During the coronavirus disease 2019 (COVID-19) pandemic, many unpredictable changes have occurred in the medical field. Risk of COVID-19 does not seem to increase in patients with inflammatory bowel ...disease (IBD) considering based on current reports. Current medications for IBD do not increase this risk; on the contrary, some of these might be used as therapeutics against COVID-19 and are under clinical trial. Unless the patients have confirmed COVID-19 and severe pneumonia or a high oxygen demand, medical treatment should be continued during the pandemic, except for the use of high-dose corticosteroids. Adherence to general recommendations such as social distancing, wearing facial masks, and vaccination, especially for pneumococcal infections and influenza, is also required. Patients with COVID-19 need to be withhold immunomodulators or biologics for at least 2 weeks and treated based on both IBD and COVID-19 severity. Prevention of IBD relapse caused by sudden medication interruption is important because negative outcomes associated with disease flare up, such as corticosteroid use or hospitalization, are much riskier than medications. The outpatient clinic and infusion center for biologics need to be reserved safe spaces, and endoscopy or surgery should be considered in urgent cases only.
Objective Crohn's disease (CD) is an intractable inflammatory bowel disease (IBD) of unknown cause. Recent meta-analysis of the genome-wide association studies (GWAS) and Immunochip data identified ...163 susceptibility loci to IBD in Caucasians, however there are limited studies in other populations. Methods We performed a GWAS and two validation studies in the Korean population comprising a total of 2311 patients with CD and 2442 controls. Results We confirmed four previously reported loci: TNFSF15, IL23R, the major histocompatibility complex region, and the RNASET2-FGFR1OP-CCR6 region. We identified three new susceptibility loci at genome-wide significance: rs6856616 at 4p14 (OR=1.43, combined p=3.60×10−14), rs11195128 at 10q25 (OR=1.42, combined p=1.55×10−10) and rs11235667 at 11q13 (OR=1.46, combined p=7.15×10−9), implicating ATG16L2 and/or FCHSD2 as novel susceptibility genes for CD. Further analysis of the 11q13 locus revealed a non-synonymous single nucleotide polymorphism (SNP) (R220W/rs11235604) in the evolutionarily conserved region of ATG16L2 with stronger association (OR=1.61, combined p=2.44×10−12) than rs11235667, suggesting ATG16L2 as a novel susceptibility gene for CD and rs11235604 to be a potential causal variant of the association. Two of the three SNPs (rs6856616 (p=0.00024) and rs11195128 (p=5.32×10−5)) showed consistent patterns of association in the International IBD Genetics Consortium dataset. Together, the novel and replicated loci accounted for 5.31% of the total genetic variance for CD risk in Koreans. Conclusions Our study provides new biological insight to CD and supports the complementary value of genetic studies in different populations.
To address a growing concern about drug-induced liver injury (DILI), a nationwide study was performed to investigate the significance of DILI in Korea.
From May 2005 to May 2007, cases of DILI ...(alanine transferase > 3 × upper normal limit or total bilirubin > 2 × upper normal limit) from 17 referral university hospitals were prospectively enrolled. Adjudication by the seven review boards was considered for the confirmation of causality and the Roussel Uclaf Causality Assessment Method (RUCAM) scale was used.
A total of 371 cases were diagnosed with DILI. The extrapolated incidence of hospitalization at university hospital in Korea was 12/100,000 persons/year. The causes included "herbal medications" (102, 27.5%), "prescription or non-prescription medications" (101, 27.3%), "health foods or dietary supplements" (51, 13.7%), "medicinal herbs or plants" (35, 9.4%), "folk remedies" (32, 8.6%), "combined" (30, 8.2%), "herbal preparations" (12, 3.2%), and others (8, 2.2%). Nine cases were linked to acetaminophen. The frequencies of hepatocellular, mixed, and cholestatic types were 76.3, 14.8, and 8.9%, respectively. A total of 234 cases met the criteria for Hy's law. Five patients died or underwent transplantation. Twenty-five cases (21 herbs and 4 medications) did not meet the time-to-onset criteria of the RUCAM.
