Disease Activity Research Articles

The phageome of patients with ulcerative colitis treated with donor fecal microbiota reveals markers associated with disease remission

Bacteriophages are influential within the human gut microbiota, yet they remain understudied relative to bacteria. This is a limitation of studies on fecal microbiota transplantation (FMT) where bacteriophages likely influence outcome. Here, using metagenomics, we profile phage populations - the phageome - in individuals recruited into two double-blind randomized trials of FMT in ulcerative colitis. We leverage the trial designs to observe that phage populations behave similarly to bacterial populations, showing temporal stability in health, dysbiosis in active disease, modulation by antibiotic treatment and by FMT. We identify a donor bacteriophage putatively associated with disease remission, which on genomic analysis was found integrated in a bacterium classified to Oscillospiraceae, previously isolated from a centenarian and predicted to produce vitamin B complex except B12. Our study provides an in-depth assessment of phage populations during different states and suggests that bacteriophage tracking has utility in identifying determinants of disease activity and resolution.

Revisiting Biomarkers of Cardiac Allograft Vasculopathy: Addressing the Achilles Heel of Heart Transplantation.

Nearly half of heart transplant recipients will be diagnosed with cardiac allograft vasculopathy (CAV) within five years after transplantation. Advanced CAV can lead to worsening heart failure as well as arrhythmias and sudden cardiac death. The only curative therapy for end-stage CAV is re-transplantation. Current diagnostic methods are invasive and limited by poor sensitivity in early disease. Despite its high prevalence in the post-transplantpopulation, the underlying pathophysiology of this condition has yet to be fully described. It is thought to be primarily related to endothelial dysfunction, immune activation, and cardiometabolic disease. Biomarkers reflecting these underlying processes, particularly endothelial injury and immune activation, have shown early promise in discriminating prevalent CAV. Next-generation sequencing technologies such as proteomic and transcriptomic profiling have also provided further insight into the pathophysiology of CAV through the identification of novel biomarkers. Ultimately, these biomarkers may have a role in not only diagnosing CAV but also highlighting potential targets for disease-specific therapies. In this article, we review the current data for biomarkers in CAV and discuss future directions for biomarker identification..

Myocardial Disarray and Fibrosis across Hypertrophic Cardiomyopathy Stages Associate with ECG Markers of Arrhythmic Risk.

Myocardial disarray, an early feature of hypertrophic cardiomyopathy (HCM) and a substrate for ventricular arrhythmia, is poorly characterised in prehypertrophic sarcomeric variant carriers (SARC+LVH-). Using diffusion tensor cardiac magnetic resonance (DT-CMR) we assessed myocardial disarray and fibrosis in both SARC+LVH- and HCM patients and evaluated the relationship between microstructural alterations and electrocardiographic (ECG) parameters associated with arrhythmic risk. Sixty-two individuals (24 SARC+LVH-, 24 HCM and 14 matched controls) were evaluated with multiparametric CMR including stimulated echo acquisition mode (STEAM) DT-CMR, and blinded quantitative 12-lead ECG analysis. Mean diastolic fractional anisotropy (FA) was reduced in HCM compared to SARC+LVH- and controls (0.49±0.05 vs 0.52±0.04 vs 0.53±0.04, p=0.009), even after adjustment for differences in extracellular volume (ECV) (p=0.038). Both HCM and SARC+LVH- had segments with significantly reduced FA relative to controls (54% vs 25% vs 0%, p=0.002). Multiple repolarization parameters were prolonged in HCM and SARC+LVH-, with corrected JT interval (JTc) being most significant (354±42ms vs 356±26ms vs 314±26ms, p=0.002). Among SARC+LVH-, JTc duration correlated negatively with mean FA (r=-0.6, p=0.002). In HCM, the JTc interval showed a stronger association with ECV (r=0.6 p=0.019) than FA (r=-0.1 p=0.72). JTc discriminated SARC+LVH- from controls (Area-under-the-receiver-operator-curve 0.88, CI 0.76-1.00, p<0.001), and in HCM correlated with the ESC HCM sudden cardiac death risk score (r=0.5, p=0.014). Low diastolic FA, suggestive of myocardial disarray, is present in both SARC+LVH- and HCM. Low FA and raised ECV were associated with repolarization prolongation. Myocardial disarray assessment using DT-CMR and repolarization parameters such as the JTc interval demonstrate significant potential as markers of disease activity in HCM.

