-arthritic beneficial effects of At decoction largely derives from its ability to counteract not only inflammation, but also osteoclastogenesis.
32274851 Active Ingredients and Anti-Arthritic Mechanisms of Ba-Wei-Long-Zuan Granule Revealed by ( 2020 Jun Ba-Wei-Long-Zuan granule (BWLZ) is a traditional herbal preparation. It has been widely used for the treatment of rheumatoid arthritis (RA). However, its active ingredients and mechanisms of action are still unclear. The present study aims to reveal the active compounds and anti-arthritic mechanisms of BWLZ against collagen-induced arthritis (CIA) by using (1) H-NMR-based metabolomics, molecular docking and network pharmacology methods. After 30 days of administration, BWLZ could effectively improve the metabolic disorders in CIA rats. The anti-arthritic effect of BWLZ was related to its restoration of 16 disturbed serum metabolites. Molecular docking and network analysis showed that 20 compounds present in BWLZ could act on multiple targets. Among them, coclaurine and hesperidin showed the highest hit rates for target proteins related to both metabolic regulation and RA, indicating that these two compounds might be potential active ingredients of BWLZ. Moreover, pathway enrichment analysis suggested that the anti-arthritic mechanisms of BWLZ might be attributed to its network regulation of several biological processes, such as steroid hormone biosynthesis, mTOR signaling pathway, alanine, aspartate and glutamate metabolism, and synthesis and degradation of ketone bodies. These results provide further evidence for the anti-arthritic properties of BWLZ and are beneficial for its quality control and clinical application. The potential targets and biological processes found in this study may provide valuable information for further studying the molecular mechanisms of BWLZ against RA. In addition, our work provides new insights for revealing the active ingredients and regulatory mechanisms of complex herbal preparations.
32382842 Anti-inflammatory Effect of Ozone Therapy in an Experimental Model of Rheumatoid Arthritis 2020 Jun To verify the influence of ozone (O(3)) therapy on an experimental model of rheumatoid arthritis (RA), 30 male Wistar rats were randomly allocated to 2 groups, control (C) and treatment (T), and subdivided into control (C12, C48, C72) and treatment (T12, T48, T72) groups. RA was induced by administration of collagenase plus complete Freud's adjuvant in the knee joint region. The animals were treated with ozone therapy (1 ml O(3) injection in the knee i.a.) according to group assignment: T12, 2 h; T48, 2 and 24 h; and T72, 2, 24, and 48 h post-RA induction. The different animal groups were euthanized 12, 24, or 72 h post-RA induction, respectively. Synovial exudate levels of IL-10, IL-12p70, TNF-α, INF-γ, and MCP-1 were assessed by flow cytometry, and histopathological analysis of the knee cartilage was conducted. Ozone therapy effectively decreases inflammation, reducing IL-12 and TNF-α, and increasing IL10. O(3) did not statistically affect INF-γ or MCP-1 levels. More expressive results were obtained with group T72, i.e., treated 2, 24, and 48 h post-RA induction, which indicates that longer-term ozone treatment is more effective than a single acute application. Ozone therapy effectively reduced inflammation with effects, at least in part, mediated through reduction of pro-inflammatory cytokines and activation of IL-10 anti-inflammatory cytokine.
32546965 Activation of Cholinergic Anti-Inflammatory Pathway in Peripheral Immune Cells Involved in 2020 BACKGROUND: Studies have shown that α-mangostin (MG) could exert anti-rheumatic effects in vivo by restoring immunity homeostasis, and have indicated that activation of the choline anti-inflammatory pathway (CAP) may contribute to this immunomodulatory property. The current study was designed to further investigate the effects of MG on the CAP in peripheral immune cells and clarify its relevance to the potential anti-rheumatic actions. METHODS: The catalytic activity of acetylcholinesterase (AChE) and expression of α7-nicotinic cholinergic receptor (α7nAChR) in peripheral blood mononuclear cells (PBMCs) from rats with collagen-induced arthritis (CIA) or human volunteers were evaluated after MG treatment. Consequent influences on the immune environment were assessed by flow cytometry and ELISA analyses. Indirect effects on joints resulting from these immune changes were studied in a co-culture system comprised of fibroblast-like synoviocytes (FLSs) and PBMCs. RESULTS: MG promoted α7nAChR expression in PBMCs both in vivo and in vitro, and inhibited the enzymatic activity of AChE simultaneously. Activation of the CAP was accompanied by a significant decrease in Th17 cells (CD4(+)IL-17A(+)), while no obvious changes concerning the distribution of other T-cell subsets were noticed upon MG treatment. Meanwhile, MG decreased the secretion of TNF-α and IL-1β under inflammatory conditions. PBMCs from MG-treated CIA rats lost the potential to stimulate NF-κB activation and pro-inflammatory cytokine production of FLSs in the co-culture system. CONCLUSION: Overall, the evidence suggested that MG can improve the peripheral immune milieu in CIA rats by suppressing Th17-cell differentiation through CAP activation, and achieve remission of inflammation mediated by FLSs.
