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ID PMID Title PublicationDate abstract
34200499 Hydroquinone Exposure Worsens Rheumatoid Arthritis through the Activation of the Aryl Hydr 2021 Jun 7 Rheumatoid arthritis (RA) development is strongly associated with cigarette smoke exposure, which activates the aryl hydrocarbon receptor (AhR) as a trigger for Th17 inflammatory pathways. We previously demonstrated that the exposure to hydroquinone (HQ), one of the major compounds of cigarette tar, aggravates the arthritis symptomatology in rats. However, the mechanisms related to the HQ-related RA still remain elusive. Cell viability, cytokine secretion, and gene expression were measured in RA human fibroblast-like synoviocytes (RAHFLS) treated with HQ and stimulated or not with TNF-α. Antigen-induced arthritis (AIA) was also elicited in wild type (WT), AhR (-/-) or IL-17R (-/-) C57BL/6 mice upon daily exposure to nebulized HQ (25ppm) between days 15 to 21. At day 21, mice were challenged with mBSA and inflammatory parameters were assessed. The in vitro HQ treatment up-regulated TNFR1, TNFR2 expression, and increased ROS production. The co-treatment of HQ and TNF-α enhanced the IL-6 and IL-8 secretion. However, the pre-incubation of RAHFLS with an AhR antagonist inhibited the HQ-mediated cell proliferation and gene expression profile. About the in vivo approach, the HQ exposure worsened the AIA symptoms (edema, pain, cytokines secretion and NETs formation) in WT mice. These AIA effects were abolished in HQ-exposed AhR (-/-) and IL-17R (-/-) animals though. Our data demonstrated the harmful HQ influence over the onset of arthritis through the activation and proliferation of synoviocytes. The HQ-related RA severity was also associated with the activation of AhR and IL-17 pathways, highlighting how cigarette smoke compounds can contribute to the RA progression.
34988340 High Red Cell Distribution Width and Low Absolute Lymphocyte Count Associate With Subseque 2021 BACKGROUND: Hepatitis-C virus (HCV) chronic infection can lead to cirrhosis, hepatocellular carcinoma (HCC), end-stage liver disease, cardiovascular disease (CVD), and mortality. Transient Elastography (TE) is used to non-invasively assess fibrosis. Whether immune monitoring provides additive prognostic value is not established. Increased red-cell distribution width (RDW) and decreased absolute lymphocyte count (ALC) predict mortality in those without liver disease. Whether these relationships remain during HCV infection is unknown. MATERIALS AND METHODS: A retrospective cohort of 1,715 single-site VA Liver Clinic patients receiving Transient Elastography (TE) 2014-2019 to evaluate HCV-associated liver damage were evaluated for RDW and ALC in relation to traditional parameters of cardiovascular risk, liver health, development of HCC, and mortality. RESULTS: The cohort was 97% male, 55% African American, 26% with diabetes mellitus, 67% with hypertension, and 66% with tobacco use. After TE, 3% were subsequently diagnosed with HCC, and 12% (n=208) died. Most deaths (n=189) were due to non-liver causes. The TE score associated with prevalent CVD, positively correlated with atherosclerotic cardiovascular disease (ASCVD) 10-Year Risk Score, age, RDW, and negatively correlated with ALC. Patients with anisocytosis (RDW above 14%) or lymphopenia (ALC level under 1.2×10(9)/L) had greater subsequent all-cause mortality, even after adjusting for age, TE score, and comorbidities. TE score, and to a modest degree RDW, were associated with subsequent liver-associated mortality, while TE score, RDW, and ALC were each independently associated with non-liver cause of death. CONCLUSION: Widely available mortality calculators generally require multiple pieces of clinical information. RDW and ALC, parameters collected on a single laboratory test that is commonly performed, prior to HCV therapy may be pragmatic markers of long-term risk of mortality.
