Real-World Experience With Janus Kinase Inhibitors in Immune-Mediated Diseases: Clinical Experience of a University Hospital.

BACKGROUND: Several Janus kinase (JAK) inhibitors have been developed in recent years. These agents are widely applicable in clinical practice as an alternative treatment for immune-mediated diseases. While the safety and efficacy profile of these drugs has been evaluated in several randomized clinical trials and studies, very few authors have assessed safety and effectiveness under the real-world conditions of daily clinical practice. OBJECTIVE: This study aims to describe the effectiveness and safety of JAK inhibitors in daily clinical practice for the treatment of immune-mediated rheumatic diseases in a university hospital. METHODS: We performed a single-center observational, descriptive, retrospective study of all patients with rheumatoid arthritis (RA), spondyloarthritis (SpA), and psoriatic arthritis (PsA) receiving active treatment with JAK inhibitors between March 2022 and February 2023. We recorded study variables from the clinical history for subsequent analysis using STATA 12.0 (StataCorp LLC, College Station, TX). A 95% confidence interval was applied. RESULTS: The final analysis was performed on 64 patients (upadacitinib: 27, baricitinib: 16, tofacitinib: 13, filgotinib: eight), with a mean age of 55.69±10.78 years (60.94% females). The distribution by disease was as follows: RA, 44 (70.31%); SpA, 11 (17.18%); and PsA, eight (12.5%). A significant improvement was observed in all groups at six to 12 months, as follows: RA, remission in 48.89% and low activity in 26.67%; SpA, remission in 9.09% and low activity in 54.54%; and PsA, low activity in 87.5%. The factors most associated with poor response to treatment were activity before initiation of treatment and previous failure of biological disease-modifying antirheumatic drugs (bDMARDs). Adverse effects and complications were detected in 26.56% (SARS-CoV-2, one case; basal cell carcinoma, one case; and herpes zoster, two cases). There were no reports of cardiovascular or thromboembolic events, opportunistic infection, or tuberculosis. CONCLUSIONS: Our real-world data show that treatment with JAK inhibitors leads to a high rate of remission/low activity that remains unchanged at six to 12 months in RA, SpA, and PsA. The predictors of a poor response to JAK inhibitors in our study population were the level of activity before initiation of treatment and previous failure of bDMARDs. No cardiovascular or thromboembolic events were reported. Of note, we did record one case of severe infection, one case of basal cell carcinoma, and two cases of herpes zoster.

Steroid pulse therapy in idiopathic nephrotic syndrome in the era of modern immunosuppressive treatment-still up to date?

BACKGROUND: Intravenous steroid pulses (SP) are successfully used for the treatment of patients with idiopathic nephrotic syndrome (INS) resistant to oral prednisone. METHODS: We performed a retrospective analysis of all patients in the three pediatric nephrology centers of the Paris region from 2002 to 2022 who were resistant to a 30-day course of oral prednisone and who received SP for their first INS flare and analyzed their disease course over 4 years. RESULTS: Forty-seven patients (17 girls), median age 3.4 years, were analyzed. Of them, 68% reached remission within 7 days of SP. No significant short-term side effects were noted. Half of the patients started immunosuppressive treatment immediately after their first remission and 62% of them relapsed at least once, whereas all the patients who did not receive immunosuppressive treatment since their first remission relapsed. Among the SP-sensitive patients, 75% needed calcineurin inhibitor (CNI) or B-cell depletion during their disease course to achieve stable remission. Forty-two percent of the whole cohort received B-cell-depleting agents. Among the 15 SP-resistant patients, all received CNI. Twelve/fifteen patients reached remission. After 4 years, 68% among the SP-sensitive patients and 87% of SP-resistant patients still had an active disease. CONCLUSIONS: SP are helpful to obtain rapid remission in pediatric INS patients resistant to oral steroids. However, as most SP-sensitive patients need immunosuppressive drugs, mainly CNI and B-cell-depleting agents it could be interesting to discuss the possibility to start CNI directly after the 30-day course of prednisone instead of SP.

Role of the C-reactive Protein-to-Albumin Ratio in Assessing Disease Activity in Elderly Patients With Rheumatoid Arthritis.