Evaluation of the immunomodulatory activity of probiotics mixture and sulfasalazine against acetic acid-induced colitis in a murine model.

Currently, the use of probiotics to treat inflammatory bowel diseases (IBD) is widely accepted because of their gut microbiota modulation capabilities and anti-inflammatory potential. The aim of this study is to examine the immunomodulatory outcomes of probiotics and sulfasalazine in the acetic acid-induced colitis murine model. The animals were randomly assigned to one of the seven groups. Following the induction of colitis, Lactobacillus acidophilus LA-5, Bifidobacterium animalis subsp. lactis BB-12, and sulfasalazine (SASP) were orally administered for 10 days. Subsequently, the in vitro anti-inflammatory effect on TNF-α and IL-10 in the supernatants of cultured spleen cells was assessed via ELISAs. Relative mRNA expression of ZO-1, MLCK, iNOS, TNFR2, ROR-γt, GATA-3, T-bet, and Foxp3 was determined using quantitative reverse‑transcription polymerase chain reaction (qRT‑PCR). The SASP plus probiotic mixture was more effective in alleviating colitis symptoms, and reducing disease activity scores, and mucosal inflammation. qRT-PCR analysis revealed a significant reduction in T-bet and RORγt levels, while Foxp3 and GATA-3 levels increased in the colons of colitis mice. In addition, the selected strains substantially inhibited the release of inflammatory markers. Administration of LA-5 + BB-12 + SASP resulted in considerably higher inhibition of NO production and cell proliferation than in the other groups (p < 0.001). Treatment with LA-5 + BB-12 + SASP also reduced TNF-α-mediated apoptosis in intestinal epithelial cells (IECs). Survey results highlight that the combination regimen could be a promising strategy for IBD therapy, warranting further study of its clinical application and long-term benefits.

Metabolic Syndrome, Adipokines, and Response to Advanced Therapies in Rheumatoid Arthritis.

We determined if metabolic syndrome, its components, and adipokines (adiponectin, leptin, Fibroblast Growth Factor-21) were associated with response to advanced therapies among patients with rheumatoid arthritis (RA). This study included participants with RA initiating either TNFi or non-TNFi biologic therapies from the Comparative Effectiveness Registry to studyTherapies forArthritis andInflammatory Conditions(CERTAIN) cohort within the CorEvitas registry. Metabolic syndrome was defined according to the National Cholesterol Education Program Adult Treatment Panel III definition. Adipokines were assessed on stored samples from a sub-sample of responders and non-responders (N=200). The primary outcome was the achievement of a change as large as the minimal clinically important difference (MCID) for the Clinical Disease Activity Index (CDAI) at 6 months. Among 2,368 participants, 687 (29%) had metabolic syndrome. Metabolic syndrome was associated with lower odds of achieving CDAI MCID [OR (95% CI): 0.69 (0.56,0.86) p=0.001] with a dose-dependent decrease in response rate according to the number of components present. Model fit was superior for metabolic syndrome compared to BMI. Associations between metabolic syndrome and MCID achievement were similar between patients receiving TNFi [OR (95% CI): 0.65 (0.49,0.87) p=0.003] v. non-TNF therapies [OR (95% CI): 0.76 (0.55,1.04) p=0.08)] (p-for-interaction=0.49). Adipokines were not associated with MCID achievement. Metabolic syndrome is associated with lower response rates with the initiation of an advanced therapy in RA, with similar effects for both TNFi and non-TNFi agents. Adipokines were strongly associated with metabolic syndrome but were not associated with clinical response.