33732711 Artificial Intelligence for Ultrasound Informative Image Selection of Metacarpal Head Cart 2021 Objectives: This study aims to develop an automatic deep-learning algorithm, which is based on Convolutional Neural Networks (CNNs), for ultrasound informative-image selection of hyaline cartilage at metacarpal head level. The algorithm performance and that of three beginner sonographers were compared with an expert assessment, which was considered the gold standard. Methods: The study was divided into two steps. In the first one, an automatic deep-learning algorithm for image selection was developed using 1,600 ultrasound (US) images of the metacarpal head cartilage (MHC) acquired in 40 healthy subjects using a very high-frequency probe (up to 22 MHz). The algorithm task was to identify US images defined informative as they show enough information to fulfill the Outcome Measure in Rheumatology US definition of healthy hyaline cartilage. The algorithm relied on VGG16 CNN, which was fine-tuned to classify US images in informative and non-informative ones. A repeated leave-four-subject out cross-validation was performed using the expert sonographer assessment as gold-standard. In the second step, the expert assessed the algorithm and the beginner sonographers' ability to obtain US informative images of the MHC. Results: The VGG16 CNN showed excellent performance in the first step, with a mean area (AUC) under the receiver operating characteristic curve, computed among the 10 models obtained from cross-validation, of 0.99 ± 0.01. The model that reached the best AUC on the testing set, which we named "MHC identifier 1," was then evaluated by the expert sonographer. The agreement between the algorithm, and the expert sonographer was almost perfect [Cohen's kappa: 0.84 (95% confidence interval: 0.71-0.98)], whereas the agreement between the expert and the beginner sonographers using conventional assessment was moderate [Cohen's kappa: 0.63 (95% confidence interval: 0.49-0.76)]. The conventional obtainment of US images by beginner sonographers required 6.0 ± 1.0 min, whereas US videoclip acquisition by a beginner sonographer lasted only 2.0 ± 0.8 min. Conclusion: This study paves the way for the automatic identification of informative US images for assessing MHC. This may redefine the US reliability in the evaluation of MHC integrity, especially in terms of intrareader reliability and may support beginner sonographers during US training.
33188918 Profiling and targeting connective tissue remodeling in autoimmunity - A novel paradigm fo 2021 Jan Connective tissue (ConT) remodeling is an essential process in tissue regeneration, where a balanced replacement of old tissue by new tissue occurs. This balance is disturbed in chronic diseases, often autoimmune diseases, usually resulting in the buld up of fibrosis and a gradual loss of organ function. During progression of liver, lung, skin, heart, joint, skeletal and kidney diseasesboth ConT formation and degradation are elevated, which is tightly linked to immune cell activation and a loss of specific cell types and extracellular matrix (ECM) structures that are required for normal organ function. Here, we address the balance of key general and organ specific components of the ECM during homeostasis and in disease, with a focus on collagens, which are emerging as both structural and signaling molecules harbouring neoepitopes and autoantigens that are released during ConT remodeling. Specific collagen molecular signatures of ConT remodeling are linked to disease activity and stage, and to prognosis across different organs. These signatures accompany and further drive disease progression, and often become detectable before clinical disease manifestation (illness). Recent advances allow to quantify and define the nature of ConT remodeling via blood-based assays that measure the levels of well-defined collagen fragments, reflecting different facets of ConT formation and degradation, and associated immunological processes. These novel serum assays are becoming important tools of precision medicine, to detect various chronic and autoimmune diseases before their clinical manifestation, and to non-invasively monitor the efficacy of a broad range of pharmacological interventions.
33029648 Edema-like marrow signal intensity: a narrative review with a pictorial essay. 2021 Apr The term edema-like marrow signal intensity (ELMSI) represents a general term describing an area of abnormal signal intensity at MRI. Its appearance includes absence of clear margins and the possibility of exceeding well-defined anatomical borders (for example, physeal scars). We can define "ELMSI with unknown cause" an entity where the characteristic MR appearance is associated with the absence of specific signs of an underlying condition. However, it is more often an important finding indicating the presence of an underlying disease, and we describe this case as "ELMSI with known cause." It presents a dynamic behavior and its evolution can largely vary. It initially corresponds to an acute inflammatory response with edema, before being variably replaced by more permanent marrow remodeling changes such as fibrosis or myxomatous connective tissue that can occur over time. It is important to study ELMSI variations over time in order to evaluate the activity state and therapeutic response of an inflammatory chronic joint disease, the resolution of a trauma, and the severity of an osteoarthritis. We propose a narrative review of the literature dealing with various subjects about this challenging topic that is imaging, temporal evolution, etiology, differential diagnoses, and possible organization, together with a pictorial essay.
