Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
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34191326 | Retraction. | 2021 Nov | Retraction: "Genetic deletion of GIT2 prolongs functional recovery and suppresses chondrocyte differentiation in rats with rheumatoid arthritis," by Hui Li, Shi-Bing Guan, Yi Lu, Fei Wang, Yu-Hong Liu, Qi-Yun Liu, J Cell Biochem. 2018; 1538-1547: The above article, published online on 04 August 2017 in Wiley Online Library (https://onlinelibrary.wiley.com/doi/10.1002/jcb.26313) has been retracted by agreement between the the journal's Editor in Chief, Prof. Dr. Christian Behl, and Wiley Periodicals LLC. The authors asked to retract this manuscript as some data and experiments are flawed and validity of the overall results could not be confirmed. During an investigation based on allegations raised by a third party, several image elements of the experimental data were found to be published elsewhere in a different scientific context. The conclusions of this article are considered to be invalid. | |
34946471 | Evaluation of a Non-Face-to-Face Multidisciplinary Health Care Model in a Population with | 2021 Dec 17 | This study evaluated a non-face-to-face-multidisciplinary consultation model in a population with rheumatoid arthritis (RA) during the COVID-19 pandemic. This is an analytical observational study of a prospective cohort with simple random sampling. RA patients were followed for 12 weeks (Jul-Oct 2020). Two groups were included: patients in telemedicine care (TM), and patients in the usual face-to-face care (UC). Patients could voluntarily change the care model (transition model (TR)). Activity of disease, quality of life, disability, therapeutic adherence, and self-care ability were analyzed. Bivariate analysis was performed. A qualitative descriptive exploratory study was conducted. At the beginning, 218 adults were included: (109/TM-109/UC). The groups didn't differ in general characteristics. At the end of the study, there were no differences in TM: (n = 71). A significant (p < 0.05) decrease in adherence, and increase in self-care ability were found in UC (n = 18) and TR (n = 129). Seven patients developed COVID-19. Four categories emerged from the experience of the subjects in the qualitative assessment (factors present in communication, information and communication technologies management, family support and interaction, and adherence to treatment). The telemedicine model keeps RA patients stable without major differences compared to the usual care or mixed model. | |
34344479 | Dissociation between 2-[(18)F]fluoro-2-deoxy-D-glucose positron emission computed tomograp | 2021 Aug 4 | BACKGROUND: Inflammation of patients joints with severe disease activity of rheumatoid arthritis (RA) has already been visualized and quantified by 2-[(18)F]fluoro-2-deoxy-D-glucose positron emission computed tomography ([(18)F] FDG PET/CT), but little is known about the metabolic status and its relationship with clinical and ultrasonography (US) metrology in patients with low/moderate activity or in remission. METHODS: Clinical assessments [based on 28-joint disease activity score (DAS(28)-CRP) and Clinical Disease Activity Index (CDAI)], [(18)F] FDG PET/CT, US and X-ray were performed on 63 RA patients classified into remission or low/moderate or severe disease activity groups. PET/CT was visually and then semi-quantitatively analysed by determining the standardized uptake value (SUV) of positive joints. RESULTS: Of the 1764 joints, 21.1% were tender only, 13.7% swollen only, 27.6% tender or swollen, 7.3% tender and swollen, 20.5% PET/CT-positive and 8.6% US-positive. PET and US measurements were correlated, albeit with poor concordance. The positive predictive value of PET/CT for clinical evaluation (tender and/or swollen) was low, whereas its negative predictive value was high. Highly significant differences were found with the number of PET/CT-positive joints and with cumulative SUV between "severe" and "non-severe" patients (including those in remission and those with low/moderate activity) and not between those classified as "remission" and "non-remission" or "remission" and "low/moderate activity". Moreover, the correlation between PET/CT measurements and clinical activity was positive only in the