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ID PMID Title PublicationDate abstract
32782445 Proteomic analysis of synovial fluid from rheumatic arthritis and spondyloarthritis patien 2020 BACKGROUND: The aetiologies and pathogeneses of the joint diseases rheumatoid arthritis (RA) and spondyloarthritis (SpA) are still not fully elucidated. To increase our understanding of the molecular pathogenesis, we analysed the protein composition of synovial fluid (SF) from rheumatoid arthritis (RA) and spondyloarthritis (SpA) patients. METHODS: Fifty-six synovial fluid samples (RA, n = 32; SpA, n = 24) were digested with trypsin, and the resulting peptides were separated by liquid chromatography and analysed by tandem mass spectrometry. Additionally, the concentration of cell-free DNA (cfDNA) in the synovial fluid was measured, and plasma C-reactive protein (CRP) was determined. RESULTS: Three hundred thirty five proteins were identified within the SF. The more abundant proteins seen in RA SF were inflammatory proteins, including proteins originating from neutrophil granulocytes, while SpA SF had less inflammatory proteins and a higher concentration of haptoglobin. The concentration of cell-free DNA in the SF increased together with proteins that may have originated from neutrophils. Plasma CRP levels in both RA and SpA, correlated to other acute phase reactants. CONCLUSIONS: The proteomic results underline that neutrophils are central in the RA pathology but not in SpA, and even though inhibitors of neutrophils (migration, proteinase inhibitors) were present in the SF it was not sufficient to interrupt the disease process.
29644928 Salivary gland ultrasound is linked to the autoimmunity profile in patients with primary S 2020 Jan OBJECTIVE: Salivary gland ultrasound (SGU) is a reliable technique for assessing the salivary glands in patients with primary Sjögren’s syndrome (pSS). The aim of this study was to elucidate the relationship between SGU findings and autoimmunity in patients with pSS. METHODS: Patients with pSS underwent an SGU assessment. The patients were classified into three groups according to their autoimmunity profile: the complete positive group (positive rheumatoid factor, antinuclear antibodies, and anti-Ro/anti-La antibodies), the partial seropositive group (positivity of at least one autoantibody but not all), and the seronegative group. RESULTS: In total, 93 patients were evaluated. Eighty-six (92.5%) were female, and their median age was 49.5 years. The median disease duration was 12.3 years. Pathological SGU findings were present in 32 (34.4%) patients [25 of 36 (78.1%) in the complete positive group and 7 of 44 (21.9%) in the partial positive group]. Patients with pathological SGU findings had a shorter disease duration and slightly higher European League Against Rheumatism Sjögren’s syndrome disease activity index. CONCLUSIONS: The autoimmunity profile and pathological SGU findings are strongly associated with each other in patients with pSS. However, the disease duration does not seem to be related to pathological SGU findings.
33162816 MicroRNA expression profile of Lacrimal Glands in rabbit autoimmune dacryoadenitis model. 2020 Purpose: To identify the differential expression of microRNAs (miRs) and the related gene networks and signal pathways in lacrimal glands (LGs) of rabbit autoimmune dacryoadenitis. Methods: Autoimmune dacryoadenitis in rabbits was induced by transferring activated peripheral blood lymphocytes (PBLs). The LGs of normal and model group rabbits were collected for small RNA sequencing. The most differentially expressed miRs were validated by quantitative real time-polymerase chain reaction (qRT-PCR). Further, bioinformatics analysis including target gene prediction, Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed. Results: A total of 15 miRs were differentially expressed in the LGs of rabbit autoimmune dacryoadenitis relative to normal controls. GO and KEGG analysis revealed that most target genes of these dysregulated miRs were implicated in MAPK signaling pathway. Conclusion: Our results showed for the first time the differentially expressed miRs and the related pathways involved in the pathogenesis of rabbit autoimmune dacryoadenitis. These results may contribute to elucidating molecular pathogenesis of Sjögren's syndrome (SS) dry eye.
