The latest medical research on Rheumatology
The research magnet gathers the latest research from around the web, based on your specialty area. Below you will find a sample of some of the most recent articles from reputable medical journals about rheumatology gathered by our medical AI research bot.
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Request AccessMyeloablation followed by hematopoietic stem cell transplantation leads to long-term normalization of systemic sclerosis molecular signatures.
Arthritis RheumatolIn the randomized Scleroderma: Cyclophosphamide Or Transplantation (SCOT trial), myeloablation, followed by hematopoietic stem cell transplantation (HSCT), led to normalization of systemic sclerosis (SSc) peripheral blood gene cell (PBC) expression signature at the 26-month visit. Herein, we examined long-term molecular changes ensuing 54 months after randomization for individuals receiving an HSCT or 12 months of intravenous cyclophosphamide (CYC).
Global PBC transcript studies were performed at pretreatment baseline, 38 months, and 54 months post-randomization, as well as in healthy controls using Illumina HT-12 arrays.
Thirty (HSCT=19 and CYC=11) participants had 38-month and 26 (HSCT=16 and CYC=11) had 54-month samples available. In the paired comparison to baseline, a significant down-regulation of interferon modules and an up-regulation of cytotoxic/NK module were observed at 38-month and 54-month visits in the HSCT arm indicating a long-term normalization of baseline SSc gene expression signature. No differentially expressed modules were detected in the CYC arm. In the comparison to healthy controls, 38-month visit samples in the HSCT arm showed an upregulation of B cell and plasmablast modules and a downregulation of myeloid and inflammation modules. Importantly, 54-month HSCT samples did not show any differentially expressed modules compared to healthy controls suggesting completion of immune reconstitution. Participants in the CYC arm continued to show an SSc transcript signature in comparison to controls at both time points.
Paralleling the observed clinical benefit, HSCT leads to durable long-term normalization of the molecular signature in SSc with completion of immune resetting to 54 months post-HSCT.
MRI-based synthetic CT: a new method for structural damage assessment in the spine in patients with axial spondyloarthritis - a comparison with low-dose CT and radiography.
Annals of the Rheumatic DiseasesTo investigate the ability of MRI-based synthetic CT (sCT), low-dose CT (ldCT) and radiography to detect spinal new bone formation (NBF) in patients with axial spondyloarthritis (axSpA).
Radiography of lumbar and cervical spine, ldCT and sCT of the entire spine were performed in 17 patients with axSpA. sCT was reconstructed using the BoneMRI application (V.1.6, MRIGuidance BV, Utrecht, NL), a quantitative three-dimensional MRI-technique based on a dual-echo gradient sequence and a machine learning processing pipeline that can generate CT-like MR images. Images were anonymised and scored by four readers blinded to other imaging/clinical information, applying the Canada-Denmark NBF assessment system.
Mean scores of NBF lesions for the four readers were 188/209/37 for ldCT/sCT/radiography. Most NBF findings were at anterior vertebral corners with means 163 on ldCT, 166 on sCT and 35 on radiography. With ldCT of the entire spine as reference standard, the sensitivity to detect NBF was 0.67/0.13 for sCT/radiography; both with specificities >0.95. For levels that were assessable on radiography (C2-T1 and T12-S1), the sensitivity was 0.61/0.48 for sCT/radiography, specificities >0.90. For facet joints, the sensitivity was 0.46/0.03 for sCT/radiography, specificities >0.94. The mean inter-reader agreements (kappa) for all locations were 0.68/0.58/0.56 for ldCT/sCT/radiography, best for anterior corners.
With ldCT as reference standard, MRI-based sCT of the spine showed very high specificity and a sensitivity much higher than radiography, despite limited reader training. sCT could become highly valuable for detecting/monitoring structural spine damage in axSpA, not the least in clinical trials.
Evidence-Based Guideline for the management of osteoporosis in men.
Nature Reviews RheumatologyHistorically, osteoporosis has been viewed as a disease of women, with research, trials of interventions and guidelines predominantly focused as su...
Quantifying the need for specialist palliative care management in systemic sclerosis.
Arthritis Care ResThe importance of early integration of palliative care in the management of complex multi-system diseases has been recognised. In this study, we aimed to quantify the need for specialist palliative care in systemic sclerosis (SSc).