CDAI severe disease group. In patients in remission or with low/moderate activity, only 20-30% of joints were PET/CT-negative. In remission, PET/CT and US were positive in different joints, and PET/CT-positive but US-negative joints mainly exhibited RA (38.1%) or normal (49.2%) and not osteoarthritic (12.7%) X-ray patterns. CONCLUSIONS: [(18)F] FDG PET/CT was effective at distinguishing patients with severely active disease from other patients. In non-severe RA patients, including those in remission, PET/CT results are discordant from US and clinical observations. A longitudinal analysis is needed to explore the clinical relevance of such infra-clinical disease. | |
34679492 | Characteristics and Predictors of Progression Interstitial Lung Disease in Rheumatoid Arth | 2021 Sep 28 | OBJECTIVES: To describe the characteristics and progression of interstitial lung disease in patients with associated systemic autoimmune disease (ILD-SAI) and to identify factors associated with progression and mortality. PATIENTS AND METHODS: We performed a multicenter, retrospective, observational study of patients with ILD-SAI followed between 2015 and 2020. We collected clinical data and performed pulmonary function testing and high-resolution computed tomography at diagnosis and at the final visit. The main outcome measure at the end of follow-up was forced vital capacity (FVC) >10% or diffusing capacity of the lungs for carbon monoxide >15% and radiological progression or death. Cox regression analysis was performed to identify factors associated with worsening of ILD. RESULTS: We included 204 patients with ILD-SAI: 123 (60.3%) had rheumatoid arthritis (RA), 58 had (28.4%) systemic sclerosis, and 23 (11.3%) had inflammatory myopathy. After a median (IQR) period of 56 (29.8-93.3) months, lung disease had stabilized in 98 patients (48%), improved in 33 (16.1%), and worsened in 44 (21.5%). A total of 29 patients (14.2%) died. Progression and hospitalization were more frequent in patients with RA (p = 0.010). The multivariate analysis showed the independent predictors for worsening of ILD-SAI to be RA (HR, 1.9 [95% CI, 1.3-2.7]), usual interstitial pneumonia pattern (HR, 1.7 [95% CI, 1.0-2.9]), FVC (%) (HR, 2.3 [95% CI, 1.4-3.9]), and smoking (HR, 2.7 [95%CI, 1.6-4.7]). CONCLUSION: Disease stabilizes or improves after a median of 5 years in more than half of patients with ILD-SAI, although more than one-third die. Data on subgroups and risk factors could help us to predict poorer outcomes. | |
33512394 | Clinical characteristics and lifestyle behaviors among individuals with arthritis: an anal | 2021 Jan 1 | CONTEXT: The combination of osteoarthritis and rheumatoid arthritis affects nearly one-fourth of Americans. Many of the risk factors for arthritis are lifestyle related, such as obesity, physical activity, dietary behaviors, and alcohol and tobacco use. OBJECTIVE: To analyze lifestyle behaviors of patients with vs. those without arthritis. METHODS: A cross-sectional analysis of 2017 Behavioral Risk Factor Surveillance System (BRFSS) data was conducted on patients with and without a history of arthritis. Physical activity, smoking status, alcohol use, and dietary behaviors were extracted. Logistic regression models were constructed to calculate adjusted risk ratios (ARRs). All confidence intervals (CIs) were reported at 95%. RESULTS: The median response rate for the 2017 BRFSS survey was 45.1% (sample n=292,808; population N=118,751,156). The overall prevalence of arthritis was 44% (n=128,850). Respondents with arthritis were significantly more likely to be physically inactive than nonarthritic respondents, with a significant gender interaction (male absolute risk reduction [ARR], 1.2 [CI, 1.15-1.25]; female ARR, 1.29 [CI, 1.24-1.33]). Those with arthritis were also more likely to be current smokers (ARR 1.1; CI, 1.05-1.15) and less likely to have attempted to quit smoking in the last 12Â months (ARR, 0.91; CI, 0.87-0.96). Finally, men with arthritis were more likely to drink alcohol heavily (ARR, 1.14; CI, 1.02-1.27]). CONCLUSION: Patients with arthritis were more likely to be women, White, current smokers, and physically inactive, and to have poor mental health, lower education levels, and difficulty paying for healthcare and medications than those without arthritis. Further efforts should be made to address these findings through resource allocation in the care of patients with arthritis. Practitioners should also seek increased understanding of the psychological, social, and economic impacts of physical activity and smoking in patients with arthritis. | |
