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1.
Inflamm Bowel Dis ; 2020 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-31895948

RESUMO

BACKGROUND: Selective blocking of HDAC6 has become a promising strategy in treating inflammatory bowel disease. CKD-506 is a novel isoform-selective inhibitor of histone deacetylase 6. The present study was performed to evaluate the effect of CKD-506 on the NF-κB signaling pathway in intestinal epithelial cells (IECs) and macrophages and on murine models of acute and chronic colitis. METHODS: RAW264RAW264.7 murine macrophages and COLO 205 human IECs were pretreated with CKD-506 and then stimulated with lipopolysaccharides (LPS). Cytokine expression of TNF-α, interleukin (IL)-6, IL-8, and IL-10 was measured by ELISA. The effect of CKD-506 on NF-κB signaling was evaluated by Western blotting of IκBα phosphorylation/degradation and electrophoretic mobility shift assay. In vivo studies were performed using a dextran sulfate sodium (DSS)-induced acute colitis model, a chronic colitis model in IL-10 knockout mice, and an adoptive transfer model. Colitis was quantified by the disease activity index, colon length, and histopathologic evaluation. RESULTS: CKD-506 suppressed the expression of pro-inflammatory cytokines such as IL-6, IL-8, and TNF-α in IECs and macrophages. CKD-506 strongly inhibited IκBα phosphorylation/degradation and the DNA-binding activity of NF-κB. Oral administration of CKD-506 attenuated DSS-induced acute colitis and chronic colitis in IL-10-/- and adoptive transfer models. CKD-506 ameliorated weight loss, disease activity, and histopathologic score in colitis mice and downregulated IκBα phosphorylation and pro-inflammatory cytokine production significantly. CONCLUSIONS: CKD-506 blocked NF-κB signaling in IECs and macrophages and ameliorated experimental acute and chronic murine colitis models, which suggests that CKD-506 is a promising candidate for inflammatory bowel disease treatment as a small molecular medicine.

2.
Aliment Pharmacol Ther ; 51(4): 446-456, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31691306

RESUMO

BACKGROUND: The relationships between lipid profiles and IBD remain elusive. AIM: To determine the association of IBD with serum lipid profiles. METHODS: A nationwide population-based study was performed using claims data from the Korean National Healthcare Insurance service. A total of 9 706 026 subjects undergoing medical check-ups in 2009 were enrolled and followed up until 2016. Individuals who developed Crohn's disease (CD) or ulcerative colitis (UC) were identified during follow-up. Adjusted hazard ratio (aHR) by age, sex, body mass index, cigarette smoking, alcohol drinking, exercise, income and underlying comorbidities was calculated to define the impact of serum lipid profiles on developing IBD. RESULTS: During a median follow-up of 7.3 years, IBD was detected in 7,058 (0.07%) individuals. Compared with the highest quartile of serum total cholesterol (TC) levels, lower TC levels were associated with higher incidence of CD (aHR: Q1, 2.52; Q2, 1.52; Q3, 1.27), but not UC. Lower serum LDL-C levels were associated with higher incidence of CD (aHR: Q1, 1.92; Q2, 1.47; Q3, 1.22), but not UC. Moreover, lower serum HDL-C levels were associated with higher incidence of CD (aHR: Q1, 2.49; Q2, 1.90; Q3, 1.43), but not UC. In contrast, lower serum triglyceride levels were associated with higher incidence of UC (aHR: Q1, 1.22; Q2, 1.19; Q3, 1.19), but not CD. CONCLUSIONS: Low serum TC, LDL-C and HDL-C levels were associated with CD. Low serum triglyceride levels were related to UC.

