Shorter Disease Research Articles

#1307 Glomerular galactose-deficient IgA1 (KM55) positive may be associated with poor prognosis in DKD patients

Abstract Background and Aims Diabetic kidney disease (DKD) and IgA nephropathy (IgAN) are prevalent renal diseases with a high incidence rate, and the prognosis is notably poorer when these two diseases coexist. However, it remains uncertain whether the pathological changes associated with DKD combined with IgA deposition (DKD-IgA deposition) are linked to a worsened prognosis. Method To address this question, we conducted an analysis comparing the clinicopathological characteristics and prognosis of DKD-IgA deposition patients to DKD patients as controls (Fig. 1). Results The results revealed that DKD-IgA patients exhibited higher cholesterol levels compared to DKD patients (6.2 ± 2.0 vs. 5.4 ± 1.9 mmol/L, p = 0.042). The group with DKD-IgA deposition had a significantly shorter follow-up duration (10.9 ± 10.6 months) compared to the control group (20.4 ± 18.7 months, p = 0.029). However, they exhibited higher levels of serum creatinine at the end of the follow-up period (343.8 ± 328.0 μ mol/L vs. 182.1 ± 124.6 μmol/L, p = 0.031). Kaplan-Meier analysis showed a higher cumulative incidence of poor events in the DKD-IgA deposition group (p = 0.036) (Fig. 2). In addition, we also detected galactose deficient IgA1 (KM55) in the kidneys and serum of patients with DKD-IgA deposition. Of the 24 patients with DKD-IgA deposition, 54.5% (24/44) showed positive glomerular KM55 results. Immunofluorescence analysis revealed that KM55 and IgA were predominantly colocalized in the mesangial and capillary regions (Fig. 3). Furthermore, the subgroup with KM55 positivity had a shorter disease duration compared to the KM55 negative subgroup (66.0 vs. 120.0 months, p = 0.048). The serum levels of galactose-deficient IgA1 (Gd-IgA1) (6296.4 ± 1535.4 vs. 4057.4 ± 1082.0 ng/mL, p = 0.010) and C4 (0.4 ± 0.1 vs. 0.3 ± 0.1 g/L, p = 0.020) were significantly higher in the KM55 positive subgroup than in the KM55 negative subgroup. Furthermore, it was observed that the KM55 positive subgroup exhibited a considerably higher incidence of reaching the renal endpoint compared to the control group (64.3% vs. 20.0%, p = 0.047). Conclusion These study results suggest that individuals with DKD who display glomerular IgA deposition alongside KM55 positivity may experience a more unfavorable prognosis.

Rituximab retention rate in systemic sclerosis: a long term real-life multicenter study.

to report real-life data on rituximab retention-rate as indicator of safety and efficacy in a multicentric national cohort of systemic sclerosis patients. SSc patients treated with rituximab and followed for at least 36 months were included, clinically characterized, and longitudinally monitored. A competing risk analysis with sub-Hazard Ratio(sHR) definition was performed to explore the clinical variables linked to specific cause of rituximab discontinuation. One-hundred-fifty-two SSc-patients (mean age 47.3 ± 12.3 years; females 79.6%; diffuse disease 77.6%; anti-topoisomerase-I positivity 63.2%) were evaluated over a median(IQR) time of 3.3(1.7-5.0) years. The primary indication for rituximab were interstitial lung disease (ILD)(38.8%), worsening skin fibrosis(36.8%), and arthritis(13.8%); 138 patients(90.8%) received more than one rituximab course. The 5-years rituximab retention rate was 59.9%(44.6-64.7%). Clinical response was the most common reason for rituximab discontinuation[5.7(3.7-8.4) per 100 patient-year] and was associated with a shorter disease duration[sHR 0.8(0.7-0.9)], anti-topoisomerase-I negativity[sHR 0.4(0.2-0.9)], previous digital ulcers[sHR 2.6(1.1-6.2] and no history of arthritis[sHR 0.3 (0.1-0.8)]. Treatment failure was the second cause of rituximab discontinuation[3.7(2.2-6.0) per 100 patient-year] and was associated with anti-centromere antibody positivity[sHR 2.8(1.1-7.4)] and anti-topoisomerase-I negativity[sHR 0.2(0.1-0.6)]. Adverse events(AEs) were the less common cause of discontinuation[3.1(1.7-5.2) per 100 patient-year], associated with limited cutaneous subset[sHR 3.4(1.2-9.7)] and previous mycophenolate mofetil treatment[sHR 4.5(1.2-16.3)]. rituximab is a safe and effective treatment in SSc: clinical response emerged as the primary reason for rituximab discontinuation, and AEs had a limited impact on treatment persistence. The identification of specific disease features associated with a response to rituximab will be useful in the management of SSc-patients.

Impact of previous treatment history and B-cell depletion treatment duration on infection risk in relapsing-remitting multiple sclerosis: a nationwide cohort study

BackgroundB-cell depletion displays striking effectiveness in relapsing-remitting multiple sclerosis (RRMS), but is also associated with increased infection risk. To what degree previous treatment history, disease-modifying therapy (DMT) switching pattern and...