OBJECTIVE: Nowadays, one measure that is more helpful in assessing the level of inflammation than either C-reactive protein (CRP) or albumin alone is the C-reactive protein-to-albumin ratio (CAR). Our study set out to assess the CAR in elderly individuals with rheumatoid arthritis (RA) and its correlation with other parameters. METHODS: Included in the research were patients who were being followed up on for RA between January 2021 and January 2024 and categorized according to their age at the time of enrolment and assigned to one of two groups: younger patients, defined as <60 years of age, and those aged ≥60 years, who were recorded as elderly patients. The clinical evaluation of the patients and laboratory data measured for each patient included age, gender, disease duration, medications, CRP, erythrocyte sedimentation rate (ESR), albumin, neutrophil-to-lymphocyte ratio (NLR), and CAR. Disease activity was assessed with the disease activity score 28 (DAS 28)-ESR. The health assessment questionnaire was used to measure the functional status. RESULTS: Ninety-four patients (<60 years: 58 and ≥60 years: 36) were included. The mean age of the elderly patients was 65.80 ± 5.33 years. Female predominance was similar in both the RA groups (<60 years: 50 patients (86.2%) vs. ≥60 years: 31 (86.1%)). The distribution of biological and disease-modifying drugs did not significantly differ between the groups. With the exception of albumin, there was no statistically significant difference between the groups for ESR, CRP, CAR, NLR, or DAS28-ESR. Elderly patients with a DAS28-ESR of 2.6 and above had a statistically significant higher CAR than the remission group (3.44±3.73 vs. 2.71±5.73, respectively). There was no statistically significant difference in the NLR value of elderly patients with a DAS28-ESR of 2.6 and above compared to the remission group (3.06 ± 2.95 vs. 2.65 ± 1.38, respectively). In addition, CAR was positively correlated with ESR, CRP, and DAS28-ESR (r = 0.726, p < 0.001; r = 0.954, p < 0.001; r = 0.339, p = 0.043, respectively). However, there was no discernible correlation between CAR and HAQ, NLR, or disease duration. CONCLUSION: In elderly RA patients, our study demonstrated the correlation between CAR and inflammatory biomarkers and the DAS28-ESR. According to this, CAR may prove to be a useful biomarker for assessing inflammation and disease activity in clinical settings.

Pulmonary and extra-pulmonary effects of lung transplantation in an Italian cohort of patients with systemic sclerosis.

OBJECTIVES: Lung transplantation (LuTx) is a life-saving intervention for Systemic Sclerosis (SSc) patients with end-stage lung disease. The aim of this study was to evaluate patients' survival and LuTx outcomes on systemic disease manifestations. METHODS: A retrospective evaluation was conducted on SSc patients who underwent LuTx between 2010 and 2021. Outcomes assessed at baseline, 6, 12, and 24 months post-LuTx included skin involvement by modified Rodnan skin score (mRSS), global disease activity using a modified EUSTAR index (0-9 scale). Lung function rescue was evaluated by forced vital capacity (FVC). Patient survival was assessed by Kaplan-Meier analysis. RESULTS: 13 SSc patients were included, with a male/female ratio 9/4 and a median age of 48.7 years. Nine patients were affected by diffuse cutaneous scleroderma (dcSSc) and four by limited cutaneous scleroderma (lcSSc). FVC significantly increased from 56% of the predicted value at baseline to 78% at 2 years (p= 0.003). mRSS decreased from 7.4 ± 3.8-3.3 ± 2.5 in patients with dcSSc (p= 0.02). The modified EUSTAR index score decreased from 2.54 ± 1.8 at baseline to 0.49 ± 0.5 at 2 years (p= 0.02). Survival rate was 92.3% at 2 years, and 76.9% at 5 years. No unexpected adverse events were observed. CONCLUSIONS: In SSc patients undergoing LuTx, an excellent 2-year survival was observed, without any disease-related adverse events. Our study supports LuTx as a viable option in SSc patients with end-stage lung disease. Apart from expected recovery of lung function, LuTx was associated with improvement of mRSS and global systemic disease activity.

[Dose-effect relationship of moxibustion for rheumatoid arthritis of liver and kidney deficiency and its effect on fatigue: a randomized controlled trial].