32613746 | The impact of gender on the clinical presentation, management, and surgical outcomes of pa | 2021 Apr | RATIONALE, AIMS AND OBJECTIVES: Approximately 20 000 cases of septic arthritis (SA) occur in the U.S. yearly. We examined whether gender-related differences exist in the presentation, management, and outcomes of patients with native joint septic arthritis (NJSA). METHODS: This was a retrospective study of medical files of patients aged 18 years and older admitted between 1998 and 2015 to a single tertiary care hospital and diagnosed with NJSA. All study subjects had positive synovial fluid or blood cultures and each was managed surgically. Patients' charts were reviewed for demographics, comorbidities, clinical presentations, microbiology profiles, management, and outcomes. Cases of osteomyelitis, septic bursitis, prosthetic joint, and culture-negative SA were excluded. RESULTS: Of 324 NJSA patients, those who were female (n = 130; 40.1%) were significantly older at presentation than males (mean age: 63.6 vs 58.3; P = .006). Prior joint pathology was more common amongst females, including osteoarthritis (20.8% vs 12.9%; P = .04) and rheumatoid arthritis (10% vs 3.6%; P = .03). Female patients had a higher frequency of hip involvement (17.7% vs 10.8%; P = .05). No differences were observed in clinical presentations, culture results, medical management, or outcomes between genders. CONCLUSIONS: Compared to men, women with NJSA presented at an older age and had more prior joint pathology and a higher frequency of hip involvement. These differences, however, had no significant impact on the clinical presentation, medical management, or outcomes of NJSA. | |
33640641 | Bilateral shoulder septic arthritis due to suspected bacterial endocarditis: A case report | 2021 Mar | INTRODUCTION: Septic arthritis is an orthopedic emergency that requires rapid diagnosis and treatment. It is typically caused by occult bacteremia which allows bacteria to seed the joint or local invasion of a soft tissue infection. Most cases of septic arthritis are caused by gram-positive bacteria, with the most common culprit being Staphylococcus Aureus. The reason septic arthritis is an orthopedic emergency is because of rapid destruction to cartilage. The mechanism of injury to cartilage is two-fold: bacterial enzymes are directly toxic to joint cartilage, and buildup of exudate can tamponade blood flow and cause anoxic injury. Typically, the knee is the most commonly involved joint. This is followed by the hip, ankle, elbow, wrist, and shoulder in descending order of occurrence. Polyarticular disease makes up a small percentage of these cases and if present, it is usually asymmetric and will involve at least one knee joint. PRESENTATION OF CASE: Bilateral joint septic arthritis is relatively rare. We present an uncommon case of atraumatic bilateral septic shoulders in an elderly man with a history of heart disease and insidious bilateral shoulder pain after golfing 18 holes. This presentation is unique not only in its rarity but also in its impact on our understanding of septic arthritis in the setting of medical comorbidities and a relatively unimpressive presentation. With a recent golfing day just prior to presentation, differential diagnoses other than septic arthritis included deltoid/rotator cuff muscle strain, acute on chronic rotator cuff tendinosis, acute on chronic rotator cuff tearing, acute flare up of osteoarthritis, rheumatoid arthritis, or crystalline arthropathy. With elevated inflammatory markers and an equivocal physical examination, our patient underwent advanced imaging via MRI and subsequent bilateral glenohumeral joint diagnostic aspirations that were consistent with septic arthritis due to his complaining of contralateral shoulder pain shortly after his admission. Immediately after said diagnosis was made, the patient was taken back for emergent bilateral open irrigation and debridement, as septic arthritis is an orthopedic emergency, and went on to recover appropriately on culture-directed intravenous antibiotic therapy. DISCUSSION/CONCLUSION: This case report is impactful with regard to clinical practice for multiple reasons. First and foremost it is a cautionary tale for all clinicians with regard to the level of suspicion one must have for polyarticular septic arthritis in the setting of the multiply painful patient. Second, it demonstrates the utility of advanced imaging in the equivocal patient. Lastly, it underscores the importance of prompt diagnosis and treatment, validating the existing algorithm for septic arthritis. | |