34029875 A biomarker for lymphoma development in Sjogren's syndrome: Salivary gland focus score. 2021 Jul The aim of this study is to explore the role of labial minor salivary gland (LMSG) focus score (FS) in stratifying Sjögren's Syndrome (SS) patients, lymphoma development prediction and to facilitate early lymphoma diagnosis. Ιn an integrated cohort of 1997 patients, 618 patients with FS ≥ 1 and at least one-year elapsing time interval from SS diagnosis to lymphoma diagnosis or last follow up were identified. Clinical, laboratory and serological features were recorded. A data driven logistic regression model was applied to identify independent lymphoma associated risk factors. Furthermore, a FS threshold maximizing the difference of time interval from SS until lymphoma diagnosis between high and low FS lymphoma subgroups was investigated, to develop a follow up strategy for early lymphoma diagnosis. Of the 618 patients, 560 were non-lymphoma SS patients while the other 58 had SS and lymphoma. FS, cryoglobulinemia and salivary gland enlargement (SGE) were proven to be independent lymphoma associated risk factors. Lymphoma patients with FS ≥ 4 had a statistically significant shorter time interval from SS to lymphoma diagnosis, compared to those with FS < 4 (4 vs 9 years, respectively, p = 0,008). SS patients with FS ≥ 4 had more frequently B cell originated manifestations and lymphoma, while in patients with FS < 4, autoimmune thyroiditis was more prevalent. In the latter group SGE was the only lymphoma independent risk factor. A second LMSG biopsy is patients with a FS ≥ 4, 4 years after SS diagnosis and in those with FS < 4 and a history of SGE, at 9-years, may contribute to an early lymphoma diagnosis. Based on our results we conclude that LMSG FS, evaluated at the time of SS diagnosis, is an independent lymphoma associated risk factor and may serve as a predictive biomarker for the early diagnosis of SS-associated lymphomas.
34806341 Fatigue Is Not Associated With Objective Assessments of Inflammation During Tocilizumab Tr 2022 Mar OBJECTIVE: In patients with rheumatoid arthritis (RA), the relation between fatigue and disease activity is not established, and our objective was to explore in post hoc analyses the associations between fatigue and subjective as well as objective assessments of inflammation during follow-up of patients with RA initiating biologic treatment. METHODS: In a Nordic multicenter study, patients with RA starting tocilizumab were examined for fatigue (Functional Assessment of Chronic Illness Therapy-Fatigue sum score) as well as patient-reported outcome measures (PROMs) (patient's global disease activity, joint pain, and Health Assessment Questionnaire Disability Index), clinical examinations (examiner's global disease activity, 28 tender/swollen joint counts), laboratory variables (erythrocyte sedimentation rate, C-reactive protein), and ultrasound assessments (semiquantitative scoring [0-3]) of gray scale and Doppler of 36 joints and 4 tendons) at baseline and 4, 12, and 24 weeks. The associations were explored by using nonparametric tests, including the Wilcoxon rank test, the Mann-Whitney U test, Spearman correlations, and a linear regression and linear mixed model. RESULTS: One hundred ten patients were included (83% female, mean [SD] age 55.6 [12.1] years, mean [SD] RA duration 8.7 [9.5] years, 81% anti-cyclic citrullinated peptide positive). Fatigue, PROMs, and clinical, laboratory, and ultrasound variables all decreased significantly during follow-up, already at 4 weeks (P < 0.001). Fatigue was both cross-sectionally and longitudinally associated with PROMs, whereas there were no or low associations with clinical, laboratory, or ultrasound assessments of inflammation. Baseline fatigue was predictive of PROMs at 12 and 24 weeks (P < 0.05 and P < 0.001, respectively) but not of any objective assessments. CONCLUSION: Fatigue was primarily associated with subjective assessments of disease activity. Thus, the present study supports fatigue to reflect other aspects of RA disease activity than inflammation.
