Long-term Course Of Disease Research Articles

Long-Term Outcomes After Septal Reduction Therapies in Obstructive Hypertrophic Cardiomyopathy: Insights From the SHARE Registry.

Septal reduction therapy (SRT) provides substantial symptomatic improvement in patients with obstructive hypertrophic cardiomyopathy (HCM). However, long-term disease course after SRT and predictors of adverse outcomes have not been systematically examined. Data from 13 high clinical volume HCM centers from the international SHARE (Sarcomeric Human Cardiomyopathy Registry) were analyzed. Patients were followed from the time of SRT until last follow-up or occurrence of heart failure (HF) composite outcome (cardiac transplantation, implantation of a left ventricular assist device, left ventricular ejection fraction <35%, development of New York Heart Association class III or IV symptoms), ventricular arrhythmias composite outcome (sudden cardiac death, resuscitated cardiac arrest, or appropriate implantable cardioverter defibrillator therapy), or HCM-related death. Cox proportional hazards models were used to identify predictors of outcome. Of the 10 225 patients in SHARE, 1832 (18%; 968 [53%] male) underwent SRT, including 455 (25%) with alcohol septal ablation and 1377 (75%) with septal myectomy. The periprocedural 30-day mortality rate was 0.4% (8 of 1832) and 1499 of 1565 (92%) had a maximal left ventricular outflow tract gradient <50 mm Hg at 1 year. After 6.8 years (range, 3.4-9.8 years; 12 565 person-years) from SRT, 77 (4%) experienced HCM-related death (0.6% per year), 236 (13%) a composite HF outcome (1.9% per year), and 87 (5%) a composite ventricular arrhythmia outcome (0.7% per year). Among adults, older age at SRT was associated with a higher incidence of HCM death (hazard ratio, 1.22 [95 CI, 1.1-1.3]; P<0.01) and the HF composite (hazard ratio, 1.14 [95 CI, 1.1-1.2] per 5-year increase; P<0.01) in a multivariable model. Female patients also had a higher risk of the HF composite after SRT (hazard ratio, 1.4 [95 CI, 1.1-1.8]; P<0.01). De novo atrial fibrillation occurred after SRT in 387 patients (21%). Among pediatric patients followed for a median of 13 years after SRT, 26 of 343 (16%) developed the HF composite outcome, despite 96% being free of recurrent left ventricular outflow tract obstruction. Successful short- and long-term relief of outflow tract obstruction was observed in experienced multidisciplinary HCM centers. A subset of patients progressed to develop HF, but event-free survival at 10 years was 83% and ventricular arrhythmias were rare. Older age, female sex, and SRT during childhood were associated with a greater risk of developing HF.

Time to Treat First Acute Attack of Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease

