Years Of Disease Onset Research Articles

Risk Factors of Relapse in Nephrotic Syndrome

Background: Nephrotic syndrome (NS) is a kidney disease with high incidence, typically in young children. NS is a disease of relapse, and it is a major problem to manage the cases with relapse. So, it is very important to find out such children who are prone to develop relapse. Hence, this study was carried out to find out the risk factors of relapse in children with NS. Objective: To determine the risk factors of relapse in patients with nephrotic syndrome. Methods: This case-control study was conducted at the Department of Paediatric Nephrology and Department of Paediatrics, Dhaka Medical College Hospital, for 12- months following ethical approval. A total of 100 NS children (age: 2-12 years) were enrolled in this study, among them 50 were cases (NS with relapse) and 50 were controls (initial attack of NS with no relapse within one year of disease onset). After obtaining written informed consent from parents/legal guardian, a detailed history, thorough clinical examination and necessary investigations were carried out in each patient during initial episode of NS. Data analysis was done by SPSS 26.0. Results: Mean age of the cases and controls was6.11±3.01years and 6.96±3.14years, respectively (p=0.169), with an overall boys-girl ration of 1.3:1. Maximum cases (56.0%) had infrequent relapse. Lower age of onset was prevalent among case group than control (31.96±15.15 months vs 46.48±27.76 months; p=0.002). Infection was significantly more prevalent among cases than controls (68.0% vs 38.0%; OR=3.46; p=0.003), UTI (38.0% vs 10.0%; OR; 5.52; p=0.001). Cases had significantly higher history of atopy (52.0% vs 30.0%; OR=2.53; p=0.025). Higher serum cholesterol (441.62±61.46 mg/dL vs 389.12±72.18 mg/dL; <0.001) and lower serum albumin (15.74±2.20 gm/L vs 17.30±2.99 gm/L; p=0.004) were seen in cases than control. Conclusion: Lower age of onset, history of atopy, infection, higher serum cholesterol and lower serum albumin level during initial attack were associated .......

Distinct plasma lipids predict axonal injury and multiple sclerosis activity

BackgroundLipids are of particular interest for the study of neuroinjury and neuroinflammation as structural lipids are major components of myelin, and a variety of lipid species modulate inflammation. In this...

Long-Term Outcomes of Living Donor Liver Transplantation for Methylmalonic Acidemia.

Despite early diagnosis and medical interventions, patients with methylmalonic acidemia (MMA) suffer from multi-organ damage and recurrent metabolic decompensations. We conducted the largest retrospective multi-center cohort study so far, involving five transplant centers (NCCHD, KUH, KUHP, ATAK, and EMC), and identified all MMA patients (n = 38) undergoing LDLT in the past two decades. Our primary outcome was patient survival, and secondary outcomes included death-censored graft survival and posttransplant complications. The overall 10-year patient survival and death-censored graft survival rates were 92% and 97%, respectively. Patients who underwent LDLT within 2 years of MMA onset showed significantly higher 10-year patient survival compared to those with an interval more than 2 years (100% vs. 81%, p = 0.038), although the death-censored graft survival were not statistically different (100% vs. 93%, p = 0.22). Over the long-term follow-up, 14 patients (37%) experienced intellectual disability, while two patients developed neurological complications, three patients experienced renal dysfunction, and one patient had biliary anastomotic stricture. The MMA level significantly decreased from 2218.5 mmol/L preoperative to 307.5 mmol/L postoperative (p = 0.038). LDLT achieves favorable long-term patient and graft survival outcomes for MMA patients. While not resulting in complete cure, our findings support the consideration of early LDLT within 2 years of disease onset. This approach holds the potential to mitigate recurrent metabolic decompensations, and preserve the long-term renal function.

Investigating the trajectory of functional disability in systemic sclerosis: group-based trajectory modelling of the Health Assessment Questionnaire-Disability Index.