3.
Inflamm Bowel Dis ; 26(2): 242-253, 2020 01 06.
Artigo em Inglês | MEDLINE | ID: mdl-31586441

RESUMO

BACKGROUND: Tumor necrosis factor (TNF)-α is a major proinflammatory cytokine that plays a key role in inflammatory bowel disease (IBD). Inactive rhomboid protein 2 (iRhom2) is essential for activating TNF-α-converting enzyme (TACE) in immune cells, which regulates TNF-α release. The aim of the study was to investigate the role of iRhom2 in intestinal inflammation in IBD. METHODS: The expression of iRhom2 and TACE in lipopolysaccharide (LPS)-stimulated COLO 205 and RAW 264.7 cells was assessed by reverse transcription polymerase chain reaction (RT-PCR) and Western blot analysis. The expression of iRhom2 and TACE in the colonic tissue of IBD patients and 2,4,6-trinitrobenzenesulfonic acid solution (TNBS)-treated mice was determined by RT-PCR and immunohistochemistry. To assess the role of iRhom2 in intestinal inflammation, colitis was induced in wild-type and iRhom2-/- mice by the administration of TNBS enema. RESULTS: In LPS-stimulated COLO 205 and RAW 264.7 cells, the mRNA and protein levels of TACE and iRhom2 were upregulated. The expression of TACE and iRhom2 in the colon of the IBD patients and TNBS-treated mice was significantly enhanced. The inflammatory cells that expressed high levels of iRhom2 in the colon were identified as macrophages. Finally, iRhom2 deficiency ameliorated TNBS-induced colitis by inhibiting TNF-α release. CONCLUSIONS: iRhom2 has an important role in intestinal inflammation through TNF-α secretion in immune cells, which suggests that iRhom2 could be a novel therapeutic target for IBD.

4.
J Gastroenterol Hepatol ; 35(1): 29-36, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31396995

RESUMO

BACKGROUND AND AIM: PBK-1701TC is a novel sulfate tablet-based that contains 320 mg of simethicone and delivers 90% of the salt and water delivered by oral sulfate solution (OSS) preparation. This study evaluated the efficacy, safety, and tolerability of PBK-1701TC compared with OSS in bowel preparation for colonoscopy. METHODS: This randomized, multicenter, phase 3 non-inferiority trial included adults aged 19 years or older with a body mass index of 19-30 kg/m2 undergoing colonoscopy at five university hospitals in Korea. The primary efficacy endpoint was successful bowel-cleansing rate, defined as Harefield Cleansing Scale grade A or B as evaluated by blinded central readers. Secondary endpoints included the presence of residual air bubbles. Adverse events and laboratory evaluations were monitored to assess safety. Tolerability was assessed via participant interview. RESULTS: Overall, 235 participants were randomized, and 224 were included in the per-protocol analysis (PBK, 112; OSS, 112). Successful bowel cleansing was achieved for 95.5% (107/112) in the PBK group, which was non-inferior to the OSS group (98.2%, 110/112) with a difference of -2.7% (one sided 97.5% confidence limit, -8.1%). The participants in the PBK group had fewer intraluminal bubbles (0.9% vs 81.3%, P < 0.001) and reported a lower incidence of nausea and vomiting, with better acceptance, taste, and willingness to repeat the regimen than those in the OSS group (all P < 0.05). CONCLUSION: The novel sulfate tablet, PBK-1701TC, was non-inferior to OSS with respect to bowel-cleansing efficacy and exhibited better safety and tolerability in adults undergoing colonoscopy.

5.
J Gastroenterol Hepatol ; 35(2): 249-255, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31420894

RESUMO

BACKGROUND AND AIM: The relationship between inflammatory bowel disease (IBD) and idiopathic pulmonary fibrosis (IPF) remains unclear. We evaluated the risk for developing IPF in patients with IBD using a nationwide population-based study. METHODS: Using claims data from the National Health Insurance service in Korea, patients with IBD, including Crohn's disease (CD) and ulcerative colitis (UC), were identified through both the 10th revision of the International Statistical Classification of Diseases and Related Health Problems and rare and intractable disease program codes from January 2010 to December 2013. We compared 38 921 IBD patients with age-matched and sex-matched individuals without IBD in a ratio of 1:3. Patients with newly diagnosed IPF were identified by both the 10th revision of the International Statistical Classification of Diseases and Related Health Problems and rare and intractable disease registration codes. RESULTS: During a mean 4.9-year follow-up, the incidence of IPF in patients with IBD was 33.21 per 100 000 person-years. The overall risk of IPF was significantly higher in IBD patients than in non-IBD controls (hazard ratio [HR], 1.62; 95% confidence interval [CI], 1.20-2.20; P = 0.003). In patients with CD, the incidence (per 100 000 person-years) of IPF was 26.04; in controls, the incidence was 9.15 (HR, 2.89; 95% CI, 1.46-5.72; P = 0.002). The incidence of IPF in patients with UC tended to be higher than in controls (36.66 vs 26.54 per 100 000 person-years; 95% CI, 0.99-1.99; HR, 1.41; P = 0.066). The risk of developing IPF in patients with IBD was higher in male patients than in female patients (P = 0.093 in CD; P = 0.147 in UC by interaction analysis). CONCLUSIONS: Patients with IBD, especially CD, have an increased risk of developing IPF.