Correlations among quality of life, spinal mobility, and disease activity in early-treated axial spondyloarthritis: a single-center cross-sectional study

BackgroundAxial spondyloarthritis (axSpA) significantly impacts patients’ lives. The ASAS-OMERACT guideline was formulated for the multidimensional evaluation of axSpA patients, employing a specific set of tools. Given the pivotal role of patient perception, comprehensive correlation among these tools, especially concerning quality of life, may provide a clinically relevant perspective and enhance treatment efficacy in the early stages of the disease. This study aims to investigate the correlation among disease activity, functional ability, and quality of life in early-treated axSpA patients. In addition, the association between high disease activity and clinical characteristics was explored.MethodsThis cross-sectional study was conducted in a tertiary hospital in Thailand. Patients diagnosed with axSpA according to ASAS classification criteria and receiving treatment from rheumatologists within three years of onset of symptoms were included. Clinical and laboratory data were retrieved from a hospital database. Disease activity was assessed using the Ankylosing Spondylitis Disease Activity Score with ESR or CRP (ASDAS-ESR/CRP) and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). Spinal mobility was measured using the Bath Ankylosing Spondylitis Metrology Index (BASMI), while quality of life and function were evaluated using the ASAS Health Index (ASAS-HI) and Bath Ankylosing Spondylitis Functional Index (BASFI), respectively. The correlation between these measurements was analyzed using the Pearson correlation coefficient (r). Additionally, factors associated with high disease activity (ASDAS/CRP > 2.1) were explored using multivariate regression analysis.ResultsSixty-six patients (41 males; mean age 49.3 ± 13.3 years) were enrolled between April to December 2022. Disease activity (ASDAS-CRP) was significantly inversely correlated with spinal mobility (BASMI), function (BASFI), and quality of life (ASAS-HI). High disease activity was associated with obesity (BMI ≥ 30 kg/m^2) and a longer duration of symptoms before treatment (≥ 2 years).ConclusionIn early-treated axSpA patients, ASDAS-CRP showed significant correlations with functional ability, quality of life, and spinal mobility. High disease activity was associated with obesity and a longer pre-treatment symptom duration in our study. Early treatment may enhance patients’ function, mobility, and quality of life, with weight reduction being possibly beneficial for obese axSpA patients.Clinical trial numberNot applicable.

Circulating Baseline CXCR3+Th2 and Th17 Cell Proportions Correlate With Trabecular Bone Loss After 48 Weeks of Biological Treatment in Early Rheumatoid Arthritis.

The high prevalence of osteoporosis in rheumatoid arthritis (RA) is due to inflammation that stimulates differentiation of osteoclasts, a process involving circulating monocytes and T cell-derived factors. The aim of this study was to evaluate relations between circulating monocytes, T cell subsets, and changes in bone characteristics before and after treatment with biological disease-modifying antirheumatic drugs (bDMARDs) in RA. Thirty patients with untreated early RA who met the American College of Rheumatology/EULAR 2010 criteria were included. Data were collected before and 48 weeks after treatment with methotrexate (MTX) together with one of three bDMARDs (abatacept, tocilizumab, or certolizumab pegol). Disease activity was measured using the Clinical Disease Activity Index, swollen or tender joint counts, C-reactive protein levels, and erythrocyte sedimentation rates. Proportions of monocyte and CD4+ T cell subsets in blood samples were analyzed by flow cytometry. Bone densitometry was performed using high-resolution peripheral quantitative computed tomography (HR-pQCT). HR-pQCT revealed an overall decrease in cortical (P = 0.009) and trabecular (P = 0.034) bone mineral density, although a subset of patients showed no bone loss after 48 weeks of treatment. The overall bone loss was not associated with age, body mass index, sex, intraarticular glucocorticoid injections, or baseline disease activity. Loss of trabecular bone volume fraction correlated with high proportions of circulating CXCR3+Th2 cells (r = -0.38, P = 0.04) and CXCR3+Th17 cells (r = -0.36, P = 0.05) at baseline. Similarly, no loss of trabecular bone volume fraction correlated with high proportions of regulatory T cells (r = 0.4, P = 0.03) at baseline. However, the associations were not significant when corrected for confounders and multiple testing. MTX together with bDMARDs efficiently reduce disease activity but only prevent bone loss in a subset of patients with RA after 48 weeks of treatment. The correlations of circulating baseline T helper cell and regulatory T cell populations with trabecular bone changes suggest a potential novel role for these cells in systemic bone homeostasis during early RA.

Systemic Sclerosis dermal fibroblast exosomes trigger a Type 1 interferon response in keratinocytes through the TBK/JAK/STAT signalling axis.