33959198 | Patient-reported outcomes from a randomized, double-blind, placebo controlled, phase III s | 2021 | INTRODUCTION: To assess the effect of baricitinib on patient-reported outcomes (PROs) in patients with moderately to severely active rheumatoid arthritis (RA) who had an inadequate response to methotrexate (MTX). METHODS: This was a 52-week, randomized, double-blind, placebo controlled, phase III study in patients with RA who had an inadequate response to MTX. Patients (n = 290) receiving stable background MTX were randomly assigned (1:1) to receive placebo or baricitinib 4 mg once daily with a primary endpoint at week 12. PROs assessed included Health Assessment Questionnaire-Disability Index (HAQ-DI), Patient's Global Assessment of Disease Activity, patient's assessment of pain, Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), European Quality of Life-5 Dimensions-5 Level index scores and visual analogue scale, and measures collected in electronic patient daily diaries: duration of morning joint stiffness, Worst Tiredness, and Worst Joint Pain. Treatment comparisons were made with logistic regression and analysis of covariance models for categorical and continuous variables, respectively. RESULTS: Statistically significant (p ⩽ 0.05) improvements in all PROs were observed in the baricitinib 4 mg group compared to placebo as early as week 1 to week 4; and were sustained to week 24. These improvements were maintained until week 52 for the baricitinib group. A significantly larger proportion of patients met or exceeded the minimum clinically important difference for HAQ-DI (⩾0.22) and FACIT-F (3.56) profiles in the baricitinib group. CONCLUSION: Baricitinib provided significant improvements in PROs compared to placebo to 52 weeks of treatment in patients with RA who had an inadequate response to MTX.Clinicaltrials.gov identifier: https://clinicaltrials.gov/ct2/show/NCT02265705; NCT02265705; RA-BALANCE. Registered 13 October 2014. | |
34448173 | Abatacept is Efficacious in the Treatment of Older Patients with csDMARD-Refractory Rheuma | 2021 Dec | INTRODUCTION: Abatacept efficacy in older patients with rheumatoid arthritis (RA) has been primarily demonstrated via retrospective comparisons with younger patients. The objective of this study was to compare efficacy of abatacept in older vs. younger patients with RA, and efficacy of abatacept with that of conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) in both age groups. METHODS: This prospective, multicenter, observational study (UMIN000014913) enrolled csDMARD-refractory patients without previous biological DMARD treatment. Abatacept (A) or csDMARDs (C) were administered at the treating physician's discretion to older (O, ≥ 65 years) and younger (Y, 20-64 years) patients, producing AO, AY, CO, and CY groups. Clinical efficacy after 24 weeks was evaluated using European League Against Rheumatism (EULAR) erythrocyte sedimentation rate response criteria. RESULTS: Overall, 202 patients were evaluated. Compared with the CO group, more patients in the AO group achieved a EULAR good or moderate response (p < 0.0001). Compared with the CY group, more patients in the AY group achieved a EULAR good or moderate response (p < 0.01). Similar proportions of patients in the AO and AY groups achieved a EULAR good response or a good or moderate response. Few adverse events were reported. CONCLUSIONS: This prospective study demonstrated that abatacept is efficacious and safe in older patients with RA and a history of being refractory to csDMARDs. Abatacept was shown to be more efficacious than adding or switching to a new csDMARD in both younger and older csDMARD-refractory patients with RA. TRIAL REGISTRATION: UMIN000014913. | |