6.
Gut Liver ; 14(1): 89-99, 2020 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-31158951

RESUMO

Background/Aims: We aimed to investigate the differences in direct healthcare costs between patients with and without inflammatory bowel disease (IBD) and changes in direct healthcare costs before and after IBD diagnosis. Methods: This population-based study identified 34,167 patients with IBD (11,014 patients with Crohn's disease and 23,153 patients with ulcerative colitis) and 102,501 age-and sex-matched subjects without IBD (the control group) from the National Health Insurance database using the International Classification of Disease, 10th revision codes and the rare intractable disease registration program codes. The mean healthcare costs per patient were analyzed for 3 years before and after IBD diagnosis, with follow-up data available until 2015. Results: Total direct healthcare costs increased and peaked at $2,396 during the first year after IBD diagnosis, but subsequently dropped sharply to $1,478 during the second year after diagnosis. Total healthcare costs were higher for the IBD patients than for the control group, even in the third year before the diagnosis ($497 vs $402, p<0.001). The costs for biologics for the treatment of IBD increased steeply over time, rising from $720.8 in the first year after diagnosis to $1,249.6 in the third year after diagnosis (p<0.001). Conclusions: IBD patients incurred the highest direct healthcare costs during the first year after diagnosis. IBD patients had higher costs than the control group even before diagnosis. The cost of biologics increased steeply over time, and it can be assumed that biologics could be the main driver of costs during the early period after IBD diagnosis.

7.
Front Oncol ; 9: 1249, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31799199

RESUMO

Background: Insulin resistance, the primary mechanism of metabolic syndrome, promotes gastric carcinogenesis. Metabolic syndrome is associated with sarcopenia. We aimed to investigate the association between sarcopenia and gastric carcinogenesis, including precancerous conditions such as atrophic gastritis (AG), intestinal metaplasia (IM), and dysplasia. Methods: The study included adult patients who underwent gastroduodenoscopy at a checkup center. AG and IM were evaluated using endoscopy. Based on muscle mass, sarcopenia was defined as a skeletal muscle index <1 standard deviation below the sex-specific mean for healthy adults aged 20-39 years (cutoff point: 29.3% for males and 26.7% for females). Obesity was defined as a body mass index (BMI) ≥25 kg/m2 according to the Asia-Pacific criteria. Sarcopenic obesity was defined as a combination of sarcopenia and obesity. The association between gastric carcinogenesis and sarcopenia was evaluated. Results: Among 8,356 enrolled participants, 0.14 and 42.5% were diagnosed with gastric cancer and precancerous conditions, respectively. Approximately 41.7% of gastric cancer patients and 16.9% of patients with precancerous conditions were diagnosed with sarcopenia. Both sarcopenic obesity (odds ratio [OR] = 4.139, P = 0.016) and diabetes mellitus (DM) (OR = 5.152, P = 0.005) were significantly associated with gastric cancer. Sarcopenia, DM, hypertension, dyslipidemia, Helicobacter pylori infection, smoking, and alcohol consumption were significantly associated with precancerous conditions. Conclusions: Sarcopenia and sarcopenic obesity were associated with gastric carcinogenesis and may be novel risk factors for gastric carcinogenesis.

