Artificial Intelligence-Based Disease Activity Monitoring to Personalized Neovascular Age-Related Macular Degeneration Treatment: A Feasibility Study.

Purpose: To evaluate the performance of a disease activity (DA) model developed to detect DA in participants with neovascular age-related macular degeneration (nAMD). Design: Post hoc analysis. Participants: Patient dataset from the phase III HAWK and HARRIER (H&H) studies. Methods: An artificial intelligence (AI)-based DA model was developed to generate a DA score based on measurements of OCT images and other parameters collected from H&H study participants. Disease activity assessments were classified into 3 categories based on the extent of agreement between the DA model's scores and the H&H investigators' decisions: agreement ("easy"), disagreement ("noisy"), and close to the decision boundary ("difficult"). Then, a panel of 10 international retina specialists ("panelists") reviewed a sample of DA assessments of these 3 categories that contributed to the training of the final DA model. A panelists' majority vote on the reviewed cases was used to evaluate the accuracy, sensitivity, and specificity of the DA model. Main Outcome Measures: The DA model's performance in detecting DA compared with the DA assessments made by the investigators and panelists' majority vote. Results: A total of 4472 OCT DA assessments were used to develop the model; of these, panelists reviewed 425, categorized as "easy" (17.2%), "noisy" (20.5%), and "difficult" (62.4%). False-positive and false negative rates of the DA model's assessments decreased after changing the assessment in some cases reviewed by the panelists and retraining the DA model. Overall, the DA model achieved 80% accuracy. For "easy" cases, the DA model reached 96% accuracy and performed as well as the investigators (96% accuracy) and panelists (90% accuracy). For "noisy" cases, the DA model performed similarly to panelists and outperformed the investigators (84%, 86%, and 16% accuracies, respectively). The DA model also outperformed the investigators for "difficult" cases (74% and 53% accuracies, respectively) but underperformed the panelists (86% accuracy) owing to lower specificity. Subretinal and intraretinal fluids were the main clinical parameters driving the DA assessments made by the panelists. Conclusions: These results demonstrate the potential of using an AI-based DA model to optimize treatment decisions in the clinical setting and in detecting and monitoring DA in patients with nAMD. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Elevated toll-like receptor 9 is associated with disease severity and kidney involvement in systemic lupus erythematosus.

OBJECTIVES: Systemic lupus erythematosus (SLE) is associated with the activation of both innate and adaptive immune system. Infection is a significant environmental factor that is responsible for the development of SLE. Toll-like receptors (TLRs) are responsible for recognizing pathogens, and the expression of TLRs has been found to differ in SLE patients. Additionally, various infections have been reported to influence TLR expression. This study aimed to explore the relationship between TLRs and the onset, severity, and symptoms of SLE in the eastern Indian population. METHODS: The study included 70 SLE patients and a control group matched for age and sex. RT-PCR was used to evaluate mRNA expression of TLRs 2, 4, 7, and 9. Statistical analyses were performed using GraphPad Prism software v.10.2.3. RESULTS: Patients with SLE expressed significantly higher levels of TLR2 (p < 0.0001) and TLR9 (p = 0.012) than healthy controls. In lupus nephritis, TLR9 expression was higher than in SLE patients without kidney involvement (p = 0.037). Furthermore, a significant relationship was found between TLR9 expression and systemic lupus erythematosus disease activity index (SLEDAI) scores (p < 0.0001, Spearman's r = 0.47), implying the potential role of TLRs in SLE development. However, mRNA expression of TLR4 and TLR7 was not associated with SLE, clinical indices, or disease severity. CONCLUSIONS: TLR9 is associated with SLE pathogenesis and clinical severity, making it a promising molecule for targeted therapy in SLE management.

Proteomic profile of extracellular vesicles from plasma and CSF of multiple sclerosis patients reveals disease activity-associated EAAT2.