34782759 | A novel cytokine consisting of the p40 and EBI3 subunits suppresses experimental autoimmun | 2022 Jan | OBJECTIVE: The interleukin (IL)-12 cytokine family is closely related to the development of T helper cells, which are responsible for autoimmune disease enhancement or suppression. IL-12 family members are generally heterodimers and share three α-subunits (p35, p19, and p28) and two β-subunits (p40 and EBI3). However, a β-sheet p40 homodimer has been shown to exist and antagonize IL-12 and IL-23 signaling (1). Therefore, we assumed the existence of a p40-EBI3 heterodimer in nature and sought to investigate its role in immune regulation. METHODS: The presence of the p40-EBI3 heterodimer was confirmed by ELISA, immunoprecipitation, and western blotting. A p40-EBI3 vector and p40-EBI3-Fc protein were synthesized to confirm the immunological role of this protein in mice with collagen-induced arthritis (CIA). The anti-inflammatory effects of p40-EBI3 were analyzed with regard to clinical, histological, and immune cell-regulating features in mice with CIA. RESULTS: Clinical arthritis scores and the expression levels of proinflammatory cytokines (e.g., IL-17, IL-1β, IL-6, and TNF-α) were significantly attenuated in p40-EBI3-overexpressing and p40-EBI3-Fc-treated mice with CIA compared to vehicle-treated mice with CIA. Structural joint damage and vessel formation-related gene expression were also reduced by p40-EBI3 heterodimer treatment. In vitro, the p40-EBI3-Fc protein significantly suppressed the differentiation of Th17 cells and reciprocally induced CD4(+)CD25(+)Foxp3(+) (regulatory T) cells. p40-EBI3 also inhibited osteoclast formation in a concentration-dependent manner. CONCLUSION: In this study, p40-EBI3 ameliorated proinflammatory conditions both in vivo and in vitro. We propose that p40-EBI3 is a novel anti-inflammatory cytokine involved in suppressing the immune response through the expansion of Treg cells and suppression of Th17 cells and osteoclastogenesis. | |
34108972 | TLR7 Signaling Drives the Development of Sjögren's Syndrome. | 2021 | Sjögren's syndrome (SS) is a chronic systemic autoimmune disease that affects predominately salivary and lacrimal glands. SS can occur alone or in combination with another autoimmune disease like systemic lupus erythematosus (SLE). Here we report that TLR7 signaling drives the development of SS since TLR8-deficient (TLR8ko) mice that develop lupus due to increased TLR7 signaling by dendritic cells, also develop an age-dependent secondary pathology similar to associated SS. The SS phenotype in TLR8ko mice is manifested by sialadenitis, increased anti-SSA and anti-SSB autoantibody production, immune complex deposition and increased cytokine production in salivary glands, as well as lung inflammation. Moreover, ectopic lymphoid structures characterized by B/T aggregates, formation of high endothelial venules and the presence of dendritic cells are formed in the salivary glands of TLR8ko mice. Interestingly, all these phenotypes are abrogated in double TLR7/8-deficient mice, suggesting that the SS phenotype in TLR8-deficient mice is TLR7-dependent. In addition, evaluation of TLR7 and inflammatory markers in the salivary glands of primary SS patients revealed significantly increased TLR7 expression levels compared to healthy individuals, that were positively correlated to TNF, LT-α, CXCL13 and CXCR5 expression. These findings establish an important role of TLR7 signaling for local and systemic SS disease manifestations, and inhibition of such will likely have therapeutic value. | |
32671658 | Lower risk of primary Sjogren's syndrome in patients with dengue virus infection: a nation | 2021 Feb | The data concerning the association between dengue viruses (DV) infection and autoimmune diseases (ADs) remain unclear and are scarce. This nationwide population-based cohort study assessed the risk of ADs among patients with DV infection. We analyzed Taiwanese medical data from the Registry of the National Notifiable Disease Reporting System of Taiwan's Centers for Disease Control between 1998 and 2015 and identified patients with DV infection. From the entire general population data in the National Health Insurance Research Database, we randomly