8.
Gut Liver ; 2019 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-31816671

RESUMO

Background/Aims: Ghrelin agonists are emerging prokinetic agents for treating gastroparesis. Although recent clinical trials have demonstrated their efficacy in patients with diabetic gastroparesis (DG), the impact of such agents on symptoms and gastric dysmotility remains unclear. We performed a systematic review and meta-analysis to evaluate the efficacy and safety of ghrelin agonists in patients with DG. Methods: A search of common electronic databases (MEDLINE, Embase, and Cochrane Central Register of Controlled Trials) was preformed, using keyword combinations that referenced ghrelin and DG and retrieving all eligible randomized controlled trials (RCTs) of ghrelin agonists versus placebo in patients with DG. The primary outcome measure was the change in patient-reported overall gastroparesis symptom scores. Secondary outcomes included the change in gastric emptying time, specific symptoms related to gastroparesis, and adverse events. A random-effects model was applied to all study outcomes. Heterogeneity among studies was determined by the chi-square test and I2 statistics. Results: We selected six RCTs of patients with DG (n=557) for meta-analysis. Ghrelin agonist administration (vs placebo) significantly improved overall gastroparesis symptoms (standardized mean difference, -0.34; 95% confidence interval, -0.56 to -0.13) and significantly improved symptoms related to gastroparesis, including nausea, vomiting, early satiety, and abdominal pain. Adverse events recorded for ghrelin agonists and placebo did not differ significantly. There was no significant heterogeneity among eligible studies. Conclusions: Compared with placebo, ghrelin agonists are effective and well-tolerated for the treatment of DG.

9.
Gut Liver ; 2019 12 11.
Artigo em Inglês | MEDLINE | ID: mdl-31816672

RESUMO

Background/Aims: The risk for colonoscopic postpolypectomy bleeding (PPB) in patients with chronic liver disease (CLD) remains unclear. We determined the incidence and risk factors for colonoscopic PPB in patients with CLD, especially those with liver cirrhosis. Methods: We retrospectively reviewed the medical records of patients with CLD who underwent colonoscopic polypectomy at Seoul National University Hospital between 2011 and 2014. The study endpoints were immediate and delayed PPB. Results: A total of 1,267 consecutive patients with CLD were included in the study. Immediate PPB occurred significantly more often in the Child-Pugh (CP) B or C cirrhosis group (17.5%) than in the CP-A (6.3%) and chronic hepatitis (4.6%) groups (p<0.001). Moreover, the incidence of delayed PPB in the CP-B or C cirrhosis group (4.4%) was significantly higher than that in the CP-A (0.7%) and chronic hepatitis (0.2%) groups (p<0.001). The independent risk factors for immediate PPB were CP-B or C cirrhosis (p=0.011), a platelet count <50,000/µL (p<0.001), 3 or more polyps (p=0.017), endoscopic mucosal resection or submucosal dissection (p<0.001), and polypectomy performed by trainees (p<0.001). The independent risk factors for delayed PPB were CP-B or C cirrhosis (p=0.009), and polyps >10 mm in size (p=0.010). Conclusions: Patients with CP-B or C cirrhosis had an increased risk for bleeding following colonoscopic polypectomy.

10.
Surg Endosc ; 2019 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-31820151

RESUMO

BACKGROUND AND STUDY AIMS: Biopsy-based histologic diagnosis is important in determining the treatment strategy for early gastric cancer (EGC). However, there are few studies on how histologic discrepancy may affect patients' treatment outcomes. We aimed to investigate the impact of histopathologic differences between biopsy and final specimens from endoscopic resection (ER) or gastrectomy on treatment outcomes in patients with EGC. We also examined the predictive factors of histologic discrepancy. PATIENTS AND METHODS: We analyzed the data of 1851 patients with EGC treated with ER or gastrectomy. We compared the histology between biopsies and final resected specimens from ER or gastrectomy. We also examined changes in treatment outcomes according to histologic differences. RESULTS: Histologic discrepancy was observed in 11.9% of patients in the ER group and 10.7% of those in the gastrectomy group. In patients treated with ER who showed histologic discrepancy, 80.9% showed differentiated-type EGC (D-EGC) on biopsy but undifferentiated-type-EGC (UD-EGC) after ER, of which 78.9% were non-curative resection. In patients treated with gastrectomy who showed histologic discrepancy, 39% showed UD-EGC on biopsy but showed D-EGC after gastrectomy. A total of these patients had absolute and expanded indications for ER. Moderately differentiated and poorly differentiated adenocarcinoma on biopsy were predictive factors of histologic discrepancy in UD-EGC and D-EGC on final resection, respectively. CONCLUSIONS: About 10% of patients showed histologic discrepancy between biopsy and final resection with ER or gastrectomy. Histologic discrepancy can affect treatment outcomes, such as non-curative resection in ER or missing the opportunity for ER in gastrectomy.