A proportion of people with myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) have a relapsing disease course and persistent anti-myelin oligodendrocyte glycoprotein immunoglobulin G (MOG-IgG) seropositivity. Few studies have investigated whether treatment of the first MOGAD attack is associated with the long-term disease course and/or MOG-IgG seronegative conversion. To investigate the association of time to treat the first acute MOGAD attack with relapse risk and MOG-IgG serostatus. This was a retrospective, nationwide, multicenter cohort study involving 14 secondary or tertiary hospitals in South Korea between November 2009 and August 2023. People with adult-onset MOGAD, who either had a relapse or were followed up for more than 12 months after disease onset and had a detailed medical record of their first attack, were included. Individuals were excluded for adolescent-onset MOGAD or short disease duration. Patients were categorized based on the time to treat the first acute MOGAD attack: early (<5 days), intermediate (5-14 days), and late (not treated within 14 days). A multivariable analysis for clinical and treatment factors associated with relapsing disease course and/or MOG-IgG seronegative conversion. Further subgroup analyses were conducted among those without long-term nonsteroidal immunosuppressant (NSIS) maintenance treatment. Among the 315 individuals screened, 75 were excluded. A total of 240 patients (median [IQR] age at onset, 40.4 [28.8-56.1] years; 125 female [52.1%]) with median (IQR) disease duration of 3.07 (1.95-6.15) years were included. A total of 110 of 240 patients (45.8%) relapsed after a median (IQR) of 0.45 (0.18-1.68) years, and 29 of 116 patients (25.0%) experienced a conversion to seronegative MOG-IgG. Both the time to treatment of the first MOGAD attack (late vs early: adjusted hazard ratio [aHR], 2.64; 95% CI, 1.43-4.84; P = .002; intermediate vs early: aHR, 2.02; 95% CI, 1.10-3.74; P = .02) and NSIS maintenance treatment (aHR, 0.24; 95% CI, 0.14-0.42; P < .001) were independently associated with the risk of relapse. In a subgroup without NSIS maintenance, the time to treat of the first MOGAD attack was still associated with higher risk of relapse (late vs early: aHR, 3.51; 95% CI, 1.64-7.50; P = .001; intermediate vs early: aHR, 2.68; 95% CI, 1.23-5.85; P = .01). Lastly, the time to treat of the first MOGAD attack was also associated with MOG-IgG seronegative conversion (early vs late: adjusted odds ratio, 7.04; 95% CI, 1.58-31.41; P = .01), whereas NSIS maintenance treatment was not. Results of this cohort study suggest that early treatment of the first acute MOGAD attack was associated with a reduction in the proportion of relapsing disease course and an increase in the likelihood of MOG-IgG seronegative conversion. These data suggest that timing of acute phase treatment for the first MOGAD attack can be associated with the long-term prognosis and autoimmune status of patients.

Effects of brain estrogen receptor on depression and its mechanism of action

Depression is a refractory disease involving multiple pathologic changes, characterized by long-term disease course, low curative rate, and complex symptoms. However, the pathologic mechanism of this disease is incompletely known. Current research mainly focuses on the monoamine neurotransmitter hypothesis, neuroendocrine-related hypothesis, neuroinflammation hypothesis, and brain structure-function hypothesis. An intimate interplay exists between estrogen with the development and progression of depression. Estrogen receptors are widely distributed in the central nervous system, the expression of which can exert genetic and nongenetic effects to improve depression through regulating the level of neurotransmitters, mediating the function of the hypothalamus-pituitarium-adrenal axis, alleviating neuroinflammation, and protecting neurons. This study elaborated on the regulatory effect and mechanism of brain estrogen receptors on depression, hoping to provide new ideas for the clinical treatment of depression.

Clinical characteristics and long-term disease course in patients with Crohn's disease as diagnosed by video capsule endoscopy: a multicenter retrospective matched case-control study.

Video capsule endoscopy is rarely used to diagnose Crohn's disease in patients with negative ileocolonoscopy or cross-sectional image findings. We evaluated clinical characteristics and long-term outcomes of these rare cases. This multicenter study included patients with Crohn's disease from 3 tertiary hospitals from January 2007 to October 2022. Patients with normal findings on ileocolonoscopy and computed tomography (CT)/magnetic resonance (MR) enterography but had ulcerations at the small bowel detected by video capsule endoscopy were included. The controls were patients with abnormal findings on endoscopy or CT/MR enterography. Controls were case-matched in a ratio of 3:1 for sex, calendar year of diagnosis, and age at diagnosis. Among 3,752 patients, 24 (0.6%) were diagnosed with Crohn's disease using video capsule endoscopy findings. The disease location (P< 0.001) and behavior at diagnosis (P= 0.013) of the cases significantly differed from that of controls. The perianal fistula modifier (25.0% vs. 33.3%, P= 0.446) did not differ significantly between the 2 groups. Initial disease activity and C-reactive protein and fecal calprotectin levels were significantly lower in cases versus controls. The median Lewis score was 838 (interquartile range, 393-1,803). Over 10 years of follow-up, the cases showed significantly lower cumulative risk of complicated behavior, biologics use, Crohn's disease-related hospitalization, and surgeries (log-rank test P< 0.05). Patients with Crohn's disease whose lesions were observed only by video capsule endoscopy were rare, and exhibit different clinical characteristics and a more favorable long-term disease course compared to those who were conventionally diagnosed.

Cardiac evaluation of patients with juvenile dermatomyositis.

