Active Disease Course Research Articles

Parenchymal Neuro-Behçet's disease or Comorbid Behçet's disease with multiple sclerosis: A discriminative analysis of a complex clinical entity

BackgroundPatients with Behçet's disease (BD) may rarely manifest with cerebral white matter lesions resembling multiple sclerosis (MS). This may result in misdiagnosis due to diagnostic difficulties between parenchymal neuro-BD (pNBD) and MS. This study aims to elucidate the distinguishing features of patients with comorbid BD and MS (BD+MS) in comparison to those with pNBD and MS alone by focusing on clinical and laboratory features. We also aimed to identify the distinctive characteristics of BD+MS patients by comparing them to patients with pNBD and MS. MethodsThe methodology of this study involved a retrospective analysis of patient records followed in the Department of Neurology at the Istanbul Faculty of Medicine, Istanbul University. The study population included patients diagnosed with pNBD, MS, and a comorbid condition of BD and MS (BD+MS). We assessed clinical, radiological, and laboratory data, including disease onset, annual relapse rates, Expanded Disability Status Scale (EDSS) progression, and cerebrospinal fluid examination. Several parameters were examined between the pNBD, MS, and BD+MS patient groups to find similarities and differences between subgroups. ResultsOur study included 1,764 patients: 172 with pNBD, 1,574 with MS, and 18 with BD+MS. A predominance of females was noted in the BD+MS (72%, p < 0.001) and MS (69 %, p < 0.001) groups compared to pNBD (30 %). The median age at the onset of neurological symptoms was 35.5 (IQR: 16.8) years for BD+MS, 34.6 (13.6) years for pNBD, and 27.6 (13.3) years for MS (BD+MS vs. MS; p = 0.3, pNBD vs. MS, p = 0.7). Additionally, the number of attacks was notably different, with BD+MS patients experiencing a median of 3.5 (2.0) attacks compared to 3.0 (3.0) for MS patients and only 1.0 (1.0) for pNBD patients, suggesting a more active disease course in the MS and BD+MS groups compared to pNBD (p < 0.001). The median annualized relapse rate for BD+MS was 0.3 (0.2), which was lower than the rate of 0.4 (0.4) in MS (p = 0.048) and equivalent to the rate of 0.2 (0.3) in pNBD (p = 0.2). The time to the first relapse was similar to those with BD+MS and MS, but considerably shorter than in individuals with pNBD (p < 0.0001). The cerebrospinal fluid (CSF) analysis showed no significant differences in neutrophil and lymphocyte counts between BD+MS and MS patients but elevated levels in pNBD patients (p < 0.05). CSF protein levels were consistent across all groups (p = 0.1 and p = 0.7). Oligoclonal bands were detected in all patients with BD+MS, in the majority of MS patients (83.6 %), and a small percentage of pNBD patients (19.7 %), showing a notable distinction between the BD+MS and pNBD groups (p < 0.001). ConclusionOur study underscores the need for a skeptical approach in diagnosing and treating patients with BD who exhibit symptomatic MS-like MRI lesions. Our findings suggest that BD+MS is a distinct clinical entity, warranting specific diagnostic and treatment approaches. Our findings highlight that BD patients with MS-like lesions meeting MS diagnostic criteria should be managed as patients with comorbid MS and BD rather than pNBD.

Early intensive versus escalation treatment in patients with relapsing–remitting multiple sclerosis in Austria

ObjectivesTo compare the effectiveness of early intensive treatment (EIT) versus escalation treatment (ESC) in a nationwide observational cohort of almost 1000 people with relapsing–remitting multiple sclerosis (RRMS).Materials and methodsThe EIT cohort started with alemtuzumab (AZM), cladribine (CLAD), fingolimod (FTY), natalizumab (NTZ), ocrelizumab (OCR), or ozanimod (OZA); whereas, the ESC cohort was escalated from dimethylfumarate (DMF) or teriflunomide (TERI) to AZM, CLAD, FTY, NTZ, OCR, or OZA within the Austrian MS Treatment Registry. Patients had to stay on therapy for at least 3 months and up to 16 years. The EIT cohort included 743 and the ESC cohort 227 RRMS patients. We used multinomial propensity scores for inverse probability weighting in generalized linear (GLM) and Cox proportional hazards models to correct for the bias of this non-randomized registry study.ResultsEstimated mean annualized relapse rates (ARR) were 0.09 for EIT and 0.4 for ESC patients. The incidence rate ratio (IRR) in the GLM model for relapses showed a decreased relapse probability of 78% for the EIT versus ESC cohort [IRR = 0.22, 95% CI (0.16–0.30), p < 0.001]. Analyzing the time to the first relapse by Cox regression, a hazard ratio (HR) of 0.17 [95% CI (0.13–0.22), p < 0.001] revealed a decreased risk of 83% for the EIT group. Regarding sustained Expanded Disability Status Scale (EDSS) progression for 12 weeks, a HR of 0.55 [95% CI (0.40–0.76), p < 0.001] showed a decreased probability of 45% for the EIT cohort.ConclusionsESC treatment after DMF and TERI revealed a higher relapse and EDSS progression probability compared to EIT in Austrian RRMS patients. Therefore, an early intensive treatment should be started in patients with an active or highly active disease course.

