Inflammatory bowel disease in families with four or more affected first-degree relatives.

BACKGROUND: Family history increases the risk for inflammatory bowel diseases (IBDs). However, data on differences in phenotypic characteristics among patients with a strong family history of IBD are scarce and controversial. The aim of the study was to compare the phenotypic features of IBD patients with four or more affected first-degree relatives with sporadic cases of IBD. METHODS: Patients with familial and sporadic IBD were identified from the institutional IBD database. IBD patients from families with at least four first-degree affected relatives were selected for analysis and were compared to non-matched sporadic cases with IBD chosen randomly. Comparison for type of IBD (Crohn's disease (CD) vs. ulcerative colitis (UC)), age at onset as well as for disease extent, behavior, extraintestinal manifestations and indicators of severe disease were analyzed. RESULTS: Thirty-five patients with familial IBD (28 CD, seven UC) were compared to 88 sporadic IBD patients (61 CD, 24 UC and three IBDU). Disease duration was 10.3 ± 8.2 in the familial and 8.0 ± 7.2 years in the sporadic cases, p=.13. The familial cases were younger at diagnosis (19.3 ± 8.6 vs. 25.7 ± 11.8, p=.004). Patients with familial compared to sporadic IBD were significantly more likely to require steroid treatment (80% vs. 54.5%, p=.009), biological treatment (94.3%, vs. 63.6%, p<.001) or surgery (25.7%, vs. 11.4%, p=.048). CONCLUSIONS: IBD with a very strong positive family history is associated with younger age at onset and a more adverse IBD phenotype compared to sporadic IBD.

Clinical predictors for a complicated course of disease in an inception cohort of patients with ulcerative colitis: results from the prospective, observational EPICOL study.

PURPOSE: The clinical course of ulcerative colitis (UC) is highly heterogeneous, with 20 to 30% of patients experiencing chronic disease activity requiring immunosuppressive or biologic therapies. The aim of this study was to identify predictors for a complicated disease course in an inception cohort of patients with UC. METHODS: EPICOL was a prospective, observational, inception cohort (UC diagnosis, ≤ 6 months) study in 311 patients with UC who were naive to immunosuppressants (IS)/biologics. A complicated course of disease was defined as the need for IS and/or biologic treatment (here therapy with a TNF-α antagonist) and/or UC-related hospitalisation. Patients were followed up for 24 months. RESULTS: Of the 307 out of 311 participants (4 patients did not meet the inclusion criteria "confirmed diagnosis of active UC within the last 6 months" (n = 2) and "immunosuppressive-naïve" (n = 2), analysis population), 209 (68.1%) versus 98 (31.9%) had an uncomplicated versus a complicated disease course, respectively. In a multivariate regression analysis, prior use of corticosteroids and prior anaemia were associated with a significantly increased risk for a complicated disease course (2.3- and 1.9-fold increase, respectively; p < 0.001 and p = 0.002). Based on these parameters, a risk model for patient stratification was developed. CONCLUSION: Our study identifies anaemia and an early need for corticosteroids as predictors for a complicated course of disease in an inception cohort of patients with UC. By determining these parameters in routine clinical practice, our results may support the identification of patients who might benefit from early escalation of therapy.

Predictors of Complicated Disease Course in Children and Adults With Ulcerative Colitis: A Nationwide Study From the epi-IIRN.

BACKGROUND: Data on predictors of complicated ulcerative colitis (UC) course from unselected populations cohorts are scarce. We aimed to utilize a nationwide cohort to explore predictors at diagnosis of disease course in children and adults with UC. METHODS: Data of patients diagnosed with UC since 2005 were retrieved from the nationwide epi-IIRN cohort. Complicated disease course was defined as colectomy, steroid-dependency, or the need for biologic drugs. Hierarchical clustering categorized disease severity at diagnosis based on complete blood count, albumin, C-reactive protein and erythrocyte sedimentation rate (ESR), analyzed together. RESULTS: A total of 13 471 patients with UC (1427 [11%] pediatric-onset) including 103 212 person-years of follow-up were included. Complicated disease course was recorded in 2829 (21%) patients: 1052 (7.9%) escalated to biologics, 1357 (10%) experienced steroid-dependency, and 420 (3.1%) underwent colectomy. Probabilities of complicated disease course at 1 and 5 years from diagnosis were higher in pediatric-onset (11% and 32%, respectively) than adult-onset disease (4% and 16%; P < .001). In a Cox multivariate model, complicated course was predicted by induction therapy with steroids (hazard ratio [HR], 1.5; 95% CI, 1.2-2.0), extraintestinal manifestations (HR, 1.3; 95% CI, 1.03-1.5) and the disease severity clusters of blood tests (HR, 1.8; 95% CI, 1.01-3.1), while induction therapy with enemas (HR, 0.6; 95% CI, 0.5-0.7) and older age (HR, 0.99; 95% CI, 0.98-0.99) were associated with noncomplicated course. CONCLUSION: In this nationwide cohort, the probability of complicated disease course during the first 5 years from diagnosis was 32% in pediatric-onset and 16% in adults with UC and was associated with more severe clusters of routinely collected laboratory tests, younger age at diagnosis, extraintestinal manifestations, and type of induction therapy.

