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ID PMID Title PublicationDate abstract
33777724 Frequency of Health Care Resource Utilization and Direct Medical Costs Associated with Pso 2021 OBJECTIVE: To estimate the frequency of health care resource utilization and direct medical costs associated with Psoriatic Arthritis (PsA) in a rheumatic care center in Colombia. METHODS: A retrospective prevalence-based cost of illness study under the Colombian health care system perspective was conducted. We analyzed the frequency of health care resource utilization and estimated direct medical costs using anonymized medical records of adult patients (≥18 years) diagnosed with PsA at a rheumatology care center in Bogotá, Colombia. Patients were required to have at least one medical visit linked to a PsA diagnosis (ICD-10 L40.5) between October 2018 and October 2019 and a previous diagnose by the CASPAR criteria. Data on hospitalization episodes was not available. Direct medical costs were estimated in Colombian pesos (COP) and reported in US dollars (USD) using an exchange rate of 1USD = 3263.4 COP. A multivariate generalized linear model was used for identifying potential cost predictors. RESULTS: A sample of 83 patients was obtained. Of these, 54.2% were women and had a mean (SD) age of 58.7 (12) years at baseline. On average, they had 2.2 and 3.8 medical visits to the dermatologist and rheumatologist in the study period. The total direct medical cost was estimated at 410,985 US Dollars. Medical visits, therapies, laboratory and imaging represented 3.2% of total expenses and medications the remaining 96.8%. Patients receiving conventional DMARDs (cDMARDs) had an associated mean cost of 1020.1 USD (CI 701.4-1338.8) in a year. Among patients treated with cDMARDs and biological DMARDs (bDMARDs) the mean cost increase to 8113.9 USD (SD 5182.0-95% CI 6575.1-9652.8). CONCLUSION: A patient under biological therapy can increase their annual cost by 7.9 times the cost of a patient in conventional therapy. This provided updated knowledge on the direct medical costs, from the provision of a rheumatic care center service, to support epidemiologic or pharmacovigilance models.
33752685 Outcome of children with oligoarticular juvenile idiopathic arthritis compared to polyarth 2021 Mar 22 BACKGROUND: Oligoarticular juvenile idiopathic arthritis (oligoJIA) is the most commonly diagnosed category of chronic arthritis in children. Nevertheless, there are no evidence- based guidelines for its treatment, in particular for the use of methotrexate (MTX). The primary objective of this analysis is to evaluate the outcomes in patients with persistent oligoJIA compared to those with extended oligoJIA and rheumatoid factor (RF) negative polyarthritis treated with methotrexate. METHODS: Patients with persistent or extended oligoJIA or RF negative PA recorded in the Biologics in Pediatric Rheumatology Registry (BiKeR), receiving methotrexate for the first time were included in the analyses. Efficacy was determined using the Juvenile Arthritis Disease Activity Score 10 (JADAS 10). Safety assessment included the documentation of adverse and serious adverse events. RESULTS: From 2005 through 2011, 1056 patients were included: 370 patients with persistent oligoJIA, 221 patients with extended oligoJIA and 467 patients with RF negative PA. Therapeutic efficacy was observed following the start of methotrexate. Over a period of 24 months JADAS-minimal disease activity (JADAS ≤2) was reached in 44% of patients with persistent oligoJIA, 38% with extended oligoJIA, 46% with RF negative PA, JADAS-remission defined as JADAS ≤1 was reached in 33% of patients with persistent oligoJIA, 29% with extended oligoJIA and 35% (RF negative PA). Patients with extended oligoJIA achieved JADAS remission significantly later and received additional biologic disease-modifying drugs significantly more often than patients with persistent oligoJIA or RF negative PA (p < 0.001). Tolerability was comparable. New onset uveitis occurred in 0.3 to 2.2 per 100 patient years. CONCLUSIONS: Patients with persistent oligoJIA taking methotrexate are at least as likely to enter remission as patients with extended oligo JIA or polyarticular JIA. Patients with extended oligoJIA achieved JADAS remission significantly later. Within 2 years, almost half of the patients with persistent oligoJIA achieved JADAS-minimal disease activity.
