Evaluation Of Disease Activity Research Articles

#5260 PLASMA AND URINE METABOLOMIC PROFILES REVEAL POTENTIAL BIOMARKERS AND PROVIDE VALUABLE INSIGHTS INTO THE MECHANISMS OF MPO-ANCA-GN

Abstract Background and Aims Currently, the precise mechanism of myeloperoxidase- anti-neutrophil cytoplasmic antibody associated glomerulonephritis (MPO-ANCA-GN) remains elusive. And there is a lack of dependable biomarkers for evaluating disease activity, therapeutic resistance, and risk of relapse. We try to seek valuable biomarkers and explore the mechanism of MPO-ANCA-GN by metabolomics. Method Urine and plasma samples from 63 MPO-ANCA-GN, 31 lupus nephritis (LN), 15 IgA nephropathy (IgAN), and 15 minimal change disease (MCD) patients and 30 HC were collected for metabolomics analysis. The samples were analyzed using Ultra Performance Liquid Chromatography (UPLC) and Tandem mass spectrometry (MS/MS). The different groups of samples were compared using Partial Least Squares-Discriminant Analysis. A Receiver Operator Characteristic (ROC) curve was constructed to assess the performance of the metabolite model in identifying active renal vasculitis. KEGG annotation and enrichment analysis were performed for key pathways. Results All metabolites in urine and plasma samples including hydrophilic compounds and hydrophobic compounds were identified. Compared with the disease control (DC) and HC, we observed 79 significantly upregulated metabolites (VIP>1, FDR<0.05, FC>1.5) and 32 downregulated metabolites (VIP>1, FDR <0.05, FC<0.67) in the plasma samples of MPO-ANCA-GN patients. KEGG enrichment analysis suggested that these upregulated metabolites were mainly associated with phenylalanine metabolism and galactose metabolism and downregulated metabolites were mainly associated with bile secretion, steroid biosynthesis, and ovarian steroidogenesis. Compared with the DC and HC, we identified a total of 122 differential metabolites in the urine samples of MPO-ANCA-GN patients, 40 of which were significantly upregulated (VIP>1, FDR<0.05, FC>1.5) and 68 of which significantly were downregulated (VIP>1, FDR <0.05, FC<0.67). Subsequently, KEGG analysis revealed that these upregulated metabolites were mainly enriched in glycerolipid metabolism, lipid and atherosclerosis, cholesterol metabolism, insulin resistance, regulation of lipolysis in adipocytes, vitamin digestion and absorption, fat digestion and absorption (Corrected P < 0.05). Downregulated metabolites were mainly enriched in steroid hormone biosynthesis (Corrected P < 0.05). Nine MPO-ANCA-GN patients with paired plasma and six MPO-ANCA-GN patients with paired urine during the active and remission phase were included in the study. A total of 504 differential metabolites in plasma samples were identified between the active and remission phase based on VIP value >1, P < 0.05, and FC >1.5 or FC < 0.6. Of these, 425 metabolites were downregulated, while 79 lipid metabolites were upregulated in the active group. MPO-ANCA-GN patients were divided into two groups according to Mayo Clinic/Renal Pathology Society Chronicity Score: Minimal-mild group and Moderate-severe group. In plasma samples, our data showed that 3-Methoxysalicylic Acid, Carnitine C20:5, and isoxanthopterin presented good ability in distinguishing between the minimal-mild group and the moderate-severe group, with an AUC > 0.7. In urine samples, cyclohexylamine and arachidonic acid (AUC > 0.8) can distinguish the two groups well. Conclusion We identified many novel potential metabolic biomarkers in urine and plasma samples for evaluating disease activity, therapeutic resistance, and risk of relapse in patients with MPO-ANCA-GN.

Role of abbreviated non-contrast-enhanced MR-enterography in the evaluation of Crohn's disease activity and complications as an alternative for full protocol contrast-enhanced study: A systematic review and meta-analysis.