33040168 Anti-Sjögren's-syndrome-related antigen A autoantibodies (Anti-SSA antibody) and meningoe 2021 Oct Aseptic meningoencephalitis (AME) constitutes a variable proportion of meningoencephalitis. Patients with AME are not routinely evaluated for autoimmune disorders. Primary Sjögren's syndrome (pSS) is a prevalent, but under suspected systemic autoimmune disease characterised by exocrinopathy, though sicca symptoms may not be the dominant or presenting feature. This study was undertaken to enumerate the clinical, radiological and laboratory features of meningoencephalitis related to pSS among the total cohort of meningoencephalitis admitted in our hospital. Retrospective patient records were screened for diagnosis of meningoencephalitis from April 2016 to March 2020. Those patients with anti-SSA positivity and clinical diagnosis of pSS were included. We have reviewed all cases of Sjögren's syndrome with meningoencephalitis available in literature. Four patients with meningoencephalitis with pSS were identified. Their clinical presentations, investigations, and good response to steroids have been described with special emphasis on evolving clinical features. In all patients, sicca features were absent. Anti-SSA was positive in all. The diagnosis of pSS was considered after ruling out all infectious and other autoimmune aetiologies. Two had extra-neurological organ manifestations and required addition of second line immunosuppressive agents for optimum disease control. Consistent with this case series, absent sicca symptoms have been described in pSS patients presenting with meningoencephalitis in literature. This case series is of special interest as it describes the initial presentation of pSS as meningoencephalitis with sicca features in absentia, thereby highlighting the need for a high index of suspicion and the need for workup for pSS in AME.
31757716 LncRNA PVT1 links Myc to glycolytic metabolism upon CD4(+) T cell activation and Sjögren' 2020 Feb The hyperproliferation and hyperactivation of CD4(+) T cells in salivary gland tissue is a hallmark of Sjögren's syndrome (SS). However, the role of long noncoding RNAs (lncRNAs) in the pathological process of SS and CD4(+) T cell activation has not been fully elucidated. Here, we reported that lncRNA PVT1 was involved in the glycolytic metabolism reprogramming and proliferation upon CD4(+) T cell activation. Expression of PVT1 was positively related with CD4(+) T cell activation both in SS patients and Ex vivo antigen simulation. Depletion of PVT1 decreased the proliferation of murine CD4(+) T cells and Jurkat T cells upon activation. We also showed that expression of the transcription factor Myc is regulated by PVT1 under antigen simulation. Depletion of PVT1 significantly decreased the expression of glycolytic genes, as well as several pivotal glycolytic proteins that were directly transcribed by Myc. Measurement of glucose content and lactate secretion indicated a defected lactate secretion and glucose uptake in PVT1-depleted T cells. Additionally, the real-time extracellular acidification rate (ECAR) and oxygen consumption rate (OCR) measurement also affirmed that PVT1 maintains glycolytic levels, glycolytic capacity under stress and ECAR/OCR ratios during T cell activation. Polarizing assays indicate that PVT1 depletion defected the function of Th1 effector cells as well as down-regulated Myc expression and glycolytic levels. Furthermore, we observed increased glycolytic levels in CD4(+) T cells from SS-like NOD/Ltj mice. Treatment with 2-deoxy-d-glucose (2-DG), an inhibitor of glycolysis, significantly decreased the extent of lymphocyte infiltration and CD4(+) T cell numbers and attenuated the defect of salivary flow in the lesioned submandibular glands of NOD/Ltj mice. Thus, our study demonstrated that lncRNA PVT1, which was upregulated in the CD4(+)T cells of SS patients, could maintain the expression of Myc, thus controlling the proliferation and effector functions of CD4(+) T cells through regulating the reprogramming of glycolysis. Inhibition of glycolysis could attenuate the proliferation of CD4(+) T cells and the SS-like autoimmune response. Our study provides a novel mechanistic function of lncRNA PVT1 in the pathogenesis of SS.