11.
Korean J Intern Med ; 2019 12 30.
Artigo em Inglês | MEDLINE | ID: mdl-31878772

RESUMO

Background/Aims: Capsule endoscopy (CE) is widely used for the diagnosis of small bowel diseases. The clinical performance and complications of small bowel CE, including completion rate, capsule retention rate, and indications, have been previously described in Korea. This study aimed at estimating the recent changes in clinical performance and complications of small bowel CE based on 17-year data from a Korean Capsule Endoscopy Registry. Methods: CE registry data from 35 hospitals were retrospectively analyzed. Clinical information, including completion rate, capsule retention rate, and indications, was collected and analyzed. In addition, the most recent 5-year data for CE examinations were compared with the previous 12-year data. Results: A total of 4,650 CE examinations were analyzed. The most common indication for CE was obscure gastrointestinal bleeding (OGIB). The overall incomplete examination rate was 16% and the capsule retention rate was 3%. Crohn's disease was a risk factor for capsule retention. Inadequate bowel preparation was significantly associated with capsule retention and incomplete examination. An indication other than OGIB was a risk factor for incomplete examination. A recent increasing trend of CE diagnosis of Crohn's disease was observed. The most recent 5-year incomplete examination rate for CE examinations decreased compared with that of the previous 12 years. Conclusions: The 17-year data suggested that CE is a useful and safe tool for diagnosing small bowel diseases. The incomplete examination rate of CE decreased with time, and OGIB was consistently the main indication for CE. Inadequate bowel preparation was significantly associated with capsule retention and incomplete examination.

12.
PLoS One ; 14(12): e0226427, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31851694

RESUMO

BACKGROUND: Gastric cancer (GC) is categorized as diffuse- and intestinal-type adenocarcinoma. Intestinal-type GC is associated with chronic gastritis, atrophic gastritis (AG), and intestinal metaplasia (IM), precursors of dysplastic changes. Diffuse-type GC is generally known to undergo de novo carcinogenesis and is not associated with chronic mucosal changes. However, clinically, AG and IM are frequently observed surrounding diffuse-type GC. This study aimed to evaluate the role of AG and IM in diffuse-type GC. METHODS: We retrospectively reviewed the data of patients undergoing surgery for early GC. We divided patients with diffuse-type GC into two groups according to the presence of AG and IM based on Kyoto classification of gastritis. The clinicopathological characteristics were compared between the groups. RESULTS: Among patients with diffuse-type GC, 52.5% patients had AG and 18.4% had severe AG. With regard to IM, 42.1% patients had IM and 17.1% had severe IM. Diffuse-type GC combined with severe AG or IM showed larger tumor size and higher submucosal invasion rate than that without severe AG or IM. However, the lymph node metastasis (LNM) rate was not significantly different between the two groups. In multivariate analysis, severe AG or IM was not an independent risk factor for LNM. CONCLUSIONS: Severe AG or IM surrounding diffuse-type gastric cancer suggests a collapse of normal mucosal barriers and leads to the spread of cancer cells. Although the association between chronic mucosal changes and LNM is unclear, more caution is needed during endoscopy especially for complete resection of diffuse-type GC with these features.