Pregnancy and breastfeeding in women with multiple sclerosis

The diagnosis of multiple sclerosis (MS) in women of reproductive age is associated with many uncertainties regarding childbearing and lactation. Pregnancies of MS patients are not usually considered high-risk pregnancies per se. The likelihood of pregnancy complications or adverse pregnancy outcomes is not increased by the disease; however, acareful planning of pregnancy is important in order to choose the treatment option with the greatest benefit for the mother and the least possible risk for the baby. For highly active courses of the disease, anti-CD20 antibodies, cladribine, or continued administration of natalizumab show the best data. Patients with MS can be supported in their desire to breastfeed. If women have had avery active disease course, it is recommended that treatment should be started as soon as possible postpartum. Interferon-beta preparations, glatiramer acetate and ofatumumab are also approved for use during breastfeeding but off-label breastfeeding is also possible with other monoclonal antibodies.

Students’ perceptions of virtual interactive clinical case-based learning: A comparative study with three different cohorts

Background/purposeSince the introduction of virtual learning into dental education, students’ perceptions of the effectiveness of virtual versus in-person learning formats have evolved for interactive clinical case-based learning (ICCBL). This study aimed to undertake a comparative analysis of three different cohorts that received various formats of ICCBL instruction. Materials and methodsA survey was distributed to the Classes of 2023, 2024, and 2025 following each class completion of interactive clinical case-based-tutorials (ICCBT) as part of the Treatment of Active Disease (TxAD) course at Harvard School of Dental Medicine. ResultsA total of eighty-five participants from the three cohorts, twenty-three students from the Class of 2023 (virtual format, 71.9 % participation rate), thirty-one students from the Class of 2024 (combination of virtual and in-person, 91.2 %), and thirty-one students from the Class of 2025 (in-person, 83.8 %) completed the post-course survey. Across three classes, all cohorts were more likely to perceive the virtual format as more effective than in-person ICCBT. In addition, the classes were more likely to prefer virtual based classes compared to in-person tutorials in the future. ConclusionThis study highlights the dynamic shifts in educational approaches to align with the evolving demands of contemporary students. Our findings show that all cohorts expressed a preference for virtual ICCBT sessions and perceived virtual ICCBT sessions as somewhat more effective for learning compared to in-person sessions. These findings challenge the notion that such sessions must be conducted in person, prompting further research and the exploration of potentially more effective and optimized educational methods.

E11 The burden of illness perception among patients with juvenile idiopathic arthritis

Abstract Background Juvenile Idiopathic Arthritis (JIA) is a debilitating condition that can negatively impact the life of children [1]. Indeed, because of a prolonged course of active disease, patients may experience several limitations and tend to have their unique perception of their illness. Objectives This study aimed to to investigate the illness perception of patients with JIA. Methods We conducted a cross-sectional study including children with JIA (according to the International League of Associations for Rheumatology (ILAR)), recruited from our rheumatology department. Sociodemographic data and disease characteristics were collected. The patients were invited to answer the Brief Illness Perception Questionnaire (BIPQ) to quantify their perception of the disease and how it affects their life. For the patients under the age of 11 years old, we asked the parents to answer the questionnaire. The BIPQ is a nine-item questionnaire rated using a 0-to10 response scale that assesses cognitive illness representations: consequences, timeline, personal control, treatment control, identity, emotional representations and illness comprehensibility [2]. Result Our study involved 31 patients with an average age of 28.7 [9–45] years and consisted of 12 (38.7%) males and 19 (61.3%) females. The mean age at onset and the duration of the disease were 6.6 years [2–13] and 255.84 [36–444] months, respectively. The distribution of the different forms of JIA was as follows: oligoarticular (n = 6), enthesitis-related arthritis (n = 4), polyarticular with positive rheumatoid factor (RF) (n = 9), polyarticular with negative RF (n = 7) and systemic form (n = 5). Regarding treatment modalities, 13 (41.9%) were on corticosteroids, 21 (67.7%) were treated with Cs-DMARDS and 11 (39.3%) were on anti-TNF alpha. Eleven patients required total hip replacement. The mean PGA was 27.6/100. Only eight patients had moderate to severe disease activity. All the patients responded to the entire BIPQ questionnaire with an average score of 46.48/80 [18–68]. Regarding the first question assessing the impact of the disease on life, our patients responded with an average score of 4.7/10 reflecting a healthy perception of the disease. There was a significant association between how much patients experience their symptoms and the emotional impact of the disease (r = 0.8; P = 0.001). Moreover, patients who had a personal and treatment control, were less prone to be affected by the disease emotionally (r = -0.006; P = 0.9). Conclusion Our work highlighted the importance of assessing illness perception of patients with JIA. This condition should be evaluated from different perspectives in order to implement a personalized management strategy. Ethics This work is ethically approved Key words: Juvenile idiopathic arthritis, illness perception