Using data from 875 patients enrolled in the Australian Scleroderma Cohort Study, we defined need for palliative care as a high symptom burden at ≥2 consecutive study visits, ≥50% of overall study visits or at the study visit immediately prior to death. Symptoms of interest included breathlessness, fatigue, pain, depression, anxiety, constipation, and diarrhoea. Logistic regression analyses evaluated the association between individual symptoms and SSc manifestations. Linear regression analysis evaluated the relationship between palliative care needs and quality of life (QoL) and function.
Almost three-quarters (72.69%) of patients met the threshold for specialist palliative care needs. Severe fatigue (54.17%) was most common, followed by breathlessness (23.66%) and severe constipation (21.14%). Concurrent severe symptoms were frequently observed. Severe breathlessness (coef -7.95, p<0.01) and pain (coef -7.70, p<0.01) were associated with the largest reductions in physical QoL. Severe mood symptoms were associated with the greatest reduction in mental QoL (coef -12.91, p<0.01). Severe pain (coef 0.56, p<0.01), breathlessness (coef 0.49, p<0.01) and mood symptoms (coef 0.40, p<0.01) had a significant impact on function.
SSc is frequently associated with multiple severe symptoms that may be amenable to palliative care intervention. Given the strong association between symptom burden and impaired QoL targeted, effective symptom management in parallel with standard-of-care treatments may improve overall patient outcomes.
The risk of relapse of ANCA-associated vasculitis in a randomized controlled trial of plasma exchange and glucocorticoids.
Arthritis RheumatolRelapses of ANCA-associated vasculitis are important events that can cause organ dysfunction and reduce quality of life. Understanding the effects of the initial treatments for ANCA-associated vasculitis on the subsequent risk of relapse may help guide monitoring and treatment.
We performed a post hoc analysis of participants with severe ANCA-associated vasculitis enrolled in an international, two-by-two factorial randomized controlled trial comparing the effects of plasma exchange (PLEX) to no PLEX and a regimen of reduced glucocorticoid exposure to a standard regimen. We estimated the effects of treatments on relapses of any severity using three competing-risk time-to-event models adjusted for patient and disease characteristics, and other treatments. Each model was adjusted for disease manifestations in different ways.
Of 704 participants, 649 (92.2%) achieved remission and 147 (22.7%) experienced 204 relapses. The relapse rate was 10.3 (95% CI 8.4 - 12.1) relapses per 100 patient-years. Neither the use of PLEX (subhazard ratio 0.91 to 0.94, 95% CI 0.66 to 1.31), nor glucocorticoid regimen (subhazard ratio 0.93 to 0.94, 95% CIs range from 0.67 to 1.35) appreciably changed the risk of relapse. Proteinase 3-ANCA and the presence of non-hemorrhagic respiratory manifestations of disease at trial entry were associated with an increased risk of relapse. Receiving dialysis at baseline and use of oral cyclophosphamide as induction therapy was associated with a lower risk of relapse.
In patients with severe ANCA-associated vasculitis, relapses remain common; neither the use of plasma exchange nor initial glucocorticoid tapering regimen impacted relapse risk.
Risk of Venous Thromboembolism with Tofacitinib Versus Tumor Necrosis Factor Inhibitors in Cardiovascular Risk-enriched Rheumatoid Arthritis Patients.
Arthritis RheumatolThe ORAL Surveillance trial found a dose-dependent increase in venous thromboembolism (VTE) and pulmonary embolism (PE) events with tofacitinib versus tumor necrosis factor inhibitors (TNFi). We aimed to assess VTE incidence over time and explore risk factors of VTE, including disease activity, in ORAL Surveillance.
Patients with rheumatoid arthritis (RA) aged ≥50 years with ≥1 additional cardiovascular risk factor received tofacitinib 5 or 10 mg twice daily (BID) or TNFi. Post hoc, cumulative probabilities and incidence rates (IRs; patients with first events/100 patient-years) by 6-month intervals were estimated for adjudicated VTE, deep vein thrombosis, and PE. Cox regression models identified risk factors. Clinical Disease Activity Index (CDAI) leading up to the event was explored in patients with VTE.