To identify the trajectories and clinical associations of functional disability in systemic sclerosis (SSc). Australian Scleroderma Cohort Study (ASCS) participants meeting ACR/EULAR criteria for SSc recruited within 5 years of disease onset, with ≥2 Health Assessment Questionnaire-Disability Index (HAQ-DI) scores were included. Group based trajectory modelling (GBTM) was used to identify the number and shape of HAQ-DI trajectories. Between group comparisons were made using the chi-squared test, two-sample t-test or Wilcoxon rank-sum test as appropriate. Multiple logistic regression was used to identify features associated with trajectory group membership. Survival analyses were performed using Kaplan Meier and Cox proportional hazard modelling. We identified two HAQ-DI trajectory groups within 426 ASCS participants with incident SSc: low-stable disability (n=221, 52%), and high-increasing disability (n=205, 48%). Participants with high-increasing disability were older at disease onset, more likely to have diffuse SSc (dcSSc), cardiopulmonary disease, multimorbidity, digital ulcers, and gastrointestinal involvement (all p≤0.01), as was use of immunosuppression (p<0.01). Multimorbidity was associated with high-increasing trajectory group membership (OR3.1, 95%CI1.1-8.8, p=0.04); independently, multiple SSc features were also strongly associated including dcSSc (OR2.3, 95%CI1.3-4.2, p<0.01), proximal weakness (OR7.3, 95%CI2.0-27.1, p<0.01) and joint contractures (OR2.7, 95%CI1.3-5.3, p<0.01). High-increasing physical disability was associated with an almost two-fold increased risk of mortality (HR1.9, 95%CI1.0-3.8, p=0.05), and higher symptom burden. Two trajectories of functional disability in SSc were identified. Those with high-increasing functional disability had a distinct clinical phenotype and worse survival compared to those with low-stable functional disability. These data highlight the pervasive nature of physical disability in SSc, and its prognostic importance.

The burden and determinants of fatigue in incident and prevalent systemic sclerosis.

To investigate the burden and clinical associations of fatigue in systemic sclerosis (SSc) as measured by FACIT-Fatigue scores. Australian Scleroderma Cohort Study participants with ≥1 FACIT-Fatigue score were included. Participants were divided into those with incident SSc (≤5 years SSc duration at recruitment and FACIT-Fatigue score recorded within 5 years of disease onset) or prevalent SSc (first FACIT-Fatigue score recorded >5 years after SSc onset). Generalised estimating equations were used to model change in FACIT-Fatigue scores over time, expressed as an increasing (improving) or decreasing (worsening) score. Of 859 participants, 215 had incident SSc and 644 prevalent SSc. First-recorded FACIT-Fatigue scores were similar in those with incident (37 units, IQR 25-45.5) and prevalent SSc (36 units, IQR 23-44; p=0.17), as were lowest-ever recorded FACIT-Fatigue scores (incident 23 units; prevalent 22 units, p=0.75). In incident SSc, higher skin scores (regression coefficient (RC) -1.5 units, 95%CI -2.3 to -0.8), PAH (RC -8.2, 95%CI -16.5 to 0.1) and reduced left ventricular function (RC -10.6, 95%CI -18.3 to -2.8) were associated with more severe fatigue. In prevalent SSc, higher skin scores (RC -0.6, 95%CI -1.3 to 0), gastrointestinal symptoms (RC -6.6, 95%CI -9.0 to -4.2), hypoalbuminaemia (RC -2.8, 95%CI -5.0 to -0.7), BMI<18.5kg/m2 (RC -6.3, 95%CI -10.3 to -2.2), raised CRP (RC -3.1, 95%CI -4.7 to -1.5), and anaemia (RC -1.7, 95%CI -3.5 to 0.1) were associated with more severe fatigue. The burden of fatigue is substantial in both incident and prevalent SSc. Cardiopulmonary and gastrointestinal involvement are associated with worse fatigue.

What Medical Specialties do ME/CFS Sufferers Consult? A Public Health Study on the need for Better Medical Education and Training

The disease ME/CFS is unknown to many doctors in Germany. Within the healthcare system, significant deficits in dealing with ME/CFS patients have been repeatedly revealed. Hence, the aim of the present study was to identify the specialties of the doctors consulted by ME/CFS patients and to find out whether information on the medical procedure in the context of the diagnosis process can be derived from this. As part of the APAV-ME/CFS survey, the quantitative responses of 674 adult ME/CFS sufferers (>20 y.; 554 ♀, 120 ♂) who already had a medical ME/CFS diagnosis were statistically examined. The sampling was done by self-activation and via the snowball principle. The data were primarily evaluated descriptively. An analysis of variance was carried out to consider possible relationships. Almost a quarter of the patients said they had suffered from ME/CFS for 6 to 10 years. Diagnosis was made within 10 years of disease onset in 62%. For 6.4% it took 21-40 years. 75% of the participants consulted 6 to 15 different doctors from a wide range of disciplines in the course of the disease, in particular from general medicine, neurology, internal medicine and psychosomatics/psychiatry. Diagnosis was made in particular by GPs and immunologists. On average, the test persons named 11 mostly neuroregulatory symptoms. The results suggest that in the context of finding a diagnosis in Germany for ME/CFS, referral behaviour to specialists based on single ME/CFS symptoms or rather arbitrary contacting of doctors from a wide variety of disciplines has prevailed so far. Therefore, training and further education measures on the subject of ME/CFS are urgently needed in all specialist disciplines in the resident, inpatient and rehabilitation sectors.