Effect of NLRP3 inflammasome genes polymorphism on disease susceptibility and response to TNF-α inhibitors in Iraqi patients with rheumatoid arthritis

BackgroundRheumatoid arthritis (RA) is a genetically predisposed, systemic, chronic, inflammatory disease. Immune system dysregulation and inherited susceptibility polymorphisms suggest that this type of variation is functional and may help predict disease susceptibility and develop new therapeutic strategies. Anti-TNF-alpha (TNF-α) drugs are highly effective RA treatments, but not all patients respond the same way. It's important to figure out whether RA risk alleles can identify and predict anti-TNF-α-responsiveness in RA patients. Aims of the studyExamine the function of the NLR family pyrin domain containing 3 (NLRP3) and caspase recruitment domain family member 8 (CARD8) genes polymorphisms and their morbid genotypes and alleles in RA patients and apparently healthy controls. In addition, their role in disease susceptibility, severity, and response to anti-TNF-α therapy. Also, examine how single nucleotide polymorphisms (SNPs) affect serum levels of pro-inflammatory cytokines like TNF-α and interleukin (IL)-1β. Materials and methods100 RA patients (88 females, 12 males) and 100 apparently healthy people (86 females, 14 males) were examined. To measure serum TNF-α and IL-1β, Elabscience sandwich ELISA kits were used. Iraq Biotech, Turkey DNA extraction kit was used to extract genomic DNA from whole blood. CARD8 (rs2043211) and NLRP3 (rs4612666) were genotyped using Agilent, AriaMx, USA, through Tri-Plex SYBR Green-based real-time PCR allelic discrimination assays. Geneious software, version 2019.2.2, used to design primers from published sequences (GenBank accession no. GCA 009914755.1). Primer specificity was determined by NCBI's BLAST. ResultsStudy found that there is association between cytokines serum level and 28-joints disease activity score (DAS-28). The level of TNF-α increases with the higher DAS-28 (r2 = 0.45, P < 0.0001). Also, IL- 1β level increases with higher DAS-28 (r2 = 0.51, P < 0.0001). There were no statistically significant variations between patients with RA and the control group in the distribution of CARD8 SNP rs2043211 and NLRP3 SNP rs4612666 genotypes (P = 0.17 and 0.08 respectively) as well their alleles (P = 0.059 and 0.879 respectively). CARD8 (rs2043211) TT genotype was more frequent in patients with higher DAS-28 (P < 0.0001) and higher TNF-α and IL-1β serum levels (P < 0.0001 for both). Also, NLRP3 (rs4612666) TT genotype was more frequent in patients with higher DAS-28 (P < 0.0001) and higher TNF-α and IL- 1β serum levels (P < 0.0001 for both). Interestingly, this study revealed that CARD8 (rs2043211) and NLRP3 (rs4612666) variant genotypes are associated with lower response to anti-TNF-α drugs. ConclusionsSerum TNF-α and IL-1β correlate with DAS-28 and disease activity. Non-responders have elevated TNF-α and IL-1β. CARD8 rs2043211 and NLRP3 rs4612666 variant polymorphisms are associated with high serum TNF-α and IL-1β, active disease course, poor disease outcomes, and low response to anti-TNF-α therapy.