Prognostic factors of complicated disease course are vital for clinical decision-making of early escalation to intensive treatment. In this nationwide cohort, one-third of children and one-fifth of adults with UC developed complicated disease course. Disease course was predicted particularly by routinely collected laboratory tests, age, extraintestinal manifestations, and type of induction therapy at diagnosis.

Alzheimer's disease hypothesis and related therapies.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder and the most common cause for dementia. There are many hypotheses about AD, including abnormal deposit of amyloid ß (Aß) protein in the extracellular spaces of neurons, formation of twisted fibers of tau proteins inside neurons, cholinergic neuron damage, inflammation, oxidative stress, etc., and many anti-AD drugs based on these hypotheses have been developed. In this review, we will discuss the existing and emerging hypothesis and related therapies.

C-myb Regulates Autophagy for Pulp Vitality in Glucose Oxidative Stress.

Diabetes mellitus is closely related to oral-complicated diseases by oxidative stress. This study investigates whether cellular myeloblastosis (c-myb) could protect human dental pulp cells against glucose oxidative stress and regulate autophagy activity for pulp vitality. Diabetes mellitus was induced by streptozotocin in Sprague-Dawley rats, and their pulp tissue in teeth was analyzed in terms of pulp cavity and molecules by hematoxylin and eosin and immunohistochemistry staining. Human dental pulp cells were serially subcultured and treated with glucose oxidase in the presence of elevated glucose to generate glucose oxidative stress. The replication-deficient adenovirus c-myb and small interfering RNA c-myb were introduced for c-myb expression. The pulp tissue from the diabetic rats was structurally different from normal tissue in terms of narrow pulp capacity, reduced c-myb, and dentinogenesis molecules. Glucose oxidase treatment decreased c-myb and dentinogenesis molecules (bone morphogenetic protein 2 and 7, dentin matrix protein 1, and dentin sialophosphoprotein) in human dental pulp cells. However, overexpression of c-myb by adenovirus c-myb increased dentinogenesis, autophagy molecules (autophagy protein 5, microtubule-associated protein 1A/1B-light chain 3, and Beclin-1), and cell survival via p-AMPK/AKT signaling even with glucose oxidative stress. In contrast, the lack of c-myb decreased the above molecules and cell survival by downregulating p-AMPK/AKT signaling. The results indicate that diabetes leads to irreversible damage to dental pulp, which is related to downexpression of autophagy via the p-AMPK/AKT pathway by decline of c-myb. The findings of this study provide a new insight that c-myb could ameliorate autophagy activity and that it is applicable for monitoring complicated diseases of dental pulp. The involvement of c-myb in pulp pathology could serve a therapeutic target in oral-complicated diseases.

Current and future role of biomarkers in Crohn's disease risk assessment and treatment.

BACKGROUND: Crohn's disease (CD), a chronic inflammatory bowel disease (IBD), occurs in genetically susceptible individuals who develop aberrant immune responses to endoluminal bacteria. Recurrent inflammation increases the risk of several complications. Despite use of a traditional "step-up" therapy with corticosteroids and immunomodulators, most CD patients eventually require surgery at some time in their disease course. Newer biologic agents have been remarkably effective in controlling severe disease. Thus, "top-down," early aggressive therapy has been proposed to yield better outcomes, especially in complicated disease. However, safety and cost issues mandate the need for careful patient selection. Identification of high-risk candidates who may benefit from aggressive therapy is becoming increasingly relevant. Serologic and genetic markers of CD have great potential in this regard. The aim of this review is to highlight the clinical relevance of these markers for diagnostics and prognostication. METHODS: A current PubMed literature search identified articles regarding the role of biomarkers in IBD diagnosis, severity prediction, and stratification. Studies were also reviewed on the presence of IBD markers in non-IBD diseases. RESULTS: Several IBD seromarkers and genetic markers appear to be associated with complex CD phenotypes. Qualitative and quantitative serum immune reactivity to microbial antigens may be predictive of disease progression and complications. CONCLUSION: The cumulative evidence provided by serologic and genetic testing has the potential to enhance clinical decision-making when formulating individualized IBD therapeutic plans.