Crohn's disease (CD) is a chronic disorder that often starts at a young age and involves periods of remission and relapse. Prompt diagnosis of relapses through screening is crucial due to the potential morbid complications of untreated active inflammation. Magnetic resonance enterography (MRE) is a noninvasive technique to screen for active inflammation. The standard protocol involves intravenous injection of contrast agents with potential side effects. Some abbreviated non-contrast-enhanced MRE protocols are proposed as alternatives for conventional MRE to identify active inflammation. Currently, there is controversy regarding the applicability and accuracy of these protocols. This study aims to describe and compare these protocols and evaluate their accuracy in detecting active inflammation and CD complications. Results from a systematic search of three databases in August 2022 were queried and screened by abstract and full text. Eligible studies were qualitatively and quantitatively analyzed by diagnostic test accuracy meta-analysis. 59 studies entered the systematic review, and 37 were eligible for meta-analysis. Diffusion-weighted imaging (DWI) and fast T2-weighted (T2w) sequences were most frequently used in abbreviated protocols and showed non-inferior accuracy compared to the full protocol in detecting active inflammation. ADC and qualitative DWI had pooled sensitivity of 90% (CI: 82-95%) and 89% (CI:82-93%) and pooled specificity of 94% (CI: 88-97%) and 89% (CI: 79-94%), respectively for detecting active inflammation. Moreover, T2w and combined T2w+DWI sequences had pooled sensitivity of 80% (CI: 64-90%) and 76% (CI: 61-86%) and pooled specificity of 90% (CI: 80-95%) and 87% (CI: 74 - 94%), respectively. Unenhanced protocols show relatively poor diagnostic accuracy in detecting penetrating complications of CD. Magnetization transfer imaging (MTI) has demonstrated excellent accuracy in detecting fibrosis. High heterogeneity was observed in all subgroups, and accuracy was reported to be highly operator dependent in most studies. An abbreviated protocol consisting of DWI and fast T2w imaging can potentially replace the full protocol MRE. Full protocol MRE will still have its role in identifying penetrating complications. MTI should be indicated in case of suspected fibrostenotic disease.

Dipeptidyl peptidase 4 as a potential serum biomarker for disease activity and treatment response in rheumatoid arthritis.

The treatment of rheumatoid arthritis (RA) related to the disease activity. However, the lack of highly sensitive and simplified markers limits the evaluation of disease activity. We sought to explore potential biomarkers associated with disease activity and treatment response in RA. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) proteomic analysis was performed to determine the differentially expressed proteins (DEPs) in serum collected from RA patients with moderate or high disease activity (determined by DAS28) before and after 24weeks of treatment. Bioinformatic analysis were performed for DEPs and hub proteins. In the validation cohort, 15 RA patients were enrolled. Key proteins were validated by enzyme-linked immunosorbent assay (Elisa), correlation analysis and ROC curve. We identified 77 DEPs. The DEPs enriched in humoral immune response, blood microparticle, and serine-type peptidase activity. KEGG enrichment analysis displayed that the DEPs were significantly enriched in cholesterol metabolism and complement and coagulation cascades. Activated CD4+T cell, T follicular helper cell, natural killer cell, and plasmacytoid dendritic cell significantly increased after treatment. Fifteen hub proteins were screened out. Among them, dipeptidyl peptidase 4 (DPP4) was the most significant protein associated with clinical indicators and immune cells. Serum concentration of DPP4 was testified to significantly increase after treatment and inversely correlate with disease activity indicators (ESR, CRP, DAS28-ESR, DAS28-CRP, CDAI, SDAI). Significant reduction was found in the serum CXC chemokine ligand10 (CXC10) and CXC chemokine receptor 3 (CXCR3) after treatment. Overall, our results suggest that serum DPP4 might be a potential biomarker for disease activity assessment and treatment response of RA.

Clinical value of fecal calprotectin for evaluating disease activity in patients with Crohn's disease.

Objective: To explore the clinical value of fecal calprotectin (FC) for evaluating disease activity in patients with Crohn's disease (CD) and its relationship with disease location. Methods: Patients with CD were enrolled retrospectively, and clinical data, including FC levels, were collected. Clinical activity was assessed using the Crohn's disease activity index (CDAI). Endoscopic activity was assessed using a simple endoscopic score for Crohn's disease (SES-CD). The partial SES-CD (pSES-CD) was scored for the size of ulcers in each segment as defined by the SES-CD and was calculated as the sum of segmental ulcer scores. Results: This study included 273 CD patients. The FC level was significantly positively correlated with the CDAI and SES-CD, with correlation coefficients of 0.666 and 0.674, respectively. The median FC levels in patients with clinical remission and mildly active and moderately-severely active disease were 41.01, 164.20, and 444.45μg/g. These values were 26.94, 66.77, and 327.22μg/g during endoscopic remission and mildly and moderately-severely active stages, respectively. Compared with c-reactive protein (CRP), the erythrocyte sedimentation rate (ESR), and other biomarker parameters, FC was better at predicting disease activity for CD patients. For an FC <74.52μg/g, the area under the curve (AUC) for predicting clinical remission was 0.86, with a sensitivity of 89.47% and a specificity of 71.70%. Moreover, endoscopic remission was predicted with a sensitivity of 68.02% and a specificity of 85.53%. The AUC was 0.83, and the cutoff value was 80.84μg/g. In patients with ileal and (ileo) colonic CD, FC was significantly correlated with the CDAI, SES-CD, and pSES-CD. The correlation coefficients were 0.711 (CDAI), 0.473 (SES-CD), and 0.369 (pSES-CD) in patients with ileal CD and 0.687, 0.745, and 0.714 in patients with (ileo) colonic CD, respectively. For patients in remission, those in the active stage, and those with large or very large ulcers, differences in FC levels were not significant between patients with ileal and (ileo) colonic CD. Conclusion: FC is a reliable predictor of disease activity in patients with CD, including those with ileal CD. FC is thus recommended for the routine follow-up of patients with CD.