BACKGROUND AND OBJECTIVES: There is an urgent need to discover blood-based biomarkers of multiple sclerosis (MS) to better define the underlying biology of relapses and monitor disease progression. The main goal of this study is to search for candidate biomarkers of MS relapses associated with circulating extracellular vesicles (EVs), an emerging tool for biomarker discovery. METHODS: EVs, purified from unpaired plasma and CSF samples of RRMS patients by size-exclusion chromatography (SEC), underwent proteomic analysis to discover novel biomarkers associated with MS relapses. The candidate biomarkers of disease activity were detected by comparison approach between plasma- and CSF-EV proteomes associated with relapses. Among them, a selected potential biomarker was evaluated in a cohort of MS patients, using a novel and highly reproducible flow cytometry-based approach in order to detect low abundant EV subsets in a complex body fluid such as plasma. RESULTS: The proteomic profiles of both SEC-purified plasma EVs (from 6 patients in relapse and 5 patients in remission) and SEC-purified CSF EVs (from 4 patients in relapse and 3 patients in remission) revealed a set of proteins associated with MS relapses significant enriched in the synaptic transmission pathway. Among common proteins, excitatory amino-acid transporter 2, EAAT2, responsible for the majority of the glutamate uptake in CNS, was worthy of further investigation. By screening plasma samples from 110 MS patients, we found a significant association of plasma EV-carried EAAT2 protein (EV-EAAT2) with MS relapses, regardless of disease-modifying therapies. This finding was confirmed by investigating the presence of EV-EAAT2 in plasma samples collected longitudinally from 10 RRMS patients, during relapse and remission. Moreover, plasma EV-EAAT2 levels correlated positively with Expanded Disability Status Scale (EDSS) score in remitting MS patients but showed a negative correlation with age in patients with secondary progressive (SPMS). CONCLUSION: Our results emphaticize the usefulness of plasma EVs as a source of accessible biomarkers to remotely analyse the CNS status. Plasma EV-EAAT2 showed to be a promising biomarker for MS relapses. Further studies are required to assess the clinical relevance of this biomarker also for disability progression independent of relapse activity and transition from RRMS towards SPMS.

Neuropathic Pain Component in Patients with Ankylosing Spondylitis and the Relationship of Neuropathic Pain and Disease Activity Parameters: A Cross-Sectional Study.

OBJECTIVE: It is known that neuropathic pain frequently accompanies rheumatological diseases. In this study, neuropathic pain in Ankylosing Spondylitis(AS) and its relationship with disease activity were investigated. METHODS: Forty patients with AS were included. Laboratory data and disease status parameters were recorded. Neuropathic pain questionnaires were administered. Electrophysiological examination was performed on all patients. The relationship between neuropathic pain and disease activity parameters was investigated. RESULTS: According to the Pain Detect and LANSS questionnaire results, the rate of neuropathic pain was 57.5% and 42.5%. ASQoL, BASDAI, and ASDAS-ESH parameters are statistically significantly higher in the group with neuropathic pain according to the PainDetect (p:0.018, p:0.04, p:0.028). MASES, ASQoL, BASDAI, BASFI, and ASDAS-ESH parameters are statistically significantly higher in the group with neuropathic pain according to the LANSS (p:0.004, p:0.005, p: 0.001, p:0.005, p:0.02). Disease activity is higher in patients with neuropathic pain for both scales. Peripheral neuropathy is detected in nine patients. There is a positive correlation between disease activity parameters and neuropathic pain scales. A strong positive correlation was detected between ASQoL and BASDAI parameters and the Pain Detect questionnaire (r:0.533, r:0.606). CONCLUSIONS: The majority of patients with AS have a neuropathic pain. This condition is associated with high disease activity and adversely affects the patient's quality of life.

Assessment of perianal fistulizing Crohn's disease activity with endoanal ultrasound: A retrospective cohort study.

BACKGROUND: Perianal fistulas pose dual challenges to Crohn's disease (CD) patients. Low patient compliance due to the complexity of existing examination methods plagues the treatment and follow-up management of perianal CD. AIM: To determine the accuracy of endoanal ultrasound (EUS) and shear wave elastography (SWE) for evaluating perianal fistulizing CD (PFCD) activity. METHODS: This was a retrospective cohort study. A total of 67 patients from August 2022 to December 2023 diagnosed with CD were divided into three groups: Non-anal fistula group (n = 23), low-activity perianal fistulas [n = 19, perianal disease activity index (PDAI) ≤ 4], high-activity perianal fistulas (n = 25, PDAI > 4) based on the PDAI. All patients underwent assessments including EUS + SWE, pelvic magnetic resonance [pelvic magnetic resonance imaging (MRI)], C-reactive protein, fecal calprotectin, CD activity index, PDAI. RESULTS: The percentage of fistulas indicated by pelvic MRI and EUS was consistent at 82%, and there was good consistency in the classification of perianal fistulas (Kappa = 0.752, P < 0.001). Significant differences were observed in the blood flow Limberg score (χ 2 = 8.903, P < 0.05) and shear wave velocity (t = 2.467, P < 0.05) between group 2 and 3. Shear wave velocity showed a strong negative correlation with magnetic resonance novel index for fistula imaging in CD (Magnifi-CD) score (r = -0.676, P < 0.001), a weak negative correlation with the PDAI score (r = -0.386, P < 0.05), and a weak correlation between the Limberg score and the PDAI score (r = 0.368, P < 0.05). CONCLUSION: EUS combined with SWE offers a superior method for detecting and quantitating the activity of perianal fistulas in CD patients. It may be the ideal tool to assess PFCD activity objectively for management strategies.

