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ID PMID Title PublicationDate abstract
31026816 Risk factor analysis of postoperative kyphotic change in subaxial cervical alignment after 2019 Apr 26 OBJECTIVELittle is known about the risk factors for postoperative subaxial cervical kyphosis following craniovertebral junction (CVJ) fixation. The object of this study was to evaluate postoperative changes in cervical alignment and to identify the risk factors for postoperative kyphotic change in the subaxial cervical spine after CVJ fixation.METHODSOne hundred fifteen patients were retrospectively analyzed for postoperative subaxial kyphosis after CVJ fixation. Relations between subaxial kyphosis and radiological risk factors, including segmental angles and ranges of motion (ROMs) at C0-1, C1-2, and C2-7, and clinical factors, such as age, sex, etiology, occipital fixation, extensor muscle resection at C2, additional C1-2 posterior wiring, and subaxial laminoplasty, were investigated. Univariate and multivariate logistic regression analyses were conducted to identify the risk factors for postoperative kyphotic changes in the subaxial cervical spine.RESULTSThe C2-7 angle change was more than -10° in 30 (26.1%) of the 115 patients. Risk factor analysis showed CVJ fixation combined with subaxial laminoplasty (OR 9.336, 95% CI 1.484-58.734, p = 0.017) and a small ROM at the C0-1 segment (OR 0.836, 95% CI 0.757-0.923, p < 0.01) were related to postoperative subaxial kyphotic change. On the other hand, age, sex, resection of the C2 extensor muscle, rheumatoid arthritis, additional C1-2 posterior wiring, and postoperative segmental angles were not risk factors for postoperative subaxial kyphosisCONCLUSIONSSubaxial alignment change is not uncommon after CVJ fixation. Muscle detachment at the C2 spinous process was not a risk factor of kyphotic change. The study findings suggest that a small ROM at the C0-1 segment with or without occipital fixation and combined subaxial laminoplasty are risk factors for subaxial kyphotic change.
30543917 Autoimmune interstitial lung disease in Latin-America. 2019 Feb Information about the prognosis and natural history of autoimmune interstitial lung diseases (Ai-ILD) is limited. The aim of the study was to evaluate the characteristics of patients diagnosed with Ai-ILD in Latin-America. We conducted an ambispective multicenter cohort study in 25 centers of Argentina, Colombia, and Uruguay between January 2015 and April 2018. Participants were included in the study if they had diagnosis of Ai-ILD performed by a multidisciplinary team. Patients were classified into the following sub-groups: connective tissue disease-associated ILD (ILD-CTD), interstitial pneumonia with autoimmune features (IPAF), and positive antineutrophils cytoplasmatic antibodies associated ILD (ILD-ANCA). All images were reviewed by a blinded thoracic radiologist. Out of the 381 patients included during the study period, 282 (74%; 95% CI; 69.39-78.16) were women. Mean age was 58 years old (SD 16). Three-hundred and twenty-five (85.1%; 95% CI 81.39-88.5) patients were classified as ILD-CTD (rheumatoid arthritis 31%, systemic sclerosis 29%, dermatomyositis 15%). Thirty-six patients were classified as IPAF (9.5%; 95% CI 6.9-12.8), and 13 (3.5%; 95% CI 2-5.75) as ILD-ANCA. Fifty percent of patients (95% CI 45.12-55.43) had a mild decrease of the forced vital capacity at the time of diagnosis. The most common treatment strategy was the combination of steroids and cyclophosphamide (30.1%; 95% CI 25.32-35.34) followed by azathioprine (20,3%; 95% CI 16.32-25.14). In conclusion, to the best of our knowledge, this is the first study to evaluate the characteristics and treatment strategies used in patients affected by Ai-ILD in Latin-America. Future studies should to evaluate the prognosis and impact of current treatment strategies in patients with Ai-ILD.