Activation of Type I IFN response has been shown to correlates with disease activity in systemic sclerosis. It is currently unknown whether the tissue-specific Type I IFN activation is a consequence of the response observed in blood or rather its source. Exosomes from SSc fibroblasts were recently shown to activate macrophages in vitro. Here, we aimed to determine the source of Type I IFN signature in SSc skin biopsies and the potential role of exosomes from SSc dermal fibroblasts in the process. Skin biopsies were obtained from healthy and SSc patients' forearms and processed for dermal fibroblasts and keratinocytes. Exosomes were isolated from healthy and SSc dermal fibroblast supernatants by ultracentrifugation and added to human skin keratinocytes. Keratinocyte transcriptome was analysed by RNA-seq analysis. TANK-binding kinase (TBK) and JAK were inhibited using a small molecule inhibitor (GSK8612) and Tofacitinib, respectively. SSc skin biopsies showed highest levels of Type I IFN response in the epidermal layer. RNA-seq analysis of keratinocytes transcriptome following exposure to dermal fibroblast exosomes showed strong upregulation of IFN signature genes induced by SSc exosomes compared to Healthy control. Inhibition of TBK or JAK activity suppressed the upregulation of the IFN signature induced by SSc exosomes. IFN activation of SSc keratinocytes is dependent on their crosstalk with dermal fibroblasts and inducible by extracellular exosomes. Our data indicates that SSc fibroblasts exosomes contributes to theType I IFN activation in SSc skin through activation of pattern recognition receptors upstream of TBK.

Identification of novel proteins in inflammatory bowel disease based on the gut-brain axis: a multi-omics integrated analysis

BackgroundThe gut-brain axis has garnered increasing attention, with observational studies suggesting its involvement in the disease activity and progression of inflammatory bowel disease (IBD), but the precise mechanisms remain unclear.Materials and methodsIn this study, we aimed to investigate “novel proteins” underlying IBD in the brain using a comprehensive multi-omics analysis approach. We performed integrated analyses of proteomics and transcriptomics in the human prefrontal cortex (PFC) tissue, coupled with genome-wide association studies (GWAS) of IBD, crohn’s disease (CD), and ulcerative colitis (UC). This included performing protein-wide association studies (PWAS), transcriptome-wide association studies (TWAS), Mendelian randomization (MR), and colocalization analysis to identify brain proteins associated with IBD and its subtypes.ResultsPWAS analyses identified and confirmation 9, 9, and 6 brain proteins strongly associated with IBD, CD, and UC, respectively. Subsequent MR analyses revealed that increased abundance of GPSM1, AUH, TYK2, SULT1A1, and FDPS, along with corresponding gene expression, led to decreased risk of IBD. For CD, increased abundance of FDPS, SULT1A1, and PDLIM4, along with corresponding gene expression, also decreased CD risk. Regarding UC, only increased abundance of AUH, along with corresponding gene expression, was significantly associated with decreased UC risk. Further TWAS and colocalization analyses at the transcriptome level supported strong associations of SULT1A1 and FDPS proteins with reduced risk of IBD and CD.ConclusionThe two “novel proteins,” SULT1A1 and FDPS, are strongly associated with IBD and CD, elucidating their causal relationship in reducing the risk of IBD and CD. This provides new clues for identifying the pathogenesis and potential therapeutic targets for IBD and CD.

Routine CSF parameters as predictors of disease course in multiple sclerosis: an MSBase cohort study

BackgroundIt remains unclear whether routine cerebrospinal fluid (CSF) parameters can serve as predictors of multiple sclerosis (MS) disease course.MethodsThis large-scale cohort study included persons with MS with CSF data documented...

Some Glycoproteins Expressed on the Surface of Immune Cells and Cytokine Plasma Levels Can Be Used as Potential Biomarkers in Patients with Colorectal Cancer