34707673 Changes of DCE-MRI Parameters in Patients with Rheumatoid Arthritis before and after Thera 2021 OBJECTIVE: To explore the changes of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) parameters in patients with rheumatoid arthritis (RA) before and after therapy and their value for the efficacy evaluation of patients. METHODS: Totally, 90 patients with RA confirmed in our hospital between January 2018 and January 2020 were enrolled. All of them were examined with a Siemens Magnetom Avanto 1.5T imaging system, and data about the rate of enhancement in early stage (REE) and steep slope maximum (SSmax) were obtained. Then, the disease activity score in 28 joints (DAS-28), REE, and SSmax were analyzed, and the associations of SSmax and REE with erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and DAS-28 were investigated. Additionally, the patients were assigned to the acute-stage group and the chronic-stage group according to their time-signal intensity curves after therapy, and the two groups were compared in SSmax, REE, ESR, CRP, and DAS-28. Corresponding receiver operating characteristic (ROC) curves were drawn for the analysis of potential markers for efficacy improvement in patients. RESULTS: After therapy, REE, SSmax, ESR, DAS-28, and CRP in the synovium of all patients declined greatly (all P < 0.05), with higher levels observed in the acute-stage group than those in the chronic-stage group (all P < 0.05). SSmax and REE of patients were positively bound up with their ESR, CRP, and DAS-28 (all P < 0.05). Additionally, according to ROC curve-based analysis, both SSmax and REE can be adopted as biological indexes for distinguishing between patients at the acute phase from those at the chronic stage, and joint detection of them can boost the sensitivity of DAS-28. CONCLUSION: The SSmax and REE levels in RA patients after treatment were significantly decreased, and the levels in patients in the chronic phase were lower than those in patients in the acute phase. SSmax and REE are highly expressed in RA patients, and the combined detection can enhance the value of DAS-28 in the assessment of RA, and it is worthy of clinical promotion.
34514946 Calcified cartilage differs in patients with end-stage primary osteoarthritis and secondar 2021 Sep 13 Objectives: Despite distinct aetiologies, the end-stages of primary osteoarthritis (OA) and secondary OA are described by common radiological features. However, the morphology of the bone-cartilage unit may differ depending on the pathogenesis. In this cross-sectional study, we aimed to investigate the histological differences in the bone-cartilage unit of the femoral head between patients with primary OA and secondary OA due to rheumatoid arthritis (RA).Method: Femoral heads were obtained from 12 patients with primary OA, six patients with secondary OA due to RA, and 12 control subjects. The femoral heads were investigated using stereological methods to ensure unbiased quantification.Results: The volume (mean difference [95% confidence interval]) (2.1 [0.5;3.8] cm(3), p = 0.016) and thickness (413 [78.9;747] µm, p = 0.029) of the articular cartilage and the thickness of the calcified cartilage (56.4 [0.4;113] µm, p = 0.017) were larger in patients with primary OA than in patients with secondary OA due to RA. Femoral head volume (1.2 [-3.6;6.1] cm(3), p = 0.598), bone volume fraction (-1.1 [-2.8;5.1] cm(3), p = 0.553), subchondral bone thickness (-2.5 [-212;207] µm, p = 0.980), and osteophyte area (25.3 [-53.6;104] cm(2), p = 0.506) did not differ between patients.Conclusion: The thicker calcified cartilage in primary OA preceding the loss of articular cartilage can be attributed to endochondral ossification. Patients with secondary OA due to RA had severely thinner calcified cartilage as the pathogenesis is driven by inflammation and is characterized by a generalized and more severe loss of articular cartilage.