34014462 En face optical coherence tomography patterns in patients with angiographically documented 2021 Oct PURPOSE: To elucidate the en face optical coherence tomography (OCT) patterns of macular edema in eyes with angiographically documented uveitic macular edema (UME) and compare visual acuity (VA), OCT and OCT-angiography (OCT-A) parameters among the morphological subgroups. METHODS: Thirty-nine eyes of 29 patients with angiographically proven UME were enrolled into the study. All patients underwent comprehensive ophthalmological examination including structural OCT and OCT-A in addition to fluorescein angiography. Eyes with UME were divided into three subgroups (petaloid, sunflower and spoke-wheel pattern) with the help of en face OCT imaging. RESULTS: Posterior uveitis was the most common type of uveitis (17 patients; 58.7%), followed by panuveitis (11 patients; 37.9%) and then intermediate uveitis (1 patient; 3.4%). Underlying causes of uveitis were Behçet's disease (13 patients; 44.8%), idiopathic (11 patients; 37.9%), rheumatoid arthritis (2 patients; 6.9%), sarcoidosis (1 patient; 3.4%), inflammatory polyarthritis (1 patient; 3.4%) and psoriatic arthritis (1 patient; 3.4%). The most common en face OCT pattern was petaloid type (25 of 39 eyes; 64.1%). Eleven eyes (28.2%) had sunflower pattern and three (7.7%) spoke-wheel pattern. There were no statistically significant difference among the subgroups regarding the age, VA, central macular thickness and vessel density. CONCLUSION: This study reveals three morphological en face OCT patterns in eyes with UME and en face OCT may find a niche in the UME classification with the accumulation of experience among the uveitis experts.
33442230 Switching and Discontinuation Patterns Among Patients Stable on Originator Infliximab Who 2021 OBJECTIVE: To compare switching and discontinuation patterns of patients stable on originator infliximab (IFX) who switched to an IFX biosimilar (switchers) or remained on originator IFX (continuers) in the United States. METHODS: Symphony Health Solutions' Patient Transactional Datasets (10/2012-03/2019) were used to identify adults with ≥2 claims for either rheumatoid arthritis (RA), psoriatic arthritis, plaque psoriasis, ankylosing spondylitis, or inflammatory bowel disease (IBD); and ≥1 claim for originator or biosimilar IFX. The index date was the first IFX biosimilar claim for switchers or a random originator IFX claim for continuers. All patients were required to have ≥5 originator IFX claims during the 12 months pre-index (prevalent population). The subset of patients with ≥12 months of observation prior to the first originator IFX claim was also analyzed (incident population). Switchers were matched 1:3 to continuers. Discontinuation was defined as having ≥120 days between 2 consecutive index treatment claims. RESULTS: Prevalent switchers (N=1109) were 3.57-times more likely than continuers (N=3327) to switch to another originator biologic (hazard ratio [HR]=3.57, p<0.001). Of 249 prevalent switchers who switched to another originator biologic, 200 (80.3%) switched back to originator IFX. Incident switchers (N=571) were 2.55-times more likely than continuers (N=1713) to switch to another originator biologic (HR=2.55, p<0.001). Of 118 incident switchers who switched to another originator biologic, 90 (76.3%) switched back to originator IFX. Prevalent switchers were 1.25-times more likely than continuers to discontinue index therapy (HR=1.25, p<0.001). Similar results were observed in RA (prevalent population; switching: HR=3.49, p<0.001; discontinuation: HR=1.23, p=0.009) and IBD (prevalent population; switching: HR=3.82, p<0.001; discontinuation: HR=1.29, p=0.003) subgroups. CONCLUSION: Patients switching from originator to biosimilar IFX were more likely to switch to another originator biologic (notably back to originator IFX) and discontinue index treatment than those remaining on originator IFX; however, reasons for switching are unknown.
32937011 Positive Psychological Factors and Impairment in Rheumatic and Musculoskeletal Disease: Do 2021 Jan OBJECTIVE: Little is known about potential mechanisms of action linking protective positive psychological variables and functional disability in patients with rheumatic and musculoskeletal disease. The present study was undertaken to examine symptoms of psychopathology, including stress, depression, anxiety, and sleep quality, as serial mediators of the association between gratitude, self-compassion, self-forgiveness, and functional impairment. METHODS: We assessed risk and protective factors for functional disability in patients with fibromyalgia (FM), osteoarthritis (OA), rheumatoid arthritis (RA), and ankylosing spondylitis (AS) who were recruited from an Austrian health care facility. Respondents completed online surveys, including the Gratitude Questionnaire 6-item form, the Self-Compassion Scale short form, the Self-Forgiveness and Forgiveness of Others Index, the Perceived Stress Scale 4, the Patient Health Questionnaire 2, the 2-item Generalized Anxiety Disorder Scale, the Sleep Condition Indicator, and the Health Assessment Questionnaire. Bivariate and serial mediation analyses were conducted. RESULTS: For our sample of 1,218 patients (52% female, n = 632; AS [37%], OA [34%], RA [14%], and FM [24%]), stress, depression, and anxiety, in parallel as first-order mediators, and sleep quality as a second-order mediator, explained the association between positive psychological variables and functional disability. CONCLUSION: Positive psychological factors exert a beneficial downstream effect on mental well-being, sleep health, and health-related functional impairment. Therapeutic promotion of gratitude, self-compassion, and self-forgiveness may improve mental and physical health in patients with rheumatic and musculoskeletal disease.