Multiple sclerosis and COVID-19: a northern China survey

BackgroundThere is insufficient data on severe acute respiratory syndrome coronavirus type-2 (SARS-CoV-2) infection in Chinese patients with multiple sclerosis (pwMS). This study aims to explore the manifestation of pwMS during the Coronavirus disease 2019 (COVID-19) pandemic and the effect of SARS-CoV-2 infection on the prognosis of MS in northern China.MethodsIn this cross-sectional study, an online self-administered questionnaire and telephone interviews were conducted among pwMS of northern China. Clinical correlation of SARS-CoV-2 infection since the onset of the COVID-19 pandemic in northern China was analyzed.Results164 patients with an average age of 38.9 ± 12.2 years were included, of which 57.3% had a disease course ≤ 5 years. 33.5% of the patients were COVID-19 vaccinated. 87.2% received disease-modifying therapy (DMT), and the average immunotherapy duration was 1.9 ± 1.6 years. 83.5% were SARS-CoV-2 infected, 14.6% reported worsening of their original condition after infection, and 5.1% had a relapse of MS. Shorter disease course was independently related to infection risk (P = 0.046), whereas increasing age was related to aggravated behavioral symptoms (P = 0.008). However, gender, vaccination, and DMT were not associated with susceptibility or poor prognosis.ConclusionA shorter disease course is independently associated with an increased risk of SARS-CoV-2 infection, and age is associated with worsening disability. It seems to be safe and necessary to use DMT during the pandemic, however, the use of B cell-depletion agents should be approached with caution.

Omalizumab withdrawal outcomes in chronic spontaneous urticaria are linked with baseline IgE and eosinophil levels

BackgroundChronic Spontaneous Urticaria (CSU) is an immune-mediated skin disease that may require prolonged treatments. Currently, there are no recommendations for treatment discontinuation once CSU symptoms are controlled, particularly among patients primarily diagnosed with severe CSU. ObjectiveIn this real-life study we aimed to describe our experience of omalizumab (Oma) treatment withdrawal in CSU and define biomarkers related to these outcomes. MethodsCSU patients followed at our allergy clinic from January 2016 to December 2022 were included. Response to Oma therapy, and Oma-withdrawal outcomes among patients who reached complete remission for >6 months were analyzed. ResultsDuring the study period 192/335(%) CSU patients were categorized as severe-CSU and entitled to receive Oma according to our country's regulations. Of them, 131/192(68%) were considered “Oma-responders”, and 95/131(72.5%) patients underwent gradual treatment withdrawal. Successful Oma-withdrawal was documented in 47/95(49.5%) whereas 48/95(50.5%) patients experienced flare and were defined as unsuccessful OMA-withdrawal. The first was associated with shorter disease duration 7.1 ± 7.4 years vs. 10.7 ± 9.4 (P = 0.042), lower baseline-IgE 81.6 ± 84.1IU/ml vs. 324.7 ± 555.9 (P = 0.005), and lower baseline-eosinophils count 131.4 ± 110.5 vs. 195.6 ± 98.4 (P = 0.043) in comparison to failure of Oma-withdrawal group. ConclusionOMA may be successfully withdrawn in up to 50% of severe CSU patients following complete remission of disease symptoms, utilizing a gradual withdrawal protocol. Oma-withdrawal failure was linked with longer duration of disease as well as high IgE and eosinophil counts prior to initiation of Oma therapy. These parameters may enable the design of a treatment withdrawal algorithm.

Prediction of subthalamic stimulation efficacy on isolated dystonia via support vector regression

IntroductionDeep brain stimulation (DBS) of subthalamic nucleus (STN) has been well-established and increasingly applied in patients with isolated dystonia. Nevertheless, the surgical efficacy varies among patients. This study aims to explore the factors affecting clinical outcomes of STN-DBS on isolated dystonia and establish a well-performed prediction model. MethodsIn this prospective study, thirty-two dystonia patients were recruited and received bilateral STN-DBS at our center. Their baseline characteristics and up to one-year follow-up outcomes were assessed. Implanted electrodes of each subject were reconstructed with their contact coordinates and activated volumes calculated. We explored correlations between distinct clinical characteristics and surgical efficacy. Those features were then trained for the model in outcome prediction via support vector regression (SVR) algorithm and testified through cross-validation. ResultsPatients demonstrated an average clinical improvement of 56 ± 25 % after STN-DBS, significantly affected by distinct symptom forms and activated volumes. The optimal targets and activated volumes were concentratedly located at the dorsal posterior region to STN. Most patients had a rapid response to STN-DBS, and their motor score improvement within one week was highly associated with long-term outcomes. The trained SVR model, contributed by distinct weights of features, could reach a maximum prediction accuracy with mean errors of 11 ± 7 %. ConclusionSTN-DBS demonstrated significant and rapid therapeutic effects in patients with isolated dystonia, by possibly affecting the pallidofugal fibers. Early improvement highly indicates the ultimate outcomes. SVR proves valid in outcome prediction. Patients with predominant phasic and generalized symptoms, shorter disease duration, and younger onset age may be more favorable to STN-DBS in the long run.

Upper motor neuron signs in primary lateral sclerosis and hereditary spastic paraplegia.