Lipoprotein glomerulopathy with markedly increased arterial stiffness successfully treated with a combination of fenofibrate and losartan: a case report

BackgroundLipoprotein glomerulopathy (LPG) is a apolipoprotein E (ApoE)-related glomerular disease and has been associated with type III hyperlipidemia. Without appropriate treatment, chronic kidney disease (CKD) caused by LPG progresses, and approximately half of the patients develop end-stage kidney disease within 1–27 years of disease onset. However, few studies have highlighted the clinical course of cardiovascular diseases (CVDs) in patients with LPG. Herein, we report the first case of LPG in which the CVD risk was assessed using arterial stiffness.Case presentationA 32-year-old Japanese man was referred to our hospital due to persistent proteinuria. Kidney biopsy showed markedly dilated capillary lumens containing pale-stained thrombi, which stained positively with Oil Red O. Electron microscopy revealed the presence of thrombi in the capillary lumen with low electron density and vacuoles of various sizes in part of the thrombi. Toluidine blue and Sudan IV stains were used to stain the thin sections of Epon-embedded tissue samples for electron microscopy. Sudan IV-positive droplets were observed in the capillary lumens, vascular walls, and cytoplasm of tubular cells. Increased serum ApoE concentration was observed. Liquid chromatography-tandem mass spectrometry of laser-microdissected glomeruli from paraffin sections revealed an increase in ApoE. Direct deoxyribonucleic acid sequencing of ApoE revealed a heterozygous ApoE Sendai mutation (Arg145Pro). The patient was finally diagnosed with LPG with heterozygosity for ApoE-Sendai mutation (Arg145Pro). Notably, at the time of diagnosis, he had markedly increased arterial stiffness for his age. Arterial stiffness was measured using brachial-ankle pulse wave velocity (baPWV), which was equivalent to that of a 56-year-old man. After three months of treatment with fenofibrate and losartan, a significant reduction in proteinuria was achieved along with an improvement in baPWV. Furthermore, these effects were maintained despite the lack of decrease in serum ApoE levels.ConclusionHerein, we report the case of a patient with LPG with markedly increased arterial stiffness at the time of diagnosis, in whom combination therapy with fenofibrate and losartan successfully improved proteinuria and arterial stiffness. To the best of our knowledge, this is the first case report of LPG in which CVD risk was assessed using arterial stiffness.

P148 CCN3-derived peptides as anti-fibrotic therapies for systemic sclerosis

Abstract Background/Aims Effective therapy for skin fibrosis in scleroderma (systemic sclerosis: SSc) remains an unmet clinical challenge. Persistently activated M2 macrophages are believed to stimulate myofibroblasts in the disease microenvironment creating a pro-fibrotic niche in the skin. Expression of the anti-fibrotic matricellular protein CCN3 is reduced in animal models of fibrosis. We have identified a small peptide based on an amino acid sequence in CCN3, BLR-200, which mimics the anti-fibrotic activity of CCN3, and propose that BLR-200 could be used to treat patients in whom lack of CCN3 activity is permissive for fibrosis. However, whether there is lack of CCN3 activity in SSc and whether BLR-200 has effective anti-fibrotic activity in SSc are unknown. Methods We used ELISAs (R&amp;D Systems) to detect CCN3 and the M2 macrophage marker CD206 in the serum of scleroderma patients with early stage diffuse subset disease (within two years of disease onset), those with late-stage diffuse subset disease (over five years duration) as well as healthy controls (all n = 20). The bleomycin-induced mouse model of skin scleroderma, in which bleomycin is injected subcutaneously every day for 21 days, was used to assess the antifibrotic ability of BLR200 in vivo. Results In scleroderma serum, CCN3 was significantly reduced, relative to matched healthy controls and patients with inactive disease, in early onset scleroderma patients with active disease that show elevated CD206 levels (p &amp;lt; 0.01). In the mouse model of human SSc, compared to injection with a scrambled control peptide and relative to control mice treated with phosphate buffered saline, injection with BLR-200 prevented bleomycin-induced changes in collagen deposition, myofibroblast differentiation and skin thickness as measured by Trichrome stain, indirect immunofluorescence analysis with an anti-a-smooth muscle actin antibody, and morphometric analysis, respectively (N = 8 mice per group, p &amp;lt; 0.05). Similarly, RNA sequencing and real-time polymerase chain reaction analysis revealed that BLR-200 significantly impaired the ability of bleomycin to induce expression of fibrogenic genes such as: integrin alpha 11, CCN2, CCN1, Smad3, wnt4, YAP1 and tenascin-C (all N = 5, p &amp;lt; 0.05). Spatial transcriptomics analysis revealed that BLR-200 impaired bleomycin-induced alterations in skin cell populations, including the activation and expansion of epithelial and reticular fibroblast niches and the induction of Wnt, hippo, focal adhesion and actin cytoskeleton gene expression cluster, all of which are known to be activators of fibrosis and myofibroblast activation and persistence. Conclusion CCN3 expression is reduced in serum of scleroderma patients with active skin disease that show M2 macrophage activation as visualized by elevated CD206 levels. Since BLR-200 has antifibrotic activity in the bleomycin model of skin scleroderma, our data are consistent with the hypothesis that BLR-200 could be used to block fibrosis progression in early onset diffuse scleroderma patients who possess both low CCN3 and high CD206 in serum. Disclosure J. Nguyen: None. K. Zestranjyan: None. S. Xu: None. B.L. Riser: Corporate appointments; CEO of BLR Bio. R.J. Stratton: None. A. Leask: None.