Colorectal cancer (CRC) is a leading cause of mortality worldwide. Its incidence holds a major position among the most common life-threatening diseases. Hence, the early identification and precise characterization of disease activity based on proper biomarkers are of utmost importance for therapeutic strategy and patient survival. The identification of new biomarkers for colorectal cancer or disease-specific levels/combinations of biomarkers will significantly contribute to precise diagnosis and improved personalized treatment of patients. Therefore, the present study aims to identify colorectal cancer-specific immunological biomarkers. The plasma levels of several cytokines (interleukin-1β /IL-1β/, IL-2, IL-4, IL-10, IL-12, IL-15, TGFβ and IFNγ) of 20 patients with colorectal cancer and 21 healthy individuals were determined by ELISA. The expression of several types of glycoproteins on the surface of peripheral blood leukocytes isolated from CRC patients and healthy volunteers was evaluated by flow cytometry. Correlations between cytokine levels and cell surface glycoprotein expression were analyzed. The obtained results demonstrated significantly elevated levels of CD80, CD86, CD279 and CD274 expressing leukocyte populations in the cancer patient group, while the numbers of NK cells and CD8- and CD25-positive cells were decreased. Based on these data and the correlations with cytokine levels, it can be concluded that CD25, CD80, CD86, CD274 and CD279 glycoproteins combined with specific plasma levels of IL-1β, IL-2, IL-15 and TGFβ could represent potential biomarkers for colorectal cancer.

Trajectories of disease evolution upon treatment initiation in systemic lupus erythematosus: results from four clinical trials of belimumab.

Upon commencement of therapy for active disease, patients with systemic lupus erythematosus (SLE) show varying evolution regarding disease activity measures and patient-reported outcomes (PROs). Our objective was to identify disease evolution trajectories to gain a deeper understanding of SLE progression, ultimately improving future trial design. Patients with ≥2 visits and available data on SLEDAI-2K, BILAG, PGA, FACIT-F, and glucocorticoid use were included in a post-hoc analysis of four randomised controlled trials of belimumab (BLISS-52, BLISS-76, BLISS-SC, EMBRACE). Growth mixture modelling identified latent classes. Among 2868 patients analysed, baseline median disease duration was 4.5 (IQR: 1.5-9.7) years and mean (± standard deviation) SDI 0.7 (±2.0), SLEDAI-2K 10.2 (±3.6), BILAG 17.0 (±7.8), PGA 1.5 (±0.5), FACIT-F 30.6 (±11.9), and prednisone dose 11.0 (±8.9) mg/day. In the initial model, glucocorticoid use and dose yielded high standard errors, indicating a weak link with the latent process. A refined model considered only clinical measures and FACIT-F, corrected for intervention and SDI; no other covariates improved the fit. Four classes best described disease evolution: highly active, responders; highly active, non-responders; moderately active, responders; moderately active, non-responders. LLDAS and DORIS remission attainment associated with latent classes. By linking disease activity measures with PROs, we identified four distinct trajectories describing SLE evolution following the initiation of therapy. This classification could be valuable for personalising treatment and guiding biological studies aimed at distinguishing patients with varying anticipated treatment responses, as no single clinical variable alone can predict disease progression.

Genetic Profiling in Chronic Lymphocytic Leukemia: The Role of TP53 Mutations and IGHV Status in Treatment Decision-Making – A Case Report

Introduction. The TP53 gene encodes the p53 protein, crucial for DNA damage response, apoptosis, and cell cycle regulation. In chronic lymphocytic leukemia (CLL), TP53 loss due to 17p deletion or mutation leads to poor chemoimmunotherapy response and shorter survival. Patients with unmutated immunoglobulin heavy chain variable (IGHV) status exhibit a more aggressive disease course, poorer outcomes, and reduced response to standard chemoimmunotherapy. These genetic variations significantly affect disease progression, treatment choice, and response to therapy. Case Report. In November 2023, a 61-year-old man presented to our clinic with complaints of generalized weakness and rapid fatigue since October 2023. CLL was diagnosed in 2018 through pathohistological and immunohistochemical analysis of the bone marrow. The patient received no therapy until 2023 due to the absence of active disease signs. From March 28, 2023, to July 25, 2023, the patient received chemoimmunotherapy with the bendamustine and rituximab (BR) regimen. Five courses of therapy were administered; however, further treatment was discontinued due to side effects that occurred during the fifth course of bendamustine administration. A subsequent diagnostic evaluation aimed at assessing treatment efficacy, prognosis, and genetic profiling included a cytomorphological analysis, which revealed that lymphocytes comprised 80% of the cellular composition. Immunocytological analysis confirmed the presence of monoclonal atypical lymphocytes, accounting for 70% of the cell population. Next-generation sequencing identified a pathogenic TP53 mutation, and fragment analysis confirmed an unmutated IGHV status. The presence of the TP53 mutation and unmutated IGHV status categorizes the patient as being in the very high-risk group, for which the use of Bruton’s tyrosine kinase inhibitors (BTKIs) and/or B-cell lymphoma-2 (BCL-2) inhibitors is recommended. Conclusions. This case highlights the significance of comprehensive genetic profiling in CLL patients using techniques such as fluorescence in situ hybridization, polymerase chain reaction, and next-generation sequencing. Such profiling detects molecular genetic alterations, facilitating personalized and effective treatment.