The frequency and distribution of upper motor neuron (UMN) signs in primary lateral sclerosis (PLS) are unknown. We aimed to study the spectrum of UMN signs in PLS and compare it with hereditary spastic paraplegia (HSP). We retrospectively analyzed the frequency of different UMN signs, including hyperreflexia (limbs and jaw), limb and tongue spasticity, Babinski, and Hoffman signs, in PLS patients at first observation and compared this respect to onset region and symptom duration. We also compared PLS versus HSP patients. We included 34 PLS and 20 HSP patients, with a median symptom duration at first visit of 3.0 (interquartile range, IQR = 4.0) and 19.0 (IQR = 22.0) years, respectively. In PLS patients, hyperreflexia of upper (UL) (88.2%) and lower (LL) (91.2%) limbs, and LL spasticity (79.4%) were the most common findings. Spasticity of LL was significantly (p = .012) more frequent in LL-spinal onset subgroup, tongue spasticity in bulbar-onset subgroup (p = .021), and Hoffman sign in UL-spinal onset subgroup (p = .024). The PLS subgroup with shorter disease duration had a higher frequency of abnormal jaw jerk reflex (p = .037). Compared with HSP, PLS patients had a higher frequency of UL hyperreflexia (88.2% vs. 42.1%, p < .001) and UL spasticity (44.1% vs. 0.0%, p < .001). Asymmetric distribution of UMN signs was present in PLS and not in HSP. In PLS, UL UMN signs are nearly always present and UMN sign distribution appears to be associated with onset region. At first observation, bulbar involvement, asymmetrical distribution of UMN signs and UL spasticity may indicate PLS versus HSP.

Real-world use of oral versus subcutaneous semaglutide in a cohort of type 2 diabetic patients: which option to which patient?

PurposeTo evaluate the variables influencing the therapeutic choice toward oral versus subcutaneous semaglutide in a cohort of diabetic subjects.MethodsWe retrospectively collected data of 292 patients followed at the Diabetes Unit of the University Hospital of Siena and the Hospital of Grosseto, who were prescribed oral (n = 115) or subcutaneous (n = 177) semaglutide between October 2021 and October 2022.ResultsOral semaglutide was preferentially prescribed in older subjects with longer disease duration in replacement of other antidiabetic drugs, while subcutaneous semaglutide was preferentially prescribed in add-on to metformin in subjects with higher body weight and BMI. After 6 months, both formulations significantly improved glycemic control and body weight, however injectable semaglutide showed a greater efficacy on A1c levels, weight loss, BMI and waist circumference reduction. No differences were found in terms of adverse events.ConclusionIn our experience, injectable semaglutide is preferred in patients with excess weight and shorter disease duration, while the oral formulation was used later and especially after therapeutic failure of previous therapies. Follow-up data indicate similar tolerability and efficacy of both formulations, despite subcutaneous semaglutide demonstrated greater efficacy.

Risk factors for hospitalization in Mexican patients with systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is an autoimmune disease that often requires hospitalization. Most hospitalizations are due to infections and/or disease activity, for which several risk factors have been described in non-Mestizo patients. To identify risk factors for hospitalization in patients with systemic lupus erythematosus (SLE). This was an observational case-control study of patients with SLE in San Luis Potosí, Mexico, evaluated from January 2019 to October 2020. We compared hospitalized lupus patients with non-hospitalized lupus patients. We used descriptive statistics and logistic regression to describe potential risk factors. Of a total of 202 patients, 89 (45.1%) were hospitalized; these patients were younger, had shorter disease duration, higher disease activity scores (systemic lupus erythematosus disease activity index-SLEDAI), and more accumulated damage than non-hospitalized patients. The primary reasons for hospitalization were disease activity (60.7%), kidney disease, infection, and drug toxicity (5.6%). Multivariate analysis revealed several risk factors associated with hospitalization, including elevated creatinine, C-reactive protein, neutrophil levels, and constitutional symptoms, while prolonged international normalized ratio (INR), longer stay in the intensive care unit (ICU), and vasopressor use were associated with mortality. The use of antimalarials was a protective factor against hospitalization. Survival analysis revealed that patients with hospital-acquired infections had a lower probability of survival. Disease activity was the most common reason for hospitalization; kidney, constitutional, and hematological factors were associated with hospitalization; and the use of antimalarial was a protective factor for hospitalization.

P161 Self-reported barriers to exercise from a national United Kingdom systemic lupus erythematosus cohort