32821952 Short to mid-term outcome of total hip arthroplasty with cementless implants in patients y 2021 Sep BACKGROUND: Total hip arthroplasty (THA) was once reserved for old patients with hip arthritis but has become more common in very young patients (≤25 years old) diagnosed with various joint disease that were not relieved with conservative treatment. The purpose of this study was to evaluate short to mid-term outcome of THA in patients younger than 25 years old. METHOD: This retrospective study included 45 patients younger than 25 years (mean age 21.8 ± 2.14 years) who underwent THA. The surgical indications, implant selection, leg length discrepancy, medication history, radiographic outcome, survival and clinical results including the modified Harris hip score (mHHS) and SF-36 score were assessed. RESULT: The mean follow-up period recorded for patients was 7.82 years (range 5-12 years). The most common diagnosis was avascular necrosis (37.7%) followed by ankylosing spondylitis (24.4%), developmental dysplasia of the hip (17.7%) and rheumatoid arthritis (8.8%). The preoperative leg length discrepancy (LLD), which ranged from 0.5-7 cm significantly improved after surgery ranging from 0-1 cm. The mean preoperative mHHS was 32.44 ± 18.90 compared with the postoperative score of 94.54 ± 5.81 (p < 0.001). The preoperative p-value of SF-36 was lower compared to the postoperative value in all subgroups of SF-36 (p < 0.001). At the latest follow-up there were no radiological signs of loosening and all the implants were classified as well-integrated. CONCLUSION: At present total hip arthroplasty is considered to be safe and a good solution for young patients below 25 years suffering from end-stage joint disease; however, longer follow-up is required to evaluate the long-term function and outcome of the prosthesis in order to restore the normal lifestyle of the patients.
33585636 Adult-onset Still's disease evolving with multiple organ failure and death: A case report 2021 Feb 6 BACKGROUND: Adult-onset Still's disease (AOSD) is a rare systemic inflammatory disease, which is characterized by daily fever and arthritis, with an evanescent rash and neutrophilic leukocytosis. To date, there has been no definite laboratory or imaging test available for diagnosing AOSD; the diagnosis is one of exclusion, which can be very challenging. In particular, AOSD patients may experience different complications affecting their clinical picture, management, and prognosis. The treatment of AOSD remains largely empirical and involves therapeutic agents. CASE SUMMARY: We report the case of a 36-year-old woman who presented with fever, red rash, arthralgia, and sore throat. Her serum ferritin level and white blood cell count were markedly elevated, and the first diagnosis 22 years prior was "juvenile rheumatoid arthritis of systemic type". The patient was treated with prednisone, sulfasalazine, methotrexate, and leflunomide. After remission of her symptoms, the patient stopped taking the medications, and the disease recurred. Ultimately, the patient was diagnosed with adult-onset Still's disease. Relapse occurred several times due to self-medication withdrawal, and an interleukin-6 antagonist (tocilizumab/Actemra) was administered to control the disease. Recently, she was hospitalized because an incision did not heal, and the patient suddenly developed high fever and diarrhea during hospitalization. The patient's disease progressed violently and quickly developed into macrophage activation syndrome, disseminated intravascular coagulation, shock, and multiple organ failure. The patient had sudden cardiac arrest, and she died despite emergency rescue efforts. CONCLUSION: AOSD patients need regular follow-up in the long-term treatment process, and must press formulary standard medication, and do not voluntarily withdraw or reduce the dose. Otherwise it may cause disease back-and-forth or serious life-threatening complications. Meanwhile, strict management of trauma, infections, tumors, and other diseases may contribute to improved outcomes in patients with complications.