The present study aims to evaluate possible cardiac involvement in juvenile dermatomyositis (JDM) patients by conventional methods and cardiac magnetic resonance imaging (MRI) along with a systematic review of the literature on cardiac features in JDM. The study group consisted of JDM patients who underwent cardiac MRI. We conducted a systematic review of the published literature involving JDM patients with cardiac involvement. In the present study, although baseline cardiologic evaluations including electrocardiography and echocardiography were within normal limits, we showed late gadolinium enhancement on cardiac MRI in 3 of 11 JDM patients. In the literature review, we identified 25 articles related to cardiac involvement in JDM. However, none of them, except one case report, included cardiac MRI of JDM patients. Cardiac abnormalities have been reported among the less frequent findings in patients with JDM. Cardiovascular complications during the long-term disease course are a leading cause of morbidity and mortality in these patients. Early detection of cardiac involvement by cardiac MRI in patients with JDM and aggressive treatment of them may improve the clinical course of these patients. The myocardium in patients with JDM may be involved by inflammation. Myocardial involvement may be evaluated by using contrast-enhanced cardiac MRI. This is the first study evaluating cardiac involvement by cardiac MRI in JDM patients. MRI may show early cardiac involvement in patients whose baseline cardiologic evaluations are within normal limits. Early detection of cardiac involvement by cardiac MRI may improve the long-term prognosis of patients with JDM.

Risk of cancer in patients with bile acid diarrhoea: a Danish nationwide matched cohort study

ObjectiveBile acid diarrhoea is a common cause of chronic diarrhoea. Increased levels of potentially carcinogenic bile acids in faeces, theoretically, may increase the risk of colorectal cancer in particular, but...

Myasthenia gravis-Gender aspects and family planning

There is evidence that gender-specific differences can influence the diagnostics, treatment and long-term disease course of myasthenia gravis (MG). In women the diagnosis is often made during childbearing age. Gender-specific differences in MG and relevant aspects in routine clinical practice are presented. In addition, current studies on family planning, pregnancy and childbirth in MG are highlighted and treatment recommendations are derived. Narrative literature review. In addition to sociodemographic data, gender-specific differences encompass clinical as well as paraclinical factors, such as disease severity and antibody status. With few exceptions pregnancy is possible with good maternal and neonatal outcome. During pregnancy and peripartum, children of MG patients should be closely monitored for early detection and treatment of potential syndromes caused by diaplacental transfer of maternal antibodies. Gender-specific factors can influence the course of MG. Adequate medical counselling and multidisciplinary collaboration are essential for MG patients who wish to have children.

Olfactory threshold as a biomarker of long-term relapse activity in multiple sclerosis

BackgroundOlfactory threshold (OT) is a marker of short-term inflammatory activity in multiple sclerosis (MS). ObjectiveTo investigate whether OT predicts long-term MS clinical disease course. MethodsThis was a 6-year prospective longitudinal study on MS patients at the MS clinic Innsbruck. Clinical visits assessing the occurrence of relapses, Expanded Disability Status Scale (EDSS) scores, and disease-modifying treatment (DMT), were conducted biannually. OT testing was performed at baseline (BL), year 1 (Y1), year 2 (Y2) and year 6 (Y6), using the threshold subscore of the “Sniffin’ Sticks” test. Cognitive function was assessed by the Symbol Digit Modalities Test. ResultsOf 139 MS patients, 92 were eligible for Y6 follow-up. 68% experienced relapses, 53% EDSS worsening, 29% progression independent of relapse activity (PIRA) and 41% cognitive deterioration. OT scores were lower at BL, Y1 and Y2 in patients requiring DMT escalation. In multivariable analysis, higher OT scores at BL, Y1, Y2 and Y6 were associated with lower risk of relapse (hazard ratio, HR: 0.65–0.92) and EDSS worsening (HR: 0.86–0.89), while no associations were found for PIRA and cognitive deterioration. ConclusionsOT is a potential surrogate marker for long-term inflammatory disease activity and DMT failure in MS.