Change in systemic steroid use and surgery rate in patients with inflammatory bowel disease: a Japanese real-world database analysis

BackgroundCorticosteroids are recommended only for induction of remission in inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn’s disease (CD). This study aimed to evaluate the change in pharmacologic treatment use, particularly systemic corticosteroids, over approximately 30 years, and the impact of biologics on IBD treatment since their appearance in the 2000s.MethodsThis retrospective study conducted in Japan used data from the Phoenix cohort database (January 1990 to March 2021). Patients with disease onset at age ≥ 10 years who received treatment for UC or CD between January 1990 and March 2021 were included. Outcome measures were change in IBD treatments used, total cumulative corticosteroid doses, initial corticosteroid dose, duration of corticosteroid treatment, and surgery rate.ResultsA total of 1066 and 579 patients with UC and CD, respectively, were included. In UC, the rate of corticosteroid use as initial treatment was relatively stable regardless of the year of disease onset; however, in CD, its rate decreased in patients who had disease onset after 2006 (before 2006: 14.3–27.8% vs. after 2006: 6.6–10.5%). Compared with patients with disease onset before biologics became available, cumulative corticosteroid doses in both UC and CD, and the surgery rate in CD only, were lower in those with disease onset after biologics became available.ConclusionsSince biologics became available, corticosteroid use appears to have decreased, with more appropriate use. Furthermore, use of biologics may reduce surgery rates, particularly in patients with CD. UMIN Clinical Trials Registry; UMIN000035384.

Phenotypic spectrum of inclusion body myositis.

Inclusion body myositis (IBM) is a progressive, debilitating muscle disease commonly encountered in patients over the age of 50. IBM typically presents with asymmetric, painless, progressive weakness and atrophy of deep finger flexors and/or quadriceps muscle. Many patients with IBM develop dysphagia. However, atypical presentations of IBM with isolated dysphagia, asymptomatic hyper-CKemia, foot drop, proximal weakness, axial weakness, and facial diplegia have been reported. Other acquired and some inherited disorders may present similar to IBM, and this list gets more expansive when considering atypical presentations. In general, disease progression of IBM leads to loss of hand function and impaired ambulation, and most IBM patients become wheelchair dependent within 13-15 years of disease onset. Hence, IBM impacts negatively patients' quality of life and reduces longevity compared to the general population. Acknowledging the complete clinical spectrum of IBM presentation and excluding mimics would shorten the time to diagnosis, lead to prompt initiation of supportive management and avoid unproven therapy. Ongoing advanced phase studies in IBM provide hope that a therapy may soon be available. Therefore, an added potential benefit of early diagnosis would be prompt initiation of disease-modifying therapy once available.