31139184 Cannabinoid Receptor 2 Agonist JWH-015 Inhibits Interleukin-1β-Induced Inflammation in Rh 2019 Management of pain in the treatment of rheumatoid arthritis (RA) is a priority that is not fully addressed by the conventional therapies. In the present study, we evaluated the efficacy of cannabinoid receptor 2 (CB2) agonist JWH-015 using RA synovial fibroblasts (RASFs) obtained from patients diagnosed with RA and in a rat adjuvant-induced arthritis (AIA) model of RA. Pretreatment of human RASFs with JWH-015 (10-20 μM) markedly inhibited the ability of pro-inflammatory cytokine interleukin-1β (IL-1β) to induce production of IL-6 and IL-8 and cellular expression of inflammatory cyclooxygenase-2 (COX-2). JWH-015 was effective in reducing IL-1β-induced phosphorylation of TAK1 (Thr(184/187)) and JNK/SAPK in human RASFs. While the knockdown of CB2 in RASFs using siRNA method reduced IL-1β-induced inflammation, JWH-015 was still effective in eliciting its anti-inflammatory effects despite the absence of CB2, suggesting the role of non-canonical or an off-target receptor. Computational studies using molecular docking and molecular dynamics simulations showed that JWH-105 favorably binds to glucocorticoid receptor (GR) with the binding pose and interactions similar to its well-known ligand dexamethasone. Furthermore, knockdown of GR using siRNA abrogated JWH-015's ability to reduce IL-1β-induced IL-6 and IL-8 production. In vivo, administration of JWH-015 (5 mg/kg, daily i.p. for 7 days at the onset of arthritis) significantly ameliorated AIA in rats. Pain assessment studies using von Frey method showed a marked antinociception in AIA rats treated with JWH-015. In addition, JWH-015 treatment inhibited bone destruction as evident from micro-CT scanning and bone analysis on the harvested joints and modulated serum RANKL and OPG levels. Overall, our findings suggest that CB2 agonist JWH-015 elicits anti-inflammatory effects partly through GR. This compound could further be tested as an adjunct therapy for the management of pain and tissue destruction as a non-opioid for RA.
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.
31777816 The Impact of Frailty on Changes in Physical Function and Disease Activity Among Adults Wi 2019 Aug OBJECTIVE: Reduced physical function and frailty are common in rheumatoid arthritis (RA). However, relationships between frailty and changes in physical function and disease activity over time in RA are unknown. We tested whether frailty is a risk factor for worsening patient-reported physical function and disease activity in RA. METHODS: Adults from a longitudinal RA cohort (N = 124) participated. By using an established frailty definition, individuals with three or more of the following deficits were considered frail: 1) body mass index less than or equal to 18.5, 2) low grip strength, 3) severe fatigue, 4) slow 4-m walking speed, and 5) low physical activity. Individuals with one to two or zero deficits were considered "pre-frail" or "robust," respectively. Physical function and RA disease activity were assessed by the Health Assessment Questionnaire (HAQ) and Rheumatoid Arthritis Disease Activity Index (RADAI), respectively, at baseline and follow-up 2 years later. Regression analyses modeled associations of frailty status with change in HAQ and RADAI scores between baseline and follow-up with and without controlling for covariates. Associations of individual frailty components with change in HAQ and RADAI scores were also examined. RESULTS: Among adults with RA, baseline frailty status predicted significant increases, or worsening, in HAQ (β: 0.4; 95% confidence interval: 0.1-0.8; P < 0.01) but not RADAI scores (β: 0.5; 95% confidence interval: -0.4 to 1.5; P > 0.05) between baseline and follow-up in fully adjusted models. Fatigue was an important contributor to this effect. CONCLUSION: Frailty may be an important risk factor for reduced physical function over time in RA. Future studies should address whether interventions to reduce frailty improve physical function in RA.
31911367 Systematic review of the efficacy of commonly prescribed pharmacological treatments for pr 2020 Feb Sleep disturbances are commonly reported by patients with autoimmune disease, and are negatively related to both disease activity and quality of life. Despite the potential for sleep disturbance to exacerbate inflammatory pathways, acute management of sleep disturbance with pharmacological aids is not well understood in this patient group. The objective of this review was to determine the efficacy of pharmacological treatments for sleep disturbance to improve sleep outcomes in adult patients with diagnosed autoimmune disease. Four databases and grey literature were searched for randomized controlled trials which used a pharmacological treatment specifically to treat sleep disturbance in patients with diagnosed autoimmune disease, both in hospitalized and non-hospitalized settings. A sleep outcome was required to be the primary endpoint of the study. Of the 409 studies identified, a total of six were included in the systematic review. Risk of bias across the studies was largely unclear, making an assessment challenging; meta-analysis was not undertaken due to clinical and methodological heterogeneity between studies. While there appeared to be perceived improvement in self-reported sleep quantity and quality in existing studies with pharmacological treatment, there was also evidence of placebo effect on some measures. Relatively small numbers of patients have undergone gold-standard polysomnographic (PSG) recording of sleep which limits our knowledge of objectively determined sleep quantity and quality in patients with autoimmune disease receiving pharmacological treatment for sleep disturbance. Presently there is insufficient evidence to determine whether pharmacological treatment of sleep disturbance is beneficial for improving sleep quantity and quality in this patient group beyond rheumatoid arthritis.