Abstract Background/Aims Patients with systemic lupus erythematosus (SLE) are more inactive than the general population. Regular physical activity (PA) positively impacts many health parameters, including cardiovascular health. To better understand patient barriers to leisure time PA we conducted a national survey of patients with SLE in the UK. Methods An online survey was disseminated via LUPUS UK social media platforms between 5/05/2023 and 28/10/2023. Participants self-reported demographic data including postcodes. Indices of Multiple Deprivation (IMD) were used to define socioeconomic deprivation and were split into quantiles, where quartile 5 represents participants living in 20% least deprived areas in England. Categorical and continuous data were analysed using Fisher’s exact test and Mann-Whitney U test respectively. Results There were 249 individual responses. Table 1 describes the cohort demographics alongside response data. On a 0-10 scale (very unsatisfied to very satisfied), 171/244 (70%) of participants rated their satisfaction with their amounts of leisure time PA as ≤ 4. The most commonly reported barriers to PA were fatigue (221/249, 88.8%), pain (155/249, 62.2%) and lupus-related symptoms/flares (145/249, 58.2%). Dislike of exercise was reported by &amp;lt; 10% of cohort (22/249, 8.8%). When asked to identify the primary barrier to PA, 119/244 (48.8%) reported fatigue. Lack of motivation (40/244, 16.4%) and knowledge about exercise (18/244, 7.4%) were other predominant barriers. Concern around injury differed between ethnic groups (p = 0.016). Other barriers did not differ by sex, ethnic group or socioeconomic deprivation. Participants reporting lack of time were younger with a median age of 45 (35-53) versus 54 (43-63) years, p = &amp;lt;0.001. Patients reporting fatigue, pain and self-consciousness had higher BMI in kg/m2 (27.7 [23.6-32.3] vs 23.4 [20.8-28.2]; 28.7 [23.8-33.1] vs 25.4 [22.6-28.8]; 31.4 [27.9-38.4] vs 25.8 [23.1-30.2]), p = &amp;lt;0.001. Lupus-related symptoms/flares and concern that PA may worsen lupus were reported by participants with a shorter disease duration in years (8 [3-17] vs 12 [4.5-24] p = 0.002, and 7 [2-15] vs 10 [4.5-23] p = &amp;lt;0.001 respectively). Conclusion 70% of patients were dissatisfied with their level of leisure time PA. Fatigue and pain were the most commonly reported barriers to PA. Reported barriers differ between patients highlighting the need for personalised exercise programmes for patients with SLE. Disclosure A. Baranskaya: None. A.J. Wadley: None. J. Reynolds: None.

P143 High throughput multiplex assay identifies clinically meaningful clusters in systemic sclerosis patients with low cardiovascular risk and no history of heart disease

Abstract Background/Aims People with systemic sclerosis (SSc) often show subclinical evidence of primary heart involvement (pHI), which when clinically evident, is a prognostic factor of poor outcome. We aimed to profile serum proteins in patients with SSc and no history of pHI and identify clinically meaningful clusters to aid early identification and stratification for pHI. Methods Serum from 78 patients from CONVAS (‘CONnective Tissue Disease and VASculitis Cohort’) and ELCASA (‘ELectrophysiology and CArdiac imaging in SclerodermA’) cohorts [no history of pHI, pulmonary hypertension, diabetes or &amp;gt; 2 traditional cardiovascular (CV) risk factors] was used to measure 355 proteins across inflammation, cardiometabolic and cardiovascular II/III Olink panels. Unsupervised hierarchical clustering using scaled normalised protein expression (NPX) was used to define clusters. Demographic and clinical characteristics were compared between clusters and significant differences reported using Kruskal-Wallis rank sum test for continuous or Pearson’s chi-squared test for categorical variables, at the 5% significance threshold. Results Clinical characteristics of the patient cohorts have been previously published (also summarised in table 1,column 2). Unsupervised hierarchical clustering revealed three patient clusters - C1 [27/78 (35%)], C2 [33/78 (42%)] and C3 [18/78 (23%)] with intermediate, low and high protein expression respectively. C2 patients were younger (median age 51 years) compared to C1 (61 years) and C3 (58 years) (p &amp;lt; 0.001). High expression cluster C3 had a significantly higher proportion of males [7/18 (39%)](p = 0.009), shorter disease duration [median 1.15 years, IQR (0.66 to 7.23)], higher modified Rodnan skin scores (MRSS) [median 5.50, IQR (3.25 to 11)] (p = 0.002) and current disease modifying anti-rheumatic drugs (DMARD) use [16/18 (89%)](p = 0.005). NTproBNP and CRP were elevated in C1 and C3, and high-sensitivity troponin I (hsTnI) was highest in C3[median 6.15 IQR (5.08 to 89.58)](p = 0.002); n = 3 within C1 showed especially high NTproBNP (median 227.50pg/ml) and CRP (median 13mg/dl). No differences in antibody profiles were noted across the three clusters (table 1). Conclusion Differences in serum protein expression identifies clinically meaningful clusters of SSc patients with elevated acute phase and serum cardiac markers despite low CV risk profile. Future work should assess their utility as prognostic biomarkers of SSc-pHI. Disclosure R. Shukla: None. R. Dumitru: Grants/research support; ACORN charity and Charitable Foundation Fellowship, Leeds Teaching Hospital. B. Erhayiem: None. G. Fent: None. F. Del Galdo: Consultancies; Abbvie, AstraZeneca, Boehringer-Ingelheim, Capella, Chemomab, GSK, Janssen, Mitsubishi-Tanabe. S. Plein: Other; funded by a British Heart Foundation Personal Chair. D. Plant: None. M.H. Buch: Consultancies; AbbVie, Arxx Therapeutics, Boehringer Ingelheim, Galapagos, Gilead, and Pfizer (all paid to host institution).