P550 Short and long-term outcomes after acute severe ulcerative colitis in adults: A 12 year Canadian experience in the post biologic era

Abstract Background Patients with acute severe ulcerative colitis (ASUC) are at increased risk of colectomy following an episode of acute severe exacerbation. Medical rescue therapy in steroid non-responders has reduced the need for emergency colectomy. However, impact of biologics on longer-term colectomy risk is unclear. Methods A retrospective cohort study of adult patients aged ≥18 years hospitalized with acute exacerbation of UC requiring hospitalization and managed with intravenous corticosteroids between 2010 and 2022 at two regional hospitals in London, Ontario, Canada. Steroid non-response was defined as requirement of medical rescue therapy or colectomy. Results A total of 264 adults hospitalized with ASUC were included in the analysis (male: 51.1% [n=136], mean age at admission: 40.8±17.8 years). The majority had extensive colitis (71.3% [n=169]) at the time of diagnosis. 46.3% (n=118/255) presented within one year of disease onset and 23% (n=61) had ASUC as their first presentation with UC. 25.7% (n=66/257) of patients had prior purine analogues and 23.3% (60/257) had previous biologics prior to ASUC presentation. After admission, 55.7% (n=147) responded to intravenous corticosteroids. Of the steroid non-responders, 37.5% (n=99) patients were managed with infliximab rescue therapy and only one patient received tofacitinib rescue therapy. Median CRP, stool frequency and Lindgren index score were statistically significant between steroid responders and non-responders (Table 1). A higher proportion of steroid non-responders had prior exposure to biologics or tofacitinib compared to steroid responders (31.9% vs 16.3%, p&amp;lt;0.01). On multivariate analysis for various factors predicting steroid non-response, assessment by Oxford criteria on day 3 was the only factor that was statistically significant (odds ratio 4.70 (95% CI 1.06-20.8), p = 0.04). Oxford criteria on day 3 had a sensitivity, specificity of 58.6% and70.8%, respectively for predicting steroid non-response. 8% (n=21) required colectomy during index admission. An additional 13% (n = 32) underwent colectomy within 12 months of discharge, for which there was no difference between steroid responders and non-responders (12.2% vs 14.7%). The short term (3 months following discharge) and long-term (3-12 months following discharge) colectomy rates following discharge were 8% (20/245) and 5.4% (12/223) respectively. Hospitalization with UC exacerbation rate following discharge was 17% (38/223). Conclusion 8% of patients admitted for ASUC require colectomy during the same admission and additional 13% required colectomy within 12 months of discharge. Despite a high initial response to corticosteroids, long term colectomy rates and re-hospitalization rates remain high.

Management of LHON ‐ An update

Leber hereditary optic neuropathy (LHON) is a devastating cause of blindness that predominantly affects young adult men. Over 90% of patients harbour one of three mitochondrial DNA point mutations, namely, m.3460G&gt;A (MT‐ND1), m.11778G&gt;A (MT‐ND4) and m.144484T&gt;C (MT‐ND6). Idebenone is the only approved treatment for LHON. New evidence has refined the management guidelines for idebenone, in particular the duration of treatment and the therapeutic window of opportunity. Gene therapy using allotopic expression is an attractive strategy for LHON as it corrects the underlying mitochondrial DNA defect. Promising results have been obtained for the m.1178G&gt;A (MT‐ND4) mutation for patients treated within 1 year of disease onset with an intravitreal injection of a modified adeno‐associated viral vector carrying the replacement gene.

Severity of white matter microstructural damage in a Brazilian relapsing-remitting multiple sclerosis cohort: A possible window to optimize treatment.

Multiple sclerosis (MS) is an important cause of acquired neurological disability in young adults, characterized by multicentric inflammation, demyelination, and axonal damage. The objective is to investigate white matter (WM) damage progression in a Brazilian MS patient cohort, using diffusion tensor imaging (DTI) post-processed by tract-based spatial statistics (TBSS). DTI scans were acquired from 76 MS patients and 37 sex-and-age matched controls. Patients were divided into three groups based on disease duration. DTI was performed along 30 non-collinear directions by using a 1.5T imager. For TBSS analysis, the WM skeleton was created, and a 5000 permutation-based inference with a threshold of p < .05 was used, to enable the identification of abnormalities in fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity (AD). Decreased FA and increased RD, MD, and AD were seen in patients compared to controls and a decreased FA and increased MD and RD were seen, predominantly after the first 5years of disease, when compared between groups. Progressive WM deterioration is seen over time with a more prominent pattern after 5years of disease onset, providing evidence that the early years might be a window to optimize treatment and prevent disability.