31046542 The in vitro effect of antirheumatic drugs on platelet function. 2020 Several antirheumatic drugs lower the cardiovascular risk among rheumatoid arthritis patients. It is, however, unknown whether inhibition of platelet function contributes to this risk reduction. Only few studies have investigated the potential role of platelets as a target of antirheumatic drugs. In this study, platelet function was tested in vitro in samples from 24 healthy individuals spiked with antirheumatic drugs in clinically relevant concentrations or vehicle. Platelet aggregation was tested with 96-well light transmission aggregometry (LTA), and when an effect ≥20% compared to vehicle was observed, flow cytometric platelet aggregation and activation were evaluated and closure time was measured by Platelet Function Analyzer (PFA-200). When evaluated by LTA, teriflunomide (the active metabolite of leflunomide), tocilizumab, and prednisolone reduced ADP- and collagen-induced platelet aggregation ≥20%, while adalimumab increased TRAP-induced platelet aggregation ≥20%. Using flow cytometry, agonist-induced platelet aggregation with teriflunomide or vehicle was mean ± standard deviation (SD); 30.7% ± 5.8 vs. 41.7% ± 6.5, p = 0.02 using ADP, and 34.7% ± 13.9 vs. 55.8% ± 3.9, p = 0.01 using collagen. Results indicate that teriflunomide, prednisolone, and tocilizumab inhibit, and adalimumab increases platelet aggregation. The study suggests that the majority of antirheumatic drugs mainly reduced cardiovascular risk through indirect effects (e.g., reducing inflammation).
30645754 Elevated anti-cyclic citrullinated peptide antibody titer is associated with increased ris 2019 Apr This paper is to examine the relationship between anti-cyclic citrullinated peptide (anti-CCP) antibody titers and the development of interstitial lung disease (ILD) in patients with and without rheumatoid arthritis (RA). A retrospective investigation was conducted on all adult patients tested for anti-CCP between January 1, 2007, and December 31, 2012, in a university healthcare system. Patients with specified exposures or conditions known to cause ILD were excluded. The prevalence of ILD was compared between those with and without a positive CCP. The study population was then divided into four titer groups based on anti-CCP titers: negative, low titer, moderate titer, high titer. Fisher's exact tests compared the prevalence of ILD among the anti-CCP titer groups. Multivariate logistic regression examined the association between anti-CCP and ILD while controlling for confounders. These analyses were repeated in two subgroups: a "confirmed RA" subgroup and an "unconfirmed RA" subgroup. Two thousand and thirty patients met inclusion criteria and 453 of those had confirmed RA. Progressively higher anti-CCP titer groups developed an increasingly higher prevalence of ILD (p < 0.01). When adjusting for age, tobacco, and a diagnosis of RA, higher anti-CCP titer groups continued to correlate with an increased prevalence of ILD (OR 1.47, 95% CI 1.10-1.96, p < 0.001). This study is the first to show that progressively higher anti-CCP titers correlate with increasing prevalence of ILD, even when adjusting for confounders.
31618993 Methyl Jasmonate Reduces Inflammation and Oxidative Stress in the Brain of Arthritic Rats. 2019 Oct 15 Methyl jasmonate (MeJA), common in the plant kingdom, is capable of reducing articular and hepatic inflammation and oxidative stress in adjuvant-induced arthritic rats. This study investigated the actions of orally administered MeJA (75-300 mg/kg) on inflammation, oxidative stress and selected enzyme activities in the brain of Holtzman rats with adjuvant-induced arthritis. MeJA prevented the arthritis-induced increased levels of nitrites, nitrates, lipid peroxides, protein carbonyls and reactive oxygen species (ROS). It also prevented the enhanced activities of myeloperoxidase and xanthine oxidase. Conversely, the diminished catalase and superoxide dismutase activities and glutathione (GSH) levels caused by arthritis were totally or partially prevented. Furthermore, MeJA increased the activity of the mitochondrial isocitrate dehydrogenase, which helps to supply NADPH for the mitochondrial glutathione cycle, possibly contributing to the partial recovery of the GSH/oxidized glutathione (GSSG) ratio. These positive actions on the antioxidant defenses may counterbalance the effects of MeJA as enhancer of ROS production in the mitochondrial respiratory chain. A negative effect of MeJA is the detachment of hexokinase from the mitochondria, which can potentially impair glucose phosphorylation and metabolism. In overall terms, however, it can be concluded that MeJA attenuates to a considerable extent the negative effects caused by arthritis in terms of inflammation and oxidative stress.