P259 Clinical characteristics and long-term disease course in patients with Crohn’s disease diagnosed by video capsule endoscopy; A retrospective multicentre matched case-control study

Abstract Background Video capsule endoscopy (VCE) is a non-invasive and accurate diagnostic modality that allows for direct visualization of the small intestinal mucosa in Crohn’s disease (CD). In rare cases, lesions not detected by other diagnostic modalities in patients suspected to have CD are solely identified through VCE. We aim to evaluate the clinical characteristics and long-term outcomes of these rare cases. Methods A retrospective multicentre matched case-control analysis was conducted in patients with CD across three hospitals in Korea, from January 2007 to April 2023. To perform a matched case-control study, we defined cases (VCE group) as patients with normal findings at colonoscopy and cross-sectional imaging, ultimately diagnosed with CD by VCE; the controls were patients with CD diagnosed with specific findings at endoscopy or cross-sectional imaging (non-VCE group). Controls were matched to cases with a ratio of 3:1 for sex, calendar year of diagnosis, and age at diagnosis. Clinical characteristics and outcomes between the two groups were compared. Results Of the 3,137 patients diagnosed with CD during the study period, 24 were diagnosed solely by VCE. When compared to 72 matched patients with CD, the mean duration from symptom onset to diagnosis did not significantly differ (27.2 months [SD 10.2] vs. 25.3 months [SD 8.9], p=0.394). There was a significant difference in the proportion of Montreal behaviour (p&amp;lt;0.001). In the VCE group, non-stricturing and non-penetrating (B1) type and stricturing (B2) type accounted for 91.7 and 8.3%, respectively. However, there was no significant difference in the perianal fistula modifier (25% vs. 33.3%, p=0.446). Within the VCE group, 45.8% underwent the examination due to abdominal pain with diarrhoea, followed by 25.0% with perianal disease, and 20.8% with unexplained iron deficiency anaemia. Regarding capsule findings, the ileum was mostly involved (87.5%), while the jejunum and duodenum were affected in 70.8 and 16.7% of cases, respectively. Fifteen patients had two or three segments affected. The Median Lewis score was 838 [IQR 393–1803]. Concerning the cumulative incidence of clinical outcomes over 10 years, complicated behaviour, need for biologics, and CD-related hospitalization and surgery were all significantly lower in the VCE group than in the non-VCE group (p&amp;lt;0.005). Conclusion Patients diagnosed with CD solely by VCE are rare. In this study, they exhibited different clinical characteristics and a more favourable long-term disease course compared to the general population of patients with CD. This included a lower incidence of complicated behaviour, reduced need for biologics, and CD-related hospitalization and surgery.

Crescent calculator: A webtool enabling objective decision-making for assessment of IgA nephropathy immune activity throughout the disease course

IgA nephropathy (IgAN) is an immune-mediated glomerulonephritis, posing a challenge for the long-term management. It is crucial to monitor the disease’s activity over the disease course. Crescent lesions have been known as an active lesion associated with immune activity. We aimed to develop the Crescent Calculator to aid clinicians in making timely and well-informed decisions throughout the long-term disease course, such as renal biopsies and immunosuppressive therapy.1,761 patients with biopsy-proven IgAN were recruited from four medical centers in Zhejiang Province, China. 16.9% presented crescent lesions. UPCR, URBC, eGFR and C4 were independently associated with the crescent lesions. By incorporating these variables, the Crescent Calculator was constructed to estimate the likelihood of crescent lesions. The predictor achieved AUC values of over 0.82 in two independent testing datasets. In addition, to fulfill varied clinical needs, multiple classification modes were established.The Crescent Calculator was developed to estimate the risk of crescent lesions for patients with IgAN, assisting clinicians in making timely, objective, and well-informed decisions regarding the need for renal biopsies and more appropriate use of immunosuppressive therapy in patients with IgAN.