Dysregulation of humoral immunity, iron homeostasis, and lipid metabolism is associated with multiple sclerosis progression

BackgroundThough most patients with multiple sclerosis (MS) presented earlier on as a relapsing-remitting (RR) disease, disability progression eventually occurred. Uncovering the mechanisms underlying progression may facilitate the unmet need for developing therapies to prevent progression. Benign MS (BMS), a rare form of MS, is the opposite from secondary progressive MS (SPMS) in that it lacks disease progression defined as Expanded Disability Status Scale (EDSS) ≤3 after at least 15 years of disease onset. BMS is characterized by rare and mild relapses with complete remission of clinical symptoms (lower activity of the disease) and lack of progression. Our study aims to identify transcriptomic and immunological differences between BMS and SPMS to unravel the pathogenesis of disease progression. MethodsWe took multi-modal approaches with microarrays, flow cytometry, and lipidomics by three-way comparisons of patients with BMS vs. RRMS (low disease activity vs. moderate or severe activity), RRMS vs. SPMS (continued activity vs. complete transformation into progressive phase) as well as BMS vs. SPMS, matched for age and disease-duration (low disease activity and no progression vs. progression with or without activity). ResultsWe found that patients with RRMS and SPMS have a significantly higher percentage of B cells than those with BMS. BMS shows a different transcriptomic profile than SPMS. Many of the differentially expressed genes (DEGs) are involved in B cell-mediated immune responses. Additionally, long-chain fatty acids (LCFA), which can act as inflammatory mediators, are also altered in SPMS. Overall, our data suggest a role for the dysregulation of B cell differentiation and function, humoral immunity, and iron and lipid homeostasis in the pathogenesis of MS disease progression. ConclusionBMS has a unique transcriptomic and immunological profile compared to RRMS and SPMS. These differences will allow for personalized precision medicine and may ultimately lead to the discovery of new therapeutic targets for disease progression.

Influence of the timing of biological treatment initiation on Juvenile Idiopathic Arthritis long-term outcomes

BackgroundJuvenile idiopathic arthritis (JIA) treatment is aimed at inducing remission to prevent joint destruction and disability. However, it is unclear what is the long-term impact on health-related outcomes of the timing of biological disease-modifying antirheumatic drug (bDMARD) initiation in JIA. Our aim was to evaluate the long-term impact of the time between JIA onset and the initiation of a bDMARD in achieving clinical remission, on physical disability and health-related quality of life (HRQoL).MethodsAdult JIA patients registered in the Rheumatic Diseases Portuguese Register (Reuma.pt) and ever treated with bDMARD were included. Data regarding socio-demographic, JIA-related characteristics, disease activity, physical disability (HAQ-DI), HRQoL (SF-36), and treatments were collected at the last visit. Patients were divided into 3 groups (≤ 2 years, 2–5 years, or > 5 years), according to the time from disease onset to bDMARD initiation. Regression models were obtained considering remission on/off medication, HAQ-DI, SF-36, and joint surgeries as outcomes and time from disease onset to bDMARD start as an independent variable.ResultsThree hundred sixty-one adult JIA patients were evaluated, with a median disease duration of 20.3 years (IQR 12.1; 30.2). 40.4% had active disease, 35.1% were in remission on medication, and 24.4% were in drug-free remission; 71% reported some degree of physical disability. Starting a bDMARD > 5 years after disease onset decreased the chance of achieving remission off medication (OR 0.24; 95% CI 0.06, 0.92; p = 0.038). Patients who started a bDMARD after 5 years of disease onset had a higher HAQ and worse scores in the physical component, vitality, and social function domains of SF-36, and more joint surgeries when compared to an earlier start.ConclusionLater initiation of bDMARDs in JIA is associated with a greater physical disability, worse HRQoL, and lower chance of drug-free remission in adulthood.

Application of the Chinese Expert Consensus on Diabetes Classification in clinical practice