31678378 Transdermal enhancement strategy of ketoprofen and teriflunomide: The effect of enhanced d 2019 Dec 15 The aim of the present work was to develop compound transdermal patch containing teriflunomide (TEF) and ketoprofen (KTP) using permeation enhancement strategy; reveal the molecular mechanism by which Azone (AZ) promoted transdermal absorption of compound patch through the enhancement of drug-drug intermolecular interaction. The formulation was optimized using in vitro skin permeation study and confirmed with pharmacodynamics study, anti-inflammatory study and analgesics study. Enhanced drug-drug interaction by AZ was characterized using FT-IR, (13)C NMR, molecular modeling and thermal analysis. The optimized formulation was composed of TEF (3%), KTP (2%), AZ (10%) and DURO-TAK® 87-4098 as adhesive matrix. The skin permeation amount of TEF-KTP combination was promoted by AZ about 1.9 times (594.2 ± 46.8 μg/cm(2)) and 1.2 times (502.92 ± 24.0 μg/cm(2)) compared with TEF-AZ and KTP-AZ individual patch. It was proved that the interaction between TEF and KTP via hydrogen bonding was further enhanced by AZ due to the increased molecular mobility of acrylate polymer (ΔT(g) = -17.7 °C), which was proved by FTIR and (13)C NMR spectra. The enhanced drug-drug intermolecular interaction increased drug dispersed status and decreased the quantity of drug's hydrogen bonding site, thus increasing the drug release amount significantly. In conclusion, a compound transdermal patch containing KTP and TEF was developed successfully and a novel enhancement mechanism was clarified at molecular level, which provided reference for the development of novel compound transdermal patch.
31244376 Effectiveness of resistance exercise in functional fitness in women with primary Sjögren' 2020 Jan Objective: The purpose of this study was to analyse the effectiveness of resistance exercise in functional fitness in women with primary Sjögren's syndrome (pSS).Method: This is a randomized controlled clinical trial with 51 volunteers: 26 allocated to the exercise group (GEX) and 25 to the control group. The GEX underwent a supervised resistance-training programme for 16 weeks, with two sessions per week. The outcomes measured were: functional capacity (FC), by the Fullerton Functional Fitness Test; Daily Motor Activity Index (DMAI), evaluated by an actigraph; disease activity, by the ESSDAI; and quality of life, by the 36-item Short Form Health Survey (SF-36). The evaluations were performed by a blind evaluator at baseline (TØ) and after 16 weeks (T16wk).Results: In the GEX, all FC parameters demonstrated improvement, except for the upper limb flexibility test (p = 0.866): upper and lower limb strength, flexibility, aerobic capacity, and agility (all p < 0.01). A similar situation occurred in the SF-36, where all domains demonstrated improvement except for the emotional aspect (p = 0.710): FC, physical aspects limitation, general health status, vitality, social aspects, and mental health (all p < 0.01). The DMAI (p = 0.2) and EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) (p = 0.284) did not change. No significant improvement was observed in the control group.Conclusion: The supervised resistance exercise programme did not worsen the DMAI or disease activity, demonstrating the safety of the intervention, and was effective in improving FC and quality of life in women with pSS.Registry identifier (clinical trials.gov): NCT03130062.
