OBJECTIVES: To investigate the efficacy and safety of empagliflozin in patients with glycogen storage disease (GSD)-associated inflammatory bowel disease (IBD). METHODS: A cross-sectional study was conducted, enrolling 25 patients with GSD-associated IBD who received empagliflozin treatment. General data, details of empagliflozin use, and adverse events were collected. Clinical symptoms and biochemical parameters before and after empagliflozin therapy were compared. RESULTS: Twenty-five patients with GSD-associated IBD were included, with a median age at diagnosis of 0.7 years, and a mean age at initiation of empagliflozin therapy of (11 ± 6) years. The initial dose of empagliflozin was (0.30 ± 0.13) mg/(kg·d), with a maintenance dose of (0.40 ± 0.21) mg/(kg·d), and a treatment duration of (34 ± 6) months. Seventy-eight percent (18/23) of patients' parents reported that empagliflozin therapy reduced the frequency of infections and oral ulcers, and increased neutrophil counts. Clinically, the number of patients with anorexia decreased from 12 to 5 after treatment, and 30% showed improved appetite (P<0.05). The numbers of patients with diarrhea, mucus/bloody stools, perianal disease, and oral ulcers decreased from 19, 9, 11, and 21 before treatment to 7, 1, 0, and 10 after treatment, respectively (P<0.05). Laboratory findings showed that absolute neutrophil counts increased, while platelet counts, lactate, and uric acid levels decreased significantly after empagliflozin treatment (P<0.05). Adverse reactions occurred in 7 patients (28%) during empagliflozin treatment. Two cases occurred in the treatment initiation phase, presenting as hypotension or profuse sweating with dehydration, along with urinary tract infections (UTIs); empagliflozin was discontinued in both cases. During the maintenance phase, 3 cases of UTIs and 2 cases of hypoglycemia (one with profuse sweating) were reported. CONCLUSIONS Empagliflozin therapy can increase neutrophil counts, reduce the incidence of infections and oral ulcers, alleviate diarrhea and abdominal pain, improve appetite, and ameliorate platelet count, lactate, and uric acid levels in patients with GSD-associated IBD, demonstrating significant clinical benefit. UTIs, hypoglycemia, hypotension, profuse sweating, and dehydration may be potential adverse reactions associated with empagliflozin therapy.
Humans ; Benzhydryl Compounds/adverse effects* ; Male ; Female ; Glucosides/adverse effects* ; Inflammatory Bowel Diseases/etiology* ; Child ; Child, Preschool ; Cross-Sectional Studies ; Adolescent ; Glycogen Storage Disease/drug therapy* ; Infant

OBJECTIVES: The risk factors and role of mother‒child gut microbiota in pediatric inflammatory bowel disease (PIBD) remain unclear. We aimed to explore the clinical risk factors associated with PIBD, analyze the characteristics of gut microbiota of children and their mothers, and examine the correlation of the microbial composition in mother‒child pairs. METHODS: We conducted a case-control study including children with PIBD and their mothers as the case group, as well as healthy children and their mothers as the control group. Questionnaires were used to collect information such as family illness history and maternal and early-life events. Fecal samples were collected from the children and mothers for microbiota 16S ribosomal RNA (rRNA) sequencing to analyze the composition and its potential association with PIBD. RESULTS: A total of 54 pairs of cases and 122 pairs of controls were recruited. A family history of autoimmune disease and antibiotic use during pregnancy were associated with an increased risk of PIBD, and a higher education level of the father was associated with a decreased risk of PIBD. Children with PIBD and mothers exhibited different gut microbiota compared to healthy children and mothers. Similarities were observed in the gut microbiota of mothers and children in the same groups. Some bacterial biomarkers of mothers discovered in this study had the power to predict PIBD in their offspring. CONCLUSIONS PIBD is influenced by maternal risk factors and has unique gut microbiota characteristics. The mother‒child gut microbiota is closely related, suggesting the transmission and influence of the gut microbiota between mothers and children. This study highlights the potential pathogenesis of PIBD and provides a basis for developing targeted interventions.
Humans ; Gastrointestinal Microbiome ; Female ; Risk Factors ; Case-Control Studies ; Male ; Child ; Inflammatory Bowel Diseases/etiology* ; Adult ; RNA, Ribosomal, 16S/genetics* ; Feces/microbiology* ; Mothers ; Pregnancy ; Child, Preschool