OBJECTIVE: To observe the effects of moxibustion with different frequency on the disease activity and fatigue of rheumatoid arthritis (RA) with liver and kidney deficiency on the basis of western medication treatment. METHODS: A total of 135 RA patients with liver and kidney deficiency were randomly divided into a high-frequency moxibustion group (45 cases, 3 cases dropped out), a low-frequency moxibustion group (45 cases, 2 cases dropped out) and a western medication group (45 cases, 2 cases dropped out, 1 case discontinued). Leflunomide tablet was taken orally in the western medication group, once a day, 20 mg a time. On the basis of the treatment in the western medication group, moxibustion was applied at ashi points and bilateral Shenshu (BL 23) and Sanyinjiao (SP 6) in the two moxibustion groups, 15 min a time. The treatment was given once a day, 5 times a week in the high-frequency moxibustion group and once every other day, 3 times a week in the low-frequency moxibustion group. A total of 12-week treatment was required in the 3 groups. Before and after treatment, the 28 joint disease activity score (DAS28), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), rheumatoid factor (RF), TCM syndrome score, average grip strength (GS) of both hands, 30-second sit-to-stand (STS), timed up and go (TUG), 20-meter walk test (20MWT), self rating anxiety scale (SAS) score and self rating depression scale (SDS) score were observed; before treatment, after treatment and in follow-up of 1, 3 months after treatment completion, the scores of fatigue visual analogue scale (VAS), Bristol rheumatoid arthritis fatigue numerical rating scale (BRAF-NRS) and Bristol rheumatoid arthritis fatigue multi-dimensional questionnaire (BRAF-MDQ) were observed, and the relieving of disease was evaluated by American College of Rheumatology (ACR)20/50/70 standards in the 3 groups. RESULTS: After treatment, the DAS28 scores, ESR, CRP, RF, TCM syndrome scores, TUG, 20MWT, SAS scores and SDS scores were decreased compared with those before treatment (P<0.01, P<0.05), while the average GS of both hands and STS were increased compared with those before treatment (P<0.01, P<0.05) in the 3 groups. After treatment, in the high-frequency moxibustion group, the DAS28 score, ESR, CRP, TCM syndrome score, SAS score and SDS score were lower (P<0.01, P<0.05), while the average GS of both hands and STS were higher (P<0.01, P<0.05) than those in the low-frequency moxibustion group and the western medication group; the TUG and 20MWT were decreased compared with those in the western medication group (P<0.01, P<0.05). After treatment, in the low-frequency moxibustion group, the DAS28 score, ESR, CRP, TCM syndrome score, TUG, SAS score and SDS score were lower (P<0.05, P<0.01), while the average GS of both hands was higher (P<0.01) than those in the western medication group. In each time point after treatment, the scores of fatigue VAS and BRAF-NRS were decreased compared with those before treatment in the 3 groups (P<0.01), while the BRAF-MDQ scores were decreased compared with those before treatment in the high-frequency moxibustion group and the low-frequency moxibustion group (P<0.01). After treatment, the BRAF-MDQ score was decreased compared with that before treatment in the western medication group (P<0.01). In the high-frequency moxibustion group, the scores of fatigue VAS, BRAF-NRS and BRAF-MDQ of each time point after treatment were lower than those in the western medication group (P<0.01), the scores of fatigue VAS and BRAF-NRS in follow-up of 1 month after treatment completion as well as the BRAF-MDQ score after treatment were lower than those in the low-frequency moxibustion group (P<0.01, P<0.05). In the low-frequency moxibustion group, the scores of fatigue VAS, BRAF-NRS and BRAF-MDQ of each time point after treatment were lower than those in the western medication group (P<0.01, P<0.05). After treatment, the proportions of ACR20 and ACR50 in the high-frequency moxibustion group and the low-frequency moxibustion group were higher than those in the western medication group (P<0.01), the proportion of ACR70 in the high-frequency moxibustion group was higher than those in the low-frequency moxibustion group and the western medication group (P<0.05, P<0.01), and the proportion of ACR70 in the low-frequency moxibustion group was higher than that in the western medication group (P<0.05). CONCLUSION: On the basis of the western medication treatment, moxibustion can effectively reduce the disease activity and improve fatigue status in RA patients with liver and kidney deficiency, and its efficacy is positively correlated with treatment frequency.

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.

Major Determinants of Well-Being in Patients With Axial Spondyloarthritis: 2 Year Follow-Up.