Relapse-Independent disease activity in neuromyelitis optica spectrum disorder: A systematic review.

INTRODUCTION: Neuromyelitis Optica Spectrum Disorders (NMOSD) is a neuroinflammatory condition characterized by optic neuritis and transverse myelitis. While the current approach to NMOSD focuses on relapse-associated worsening (RAW), recent evidence indicates Relapse-Independent Disease Activity (RIDA) in patients. METHOD: Databases including Embase, PubMed, Scopus, and Web of Sciences were systematically searched up to December 2023. No restrictions were applied. Inclusion criteria focused on studies reporting evidence of RIDA in NMOSD patients. Data extraction involved details such as study title, author, participant characteristics, treatment, evaluation methods, positive findings according to RIDA, and prevalence of findings in NMOSD patients. This study is conducted following the PRISMA guidelines with a registered protocol on PROSPERO (ID = CRD42023492352). RESULT: Of 802 studies, 38 were included in the systematic review, covering 1881 NMOSD patients. AQP4-IGg status was positive in 90.6 % of the patients. Ocular findings indicative of RIDA were reported in 23 studies, including thinning of GCIPL, RNFL, GCC, and GCL layers, foveal and macular shape and volume abnormalities, vessel loss, and visual evoked potentials (VEPs) abnormalities. MRI findings supporting the RIDA were reported in 13 studies, including new lesion incidence and brain and spinal cord atrophy. Serum and CSF RIDA-supporting findings were reported in five studies, including elevation in sGFAP and sNFL. Biopsies and autopsies suggested inflammatory processes in relapse-free patients in 2 studies. The predominant manifestation of RIDA in NMOSD was identified in the visual system, suggesting the impaired retinal glial cells like Müller cells during the relapse-free period in NMOSD. INTERPRETATION: Our systematic review provides valuable insights into RIDA in NMOSD. Establishing guidelines for the diagnosis and treatment of RIDA is crucial. Further studies are needed to provide robust evidence on RIDA in NMOSD patients.

Exploring the therapeutic potential of autologous hematopoietic stem cell transplantation in progressive multiple sclerosis-a systematic review.

BACKGROUND AND PURPOSE: The aim was to determine the value of autologous haematopoietic stem cell transplantation (aHSCT) as a therapeutic intervention for progressive multiple sclerosis (PMS) based on a systematic review of the current literature. METHODS: All studies from the databases PubMed and Google Scholar published in English before February 2024 which provided individual data for PMS patients were systematically reviewed. PICO was defined as population (P), primary progressive MS and secondary progressive MS patients; intervention (I), treatment with aHSCT; comparison (C), none, disease-modifying therapy treated/relapsing-remitting MS cohorts if available; outcome (O), transplant-related mortality, progression-free survival (PFS) and no evidence of disease activity. RESULTS: A total of 15 studies met the criteria including 665 patients with PMS (74 primary progressive MS, 591 secondary progressive MS) and 801 patients with relapsing-remitting MS as controls. PFS data were available for 647 patients. PMS patients showed more severe disability at baseline than relapsing-remitting MS patients. The average transplant-related mortality for PMS in 10 studies was 1.9%, with 10 deaths in 528 patients. PFS ranged from 0% to 78% in PMS groups 5 years after treatment initiation, demonstrating a high variability. No evidence of disease activity scores at 5 years ranged from 0% to 75%. CONCLUSION: Based on the available data, aHSCT does not halt progression in people with PMS. However, there appears to be evidence of improved outcome in selected patients. Due to the heterogeneity of the available data, more comprehensive clinical trials assessing the efficacy of aHSCT across different patient groups are urgently needed to reduce variability and improve patient stratification.

The epigenetic determinants for systemic juvenile idiopathic arthritis phenotyping and treatment response.