Cumulative probabilities for VTE and PE were higher with tofacitinib 10 mg BID, but not 5 mg BID, versus TNFi. IRs were consistent across 6-month intervals within treatments. Across treatments, risk factors for VTE included prior VTE, body mass index (BMI) ≥35 kg/m2 , older age, and history of chronic lung disease. At the time of the event, most patients with VTE had CDAI-defined active disease.
Incidences of VTE and PE were higher with tofacitinib (10>5 mg BID) versus TNFi and were generally consistent over time. Across treatments, VTE risk factors were aligned with previous studies in the general RA population. These data highlight the importance of assessing VTE risk factors, including age, BMI, and VTE history, when considering initiation of tofacitinib or TNFi in patients with active RA.
Primary osteoarthritis chondrocyte map of chromatin conformation reveals novel candidate effector genes.
Annals of the Rheumatic DiseasesOsteoarthritis is a complex disease with a huge public health burden. Genome-wide association studies (GWAS) have identified hundreds of osteoarthritis-associated sequence variants, but the effector genes underpinning these signals remain largely elusive. Understanding chromosome organisation in three-dimensional (3D) space is essential for identifying long-range contacts between distant genomic features (e.g., between genes and regulatory elements), in a tissue-specific manner. Here, we generate the first whole genome chromosome conformation analysis (Hi-C) map of primary osteoarthritis chondrocytes and identify novel candidate effector genes for the disease.
Primary chondrocytes collected from 8 patients with knee osteoarthritis underwent Hi-C analysis to link chromosomal structure to genomic sequence. The identified loops were then combined with osteoarthritis GWAS results and epigenomic data from primary knee osteoarthritis chondrocytes to identify variants involved in gene regulation via enhancer-promoter interactions.
We identified 345 genetic variants residing within chromatin loop anchors that are associated with 77 osteoarthritis GWAS signals. Ten of these variants reside directly in enhancer regions of 10 newly described active enhancer-promoter loops, identified with multiomics analysis of publicly available chromatin immunoprecipitation sequencing (ChIP-seq) and assay for transposase-accessible chromatin using sequencing (ATAC-seq) data from primary knee chondrocyte cells, pointing to two new candidate effector genes SPRY4 and PAPPA (pregnancy-associated plasma protein A) as well as further support for the gene SLC44A2 known to be involved in osteoarthritis. For example, PAPPA is directly associated with the turnover of insulin-like growth factor 1 (IGF-1) proteins, and IGF-1 is an important factor in the repair of damaged chondrocytes.
We have constructed the first Hi-C map of primary human chondrocytes and have made it available as a resource for the scientific community. By integrating 3D genomics with large-scale genetic association and epigenetic data, we identify novel candidate effector genes for osteoarthritis, which enhance our understanding of disease and can serve as putative high-value novel drug targets.
LAMP3 induces ectopic TLR7 expression in salivary gland epithelial cells and amplifies type I IFN production in Sjögren's disease.
Arthritis RheumatolLysosome-associated membrane protein 3 (LAMP3) misexpression in salivary gland epithelial cells plays a causal role in the development of salivary gland dysfunction and autoimmunity associated with Sjögren's disease (SjD). This study aimed to clarify how epithelial LAMP3 misexpression is induced in SjD.
To explore upstream signaling pathways associated with LAMP3 expression, we conducted multiple RNA sequencing analyses of minor salivary glands from patients with SjD, submandibular glands from a mouse model of SjD, and salivary gland epithelial cell lines. A hypothesis generated by the RNA sequencing analyses was further tested by in vitro and in vivo assays with gene manipulation.
Transcriptome analysis suggested LAMP3 expression was associated with enhanced type I interferon (IFN) and IFNγ signaling pathways in patients with SjD. In vitro studies showed that type I IFN but not IFNγ stimulation could induce LAMP3 expression in salivary gland epithelial cells. Moreover, we discovered that LAMP3 overexpression could induce ectopic toll-like receptor 7 (TLR7) expression and type I IFN production in salivary gland epithelial cells both in vitro and in vivo. TLR7 knock-out mice did not develop any SjD-related symptoms following LAMP3 induction.