Optic canal stenosis in Crouzon syndrome: a case report and literature review

Incidence of Crouzon syndrome is 1 per 25.000-31.000 newborns. This syndrome is extremely rarely accompanied by optic canal stenosis. To present a patient with Crouzon syndrome and optic canal stenosis, to discuss the management of such patients considering own and literature data. A 6-year-old boy presented with Crouzon syndrome (verified by molecular genetic research, i.e. FGFR2 gene mutation). The patient underwent 3 surgeries for craniosynostosis and hydrocephalus. Nevertheless, visual acuity progressively decreased despite patent ventriculoperitoneal shunt. Examination revealed severe decrease in visual functions with optic disc congestion under secondary atrophy. MRI data on subarachnoid CSF accumulation over both optic nerves potentially indicated optic canal stenosis. This assumption was confirmed by 3D CT. The patient underwent decompression of both optic canals with subsequent improvement of visual functions. Vision decrease following Crouzon syndrome may be due to optic canal stenosis. Decompression may be effective, even in long-term course of disease, and improve visual functions.

A Continuous Registry of Medical Record, Patient Input, and Epidemiological Data of Patients With Ulcerative Colitis: a Multicentre, Prospective, Observational Clinical Registry Study in Japan.

This registry aims to allow for a prospective non-interventional observational study of ulcerative colitis. This will facilitate monitoring of the current state of ulcerative colitis in Japan and improving the long-term disease course and adverse events associated with current treatment options. Inclusion of patients from five centres in Japan is planned. The study is expected to take place from July 15, 2020, to November 30, 2024. Background, demographics, and medical history/information will be collected from electronic medical records at enrolment. Medical information including medications, laboratory data, and disease activity will be collected automatically from electronic medical records throughout the study. Patient-reported quality of life data will be collected directly from patients via smartphone. Efficacy endpoints (clinical remission rate, clinical improvement rate, and endoscopic healing rate) and safety endpoints (incidence of adverse events and specific ulcerative colitis-related events) will be collected according to treatment administered. Treatment categories include no treatment, 5-aminosalicylic acids, corticosteroids, immunomodulators, immunosuppressants, anti-tumour necrosis alpha agents, cytapheresis, Janus kinase inhibitors, anti-integrin antibodies, and anti-interleukin-12/23 antibodies. The dataset will include cross-sectional and longitudinal data and is expected to capture the state of ulcerative colitis in Japan. Patients will be included on a large scale, and the registry will be established automatically from electronic medical records and direct patient input, facilitating the accurate recording of medical information for patients with ulcerative colitis in Japan and minimizing limitations intrinsic to databases that require manual data entry, such as the burden on participating investigators and entry of data with errors/typos.

Patterns of comorbidities differentially affect long-term functional evolution and disease activity in patients with ‘difficult to treat’ rheumatoid arthritis

BackgroundCharacterisation of the long-term outcome of patients with ‘difficult to treat’ (D2T) rheumatoid arthritis and factors contributing to its evolution are unknown. Herein, we explored the heterogeneity and contributing factors...

Early intervention and disease modification in atopic dermatitis-the current state of the field and barriers to progress.

Atopic dermatitis (AD) is a highly prevalent chronic inflammatory skin disease representing a major source of global disability burden. Disease-modifying therapies are showing promise in chronic inflammatory disorders such as rheumatoid arthritis and Crohn's disease with method and timing of initial treatment impacting long-term disease outcomes. Whether disease-modifying therapies, specifically those used as an early interventional approach, impacts disease course and comorbidity development in AD is not well-understood. We reviewed the progress in disease modification strategies, emphasizing early intervention approaches in common (or proto-typical) inflammatory diseases. Although more common in other fields, disease modification approaches are becoming increasingly investigated in dermatology, though studies in AD are lacking. Despite significant limitations in ongoing and completed studies, early data are promising and suggest that both the choice and timing of early intervention approach can affect long-term disease course and comorbidity development. To best improve AD patient outcomes, more research is needed to further explore the impact of early disease-modifying therapies. Future studies should focus on identifying the most effective approaches and extend the early results to a more inclusive set of comorbidities and longer-term outcomes.

Long-Term Efficacy and Safety of Fecal Microbiota Transplantation for C. difficile Infections Across Academic and Private Clinical Settings.