Intrahepatic Cholestasis in Non-Alcoholic Fatty Liver Disease: Pathogenesis and Role of Ademetionine in Treatment

Aim: to evaluate features of intrahepatic cholestasis (IHC) pathogenesis in non-alcoholic fatty liver disease (NAFLD), as well as role of ademetionine in treatment of this condition.Key statements. NAFLD is the most frequent chronic diffuse liver disease. Increase in proportion of people with excess weight, obesity, and metabolic dysregulation leads to higher rates of NAFLD. Concomitant IHC is present in 30 % of NAFLD patients, while it is associated with more active disease course and possible worsening of prognosis. Impairment of adipocyte and hepatocyte metabolism, gut dysbiosis, and inherent factors are recognized as significant factors for NAFLD development. In NAFLD patients most of IHC cases are related to functional cholestasis. IHC in NAFLD is associated with increased risks of fibrosis and all-cause death. Ademetionine may restore transmethylation and improve rheologic properties of hepatocyte membranes in liver disease. In IHC patients treatment with ademetionine led to decreased serum bilirubin concentrations, as well as lowering of the liver transaminases' and alkaline phosphatase activities. At the same time improvement of symptoms severity, including itching, was noted. Taking into account the efficacy of ademetionine in IHC in NAFLD patients, its' use was included in the national clinical guidelines.Conclusion. Use of ademetionine in NAFLD with concomitant IHC is feasible from pathogenesis perspective and may be effective in clinical practice.

Low Adherence is Associated with Chronic Active Disease in Ulcerative Colitis: A Retrospective Study from a Single Referral Center.

New therapeutic approaches for ulcerative colitis (UC) are now available, but there is still no robust evidence for predictors of poor outcomes. We aimed to evaluate the factors associated with a chronic active UC disease course. Data of all UC outpatients followed for at least 3 years after diagnosis between 2005 and 2018 were retrospectively collected. The primary aim was to identify risk factors for chronic active disease 3 years after diagnosis. Moreover, the following variables were investigated: proximal disease extension or disease regression, proctocolectomy, early use of biologics (BIO) or immunomodulators (IMM), hospitalization, colorectal cancer, and adherence. We defined adherence as both, taking the prescribed therapy and constancy in scheduled follow-up visits. A total of 345 UC patients followed for a median period of 82 months were included. Patients with extensive colitis at diagnosis had a higher rate of chronic active disease 3 years after diagnosis (p<0.012) together with a higher rate of surgery (p<0.001) at maximum follow-up. Patients with pancolitis showed significant disease regression over time (51%) without differences in treatment. The only factor associated with chronic active disease was non-adherence (p < 0.03; OR 0.49, 95% CI: 0.26-0.95). Adherent patients developed chronic active disease (p<0.025) less frequently but did receive more frequent IMM (p<0.045) or BIO (p<0.009) therapy. Patients diagnosed with pancolitis were more likely to have chronic active disease and to undergo colectomy. The only predictor for developing chronically active UC regardless of disease extension was the lack of adherence to therapy within the first 3 years after diagnosis, underlining the importance of tight control of UC patients and the need to timely identify potential risk factors for non-adherence.

Left atrial longitudinal strain analysis in long Covid-19 syndrome

It is known that during the active course of Coronavirus disease 2019 (COVID-19), myocardial injury has an established pathological base, while its myocardial injury post-recovery is still obscured.The aim of this study was to evaluate the longitudinal left atrial strain (LAS) using speckle tracking echocardiography (STE) in COVID-19-recovered patients who are previously healthy without confounder comorbidities to detect the potential cardiac dysfunction.200 patients were prospectively included and examined 4?12 weeks after recovery from COVID-19 infection. 137 participants with comorbidities or previous history of cardiopulmonary disease were excluded from the analysis. A total of 63 patients who fulfilled our inclusion criteria were recruited into two groups according to thepresence or absence of persistent dyspnoea and exercise intolerance. Clinical, laboratory & comprehensive echocardiographic examinations were done for all. We observed that 31.7% of the previously healthy individuals developed dyspnoea & exercise intolerance post-COVID-19 infection. There were significantly impaired LAS parameters in the symptomatic group (LA reservoir, contraction & conduit strain, 22.7%, -6.6% & -16.1% versus 40%, -12%, and ? 27% in the asymptomatic group with P < 0.000). Only LA reservoir strain and LA stiffness can independently predict the development of dyspnoea & exercise intolerance post-COVID-19 at cut-off values of 30% & 24.5% respectively with a sensitivity of 90% and a specificity of 91%, P < 0.001. These impaired LAS parameters could explain the developed symptoms post-COVID-19 recovery, even before disturbed conventional diastolic echocardiographic parameters.LAS parameters are significantly associated with the developed exertional dyspnoea & exercise intolerance post-COVID-19. LA reservoir strain & LA stiffness could provide a simple, easily available tool that points to early LV diastolic dysfunction and may direct the therapy in this subset of the population.