BACKGROUND: Determining the role of epigenetics in systemic juvenile idiopathic arthritis (SJIA) provides an opportunity to explore previously unrecognized disease pathways and new therapeutic targets. AIM: We aimed to identify the clinical significance of microRNAs (miRNA-26a, miRNA-223) in SJIA. MATERIALS AND METHODS: This cross-sectional study was conducted on a group of children with SJIA attending to pediatric rheumatology clinic, at Mansoura University Children's Hospital (MUCH) from December 2021 to November 2022. Patient demographics, and clinical, and laboratory data were collected with the measurement of microRNAs by quantitative real-time PCR. The Mann-Whitney, Kruskal-Wallis, and Spearman correlation tests were used for variable comparison and correlations, besides the receiver operating characteristic (ROC) curve for microRNAs disease activity and treatment non-response discrimination. RESULTS: Forty patients were included in the study. On comparison of miRNA-26a, and miRNA-223 levels to the clinical, assessment measures, and laboratory features, miRNA-26a was statistically higher in cases with systemic manifestations versus those without. Similarly, it was higher in children who did not fulfill the Wallace criteria for inactive disease and the American College of Rheumatology (ACR) 70 criteria for treatment response. Meanwhile, miRNA-223 was not statistically different between cases regarding the studied parameters. The best cut-off value for systemic juvenile arthritis disease activity score-10 (sJADAS-10) and the ability of miRNA-26a, and miRNA-223 to discriminate disease activity and treatment non-response were determined by the (ROC) curve. CONCLUSION: The significant association of miRNA-26a with SJIA features points out that this molecule may be preferentially assessed in SJIA disease activity and treatment non-response discrimination.

Profiles of cytokines in patients with antineutrophil cytoplasmic antibody-associated vasculitis.

Objective: This study aimed to identify plasma biomarkers that are significantly altered in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) and are closely associated with AAV disease activity, as well as to explore their role in the pathogenesis of AAV. Methods: Cytokines were measured using Human Immune Response Panel 80-Plex in plasma from 59 patients with AAV and 20 healthy controls (HCs). The differentially expressed cytokines between the two groups and the possible signaling pathway involved in the pathogenesis of AAV were analyzed by bioinformatics. Relationship analysis was performed between these cytokines and clinical parameters to identify the biomarkers that can effectively indicate disease activity. Results: We identified 65 differentially expressed cytokines between the two groups. Among them, 43 cytokines significantly affected the risk of AAV. Bioinformatic analysis showed that the 43 cytokines were primarily enriched in signaling pathways such as cytokine-cytokine receptor interaction, viral protein interaction with cytokine and cytokine receptor, chemokine signaling pathway, and IL-17 signaling pathway. The levels of 25 cytokines were significantly positively correlated with Birmingham Vasculitis Activity Score (BVAS), and the levels of 2 cytokines were significantly negatively correlated with BVAS. Receiver operating characteristic analysis showed that 9 cytokines can distinguish between disease relapse and remission (PTX3: area under curve (AUC)=0.932, IL34: AUC=0.856, IL2RA: AUC=0.833, CCL23: AUC=0.826, VEGFA: AUC=0.811, TNFSF13: AUC=0.795, Granzyme A: AUC=0.788, CSF3: AUC=0.773 and IL1A: AUC=0.765). The elevated levels of these 9 cytokines suggested a risk of disease relapse. The AUC of CCL11 in disease relapse and remission was 0.811 (p=0.0116). Unlike the other 9 cytokines, a negatively association existed between CCL11 level and the risk of disease relapse. Conclusion: A group of cytokines that may be involved in AAV pathogenesis was identified. Increased PTX3, IL34, IL2RA, CCL23, and VEGFA levels correlate with active disease in AAV and may be used as biomarkers to identify the disease relapse of AAV.

The Prevalence of Fibromyalgia in Rheumatoid Arthritis Patients Using the Fibromyalgia Assessment Screening Tool (FAST 4) Based on the Multidimensional Health Assessment Questionnaire (MDHAQ).