Magnetic resonance imaging for evaluation of bowel inflammation and disease activity in Crohn's disease: A systematic review and meta-analysis

The aim of this systematic review and meta-analysis was to determine the performance of magnetic resonance imaging (MRI) in the diagnosis of bowel inflammation and disease activity in Crohn's disease (CD). MEDLINE, Embase and Web of Science databases of biomedical literature were systematically searched to identify studies that investigated the diagnostic accuracy of MRI in diagnosing bowel inflammation and disease activity in CD by comparing it with reference standards. Quality Assessment of Diagnostic Accuracy Studies-2 tool was used to assess study quality. The summary sensitivity and specificity were estimated using the bivariate model, and hierarchical summary receiver operating characteristic (HSROC) parameters were calculated and plotted. Of 5492 citations of interest, 34 articles contained the diagnostic accuracy data. Of these, results for the small bowel and the colorectum were reported separately in 19 studies and jointly by 21 studies. The meta-analytic summary sensitivity and specificity under the bivariate model were 90.9% (95% CI, 85.8%–94.2%) and 90.2% (95% CI, 81.9%–95.0%), respectively. The sensitivities and specificities of individual studies ranged from 55% to 100% and 51% to 100%, respectively. Substantial heterogeneity was observed in both sensitivity (I2 = 84.9%) and specificity (I2 = 78.8%). The HSROC curve also showed considerable heterogeneity between studies. Although the meta-analytic summary accuracy of MRI was high for the diagnosis of bowel inflammation in CD, the summary estimates might be unreliable due to the presence of high heterogeneity. El objetivo de esta revisión sistemática y metaanálisis fue determinar el rendimiento de la resonancia magnética nuclear (RM) en el diagnóstico de la inflamación intestinal y la actividad de la enfermedad en la enfermedad de Crohn (EC). Se realizaron búsquedas sistemáticas en las bases de datos de literatura biomédica de MEDLINE, Embase y Web of Science para identificar estudios que investigaran la precisión diagnóstica de la RM en el diagnóstico de la inflamación intestinal y la actividad de la enfermedad en la EC comparándola con estándares de referencia. Evaluación de la calidad de los estudios de precisión diagnóstica: se utilizó la herramienta 2 para evaluar la calidad del estudio. La sensibilidad y la especificidad resumidas se estimaron mediante el modelo bivariado, y se calcularon y trazaron los parámetros de características operativas del receptor resumidas jerárquicas (HSROC). De 5.492 citas de interés, 34 artículos contenían datos de precisión diagnóstica. De estos, los resultados para el intestino delgado y el colorrectal se informaron por separado en 19 estudios y en forma conjunta en 21 estudios. La sensibilidad y la especificidad del resumen metanalítico bajo el modelo bivariado fueron del 90,9% (IC del 95%, 85,8%-94,2%) y el 90,2% (IC del 95%, 81,9%-95,0%), respectivamente. Las sensibilidades y especificidades de los estudios individuales variaron del 55 al 100% y del 51 al 100%, respectivamente. Se observó heterogeneidad sustancial tanto en la sensibilidad (I2 = 84,9%) como en la especificidad (I2 = 78,8%). La curva HSROC también mostró una considerable heterogeneidad entre los estudios. Aunque la precisión del resumen metaanalítico de la RM fue alta para el diagnóstico de inflamación intestinal en la EC, las estimaciones del resumen pueden no ser confiables debido a la presencia de una gran heterogeneidad.

Correlation of serum adenosine deaminase activity with disease activity in patients with primary Sjögren's syndrome

BackgroundPrimary Sjögren's syndrome (pSS) is a chronic inflammatory autoimmune disease primarily affecting the exocrine glands, which has a variety of clinical manifestations and unclear pathogenic mechanisms. Adenosine deaminase (ADA) is an enzyme involved in the breakdown of purines, and changes in its activity have been associated with a number of autoimmune diseases. This study aims to investigate the relationship between serum ADA activity and disease activity in patients with pSS. MethodsIn this study, 196 patients with pSS and 196 healthy controls were enrolled. Serum ADA activity and clinical laboratory parameters were collected and analyzed in both groups. Pearson correlation analysis was used to examine the correlation between ADA activity and clinical laboratory parameters, as well as the correlation between ADA activity and the disease activity score. ResultsCompared with healthy controls, the activity of ADA in the serum of pSS patients was significantly increased (P < 0.0001), and the ADA activity was significantly decreased after immunosuppressive treatment (P < 0.0001). Correlation analysis revealed that the activity of ADA was significantly positively correlated with erythrocyte sedimentation rate (ESR) (r = 0.3, P < 0.0001) and serum immunoglobulin G (IgG) levels (r = 0.5, P < 0.0001), and significantly negatively correlated with high-density lipoprotein (HDL) (r = −0.4, P < 0.0001). Furthermore, there was a significant positive correlation between ADA activity and the disease activity score as measured by the Sjögren's Syndrome Disease Activity Index (SSDAI) (r = 0.4, P < 0.0001). ConclusionThis study found that patients with pSS have higher activity of ADA in serum, which is associated with disease activity as measured by SSDAI. These results suggest that ADA activity may be a potential biomarker for evaluating disease activity and treatment efficacy in pSS patients. Additionally, ADA may be a potential target for the treatment of pSS patients.