P050 Determining the feasibility of a multi-centre randomised clinical trial to test the effectiveness of integrated symptom tracking for managing rheumatoid arthritis

Abstract Background/Aims In a series of studies, we co-developed and piloted the remote monitoring of rheumatoid arthritis (REMORA) system. REMORA enables patients to daily track symptoms via their smartphone and integrates this data into their electronic health record for discussion during routine clinic visits. This offers the opportunity to make better, and shared, treatment decisions and improve disease management. The effectiveness of integrated daily symptom tracking on clinical and patient-reported outcomes will be tested in a multi-centre stepped wedge randomised clinical trial (RCT). Here, we present the results of the REMORA feasibility study to test trial procedures and intervention delivery. Methods Across two NHS sites in the Northwest of England we aimed to recruit 60 patients, aged ≥18 years with rheumatoid arthritis (RA) or inflammatory arthritis (IA), and access to an Android/iOS smartphone with daily internet access. Participants were asked to complete a baseline web-survey and use the REMORA app to collect daily symptom reports for up to six months. Clinical care teams extracted data from participants’ medical records for all baseline and follow-up appointments, including disease activity scores. To assess feasibility, we reported recruitment rates, participants’ uptake of and adherence to daily symptom tracking, and outcome data completeness. We also compared characteristics of a) those who consented vs. trackers (defined as submitting ≥1 symptom report, i.e., successful intervention uptake), and b) high adherers (symptoms reported on &amp;gt; 60% days) vs. low adherers (symptoms reported on &amp;lt; 25% days). Results A total of 130 patients were screened across study sites, and 52 were eligible and provided consent to take part (40.0%). Of those, 32 (61.5%) initiated symptom tracking; their demographic characteristics were broadly similar to those who consented, though more people of white ethnicity appeared higher in the tracker group (93.8% (95% CI 79.2-99.2) vs 86.5% (74.2-94.4), respectively). Participants completed at least one symptom report on 63.2% of study days (2384/3771 days). We observed few differences between low vs high adherers, though low adherers (n = 6) were younger (median (IQR) years: 41.5 (34.5-55.3)) than the high engagers (n = 20; 61.0 (50.5-65.3)) and had a shorter disease duration (years: 1.0 (0-5.8) vs 3.0 (0.8-10.8)). In total, 48 consented participants had at least one follow-up appointment during the study window; 46 (95.8%) had complete primary outcome data. Conclusion Across two clinical sites, we determined that the procedures and intervention delivery designed for use within a future multi-centre stepped wedge RCT of the REMORA system were feasible for recruitment, adherence to the intervention and completion of the primary outcome. However, uptake of the intervention was lower than we hoped. To enhance intervention uptake in the main trial, we clarified inclusion criteria, improved patient information on what is required to initiate symptom tracking and modified our supporting materials. Disclosure K.L. Druce: None. M. Parkes: None. R. Bravo: None. D. Griffiths-Jones: None. S.N. van der Veer: None. W. Dixon: Consultancies; consultancy fees from Google unrelated to this work. J. McBeth: None.

E059 Identifying the associations between anxiety/depression and disease activity in idiopathic inflammatory myopathy

Abstract Background/Aims Idiopathic inflammatory myopathy (IIM) is characterised by myositis, which can impact activities of daily living. The 2022 BSR IIM management guideline recommends assessing/managing factors associated with poor mental wellbeing and quality of life. Research into anxiety and depression associated with IIM is limited. This study aims to investigate associations between anxiety/depression and IIM disease activity. Methods The MYOPROSP study recruited UK adults with verified IIM throughout a 36 month period between 2016 and 2020. Patient questionnaires were collected at three, six, and 12 months. Participants completed the EQ-5D-5L questionnaire, which includes a question relating to anxiety and depression with five possible responses: “I am (not/slightly/moderately/severely/extremely) anxious or depressed”. The cohort was divided by response to the EQ-5D-5L anxiety/depression question at the time of recruitment. Disease activity was assessed using International Myositis Assessment &amp; Clinical Studies Group (IMACS) Disease Activity Core Set Measures (see Table 1) and summarised across each EQ-5D-5L anxiety/depression group. The EQ-5D-5L visual analogue scale (VAS) relating to “overall health” (higher values correspond to better health) this value was summarised across each EQ-5D-5L anxiety/depression group. Only participants with complete data at recruitment were included in analysis. One-way ANOVA was performed to determine statistical significance (p &amp;lt; 0.05) of each IMACS Disease Activity Core Set Measure and EQ-5D-5L VAS across anxiety/depression groups. Results Complete data on 35 participants (71% female) was collected. All participants reported to have no, slight, or moderate anxiety/depression (i.e. no participant reported severe or extreme anxiety/depression) (Table 1). The “not anxious/depressed” group demonstrated higher EQ-5D VAS values (reflecting better perceived health), shorter disease duration, and higher CK levels, compared to groups with “slight” and “moderate” anxiety/depression. All other investigated variables did not consistently vary across anxiety/depression groups. One-way ANOVA identified that only disease duration and EQ-5D VAS were significantly associated with EQ-5D-5L anxiety/depression group. Conclusion Anxiety and depression are associated with longer disease duration and poorer overall health in adults with IIM. These findings suggest that anxiety/depression in adults with IIM may be due to sustained muscle damage and resulting impacts upon activities of daily living and quality of life, rather than disease activity. Disclosure N.Z. Aziz: None. A. Oldroyd: None. F. Bozan: None. X. Lyu: None. J.A. Lamb: None. P. Gordon: None. D.A. Isenberg: None. N. McHugh: None. H. Gunawardena: None. P. Kiely: None. P.M. Machado: Consultancies; PMM has received consulting/speaker’s fees from Abbvie, BMS, Celgene, Eli Lilly, Janssen, MSD, Novartis, Orphazyme, Pfizer, Roche and UCB. J. Miller: None. S. Tansley: None. A. Bharadwaj: None. R. Laxminarayan: None. N. Jordan: None. C. Yee: None. D. Makkuni: None. J. Taylor: None. P.C. Lanyon: Consultancies; PCL has received consultancy fees from Pfizer. Grants/research support; PCL has received research grants, speaker fees and conference attendance support from CSL Vifor. V.H. Ong: None. A. Prabu: None. M. Akil: None. K.M. Douglas: None. E. Stathopoulou: None. M. Regan: None. H. Chinoy: None.