34414491 Elimination of irreducible intercalary fragment and fixation using locking plate for Mayo 2021 Aug 19 BACKGROUND: We hypothesized that the outcomes of articular reduction with elimination of irreducible articular intercalary fragments for Mayo type IIB fractures fixed using olecranon locking plates would be as satisfactory as those of noncomminuted fractures. METHODS: A total of 65 patients were enrolled from among 92 who had undergone operative treatment for olecranon fractures between March 2008 and February 2015. Patients with fragments that were eliminated because they were too comminuted to be fixed during surgery (type IIB) were included in group 1. Patients without intraarticular comminuted fragments (type IIA) or with very few fragments were assigned to group 2. In group 1, articular congruency and reduction status were confirmed by direct visualization. The fracture was then fixed with a locking plate and irreducible intercalary fragments were eliminated. RESULTS: There were no significant differences in demographic characteristics, such as age and gender, between the two groups. Both groups achieved bony union within the approximately 6-year follow-up period and there were no serious complications in either group. The grades of heterotrophic ossification and ulnohumeral arthritis were not significantly different between the groups. The mean flexion-extension and pronation-supination arcs were similarly satisfactory in both groups (127.35° and 134.39° vs. 129.69° and 133.75° in groups 1 and 2°, respectively). Clinical outcomes including visual analog scale pain scores, as well as the Mayo Elbow Performance scores (87.73 vs. 88.28 in groups 1 and 2, respectively), were also similarly satisfactory in both groups. CONCLUSIONS: Locking plate fixation under direct visualization (to reduce the articular surface in Mayo type IIB fractures) and elimination of articular intercalary fragments resulted in satisfactory radiologic and clinical outcomes, similar to those of noncomminuted fractures also treated using a locking plate. LEVEL OF EVIDENCE: Level IV, Retrospective therapeutic study.
33767707 Activation of Toll-Like Receptor 7 Signaling Pathway in Primary Sjögren's Syndrome-Associ 2021 Objectives: To identify the importance of the Toll-like receptor (TLR) pathway using B cell high-throughput sequencing and to explore the participation of the TLR7 signaling pathway in primary Sjogren's syndrome (pSS)-associated thrombocytopenia in patient and mouse models. Methods: High-throughput gene sequencing and bioinformatic analyses were performed for 9 patients: 3 patients with pSS and normal platelet counts, 3 patients with pSS-associated thrombocytopenia, and 3 healthy controls. Twenty-four patients with pSS were recruited for validation. Twenty-four non-obese diabetic (NOD) mice were divided into the TLR7 pathway inhibition (CA-4948), activation (Resiquimod), and control groups. Serum, peripheral blood, bone marrow, and submandibular glands were collected for thrombocytopenia and TLR7 pathway analysis. Results: Seven hub genes enriched in the TLR pathway were identified. Compared to that in control patients, the expression of interleukin (IL)-8 and TLR7 pathway molecules in B-cells was higher in patients with pSS-associated thrombocytopenia. Platelet counts exhibited a negative correlation with serum IL-1β and IL-8 levels. In NOD mice, CA-4948/Resiquimod treatment induced the downregulation/upregulation of the TLR7 pathway, leading to consistent elevation/reduction of platelet counts. Megakaryocyte counts in the bone marrow showed an increasing trend in the Resiquimod group, with more naked nuclei. The levels of IL-1β and IL-8 in the serum and submandibular gland tissue increased in the Resiquimod group compared with that in CA-4948 and control groups. Conclusion: pSS-associated thrombocytopenia may be a subset of the systemic inflammatory state as the TLR7 signaling pathway was upregulated in B cells of patients with pSS-associated thrombocytopenia, and activation of the TLR7 pathway led to a thrombocytopenia phenotype in NOD mice.
34044081 Chemical profiling and in-vitro anti-inflammatory activity of bioactive fraction(s) from T 2021 Oct 28 ETHNOPHARMACOLOGICAL RELEVANCE: Trichodesma indicum (L.) R. Br. (family: Boraginaceae) is a medicinal herb largely used to treat arthralgia, rheumatoid arthritis, wound healing, dysentery, etc. It's mechanism of anti-inflammatory activity has not been systematically analyzed yet. AIM OF THE STUDY: The present study was undertaken to examine the anti-inflammatory effects of successive solvent extracts (n-hexane extract (HE), ethyl acetate extract (EA), ethanol extract (EE), aqueous extract (AE) and fractions of HE) from the aerial parts of Trichodesma indicum (TI) against lipopolysaccharide (LPS) stimulated inflammatory reaction using mouse macrophage RAW 264.7 cells. MATERIALS AND METHODS: Cytotoxic effects of the extracts and fractions of TI were assessed by MTT assay. The effect of extracts and fractions on the production of nitric oxide (NO) in RAW 264.7 macrophages were measured using the Griess reagent method. IL - 6, IL - 1β, TNF-α, iNOS and COX-2 gene expressions were examined by a qRT-PCR method. RESULTS: RAW 264.7 macrophages pretreated with HE, EA, EE and AE of TI showed a significant decrease in the production of proinflammatory cytokines and NO without exhibiting cytotoxicity. The potent HE was fractionated using flash chromatography into FA, FB, FC, FD and FE. Among the five fractions, FE displayed a stronger ability to reduce IL - 1β, TNF-α, iNOS, COX2 and NO importantly no cytotoxicity was observed. The phytochemical compounds present in FE were further screened by Gas chromatography - Mass spectroscopy (GC-MS). GC-MS analysis revealed that 1,2-benzenedicarboxylic acid diisooctyl ester is the major compound in FE. Molecular docking analysis showed good inhibition of 1,2-benzenedicarboxylic acid diisooctyl ester against TLR-4, NIK and TACE. CONCLUSION: Our results suggested that 1,2-benzenedicarboxylic acid diisooctyl ester could be a potential candidate in alleviating inflammatory reactions in TI.