Fecal microbiota transplant (FMT) is increasingly performed for Clostridioides difficile infection (CDI), although long-term efficacy and safety data are limited and are focused on results from academic medical centers rather than private settings where most patients receive care. Medical records of 165 patients who received FMTs for CDI were reviewed from an academic medical center and an adjacent, unaffiliated private practice. Of these patients, 68 also completed a survey regarding their long-term disease course and interval health. CDI resolution occurred in 81.3% (100/123) at the academic center and 95.2% (40/42) in the private setting. Private practice patients were more likely to present with recurrent, rather than refractory, CDI (92.9% vs. 66.7% P <0.001). Those from the academic center were more likely to have comorbid IBD, recent hospitalization, recent proton pump inhibitor use, ongoing immunosuppression, and inpatient FMT (all P values <0.05).Among surveyed patients, 29.4% developed interval comorbidities or changes to pre-existing conditions after a median follow-up of 33.7 months (IQR 13.2 to 44.3mo). Of 30 patients requiring subsequent antibiotics, 13.3% suffered CDI relapse. All subjects who had initially responded to FMT but had a subsequent CDI (17.9%, 10/56) responded to another FMT. In a real-world setting, patients who underwent FMT at academic centers differed significantly in clinical characteristics from those treated at a private practice. In both settings, FMT is an effective treatment for CDI not responding to standard therapies, even after subsequent antibiotic use. New diagnoses following FMT, however, are common and merit further exploration.

Odour discrimination and identification as a biomarker of long-term disability worsening in multiple sclerosis

Background: Odour discrimination and identification (DI) are markers associated with disability worsening and neuroaxonal damage in multiple sclerosis (MS). Objective: The main objective of this research is to investigate whether longitudinal change of DI predicts long-term MS disease course. Methods: This is a 6-year prospective longitudinal study on MS patients at the MS Clinic Innsbruck. Clinical, bi-annual visits assessed patients’ history and Expanded Disability Status Scale (EDSS) score. DI and cognitive function were assessed at baseline (BL), Year 1 (Y1), Year 2 (Y2) and Year 6 (Y6) by the ‘Sniffin’ Sticks’/Symbol Digit Modalities Test. Results: Around 92 of 139 patients were available for Y6 follow-up. Mean DI scores significantly decreased over time (BL = 27.8, Y1 = 27.5, Y2 = 26.3 and Y6 = 26.3; p < 0.001) and negatively correlated with patients’ age (rs = −0.120, p = 0.032) and disease duration (rs = −0.103, p = 0.041). Multivariable regression analyses revealed that lower absolute DI scores and larger DI score loss over time were associated with higher probability of EDSS worsening (per −1 point: hazard ratio (HR) = 1.40 (1.16–1.68) and 2.34 (1.27–4.21)), progression independent of relapse activity (PIRA) (HR = 1.49 (1.20–1.85) and 2.22 (1.33–3.31)) and cognitive deterioration (HR = 1.75 (1.35–2.27) and 4.29 (1.26–2.84)) at Y6, but not with time to first relapse. Conclusion: Odour DI is an irreversible marker of neuroaxonal damage, associated with PIRA, cognitive deterioration and EDSS worsening.

Earlier clinical response predicts low rates of radiographic progression in biologic-naïve patients with active psoriatic arthritis receiving guselkumab treatment