DILI appears to be a highly relevant health problem in Korea. "Herbal medications" are the principal cause of DILI. A more objective and reproducible causality assessment tool is strongly desired as the RUCAM scale frequently undercounts the cases caused by herbs owing to a lack of previous information and incompatible time criteria.
We aimed to determine whether Crohn's disease (CD) activity patterns assessed via a web-based symptom diary can help predict clinical outcomes in patients with newly diagnosed CD. Patients diagnosed ...with CD within the preceding 3 months were prospectively enrolled at four tertiary centers. All patients recorded their symptoms on a website using a smartphone at least once a week. The index outcomes were disease-related admission and surgery during follow-up. The disease activity from enrollment to outcome or last follow-up was reviewed for pattern analysis. Cox regression analysis was used to identify the predictors of disease outcomes. A total of 102 patients were enrolled. During a median follow-up period of 42 months, 25 (24.5%) and 6 (5.9%) patients required admission and surgery, respectively. Poor activity pattern was an independent predictor of disease-related hospitalization (adjusted hazard ratio aHR, 3.96; 95% confidence interval CI 1.5-10.45; p = 0.005). A poor activity pattern (aHR, 19.48; 95% CI 1.86-203.95; p = 0.013) and female sex (aHR, 11.28; 95% CI 1.49-85.01; p = 0.018) were found to be independent predictors of bowel resection. CD disease activity patterns monitored through the mobile monitoring system may help predict clinical outcomes, such as disease-related hospitalization and surgery, in patients with newly diagnosed CD.
Background Various training programs in colonoscopy recommend that trainees should perform at least 100 to 200 procedures to be considered technically competent at diagnostic colonoscopy. Objective ...Our purpose was to determine the adequate level of training for technical competence in screening and diagnostic colonoscopy. Design A prospective multicenter trial. Setting Fifteen tertiary care academic medical centers. Patients Over 8 months we prospectively evaluated the procedures of 24 first-year GI fellows in 15 tertiary care academic medical centers. A total of 4351 colonoscopies were assessed prospectively with variable clinical factors. Intervention Cecal intubation was documented by photographing the identified cecal landmarks, including the appendiceal orifice and the ileocecal valve. Main Outcome Measurements Acquisition of competence (success rate) was evaluated for colonoscopic training on the basis of 2 objective criteria: (1) adjusted completion rate (>90%) and (2) cecal intubation time (<20 minutes). Results The overall success rate was 83.5% (3635/4351). The mean cecal intubation time was 9.23 ± 4.63 minutes. The success rate significantly improved and reached the requisite standard of competence after 150 procedures (71.5%, 82.6%, 91.3%, 94.4%, 98.4%, and 98.7%, respectively, for every 50 consecutive blocks). The polyp detection rate did not improve significantly during the 8 months and was not correlated with the learning curve. In addition, mean time to cecal intubation decreased significantly, from 11.16 to 8.39 minutes, after 150 procedures. Logistic regression analysis found that prolonged cecal intubation was caused by the following factors: elderly patients, female sex, low body mass index, poor bowel preparation, poor American Society of Anesthesiologists status, abdominal pain as an indication, instructor's supervision, and low case volume. Limitations We did not record final pathologic reports of detected polyps and withdrawal time. Conclusions Competence in technically efficient screening and diagnostic colonoscopy generally requires experience with more than 150 cases. Also, factors associated with prolonged cecal intubation for typical trainees did not differ from those for experienced colonoscopists.
BACKGROUND AND AIM:Clostridium difficile has been increasingly diagnosed in hospitalized patients. An association between proton pump inhibitors (PPIs) use and Clostridium difficile-associated ...disease (CDAD) and between recurrent CDAD has been suggested. The aim of this study is to investigate whether PPI use is associated with the development of recurrent CDAD.
METHODS:This was a retrospective case-control study of patients with CDAD at Yeungnam University Medical Center, seen from January 2004 to December 2008. C. difficile infection was diagnosed by the presence of C. difficile toxin in the stool. Those with recurrent disease were matched with nonrecurrent controls using multivariate matched sampling methods that incorporated the propensity score.