32896258 Immune-related adverse events in patients with solid-organ tumours treated with immunother 2021 May OBJECTIVES: Immune checkpoint blockade therapy (ICBT) increases the anti-tumoural function of the immune system, but it can also induce immune-related adverse events (irAEs). Our aim was to assess the irAEs due to ICBT in patients from a single centre of Northern Spain. METHODS: We set up an observational study of patients treated in monotherapy with ICBT targeted against cytotoxic T-lymphocyte antigen 4 (CTLA-4), programmed cell death 1 (PD-1) or its ligand (PD-L1) for solid organ tumours. All patients were followed up in a single University Hospital from March 2015 to September 2018. RESULTS: We studied 102 patients (63 men/39 women); mean age 60.6±9.7 years, with lung (n=63), melanoma (n=21), kidney (n=11), gastric (n=3), colon (n=3) or bladder (n=1) cancer. Only 7 patients had a previous diagnosis of an immune-mediated disease, specifically: psoriasis (n=2), psoriatic arthritis (n=1), systemic lupus erythematosus (n=1), spondyloarthitis (n=1), rheumatoid arthritis (n=1) and cutaneous lupus (n=1). One of the following ICBT was administered: nivolumab (n=52), pembrolizumab (n=35), atezolizumab (n=10) and ipilimumab (n=5). After a mean follow-up time of 14.4±7.7 months since ICBT onset, 87 (85.3%) patients had experienced irAEs, mostly gastrointestinal, thyroid and musculskeletal manifestations including inflammatory arthralgia (n= 8), arthritis (n= 6) and myositis (n=2). ICBT was discontinued in 41 patients but it was reintroduced in 30 of them after resolution of the adverse event, with a good tolerance in all cases. Thirty-six (41.4%) of the 87 patients required specific treatment (prednisone, levothyroxine, and thiamazol) for the irAEs. CONCLUSIONS: irAEs are frequent in patients undergoing ICBT. Almost half of the patients that have irAEs require treatment. Musculoskeletal manifestations are not uncommon.
32613397 The multifaceted functional role of DNA methylation in immune-mediated rheumatic diseases. 2021 Feb Genomic predisposition cannot explain the onset of complex diseases, as well illustrated by the largely incomplete concordance among monozygotic twins. Epigenetic mechanisms, including DNA methylation, chromatin remodelling and non-coding RNA, are considered to be the link between environmental stimuli and disease onset on a permissive genetic background in autoimmune and chronic inflammatory diseases. The paradigmatic cases of rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), systemic sclerosis (SSc), Sjogren's syndrome (SjS) and type-1 diabetes (T1D) share the loss of immunological tolerance to self-antigen influenced by several factors, with a largely incomplete role of individual genomic susceptibility. The most widely investigated epigenetic mechanism is DNA methylation which is associated with gene silencing and is due to the binding of methyl-CpG binding domain (MBD)-containing proteins, such as MECP2, to 5-methylcytosine (5mC). Indeed, a causal relationship occurs between DNA methylation and transcription factors occupancy and recruitment at specific genomic locus. In most cases, the results obtained in different studies are controversial in terms of DNA methylation comparison while fascinating evidence comes from the comparison of the epigenome in clinically discordant monozygotic twins. In this manuscript, we will review the mechanisms of epigenetics and DNA methylation changes in specific immune-mediated rheumatic diseases to highlight remaining unmet needs and to identify possible shared mechanisms beyond different tissue involvements with common therapeutic opportunities. Key Points • DNA methylation has a crucial role in regulating and tuning the immune system. • Evidences suggest that dysregulation of DNA methylation is pivotal in the context of immune-mediated rheumatic diseases. • DNA methylation dysregulation in FOXP3 and interferons-related genes is shared within several autoimmune diseases. • DNA methylation is an attractive marker for diagnosis and therapy.