selected a comparison cohort that was individual matching by age, sex, residence, and index date. We analyzed the risk of ADs using a Cox proportional hazards regression model stratified by sex, age, and residence. We enrolled 29,365 patients with DV infection (50.68% men; mean age, 44.13 years) and 117,460 age-, sex-, and residence-matched controls in the present study. The incidence rates of organ-specific ADs were nonsignificantly higher in the DV cohort than in the non-DV control cohort. An approximately 70% lower risk of primary Sjogren syndrome (pSS) was evident in the DV cohort than in the non-DV control cohort with an adjusted hazard ratio of 0.30 (95% confidence interval 0.13-0.67) after adjusting for comorbidities in matched design. By contrast, the other systemic ADs were nonsignificantly lower in the DV cohort than in the non-DV control cohort. This nationwide long-term cohort study demonstrated that patients with DV infection had a lower risk of primary Sjogren syndrome than those without DV infection. Key Points • This retrospective, longitudinal cohort observational study shows that patients with DV infection had a lower risk of pSS than those without DV infection. • The DV cohort had an approximately 70% lower risk of pSS than the control group, with a multivariate-adjusted HR of 0.30. • On the basis of this result, we contended that DV infection has a protective effect that reduces the risk of pSS. | |
33369527 | Golimumab (anti-TNF monoclonal antibody): where we stand today. | 2021 Jun 3 | Tumor necrosis factor (TNF) is a pro-inflammatory cytokine and its overexpression has been implicated in the pathophysiology of several chronic immune-mediated inflammatory diseases. Biological therapies, like TNF inhibitors, have been revolutionizing the course of these disorders. Golimumab is a transgenic anti-TNF monoclonal antibody that acts primarily by targeting and neutralizing TNF, thus preventing inflammation. It is approved for the treatment of Rheumatoid Arthritis, Psoriatic Arthritis, Ankylosing Spondylitis, Nonradiographic axial Spondyloarthritis, Juvenile Idiopathic Arthritis, and Ulcerative Colitis. Clinical trials are also being conducted in other conditions. This review charts the clinical development of golimumab and outlines the data that support its potential use across several Immune-mediated inflammatory diseases. | |
33384928 | Rice body formation due to Haemophilus parainfluenza-associated chronic arthropathy. | 2021 | A 68-year-old woman with a medical history significant for psoriatic arthritis was found to have an enlarged, painful lump on her left hip 15 months after intramedullary rod placement for a left subtrochanteric femur fracture sustained in a fall. Histopathological findings showed rice body formation (RBF) with concurrent H. parainfluenza. RBF is a relatively rare arthropathy of a subset of chronic inflammatory disease such as rheumatoid arthritis or tuberculous arthropathy. RBF associated with psoriatic arthritis or orthopedic hardware placement has been reported in a handful of cases in the literature but there has not been any definitive evidence for RBF as a result of Haemophilus parainfluenza infections and is a rather unusual characteristic of this case. | |
33258533 | Consequences of a Great Crisis on Chronic Diseases: How Childhood Exposures May Shape Futu | 2021 Apr | History, as the saying goes, repeats itself. And, during these historical COVIDâ€19 pandemic times, a rheumatologist may wonder †what does the COVIDâ€19 pandemic mean for rheumatology patients?(1) No one knows for sure, of course. But, if history really does repeat itself, infants and toddlers worldâ€wide may be at risk. This is the focus of the study by VanEvery et al. in this issue of Arthritis and Rheumatology where they examined the association between early life exposure to a prolonged crisis and the future risk of rheumatoid arthritis (RA).(2) Specifically, the authors analyzed data collected from adult participants enrolled in the Kailuan Study in China who were exposed to the Great Chinese Famine (1959â€1961) at early life. | |