ObjectiveAssess relationship between earlier clinical improvement and radiographic progression (RP) over 2 years in guselkumab-treated patients with active psoriatic arthritis (PsA).MethodPost hoc analyses combined data from DISCOVER-2 biologic-naïve adults with active PsA randomized to either guselkumab 100 mg every 4 weeks (Q4W) or guselkumab at W0, W4, then Q8W. Correlations (Spearman’s coefficient) between baseline disease parameters and total PsA-modified van der Heijde-Sharp (vdH-S) score were examined. Repeated-measures mixed models, adjusted for known RP risk factors, assessed the relationship between Disease Activity Index in PsA (DAPSA) improvement, DAPSA improvement exceeding the median or the minimal clinically important difference (MCID), or DAPSA low disease activity (LDA) at W8 and RP rate, assessed by change from baseline in vdH-S score through W100.ResultsBaseline age, PsA duration, CRP level, and swollen joint count, but not psoriasis duration/severity, weakly correlated with baseline vdH-S score. Elevated baseline CRP (parameter estimate [β] = 0.17–0.18, p < 0.03) and vdH-S score (β = 0.02, p < 0.0001) significantly associated with greater RP through W100. Greater improvement in DAPSA (β = -0.03, p = 0.0096), achievement of DAPSA improvement > median (least squares mean [LSM] difference: -0.66, p = 0.0405) or > MCID (-0.67, p = 0.0610), or DAPSA LDA (-1.44, p = 0.0151) by W8 with guselkumab significantly associated with less RP through W100. The effect of W8 DAPSA LDA on future RP was strengthened over time among achievers vs. non-achievers (LSM difference enhanced from -1.05 [p = 0.0267] at W52 to -1.84 [p = 0.0154] at W100).ConclusionsIn guselkumab-treated patients with active PsA, earlier improvement in joint symptoms significantly associated with lower RP rates through 2 years, indicating blockade of the IL-23 pathway may modify long-term disease course and prevent further joint damage.Key Points• Greater improvement in DAPSA at Week 8 of guselkumab treatment was significantly associated with less progression of structural joint damage at 2 years in patients with active psoriatic arthritis (PsA).• Early control of peripheral joint disease activity with blockade of the IL-23 pathway may modify long-term PsA trajectory and prevent further joint damage.

Genetic influences on disease course and severity, 30 years after a clinically isolated syndrome.

Multiple sclerosis risk has a well-established polygenic component, yet the genetic contribution to disease course and severity remains unclear and difficult to examine. Accurately measuring disease progression requires long-term study of clinical and radiological outcomes with sufficient follow-up duration to confidently confirm disability accrual and multiple sclerosis phenotypes. In this retrospective study, we explore genetic influences on long-term disease course and severity; in a unique cohort of clinically isolated syndrome patients with homogenous 30-year disease duration, deep clinical phenotyping and advanced MRI metrics. Sixty-one clinically isolated syndrome patients [41 female (67%): 20 male (33%)] underwent clinical and MRI assessment at baseline, 1-, 5-, 10-, 14-, 20- and 30-year follow-up (mean age ± standard deviation: 60.9 ± 6.5 years). After 30 years, 29 patients developed relapsing-remitting multiple sclerosis, 15 developed secondary progressive multiple sclerosis and 17 still had a clinically isolated syndrome. Twenty-seven genes were investigated for associations with clinical outcomes [including disease course and Expanded Disability Status Scale (EDSS)] and brain MRI (including white matter lesions, cortical lesions, and brain tissue volumes) at the 30-year follow-up. Genetic associations with changes in EDSS, relapses, white matter lesions and brain atrophy (third ventricular and medullary measurements) over 30 years were assessed using mixed-effects models. HLA-DRB1*1501-positive (n = 26) patients showed faster white matter lesion accrual [+1.96 lesions/year (0.64-3.29), P = 3.8 × 10-3], greater 30-year white matter lesion volumes [+11.60 ml, (5.49-18.29), P = 1.27 × 10-3] and higher annualized relapse rates [+0.06 relapses/year (0.005-0.11), P = 0.031] compared with HLA-DRB1*1501-negative patients (n = 35). PVRL2-positive patients (n = 41) had more cortical lesions (+0.83 [0.08-1.66], P = 0.042), faster EDSS worsening [+0.06 points/year (0.02-0.11), P = 0.010], greater 30-year EDSS [+1.72 (0.49-2.93), P = 0.013; multiple sclerosis cases: +2.60 (1.30-3.87), P = 2.02 × 10-3], and greater risk of secondary progressive multiple sclerosis [odds ratio (OR) = 12.25 (1.15-23.10), P = 0.031] than PVRL2-negative patients (n = 18). In contrast, IRX1-positive (n = 30) patients had preserved 30-year grey matter fraction [+0.76% (0.28-1.29), P = 8.4 × 10-3], lower risk of cortical lesions [OR = 0.22 (0.05-0.99), P = 0.049] and lower 30-year EDSS [-1.35 (-0.87,-3.44), P = 0.026; multiple sclerosis cases: -2.12 (-0.87, -3.44), P = 5.02 × 10-3] than IRX1-negative patients (n = 30). In multiple sclerosis cases, IRX1-positive patients also had slower EDSS worsening [-0.07 points/year (-0.01,-0.13), P = 0.015] and lower risk of secondary progressive multiple sclerosis [OR = 0.19 (0.04-0.92), P = 0.042]. These exploratory findings support diverse genetic influences on pathological mechanisms associated with multiple sclerosis disease course. HLA-DRB1*1501 influenced white matter inflammation and relapses, while IRX1 (protective) and PVRL2 (adverse) were associated with grey matter pathology (cortical lesions and atrophy), long-term disability worsening and the risk of developing secondary progressive multiple sclerosis.