30813923 Clinical features and outcomes of patients with fever of unknown origin: a retrospective s 2019 Feb 27 BACKGROUND: Few studies have reported the long-term clinical outcome of patients discharged with undiagnosed fever of unknown origin (FUO). In this study, the clinical features and outcomes of patients with unexplained fever were explored to improve our understanding of FUO. METHOD: Patients diagnosed with FUO at admission and discharged without final diagnoses after systematic examination in the department of infectious diseases at Peking Union Medical College Hospital between 2004 and 2010 were followed up by telephone. Medical records were reviewed, and the clinical features and outcomes of patients for whom follow-up data were available were summarized. RESULTS: Between 2004 and 2010, 58 patients with follow-up data, who were diagnosed with FUO at admission and did not have a final diagnosis at discharge, were enrolled in this study. The median duration of follow-up was 518 (0.4-830) weeks, and the fever duration was 24.6 (6.7-763.2) weeks. Final diagnoses were established in 11 cases (19%), and the diagnostic methods included clinical diagnosis, diagnostic therapy, genetic screening and biopsy pathology. The fever in 35 patients (60%) subsided during hospitalization or after discharge. Their condition was stable and self-limited after long-term follow-up, and they were ultimately thought to be cured. Two patients had periodic fever during prolonged observation: one patient needed intermittent use of nonsteroidal antiinflammatory drugs (NSAIDs), and the other needed intermittent use of NSAIDs and a steroid. Ten patients died during follow-up, with 9 deaths being caused by severe and worsening conditions related to the febrile illness. CONCLUSIONS: Long-term follow-up should be performed for patients with undiagnosed FUO. Some patients can obtain a definitive diagnosis by repeated multiple invasive examinations and diagnostic treatment. Most patients have a self-limited illness, and their prognosis is good.
30682150 Different operators and histologic techniques in the assessment of germinal center-like st 2019 OBJECTIVE: A standardization of minor salivary gland (MSG) histopathology in primary Sjögren's syndrome (pSS) has been recently proposed. Although there is strong agreement that germinal center (GC)-like structures should be routinely identified, due to their prognostic value, a consensus regarding the best protocol is still lacking. Aim of this study was to compare the performance of different histological techniques and operators to identify GC-like structures in pSS MSGs. MSG biopsies from 50 pSS patients were studied. METHODS: Three blinded operators (one pathologist and two rheumatologists with different years of experience in pSS MSG assessment) assessed 50 MSGs of which one slide was stained with haematoxylin and eosin (H&E) and consecutive slides were processed to investigate CD3/CD20, CD21 and Bcl-6 expression. RESULTS: By assessing 225 foci, the best agreement was between H&E-stained sections evaluated by the rheumatologist with more years of experience in pSS MSG assessment and CD3/CD20 segregation. In the foci with CD21 positivity, the agreement further increased. Bcl-6- foci could display a GC, detected with other staining, but not vice versa. CONCLUSION: GC assessment on H&E-stained sections should be performed with caution, being operator-dependent. The combination of H&E with CD3/CD20 and CD21 staining should be recommended as it is reliable, feasible, able to overcome the bias of operator experience and easily transferrable into routine practice.
30487596 The role of Ca(2+) in acid-sensing ion channel 1a-mediated chondrocyte pyroptosis in rat a 2019 Apr Rheumatoid arthritis is an autoimmune disease with a poor prognosis. Pyroptosis is a type of proinflammatory programmed cell death that is characterised by the activation of caspase-1 and secretion of the proinflammatory cytokines interleukin (IL)-1β/18. Previous reports have shown that pyroptosis is closely related to the development of some autoimmune diseases, such as rheumatoid arthritis. The decrease in the pH of joint fluid is a main pathogenic feature of RA and leads to excessive apoptosis in chondrocytes. Acid-sensitive ion channels (ASICs) are extracellular H(+)-activated cation channels that mainly influence Na(+) and Ca(2+) permeability. In this study, we investigated the role of Ca(2+) in acid-sensing ion channel 1a-mediated chondrocyte pyroptosis in an adjuvant arthritis rat model. The expression of apoptosis-associated speck-like protein, NLRP3, caspase-1, ASIC 1a, IL-1β and IL-18 was upregulated in the joints of rats compared with that in normal rats, but the expression of Col2a in cartilage was decreased. However, these changes were reversed by amiloride, which is an inhibitor of ASIC1a. Extracellular acidosis significantly increased the expression of ASIC1a, IL-1β, IL-18, ASC, NLRP3 and caspase-1 and promoted the release of lactate dehydrogenase. Interestingly, Psalmotoxin-1 (Pctx-1) and BAPTA-AM inhibited these effects. These results indicate that ASIC1a mediates pyroptosis in chondrocytes from AA rats. The underlying mechanism may be associated with the ability of ASIC1a to promote [Ca(2+)](i) and upregulate the expression of the NLRP3 inflammasome.