Predictors of surgical outcomes in patients with drug-resistant temporal lobe epilepsy

Aim. To identify predictors of surgical outcomes in patients with drug-resistant temporal lobe epilepsy in a multivariate model.Materials and methods. Aretrospective study included 69 patients with drug-resistant temporal lobe epilepsy who underwent microsurgical anterior temporal lobectomy. The study included 31 (45%) men and 38 (55%) women. The median age was 28 (21; 36). Surgical treatment outcomes were assessed at 6, 12, 36, and 60 months after surgical intervention according to the Engel Epilepsy Surgery Outcome Scale. Logistic regression equations were calculated, a ROC curve was constructed, and odds ratio (OR) with 95% confidence interval (CI), sensitivity, specificity, area under the ROC curve (AUC) were calculated.Results. In all assessed time periods, 88.3–93.0% of patients had outcomes consistent with Engel classes I and II. The distribution of patients by outcome classes did not change statistically significantly over the entire follow-up period. There were the following predictors of high efficacy of surgical treatment at 6 months after surgery: relatively shorter duration of active disease course (OR 0.719, 95%, CI: 0.437–0.966, p &lt; 0.05), absence of status epilepticus (OR 0.048, 95% CI: 0.002–0.472, p &lt; 0.05), absence of subdominant foci of irritative activity (OR 0.123, 95% CI: 0.012–0.845, p &lt; 0.01), presence of mesial temporal sclerosis (OR 1008, 95% CI: 21.59–1310851, p &lt; 0.01), a relatively longer resection margin on the temporal lobe (OR 637.32, 95% CI: 5.43–1960062, p &lt; 0.05), lateralization of epileptogenic zone in subdominant hemisphere (OR 0.103, 95% CI 0.004–0.937, p = 0.0532). AUC was 0.957 (0.917–0.997), p &lt; 0.0001; sensitivity 87.5%, and specificity 82.8%.Conclusion. Independent predictors of the efficacy of microsurgical anterior temporal lobectomy in patients with drug-resistant temporal lobe epilepsy are the following: shorter duration of active disease course, absence of status epilepticus in the history, absence of subdominant foci, presence of mesial temporal sclerosis, a relatively longer resection margin on the temporal lobe, and lateralization of the epileptogenic zone in the temporal lobe of the subdominant hemisphere.

Narrative review based on fingolimod therapy in pediatric MS.

The course of pediatric-onset multiple sclerosis and adult multiple sclerosis shows some clinical differences. The rate of having a second attack after the first clinical event is 80% in children and around 45% in adults but the time to the second event is similar in all age groups. The pediatric group usually has a more aggressive onset than adults. On the other hand, a higher rate of complete recovery is observed in pediatric-onset multiple sclerosis after the first clinical event compared to the adult group. Despite a highly active initial disease course, pediatric-onset multiple sclerosis patients show a slower increase in disability than patients with adult-onset disease. This is thought to be due to greater remyelination capacity and plasticity of the developing brain. The management of pediatric-onset multiple sclerosis includes safety issues as well as effective disease control. In the pediatric-onset multiple sclerosis group, similar to adult multiple sclerosis, injectable treatments have been used for many years with reasonable efficacy and safety. Since 2011, oral treatments and then infusion treatments have been approved and used effectively in adult multiple sclerosis and have gradually entered clinical use in the pediatric-onset multiple sclerosis group. However, clinical trials are fewer, smaller, and include shorter follow-up due to the much lower prevalence of pediatric-onset multiple sclerosis than adult multiple sclerosis. This is particularly important in the era of recent disease-modifying treatments. This review of the literature presents existing data on the safety and efficacy of fingolimod, pointing to a relatively favorable profile.

Management of acute abdomen during the active disease course of COVID-19 and multisystem inflammatory syndrome in children.

PurposeTo evaluate the management of children with severe gastrointestinal symptoms during the disease course of COVID-19 and multisystem inflammatory syndrome (MIS-C).MethodsAfter ethical approval, we reviewed the medical records, retrospectively, of children with COVID-19 or MIS-C requiring surgical consultation for severe gastrointestinal symptoms.ResultsThe subjects comprised 15 children, 13 with MIS-C and 2 with COVID-19. Twelve children (80%) had been in known close contact with a person with SARS-CoV-19 and 13 were positive for Anti-SARS-CoV-2 IgG. All the children had experienced fever for at least 1 day and had signs of involvement of two or more systems. Three patients required surgical intervention: one underwent surgical exploration with a presumptive diagnosis of acute appendicitis in the referring center and was transported to our center following clinical deterioration, where a diagnosis of MIS-C was confirmed; and the remaining two developed appendicitis during hospitalization for COVID-19. All three patients had a longer duration of abdominal pain, a higher number of lymphocytes, and a lower level of inflammatory markers than the non-surgically managed patients. None of the patients presenting with MIS-C underwent surgical exploration.ConclusionGastrointestinal involvement may mimic acute abdomen in children with COVID-19. Thus, children presenting with acute abdomen in the pandemic era require careful evaluation and prompt diagnosis to avoid unnecessary surgical intervention.