32402519 Perioperative axial loading computed tomography findings in varus ankle osteoarthritis: Ef 2021 Feb BACKGROUND: We used axial loading computed tomography (AL CT) to evaluate preoperative and postoperative talocrural joints of patients who underwent supramalleolar osteotomy (SMO) to treat varus ankle osteoarthritis. METHODS: We performed retrospective analyses of 16 patients (18 feet) who underwent SMO including fibular osteotomy. Radiographic assessment was performed with weightbearing radiographs and AL CT. Clinical outcomes were assessed based on American Orthopedic Foot & Ankle Society (AOFAS) scale, visual analog scale (VAS) for pain, and Foot and Ankle Ability Measure (FAAM). RESULTS: The mean 2-year follow-up tibial-ankle surface angle, talar tilt angle, Takakura stage, and tibial-lateral surface angle were all significantly different relative to preoperative parameters (P<.05). The mean 6-month follow-up talus rotation ratio was significantly corrected compared to the preoperative value (P=.001). The mean 2-year follow-up AOFAS, VAS at gait, and FAAM scores were all significantly improved relative to preoperative measurements (P=.001). CONCLUSIONS: Abnormal internal rotation of the talus in mild to moderate varus ankle osteoarthritis found on AL CT was significantly corrected after SMO. LEVEL OF EVIDENCE: Therapeutic Level IV.
33189546 Evaluation of the uninjured anterior talofibular ligament by ultrasound for assessing gene 2021 Apr BACKGROUND: Most clinicians use the Beighton score to assess generalized joint hypermobility (GJH) when deciding on the treatment of chronic lateral ankle instability (CLAI). The purpose of the study was to evaluate anterior talofibular ligament (ATFL) status by ultrasound and correlate these values with Beighton scores and the manual anterior drawer test (ADT). METHODS: The participants were divided into two groups, those without GJH (24 ankles) and with GJH (20 ankles). For the investigation of ATFL, resting and stress ultrasonography was performed to assess the length, height (degree of loosening) and thickness. Beighton scores, manual ADT grades and ultrasound parameters of participants with and without GJH were compared. The correlation coefficients among those values were analyzed. RESULTS: The mean ATFL length, resting height, stress height and mean difference in height between resting and stress ATFL were all significantly different between the two groups (P < .05). The resting and stress ATFL length, height, and difference in height between resting and stress ATFL showed a positive linear relationship with Beighton scores and manual ADT grades (P < .05). CONCLUSIONS: The ATFL stress ultrasound parameters showed significant differences between participants with high and low Beighton scores and were correlated with Beighton scores and manual ADT grades. LEVEL OF EVIDENCE: Cross-sectional cohort study; Level of evidence IV.
34760342 Psychometric evaluation of an Italian custom 4-item short form of the PROMIS anxiety item 2021 BACKGROUND: There has recently been growing interest in the roles of inflammation in contributing to the development of anxiety in people with immune-mediated inflammatory diseases (IMID). Patient-reported outcome measures can facilitate the assessment of physical and psychological functioning. The National Institutes of Health (NIH)'s Patient-Reported Outcomes Measurement Information System (PROMIS®) is a set of Patient-Reported Outcomes (PROs) that cover physical appearance, mental health, and social health. The PROMIS has been built through an Item Response Theory approach (IRT), a model-based measurement in which trait level estimates depend on both persons' responses and on the properties of the items that were administered. The aim of this study is to test the psychometric properties of an Italian custom four-item Short Form of the PROMIS Anxiety item bank in a cohort of outpatients with IMIDs. METHODS: We selected four items from the Italian standard Short Form Anxiety 8a and administered them to consecutive outpatients affected by Inflammatory Bowel disease (n = 246), rheumatological (n = 100) and dermatological (n = 43) diseases, and healthy volunteers (n = 280). Data was analyzed through an Item Response Theory (IRT) analysis in order to evaluate the psychometric properties of the Italian adaptation of the PROMIS anxiety short form. RESULTS: Taken together, Confirmatory Factor Analysis and Exploratory Factor analysis suggest that the unidimensionality assumption of the instrument holds. The instrument has excellent reliability from a Classical Theory of Test (CTT) standpoint (Cronbach's α = 0.93, McDonald's ω = 0.92). The 2PL Graded Response Model (GRM) model provided showed a better goodness of fit as compared to the 1PL GRM model, and local independence assumption appears to be met overall. We did not find signs of differential item functioning (DIF) for age and gender, but evidence for uniform (but not non-uniform) DIF was found in three out of four items for the patient vs. control group. Analysis of the test reliability curve suggested that the instrument is most reliable for higher levels of the latent trait of anxiety. The groups of patients exhibited higher levels of anxiety as compared to the control group (ps < 0.001, Bonferroni-corrected). The groups of patients were not different between themselves (p = 1, Bonferroni-corrected). T-scores based on estimated latent trait and raw scores were highly correlated (Pearson's r = 0.98) and led to similar results. DISCUSSION: The Italian custom four-item short form from the PROMIS anxiety form 8a shows acceptable psychometric properties both from a CTT and an IRT standpoint. The Test Reliability Curve shows that this instrument is mostly informative for people with higher levels of anxiety, making it particularly suitable for clinical populations such as IMID patients.