E072 The psoriatic arthritis disease activity score demonstrates excellent test-retest reliability in early, untreated psoriatic arthritis

Abstract Background/Aims Psoriatic arthritis (PsA) is a chronic inflammatory arthritis characterised by heterogenous clinical features including peripheral arthritis, spondylitis, enthesitis, dactylitis, skin and nail disease. Historically, outcome measures in PsA trials focused on the articular manifestations of disease, with a recent emphasis in composite tools. The Psoriatic Arthritis Disease Activity Score (PASDAS) is a validated, composite measure with defined cut-off and excellent responsiveness when compared with other PsA-specific and non-specific composite measures. Although PASDAS is one of the recommended GRAPPA measures for research trials, data on its test-retest reliability are limited particularly in PsA of short disease duration. Aims and Objectives - To assess the test-retest reliability of the PASDAS composite index in a cohort of early, untreated PsA patients. Methods Data were collected from a subset of participants recruited to the GOLMePsA clinical trial (EudraCT Number: 2013-004122-28), after a minor protocol amendment enabling additional data collection at the screening visit. The test-retest reliability of PASDAS was performed by calculating the intraclass correlation coefficient (ICC) between measurements collected at screening and baseline time-points (maximum 4 weeks apart, by protocol). Table 1 details the sample size calculation. Baseline variables collected in the GOLMePsA trial were described by absolute numbers, percentages, means, medians, absolute and inter-quartile ranges (IQR). Results The PASDAS test-retest reliability was assessed in 37 consecutive participants. Average time between the two time-points was 1.9 weeks (range 0.4 to 4.0). Baseline characteristics of test-retest subset compared to all GOLMePsA participants were similar (table 1). The ICC was 0.85 (95% confidence interval 0.73-0.92). The observed ICC was identical to the value assumed in the sample size calculation for this analysis, yielding an acceptably narrow confidence interval around the estimate. There was no substantial correlation between the means of the two measurements and the differences between them (Pearson’s r=-0.26). The Bland-Altman limits of agreement were -0.11 ± 1.24 (-1.35 to 1.13). Conclusion These results confirm the excellent test-retest reliability of PASDAS in early, untreated PsA, supporting its use as an outcome measure in interventional studies in newly diagnosed disease of short-duration. Disclosure G. De Marco: Consultancies; Janssen, Novartis. E.M.A. Hensor: None. D.G. McGonagle: Consultancies; AbbVie, Celgene, Eli Lilly, Janssen, Merck, Novartis, Pfizer, UCB. Grants/research support; AbbVie, BMS, Celgene, Eli Lilly, Janssen, Merck, Novartis, Pfizer, UCB. A. Tan: None. L.C. Coates: Consultancies; AbbVie, Amgen, Bristol Myers Squibb, Celgene, Eli Lilly, Gilead, Galapagos, Janssen, Moonlake, Novartis, Pfizer and UCB. Honoraria; AbbVie, Amgen, Biogen, Celgene, Eli Lilly, Galapagos, Gilead, GSK, Janssen, Medac, Novartis, Pfizer and UCB. Grants/research support; AbbVie, Amgen, Celgene, Eli Lilly, Janssen, Novartis, Pfizer and UCB. P. Emery: None. P.S. Helliwell: None. H. Marzo Ortega: Consultancies; AbbVie, Celgene, Eli-Lilly, Janssen, Moonlake, Novartis, Pfizer, Takeda and UCB. Grants/research support; Janssen, Novartis and UCB.

Patient trust, quality communication, and medication adherence in rheumatoid arthritis patients highly affected by social determinants of health.

Because medication adherence is essential to the management of rheumatoid arthritis (RA), identifying (1) subgroups at high risk for low medication adherence and (2) modifiable factors potentially contributing to low adherence can impact patient outcomes. This study aims to describe the relationships between anxiety, trust in the provider, quality patient-provider communication, fatigue, RA knowledge, adverse medication effects, disease activity, RA medications, disease duration, patient satisfaction, and medication intolerance and cluster factors to differentiate RA-patient subgroups. This observational study used correlation analysis, linear regression, and cluster analysis with determination decisions based on Schwarz's Bayesian Criterion. Medication adherence was higher in non-Hispanic, White participants, inversely correlated with disease activity and pain intensity, and positively correlated with trust in the provider. Patient satisfaction was higher among those with a shorter time since diagnosis, and was negatively associated with disease activity, pain intensity and interference, fatigue, and anxiety. It was positively associated with RA knowledge, trust in provider and quality of patient-provider communication. Medication intolerance differed by disease duration and was positively correlated with disease activity, pain interference, and fatigue. Of the two clusters, Cluster 1 participants had greater medication adherence and patient satisfaction, and lower medication intolerance. They were of higher income, employed, and non-Hispanic, White persons with a shorter disease duration and lower perceived pain intensity/interference, fatigue, and anxiety. They were more knowledgeable about RA with higher trust in their provider and perceived quality of patient-provider communication. A low medication adherence RA-patient subgroup-highly affected by social determinants of health and with unique relational and clinical characteristics was identified.