34263716 Comparison between 1.5T and 3.0T MRI: both field strengths sensitively detect subclinical 2021 Jul 15 Objective: Magnetic resonance imaging (MRI) of small joints sensitively detects inflammation. This inflammation, and tenosynovitis in particular, has been shown to predict rheumatoid arthritis (RA) development in arthralgia patients. These data have predominantly been acquired on 1.0-1.5 T MRI. However, 3.0 T is now commonly used in practice. Evidence on the comparability of these field strengths is scarce and has never included subtle inflammation in arthralgia patients or tenosynovitis. Therefore, we assessed the comparability of 1.5 T and 3.0 T in detecting subclinical inflammation in arthralgia patients.Method: A total of 2968 locations (joints, bones, tendon sheaths) in the hands and forefeet of 28 patients with small-joint arthralgia, at risk for RA, were imaged on both 1.5 and 3.0 T MRI. Two blinded readers independently scored erosions, osteitis, synovitis, and tenosynovitis, in line with the Rheumatoid Arthritis Magnetic Resonance Imaging Score (RAMRIS). Features were summed into inflammation (osteitis, synovitis, tenosynovitis) and RAMRIS (inflammation and erosions). Agreement was assessed with intraclass correlation coefficients (ICCs) for continuous scores and after dichotomization into presence or absence of inflammation, on patient and location levels.Results: Interreader ICCs were excellent (> 0.90). Comparing 1.5 and 3.0 T revealed an ICC of 0.90 for inflammation and RAMRIS. ICCs for individual inflammation features were: tenosynovitis 0.87 (95% confidence interval 0.74-0.94), synovitis 0.65 (0.24-0.84), and osteitis 0.96 (0.91-0.98). Agreement was 83% for inflammation and 89% for RAMRIS. Analyses on the location level showed similar results.Conclusion: Agreement on subclinical inflammation between 1.5 T and 3.0 T was excellent. Although synovitis scores were slightly different, synovitis often occurs simultaneously with other inflammatory signs, suggesting that scientific results on the predictive value of MRI-detected inflammation for RA, obtained on 1.5 T MRI, can be generalized to 3.0 T MRI.
34096434 Modified lung ultrasound scoring system to evaluate the feasibility of pregnant women with 2021 Jun 6 OBJECTIVE: To investigate whether physicians with short-term training can use a modified lung ultrasound scoring system for coronavirus disease 2019 (COVID-19) pneumonia to assess lung damage in pregnant women. METHODS: Sixteen consecutively hospitalized third-trimester pregnant women with pregnancy-induced hypertension, preeclampsia, rheumatoid arthritis or connective tissue disease were selected as the study subjects for the simulation of COVID-19 pneumonia. Two physicians (imaging and internal medicine) without ultrasonic experience performed lung examinations on pregnant women after six days of lung ultrasound training, and their consistency with examinations by the expert was assessed. In addition, 54 healthy third-trimester pregnant women and 54 healthy nonpregnant women of the same age who were continuously treated in the outpatient clinic of this hospital were selected for comparisons of abnormalities on lung ultrasound. RESULTS: (1) Third trimester pregnant women with pregnancy-induced hypertension, preeclampsia, rheumatoid arthritis or connective tissue disease had the same lung ultrasound patterns as those associated with COVID-19 pneumonia. (2) There was no statistically significant difference between the scores of the two trained doctors and the expert when the modified ultrasound scoring system was used (p > .05). (3) The evaluations of the two trained doctors and the expert showed good consistency (kappa value = 0.833-0.957). (4) The incidence of abnormal ultrasound manifestations of the pleura and lung parenchyma was higher among healthy third-trimester pregnant women than among healthy women of the same age (p < .001). CONCLUSIONS: After receiving short-term training, imaging and internal medicine physicians can use the modified lung ultrasound scoring system to evaluate pregnant women's pulmonary damage, but caution is needed to avoid false-positive results among pregnant women with suspected COVID-19 pneumonia.