33432658 Molecular markers of telomere dysfunction and senescence are common findings in the usual 2021 Jul AIMS: Idiopathic pulmonary fibrosis (IPF) is a genetically mediated, age-associated, progressive form of pulmonary fibrosis characterised pathologically by a usual interstitial pneumonia (UIP) pattern of fibrosis. The UIP pattern is also found in pulmonary fibrosis attributable to clinical diagnoses other than IPF (non-IPF UIP), whose clinical course is similarly poor, suggesting common molecular drivers. This study investigates whether IPF and non-IPF UIP lungs similarly express markers of telomere dysfunction and senescence. METHODS AND RESULTS: To test whether patients with IPF and non-IPF UIP share molecular drivers, lung tissues from 169 IPF patients and 57 non-IPF UIP patients were histopathologically and molecularly compared. Histopathological changes in both IPF and non-IPF UIP patients included temporal heterogeneity, microscopic honeycombing, fibroblast foci, and dense collagen fibrosis. Non-IPF UIP lungs were more likely to have lymphocytic infiltration, non-caseating granulomas, airway-centred inflammation, or small airways disease. Telomeres were shorter in alveolar type II (AECII) cells of both IPF and non-IPF UIP lungs than in those of age-similar, unused donor, controls. Levels of molecular markers of senescence (p16 and p21) were elevated in lysates of IPF and non-IPF UIP lungs. Immunostaining localised expression of these proteins to AECII cells. The mucin 5B (MUC5B) gene promoter variant minor allele frequency was similar between IPF and non-IPF UIP patients, and MUC5B expression was similar in IPF and non-IPF UIP lungs. CONCLUSIONS: Molecular markers of telomere dysfunction and senescence are pathologically expressed in both IPF and non-IPF UIP lungs. These findings suggest that common molecular drivers may contribute to the pathogenesis of UIP-associated pulmonary fibrosis, regardless of the clinical diagnosis.
34528015 Clinical remission of rheumatoid arthritis in a multicenter real-world study in Asia-Pacif 2021 Oct BACKGROUND: Clinical remission is an attainable goal for Rheumatoid Arthritis (RA). However, data on RA remission rates from multinational studies in the Asia-Pacific region are limited. We conducted a cross-sectional multicentric study to evaluate the clinical remission status and the related factors in RA patients in the Asia-Pacific region. METHODS: RA patients receiving standard care were enrolled consecutively from 17 sites in 11 countries from APLAR RA SIG group. Data were collected on-site by rheumatologists with a standardized case-report form. Remission was analyzed by different definitions including disease activity score using 28 joints (DAS28) based on ESR and CRP, clinical disease activity index (CDAI), simplified disease activity index (SDAI), Boolean remission definition, and clinical deep remission (CliDR). Logistic regression was used to determine related factors of remission. FINDINGS: A total of 2010 RA patients was included in the study, the overall remission rates were 62•3% (DAS28-CRP), 35•5% (DAS28-ESR), 30•8% (CDAI), 26•5% (SDAI), 24•7% (Boolean), and 17•1% (CliDR), respectively, and varied from countries to countries in the Asia-Pacific region. Biological and targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) prescription rate was low (17•9%). Compared to patients in non-remission, patients in remission had higher rates of b/tsDMARDs usage and lower rates of GC usage. The favorable related factors were male sex, younger age, fewer comorbidities, fewer extra-articular manifestations (EAM), and use of b/tsDMARDs, while treatment with GC was negatively related to remission. INTERPRETATION: Remission rates were low and varied in the Asia-Pacific region. Treatment with b/tsDMARDs and less GC usage were related to higher remission rate. There is an unmet need for RA remission in the Asia-Pacific region.