Dynamic fluctuations of salivary CGRP levels during migraine attacks: association with clinical variables and phenotypic characterization

BackgroundMigraine is a complex neurological disorder with significant heterogeneity in its clinical presentation and molecular mechanisms. Calcitonin gene-related peptide (CGRP) has emerged as a key player in migraine pathophysiology, but challenges remain in its utilization as a biomarker. This study aimed to investigate salivary CGRP levels during migraine attacks across the frequency spectrum and explore associations with clinical variables.MethodsA prospective longitudinal pilot study was conducted, recruiting migraine patients from an outpatient headache clinic. Salivary CGRP levels were measured at interictal, onset, post-2 h of onset and end-of-attack. Using generalized linear mixed models, we explored the effect of CGRP changes over the attack in presence of depressive symptoms (DS), acute attack treatment, and after three-months of erenumab treatment. Finally, patients were classified and compared according to their CGRP phenotype.ResultsA total of 44 migraine patients were included (90.9% women), with 80 migraine attacks analyzed. Salivary CGRP levels increased at the onset of migraine attacks. We observed statistically significant interactions between DS and both the linear (Est. [SE]: 19.4 [5.8], p = 0.001) and quadratic terms of time (-19.1 [6.0], p = 0.002). Additionally, a significant three-way interaction within the use of acute treated attack (linear-term: -18.5 [6.2], p = 0.005; quadratic-term: 19.2 [6.8], p = 0.005) was also found. Molecular phenotyping revealed that 72.7% (32/44) of patients presented only CGRP-dependent attacks, while 27.3% (12/44) presented non-CGRP-dependent migraine attacks. Patients with only CGRP-dependent attacks were associated with younger age, shorter disease evolution time, a higher proportion of aura, and fewer monthly headache days (p < 0.05). Exploratory analysis of erenumab treatment effects did not result in changes in CGRP levels during migraine attacks.ConclusionsOur study underscores the dynamic nature of migraine at a molecular level and emphasizes the importance of integrating clinical variables, such as depressive symptoms, in understanding its pathophysiology. The identification of distinct migraine subtypes based on CGRP dependence suggests potential opportunities for personalized treatment approaches.

Serum levels of AGGF1: Potential association with cutaneous and cardiopulmonary involvements in systemic sclerosis.

Systemic sclerosis (SSc) is an autoimmune disease characterized by vasculopathy, aberrant immune activation, and extensive tissue fibrosis of the skin and internal organs. Because of the complicated nature of its pathogenesis, the underlying mechanisms of SSc remain incompletely understood. Angiogenic factor with a G-patch domain and a Forkhead-associated domain 1 (AGGF1) is a critical factor in angiogenesis expressed on vascular endothelial cells, associated with inflammatory and fibrotic responses. To elucidate the possible implication of AGGF1 in SSc pathogenesis, we investigated the association between serum AGGF1 levels and clinical manifestations in SSc patients. We conducted a cross-sectional analysis of AGGF1 levels in sera from 60 SSc patients and 19 healthy controls with enzyme-linked immunosorbent assay. Serum AGGF1 levels in SSc patients were significantly higher than those in healthy individuals. In particular, diffuse cutaneous SSc patients with shorter disease duration had higher levels compared to those with longer disease duration and limited cutaneous SSc patients. Patients with higher serum AGGF1 levels had a higher incidence of digital ulcers, higher modified Rodnan Skin Scores (mRSS), elevated serum Krebs von den Lungen-6 (KL-6) levels, C-reactive protein levels, and right ventricular systolic pressures (RVSP) on the echocardiogram, whereas they had reduced percentage of vital capacity (%VC) and percentage of diffusing capacity of the lungs for carbon monoxide (%DLCO) in pulmonary functional tests. In line, serum AGGF1 levels were significantly correlated with mRSS, serum KL-6 and surfactant protein D levels, RVSP, and %DLCO. These results uncovered notable correlations between serum AGGF1 levels and key cutaneous and vascular involvements in SSc, suggesting potential roles of AGGF1 in SSc pathogenesis.

Sensorimotor Network Segregation Predicts Long-Term Learning of Writing Skills in Parkinson's Disease.