Screening for Anti-HMGCR Antibodies in a Large Single Myositis Center Reveals Infrequent Exposure to Statins and Diversiform Presentation of the Disease.

BackgroundThe objective of this study is to assess the frequency of autoantibodies against 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase (HMGCR) in a single center myositis cohort and to analyze associations with statin exposure, clinical features, and outcome of disease course.MethodsA total of 312 patients with idiopathic inflammatory myopathies (IIMs) followed at the rheumatology clinic, Karolinska University Hospital, were identified in the Euromyositis registry between 1988 and 2014 and were classified according to the 2017 European Alliance of Associations for Rheumatology/American College of Rheumatology (EULAR/ACR) criteria. Available serum samples were analyzed for anti-HMGCR autoantibodies by ELISA. Positive sera were confirmed by immunoprecipitation. Clinical data were extracted from Euromyositis registry and medical records. Muscle samples were examined by two pathologists blinded to the subjects’ autoantibody status.ResultsOf 312 patients, 13 (4.3%) were positive for anti-HMGCR. Two of the 13 (15%) anti-HMGCR–positive patients had histories of statin use versus 12 (4.2%) in the anti-HMGCR–negative group. In the anti-HMGCR–positive group, five (38%) had a clinical phenotype compatible with dermatomyositis. Muscle biopsies of patients with HMGCR autoantibodies showed findings consistent with immune-mediated necrotizing myopathy in all cases except for one. Five (38%) patients required treatment with intravenous immunoglobulin compared to seven (2.3%) without this antibody. At the last visit, seven patients had chronic, active disease course, and five of 13 patients were in remission, including three without treatment.ConclusionsPatients with IIM related to anti-HMGCR autoantibodies may present with a wide range of symptoms, more than previously anticipated. When a broad approach to screening for these antibodies is applied, only a minority of patients was found to have previous statin exposure. The results of this study justify the addition of anti-HMGCR autoantibodies to routine diagnostic procedures in patients with myositis.

Renal manifestations of paediatric systemic lupus erythematosus.

Systemic lupus erythematosus is a lifelong, multisystemic disease. Around a fifth of patients present during childhood. Children are recognized to have a more active disease course with more renal involvement (lupus nephritis) when compared with adults. This review article summarizes the current literature surrounding the management of paediatric lupus nephritis. International recommendations agree that active, proliferative forms of lupus nephritis are treated with a period of intense induction therapy aimed at inducing remission followed by maintenance immunosuppressive therapy for at least 3 years. Complete response rates in lupus nephritis remain inadequate, in the region of 40-60%, and disease flares are common. Revised histological classification have been proposed but they are yet to be adopted in clinical practice. Lupus nephritis progresses to chronic kidney disease (CKD) stage 5 (kidney failure) in more than 10% of patients within 10 years however the rates of CKD stages 1-4 remain largely unknown. Current trials are focused on the use of biologic agents as adjuncts to current therapy. There is an urgent need for better outcomes in paediatric lupus nephritis. The use of biomarkers to monitor lupus nephritis and scientific studies to improve our understanding of the pathogenesis offer hope of improved outcomes.

Factors and glucocorticoid usage affecting the prognosis of systemic juvenile idiopathic arthritis.