34470798 COVID-19 in Pregnant Women With Rheumatic Disease: Data From the COVID-19 Global Rheumatol 2022 Jan OBJECTIVE: To describe coronavirus disease 2019 (COVID-19) and pregnancy outcomes in patients with rheumatic disease who were pregnant at the time of infection. METHODS: Since March 2020, the COVID-19 Global Rheumatology Alliance has collected cases of patients with rheumatic disease with COVID-19. We report details of pregnant women at the time of COVID-19 infection, including obstetric details separately ascertained from providers. RESULTS: We report on 39 patients, including 22 with obstetric detail available. The mean and median age was 33 years, range 24-45 years. Rheumatic disease diagnoses included rheumatoid arthritis (n = 9), systemic lupus erythematosus (n = 9), psoriatic arthritis/other inflammatory arthritides (n = 8), and antiphospholipid syndrome (n = 6). Most had a term birth (16/22), with 3 preterm births, 1 termination, and 1 miscarriage; 1 woman had yet to deliver at the time of report. One-quarter (n = 10/39) of pregnant women were hospitalized following COVID-19 diagnosis. Two of 39 (5%) required supplemental oxygen (both hospitalized); no patients died. The majority did not receive specific medication treatment for their COVID-19 (n = 32/39, 82%), and 7 patients received some combination of antimalarials, colchicine, anti-interleukin 1β, azithromycin, glucocorticoids, and lopinavir/ritonavir. CONCLUSION: Women with rheumatic diseases who were pregnant at the time of COVID-19 had favorable outcomes. These data have limitations due to the small size and methodology; however, they provide cautious optimism for pregnancy outcomes for women with rheumatic disease particularly in comparison to the increased risk of poor outcomes that have been reported in other series of pregnant women with COVID-19.
34030135 Adalimumab ameliorates memory impairments and neuroinflammation in chronic cerebral hypope 2021 May 24 Vascular dementia (VaD) is the second most common type of dementia worldwide. Although there are five FDA-approved drugs for the treatment of Alzheimer's disease (AD), none of them have been applied to treat VaD. Adalimumab is a TNF-α inhibitor that is used for the treatment of autoimmune diseases such as rheumatoid arthritis. In a recent retrospective case-control study, the application of adalimumab for rheumatoid or psoriasis was shown to decrease the risk of AD. However, whether adalimumab can be used for the treatment of VaD is not clear. In this study, we used 2VO surgery to generate a VaD rat model and treated the rats with adalimumab or vehicle. We demonstrated that VaD rats treated with adalimumab exhibited significant improvements in memory. In addition, adalimumab treatment significantly alleviated neuronal loss in the hippocampi of VaD rats. Moreover, adalimumab significantly reduced microglial activation and reversed M1/M2 polarization in VaD rats. Furthermore, adalimumab treatment suppressed the activity of NF-κB, an important neuroinflammatory transcription factor. Finally, adalimumab displayed a protective role against oxidative stress in VaD rats. Our results indicate that adalimumab may be applied for the treatment of human patients with VaD.
34867938 Therapeutic Potential of Anti-Interferon α Vaccination on SjS-Related Features in the MRL 2021 Sjögren's syndrome (SjS) is a frequent systemic autoimmune disease responsible for a major decrease in patients' quality of life, potentially leading to life-threatening conditions while facing an unmet therapeutic need. Hence, we assessed the immunogenicity, efficacy, and tolerance of IFN-Kinoid (IFN-K), an anti-IFNα vaccination strategy, in a well-known mouse model of systemic autoimmunity with SjS-like features: MRL/MpJ-Faslpr/lpr (MRL/lpr) mice. Two cohorts (with ISA51 or SWE01 as adjuvants) of 26 female MRL/lpr were divided in parallel groups, "controls" (not treated, PBS and Keyhole Limpet Hemocyanin [KLH] groups) or "IFN-K" and followed up for 122 days. Eight-week-old mice received intra-muscular injections (days 0, 7, 28, 56 and 84) of PBS, KLH or IFN-K, emulsified in the appropriate adjuvant, and blood samples were serially collected. At sacrifice, surviving mice were euthanized and their organs were harvested for histopathological analysis (focus score in salivary/lacrimal glands) and IFN signature evaluation. SjS-like features were monitored. IFN-K induced a disease-modifying polyclonal anti-IFNα antibody response in all treated mice with high IFNα neutralization capacities, type 1 IFN signature's reduction and disease features' (ocular and oral sicca syndrome, neuropathy, focus score, glandular production of BAFF) improvement, as reflected by the decrease in Murine Sjögren's Syndrome Disease Activity Index (MuSSDAI) modelled on EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI). No adverse effects were observed. We herein report on the strong efficacy of an innovative anti-IFNα vaccination strategy in a mouse model of SjS, paving the way for further clinical development (a phase IIb trial has just been completed in systemic lupus erythematosus with promising results).