Objective: To evaluate the diagnostic for classification of newly diagnosed diabetes patients and assess the application of the screening tests recommended by the 2022 Chinese Expert Consensus on Diabetes Classification. Methods: Retrospective case series study. The data from the electronic medical record system of patients with new-onset diabetes mellitus (within 1 year of disease onset) who attending the Diabetes Specialist Outpatient Clinic at the Second Xiangya Hospital of Central South University from January 1, 2018 to December 31, 2021 were collected for the analysis. Based on the consensus, patients were categorized according their age of onset, body mass index (BMI), and suspicion of type 1 diabetes mellitus (T1DM). The chi-square statistic was used to compare key classifier indicators, including C-peptide, islet autoantibodies, and genetic markers, in the subgroups. The diagnosis in suspected T1DM patients was also evaluated. The screening strategy recommended in the consensus was further assessed using a logistic regression model and the area under the receiver-operating curve (AUC). Results: A total of 3 384 patients with new-onset diabetes were included. The average age of disease onset was (46.3±13.9) years, and 61.0% (2 065/3 384) of the patients were male. The proportions of patients who completed C-peptide and glutamic acid decarboxylase antibody (GADA) tests were 36.6% (1 238/3 384) and 37.5% (1 269/3 384), respectively. There were no significant differences in C-peptide test results among the subgroups (all P>0.05). In contrast, the GADA detection rate was higher in patients with young age of onset (<30 years old), in those who were non-obese (BMI<24 kg/m2), and in those clinically suspected of T1DM (all P<0.05). According to the diagnostic pathway proposed by the consensus, only 57.4% (1 941/3 384) of patients could be subtyped. For a definitive diagnosis, the remaining patients needed completion of C-peptide, islet autoantibody, genetic testing, or follow-up. Furthermore, among patients with clinical features of suspected T1DM, the antibody positivity rate was higher than in non-suspected T1DM patients [24.5% (154/628) vs. 7.1% (46/646), P<0.001]. When the clinical features of suspected T1DM defined in the consensus were taken as independent variables and antibody positivity was considered the outcome variable in the logistic regression model, young onset, non-obese onset, and ketosis onset could enter the model. Based on AUC analysis, the accuracy of the diagnostic model was 0.77 (95%CI 0.73-0.81), suggesting that the clinical features of suspected T1DM in the consensus have good clinical diagnostic value for this patient subgroup. Conclusions: There was a significant discrepancy between the clinical practice of diabetes classification and the process recommended by the consensus, which was specifically reflected in the low proportions of both subtyping indicator testing and definitively subtyped diabetes patients. Attention should be pay to the classification diagnosis process proposed in the consensus and the clinical detection rate of key diabetes subtyping indicators such as C-peptide and islet autoantibodies for diabetes classification should be improved. Noteworthy, the screening strategy for T1DM proposed by the consensus showed good clinical application value.

Cerebrospinal fluid camk2a levels at baseline predict long-term progression in multiple sclerosis

BackgroundMultiple sclerosis (MS) remains a highly unpredictable disease. Many hope that fluid biomarkers may contribute to better stratification of disease, aiding the personalisation of treatment decisions, ultimately improving patient outcomes.ObjectiveThe objective of this study was to evaluate the predictive value of CSF brain-specific proteins from early in the disease course of MS on long term clinical outcomes.MethodsIn this study, 34 MS patients had their CSF collected and stored within 5 years of disease onset and were then followed clinically for at least 15 years. CSF concentrations of 64 brain-specific proteins were analyzed in the 34 patient CSF, as well as 19 age and sex-matched controls, using a targeted liquid-chromatography tandem mass spectrometry approach.ResultsWe identified six CSF brain-specific proteins that significantly differentiated MS from controls (p < 0.05) and nine proteins that could predict disease course over the next decade. CAMK2A emerged as a biomarker candidate that could discriminate between MS and controls and could predict long-term disease progression.ConclusionTargeted approaches to identify and quantify biomarkers associated with MS in the CSF may inform on long term MS outcomes. CAMK2A may be one of several candidates, warranting further exploration.

Filling the Gap by Targeting the Gut: First Disease-Modifying Treatment Approved for IgA Nephropathy