33912401 Support for a non-therapist assisted, Internet-based cognitive-behavioral therapy (iCBT) i 2021 Apr BACKGROUND: Anxiety is common in patients with rheumatoid arthritis (RA) and associated with worse RA outcomes. This study assessed the feasibility and preliminary health impacts (mental and physical) of a non-therapist assisted, online mental health intervention targeting anxiety in this population. METHODS: Participants with confirmed RA and elevated anxiety symptoms were enrolled into the Worry and Sadness program, an Internet-based cognitive-behavioral therapy (iCBT) intervention for anxiety and depression shown to be effective in the general population. Validated self-report measures of anxiety, depression, pain interference, fatigue, physical health-related quality of life, functional status, and patient-reported disease severity were collected at baseline, post-intervention, and at three-month follow-up. Emotional distress scores were tracked between lessons. Participants provided qualitative feedback in writing post-intervention. RESULTS: We analyzed the responses of 34 participants; the majority was female (86%) and the mean age was 57 (SD = 13). Of these, 80% (n = 28) completed the study in its entirety. Among these completers, 94.1% described the program as worthwhile. We found statistically significant improvements in anxiety, depression and fatigue from baseline to three-month follow-up, with small to large effect sizes (d = 0.39-0.81). Post-hoc analyses revealed that statistically significant change occurred between baseline and post-intervention for anxiety and depression and was maintained at three-month follow-up, whereas statistically significant change occurred between baseline and three-month follow-up for fatigue. Statistically significant reductions in emotional distress occurred across the program, with a large effect size (d = 1.16) between the first and last lesson. CONCLUSION: The Worry and Sadness program shows promise as a feasible resource for improving mental health in RA.
33164739 Treating rheumatoid arthritis with leflunomide monotherapy versus combination therapy with 2021 Jan OBJECTIVE: Combination therapies have been proposed as a strategy to control inflammation more effectively in patients with rheumatoid arthritis (RA). Few studies examine the combined effect of methotrexate (MTX) and leflunomide (LFN). This study evaluated the symptom control and side effects of the combination of MTX and LFN compared with LFN monotherapy. METHODS: We conducted a retrospective analysis of 113 patients with RA treated with either LFN alone (n=22) or in combination with MTX (n=91). Data on disease activity score 28 erythrocyte sedimentation rate (DAS-28 ESR), DAS-28 C-reactive protein (DAS-28 CRP), blood cell count, liver enzymes, and creatinine levels were determined. Samples were collected on day 0 (initiation of LFN) and at 6 and 12 months. RESULTS: We found no differences between the 2 groups in DAS-28 on day 0 and at 6 and 12 months (p=0.89, p=0.42, and p=0.09, respectively, for DAS-28 ESR; p=0.97, p=0.27, and p=0.63, respectively, for DAS-28 CRP). In addition, we observed no differences in the blood cell count, liver enzymes, and creatinine levels between the treatment groups at any of the time points (all p>0.05). CONCLUSION: Our results suggest that the efficacy of the combined treatment with MTX and LFN is similar to that of LFN alone. No increase in toxicity was observed with the combination therapy.
34957056 Triterpenoids From Kadsura coccinea With Their Anti-inflammatory and Inhibited Proliferati 2021 One new 3,4-seco-17,13-friedo-lanostane triterpenoid heilaohuacid A (1), one new 3,4-seco-17,14-friedo-lanostane triterpenoid heilaohuacid B (2), five new 3,4-seco-lanostane triterpenoids heilaohuacids C-D (3-4) and heilaohumethylesters A-C (7-9), one new 3,4-seco-cycloartane triterpenoid heilaohuacid E (5), and one new intact-lanostane triterpenoid heilaohuacid F (6), together with twenty-two known analogues (10-31), were isolated from heilaohu. Their structures were determined using HR-ESI-MS data, 1D and 2D NMR spectra, (13)C NMR calculations, and electronic circular dichroism (ECD) calculations. Heilaohuacids A and B (1 and 2) contain a 3,4-seco ring A and unprecedented migration of Me-18 from C-13 to C-17 or C-14 to C-18. This type of lanostane triterpenoid derivatives was rarely reported so far. More importantly, all compounds against inflammatory cytokines IL-6 and TNF-α levels on LPS-induced RAW 264.7 macrophages were evaluated, and compounds 4 and 31 significantly inhibited the release level of IL-6 with IC(50) values of 8.15 and 9.86 μM, respectively. Meanwhile, compounds 17, 18, and 31 significantly inhibited proliferation of rheumatoid arthritis-fibroblastoid synovial (RA-FLS) cells in vitro with IC(50) values of 7.52, 8.85, and 7.97 μM, respectively.