OBJECTIVES: Bath Ankylosing Spondylitis Patient Global Score (BAS-G) is a uni-dimensional scale that enables patients to evaluate the effects of their illness on their health. The aim of this study was to determine the impact of disease related outcomes on the BAS-G scores in patients with axSpA. METHODS: A total of 309 patients (56.6% of whom were male, mean age 44 ± 11) were included in the study. Socio-demographic characteristics (age, sex and education level) and clinical characteristics such as disease activity (BASDAI and CRP), spinal mobility (BASMI), functional status (BASFI), radiographic structural damage (mSASS, mNY, and BASRI-hip), and health related quality of life (SF-36 and ASQoL) of the patients were recorded at baseline. In addition, BASDAI total and each item score, BASFI, BAS-G, and CRP levels were collected at 6, 12, and 24 months. RESULTS: Female patients had significantly higher BAS-G scores (p = 0.037). Baseline BASDAI total score (p < 0.001) and all BASDAI item scores (p < 0.001 for each item), BASFI total score (p < 0.001), ASQoL total score (p < 0.001), and SF-36 PCS sum-score (p < 0.001) were moderately/highly correlated with BAS-G. Multivariate analysis revealed that back pain (BASDAI Q2) (p < 0.001) and the severity of morning stiffness (BASDAI Q5) (p < 0.001) were the main determinants of BAS-G in patients with axSpA. In 2-year follow-up, BASDAI Q1, BASDAI Q5, and BASFI scores were independent determinants of BAS-G in patients with axSpA. CONCLUSION: According to the results of the present study, patients with axSpA mainly rely on morning stiffness and back pain to determine their global health status. Moreover, fatigue, severity of morning stiffness and function are the determinants of BAS-G during follow-up.

Early Improvements with Guselkumab Associate with Sustained Control of Psoriatic Arthritis: Post hoc Analyses of Two Phase 3 Trials.

INTRODUCTION: Patterns of treatment response can inform clinical decision-making. This study assessed the course and impact of achieving minimal clinically important improvement (MCII) in clinical measures and patient-reported outcomes (PROs) with guselkumab in patients with active psoriatic arthritis (PsA). METHODS: Post hoc analyses evaluated 1120 patients with PsA receiving guselkumab every 4 or 8 weeks (Q4W/Q8W) or placebo from DISCOVER-1 (31% tumor necrosis factor inhibitor-experienced) and DISCOVER-2 (biologic-naïve). Achievement of MCII in clinical Disease Activity Index for PsA (cDAPSA), patient global assessment (PtGA) of arthritis, PtGA of psoriasis, patient-reported pain, Functional Assessment of Chronic Illness Therapy-Fatigue, Health Assessment Questionnaire-Disability Index, 36-item Short-Form Health Survey Physical Component Summary score, PtGA Arthritis + Psoriasis, and PsA Disease Activity Score (PASDAS) was compared between the guselkumab and placebo groups using Cox regression. Logistic regression adjusting for baseline factors evaluated associations between early (W4/W8) MCII achievement and stringent response (≥%50/%70 improvement in American College of Rheumatology response criteria, cDAPSA low disease activity [LDA], PASDAS LDA, and minimal disease activity) at W24/W52 among guselkumab-randomized patients. RESULTS: Among patients with highly active PsA (baseline cDAPSA = 44.1-45.0, PASDAS = 6.4-6.5), times to MCII were significantly faster for guselkumab vs. placebo (hazard ratios 1.3-2.5; P < 0.05). Across measures, at first timepoint assessed, MCII rates were significantly higher with guselkumab (Q4W/Q8W 28-68%/29-65%) vs. placebo (19-47%; both P < 0.05). Early (W4/W8) MCII with guselkumab associated with higher odds of achieving stringent responses at W24/W52 (odds ratios 1.4-17.2/1.4-5.4). CONCLUSIONS: In a mixed PsA population, significant proportions of patients treated with guselkumab achieved early (W4/W8) MCII across clinical and PRO measures, which associated with a higher likelihood of attaining clinically relevant improvements and low levels of disease activity at W24/W52. TRIAL REGISTRATION: DISCOVER-1 (NCT03162796). DISCOVER-2 (NCT03158285).

Extensive study of CCN4, VCAM-1, MMP-3, and GM-CSF as reliable markers for disease activity in rheumatoid arthritis.