This symposium took place during the 60th European Renal Association (ERA) Congress, held in Milan, Italy, and virtually. Bengt Fellström, Uppsala University, Sweden, described the relationship between IgA nephropathy (IgAN) and gastrointestinal mucosal reactivity. Fellström then outlined the history of Nefecon (Calliditas Therapeutics, Stockholm, Sweden, and STADA Arzneimittel, Bad Vilbel, Germany), which was developed based on the assumption that the gut plays a major role in the pathophysiology of the disease, and that there was a high unmet need for a well-tolerated and effective therapy. Nefecon was specifically designed to target the origins of IgAN. A Phase IIb clinical trial showed, for the first time, that 9 months of treatment with Nefecon was well-tolerated and effective in patients at risk of disease progression. Jonathan Barratt, University of Leicester, UK, and John Walls Renal Unit, Leicester General Hospital, UK, presented biomarker data supporting the efficacy data in clinical trials, and presented topline data from Part B of the Phase III NefIgArd trial. Specifically, the results demonstrated an average 5.05 mL/min/1.73 m2 estimated glomerular filtration rate (eGFR) treatment benefit in favour of Nefecon versus placebo over 2 years. This confirmed that the eGFR benefit of 9 months of active treatment with Nefecon was maintained during the observational follow-up. The eGFR benefit with Nefecon versus placebo was consistent regardless of baseline urine protein-creatinine ratio (UPCR). At 2 years, the 30% reduction in UPCR in the Nefecon versus placebo arm was similar to the percentage reduction at the end of the 9-month treatment period, plus 15 months follow-up off treatment. Patients treated with Nefecon experienced decreasing levels of proteinuria while on active treatment and for 3 months afterwards, suggesting a continued biologic effect. Barratt presented UK registry data showing that, despite being treated with the current standard of care for IgAN, three-quarters of adults and half of paediatric patients developed kidney failure or died within 20 years of disease onset. Barratt suggested a paradigm shift in the treatment approach for all patients with IgAN, who have a risk of developing kidney failure in their lifetime.

Evaluating clinical efficacy of hospital-based surveillance with mammography and ultrasonography for breast cancer

Periodic mammography and/or sonography examinations are conducted across numerous hospitals nationalwidely, especially for antedees with a positive mammography screening. Despite the regular practice, clinical efficacy of hospital-based breast cancer surveillance remains unclear. Specifically, the impact of surveillance interval upon survival and prognostic surrogates stratified by menopausal status, as well as malignant transition rate should be deciphered. We retrieved cancer registry to ascertain 841 breast cancers with surveillance history through administration data. Healthy controls underwent breast surveillance and were concurrently free of cancer. More benign diseases rather than cancers were identified from premenopausal women (age ≤50 years) with sonography alone within one year, as well as older women (age >50) with both mammography and sonography one to two years before a cancer or benign diagnosis. Among breast cancers, mammography alone during the antecedent one to two years had a protective effect for diagnosing carcinoma in situ rather than invasive cancer (age-adjusted odds ratio: 0.048, P=0.016). Three-state time homogeneous Markov model showed that hospital-based breast surveillance within 2 years of disease onset reduced the malignant transition rate by 65.16% (59.79-76.74%). The clinical efficacy of breast cancer surveillance was evidenced.

1492-P: IL-8/CXCL8 May Identify a New Type 1 Diabetes Endotype

Recent research focused on identifying mechanisms explaining the observed heterogeneity of type 1 diabetes (T1D) in age at onset, residual β-cell function and rate of disease progression. Mechanisms include changes in both the immune system and β-cells, leading to the loss of tissue-specific immune tolerance and disease onset. Interleukin-8 (IL-8; CXCL8) is a pro-inflammatory chemokine released by macrophages, endothelial, epithelial and airway smooth muscle cells playing a major role in the innate immune response. Macrophages release IL-8 at the site of an injury where they recruit and activate neutrophils by interacting with the IL-8 receptors CXCR1 and CXCR2. An increase in circulating IL-8 has been shown in several autoimmune disorders. IL-8 levels, but not IL-6 or TNF-α, are elevated in adolescents with T1D, and also associated with insulin resistance, suggesting a role for IL-8 beyond acute inflammation in this setting. In vitro experiments revealed that IL-8 transcription is induced by hyperglycaemia. In the present study newly diagnosed T1D patients within the first year of disease onset (mean age 16.2 ± 7.6 yrs and % HbA1c of 10.7 ± 2.7) (N=42) were studied. Clinical and laboratory features included age, gender, body mass index (BMI), disease duration, HbA1c, and C-peptide. Serum IL-8 and myeloperoxidase (MPO) were measured with commercial enzyme-linked Immunosorbent assays. When compared to normal subjects, T1D patients showed a significantly higher IL-8 values (median [IQR] 112.0 [64.74-311.8] vs 43.05 [30.94-49.70], p-value= 0.002, respectively). Furthermore, T1D patients showed a significantly higher MPO levels than controls (median [IQR], 95327 [55718 - 168974] vs 42729 [24147 - 95327], p-value= 0.0349, respectively). This study shows for the first time that IL-8 and MPO are elevated in patients with recent onset T1D compared to normal subjects. There is also a trend for a positive correlation between IL-8 and HbA1c levels suggesting that elevated IL-8 values are associated with poor metabolic control. Disclosure G.Alhamar: None. S.Fallucca: Consultant; Dompé. S.Pieralice: None. L.Valente: None. P.Pozzilli: None.