Introduction Fibromyalgia (FM) is characterized by widespread pain and fatigue, accompanied by symptoms such as decreased concentration, autonomic dysfunction, and abdominal pain. It can be either primary or secondary, notably to rheumatoid arthritis (RA). The Fibromyalgia Assessment Screening Tools (FAST 4), derived from the Multidimensional Health Assessment Questionnaire (MDHAQ), is a composite tool allowing for the rapid screening of FM. Our primary objective is to determine the prevalence of FM among RA patients using the FAST 4 index. Secondary objectives include comparing the FAST 4 index with the FiRST score and describing the correlation between FM and RA activity and different factors associated with FM in RA patients. Methods This was an observational cross-sectional study including patients diagnosed with RA according to the ACR/EULAR criteria. The FAST questionnaire comprises four sections assessing pain and fatigue on a visual analog scale, painful joints reported by the patient, and a list of 60 symptoms. A FAST 4 score of ≥ 3/4 indicates a positive screening for FM. Demographics and disease features were compared using descriptive statistics. Univariate and multivariate analyses using logistic regression models were performed to calculate odds ratios (ORs) with 95% CI. The sensitivity and specificity of the FAST 4 index were evaluated, and Fagan's nomograms were used to illustrate post-test probability. Statistically significant results were considered for p-values less than 0.05. Results The study enrolled 97 patients diagnosed with RA. The mean age of the patients was 56 ± 12.7 years, with a predominance of females (90.7%, N=88). The mean duration of RA was 13.5 ± 8.69 years. RA activity measured by DAS 28-ESR showed that 40.2% (N=39) had high disease activity, 38.1% (N=37) had moderate disease activity, 11.3% (N=11) had low disease activity, and 10.3% (N=10) were in remission. The prevalence of comorbid FM, according to the FAST 4 index, was 30.9% (N=30). Based on the Multidimensional Health Assessment Questionnaire (MDHAQ), depression was observed in 66.7% (N=20) patients with FM, while anxiety was reported in 60% (N=18). Moreover, 30.4% of patients screened positive for FM using the FiRST score. The FAST 4 index detected FM patients defined by FiRST with a sensitivity of 78.6% and a specificity of 87.1%. The positive predictive value (PPV) was 73.3%, and the negative predictive value (NPV) was 90%. Univariate analysis revealed that a positive FAST 4 index was associated with the number of painful and swollen joints (p<0.001 and 0.03, respectively). Additionally, patients with a positive FAST 4 index showed higher DAS 28 scores (p=0.002). No significant association was found with CRP levels (p=0.328), ESR (p=0.499), or the use of biological treatments (p=0.146) or corticosteroids (p=0.940). In multivariate analysis, only depression remained a risk factor, increasing the risk sixfold with an OR of 5.917, 95% CI (1.91-18.3), p=0.002. Conclusion Our study suggests a high prevalence of concomitant FM in our population, highlighting the importance of screening for FM, particularly using the FAST 4 index based solely on the MDHAQ questionnaire.

Exploring the association of serum prolactin with serum glucose levels and clinical findings in a cohort of patients with early rheumatoid arthritis.

BACKGROUND: In the context of rheumatoid arthritis and its systemic inflammatory implications, there is an increasing interest in investigating the role of prolactin in the clinical and metabolic aspects of the disease. This study aimed to explore the potential links between serum prolactin levels, serum glucose levels, and the clinical manifestations of arthritis. METHODS: This exploratory, cross-sectional, observational study focused on women diagnosed with rheumatoid arthritis. The research involved assessing prolactin and blood glucose concentrations, alongside specific clinical traits such as disease-related inflammation, morning stiffness, and fatigue intensity. The presence of changes in serum prolactin (PRL) was initially compared among the groups based on disease activity intensity. Using a multinomial regression analysis, the study analyzed the impact of predetermined clinical and metabolic factors on various categories of prolactin concentration. RESULTS: Out of the 72 participants included in the study, hyperprolactinemia was detected in 9.1% of the sample. No differences in serum PRL were identified among the evaluated groups based on disease activity. Following multivariate analysis, no statistically significant differences were identified for the outcomes of inflammatory activity and morning stiffness within each PRL category when compared to the reference category for PRL. There was no increased likelihood of encountering blood glucose levels below 100 mg/dl among individuals with higher prolactin concentrations compared to those in the lowest prolactin category (OR 5.43, 95% CI 0.51-58.28). The presence of clinically significant fatigue revealed a higher likelihood of encountering this outcome among patients with intermediate PRL values (prolactin categories 7.76-10.35 with OR 5.18, 95% CI 1.01-26.38 and 10.36-15.29 with OR 6.25, 95% CI 1.2-32.51) when compared to the reference category. CONCLUSIONS: The study found no discernible correlation between prolactin concentrations and worse scores for inflammatory activity of the disease, nor between prolactin concentrations and serum glucose levels. The findings regarding fatigue should be approached with caution given the exploratory nature of this study.

Activity Prediction Modeling Based on a Combination of Growth Differentiation Factor 15 and Serum Biomarker Levels in Dermatomyositis and Polymyositis.

AIMS: Growth differentiation factor 15 (GDF15) plays an important role in multiple inflammatory disorders. We aimed to analyze serum GDF15 levels in adult patients with idiopathic inflammatory myopathies (IIMs). METHODS: Serum GDF15 levels were measured in 179 adult patients with IIMs and 76 healthy controls (HCs). The association between GDF15 levels and disease variables was analyzed using Spearman's rank correlation. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the discriminatory ability of GDF15 and the GDF15-to-lymphocyte ratio (GLR). Machine learning methods were applied to build predictive models. RESULTS: GDF15 levels and GLR were significantly elevated in patients with adult IIMs than in HCs. Compared with patients in remission, both GDF15 and GLR were significantly higher in myositis patients in an active phase. GDF15 levels correlated positively with myositis disease activity indices and negatively correlated with lymphocyte and platelet counts. ROC curve analysis revealed that GDF15 levels and GLR outperformed muscle enzymes and distinguished well between patients with active disease and those in remission. Furthermore, even in the normal muscle enzyme group, GDF15 levels and GLR were also well-distinguished between patients with active disease and those in remission. Using machine learning, a logistic regression model of GDF15 combined with creatine kinase and lymphocyte count was constructed and had a reliable predictive value for disease activity. CONCLUSIONS: GDF15, particularly GLR, was significantly correlated with disease activity in adult patients with IIMs. They could serve as useful biochemical markers for evaluating disease activity, monitoring disease progression, and guiding treatment in adult patients with IIMs.