An Interim Analysis of Efficacy and Safety Data in Black and Hispanic Patients With Multiple Sclerosis Receiving Ocrelizumab Treatment in the CHIMES Trial (S31.006)

An Interim Analysis of Efficacy and Safety Data in Black and Hispanic Patients With Multiple Sclerosis Receiving Ocrelizumab Treatment in the CHIMES Trial (S31.006)

P173 Evaluating disease activity in established psoriatic arthritis with ultrasound

Abstract Background/Aims Early diagnosis, tight disease activity control and a treat-to-target approach are now recognised as critical factors that improve the outcome of patients with psoriatic arthritis (PsA). The traditional method used to assess disease activity is clinical examination (CE) by counting the number of tender and swollen joints. Ultrasound (US) has proven its superiority over CE for assessing the presence of synovitis in some studies. We aimed to identify the frequency and location of subclinical synovitis in a cohort of PsA patients with established disease. Methods Patients with established PsA were recruited. All gave informed, written consent and local ethical approval was obtained. All patients had a standard CE including 68/66 tender/swollen joint count. Grayscale (GS) and power doppler (PD) US of a standard set of 44 joints was performed using a GE logiq-P9 machine utilising 6-15-MHz and 8-18-MHz linear transducers. GS and PD were scored on a 0-3 semiquantitative scale for each joint. The presence of US active joints was defined as a GS-score ≥2 and/or PD-score ≥1. Results 78 patients were enrolled; 46/78 were female with a median age = 61 years (range 41-80). Median duration of PsA disease = 31.5 years (range 41-80), 40/78 were on bDMARDs and 27/78 on csDMARDs. The median TJC = 2 (range of 0-6) and mean CRP = 3.2 (SD 3.5). The most common sites for subclinical synovitis were wrists, knees, and metatarsophalangeal joints (see Table 1). 36 patients (46.2%) achieved a clinical state of minimal disease activity (MDA). 11 patients in MDA (30.5%) had a PD-score of &amp;gt; 1, suggesting they did not achieve minimal ultrasound disease activity (MUDA). Conclusion These data demonstrate that a proportion of established PsA patients deemed to have MDA actually have sonographic evidence of active disease. A previous study showed that PD-synovitis in PsA patients in clinical remission was a strong predictor of disease flare. It is unclear if subclinical synovitis in PsA is linked to radiographic progression. Combining CE and sonographic evaluation is an attractive approach to identifying subclinical disease. However, a validated ultrasound composite index, which includes the key joint areas frequently affected in PsA, is needed. Disclosure S. Sundanum: None. H. Darcy: None. P. Gallagher: None. F. Young: None. L. O'Neill: None. D. Veale: None.

P014 Experience of baricitinib in a real-world population with efficacy and side effects: a South London regional analysis

Abstract Background/Aims Baricitinib is the most common Janus Kinase inhibitor (JAKi) used in the treatment of rheumatological conditions. Whilst randomised controlled trials have demonstrated the efficacy and safety profile of baricitinib, real-world data on the experience of JAKi use in clinical practice is lacking. The aim of this analysis was to evaluate baricitinib use in a real-world patient population in South London. Methods We looked at two rheumatology departments in South London (St George’s Hospital; a tertiary teaching centre and Kingston Hospital; a district general hospital). All patients prescribed baricitinib between January 2017 to June 2022 were included. A retrospective assessment of electronic patient notes was performed to evaluate disease activity (determined by DAS-28 scores at baseline, 3-6 months and presently); adverse effects including side effects, rates of and reasons for discontinuation; and prescribing practice, including previous use of other biological disease modifying anti-rheumatic drugs (bDMARDs). Baseline data including age, gender, co-morbidities and rheumatological diagnoses were also included. Results 233 patients were included in this evaluation, with seropositive rheumatoid arthritis being the most common diagnosis (58%) and with a significant female population (87%). Baricitinib improved average DAS-28 scores from 5.75 (range 3.57-8.3) at baseline to 3.23 (range 0.28-7.49) at 3-6 months post-baricitinib, with the most recent DAS-28 score of 2.90 (range 0.56-6.77). Rates of adverse effects were low as shown in Table 1. Baricitinib was discontinued in 60/233 patients, with average duration to discontinuation of 9.5 months. The most common reasons for discontinuation were: ineffective disease control (28/60), recurrent bacterial infection (5/60), deranged liver function (3/60) and venous thromboembolism (2/60). Eight patients died whilst taking baricitinib. Where documented, the causes of death were Covid-19 (4/8) and malignancy (1/8). 110 out of 233 patients had received other bDMARDs before starting baricitinib. Documented reasons for baricitinib choice over tumour necrosis factor inhibitors (TNFi) included: previous lack of response to TNFi (89/233), contra-indication to TNFi (11/233) and preference of oral route (10/233). Conclusion Our real-world study of JAKi use shows that baricitinib is efficacious in the treatment of rheumatological conditions. Moreover, baricitinib is well tolerated, with low rates of adverse effects and subsequent discontinuation. Disclosure O. Buckeldee: None. K. Biddle: None. A. Latheef: None. I. Al-Shakarchi: None. N. Sofat: None.