33120855 Tracheobronchial amyloidosis in primary Sjögren syndrome: A case report. 2020 Oct 23 RATIONALE: Tracheobronchial amyloidosis (TBA) associated with Sjögren syndrome is very rare. Here, we describe a case with this phenomenon, in order to better understand the condition. PATIENT CONCERNS: A 52-year-old woman presented after 6 months of coughing, sputum, and dyspnea. Chest computed tomography revealed thickened bronchial walls, which were irregular on the left side the trachea. She had a history of dry eye and dry mouth of at least 3 years' duration. DIAGNOSES: Sjögren syndrome was diagnosed based on her symptoms, ophthalmological and parotid examination, and immunological and autoantibody tests. The diagnosis of TBA was confirmed by Congo red staining of a tracheal biopsy. INTERVENTIONS: The patient was given glucocorticoids without any other immunosuppressants. OUTCOMES: The symptoms improved after 6 months. LESSONS: TBA associated with Sjögren syndrome is a rare condition. TBA is characterized by amyloid deposition to the trachea in the absence of systemic amyloidosis. Diagnosis requires tissue biopsy with demonstration of amyloid deposition.
32415709 Immune-mediated axonal dysfunction in seropositive and seronegative primary Sjögren's syn 2020 May OBJECTIVE: The present study investigates the peripheral neuropathy in Primary Sjögren's syndrome (pSS) using the nerve excitability test to further elucidate how peripheral nerves are affected by the autoantibodies. METHODS: Each patient received clinical evaluation, examination for anti-SSA/Ro and anti-SSB/La antibodies titer, paired motor and sensory nerve excitability test, thermal quantitative sensory test (QST), and nerve conduction study (NCS). RESULTS: A total of 40 pSS patients wasenrolled. Motor axonal study of the pSS with positive anti-SSA/Ro or anti-SSB/La antibodies (n = 28) was found to have increased stimulus for 50% compound muscle action potential (CMAP) (P < 0.05), increased rheobase (P < 0.01), increased minimum I/V slope (P < 0.01) and hyperpolarizing I/V slope (P < 0.05), increased relative refractory period (RRP, P < 0.001), decreased accommodation of threshold electrotonus toward depolarizing current (P < 0.05), and increased accommodation toward hyperpolarizing current (P < 0.05). Seronegative pSS (n = 10) showed much less prominent motor axonal changes, showing only increased minimum I/V slope (P < 0.05). Sensory axonal study in seropositive pSS patients is found to have increased stimulus for 50% sensory nerve action potential (SNAP) (P < 0.01), decreased latency (P < 0.01), increased RRP (P < 0.01), and increased subexcitability (P < 0.05). Seronegative pSS patients have shown no significant sensory axonal changes. Thermal QST showed more prominent abnormalities in seronegative pSS compared to seropositive pSS. INTERPRETATION: Anti-SSA/Ro and anti-SSB/La autoantibodies might cause dysfunction in nodal and internodal region of the axon and small nerve fibers; meanwhile, autoreactive antibodies in seronegative pSS mainly affect small nerve fibers. Thus, the underlying pathophysiology for the two types of pSS is different.
33062067 Real-world evidence of the impact of adalimumab on work productivity and sleep measures in 2020 OBJECTIVE: Our aim was to evaluate the effect of adalimumab on work productivity measures, overall activity impairment, and sleep quality in patients with active moderate to severe rheumatoid arthritis (RA), psoriatic arthritis (PsA), or ankylosing spondylitis (AS) treated in routine care settings in Greece and determine factors associated with work impairment and sleep disturbance. METHODS: Patients with active moderate to severe RA (n = 184), PsA (n = 166), and AS (n = 150) were enrolled in this 24-month, prospective, observational study at 80 hospital outpatient clinics and private practices throughout Greece. Patients received adalimumab alone or in combination with standard antirheumatic therapies according to routine care. Work productivity and sleep were assessed through two patient-reported outcome measures: the Work Productivity and Activity Impairment-General Health questionnaire and the Medical Outcomes Study Sleep Scale (MOS-SS). Pearson correlation coefficients were estimated to assess the association of work impairment and sleep disturbances with disease activity scores. RESULTS: In the overall population, adalimumab significantly lowered absenteeism [mean (95% confidence interval) reduction, 18.9% (13.3-24.5%); n = 100]; presenteeism [40.0% (33.8-46.3%); n = 98], overall work productivity impairment [46.8% (40.4-53.2%); n = 94], activity impairment [47.0% (44.3-49.6); n = 421], and the MOS-SS sleep problems index [31.6 (29.5-34.1); n = 421] after 24-month treatment (p < 0.001). Significant improvements were also noted across the RA, PsA, and AS subpopulations (p < 0.05). Improvements in overall work impairment and sleep disturbance positively correlated with improvements in disease activity measures. CONCLUSION: Adalimumab improves work productivity and sleep problems while lowering disease activity in patients with moderate to severe RA, PsA, and AS managed in real-world settings.