Long-term outcomes following ileocolic resection for Crohn's disease: does earlier elective resection affect disease recurrence rates?

Surgical resection in Crohn's disease is sometimes the only alternative treating disease complications or refractory disease. The implications of early resection on disease course are still debatable. We aimed to assess the influence of preoperative disease duration on long-term postoperative disease course. A retrospective analysis of all Crohn's disease patients who underwent an elective primary ileocolic resection between 2010 and 2021 in a single tertiary medical center. The cohort was divided based on disease duration, Group A (47 patients) had a disease duration shorter than 3 years (median of 1 year) and Group B (139 patients) had a disease duration longer than 3 years (median of 11 years). Surgeries were less complex among Group A as noted by higher rates of laparoscopic assisted procedures (68.1% vs. 45.3%, P = 0.006), shorter surgery duration (134 vs. 167 min, P < 0.0001) less estimated blood loss (72.5 vs. 333 mL, P = 0.016) and faster return of bowel function (3 vs. 4 days, P = 0.011). However, propensity score matching nullified all the differences. Younger age (OR = 0.86, P = 0.004), pre-op steroids (OR = 3.69, P = 0.037) and longer disease duration (OR = 1.18, P = 0.012) were found to be independently significantly associated with severe complications. After a median follow-up time of 71.38 months no significant differences were found between the groups in terms of endoscopic (P = 0.59), or surgical recurrences rates (P = 0.82). The main effect of preoperative short disease duration was noted within the surgical complexity; however, matching suggests confounders as cause of the difference. No significant long-term implication was noted on disease recurrence.

Long-term follow up of patients with WHO grade 2 oligodendroglioma

PurposeSince the introduction of the molecular definition of oligodendrogliomas based on isocitrate dehydrogenase (IDH)-status and the 1p19q-codeletion, it has become increasingly evident how this glioma entity differs much from other diffuse lower grade gliomas and stands out with longer survival and often better responsiveness to adjuvant therapy. Therefore, apart from using a molecular oligodendroglioma definition, an extended follow-up time is necessary to understand the nature of this slow growing, yet malignant condition. The aim of this study was to describe the long-term course of the oligodendroglioma disease in a population-based setting and to determine which factors affect outcome in terms of survival.MethodsAll adults with WHO-grade 2 oligodendrogliomas with known 1p19q-codeletion from five Scandinavian neurosurgical centers and with a follow-up time exceeding 5 years, were analyzed regarding survival and factors potentially affecting survival.Results126 patients diagnosed between 1998 and 2016 were identified. The median follow-up was 12.0 years, and the median survival was 17.8 years (95% CI 16.0–19.6).Factors associated with shorter survival in multivariable analysis were age (HR 1.05 per year; CI 1.02–1.08, p < 0.001), tumor diameter (HR 1.05 per millimeter; CI 1.02–1.08, p < 0.001) and poor preoperative functional status (KPS < 80) (HR 4.47; CI 1.70–11.78, p = 0.002). In our material, surgical strategy was not associated with survival.ConclusionIndividuals with molecularly defined oligodendrogliomas demonstrate long survival, also in a population-based setting. This is important to consider for optimal timing of therapies that may cause long-term side effects. Advanced age, large tumors and poor function before surgery are predictors of shorter survival.Graphical