Assessing the construct validity of musculoskeletal ultrasound and the rheumatoid arthritis foot disease activity index (RADAI-F5) for managing rheumatoid foot disease.

The RA foot disease activity index (RADAI-F5) is a valid, reliable and clinically feasible patient-reported outcome measure (PROM) for the measurement of RA foot disease activity. Further validation of the RADAI-F5 against musculoskeletal ultrasonography (MSUS) for foot disease activity is necessary before clinical implementation. The aim of this study was to examine the construct validity of the RADAI-F5 in relationship to MSUS and clinical examination. Participants with RA completed the RADAI-F5. MSUS was used to evaluate disease activity (synovial hypertrophy/synovitis/tenosynovitis/bursitis) and joint damage (erosion) using greyscale (GS) and power Doppler (PD) at 16 regions in each foot, including joints and soft tissues. These same regions were examined clinically for swelling and tenderness. The construct validity of the RADAI-F5 was assessed using correlation coefficients and a priori-specified hypotheses for the strength of associations. Of 60 participants, 48 were female, with a mean (s.d.) age of 62.6 (9.96)years and median disease duration of 15.49 (interquartile range 6-20.5) years. Theoretically consistent associations confirming construct validity [95% CI] were observed between the RADAI-F5 and MSUS GS (0.76 [0.57, 0.82]; strong), MSUS PD (0.55 [0.35, 0.71]; moderate), MSUS-detected erosions (0.41 [0.18, 0.61]; moderate), clinical tenderness (0.52 [0.31, 0.68]; moderate) and clinical swelling (0.36 [0.13, 0.55]; weak). Moderate to strong correlations between RADAI-F5 and MSUS demonstrate the good measurement properties of this instrument. With greater confidence in the utility of the RADAI-F5, clinical use of this new instrument as an adjunct to the disease activity score for 28 joints (DAS-28) could help to identify RA patients at risk for poor functional and radiological outcomes.

Computed Tomography in Diagnosis of Lesions of Pulmonary Tuberculosis

Pulmonary tuberculosis (MTB) is dangerous bacterial infection primarily affecting lungs and is capable of infecting everyone exposed to Mycobacterium tuberculosis. AFB and CXR are useful preliminary investigative tools, but CT scan are invaluable diagnostic tool for establishing a diagnosis and monitoring disease activity. Objectives: To diagnose the lesions of PTB and assess the CT scan findings in AFB-positive patients. Methods: The AFB-positive patients were examined using CT scan to reveal their mediastinal and pulmonary pathological conditions and activities and disease propagation using imaging technology of CT scan. In cases of PTB with lymphadenopathy, 50cc of non-ionic contrast was administered intravenously to examine the low attenuation area. Results: The findings of CT scan regarding micronodules, nodular masses and other foci and lymphadenopathy were scrutinized, and major diagnostic CT scan findings were Centrilobular nodules (97.40%), Parenchymal nodules (84.43%), Paratracheal and mediastinal lymphadenopathy (74.85%), air space consolidation and paucity (62.07%), Pulmonary calcification (31.73%), Pleural effusion (29.34%) and Bronchiectasis (12.77%). Conclusions: CT scan is the most sensitive and accurate tool for diagnosis confirmation and disease activity evaluation. In addition, it details the abnormalities and prognosis of organ deformity in PTB patients.

Utility of the visual system to monitor neurodegeneration in multiple sclerosis.

Neurodegeneration occurs early in the multiple sclerosis (MS) disease course and is an important driver of permanent disability. Current immunomodulatory therapies do not directly target neuronal health; thus, there is a critical need to develop neuroprotective strategies in MS. Outcome measures in clinical trials primarily evaluate disease activity and clinical disability scores rather than measures of neurodegeneration. The visual system provides a noninvasive correlate of brain atrophy and neuronal function through structural and functional exams. Furthermore, optic nerve axons and their respective neuronal cell bodies in the retina, in addition to their synaptic input to the thalamus, provide a distinct anatomy to investigate neurodegenerative processes. This review discusses the utility of the visual system as an early output measure of neurodegeneration in MS as well as an important platform to evaluate neuroprotective strategies in preclinical models.