33496118 [Anti-arthritic-related metal bioavailability for optimal compatibility ratio of Aconiti R 2020 Dec Trace metals deficiency or excess are associated with the etiology and pathogenesis of rheumatoid arthritis(RA). Aconiti Radix Cocta(A) and Paeoniae Radix Alba(B) are commonly used together for the treatment of RA. In this study, we aim to determine anti-arthritic-related metal bioavailability in the compatibility of herb A and B for avoiding metal deficiency or excess, and optimize the combination ratio of herb A and B, accordingly. Anti-arthritic-related metal bioaccessibility were evaluated by in vitro simulator of all gastrointestinal tract(including mouth, stomach, small and large intestines), and the roles of gastrointestinal digestive enzymes and intestinal microflora were investigated. Anti-arthritic-related metal bioavailability was assessed by the affinity adsorption with liposomes. The results indicated that compatibility proportion of corresponding herbal plants, gastrointestinal digestion and microbial metabolic, which could affect metal digestion and absorption. The optimal compatibility proportion of 1 A∶1 B is recommended, according to the dose of anti-arthritic-related metal bioavailability, which is often chosen for clinical practice of RA therapy. Thus, anti-arthritic-related metal bioavailability might be the key active substances for RA treatment.
33076422 Diagnostic Power of Galectin-3 in Rheumatic Diseases. 2020 Oct 15 BACKGROUND: The purpose of our study was to assess the diagnostic power of galectin-3 and compare its between rheumatic diseases and with routinely used tests such as CRP and ESR. METHODS: Eighty-two patients with rheumatoid arthritis (RA), 49 patients with systemic sclerosis (SSc), and 18 patients with systemic lupus erythematosus (SLE) were enrolled in this study. The control group comprised 30 healthy controls. Serum galectin-3 concentration was measured using immunochemical method. RESULTS: The galectin-3 concentration were significantly elevated in the RA, SSc, and SLE in comparison to the controls (p = 0.000, p = 0.000, p < 0.001; respectively). However, there were no significant differences in the serum galectin-3 levels between rheumatic diseases (H = 0.395, p = 0.821). In RA and SSc patients, galectin-3 positively correlated with erythrocyte sedimentation rate (R = 0.332, p = 0.004; R = 0.384, p = 0.009; respectively). ROC analysis revealed that galectin-3 had an excellent diagnostic power in RA (AUC = 0.911) and SSc (AUC = 0.903) and very good for SLE (AUC = 0.859). CONCLUSION: We concluded that diagnostic power of serum galectin-3 is as great as CRP and ESR in rheumatic diseases and it can be a very good laboratory marker in RA and SSc patients and a useful tool in the diagnosis of SLE.