Immunomodulatory effect of Dicrocoelium dendriticum ova on DSS-induced experimental colitis in C57BL/6 mouse

Inflammatory bowel disease (IBD) significantly diminishes an individual’s quality of life and increases the risk of colorectal cancer. Recent clinical and experimental findings suggest that infection with parasitic helminths may suppress the development of certain inflammatory conditions. The objective of this study was to evaluate the immunoregulatory effects of Dicrocoelium eggs on experimentally induced colitis in C57BL/6 mice using dextran sulfate sodium (DSS). C57BL/6 mice received 3.5% DSS orally for 7 days to induce colitis, during which they were treated intraperitoneally with Dicrocoelium eggs. The severity of colitis was assessed through parameters such as body weight, stool consistency or bleeding, disease activity index (DAI), colon lengths, macroscopic scores, histopathological findings, colon gene expression levels, and serum cytokine levels. Our results indicated that Dicrocoelium eggs administration significantly reduced the severity of colitis and disease activity. Histopathological scores improved, correlating with downregulation of IFN-γ and upregulation of IL-4 expression. This findings suggest the therapeutic potential of Dicrocoelium eggs in treating colitis. Immunotherapy involving Dicrocoelium eggs primarily induces a Th2 response and modulates IFN-γ, contributing to reduced inflammation in colitis. Thus, this approach could be a promising therapeutic strategy for alleviating inflammation in IBD.

Ocular Manifestation of Granulomatosis with Polyangiitis Presenting as Serous Retinal Detachment: A Case Report

Background: Ocular involvement is relatively common in granulomatosis with polyangiitis (GPA); however, choroidal involvement is rare. We present a case of serous retinal detachment resulting from choroidal involvement in GPA. Case presentation: A 55-year-old male presented to our clinic with bilateral eye redness and pain. Ocular examination revealed bilateral conjunctival injection, and dilation of the episcleral and scleral vessels. Slit-lamp examination revealed anterior chamber cells. Optical coherence tomography (OCT) confirmed serous retinal detachment (SRD) in the left eye. The patient had recently been diagnosed with GPA following a lung biopsy and had received immunosuppressive therapy, including systemic steroids, cyclosporine, mycophenolate mofetil, and rituximab. Five weeks after treatment, the clinical symptoms of the patient, including SRD, improved with alleviation of systemic symptoms. However, tapering systemic steroids and immunosuppressants and discontinuing rituximab led to disease reactivation. OCT demonstrated a recurrence of subretinal fluid, which had previously resolved, and slit-lamp examination showed mild bilateral engorged scleral vessels. Conclusions: Choroidal involvement can present as SRD and may indicate disease activity in patients with GPA.

Remote monitoring of rheumatoid arthritis (REMORA): study protocol for a stepped wedge cluster randomized trial and process evaluation of an integrated symptom tracking intervention