31948706 Functional Outcomes After Sauve-Kapandji Arthrodesis. 2020 May PURPOSE: The Sauve-Kapandji procedure (SK) combines a distal radioulnar joint (DRUJ) arthrodesis with the creation of an ulnar pseudarthrosis for the salvage of DRUJ instability or arthritis. Despite several published case series, there are limited data on postoperative functional outcomes. This study evaluates patient-reported outcomes of SK using a validated functional outcomes scale. METHODS: We performed a retrospective review of patients who underwent SK in 2 health care systems over 10 years (2008-2018). Preoperative and postoperative range of motion, Quick-Disabilities of the Arm, Shoulder, and Hand (QuickDASH) scores, and wrist plain film radiographic measurements were recorded. Preoperative and postoperative outcomes analyses and subgroup comparisons were performed. RESULTS: We included 57 patients in the study. Surgical indications included posttraumatic DRUJ arthritis (n = 35), rheumatoid arthritis (n = 10), degenerative DRUJ arthritis (n = 7), Madelung deformity (n = 3), psoriatic arthritis (n = 1), and giant cell tumor of bone (n = 1). During the first postoperative year, QuickDASH scores decreased from a mean of 52 before surgery to 28 at 12 months. The QuickDASH scores at final follow-up demonstrated significant improvement in patients with osteoarthritis and inflammatory arthritis. Supination significantly improved after surgery, from 48° to 74°, whereas wrist flexion, wrist extension, and pronation remained unchanged. Radiographically, significant postoperative decreases were seen in ulnar variance and McMurtry's translation index. The postoperative complication rate was 21%, including revision osteotomy in 4 patients (7.0%) and hardware removal in 4 patients (7.0%). No DRUJ nonunions were seen. CONCLUSIONS: The Sauve-Kapandji procedure for DRUJ salvage significantly improved patient-reported outcomes after 1 year and significantly improved supination. Similar functional improvements after SK were seen in both osteoarthritis and inflammatory arthritis. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.
33086964 Assessing an alpha-defensin lateral flow device for diagnosing septic arthritis: reporting 2020 Jan Alpha-defensin (αD), an antimicrobial peptide released by neutrophils in response to bacterial pathogens, was proposed as a novel diagnostic biomarker in synovial fluid. Several reports have shown that αD can serve as a reliable biomarker in the diagnosis of periprosthetic joint infection (PJI). We assessed whether αD could also serve to diagnosis of septic arthritis, a similarly difficult to diagnose PJI. To our knowledge, besides PJI, few reports exist assessing the utility of αD for septic arthritis. We have attempted to diagnose several cases of suspected septic arthritis using the Synovasure(®) αD detection lateral flow device. We report a false-positive case and a false-negative case. The false-negative case we experienced was caused by Staphylococcus capitis, which is coagulase-negative, and possibly represents a low virulence micro-organism infection. The false-positive case was ultimately diagnosed as seronegative rheumatoid arthritis and possessed calcium pyrophosphate depositions. False positives have been suggested to occur in conditions where neutrophils are mobilised. As for PJI, in cases where diagnosis is difficult, αD can be an additional diagnostic indicator. However, making a definitive diagnosis using the αD lateral flow device alone was found to be difficult. The utility of αD in assessing septic arthritis is inconclusive; therefore, larger prospective clinical studies should be considered for a better assessment.
31161663 Epidemiology of uveitis in a region of southern Sweden. 2020 Feb PURPOSE: To analyse the distribution and treatment of uveitis in a region of southern Sweden and compare the results with previously reported European data. METHODS: Anonymized data for all individuals in the region with an ICD-10 diagnosis that indicated uveitis between 2013 and 2017 were extracted from a computerized healthcare register. RESULTS: In total, 2483 patients were diagnosed with uveitis during 2013-2017. Anterior uveitis was diagnosed in 93%, intermediate in 1%, posterior in 5% and panuveitis in 1% of cases. An associated diagnosis was found in 14%, and the five most common associated diseases were herpes simplex/zoster (4.9%), inflammatory bowel disease (2.2%), rheumatic arthritis (1.9%), ankylosing spondylitis (1.8%) and sarcoidosis (1.8%). Systemic treatment was used in 14% of the cases. The period prevalence of uveitis was 700 cases per 100 000 individuals, and the yearly incidence was estimated to 108 cases/year/100 000 individuals. CONCLUSIONS: Compared with studies from referral clinics, this community-based study had a large proportion of anterior uveitis (93%) and uveitis without associated diagnosis (86%). Uveitis was also much more common among elderly than shown in previous research. The distribution of possible associated diagnosis conformed to several previous European studies.