Impact of concomitant methotrexate on disease activity in patients with rheumatoid arthritis tapering abatacept: results from KOBIO registry.

Objectives: Tapering biologic agents can be considered for patients with stable disease activity in rheumatoid arthritis (RA). However, the specific strategy for abatacept is uncertain. This study aimed to examine the impact of tapering abatacept on disease activity in RA patients and assess the potential influence of concomitant methotrexate (MTX) treatment. Methods: Using data from the KOBIO registry, we included 505 1 year intervals from 176 patients with RA that initiated abatacept with concomitant MTX at baseline. The intervals were divided into two groups based on the dose quotient (DQ) of abatacept during each period (i.e., the tapering group (DQ < 1) and control group (DQ = 1)). The primary outcome was achieving DAS28-remission at 1 year intervals. Marginal structural models (MSM) were used to minimize confounding caused by an imbalance in time-varying variables. Results: Abatacept was tapered at 146 (28.9%) intervals, and the mean DQ was 0.68. DAS28-remission was achieved in 207 (41.8%) intervals. Tapering abatacept did not affect the odds of achieving DAS28-remission compared with the control group (OR 1.04 [0.67-1.62]). The odds remained unaffected in the subgroup that continued MTX (OR 1.42 [0.88-2.30]) but not in the subgroup that discontinued MTX (OR 0.26 [0.10-0.57]). The effects of interaction between tapering abatacept and concomitant MTX use on DAS28 and patient's functional status showed consistent results. The incidence of adverse events within a 1 year interval was comparable between the two groups. Conclusion: Withdrawal of MTX while tapering abatacept may compromise meeting the treatment goal for patients with RA.

Assay for interferon gamma release as a novel marker in pediatric patients with systemic lupus erythematosus.

BACKGROUND: The interferon-gamma (IFN-γ) release assay (IGRA) is an important laboratory diagnosis for latent Mycobacterium tuberculosis (TB) infection. The TB-IGRA measures the release of IFN-γ from peripheral blood cells, who are exposed to TB antigen (Ag), mitogen (MT), or negative/nil control (NL) in vitro. While, an exceptional higher TB Ag-NL level will reflect an elevation of peripheral lymphocytes released IFN-γ in a same condition. Therefore, we found that the elevated levels of TB Ag-NL could become a new biomarker for the diagnosis and treatment of pediatric systemic lupus erythematosus (SLE) patients. METHODS: We have analyzed the clinical data of 776 children who are underwent TB-IGRA testing in the Department of Allergy and Rheumatology of Guangzhou Women and Children's Medical Center from 2018 to 2020. To investigate the association between TB Ag-NL and SLE, we have analyzed the clinical data of 47 SLE patients and TB Ag-NL testing results, and then evaluated the association between TB Ag-NL and SLE disease activity. RESULTS: The TB Ag-NL levels were significantly higher in patients with active SLE than those in inactive SLE (p = 0.0002). The TB Ag-NL levels were positively correlated with the SLE disease activity index (SLEDAI) and laboratory diagnosis parameters. The mean value of TB Ag-NL in SLE patients (0.04191 ± 0.07955, IU/mL) were significantly higher than those in patients with juvenile dermatomyositis (JDM) (0.0158 ± 0.0337, IU/mL, p = 0.036), juvenile idiopathic arthritis (JIA) (0.0162 ± 0.0388, IU/mL, p = 0.001), and healthy controls (HC) (0.0001 ± 0.0027, IU/mL, p = 0.0003). Therefore, the elevated TB Ag-NL levels could serve as a potential diagnostic biomarker of SLE, especially for the active SLE. CONCLUSION: The detection of IFN-γ release levels by the TB-IGRA may be useful to assess SLE disease activity in pediatric patients with active SLE.

Complete Description of the Three Pathways of the Complement System in a Series of 430 Patients with Rheumatoid Arthritis.