Exploring Imaging Characteristics Associated With Disease Activity in Idiopathic Multifocal Choroiditis: A Multimodal Imaging Approach

To identify characteristics on multimodal imaging (MMI) in idiopathic multifocal choroiditis (MFC) that can identify inflammatory activity and distinguish choroidal neovascularization (CNV) activity from inflammatory activity. Prospective cohort study. MMI consisted of spectral-domain optical coherence tomography (angiography) (SD-OCT(A)), fundus autofluorescence, fundus photography, infrared imaging, fluorescein angiography (FA), and indocyanine green angiography (ICGA). MMI characteristics obtained during active and inactive disease were compared within the same lesion. Secondly, MMI characteristics were compared between active inflammatory lesions with and without CNV activity. Fifty patients (110 lesions) were included. In 96 lesions without CNV activity, the mean focal choroidal thickness was increased during the active disease (205 µm) compared to the inactive disease (180 µm) (P ≤ .001). Lesions with inflammatory activity typically demonstrated moderately reflective material located in the sub-retinal pigment epithelium (RPE) and/or in the outer retina with disruption of the ellipsoid zone. During the inactive stage of the disease, the material disappeared or became hyperreflective and indistinguishable from the RPE. During the active stage of the disease, the area of hypoperfusion in the choriocapillaris significantly increased as visualized on both ICGA and SD-OCTA. CNV activity in 14 lesions was associated with subretinal material with a mixed reflectivity and hypotransmission of light to the choroid on SD-OCT and leakage on FA. SD-OCTA identified vascular structures in all active CNV lesions and in 24% of lesions without CNV activity (showing old, quiescent CNV membranes). Inflammatory activity in idiopathic MFC was associated with several MMI characteristics, including focally increased choroidal thickness. These characteristics can guide clinicians in the challenging process of the evaluation of disease activity in idiopathic MFC patients.

Serum Interleukin-37 Levels in Patients with Systemic Sclerosis and its Relation with Clinical Findings

Aim: This study investigates serum interleukin(IL)-37 levels in patients with systemic sclerosis (SS) and assesses its relationship with clinical findings.&#x0D; Methods: This study included 35 patients with SS and 30 healthy control subjects. The demographic and clinical characteristics of the patients, such as the presence of Raynaud’s phenomenon, SS subtype, digital ulcers, gastrointestinal and lung involvement, and disease activity, were recorded. The medications used by the patients were recorded, and Serum IL-37 levels were measured using an enzyme-linked immunosorbent assay. The United Kingdom Functional Scoring system was used to evaluate the functional status of the patients, while the Valentini criteria were used to evaluate disease activity. Skin involvement was evaluated based on the modified Rodnan skin score.&#x0D; Results: Although serum IL-37 levels were found to be lower in patients with SS than in the control group, the difference was not statistically significant (p= 0.078). A negative correlation was identified between serum IL-37 levels and C3 levels in patients with SS (p= 0.046). No significant relationship was found between IL-37 levels and other clinical and laboratory parameters.&#x0D; Conclusion: Unlike in patients with autoimmune disorders, serum IL-37 levels were found to be lower in patients with SS than in the control subjects, and IL-37 demonstrated a negative correlation with C3 levels.

Elevated serum immunoglobulin level predicts high risk of 1-year recurrence in patients with Takayasu arteritis

BackgroundThe mechanism of humoral immunity to Takayasu arteritis (TAK) is not clear. In our study, we aimed to investigate the correlation between immunoglobulins and disease activity and the relationship between immunoglobulins and the prognosis of TAK patients.MethodsOne hundred ninety TAK patients divided into two groups according to whether they had elevated immunoglobulins or not. We compared the demographic data and the clinical data between the two groups. Pearson correlation was used to analyze the relationship between immunoglobulin and disease activity, as well as the relationship between their changes. Immunohistochemical staining was used to compare the expression of humoral immune cells in TAK and atherosclerotic patients. One hundred twenty TAK patients who achieved remission within 3 months after discharge were followed up for 1 year. Logistic regression was used to explore the relationship between elevated immunoglobulins and recurrence.ResultsDisease activity and inflammatory factors were significantly higher in the group with elevated immunoglobulins than in the normal group [NIH (3.0 vs. 2.0, P = 0.001), ITAS-A (9.0 vs. 7.0, P = 0.006)]. Compared with atherosclerotic patients, CD138 + plasma cells were significantly increased in the aortic wall of patients with TAK (P = 0.021). Changes in IgG correlated well with CRP and ESR [CRP (r = 0.40, P = 0.027), ESR (r = 0.64, P < 0.001)]. For patients with TAK in remission, elevated immunoglobulins was associated with 1-year recurrence [OR95%, CI: 2.37 (1.03, 5.47), P = 0.042].ConclusionsImmunoglobulins is of clinical value in evaluating disease activity in TAK patients. Moreover, the dynamic changes of IgG were correlated with the changes in inflammatory indicators in TAK patients.