34127620 | The other connective tissue disease-associated interstitial lung diseases: Sjogren's syndr | 2021 Sep 1 | PURPOSE OF REVIEW: We review the clinical manifestations of three less common connective tissue disease (CTD)-associated interstitial lung diseases (ILDs): Sjogren's syndrome (SjS), mixed CTD (MCTD), and systemic lupus erythematosus (SLE). RECENT FINDINGS: SjS is classically associated with lymphocytic interstitial pneumonia and cystic lung disease, but the most common type of ILD in Sjogren's patients is nonspecific interstitial pneumonia. ILD is prevalent in MCTD and associated with worse survival. SLE-associated ILD, while rare, is more common in those with CTD overlap syndromes. Regardless of underlying cause, a subset of patients with fibrotic CTD-associated ILD develop a progressive course for which antifibrotic agents and lung transplantation should be considered. SUMMARY: An understanding of the characteristics of ILD in SjS, MCTD, and SLE is important for the pulmonary specialist. Future research should identify risk factors for progression and develop additional treatment modalities for both CTD-related autoimmune features and progressive ILD. | |
33560182 | Effectiveness of subcutaneous tocilizumab in refractory adult Still's disease: report of t | 2021 Jul | Adult Still's disease (ASD) is a systemic inflammatory disorder characterised by spiking fever, skin rash, arthritis, hepatosplenomegaly, and elevated inflammatory markers. Several proinflammatory cytokines, including interleukin (IL)-6, contribute to its pathogenesis. There have been some recent reports on the efficacy of tocilizumab (TCZ), a humanised anti-IL-6 receptor antibody, in the treatment of ASD refractory to conventional therapy. However, most of the evidence is for intravenous administration of TCZ, whereas subcutaneous injection is often preferred in terms of efficiency in cost and labour. We have experienced three patients whose ASD was refractory to corticosteroid and immunosuppressant therapy but showed a marked response to off-label use of subcutaneous TCZ (TCZ-SC). Patient 1 received TCZ-SC 162 mg on days 0 and 14 and every week thereafter. Patients 2 and 3 received TCZ-SC every 2 weeks. At the time of initiation of TCZ-SC, all three patients had elevated inflammatory markers and two had fever despite previous therapy. After the first TCZ-SC injection, the patients became afebrile within one day and inflammatory parameters (i.e. C-reactive protein and erythrocyte sedimentation rate) returned to normal within 2 weeks. None of the patients developed severe infection or other serious side effects during 104 weeks of follow-up. There have been only a limited number of case reports showing that TCZ-SC significantly improves refractory ASD during its active phase. Our experience with these patients suggests that TCZ-SC could, as well as offering cost efficiency in clinical practice, be a potent treatment option for refractory ASD. | |
33536075 | Unstimulated whole salivary flow in Sjögren's Syndrome: systematic literature review and | 2021 Feb 3 | BACKGROUND: Sjögren's Syndrome compromises the exocrine function, producing xerostomia and xerophthalmia. It can appear as an isolated condition or associated with other autoimmune diseases (polyautoimmunity). The Unstimulated Salivary Flow rate (UWSF) is used to quantify saliva production. There is no objective evidence to differentiate the values in patients with Sjögren's versus healthy people or patients with non-Sjögren's sicca. The objective of the present review was to evaluate the UWSF in patients with Sjögren's syndrome in comparison to controls (healthy and non-Sjögren's sicca patients). METHODS: A systematic literature review was carried out (PRISMA guidelines). Analytical observational studies of cases and controls, cross-sectional studies, cohort studies and randomized clinical trials (including healthy controls) were considered. The Medline/OVID, Lilacs, Embase, and Cochrane/OVID databases were consulted. MeSH, DeCS, keywords, and Boolean operators were used. The meta-analysis (RevMan 5.2) was done through the random-effects model [mean difference (MD)]. Level and quality of evidence were evaluated by the Oxford Center Levels of Evidence and Joanna Brigs list respectively. RESULTS: Thirty-two articles were included (20 were case-control studies, 6 were cross-sectional, 2 prospective cohort, 2 retrospective cohort, and 2 studies were abstracts) and 28 were meta-analyzed. The unstimulated whole salivary flow rate in the Sjögren's group was lower than in controls (healthy and patients with non-Sjögren Sicca syndrome) (MD-0.18 ml/min; 95% CI, - 0.24 to - 0.13; chi(2)-P-value < 0.00001). Heterogeneity was 97% and there was publication bias (funnel plot). The level of evidence was mostly 3 or 4. The quality of evidence was met (97% of items valued). CONCLUSION: For the first time, the unstimulated whole salivary flow rate is found to be lower in patients with Sjögren's syndrome compared to controls (healthy and non-SS sicca) through a meta-analysis. TRIAL REGISTRATION: PROSPERO CRD42020211325 . | |