32582289 Impact of Diverse Data Sources on Computational Phenotyping. 2020 Electronic health records (EHRs) are widely adopted with a great potential to serve as a rich, integrated source of phenotype information. Computational phenotyping, which extracts phenotypes from EHR data automatically, can accelerate the adoption and utilization of phenotype-driven efforts to advance scientific discovery and improve healthcare delivery. A list of computational phenotyping algorithms has been published but data fragmentation, i.e., incomplete data within one single data source, has been raised as an inherent limitation of computational phenotyping. In this study, we investigated the impact of diverse data sources on two published computational phenotyping algorithms, rheumatoid arthritis (RA) and type 2 diabetes mellitus (T2DM), using Mayo EHRs and Rochester Epidemiology Project (REP) which links medical records from multiple health care systems. Results showed that both RA (less prevalent) and T2DM (more prevalent) case selections were markedly impacted by data fragmentation, with positive predictive value (PPV) of 91.4 and 92.4%, false-negative rate (FNR) of 26.6 and 14% in Mayo data, respectively, PPV of 97.2 and 98.3%, FNR of 5.2 and 3.3% in REP. T2DM controls also contain biases, with PPV of 91.2% and FNR of 1.2% for Mayo. We further elaborated underlying reasons impacting the performance.
32540237 Validity and Responsiveness of Preference-Based Quality-of-Life Measures in Informal Carer 2020 Jun OBJECTIVES: Carer quality-of-life (QoL) effects are recommended for inclusion in economic evaluations, but little is known about the relative performance of different types of QoL measures with carers. This study evaluated the validity and responsiveness of 3 care-related QoL measures (the Carer Experience Scale [CES], CarerQoL-7D, and ASCOT-Carer), 1 health-related QoL measure (the EQ-5D-5L), and 1 generic QoL measure (the ICECAP-A). METHODS: Validity and responsiveness were assessed in a UK sample of informal carers of adults with dementia, stroke, mental illness, or rheumatoid arthritis. A questionnaire containing the 5 QoL measures was posted to carers identified through the Family Resources Survey (N = 1004). Hypotheses regarding the anticipated associations between constructs related to the QoL of carers were tested to investigate construct validity and responsiveness. RESULTS: Each measure exhibited some level of construct validity. In general, larger effect sizes and stronger associations were detected for the ASCOT-Carer and ICECAP-A measures in the pooled sample and across all conditions. The 5 measures did not exhibit clear responsiveness to changes over a 12-month period in care recipient health status or hours of care provided per week. CONCLUSION: The results of this study provide initial evidence of the validity of care-related, health-related, and generic QoL (capability) measures in informal carers of adults with 4 highly prevalent conditions. Care-related measures were not always more sensitive to constructs associated with QoL of carers compared with generic measures. The performance of the ICECAP-A was comparable with that of the best-performing care-related measure, the ASCOT-Carer.
32440826 Biologic Disease-Modifying Antirheumatic Drug Prescription Patterns Among Rheumatologists 2020 Sep INTRODUCTION: Tumor necrosis factor inhibitors (TNFi) are commonly used as first-line therapy (biologic disease-modifying antirheumatic drug [bDMARD] and targeted synthetic DMARD [tsDMARD]: defined as targeted therapy) for patients with moderate-to-severe rheumatoid arthritis (RA), usually combined with conventional synthetic DMARDs (csDMARDs) but sometimes as monotherapy. If treatment fails, patients cycle to another TNFi (cycling) or switch to a targeted therapy with a different mode of action (MOA; switching). The study aimed to examine prescribing patterns and reasons for current RA treatment practice in Europe (EU5: France, Germany, Italy, Spain, UK) and Japan. METHODS: Data were collected from the Adelphi Disease Specific Programme™ (DSP; Q1-Q2 2017). Rheumatologists seeing ≥ 10 (EU5) and ≥ 5 (Japan) patients with RA a month completed Patient Record Forms. Patients ≥ 18 years old, with RA diagnosis and complete RA-targeted therapy history were included. Patients were grouped based on first-line targeted therapy class, and on whether first-line targeted therapy was monotherapy (targeted therapy alone) or combination therapy (targeted therapy and csDMARD). Those patients receiving TNFi at first-line and with ≥ 1 targeted therapy were classified as TNFi cyclers or MOA switchers. Univariate analysis compared factors across groups. Patient demographics and characteristics compared across groups; physician reasoning for targeted therapy change; and time to discontinuation of targeted therapy. RESULTS: In EU5 and Japan, respectively, 1741 and 147 patients were included; at first-line, 80.8% and 64.6% received TNFi and 76.0% and 77.6% received combination therapy. Overall in EU5, more combination therapy than monotherapy patients reached maximum csDMARD dose before first-line targeted therapy (P < 0.05); disease severity was higher in patients initiating TNFi versus non-TNFi (P < 0.05). In Japan, trends were similar but not significant. The most common reason physicians gave for changing therapy following first-line targeted therapy was 'secondary lack of efficacy' (EU5: 46.2%; Japan: 53.8%). In EU5 and Japan, respectively, of 365 and 22 patients who received second-line targeted therapy, 52.1% and 54.5% were MOA switchers. In EU5, TNFi cyclers had longer time from diagnosis to second-line targeted therapy initiation than MOA switchers (P = 0.04). CONCLUSIONS: TNFis were the most commonly prescribed targeted therapy at first-line. Between 10 and 20% of patients prescribed a TNFi as first-line targeted therapy did so without concomitant csDMARD. Almost half of patients cycled to another TNFi at second-line.