Monitoring of Serum TWEAK Level Guides Glucocorticoid Dosages in the Treatment of Systemic Lupus Erythematosus

Objective: Accurate assessment of systemic lupus erythematosus (SLE) disease activity is critical. This study explored the relationship between the serum level of tumor necrosis factor-like weak inducer of apoptosis (TWEAK) and the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score as well as the role of TWEAK in guiding the glucocorticoid dosage in SLE treatment. Methods: This study involved 131 patients with SLE, 34 with subacute cutaneous lupus erythematosus (SCLE), 22 with discoid lupus erythematosus (DLE), and 32 healthy volunteers. The serum and urinary TWEAK levels were determined. Monomeric C-reactive protein (mCRP), anti-dsDNA IgG, antinuclear antibody (ANA), complements in serum and urinary albumin level were measured. The SLEDAI 2000 (SLEDAI-2K) was used to evaluate disease activity. The correlation of the SLEDAI-2K score with all biomarkers was determined. Methylprednisolone was orally administered to patients with SLE depending on the serum level of TWEAK. Results: TWEAK levels were higher in patients with SLE or SCLE than in patients with DLE or healthy controls. The serum TWEAK level was positively correlated with the SLEDAI-2K score in patients with SLE (P &lt; 0.001), and was more strongly correlated with the SLEDAI-2K score than other parameters (P &lt; 0.001). Moreover, TWEAK-based glucocorticoid therapy was associated with lower SLEDAI-2K scores, better tapering of glucocorticoid doses, and fewer lupus flares in patients with SLE. Conclusions: Serum TWEAK is a useful biomarker reflecting SLE disease activity. Monitoring of the serum TWEAK level can improve the outcomes of glucocorticoid therapy in patients with SLE.

Efficacy and safety of selective JAK 1 inhibitor filgotinib in active rheumatoid arthritis patients with inadequate response to methotrexate: comparative study with filgotinib and tocilizumab examined by clinical index as well as musculoskeletal ultrasound assessment (TRANSFORM study): study protocol for a randomized, open-label, parallel-group, multicenter, and non-inferiority clinical trial

BackgroundAdministration of Janus kinase (JAK) inhibitors and biological disease-modifying antirheumatic drugs has dramatically improved even the clinical outcomes in patients with rheumatoid arthritis (RA) and an inadequate response to methotrexate (MTX). Dysregulation of JAK-STAT pathways via overproduction of cytokines, such as interleukin-6, is involved in the pathogenesis of RA. Filgotinib is a selective JAK1 inhibitor pending approval for use in RA. By inhibition of the JAK-STAT pathway, filgotinib is effective in suppressing disease activity and preventing the progression of joint destruction. Similarly, interleukin-6 inhibitors such as tocilizumab also inhibit the JAK-STAT pathways by inhibition of interleukin-6 signaling. We present the protocol for a study that will evaluate whether the effectiveness of filgotinib monotherapy is non-inferior to that of tocilizumab monotherapy in RA patients with an inadequate response to MTX.MethodsThis study is an interventional, multicenter, randomized, open-label, parallel-group, and non-inferiority clinical trial with a 52-week follow-up. Study participants will be 400 RA patients with at least moderate disease activity during treatment with MTX. Participants will be randomized in a 1:1 ratio to administer filgotinib monotherapy or subcutaneous tocilizumab monotherapy switched from MTX. We will evaluate disease activity by measuring clinical disease activity indices and by using musculoskeletal ultrasound (MSUS). The primary endpoint is the proportion of patients who achieve an American College of Rheumatology 50 response at week 12. Secondary endpoints are changes from baseline in the MSUS scores. We will also comprehensively analyze serum levels of multiple biomarkers, such as cytokines and chemokines.DiscussionThe study results are expected to show the non-inferiority of the effectiveness of filgotinib monotherapy to that of tocilizumab monotherapy in RA patients with inadequate response to MTX. The strength of this study is its prospective evaluation of therapeutic efficacy using not only clinical disease activity indices, but also MSUS, which accurately and objectively evaluates disease activity at the joint level among patients drawn from multiple centers with a standardized evaluation by MSUS. We will evaluate the effectiveness of both drugs by integrating multilateral assessments—clinical disease activity indices, MSUS findings, and serum biomarkers.Trial registrationJapan Registry of Clinical Trials (https://jrct.niph.go.jp) jRCTs071200107. Registered on March 3, 2021. ClinicalTrials.gov NCT05090410. Registered on October 22, 2021.