31600995 Solid Nanocrystals of Rebamipide Promote Recovery from Indomethacin-Induced Gastrointestin 2019 Oct 9 Indomethacin (IMC)-induced gastrointestinal (GI) injuries are more common in rheumatoid arthritis (RA) patients than in other IMC users, and the overexpression of nitric oxide (NO) via inducible NO synthase (iNOS) is related to the seriousness of IMC-induced GI injuries. However, sufficient strategies to prevent IMC-induced GI injuries have not yet been established. In this study, we designed dispersions of rebamipide (RBM) solid nanocrystals (particle size: 30-190 nm) by a bead mill method (RBM-NDs), and investigated whether the oral administration of RBM-NDs is useful to prevent IMC-induced GI injuries. The RBM nanocrystals were spherical and had a solubility 4.71-fold greater than dispersions of traditional RBM powder (RBM-TDs). In addition, the RBM-NDs were stable for 1 month after preparation. The RBM contents in the stomach, jejunum, and ileum of rats orally administered RBM-NDs were significantly higher than in rats administered RBM-TDs. Moreover, the oral administration of RBM-NDs decreased the NO levels via iNOS and area of the GI lesions in IMC-stimulated RA (adjuvant-induced arthritis rat) rats in comparison with the oral administration of RBM-TDs. Thus, we show that the oral administration of RBM-NDs provides a high drug supply to the GI mucosa, resulting in a therapeutic effect on IMC-induced GI injuries. Solid nanocrystalline RBM preparations may offer effective therapy for RA patients.
31464678 Application of artificial neural network analysis in the evaluation of cardiovascular risk 2019 May OBJECTIVES: The aim of the present study was to verify whether artificial neural networks (ANNs) might help to elucidate the mechanisms underlying the increased prevalence of cardiovascular events (CV) in primary Sjögren's syndrome (pSS). METHODS: 408 pSS patients (395 F: 13 M), with a mean age of 61 (±14) years and mean disease duration of 8.8 (±7.8) years were retrospectively included. CV risk factors and events were analysed and correlated with the other pSS clinical and serological manifestations by using both a traditional statistical approach (i.e. Agglomerative Hierarchical Clustering (AHC)) and Auto-CM, a data mining tool based on ANNs. RESULTS: Five percent of pSS patients experienced one or more CV events, including heart failure (8/408), transient ischaemic attack (6/408), stroke (4/408), angina (4/408), myocardial infarction (3/408) and peripheral obliterative arteriopathy (2/408). The AHC provided a dendrogram with at least three clusters that did not allow us to infer specific differential associations among variables (i.e. CV comorbidity and pSS manifestations). On the other hand, Auto-CM identified two different patterns of distributions in CV risk factors, pSS-related features, and CV events. The first pattern, centered on "non-ischaemic CV events/generic condition of HF", was characterised by the presence of traditional CV risk factors and by a closer link with pSS glandular features rather than to pSS extra-glandular manifestations. The second pattern included "ischaemic neurological, cardiac events and peripheral obliterative arteriopathy" and appeared to be strictly associated with extra-glandular disease activity and longer disease duration. CONCLUSIONS: This study represents the first application of ANNs to the analysis of factors contributing to CV events in pSS. When compared to AHC, ANNs had the advantage of better stratifying CV risk in pSS, opening new avenues for planning specific interventions to prevent long-term CV complications in pSS patients.
30572133 Lymphomagenesis in Sjögren's syndrome: Predictive biomarkers towards precision medicine. 2019 Feb Sjögren's syndrome (SS) is characterized by B cell hyperactivity documented by the production of plethora of autoantibodies and a strong tendency for NHL of B cell origin. Classical predictors of lymphoma have been already proposed and proved their validity, including clinical, serological and histopathologic biomarkers. The process of lymphomagenesis is multistep and encompasses mechanisms of antigen driven selection of the BCR with RF activity and various genetic contributors implicated in B cell proliferation, cell growth and cell cycle control, enhanced by a complex milieu of cytokines and trophic agents that are abundant within the inflammatory lesion of minor salivary glands of SS patients. Extensive efforts in the basic research field have revealed several novel biomarkers for lymphoma prediction while the major cellular and molecular mechanisms of evolutionary transition of B cells towards malignancy are under investigation. In this review, we present the current data regarding the newly proposed biomarkers for SS associated lymphoma prediction and a hypothetical model of lymphomagenesis based on the emerging data.