32952620 Effects of intra-articular pulsed radiofrequency current administration on a rabbit model 2020 Nov Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by synovial proliferation and inflammation. Intra-articular corticosteroid injections are commonly used for the treatment of arthritis affecting one or two joints. Although corticosteroid injections are fast-acting, repeated usage can result in severe adverse events. Recently, intra-articular pulsed radiofrequency (PRF) stimulation has been proposed to treat arthritis. The aim of the present study was to compare the effectiveness of intra-articular PRF with corticosteroid injection based on histopathological and motion analysis of an ovalbumin (OVA)-induced RA rabbit model. RA was induced in the right knee joint of 18 rabbits via OVA injection. The rabbits were randomly allocated into a PRF, an intra-articular corticosteroid injection or a sham PRF stimulation group. Movement was assessed in the rabbits before treatment, then at 2, 4 and 8 weeks after treatment using walking distance, fast walking time and mean walking speed. Histopathological evaluation of the distal femur and synovium was conducted 2, 4 and 8 weeks after treatment. Motion analysis demonstrated that changes in all movement variables showed significant group and time interaction as well as group effect among the three groups. The semiquantitative score based on the histopathological findings for the distal femoral condyle decreased 2 and 4 weeks after both the PRF and steroid groups, compared with the sham PRF group. Moreover, in the synovium, the semiquantitative histological score in the PRF and steroid groups tended to be lower compared with the sham PRF group, although this result was not statistically significant. Thus, intra-articular PRF stimulation may delay cartilage destruction and improve functional motion in RA.
32725138 NLRP12 gene mutations and auto-inflammatory diseases: ever-changing evidence. 2020 Nov 1 Systemic auto-inflammatory diseases (SAID) are a group of rare inherited conditions characterized by a dysregulation of the immune system and associated with recurrent episodes of fever and systemic inflammation. Patients with NLRP12 variants develop a rare autosomal dominant condition known as familial cold-induced autoinflammatory syndrome (FCAS2, OMIM #611762) that has been related to several different clinical manifestations including autoimmunity and immune deficiencies. In past years, several new variants have been described; however, their clinical relevance is sometimes uncertain, especially when they have been detected in healthy subjects. To our knowledge 61 patients with NLRP12 variants have been reported so far in the literature. Here we report the case of a 33-year-old woman with a history of recurrent fever and symmetric and additive poly-arthritis, fulfilling diagnostic criteria for RA, who was found to harbour two variants in the NLRP12 gene (OMIM *609648) and provide a review of the literature on similar cases.
31643544 Methotrexate. 2012 Methotrexate is an antineoplastic and immunosuppressive agent widely used in the therapy of leukemia, lymphoma, solid tumors, psoriasis and rheumatoid arthritis. When given in high intravenous doses, methotrexate can cause acute elevations in serum enzymes, and long term methotrexate therapy has been associated with frequent but mild elevations in serum liver enzymes and, more importantly, with development of chronic liver injury, progressive fibrosis, cirrhosis and portal hypertension.
32798283 Improvement of Severe Fatigue Following Nuclease Therapy in Patients With Primary Sjögren 2021 Jan OBJECTIVE: To assess the safety and efficacy of RSLV-132, an RNase Fc fusion protein, in a phase II randomized, double-blind, placebo-controlled clinical trial in patients with primary Sjögren's syndrome (SS). METHODS: Thirty patients with primary SS were randomized to receive treatment with RSLV-132 or placebo intravenously once per week for 2 weeks, and then every 2 weeks for 12 weeks. Eight patients received placebo and 20 patients received RSLV-132 at a dose of 10 mg/kg. Clinical efficacy measures included the European League Against Rheumatism (EULAR) Sjögren's Syndrome Disease Activity Index, EULAR Sjögren's Syndrome Patient Reported Index (ESSPRI), Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), Profile of Fatigue (ProF), and the Digit Symbol Substitution Test (DSST). RESULTS: Patients randomized to receive RSLV-132 experienced clinically meaningful improvements in the ESSPRI score (P = 0.27), FACIT-F score (P = 0.05), ProF score (P = 0.07), and DSST (P = 0.02) from baseline to day 99, whereas patients who received placebo showed no changes in any of these clinical efficacy measures. This improvement was significantly correlated with increased expression of selected interferon-inducible genes (Pearson's correlations, each P < 0.05). CONCLUSION: Administration of RSLV-132 improved severe fatigue, as determined by 4 independent patient-reported measures of fatigue, in patients with primary SS.