External validation and comparison of simple ultrasound activity score and international bowel ultrasound segmental activity score for Crohn’s disease

Background Intestinal ultrasound (IUS) is a non-invasive tool for monitoring Crohn’s disease (CD) activity. Recently, sonographic activity scores, including the International Bowel Ultrasound Segmental Activity Score (IBUS-SAS) and Simple Ultrasound Activity Score for CD (SUS-CD), were developed. This study aimed to assess their clinical application value. Methods This retrospective study enrolled patients with CD from March 2021 to June 2022. The diagnostic performance of the ultrasound scores was evaluated using the simplified endoscopic score for CD (SES-CD). Correlations of ultrasound scores with SES-CD, CD activity index (CDAI), and inflammatory biomarkers were assessed. Inter-rater reliability was compared. Results In total, 140 patients were included. The IBUS-SAS for evaluating disease activity had an area under the curve (AUC) of 0.895, sensitivity of 85.4%, and specificity of 82.4% for the cut-off value of 48.7. The SUS-CD revealed an AUC of 0.835, sensitivity of 92.7%, and specificity of 64.7% for the cut-off value of 2.5. The IBUS-SAS and SUS-CD were positively correlated with SES-CD (r = 0.511 and 0.534, respectively). The scores correlated significantly with the CDAI and inflammatory biomarkers (all p < 0.01). The IBUS-SAS was more strongly correlated with CDAI (r = 0.666 vs 0.486) and C-reactive protein (r = 0.645 vs 0.434) than the SUS-CD. The intraclass correlation coefficient (ICC) of the IBUS-SAS and SUS-CD between the two sonologists was excellent (ICC = 0.96 and 0.78, respectively). Conclusion Both the IBUS-SAS and SUS-CD can evaluate disease activity in CD and exhibited a significant correlation with activity indices and inflammatory biomarkers. Clinical trial registration ChiCTR2200055221

Artificial Intelligence Enables Quantitative Assessment of Ulcerative Colitis Histology

Ulcerative colitis is a chronic inflammatory bowel disease that is characterized by a relapsing and remitting course. Assessment of disease activity critically informs treatment decisions. In addition to endoscopic remission, histologic remission is emerging as a treatment target and a key factor in the evaluation of disease activity and therapeutic efficacy. However, manual pathologist evaluation is semiquantitative and limited in granularity. Machine learning approaches are increasingly being developed to aid pathologists in accurate and reproducible scoring of histology, enabling precise quantitation of clinically relevant features. Here, we report the development and validation of convolutional neural network models that quantify histologic features pertinent to ulcerative colitis disease activity, directly from hematoxylin and eosin–stained whole slide images. Tissue and cell model predictions were used to generate quantitative human-interpretable features to fully characterize the histology samples. Tissue and cell predictions showed comparable agreement to pathologist annotations, and the extracted slide-level human-interpretable features demonstrated strong correlations with disease severity and pathologist-assigned Nancy histological index scores. Moreover, using a random forest classifier based on 13 human-interpretable features derived from the tissue and cell models, we were able to accurately predict Nancy histological index scores, with a weighted kappa (κ = 0.91) and Spearman correlation (⍴ = 0.89, P < .001) when compared with pathologist consensus Nancy histological index scores. We were also able to predict histologic remission, based on the absence of neutrophil extravasation, with a high accuracy of 0.97. This work demonstrates the potential of computer vision to enable a standardized and robust assessment of ulcerative colitis histopathology for translational research and improved evaluation of disease activity and prognosis.

Abstract TP89: Ldl Levels May Correlate With Intracranial Atherosclerotic Plaque Enhancement

Introduction: The enhancement of atherosclerotic plaques after the intravenous administration of gadolinium (Gd) has been correlated with the presence of culprit plaques in patients with acute strokes due to underlying intracranial atherosclerosis (ICAS). A new method to objectively quantify Gd-enhancement was used to monitor plaques over time after an acute stroke. Currently there is no imaging method to accurately monitor atherosclerotic activity. Methods: Patients with stroke or transient ischemic attack caused by ICAS were included. Every patient was started on high-dose statins after ictus. 7T MRI images were obtained at baseline and after at least 6 months. LDL levels were obtained at the time of the event and at follow-up. Culprit plaques were identified based on degree of stenosis, presence of positive remodeling and Gd-enhancement. Arterial 3D enhancement maps in the territory of the culprit plaque were generated. Orthogonal signal intensity (SI) probes were expanded into the plaque and parent vessel to generate 3D enhancement color maps. Arterial segment variance (ASV) (SD 2 Arterial segment Baseline T1+Gd - SD 2 Arterial segment Follow up T1+Gd ) was used to compare the plaque and parent vessel enhancement. Results: Five patients underwent baseline and follow-up imaging. The median time between scans was 13.3 (IQR=13.3) months. ASV was strongly correlated with changes in LDL (Rho=0.9, p=0.037). Additionally, Gd-enhancement and plaque burden correlated with levels of LDL (Figure): Gd uptake (Rho=0.7, p=0.22) and plaque burden (Rho=0.67, p=0.22). Conclusion: This pilot study demonstrates that high-resolution imaging can be used in determining the response to statins in patients with high atherosclerotic burden. Gd-enhancement and plaque burden correlated with serum values of LDL. 3D enhancement maps and histogram analysis of atherosclerotic plaques are promising tools for evaluating disease activity and response to medical therapy.