Background: The involvement of Wnt-1-induced secreted protein-1 (WISP1/CCN4) in several inflammatory reaction has recently been proposed. Nevertheless, this protein's involvement in rheumatoid arthritis (RA) remains debated. Associations between poorly diagnosed RA and several classical markers derived from demography and biochemistry have been reported. Aim: We sought to investigate the reliability and effectiveness of serum concentrations of CCN4, vascular cell adhesion molecule-1 (VCAM-1), matrix melloprotenase-3 (MMP-3), and granulocyte-macrophage colony-stimulating factor (GM-CSF) in monitoring and predicting RA and bone damage, and their correlation with RA disease course. Methods: The study analyzed 128 patients with RA, comprising 68 newly diagnosed and 60 previously diagnosed patients, as well as 60 controls. Biomarker levels were measured with enzyme linked immuno-sorbent assays. Routine laboratory parameters such as serological, clinical, biochemical, and hematological parameters were additionally measured. Demography, anthropometry, and clinical symptom data were collected through interviews and a questionnaire. The joint disease activity score 28 (DAS28) was used to determine disease activity. Results: Concentrations of four biomarkers were significantly higher in the RA group than the healthy controls. Elevated biomarker concentrations were also observed in patients with high, rather than moderate or low, DAS28-ESR activity status, except for monocyte count, hematocrit (%), and urea level. Furthermore, CCN4 level positively correlated with VCAM-1, MMP-3, and GM-CSF levels, DA-S28-CRP and DAS28-ESR. The levels of three predictive markers, CCN4, VCAM-1, and MMP-3, were elevated in non-treated patients, whereas GM-CSF level showed no difference. The highest area under the curve was 73.3% for CCN4, with 93.3% sensitivity and 64.7% specificity. Conclusion: Our data suggest that CCN4 can be reliably used to indicate activity and therapeutic response associated with RA, thus facilitating earlier RA diagnosis.

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.

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.

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.

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.

Disease activity score for still's disease.

OBJECTIVE: To develop the Still's Disease Activity Score (SDAS). METHODS: We used data from the prospective adult-onset Still's disease cohort study and evaluated the disease activity. An expert group selected the most frequent, reproducible, and objective variables significantly modified in statistical analysis when comparing patients in the active group and in the remission group. These criteria were weighted to design the Still's Disease Activity Score (SDAS). The Delphi method was used to appreciate the level of disease activity. Total SDAS was calculated for each patient and compared to final consensus experts. RESULTS: At the diagnosis, all patients had an active disease (n = 80), while 48 patients were in remission at 6 months. The SDAS criteria were weighted as follows: fever ≥ 38.5 °C (1 point), rash (1 point), joint involvement (arthralgia: 1 point, swollen joints count "SJC": 1-3 SJC: 2 points, ≥ 4 SJC: 3 points), physician global assessment VAS ≥ 5/10 or a raise in physician VAS ≥ 2/10 (3 points), patient VAS ≥ 5 or a raise in patient VAS ≥ 2/10 (1 point), and CRP (> 10 mg/l: 1 point, ≥ 100 mg/l: 2 points). At 6 months, the consensus was achieved for 76 (95%) patients with 40 in remission (0-1 point), 8 in low disease activity (2-3 points), 16 in moderate disease activity (4-7 points), and 12 in severe disease activity (≥ 8 points). CONCLUSION: The Still's Disease Activity Score is a valid and sensitive assessment of the disease activity and the therapeutic response in Still's disease, despite its heterogeneous manifestations and patterns with systemic and articular forms. Key Points • The Still's Disease Activity Score (SDAS) is a good simple tool to assess the activity of the disease in a stable state for a week. • The SDAS is developed specifically for Still's disease without the need for an application or a calculator to calculate SDAS in routine clinical practice. • SDAS is a composite score classifying the disease activity in remission, low disease activity, moderate disease activity, and severe disease activity despite its heterogeneous patterns (systemic and articular forms). • The SDAS is a valid, reliable, and sensitive score and can be useful to guide the therapeutic strategy in clinical practice and in research.

Imaging of Ulcerative Colitis: The Role of Diffusion-Weighted Magnetic Resonance Imaging.