The rate of glucocorticoid (GC) use is significantly higher in systemic juvenile idiopathic arthritis (SJIA) than other juvenile idiopathic arthritis subtypes. There is no consensus on the duration and dosage of GC treatment. We aimed to investigate the risk factors for a polyphasic / persistent disease course and the effect of dose and duration of GC treatment on SJIA prognosis. Forty-two patients who were diagnosed with SJIA, and for whom the duration of disease was longer than 2 years, were included. Patients were divided into monophasic and others (polyphasic / persistent disease course). Risk factors for polyphasic / persistent disease course, which were clinical and laboratory findings regarding the patients, treatment options, dose, and duration of GCs, were evaluated for the first active disease periods and for all flares in the entire disease course. Of the 42 SJIA patients, 21 had monophasic, and 21 had polyphasic / persistent disease. Cumulative dosages and durations of glucocorticoid treatment were similar in the two groups at the first flare (odds ratio (OR): 1.032 P: 0.671; OR:1,113 P: 0.115). Durations of the first active disease period were longer in the polyphasic / persistent group (OR:1.275, P: 0.01). Active disease duration cut-off values of 1.5 months with sensitivity 85.7%, specificity 52.4% were observed on receiver operating characteristic curve analysis. The presence of hepatosplenomegaly at first flare was detected as an independent risk factor of polyphasic/persistent disease by multivariate analysis included both dosage and duration of a steroid (hazard ratio (HR): 4.129, P: 0.034), (HR: 3.992, P: 0.038). Multivariate recurrent events survival analysis determined ALT levels as a risk factor affecting polyphasic / persistent disease (HR: 0.986, P: 0.037). Glucocorticoid dose and duration did not affect the active disease periods and disease course in SJIA. An active disease period longer than 1.5 months, presentation of hepatosplenomegaly at the initial disease course, and high ALT levels at the recurrences should warn physicians of polyphasic / persistent disease.

Calprotectin in Chronic Inflammatory Demyelinating Polyneuropathy and Variants-A Potential Novel Biomarker of Disease Activity.

Background: In chronic inflammatory demyelinating polyneuropathy (CIDP), there is an urgent need for biomarkers to monitor ongoing disease activity. Serum calprotectin (CLP) induces signaling pathways involved in inflammatory processes and has been shown to correlate with markers of disease activity in other autoimmune disorders. Thus, we wanted to study the potential value of CLP in comparison to serum neurofilament light chain (sNfl) to monitor disease activity.Materials and Methods: Sera from 63 typical and atypical CIDP and 6 MMN patients with varying degrees of disease activity were analyzed in comparison with 40 healthy controls (HC) in a cross-sectional design. Association of CLP and sNfl levels with socio-demographics, disease duration, CIDP disease activity scale (CDAS), and impairment status [medical research council-sum score (MRC-SS), the inflammatory neuropathy cause and treatment disability score (INCAT-DS), grip strength, and maximum walking distance], patient-reported outcome (PRO) parameters [SF-36 questionnaire, Beck's depression index (BDI), and fatigue severity scale (FSS)], as well as treatment regime were investigated using uni- and multivariate analysis.Results: CLP and sNfl levels were significantly higher in all CIDP patients compared to HC (p = 0.0009). Multivariate analysis adjusted for age and gender revealed that CLP acts as an independent predictor for CIDP and MMN. CLP was significantly associated with active disease course according to CDAS and correlated with MRC-SS, whereas sNfl correlated with parameters of disease impairment. There was no correlation with PRO, except for sNfl and the mental health composite score. Subgroup analysis revealed no differences between typical CIDP and atypical variants.Conclusions: CLP was elevated in CIDP and variants and was associated with active disease course, whereas sNfl shows further potential as biomarker of axonal degeneration. Thus, CLP might be a suitable additive biomarker for measurement of ongoing inflammation, which is greatly needed to guide better patient care in CIDP.

OP32 Stool microbiome communities predict remission in treatment-naïve Pediatric Crohn’s Disease patients

Abstract Background Early relapse in paediatric Crohn’s Disease (CD) is associated with severe disease course that heavily impairs quality of life. Changes in gut microbiome composition have been linked to active CD and disease course. This has led to development of microbiome-based prediction models for diagnosis and response to treatment. Our aim was to identify community-level microbiome signatures of treatment-naïve children with mild-to-moderate CD who did not require anti-TNF or surgery at diagnosis, with the goal of predicting need for re-induction or treatment escalation within the first year after diagnosis. Methods We selected de novo, treatment-naïve paediatric CD patients from the RISK cohort(Gevers 2014). Taxonomic labels were assigned to the 16s rRNA amplicon data using QIIME and closed OTU-picking. A hierarchical Bayesian model for microbial community structure was used to learn how baseline gut microbiomes differed according to treatment outcome. Model predictions were assessed using a leave-one-out analysis. We compared 16S rRNA sequences of CD patients with non-IBD controls(Gevers 2014) and healthy siblings of CD patients(Turpin 2016). Results Metadata and 16S rRNA amplicon data were available from 197 stool samples of de novo paediatric CD patients from the RISK cohort. We selected 44 out of 197 samples of patients that were treatment-naïve. Prior to treatment, PCDAI scores were similar between patients reaching remission and those that did not at 6 months. Bayesian analysis characterized 4 assemblages that accounted for 93% of the posterior probability distribution. The Bayesian model on pre-treatment stool microbiomes was able to predict 6-month outcome of patients that maintained remission and those that did not from the pre-treatment microbiome in 81% and 75% of samples (AUC=0.79). When comparing CD samples to 28 non-IBD controls (many with GI symptoms but negative for IBD during endoscopy, e.g. Irritable Bowel Syndrome), 6 assemblages were characterized with 44% of distributions shared between groups (AUC=0.61). In contrast, in CD samples compared to 728 healthy sibling samples (with increased genetic susceptibility), shared distribution within 4 characterized assemblages was less than 1% (AUC=1). Conclusion A Bayesian approach predicted clinical course in treatment-naïve children with CD in the first year after diagnosis with high accuracy, when ensuring only treatment-naïve faecal samples in the analysis. This classification level is comparable to previous findings using mucosal samples. Further study is needed to validate these pre-treatment microbiome signatures of newly diagnosed paediatric CD patients to allow identification of patients with mild-to-moderate disease who are most likely to require treatment escalation.