The complement (C) system is implicated in the etiopathogenesis of rheumatoid arthritis (RA). However, there is a lack of studies characterizing all three C pathways in RA patients. This study aimed to evaluate the association between an in-depth examination of the C system and RA patient characteristics, focusing on disease activity and the presence of rheumatoid factor and anti-citrullinated protein autoantibodies (ACPA). In a cohort of 430 RA patients, functional assays of the three C pathways (classical, alternative, and lectin) and serum levels of their components were assessed. Components included C1q (classical); factor D and properdin (alternative); lectin (lectin); C1-inhibitor; C2, C4, and C4b (classical and lectin); C3, C3a, and C4b (common); and C5, C5a, and C9 (terminal). A multivariable linear regression analysis showed significant positive correlations between C-reactive protein and C system proteins and functional assays, especially in the terminal and common pathways. Disease activity, measured by scores with or without acute phase reactants, positively correlated with the classical pathway functional test and terminal pathway products. Conversely, rheumatoid factor or ACPA presence was associated with lower classical pathway values and decreased C3a and C4b levels, suggesting complement depletion. In conclusion, RA disease activity increases C molecules and functional complement assays, while rheumatoid factor or ACPA positivity is linked to C consumption. Our study offers a detailed analysis of the complement system's role in RA, potentially guiding the development of more targeted and effective treatment strategies.

Development and validation of the Oral Lichen Planus-Disease Activity Scale: a novel tool for comprehensive clinical assessment.

OBJECTIVE: To develop and validate the Oral Lichen Planus-Disease Activity Scale (OLP-DAS) for assessing overall disease activity of OLP. METHODS: The OLP-DAS was created by refining the Thongprasom criteria, incorporating inputs from the literature and expert review, and integrating pain assessment. Content validity was evaluated in a virtual meeting with 8 Oral Medicine specialists. Reliability and validity of the final version were examined. Seventeen OLP subjects were assessed for disease activity by 10 investigators using the OLP-DAS, Oral Disease Severity Score (ODSS), OLP-Investigator Global Assessment (OLP-IGA), and Reticular-Erythema-Ulcerative (REU) scale. Convergent validity was assessed by rating 160 OLP subjects using the OLP-DAS, ODSS, and OLP-IGA. Inter-rater and intra-rater reliability, along with convergent validity, were analyzed using intraclass correlation coefficients (ICCs) and Spearman's rank correlation coefficients (rs). RESULTS: The final OLP-DAS achieved excellent content validity indices. Inter-rater and intra-rater ICCs for total OLP-DAS scores were 0.93 and 0.96, respectively. Total OLP-DAS scores exhibited strong positive correlations with the ODSS and OLP-IGA (rs = 0.94 and rs = 0.76; P < 0.001, respectively). The OLP Severity Index (OLP-SI), a component of the OLP-DAS, showed very strong positive correlations with OLP disease activity parameters of the ODSS (rs = 0.90; P < 0.001). CONCLUSIONS: The OLP-DAS is a valid and reliable clinician-reported outcome measure (CROM) for evaluating OLP disease activity. CLINICAL RELEVANCE: The OLP-DAS, as a standardized CROM for OLP, is valuable for both routine clinical assessments and research applications.

Subjective Symptoms and Disease Activity Related to Serum Zinc Concentration in Primary Sjögren's Syndrome.

Background/Objectives: We examined the frequency of zinc deficiency in patients with Sjögren's syndrome (SS) and the relationship between zinc deficiency and each of the subjective symptoms and disease activity. Methods: We enrolled 164 patients aged ≥ 20 years with primary SS (pSS) based on the revised diagnostic criteria of the Ministry of Health, Labor and Welfare (1999) and 144 patients with RA diagnosed according to the ACR/EULAR classification criteria for RA (2010) as a comparison group. Subjective symptoms were confirmed using an original questionnaire, and disease activity was determined using the European League Against Rheumatism Sjögren's Syndrome Disease Activity Index (ESSDAI). The serum zinc concentrations were measured in both SS and RA patients. Results: The rate of zinc deficiency in the SS group was 26.1%, significantly higher than that in the RA group (7.6%). The rate of zinc deficiency was significantly higher in the pSS group compared with Japanese health checkup recipients reported in the literature. The mean serum zinc concentration in primary SS was 60.6 ± 7.3 µmol/L in the high disease activity group with an ESSDAI of ≥5 points, which was significantly lower than the concentration of 69.7 ± 10.2 µmol/L in patients with an ESSDAI of ≤4 points. Conclusions: The frequency of zinc deficiency was higher in patients with pSS than in patients with RA. Disease activity was also higher in patients with zinc deficiency, suggesting an association between zinc concentration and organ involvement in pSS.

Impact of Helicobacter pylori Eradication on Inflammatory Bowel Disease Onset and Disease Activity: To Eradicate or Not to Eradicate?