32774633 Cricoarytenoid joint arthritis: a possible complication of dermatomyositis. 2020 Cricoarytenoid joint arthritis is most frequently reported in Rheumatoid Arthritis and in other systemic diseases such as Sjogren's syndrome, Systemic Lupus Erythematosus, Ankylosing Arthritis, Juvenile Chronic Arthritis, and autoimmune hepatitis but it has not been reported in dermatomyositis. In this paper, we report the case of a 43 years-old woman treated for dermatomyositis who presented with hoarseness and severe odynophagia. The laryngoscopy revealed the presence of an extensive white swelling of the left cricoarytenoid joint with reduced mobility of the left vocal cord, consistent with left cricoarytenoid joint arthritis, which has not previously been described in dermatomyositis to our knowledge. Treatment with high doses of prednisone produced a complete resolution of the laryngeal symptoms.
33116698 A Cost per Responder Model for Abatacept versus Adalimumab Among Rheumatoid Arthritis Pati 2020 PURPOSE: The primary objective of this study was to compare the cost per responder (CPR) between abatacept and adalimumab among seropositive rheumatoid arthritis (RA) patients. PATIENTS AND METHODS: CPR analysis was conducted from a US payer perspective over 24 weeks for early moderate-to-severe seropositive RA patients. Efficacy data (American College of Rheumatology [ACR] improvement criteria [ACR20/50/70] and DAS28-C reactive protein <2.6) for abatacept and adalimumab were sourced from the post hoc analysis of the Early AMPLE trial (NCT02557100). Medication costs were considered assuming complete adherence. A 30% rebate was applied for adalimumab in the base case. RESULTS: At week 24, the total per patient pharmacy cost was $26,273.34 and $21,731.18, whereas the CPR (using ACR70 as the responder definition) was $46,337.46 and $74,935.10 (difference of -$28,597.64) for abatacept and adalimumab, respectively. The CPR was consistently lower for abatacept compared to adalimumab across all clinical measures, with differences ranging from -$7099.32 to -$43,608.97. CONCLUSION: While the pharmacy cost was higher for abatacept compared to adalimumab, due to its higher clinical efficacy, the CPR was consistently lower for seropositive RA patients treated with abatacept. The results may be useful for healthcare decision-makers in understanding how to optimize treatment for seropositive RA patients while minimizing costs in today's budget-constrained health environment.