13.
World J Gastroenterol ; 25(42): 6354-6364, 2019 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-31754295

RESUMO

BACKGROUND: There is a growing evidence regarding an increased risk of inflammatory bowel disease (IBD) among patients with airway diseases. AIM: To investigate the influence of chronic obstructive pulmonary disease (COPD) on the risk of IBD. METHODS: A nationwide, population-based study was conducted using data from the National Health Insurance Service database. A total of 1303021 patients with COPD and 6515105 non-COPD controls were identified. The COPD group was divided into the severe and the mild COPD group according to diagnostic criteria. The risk of IBD in patients with COPD compared to controls was analyzed by Cox proportional hazard regression models. The cumulative incidences of IBD were compared between the groups. RESULTS: The COPD group had higher incidences of IBD compared to non-COPD controls (incidence rate, 9.98 vs 7.18 per 100000 person-years, P < 0.001). The risk of IBD in the COPD group was increased by 1.38 (adjusted hazard ratio (HR); 95%CI: 1.25-1.52). The incidence rate of IBD was higher in the severe COPD group than in the mild COPD group (12.39 vs 9.77 per 100000 person-year, P < 0.001). The severity of COPD was associated with an increased risk of IBD (adjusted HR 1.70 in severe COPD, 95%CI: 1.27-2.21 and adjusted HR 1.35 in mild COPD, 95%CI: 1.22-1.49). CONCLUSION: The incidences of IBD were significantly increased in COPD patients in South Korea and the risk of developing IBD also increased as the severity of COPD increased.

14.
Korean J Gastroenterol ; 74(3): 168-174, 2019 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-31554033

RESUMO

Anti-tumor necrosis factor (anti-TNF) is an effective biological agent for the treatment of moderate-to-severe active ulcerative colitis (UC) refractory to conventional therapy. On the other hand, anti-TNF therapy is strongly associated with a potential risk of tuberculosis (TB). Active TB is a critical complication that makes it difficult to treat patients who require anti-TNF for the treatment of UC refractory to conventional therapy. Based on the clinical guidelines, patients with inflammatory bowel disease (IBD) are strongly recommended to screen for latent TB before anti-TNF administration. Considering the possibility of active or reactivated TB related to anti-TNF therapy, all patients with IBD should be monitored closely for TB during anti-TNF therapy, irrespective of the screening results for latent TB. In particular, the risk of anti-TNF-related multidrug-resistant TB (MDR-TB) in patients with IBD has not been elucidated. This paper reports the first case of disseminated MDR-TB that developed in a UC patient receiving infliximab despite the negative evaluation for latent TB screening.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Colite Ulcerativa/tratamento farmacológico , Infliximab/uso terapêutico , Tuberculose Resistente a Múltiplos Medicamentos/diagnóstico , Adulto , Anticorpos Monoclonais/efeitos adversos , Antituberculosos/uso terapêutico , Colite Ulcerativa/diagnóstico , Colonoscopia , Quimioterapia Combinada , Feminino , Humanos , Infliximab/efeitos adversos , Tuberculose Latente/diagnóstico , Linfonodos/patologia , Tomografia Computadorizada por Raios X , Tuberculose , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Tuberculose Resistente a Múltiplos Medicamentos/etiologia
15.
J Clin Med ; 8(8)2019 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-31398905

RESUMO

Background and Aims: It is not known whether inflammatory bowel disease (IBD) enhances the risk of Parkinson's disease (PD) or whether PD diagnosis is the result of increased health care use. We determined the risk of developing PD among patients with IBD in terms of health care and medication use. Methods: A nationwide population-based study was conducted using claims data from the Korean National Health care Insurance service. From 2010 to 2013, patients with Crohn's disease (CD) and ulcerative colitis (UC) were identified through both International Classification of Disease, Tenth Revision (ICD-10) and national rare intractable disease (RID) registration program codes. We compared 38,861 IBD patients with age and sex-matched non-IBD individuals at a ratio of 1:3. Patients with newly diagnosed PD were identified through both ICD-10 and RID codes. Results: The incidence of PD among patients with IBD was 49 per 100,000 person-years. The risk of developing PD in patients with IBD was significantly higher than controls even after adjustment for health care use (adjusted hazard ratio (aHR), 1.87; P < 0.001). Compared to controls, the risk of PD was significantly higher in patients with CD (aHR, 2.23; P = 0.023) and UC (aHR, 1.85; P < 0.001). Corticosteroid use showed a preventive effect on developing PD in patients with CD (aHR 0.08; P < 0.001), but not UC (aHR, 0.75; P = 0.213). Among 2110 patients receiving anti-tumor necrosis factor (anti-TNF), none of the treated patients experienced PD during 9950 person-years. Conclusion: Patients with IBD are at an increased risk of PD, regardless of health care use. Corticosteroid and anti-TNF use may prevent PD in patients with IBD.