OBJECTIVE: Observational studies have found associations between inflammatory bowel disease (IBD) and the risk of dementia, including Alzheimer's dementia (AD) and vascular dementia (VD); however, these findings are inconsistent. It remains unclear whether these associations are causal. METHODS: We conducted a meta-analysis by systematically searching for observational studies on the association between IBD and dementia. Mendelian randomization (MR) analysis based on summary genome-wide association studies (GWASs) was performed. Genetic correlation and Bayesian co-localization analyses were used to provide robust genetic evidence. RESULTS: Ten observational studies involving 80,565,688 participants were included in this meta-analysis. IBD was significantly associated with dementia (risk ratio [ RR] =1.36, 95% CI = 1.04-1.78; I ² = 84.8%) and VD ( RR = 2.60, 95% CI = 1.18-5.70; only one study), but not with AD ( RR = 2.00, 95% CI = 0.96-4.13; I ² = 99.8%). MR analyses did not supported significant causal associations of IBD with dementia (dementia: odds ratio [ OR] = 1.01, 95% CI = 0.98-1.03; AD: OR = 0.98, 95% CI = 0.95-1.01; VD: OR = 1.02, 95% CI = 0.97-1.07). In addition, genetic correlation and co-localization analyses did not reveal any genetic associations between IBD and dementia. CONCLUSION Our study did not provide genetic evidence for a causal association between IBD and dementia risk. The increased risk of dementia observed in observational studies may be attributed to unobserved confounding factors or detection bias.
Humans ; Mendelian Randomization Analysis ; Inflammatory Bowel Diseases/complications* ; Dementia/etiology* ; Observational Studies as Topic ; Genome-Wide Association Study

Inflammatory bowel disease (IBD) is a chronic nonspecific intestinal inflammatory disease of unknown etiology. This disease includes three main types: Crohn′s disease (CD), ulcerative colitis (UC), and IBD-unclassified (IBD-U). IBD is frequently presented in adults, but in recent years, there is a rising incidence in pediatric populations. Very early onset IBD (VEO-IBD) is a fraction of pediatric IBD, but they have exclusive phenotypic and genetic characteristics such that they are accompanied by severe disease course and resistance to conventional therapy. The purpose of this review is to provide a contemporary overview of the clinical features, pathogenesis, and management of VEO-IBD.
Humans ; Inflammatory Bowel Diseases ; etiology ; therapy ; Nutritional Support ; Stem Cell Transplantation

Behcet's disease (BD) is a multi-systemic inflammatory disorder of an unknown etiology and shows a chronic recurrent clinical course. When the disease involves the alimentary tract, it is called intestinal BD because of its clinical importance. Intestinal BD is more frequently reported in East Asian countries than in Western or Middle Eastern countries. While any part of the gastrointestinal tract can be involved, the most common location of intestinal BD is the ileocecal area. A few, large, deep ulcerations with discrete border are characteristic endoscopic findings of intestinal BD. Currently, there is no single gold standard test or pathognomonic finding of intestinal BD. However, recently developed novel diagnostic criteria and a disease activity index have helped in assessing intestinal BD. As intestinal BD shares a lot of characteristics with inflammatory bowel disease, including genetic background, clinical manifestations, and therapeutic strategies, distinguishing between the two diseases in clinical practice is quite difficult. However, biologic agents such as anti-tumor necrosis factor alpha antibody shows a considerable efficacy similar to inflammatory bowel disease cases. It is important to distinguish and treat those two disease entities separately from the standpoint of precise medicine. Clinicians should require comprehensive knowledge regarding the similarities and differences between intestinal BD and inflammatory bowel disease for making an accurate clinical decision.
Behcet Syndrome/*diagnosis/therapy ; Diagnosis, Differential ; Gastrointestinal Diseases/*diagnosis/therapy ; Humans ; Inflammatory Bowel Diseases ; Male ; Middle Aged ; Systemic Vasculitis/*diagnosis/etiology ; Treatment Outcome ; Tumor Necrosis Factor-alpha/therapeutic use

Ulcerative colitis is an idiopathic chronic inflammatory bowel disease and its incidence in Korea has rapidly increased over the past two decades. Since ulcerative colitis is associated with increased risk for colorectal cancer, annual or biannual colonoscopy with four quadrant random biopsies at every 10 cm segments has been recommended for surveillance of colitic cancer in patients with long standing left-sided or extensive colitis. Recent epidemiologic data and meta-analysis suggest that the increment of colorectal cancer risk in ulcerative colitis was not larger than that of previous studies. Moreover, in addition to the extent and duration of colitis, other risk factors such as family history of colorectal cancer, primary sclerosing cholangitis, stricture, pseudopolyps, and histologic severity of inflammation have been recognized. As a result, updated guidelines provide surveillance strategies adjusted to the individual patient's risk for colitic cancer. Regarding surveillance method, target biopsy under panchromoendoscopy is preferentially recommended rather than random biopsy.
Cholangitis, Sclerosing/complications ; Colitis, Ulcerative/*complications ; Colon/pathology ; Colorectal Neoplasms/epidemiology/*etiology ; Humans ; Inflammatory Bowel Diseases/complications ; Polyps ; Risk Factors