RESULTS:Recurrent CDAD developed in 28 (14.1%) of the 198 patients with diarrhea and positive C. difficile stool toxin assays. Multivariate analysis of the total population of recurrent versus nonrecurrent CDAD revealed that additional use of non-C. difficile antimicrobial therapy (concomitant with the treatment or after or both), poor response to therapy with metronidazole or vancomycin, and recent gastrointestinal surgery were risk factors for recurrent CDAD. We were able to match 21 recurrent CDAD subjects with 21 without recurrent CDAD. Among the matched patients only PPI use was associated with recurrent CDAD (ie, 47.6% vs. 4.8%, P=0.004 for recurrent vs. nonrecurrent CDAD, respectively).
CONCLUSIONS:Among the matched patient groups, only PPI therapy was associated with recurrent CDAD. Prospective studies are needed to clarify whether avoidance of PPIs or specific cotherapies will reduce the incidence of recurrent C. difficile-associated diarrhea.
Excessive oxidative stress plays a role in hepatotoxicity and the pathogenesis of hepatic diseases. In our previous study, the phenolic extract of beluga lentil (BLE) showed the most potent in vitro ...antioxidant activity among extracts of four common varieties of lentils; thus, we hypothesized that BLE might protect liver cells against oxidative stress-induced cytotoxicity. BLE was evaluated for its protective effects against oxidative stress-induced hepatotoxicity in AML12 mouse hepatocytes and BALB/c mice. H
O
treatment caused a marked decrease in cell viability; however, pretreatment with BLE (25-100 μg/mL) for 24 h significantly preserved the viability of H
O
-treated cells up to about 50% at 100 μg/mL. As expected, BLE dramatically reduced intracellular reactive oxygen species (ROS) levels in a dose-dependent manner in H
O
-treated cells. Further mechanistic studies demonstrated that BLE reduced cellular ROS levels, partly by increasing expression of antioxidant genes. Furthermore, pretreatment with BLE (400 mg/kg) for 2 weeks significantly reduced serum levels of alanine transaminase and triglyceride by about 49% and 40%, respectively, and increased the expression and activity of glutathione peroxidase in CCl
-treated BALB/c mice. These results suggest that BLE protects liver cells against oxidative stress, partly by inducing cellular antioxidant system; thus, it represents a potential source of nutraceuticals with hepatoprotective effects.
Chronic recurrent multifocal osteomyelitis (CRMO) is a rare condition characterized by chronic relapsing noninfectious bone inflammation of unknown etiology. Although CRMO is considered an ...extraintestinal manifestation in patients with inflammatory bowel disease, most cases of CRMO are associated with Crohn’s disease; very few are associated with ulcerative colitis (UC). We herein describe a 21-year-old patient with UC who developed recurrent left thigh pain. The patient was diagnosed with CRMO associated with UC, which was well controlled with azathioprine treatment.
The orphan nuclear receptor 4A1 (NR4A1) is highly expressed in human pancreatic cancer cells and exerts pro-oncogenic activity. In a previous study, we demonstrated that fangchinoline (FCN), a ...natural inhibitor of nuclear NR4A1, induces NR4A1-dependent apoptosis in human pancreatic cancer cells. In this study, we evaluated FCN and its structural analogs (berbamine, isotetrandrine, tetrandrine, and tubocurarine) for their inhibitory effects on NR4A1 transactivity, and confirmed that tetrandrine (TTD) showed the highest inhibitory effect in pancreatic cancer cells. Moreover, in a tryptophan fluorescence quenching assay, TTD directly bound to the ligand binding domain (LBD) of NR4A1 with a K
value of 10.60 μM. Treatment with TTD decreased proliferation and induced apoptosis in Panc-1 human pancreatic cancer cells in part through the reduced expression of the Sp1-dependent anti-apoptotic gene survivin and induction of ROS-mediated endoplasmic reticulum stress, which are the well-known NR4A1-dependent proapoptotic pathways. Furthermore, at a dose of 25 mg/kg/day, TTD reduced tumor growth in an athymic nude mouse xenograft model bearing Panc-1 cells. These data show that TTD is an NR4A1 antagonist and that modulation of the NR4A1-mediated pro-survival pathways is involved in the antitumor effects of TTD.
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