34913402 Incidence and prevalence of rheumatoid arthritis in Denmark from 1998 to 2018: a nationwid 2021 Dec 16 Objective: To investigate the incidence and prevalence of rheumatoid arthritis (RA) in the adult Danish population.Method: In this nationwide register-based cohort study, patients with incident RA between 1998 and the end of 2018 were identified using Danish administrative registries. The age- and sex-standardized incidence rate (IR), incidence proportion (IP), lifetime risk (LR), and point prevalence (PP) of RA were calculated. RA was defined as a first-time RA diagnosis registered in the Danish National Patient Registry combined with a redeemed prescription of a conventional synthetic disease-modifying anti-rheumatic drug in the following year. In addition, three different case definitions of RA were explored.Results: The overall age- and sex-standardized IR of RA from 1998 to 2018 was 35.5 [95% confidence interval (CI) 35.1-35.9] per 100 000 person-years while the IP was 35.2 (95% CI 34.8-35.5) per 100 000 individuals. The IR was two-fold higher for women than for men. The LR of RA ranged from 2.3% to 3.4% for women and from 1.1% to 1.5% for men, depending on the RA case definition used. The overall PP of RA was 0.6% (95% CI 0.5-0.6%) in 2018: 0.8% (95% CI 0.7-0.8%) for women and 0.3% (95% CI 0.3-0.4%) for men. The prevalence increased about 1.5-fold from 2000 to 2018.Conclusion: The IR and PP were approximately two-fold higher for women than for men. The prevalence of RA in Denmark increased significantly from 2000 to 2018. The RA case definition had more impact on the results than the choice of denominator.
34643165 The validity of rheumatoid arthritis diagnoses in Finnish biobanks. 2021 Oct 13 OBJECTIVE: The aim of this study was to determine the validity of rheumatoid arthritis (RA) diagnoses in patients participating in Finnish biobanks. METHOD: We reviewed the electronic medical records of 500 Finnish biobank participants: 125 patients with at least one visit with a diagnosis of seropositive RA, 125 patients with at least one visit with a diagnosis of seronegative RA, and 250 age- and gender-matched controls. The patients were chosen from five different biobank hospitals in Finland. A rheumatologist reviewed the medical records to assess whether each patients' diagnosis was correct. The diagnosis was compared with the diagnostic codes in the Finnish Care Register for Health Care (CRHC) and special reimbursement data of the Social Insurance Institution of Finland. RESULTS: The positive predictive value (PPV) of CRHC diagnosis of RA (for seropositive and seronegative RA combined) was 0.82. For patients with a special reimbursement for anti-rheumatic medications for RA, the PPV was 0.89. The PPV was higher in patients with more than one visit. For one, two, five, and 10 visits, the PPV was 0.82, 0.85, 0.89, and 0.90, respectively, and for patients who also had the special reimbursement, the PPV was 0.89, 0.91, 0.93, and 0.94 for one, two, five, and 10 visits, respectively. In patients positive for anti-citrullinated protein antibodies, the PPV was 0.98. CONCLUSION: These results demonstrate that the validity of RA diagnoses in Finnish biobanks was good and can be further improved by including data on special reimbursement for medication, number of visits, and serological data.
34452152 External Evaluation of Population Pharmacokinetic Models and Bayes-Based Dosing of Inflixi 2021 Aug 3 Despite the well-demonstrated efficacy of infliximab in inflammatory diseases, treatment failure remains frequent. Dose adjustment using Bayesian methods has shown in silico its interest in achieving target plasma concentrations. However, most of the published models have not been fully validated in accordance with the recommendations. This study aimed to submit these models to an external evaluation and verify their predictive capabilities. Eight models were selected for external evaluation, carried out on an independent database (409 concentrations from 157 patients). Each model was evaluated based on the following parameters: goodness-of-fit (comparison of predictions to observations), residual error model (population weighted residuals (PWRES), individual weighted residuals (IWRES), and normalized prediction distribution errors (NPDE)), and predictive performances (prediction-corrected visual predictive checks (pcVPC) and Bayesian simulations). The performances observed during this external evaluation varied greatly from one model to another. The eight evaluated models showed a significant bias in population predictions (from -7.19 to 7.38 mg/L). Individual predictions showed acceptable bias and precision for six of the eight models (mean error of -0.74 to -0.29 mg/L and mean percent error of -16.6 to -0.4%). Analysis of NPDE and pcVPC confirmed these results and revealed a problem with the inclusion of several covariates (weight, concomitant immunomodulatory treatment, presence of anti-drug antibodies). This external evaluation showed satisfactory results for some models, notably models A and B, and highlighted several prospects for improving the pharmacokinetic models of infliximab for clinical-biological application.