Although inflammatory bowel disease (IBD) is a chronic disorder that mainly affects the gastrointestinal tract, extraintestinal complications can occur in IBD patients. Among many extraintestinal complications, venous thromboembolism (VTE) is particularly a feared complication due to its significant morbidity and mortality. IBD patients have about 2 to 3 fold higher risk of developing VTE compared with the general population, and the current management guidelines for IBD patients propose recommendations for the prevention of VTE. This review aims to summarize clinical characteristics of VTE in IBD patients and to outline strategies for preventing and treating VTE in these patients.
Anticoagulants/*therapeutic use ; Heparin, Low-Molecular-Weight/therapeutic use ; Humans ; Inflammatory Bowel Diseases/complications/*diagnosis ; Platelet Aggregation Inhibitors/therapeutic use ; Risk Factors ; Venous Thromboembolism/*drug therapy/etiology/prevention & control

Anemia is one of the commonest extraintestinal manifestations of inflammatory bowel disease (IBD). The pathogenesis of anemia in IBD is complex but iron deficiency combined with inflammation is the most common factor related to the development of anemia. However, other causes such as vitamin B12 and folate deficiency, hemolysis, myelosuppression and drug also should not be overlooked. In addition to ferritin, inflammatory markers and new biochemical parameters such as hepcidin and ferritin index are being tested as diagnostic a tool. First step for treatment is disease activity control and iron supplementation. Although oral iron is widely used, intravenous iron therapy should be considered in patients who are intolerant to oral iron therapy, have severe and refractory anemia or are in active disease state. Recently, new intravenous iron formulations have been introduced and due to their safety and easy usage, they have become the standard treatment modality for managing anemia in IBD. Erythropoietin and transfusion can be considered in specific situations. Vitamin B12 and folate supplementation is also important in patients who are deficient of these micronutrients. Since anemia in IBD patients could significantly influence the disease outcome, further studies and standard guideline for IBD are needed.
Anemia/*drug therapy/etiology ; Biomarkers/analysis ; Ferritins/analysis ; Hepcidins/analysis ; Humans ; Inflammatory Bowel Diseases/complications/*diagnosis ; Iron/*therapeutic use ; Vitamin B 12/therapeutic use

China ; Colitis, Ulcerative ; epidemiology ; etiology ; Crohn Disease ; epidemiology ; etiology ; Humans ; Inflammatory Bowel Diseases ; epidemiology ; etiology ; Sweetening Agents ; adverse effects

BACKGROUND/AIMS: Azathioprine (AZA) has been widely used in the therapy of inflammatory bowel disease (IBD) and autoimmune hepatitis (AIH). However, studies evaluating the adverse effects of AZA in these two diseases are lacking. The aim of this study was to compare the adverse effects of AZA in Korean IBD and AIH patients. METHODS: Patients with IBD or AIH who were treated with AZA at Keimyung University Dongsan Medical Center (Daegu, Korea) between January 2002 and March 2011 were enrolled. Their medical records were reviewed retrospectively in terms of clinical characteristics and adverse effects of AZA. RESULTS: A total of 139 IBD patients and 55 AIH patients were finally enrolled. Thirty IBD patients (21.6%) and eight AIH patients (14.5%) experienced adverse effects of AZA. In particular, the prevalence of leukopenia was significantly higher in the IBD group than in the AIH group (p=0.026). T474C mutation was observed in three of 10 patients who were assessed for thiopurine methyltransferase (TPMT) genotype. CONCLUSIONS: IBD patients are at increased risk for the adverse effects of AZA compared with AIH patients, of which leukopenia was the most commonly observed. Therefore, IBD patients receiving AZA therapy should be carefully monitored.
Adolescent ; Adult ; Aged ; Azathioprine/adverse effects/*therapeutic use ; Base Sequence ; Female ; Genotype ; Hepatitis, Autoimmune/*drug therapy ; Humans ; Immunosuppressive Agents/adverse effects/*therapeutic use ; Inflammatory Bowel Diseases/*drug therapy ; Leukopenia/epidemiology/etiology ; Male ; Methyltransferases/chemistry/genetics ; Middle Aged ; Polymorphism, Single Nucleotide ; Republic of Korea ; Retrospective Studies ; Young Adult