BackgroundManagement of rheumatoid arthritis (RA) relies on symptoms reported by patients during infrequent outpatient clinic visits. These reports are often incomplete and inaccurate due to poor recall, leading to suboptimal treatment decisions and outcomes. Asking people to track symptoms in-between visits and integrating the data into clinical pathways may improve this. However, knowledge on how to implement this into practice and its impact on services and outcomes remains scarce in RA. Therefore, we evaluate the comparative effectiveness and cost-effectiveness of integrated symptom tracking in people with RA over and above usual care, while generating insights on factors for successful implementation.MethodsIn this superiority stepped wedge cluster-randomized controlled trial with continuous recruitment short exposure design, 16 rheumatology outpatient departments (clusters) recruit a total of 732 people with active RA. They initially offer clinic visits according to standard of care before switching in pairs to visits with integrated symptom tracking. Clusters switch in randomized order every 3 weeks. Integrated symptom tracking consists of (1) a mobile app for patients to track their symptoms daily and other RA aspects weekly/monthly, and (2) an interactive dashboard visualizing the app data, which healthcare professionals access from their electronic health record system. Clinic visits happen according to usual practice, with tracked symptom data only reviewed during visits. Our primary outcome is a difference in marginal mean disease activity score at 12 ± 3 months between standard of care and integrated symptom tracking, after accounting for baseline values, cluster, and other covariates. Secondary outcomes include patient-reported disease activity, quality of life and quality-adjusted life-years, medication/resource use, consultation and decision-making experience, self-management, and illness perception. We also conduct interviews and observations as part of a parallel process evaluation to gather information on implementation.DiscussionOur trial will generate high-quality evidence of comparative and cost-effectiveness of integrated symptom tracking compared to standard of care in people with RA, with our process evaluation delivering knowledge on successful implementation. This optimizes the chances of integrated symptom tracking being adopted more widely if we find it is (cost-) effective.Trial registrationRegistered 4-Jun-2024 on https://www.isrctn.com/, ISRCTN51539448.Trial open science framework repositoryhttps://osf.io/sj9ha/.

Epidemiological characteristics of patients with juvenile dermatomyositis in China: a multicenter study.

Juvenile dermatomyositis (JDM) is a rare but chronic autoimmune disease with systemic nonsuppurative inflammation. Many studies have focused on the clinical characteristics and therapy of JDM. A few studies have reported the epidemiological characteristics and social burden of JDM patients abroad, but there has been no study in China. This study was based on the FUTang Updating medical REcords Database. Data was extracted from the registry information of inpatient medical records. The epidemiological characteristics and economic burden of Chinese JDM patients were analyzed. A total of 1164 JDM patients from 24 hospitals were enrolled from Jan 2016 to Dec 2021. The ratio of boys to girls was 1:1.23, and half were between 6 and 12 years old. Over half(n=629) were admitted to the hospital at least twice for intensive treatment. 20% of JDM patients suffered from lung involvement and 2.2% suffered from subcutaneous calcification. The median days of hospitalization were 10 (range 6 to 14), in addition, the median United States dollar (USD) of expense was 2370.5(1373.7,3541.9). Lung involvement was the major factor causing high inpatient burden, length of stay, and expense. Nearly, 17% of JDM patients were admitted to the hospital as emergencies, suggesting sever disease activity stage needing urgent treatment. No deaths occurred in our study. Our study documents the epidemiological characteristics and social burden of JDM patients in China, contributing to the enhanced comprehension and effective management of JDM in the country.

Improved Pain, Morning Stiffness, and Fatigue With Bimekizumab in Axial Spondyloarthritis: Results From the Phase III BE MOBILE Studies.

To assess the effect of bimekizumab on pain, morning stiffness, and fatigue in patients with nonradiographic and radiographic axial spondyloarthritis (axSpA) in the phase III BE MOBILE studies (ClinicalTrials.gov: NCT03928704 and NCT03928743). Patients were randomized to bimekizumab 160 mg or placebo every 4 weeks; and all patients received bimekizumab from week 16. Patients reported spinal pain, peripheral pain, morning stiffness, and fatigue to week 52. Total and nocturnal spinal pain were each assessed on a 0-10 numerical rating scale (NRS). Individual Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) items (0-10-point NRS) assessed peripheral arthritis pain (question [Q] 3), enthesitis pain/discomfort (Q4), morning stiffness (mean of Q5 and Q6), and fatigue (Q1). Functional Assessment of Chronic Illness Therapy Fatigue subscale score (FACIT-Fatigue) is also reported. At week 16, bimekizumab-treated patients reported lower mean nocturnal spinal pain, total spinal pain, and BASDAI scores (nominal except for nocturnal spinal pain; all P ≤ 0.001), as well as higher FACIT-Fatigue scores (nominal P < 0.05) vs placebo, indicating improved symptom levels. Improvements continued to week 52 in continuous bimekizumab-treated patients and in placebo-bimekizumab switchers. A higher proportion of bimekizumab- vs placebo-randomized patients achieved increasingly stringent thresholds for low spinal and peripheral pain at week 16; this was sustained or improved at week 52. Results were similar for morning stiffness and fatigue. At week 52, over half of patients were considered FACIT-Fatigue responders (≥ 8-point increase in score). Bimekizumab treatment led to rapid improvements in levels of pain and morning stiffness. Substantial improvements were seen in all domains across the full disease spectrum of axSpA and continued to week 52.