16.
Artigo em Inglês | MEDLINE | ID: mdl-31446180

RESUMO

BACKGROUND & AIMS: Thiopurine-related myelosuppression (most frequently leukopenia) interferes with thiopurine therapy for patients with inflammatory bowel diseases (IBD). We investigated whether pretreatment analyses genetic variants associated with thiopurine-induced leukopenia could be used to effectively identify patients who required dose adjustments. METHODS: We performed a multicenter, prospective study of patients with IBD at 5 tertiary medical centers in Korea, from January 2016 through September 2018. Seventy-two patients were randomly assigned to a group that underwent genotype analysis for the NUDT15 variant (rs116855232) and FTO variant (rs79206939) and 3 common TPMT variants (rs1800460, rs1800462, rs1142345) associated with myelosuppression and 92 patients were assigned to a group that did not undergo genotype analysis (non-genotyping group). Patients heterozygous for any variant received 50 mg azathioprine equivalents, whereas those who were homozygous for any variant received alternative drugs. Patients who did not carry any of the genetic variants and patients in the non-genotyping group received 50 mg azathioprine equivalents followed by dose escalation up to 2-2.5 mg/kg. Myelosuppression was defined as white blood cell counts below 3000/µL, levels of hemoglobin 10 g/dL, or platelet counts below 100 K/µL. RESULTS: Twelve patients (16.7%) in the genotype analysis group and 33 patients (35.9%) in the non-genotyping group developed myelosuppression (P=.005). A multivariate analysis revealed that body mass indices above 21 kg/m2 (hazard ratio [HR], 0.43; 95% CI, 0.22-0.81; P = .009), pretreatment genotype analysis (HR, 0.37; 95% CI, 0.18-0.77; P = .008), and the maximum dose of thiopurines (HR, 0.34; 95% CI, 0.19-0.59; P < .001) independently decreased risk of myelosuppression. Pretreatment genotype analysis reduced numbers of outpatient clinic visit and numbers of patients with drug discontinuation or dose reductions. CONCLUSIONS: In a randomized controlled study of patients undergoing thiopurine therapy for IBD, we found that selection of therapy based on genetic variants associated with thiopurine-induced leukopenia significantly reduced the proportion of patients with myelosuppression during treatment. ClinicalTrials.gov no: NCT03719118.

17.
J Clin Med ; 8(9)2019 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-31454949

RESUMO

In early gastric cancer (EGC), tumor invasion depth is an important factor for determining the treatment method. However, as endoscopic ultrasonography has limitations when measuring the exact depth in a clinical setting as endoscopists often depend on gross findings and personal experience. The present study aimed to develop a model optimized for EGC detection and depth prediction, and we investigated factors affecting artificial intelligence (AI) diagnosis. We employed a visual geometry group(VGG)-16 model for the classification of endoscopic images as EGC (T1a or T1b) or non-EGC. To induce the model to activate EGC regions during training, we proposed a novel loss function that simultaneously measured classification and localization errors. We experimented with 11,539 endoscopic images (896 T1a-EGC, 809 T1b-EGC, and 9834 non-EGC). The areas under the curves of receiver operating characteristic curves for EGC detection and depth prediction were 0.981 and 0.851, respectively. Among the factors affecting AI prediction of tumor depth, only histologic differentiation was significantly associated, where undifferentiated-type histology exhibited a lower AI accuracy. Thus, the lesion-based model is an appropriate training method for AI in EGC. However, further improvements and validation are required, especially for undifferentiated-type histology.