33260099 | Deep learning segmentation of Primary Sjögren's syndrome affected salivary glands from ul | 2021 Feb | Salivary gland ultrasonography (SGUS) has proven to be a promising tool for diagnosing various diseases manifesting with abnormalities in salivary glands (SGs), including primary Sjögren's syndrome (pSS). At present, the major obstacle for establishing SUGS as a standardized tool for pSS diagnosis is its low inter/intra observer reliability. The aim of this study was to address this problem by proposing a robust deep learning-based solution for the automated segmentation of SGUS images. For these purposes, four architectures were considered: a fully convolutional neural network, fully convolutional "DenseNets" (FCN-DenseNet) network, U-Net, and LinkNet. During the course of the study, the growing HarmonicSS cohort included 1184 annotated SGUS images. Accordingly, the algorithms were trained using a transfer learning approach. With regard to the intersection-over-union (IoU), the top-performing FCN-DenseNet (IoU = 0.85) network showed a considerable margin above the inter-observer agreement (IoU = 0.76) and slightly above the intra-observer agreement (IoU = 0.84) between clinical experts. Considering its accuracy and speed (24.5 frames per second), it was concluded that the FCN-DenseNet could have wider applications in clinical practice. Further work on the topic will consider the integration of methods for pSS scoring, with the end goal of establishing SGUS as an effective noninvasive pSS diagnostic tool. To aid this progress, we created inference (frozen models) files for the developed models, and made them publicly available. | |
34325118 | Biomarker screening and validation for the differentiation of bloodstream infection from a | 2021 Oct | OBJECTIVES: Distinguishing between bloodstream infection (BSI) and adult-onset Still's disease (AOSD) is challenging in practice due to similarities in their clinical and laboratory characteristics. We aimed to identify biomarkers in a prospective cohort of patients with BSI and AOSD for differential diagnosis and prognosis prediction. METHODS: Sixty-four individuals were enrolled in the training set (37 with BSI, 17 with AOSD, and 10 healthy controls). Furthermore, 86 individuals were enrolled in the validation cohort (67 with BSI and 19 with AOSD). Clinical and laboratory data were collected. Blood samples were stimulated using bacteria-specific antigens and levels of several cytokines were detected in the supernatant via Luminex or enzyme-linked immunosorbent assay. RESULTS: Escherichia coli and Klebsiella pneumoniae were the pathogens most frequently responsible for BSI. In the training cohort, the incidence of rash, arthralgia, myalgia, sore throat, lymphadenopathy, leukocytosis, and hyperferritinemia was higher in patients with AOSD than in those with BSI. Procalcitonin was significantly higher in patients with BSI than that in those with AOSD. Interleukin (IL)-6, IL-17A, C-X3-C motif chemokine ligand (CX3CL)-1, and C-X-C motif chemokine ligand 10 (CXCL10) levels were higher in patients with BSI than in those with AOSD. IL-18 was higher among patients with AOSD than in those with BSI. A decision tree analysis showed that a combination of plasma IL-18 and ferritin levels can be used to distinguish BSI from AOSD (diagnostic accuracy: 97.67%, sensitivity: 96.15%, specificity: 100%). Plasma IL-18 levels were positively correlated with ferritin, and were decreased after treatment in both BSI and ASOD groups. CONCLUSIONS: Plasma IL-18 and ferritin levels can be used to differentiate BSI from AOSD. IL-18 may be a potential biomarker for prognosis prediction in BSI and AOSD. |