33146470 Impact of hydroxychloroquine on the gestational outcomes of pregnant women with immune sys 2021 Feb AIM: To evaluate the impact of hydroxychloroquine (HCQ) on the perinatal outcomes of pregnancies with immune system disorders that necessitate the use of the drug. METHODS: This cohort consisted of 202 pregnancies with poor obstetric history and immune system problems. Patients enrolled in special antenatal care program were administered low-dose low-molecular-weight heparin, low-dose salicylic acid and low-dose corticosteroid (prophylaxis protocol) as soon as their pregnancies were confirmed. Pregnancies with systemic lupus erythematosis, Sjogren syndrome and rheumatoid arthritis were additionally administered HCQ 200 mg daily as a part of their routine treatment. Pregnancies using HCQ were included in the study group (n = 39) while the remainders were included in control group (n = 163). We compared the groups in terms of the presence of miscarriage, fetal growth restriction (FGR), preeclampsia and preterm birth, as well as gestational week at birth, birthweight and "APGAR score of <7" at 10th minute. RESULTS: Miscarriage rates were 28.2% and 28.2% while preterm birth rates were 16.6% and 28.2% in the control and study groups, respectively (P = 0.215). Preeclampsia and HCQ-related side effects were not detected in the groups. There were also no significant differences between the groups in terms of FGR, gestational day at birth, birthweight and the presence of "APGAR score <7" at 10th minute (P = 0.462, P = 0.064, P = 0.273 and P = 0.627, respectively). CONCLUSION: Low-dose low-molecular-weight heparin, low-dose salicylic acid and low-dose corticosteroid prophylaxis together with HCQ seem to be promising in pregnancies with immune system disorders. HCQ seems to be a safe and effective drug in low dosages.
32607017 Functional Disability and Its Determinants in Ecuadorian Patients with Rheumatoid Arthriti 2020 INTRODUCTION: Disability in RA is associated with loss of workdays, greater use of health resources and a higher prevalence of depression. The purpose of this study was to determine the prevalence of functional disability and the factors associated with it. METHODS: A cross-sectional study was carried out during January-June 2019 at a rheumatology clinic in the city of Guayaquil. Patients with pre-established RA were included. Functional disability was measured using the HAQ-DI. Data were analyzed using the statistical program SPSS v22. We compared characteristics between patients with and without disability using Student's t-test and chi-square. A multiple logistic regression model for functional disability was made. RESULTS: We included 395 patients, 87.8% female and 12.2% male with a mean age of 51.4±12 years and mean duration of disease 13.8±7 years. Most patients had extra-articular manifestations (80.8%) and comorbidities (81.3%). The mean HAQ-DI was 0.8±0.9, with a prevalence of disability of 26.6%. We found a statistically significant relationship between disability and female sex (p=0.018), age (p=0.020), presence of extra-articular manifestations (p=0.008), myalgia (p<0.001) and fatigue (p<0.001). In addition, patients with disabilities had a lower employment rate (26.7%) compared to those without disability (45.5%, p=0.001). In the multivariate logistic analysis, only depression (p=0.029), diabetes (p=0.003), SJC (p=0.001) and VAS of pain (p=0.004) were significantly related to functional disability. CONCLUSION: Disability affects a quarter of patients with RA. Among the determinants of disability, we found female sex, older age, grade of pain, inflammatory markers and the level of disease activity.
32501653 Drug discontinuation in pregnant women with psoriasis: The PSO-MOTHER cohort study. 2020 Aug PURPOSE: To analyse the drug use pattern in women with psoriasis before, during and after pregnancy. METHODS: All children born (2009-2016) in a central Italian region (Lazio) to mothers with a diagnosis of psoriasis were identified. Drug use patterns (biologicals, systemic, and topical), and discontinuation and switching of drug therapies before, during, and after pregnancy were studied. Findings were compared with data from a population exposed to similar drug therapies (eg, antirheumatic drugs). RESULTS: Among 3499 deliveries by women affected by psoriasis, 1876 (53.6%) were diagnosed with this condition before the Last Menstrual Period (LMP). Of these, 525 (27.9%) had at least one drug prescription for psoriasis therapy during 6 months before LMP. For each class of drugs considered, there was a general decrease in its use during pregnancy. Considering the two trimesters preceding LMP and the three trimesters of pregnancy, the following percentages of prescriptions were observed: from 10.5% to 0% for biologicals, 7.2% to 2.5% for the conventional systemic drugs, and 51.1% to 9.4% for the topical treatments. After delivery, previous treatments were resumed. Similar results were observed for rheumatoid arthritis, a chronic condition. CONCLUSIONS: Majority of drugs come with warnings regarding potential embryo-fetotoxicity, which might play a role in the decision to continue treatments during pregnancy. According to our study pregnancy appears to have a significant influence on drug prescriptions of different pharmacological treatments for psoriasis.