The prediction of motor learning in Parkinson's disease (PD) is vastly understudied. Here, we investigated which clinical and neural factors predict better long-term gains after an intensive 6-week motor learning program to ameliorate micrographia. We computed a composite score of learning through principal component analysis, reflecting better writing accuracy on a tablet in single and dual task conditions. Three endpoints were studied-acquisition (pre- to post-training), retention (post-training to 6-week follow-up), and overall learning (acquisition plus retention). Baseline writing, clinical characteristics, as well as resting-state network segregation were used as predictors. We included 28 patients with PD (13 freezers and 15 non-freezers), with an average disease duration of 7 (±3.9) years. We found that worse baseline writing accuracy predicted larger gains for acquisition and overall learning. After correcting for baseline writing accuracy, we found female sex to predict better acquisition, and shorter disease duration to help retention. Additionally, absence of FOG, less severe motor symptoms, female sex, better unimanual dexterity, and better sensorimotor network segregation impacted overall learning positively. Importantly, three factors were retained in a multivariable model predicting overall learning, namely baseline accuracy, female sex, and sensorimotor network segregation. Besides the room to improve and female sex, sensorimotor network segregation seems to be a valuable measure to predict long-term motor learning potential in PD.

Correlation between Clinical and Audiological Factors with Ossicular Chain Continuity in Chronic Otitis Media

Introduction: Chronic otitis media (COM) with the perforation of the tympanic membrane, myringoplasty is preferred treatment, but if ossicles are involved, myringoplasty is done with ossiculoplasty which is termed as tympanoplasty. Preoperative assessment of ossicular status is important to decide the type of tympanoplasty. Ossicular chain continuity is generally seen in the patient who has short duration of disease and smaller air–bone gap. Our study was conducted to support the relationship between preoperative clinical, audiological, and other factors in relation to the ossicular chain status. Materials and Methods: This was a prospective, cross-sectional study conducted at a tertiary care center, for 2-year duration (November 2019 to November 2021), on 100 patients who presented with COM (mucosal type). Preoperative diagnosis and assessment based on the clinical examination and investigations were compared with operative findings. Results: Thirty percent of the patients had ear discharge duration &lt;1 year, 28% had 1–5 years, and 18% patients had 6–10-year duration. Hearing loss was present in 80% of the cases. Correlation of pure-tone average (PTA) with ossicular chain status was significant with P = 0.028. The majority of patients were in the moderate category 31% and 19.36% of patients had ossicular chain defect. The second common category was mild hearing loss (24%), of which 4.17% of patients showed ossicular chain defect. Conclusion: Maximum percentages of patients with severe hearing loss had ossicular chain discontinuity followed by profound hearing loss. Most of cases had moderate to moderately severe conductive hearing loss in PTA. As the air–bone gap increases, the possibility of ossicular discontinuity increases.

ПРОГНОЗИРОВАНИЕ ПРОГРЕССИРОВАНИЯ ИНТЕРСТИЦИАЛЬНОГО ЗАБОЛЕВАНИЯ ЛЁГКИХ У ПАЦИЕНТОВ С СИСТЕМНОЙ СКЛЕРОДЕРМИЕЙ: АНАЛИЗ ДАННЫХ КОГОРТНОГО ИССЛЕДОВАНИЯ

Introduction. Systemic sclerosis (scleroderma) is an autoimmune disease that often causes inflammatory fibrosing lesions of the pulmonary interstitial tissue, referred to as interstitial lung disease. It is associated with a significant reduction in survival and is the leading immediate cause of the systemic scleroderma patients’ death. Progression rate of interstitial lung disease varies greatly. Since the specific immunosuppressive and antifibrotic treatment is only justified in case of progressive lesions, predicting the interstitial lung disease progression is of great practical importance. Aim: To develop approaches to predicting the progression of interstitial lung disease in systemic scleroderma patients. Materials and Methods. Our analysis included the data of patients observed in the Registry of Myositis, Systemic Scleroderma and Mixed Diseases (REMISSiZ). Inclusion criteria: Age 18+ years, the proven case of systemic scleroderma, eligibility for ACR/EULAR (2013), and the repeated high-resolution computed tomography of lungs with an interval of at least 1 year. All patients underwent 6-minute walking tests. Results and Discussion. The study included 44 patients (43 women) aged 62.9 ± 11.5 years in average. The average follow-up duration was 530 ± 231 days. Radiological progression was associated with younger age, p=0.03, severity of Raynaud’s phenomenon, p=0.032, shorter disease duration, p=0.038, and shorter distance covered in the 6-minute walk test, p=0.05. The progression of functional impairment, determined by the dynamics of the distance covered in the 6-minute walk test, was associated with a decrease in blood oxygen saturation at rest (p=0.003), the severity of breath shortness according to the Borg scale (p=0.006), the initial distance of the 6-minute walk test (p &lt;0.001), the presence of topoisomerase I antibodies (anti-Scl-70, p=0.034), and complaints of breath shortness (p=0.043) and dysphagia (p=0.034). As a result of reverse stepwise selection of variables, three independent significant predictors were selected from the above indicators: Dysphagia, anti-Scl-70, and the initial walking distance in the 6-minute walk test. Based on these indicators, a regression formula is presented for predicting the progression of functional impairment in systemic scleroderma patients. Conclusions. X-ray-detected progression of interstitial lung disease in systemic sclerosis patients is associated with younger age and Raynaud’s phenomenon severity. To predict the decline in the systemic sclerosis patients’ functionality, it is advisable to consider the presence of dysphagia and topoisomerase I antibodies (anti-Scl-70).