34402602 Patients' Perceptions of Person-Centered Care in Early Rheumatoid Arthritis: A Qualitative 2021 Nov OBJECTIVE: Most research on patient experiences of rheumatoid arthritis (RA) care is performed with patients who have established RA and less often with patients with early RA. Experiences of and expectations about health care may change over time, which is why the aim was to explore patients' perceptions of person-centered care (PCC) early in the RA disease course. METHODS: Thirty-one patients with early RA were interviewed in this qualitative study. An abductive qualitative content analysis was conducted based on the framework of McCormack and McCance (1,2). The four constructs, prerequisites, care environment, person-centered processes, and person-centered outcomes, constituted the four categories in the deductive part of the study. An inductive analysis generated 11 subcategories exploring the content of PCC. RESULTS: For patients with early RA, PCC was described in terms of 1) prerequisites including being treated with respect, meeting dedicated health care professionals, and meeting professional competence; 2) care environment including having access to a multidisciplinary team, having access to health care, and encountering a supportive organization; 3) person-centered processes including being listened to, being supported, and being involved in decision-making; and 4) person-centered outcomes including being satisfied with received health care and achieving optimal health. CONCLUSION: Genuine PCC is important for patients early in the RA disease course, supporting the implementation of a person-centered approach during all stages in the health care system. This study contributes to information about how to further develop person-centeredness in rheumatology care.
34295334 Role of Th22 Cells in the Pathogenesis of Autoimmune Diseases. 2021 Upon antigenic stimulation, naïve CD4(+)T cells differentiate into different subsets and secrete various cytokines to exert biological effects. Th22 cells, a newly identified CD4(+)T cell subset,are distinct from the Th1, Th2 and Th17 subsets. Th22 cells secrete certain cytokines such as IL-22, IL-13 and TNF-α, but not others, such as IL-17, IL-4, or interferon-γ (IFN-γ), and they express chemokine receptors CCR4, CCR6 and CCR10. Th22 cells were initially found to play a role in skin inflammatory diseases, but recent studies have demonstrated their involvement in the development of various autoimmune diseases. Here, we review research advances in the origin, characteristics and effector mechanisms of Th22 cells, with an emphasis on the role of Th22 cells and their main effector cytokine IL-22 in the pathogenesis of autoimmune diseases. The findings presented here may facilitate the development of new therapeutic strategies for targeting these diseases.
33447873 Humeral amputation following total elbow arthroplasty. 2021 May PURPOSE: Total elbow arthroplasty (TEA) is associated with a relatively high complication rate, and exceptionally catastrophic complications might lead to amputation. The purpose of this study was to determine the incidence and aetiology of amputation performed at our institution in upper extremity limbs with a prior TEA. METHODS: Between 1973 and 2018, 1906 consecutive TEAs were performed at our institution. Upper extremity amputation was performed in seven (0.36%) elbows with five transhumeral amputations and two shoulder disarticulations. The group consisted of five females and two males with a mean age of 64 years (range, 37-80). The index TEA had been performed for rheumatoid arthritis (n = 2), rheumatoid arthritis with acute fracture (n = 2), radiation associated nonunion (n = 2), and metastatic cancer (n = 1). Mean follow-up after amputation was three years (range, 3 months-5 years). RESULTS: Mean time between amputation and TEA was 5 years (range, 2 months-13 years). The indications for amputation included uncontrolled deep infection in six (86%) elbows and tumor recurrence in one (14%) elbow. Only one elbow (14%) was fitted with a prosthesis. Six (86%) patients died at a mean of three years (range, 3 months-5 years) after amputation. CONCLUSION: The results of this study highlight a low incidence of amputation after TEA. Most amputations were the direct result of TEA complications, with infection being the most common cause of amputation. Outcomes after amputation are concerning, with poor overall survival and few patients being fit for a prosthesis.