Helicobacter pylori infection has significant epidemiological relevance due to the carcinogenic nature of this bacterium, which is potentially associated with cancer. When detected, it should ideally be eradicated using a treatment that currently involves a combination of gastric acid suppressors and multiple antibiotics. However, this treatment raises questions regarding efficacy and safety profiles in patients with specific comorbidities, including inflammatory bowel diseases (IBD). Eradication therapy for H. pylori includes components associated with adverse gastrointestinal events, such as Clostridioides difficile colitis. This necessitates quantifying this risk through dedicated studies to determine whether this antimicrobial treatment could be significantly associated with IBD relapse or exacerbation of pre-existing IBD, as well as whether it could potentially lead to the de novo onset of IBD. Although the available evidence is reassuring about the safety of eradication therapy in patients with IBD, it is limited, and there are no specific recommendations for this particular situation in the leading international IBD and H. pylori guidelines. Therefore, studies need to evaluate the efficacy and safety profiles of the available antimicrobial regimens for H. pylori eradication in patients with IBD, both in clinical trial settings and in real-life studies.

Effects of Nutritional Status and Foods Consumed on Inflammation and Disease Activity in Patients with Rheumatoid Arthritis.

Background and Objectives: This study investigated the impact of nutritional status and foods consumed on inflammation and disease activity in patients with rheumatoid arthritis (RA). Materials and Methods: We designed a cross-sectional observational study, involving 110 patients diagnosed with RA. The patients included were between 18 and 75 years old, diagnosed with rheumatoid arthritis two years ago or earlier, with stable treatment for the last 8 weeks. Data on anthropometric parameters, body mass composition, nutritional status, individual food consumption records, inflammation, disease activity, quality of life, clinical, and laboratory parameters were collected for each study participant. The evaluation parameters of the patients were the simple disease activity index (SDAI), clinical disease activity index (CDAI), systemic immune-inflammation index (SII) and individual food consumption records. A bioimpedance device and measuring tape were used to take body composition and anthropometric measurements of the patients. Results: According to the body mass index, waist circumference and waist-to-height ratio, in our study, we found that 60% of the patients were obese, 80% were at a very high health risk, and approximately 91% were in need of nutritional treatment. There was a significant negative correlation between the dietary intake of total energy, total fat, omega 3, calcium, zinc, cobalamin and the disease activity (SDAI, CDAI). There was a significant negative correlation between polyunsaturated fatty acids, omega 3, carotene, vitamin E, selenium and the SII. Additionally, there was a positive correlation between omega 6 and the SII, SDAI, CDAI (p < 0.05). Conclusions: The results of this study show that the foods consumed in the nutrition of RA patients may have effects on their inflammation and disease activity.

The effects of lifestyle interventions on disease activity and quality of life in patients with systemic lupus erythematosus: A systematic review.

INTRODUCTION: Systemic Lupus Erythematosus (SLE) is an autoimmune disease affecting multiple organs, characterized by flares and remission. Treatment aims to reduce flare severity and prevent long-term damage, but remission is often elusive, and patients may still experience flares and a reduced quality of life (QoL). This had led to a growing interest in non-pharmacological therapies to improve patient wellbeing. OBJECTIVE: We aimed to assess and summarize the efficacy of lifestyle interventions in SLE patients on disease activity and QoL. METHODS: A systematic search on lifestyle interventions, SLE, disease activity, and QoL was conducted in PubMed/Medline, Embase and Clinicaltrials.gov in August 2024. Included studies were randomized controlled trials on lifestyle interventions in adult SLE patients. Each trial was appraised using Scottish Intercollegiate Guidelines Network (SIGN) criteria, with participant numbers, study duration, intervention type and outcome measures detailed in separate tables. RESULTS: A total of 3564 articles were screened, resulting in the inclusion of 25 randomized controlled trials with 1521 patients. Study quality varied from high (11 studies) to low (6 studies) with considerable intervention heterogeneity. The interventions fell into five categories: physical activity, psychotherapy, lifestyle coaching, supplements and dietary interventions. Physical activity (2 studies, 116 patients), psychotherapy (5 studies, 507 patients) and coaching (1 study with 30 patients) had no significant effect on disease activity, while fish oil supplementation showed a slight benefit in two studies with a total of 102 patients. Quality of life generally improved with physical activity (4 studies with in total 253 patients) and psychotherapy (9 studies with in total 623 patients), with significant mental health benefits, but coaching (3 studies with in total 186 patients) showed no effect. CONCLUSION: Various lifestyle interventions influence quality of life in SLE patients. Consistent with recent guidelines, both exercise and psychotherapy may positively impact the health-related quality of life in these patients. However, some studies were biased due to self-reported outcomes and the Hawthorne effect, where participants' behavior changed from receiving extra attention. Further research with larger patient cohorts is necessary to reduce the influence of heterogeneity across different studies and to better understand the potential of these promising therapies.