18.
J Clin Med ; 8(5)2019 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-31083476

RESUMO

BACKGROUND AND AIMS: Inflammatory bowel disease (IBD) may be associated with anxiety and depression. The aim of this study was to evaluate the incidence of anxiety and depression in patients with IBD compared to the general population. Methods: A nationwide population-based cohort study was conducted using claims data from the National Healthcare Insurance service in Korea. We compared the incidence of anxiety and depression between 15,569 IBD patients and 46,707 non-IBD controls, age and sex matched at a ratio of 1:3. RESULTS: During a mean follow-up of six years, IBD patients experienced significantly more anxiety (12.2% vs. 8.7%; p < 0.001) and depression (8.0% vs. 4.7%; p < 0.001) compared to controls. The curves showing cumulative incidences of anxiety and depression showed a steep rise within one year following a diagnosis of IBD, leading to lines with a constant slope. The hazard ratio (HR) for new onset anxiety following a diagnosis of Crohn's disease (CD) and ulcerative colitis (UC) was 1.63 and 1.60, respectively, compared to controls (p < 0.001). Compared to controls, the HR for developing depression after a diagnosis of CD and UC was 2.09 and 2.00, respectively (p < 0.001). The risks of anxiety and depression in patients with IBD were higher compared to controls, except in those with diabetes mellitus, hypertension, and dyslipidemia, or who required immunomodulators and biologics within one year of the IBD diagnosis. CONCLUSIONS: The risk of anxiety and depression increased after a diagnosis of IBD compared to the general population.

19.
Dig Dis Sci ; 64(11): 3240-3246, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31076988

RESUMO

BACKGROUND: The most concerning complication of capsule endoscopy (CE) is capsule retention (CR) in the gastrointestinal (GI) tract; however, the clinical outcomes and management of patients with CR are still uncertain. AIMS: This study aimed to investigate the clinical outcomes and management of CR. METHODS: The outcomes of CR in multiple centers between October 2002 and June 2018 were retrospectively reviewed. Data on CE indication, findings, and management details were analyzed. RESULTS: A total of 2705 consecutive small-bowel CE procedures were performed. CR was detected in 20 cases (0.7%). The most common site of CR was the small bowel (19 cases), followed by the esophagus (one case). In patients who underwent CE, CR was detected in nine (0.6%) of 1397 patients with obscure GI bleeding. Further, CR occurred in 11 (6.5%) of 169 patients with Crohn's disease based on the final diagnoses after CE. Capsule retrieval was safely performed surgically in nine cases and endoscopically in six cases. The retained capsules dislodged after steroid treatment in two cases, whereas three cases of CR resolved without any intervention. In multivariate analysis, the development of abdominal symptoms after CR was a significant predictive factor for requiring endoscopic or surgical interventions for capsule extraction. CONCLUSIONS: This large multicenter study shows that CR is a rare complication with favorable clinical outcomes. Three-fourths of the patients with CR were managed with endoscopic or surgical intervention, which was required particularly in patients with abdominal symptoms after CR.

20.
J Gastroenterol ; 54(10): 881-890, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31093771

RESUMO

BACKGROUND: Former cigarette smokers are at risk of developing ulcerative colitis (UC). However, the impact of smoking behavior on the occurrence of UC according to the amount smoked remains elusive. We aimed to determine the relationship between smoking behavior and the risk of UC development. METHODS: We conducted a retrospective population-based cohort study using the National Health Insurance Service database in South Korea. From January 2009 to December 2012, 23,235,771 individuals over 18 years of age who underwent a national health examination were enrolled and followed until 2016. All study participants were divided into the following 3 groups: nonsmokers, former smokers, and current smokers. The primary endpoint was newly developed UC. RESULTS: Compared with nonsmokers, the risk of UC development was significantly higher in former smokers [adjusted hazard ratio (aHR) 1.83; 95% confidence interval (CI) 1.73-1.95] but significantly lower in current smokers (aHR 0.92; 95% CI 0.87-0.98). Among current smokers, individuals who stopped smoking after the baseline evaluation had a significantly higher risk of UC development than those who continued to smoke (aHR 2.42; 95% CI 2.10-2.80). The risk of UC development among former smokers was significantly associated with smoking amount and duration. Among current smokers, however, the risk of UC development was not correlated with the cumulative lifetime smoking exposure. The preventive effect of current smoking on UC development was observed only in men (aHR 0.90; 95% CI 0.84-0.96). CONCLUSIONS: Compared with nonsmokers, former smokers have a significantly higher risk of UC development that may be proportional to the cumulative smoking exposure.

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