Magnetic resonance imaging (MRI) has emerged as a promising and appealing alternative to endoscopy in the objective assessment of patients with inflammatory bowel disease (IBD). Diffusion-weighted imaging (DWI) is a specialized imaging technique that enables the mapping of water molecule diffusion within biological tissues, eliminating the need for intravenous gadolinium contrast injection. It is expanding the capability of traditional MRI sequences in Ulcerative Colitis (UC). Recently, there has been growing interest in the application of intravoxel incoherent motion (IVIM) imaging in the field of IBD. This technique combines diffusion and perfusion information, making it a valuable tool for assessing IBD treatment response. Previous studies have extensively studied the use of DWI techniques for evaluating the severity of activity in IBD. However, the majority of these studies have primarily focused on Crohn's disease (CD), with only a limited number of reports specifically examining UC. Therefore, this review briefly introduces the basics of DWI and IVIM imaging and conducts a review of relevant studies that have investigated its application in UC to show whether these techniques are useful techniques for evaluating patients with UC in terms of detection, characterization, and quantification of disease activity. Through the extensive literature survey, most of these studies indicate that DWI proves valuable in the differential diagnosis of UC and could be used as an effective modality for staging UC.

Is vitamin D associated with disease activity in patients with axial or peripheral spondyloarthritis? A real-life study.

Vitamin D plays important role in inflammatory rheumatic diseases, which in turn rose an interest for investigating association of its deficiency with disease activity. In this research we aimed to evaluate this matter in the context of spondyloarthritis (SpA), together with treatment modalities and bone density in people diagnosed with axial or peripheral SpA in real-life setting. In our study we enrolled 99 patients with diagnosis of SpA treated at the tertiary level rheumatology department. Serum 25(OH)D levels, treatment modality (NSAIR or DMARDs), disease activity, tobacco smoking habits, mineral density of bone, supplementation and seasonal variations were assessed. We used standardized questionnaires such as ASDAS-CRP, BASFI and joint count, among many others, to evaluate some of the mentioned parameters. Sixty-five percent of patients had vitamin D deficiency. We found marginaly higher activity of disease in subjects with low vitamin D. In cases of peripheral SpA, there was a significant association of higher number of swollen joints and lower vitamin D levels. Additionally, the significant correlation was seen between normal serum vitamin D and supplementation. In our real-life study of patients with SpA we found a significant percentage of vitamin D deficit, with a tendency of slightly higher disease activity in those patients.In order to clarify the impact of the vitamin on disease activity in SpA and the supplementation recommendations for patients with these conditions, the conduction of further studies is required.

Utility of pan-immune-inflammation value as a predictor of the prognosis of childhood lupus.

BACKGROUND: Systemic lupus erythematosus (SLE) is a chronic inflammatory multisystemic disease. Monitoring disease activity thoughtout the disease course is important for effective management and assessment of disease outcome. OBJECTIVE: To assess whether the pan-immune inflammation value (PIIV) at diagnosis could predict organ involvement and disease activity in childhood SLE (cSLE) patients after 12 months of disease onst. METHODS: This is an observational retrospective multicenter study that comprised cSLE patients seen and followed at the participating centers between January 2010 and December 2022. All patients met the EULAR/ACR-19 criteria, were immunosuppressive drug-naïve at the time of SLE diagnosis and had a minimal follow-up period of 12 months. The data included clinical and laboratory findings and disease activity using the SLEDAI-2K. Receiver operating characteristic (ROC) curves were employed to determine the optimal cut-off value of PIIV and assess its predictive potential for disease activity, and organ involvement. RESULTS: A total of 125 patients (104 female) with a median age of 16.0 (IQR 5.6) years, a median age at disease onset of 10.9 (IQR 3.0) years, and a median disease duration of 4.8 (IQR 5.3) years were included. The most frequent involved organs at diagnosis were hematological (89.6%), musculoskeletal (68.8%), mucocutaneous (63.2%), and renal (58.4%). However, at a 12-month follow-up visit, the most frequent involved organs were renal (40.0%), hematological (39.2%), musculoskeletal (15.2%), and mucocutaneous (10.4%). The median PIIV at diagnosis was 139 (IQR 229.6), while the median SLEDAI was 12 (IQR 6.5) and 3.5 (IQR 7.0) at diagnosis and 12 months, respectively. An optimal PIIV cut-off of 250 was found to be a predicative for disease activity, with a sensitivity of 45% and a specificity of 86%. The study revealed that the PIIV successfully predicted four systems in our cohort of patients. CONCLUSION: Our work suggests the PIIV might be a reasonable predictor for organ involvement and disease activity in newly diagnosed cSLE, though further research, particularly larger studies, is required to validate these findings, especially regarding organ involvement.

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.

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.