Epithelial LAMP3 misexpression can be induced through enhanced type I IFN response in salivary glands. In addition, LAMP3 can promote type I IFN production via ectopic TLR7 expression in salivary gland epithelial cells. This positive feed-back loop can contribute to maintaining LAMP3 misexpression and amplifying type I IFN production in salivary glands, which plays an essential role in the pathophysiology of SjD.
The clinical benefits of sodium-glucose cotransporter type 2 inhibitors in people with gout.
Nature Reviews RheumatologyGout is the most common form of inflammatory arthritis worldwide and is characterized by painful recurrent flares of inflammatory arthritis that ar...
TYK2: an emerging therapeutic target in rheumatic disease.
Nature Reviews RheumatologyTyrosine kinase 2 (TYK2) is a member of the JAK kinase family of intracellular signalling molecules. By participating in signalling pathways downst...
Cost-Effectiveness of Community-Based Diet and Exercise for Patients with Knee Osteoarthritis and Obesity or Overweight.
Arthritis Care ResObesity exacerbates pain and functional limitation in persons with knee osteoarthritis (OA). In the Weight Loss and Exercise for Communities with Arthritis in North Carolina (WE-CAN) study, a community-based diet and exercise (D+E) intervention led to an additional 6kg weight loss and 20% greater pain relief in persons with knee OA and BMI>27 kg/m2 relative to a group-based health education (HE) intervention. We sought to determine the incremental cost-effectiveness of the Usual Care (UC), UC+HE, and UC+(D+E) programs, comparing each strategy to the 'next-best' strategy, ranked by increasing lifetime cost.
We used the Osteoarthritis Policy Model to project long-term clinical and economic benefits of the WE-CAN interventions. We considered three strategies: UC, UC+HE, and UC+(D+E). We derived cohort characteristics, weight, and pain reduction from the WE-CAN trial. Our outcomes included quality-adjusted life years (QALYs), cost, and incremental cost-effectiveness ratios (ICERs).
In a cohort with mean age 65 years, BMI 37 kg/m2 , and WOMAC pain 38 (scale 0-100, 100 worst), UC leads to 9.36 QALYs/person, compared to 9.44 QALYs for UC+HE and 9.49 QALYS for UC+(D+E). The corresponding lifetime costs are $147,102, $148,139, and $151,478. From the societal perspective, UC+HE leads to an ICER of $12,700/QALY; adding D+E to UC leads to an ICER of $61,700/QALY.
The community-based D+E program for persons with knee OA and BMI>27kg/m2 could be cost-effective for willingness to pay thresholds greater than $62,000/QALY. These findings suggest that incorporation of community-based D+E programs into OA care may be beneficial for public health.
Evaluation of osteoarthritis disease burden in China during 1990-2019 and forecasting its trend over the future 25 years.
Arthritis Care ResThis study aimed to estimate the temporal trend of osteoarthritis (OA) burden in China by age, sex, and joint sites from 1990 to 2019 and predict the long-term trend over the next 25 years.
Using data from the Global Burden of Disease (GBD) Study 2019, we estimated incident cases, prevalent cases, disability-adjusted life years (DALYs) of OA, and the DALYs of OA attributed to high body mass index (BMI), as well as corresponding age-standardized rates (ASRs) for aforementioned indicies. Estimated annual percentage change (EAPC) and Nordpred age-period-cohort model were used to describe temporal trend changes and predict future disease burden.
From 1990 to 2019, the ASR of OA incidence increased from 472.53/100,000 to 509.84/100,000 (EAPC: 0.36, 95% confidence interval [95% CI] 0.29-0.44); the ASR of OA prevalence increased from 5880.58/100,000 to 6330.06/100,000 (EAPC: 0.35, 95% CI: 0.28-0.42); the ASR of OA DALYs increased from 206.38/100,000 to 224.78/100,000 (EAPC: 0.40, 95% CI: 0.32-0.48). The ASR of OA DALYs attributed to high BMI increased rapidly, especially in males and hip OA patients. Projections suggest an increasing trend in the incidence, prevalence, and DALYs of OA from 2019 to 2044, with the prevalent cases and DALYs of OA in China expected to increase by approximately 1.5 times over the next 25 years.
The disease burden of OA has increased in China over the past 30 years and is expected to continue rising over the next 25 years. This article is protected by copyright. All rights reserved.