Normocalcemic primary hyperparathyroidism is not associated with cardiometabolic alterations.

Cardiometabolic disorders are non-classical complications of hypercalcemic primary hyperparathyroidism (HC-PHPT), but whether this risk connotes normocalcemic PHPT (NC-PHPT) remains to be elucidated. We investigated cardiometabolic alterations in both forms of PHPT, looking for their association with indices of disease activity. Patients with HC-PHPT (n = 17), NC-PHPT (n = 17), and controls (n = 34) matched for age, sex, and BMI were assessed for glucose, lipid, blood pressure alterations, and history of cardiovascular events to perform a case-control study at an ambulatory referral center for Bone Metabolism Diseases. NC-PHPT, in comparison to controls, showed similar glucose (mean ± SD, 88 ± 11 vs 95 ± 22 mg/dl), total cholesterol (199 ± 25 vs 207 ± 36 mg/dl), and systolic blood pressure levels (SBP, 132 ± 23 vs 132 ± 19 mmHg), together with a comparable frequency of glucose alterations (6% vs 9%), lipid disorders (41% vs 50%) and hypertension (53% vs 59%, p = NS for all comparisons). Conversely, all these abnormalities were more prevalent in HC-PHPT vs controls (p < 0.05). When compared to NC-PHPT, HC-PHPT showed higher glucose (113 ± 31 mg/dl), total cholesterol (238 ± 43 mg/dl), and SBP levels (147 ± 15 mmHg) as well as an increased frequency of glucose (41%) and lipid alterations (77%) and a higher number of cardiovascular events (18% vs 0%, p < 0.05 for all comparisons). Among indices of PHPT activity, calcium levels displayed a significant correlation with glucose (R = 0.46) and SBP values (R = 0.60, p < 0.05). NC-PHPT is not associated with cardiovascular alterations. The predominant pathogenetic role of hypercalcemia in the development of cardiometabolic disorders could account for the absence of such alterations in NC-PHPT.

ACHIEVING BETTER QUALITY OF LIFE THROUGH THE PROVISION OF SUPPLEMENTS, MEDICAL AIDS, AND COUNSELLING OF SLE PEDIATRIC PATIENTS AT RSSA MALANG

Introduction: Systemic lupus erythematosus (SLE) in children can interfere with their growth and social functioning and the treatment process is often hampered by low compliance and the unmet secondary needs of the patient. The aim of this community service activity is to improve the quality of life of patients by fulfilling their secondary needs and providing free consultation and education. Methods: This community service was carried out by educating and provide free consultation for 38 SLE pediatric patients accompanied by their parents directly at RSSA, monthly for 6 months, and we emphasise topics on management and healthy lifestyle for SLE patients. We also make this opportunity as a means of monitoring patient's condition which includes disease activity through SLEDAI Score, clinical symptoms, and psychosocial support, and we complete it by providing vitamin D supplements, sunblock, and wheelchairs. Results: All the subjects in this community service were 100% girls and 50% of them had active SLE status with various clinical manifestations. 79% of patients never took vitamin D supplements and all patients did not use sunblock. There were 3 patients with neurological disorders who needed a wheelchair. We provide their secondary needs to maximize the standard therapy we have been doing. After 6 months, there was a decrease in the number of patients who missed monthly controls, and a decrease in patients SLEDAI Score indicating that their lupus activity was appropriately controlled. Conclusion: Although rarely considered, the fulfillment of secondary needs in SLE patients such as vitamin D, sunblock, and wheelchairs for patients with mobility problems is very meaningful to them, which can optimize the main therapy given and make patients routinely attend monthly controls, because they find it helpful in terms of mobility. In addition, they do not need to buy vitamin D and sunblock themselves.