30170935 An unusual manifestation of Sjögren syndrome encephalitis. 2019 Feb Sjögren syndrome (SS) is a systemic inflammatory and autoimmune disease characterized by systemic disorders of the exocrine glands, predominantly the salivary and lacrimal glands. Here, we report a 4-year-old boy who presented with the repetition of generalized tonic-clonic seizures for 1-2 min. Initially, he was diagnosed with idiopathic autoimmune encephalitis and was treated with steroids. He was eventually diagnosed with SS based on the examination results, such as inflammatory cell infiltration into the minor salivary glands and positive serum anti-SSA/Ro antibody. Although central nervous system complications are rare in pediatric SS, this condition should be considered in the differential diagnosis when a patient presents with idiopathic autoimmune encephalitis of unknown cause. Furthermore, SS can occur in relatively young children and can present without imaging abnormalities.
31303456 Application of classification criteria of Sjogren syndrome in patients with sicca symptoms 2020 Jan BACKGROUND: Patients who have symptoms of sicca, such as dry eyes and mouth, may have Sjögren's syndrome (SS). However, the conservative culture makes patients hesitate to undergo an invasive biopsy, which contributes to the difficulty of confirming a diagnosis. We aimed to identify the characteristics of patients with sicca symptoms to develop a better predictive value for each item included in the three different diagnostic criteria for SS and clarify the best diagnostic tools for the local population. METHODS: This is a single-center retrospective case-control study from January 2016 to December 2017. Patients who underwent sialoscintigraphy because of clinical symptoms of xerostomia and xerophthalmia at one medical center were reviewed via the patients' electronic medical records. RESULTS: Of 515 patients enrolled, the severity of results for sialoscintigraphy and Schirmer's test was correlated with a diagnosis of SS and generated receiver operator characteristic curve. The area under curve (AUC) was 0.603 for positive Schirmer's test, 0.687 for positive anti-Ro/La results, 0.893 for a positive salivary gland biopsy. The AUC was 0.626 and 0.602 for Schirmer's test which is redefined as <10 mm/5 minutes in either eye and according to 2016 the American College of Rheumatology/ European League Against Rheumatism criteria, respectively. CONCLUSION: Our results indicate the cut-off point for defining a positive test result in the Schirmer's test is worth modified to <10 mm/5 minutes in either eye.
31161440 Changes of Intestinal Microecology in Patients with Primary Sjogren's Syndrome after Thera 2019 Sep OBJECTIVE: To explore the change of intestinal microecology in patients with primary Sjogren's syndrome (pSS) and correlation with disease activity, and also discuss the therapy effect of Yangyin Yiqi Huoxue Recipe (, YYHD). METHODS: Sixteen pSS patients were enrolled in the present study, who received 3-month treatment of YYHR, 200 mL orally twice daily. Their pre-and post-test ESSDAI scores, erythrocyte sedimentation rate (ESR) and serum immunoglobulin G (IgG) levels were measured respectively. The 16SrDNA metagenomic sequencing was used to detect and analyze the abundance and diversity of intestinal bacteria flora and the proportion of bacteria at the levels of phylum, family, and genus, in comparision with those of 6 healthy subjects in the control group. RESULTS: The abundance and diversity of intestinal bacteria flora in pSS patients were lower than those of healthy subjects (P<0.05). After the treatment with YYHD, patients' ESSDAI score and levels of IgG and ESR have decreased significantly (P<0.05). At the phylum level, the proportions of Actinobacteria, Firmicutes, Fusobacteria and Proteobacteria have reduced sharply, while the proportions of Bacteroidetes, Teneriquetes and Candidate-division-TM7 have increased significantly by treatment (all P<0.05). At the classification level, such treatment has caused a significant decrease in the proportions of Bacteroidaceae, Ruminococcaceae, Veillonellaceae, and Enterobacteriacea (all P<0.05), but a significant increase in the proportion of Lachnospiraceae (P<0.05). At the genus level, the treatment has significantly decreased the proportions of Bifidobacterium, Bacteroides, Escherichia-Shigella, Faecalibacterium and Prevotella (all P<0.05), but significantly increased the proportion of Clostridia (P<0.05), close to the levels of healthy subjects (P>0.05). CONCLUSIONS: There exists an imbalance of intestinal microecology in pSS patients, which can be improved through the treatment with YYHD. Besides, such treatment can also improve the disease activity and adjust the diversity of intestinal bacteria flora, the composition and the abundance of intestinal flora.