31853295 Role and mechanism of miR-144-5p in LPS-induced macrophages. 2020 Jan The aim of the present study was to explore the possible role of microRNA-144-5p (miR-144-5p) in rheumatoid arthritis (RA) and the associated mechanism. Following the induction of THP-1 cell differentiation into macrophages by phorbol ester (100 ng/ml) treatment, an in vitro inflammatory model of RA was established by treating the THP-1 macrophages with 1 µg/ml lipopolysaccharide (LPS). The level of miR-144-5p was subsequently measured using reverse transcription-quantitative PCR, which found that the expression of miR-144-5p was significantly reduced in LPS-treated THP-1 macrophages. Bioinformatics analysis and a dual-luciferase reporter assay were used to predict and confirm TLR2 as a direct target of miR-144-5p, respectively. Toll-like receptor 2 (TLR2) was then validated as a target gene of miR-144-5p. The effects of miR-144-5p upregulation and TLR2 silencing on LPS-treated THP-1 macrophages were then determined by transfection with miR-144-5p mimic and TLR2-siRNA, respectively. Cell viability was subsequently measured using a Cell Counting Kit-8 assay, whilst the expression of tumor necrosis factor-α (TNF-α), interleukin (IL)-6 and IL-8 secreted by THP-1 macrophages was measured using ELISA. Western blotting was performed to measure p65 phosphorylation (p-p65) in the NK-κB signaling pathway. It was found that miR-144-5p overexpression reduced macrophage cell viability, reduced the expression of TNF-α, IL-6 and IL-8, and reduced the expression of TLR2 and p-p65 compared with the control group. Likewise, TLR2 silencing also reduced macrophage cell viability and reduced the expression of TNF-α, IL-6 and IL-8 in THP-1 macrophages. In conclusion, the data from the present study suggested that miR-144-5p overexpression reduced THP-1 macrophage cell viability and inhibited the expression of TNF-α, IL-6 and IL-8 in cells, possibly by inhibiting the expression of TLR2 and suppressing the activation of NK-κB signaling. Therefore, miR-144-5p may serve as a novel therapeutic target for the treatment of RA.
33134809 Incidence, predictive factors and severity of methotrexate-related liver injury in rheumat 2020 OBJECTIVES: The aims were to determine the incidence rate, predictive factors and severity of liver injury that develops during MTX treatment for RA and to evaluate the role of pretreatment hepatic fat deposition. METHODS: We used an ongoing real-life registry containing RA patients who had started MTX between August 2007 and April 2018 at participating institutions. The liver-to-spleen attenuation ratio on CT scans at enrolment was used to evaluate pretreatment fat deposition quantitatively. Patients were followed until persistent transaminitis developed or until the end of the study. Liver biopsy was performed for patients who presented with persistent transaminitis. RESULTS: We followed 289 new MTX users without pretreatment elevations of transaminases (mean follow-up time, 58.3 months). Hepatic fat deposition was detected in half of the patients at enrolment. During follow-up, persistent transaminitis occurred at a crude incidence rate of 3.13 per 100 person-years, and the cumulative incidence at 5 years was estimated to be 13%. A multivariate Fine-Gray regression analysis showed that the most important predictive factors were pre-existing moderate to severe fat deposition (adjusted hazard ratio, 7.69; 95% CI: 3.10, 19.10) and obesity (adjusted hazard ratio, 2.68; 95% CI: 1.37, 5.25). Non-alcoholic steatohepatitis (NASH) was the most predominant pattern in liver biopsy samples. Hepatic fibrosis was found in 90% of samples, but most cases were not advanced. CONCLUSION: Aggravation of underlying fatty liver to NASH with fibrosis seems to be an important mechanism of liver injury that occurs in MTX-treated RA patients.