New EULAR/ACR 2019 SLE Classification Criteria: defining ominosity in SLE

ObjectiveTo determine the ominosity of the European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) Systemic Lupus Erythematosus Classification Criteria by determining its predictive role for disease severity in the...

Effectiveness of aerobic exercise training program on cardio-respiratory fitness and quality of life in patients recovered from COVID-19

Background This study aimed to determine the effect of moderate to high-intensity aerobic and breathing exercise on cardiorespiratory fitness and health-related Quality of Life (QoL) in post-discharge COVID-19 patients. The study included two groups of participants. Methods A prospective interventional study was conducted at the Bin-Inam Rehabilitation centre at the outpatient department, with 20 recruited patients having below standard 6-min walk test and QoL score at baseline. All the participants underwent five weeks (3 sessions/week) of aerobic training (20–60 min/session) and breathing exercise training (10 min/session). SF-36 health-related QoL modified Borg dyspnoea scale, and 6-min walk test measurements were collected at baseline and final intervention. Paired sample t-test was applied to determine the improvement after 5 weeks of intervention. Sub-group analysis according to inpatient ventilatory support used in active course of disease was also performed. A two-factor repeated measure ANOVA was applied to determine the time difference between sub-groups. All the data were analysed by using SPSS 24.0. Results Cardiorespiratory fitness, dyspnoea and quality of life has been significantly improved after 5-weeks of training. Sub-group analysis revealed that both groups significantly improved over time in measures of endurance, dyspnoea and quality of life (Time effect p < 0.05). An increase in exercise tolerance was observed in sub-group 1 (who did not used inpatient ventilatory support) manifested by a longer 6-min walk distance 667.8 (35.32) m compared to sub-group 2 (who used inpatient ventilatory support) 602.9 (46.1) m. There were trends towards greater improvement in General health and Body pain domains of health-related quality of life and dyspnoea in sub-Group 1 compared to sub-Group 2. Conclusions This study provides evidence that rehabilitation training in COVID-19 recovered patients may benefit the recovery after COVID-19. Clinical trial registration number NCT04445376

Effects of Long-Term Endogenous Corticosteroid Exposure on Brain Volume and Glial Cells in the AdKO Mouse.

Chronic exposure to high circulating levels of glucocorticoids has detrimental effects on health, including metabolic abnormalities, as exemplified in Cushing’s syndrome (CS). Magnetic resonance imaging (MRI) studies have found volumetric changes in gray and white matter of the brain in CS patients during the course of active disease, but also in remission. In order to explore this further, we performed MRI-based brain volumetric analyses in the AdKO mouse model for CS, which presents its key traits. AdKO mice had reduced relative volumes in several brain regions, including the corpus callosum and cortical areas. The medial amygdala, bed nucleus of the stria terminalis, and hypothalamus were increased in relative volume. Furthermore, we found a lower immunoreactivity of myelin basic protein (MBP, an oligodendrocyte marker) in several brain regions but a paradoxically increased MBP signal in the male cingulate cortex. We also observed a decrease in the expression of glial fibrillary acidic protein (GFAP, a marker for reactive astrocytes) and ionized calcium-binding adapter molecule 1 (IBA1, a marker for activated microglia) in the cingulate regions of the anterior corpus callosum and the hippocampus. We conclude that long-term hypercorticosteronemia induced brain region-specific changes that might include aberrant myelination and a degree of white matter damage, as both repair (GFAP) and immune (IBA1) responses are decreased. These findings suggest a cause for the changes observed in the brains of human patients and serve as a background for further exploration of their subcellular and molecular mechanisms.