Publications by authors named "Jong Pil Im"

181 Publications

Patient-derived organoids as a preclinical platform for precision medicine in colorectal cancer.

Mol Oncol 2021 Nov 30. Epub 2021 Nov 30.

Department of Molecular Medicine & Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul, Korea.

Patient-derived organoids are being considered as models that can help guide personalized therapy through in vitro anti-cancer drug response evaluation. However, attempts to quantify in vitro drug responses in organoids and compare them with responses in matched patients remain inadequate. In this study, we investigated whether drug responses of organoids correlate with clinical responses of matched patients and disease progression of patients. Organoids were established from 54 patients with colorectal cancer who (except for one patient) did not receive any form of therapy before, and tumor organoids were assessed through whole-exome sequencing. For comparisons of in vitro drug responses in matched patients, we developed an "organoid score" based on the variable anti-cancer treatment responses observed in organoids. Very interestingly, a higher organoid score was significantly correlated with a lower tumor regression rate after the standard-of-care treatment in matched patients. Additionally, we confirmed that patients with a higher organoid score (≥ 2.5) had poorer progression-free survival compared with those with a lower organoid score (< 2.5). Furthermore, to assess potential drug repurposing using an FDA-approved drug library, ten tumor organoids derived from patients with disease progression were applied to a simulation platform. Taken together, organoids and organoid scores can facilitate the prediction of anti-cancer therapy efficacy, and they can be used as a simulation model to determine the next therapeutic options through drug screening. Organoids will be an attractive platform to enable the implementation of personalized therapy for colorectal cancer patients.
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http://dx.doi.org/10.1002/1878-0261.13144DOI Listing
November 2021

Capillary-Induced Clustering of Thermoresponsive Micropillars.

ACS Appl Mater Interfaces 2021 Nov 24. Epub 2021 Nov 24.

Department of Mechanical Engineering, Chungnam National University, Daejeon 34134, Republic of Korea.

In this study, we demonstrate the controllable clustering of thermoresponsive high-aspect-ratio hydrogel pillars by modulating the elastic modulus of the materials. Generally, high-aspect-ratio polymeric pillars readily cluster owing to the effect of capillary force and adhesion. However, this unstable behavior hinders the implementation of various functionalities such as wetting, adhesion, and energy harvesting on surfaces with such pillars. Conversely, clustering behavior may be required in the case of digital microfluidic platforms that grip tiny particles or perform biological and chemical analyses. Therefore, it is necessary to develop a reliable method for controlling the clustering behavior. To this end, we fabricate high-aspect-ratio pillars that exhibit capillary-induced clustering behavior based on the cross-linker density of the thermoresponsive hydrogel and the temperature of the surrounding environment. Through experimental and theoretical analyses, a criterion for controlling the clustering and recovery behavior of the fabricated pillars is determined. The established criterion is employed to fabricate a smart mobile camera lens cover that can produce blurred and deblurred images based on optical variations resulting from the clustering and recovery of the pillars. The results of this study can be used to fabricate high-aspect-ratio polymeric pillars for use in diverse applications.
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http://dx.doi.org/10.1021/acsami.1c18634DOI Listing
November 2021

Risk of Diabetes in Subjects with Positive Fecal Immunochemical Test: A Nationwide Population-Based Study.

Endocrinol Metab (Seoul) 2021 Oct 28;36(5):1069-1077. Epub 2021 Oct 28.

Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea.

Background: Positive fecal immunochemical test (FIT) results have been recently suggested as a risk factor for systemic inflammation. Diabetes induces inflammation in the gastrointestinal tract via several ways. We investigated the association between FIT results and the incidence of diabetes.

Methods: A total of 7,946,393 individuals aged ≥50 years from the National Cancer Screening Program database who underwent FIT for colorectal cancer (CRC) screening from 2009 to 2012 were enrolled. The primary outcome was newly diagnosed diabetes based on the International Classification of Disease 10th revision codes and administration of anti-diabetic medication during the follow-up period.

Results: During a mean follow-up of 6.5 years, the incidence rates of diabetes were 11.97, 13.60, 14.53, and 16.82 per 1,000 personyears in the FIT negative, one-positive, two-positive, and three-positive groups, respectively. The hazard ratios (HRs) for the incidence of diabetes were 1.14 (95% confidence interval [CI], 1.12 to 1.16; HR, 1.21; 95% CI, 1.16 to 1.27; and HR, 1.40; 95% CI, 1.28 to 1.55) in the one-positive, two-positive, and three-positive FIT groups compared with the FIT negative group, respectively. The effect was consistent in individuals with normal fasting blood glucose (adjusted HR 1.55 vs. 1.14, P for interaction <0.001).

Conclusion: Positive FIT results were associated with a significantly higher risk of diabetes, suggesting that the FIT can play a role not only as a CRC screening tool, but also as a surrogate marker of systemic inflammation; thus, increasing the diabetes risk.
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http://dx.doi.org/10.3803/EnM.2021.1119DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8566131PMC
October 2021

Factors Affecting Route Selection of Balloon-Assisted Enteroscopy in Patients with Obscure Gastrointestinal Bleeding: A KASID Multicenter Study.

Diagnostics (Basel) 2021 Oct 10;11(10). Epub 2021 Oct 10.

Department of Internal Medicine, Eunpyeong St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul 03312, Korea.

Balloon-assisted enteroscopy (BAE) is an important diagnostic modality for ongoing obscure gastrointestinal bleeding (OGIB). However, it is difficult to determine the optimal insertion route. We retrospectively analyzed the records of patients with OGIB contained in a multicenter enteroscopy database of 1108 balloon-assisted enteroscopy (BAE) procedures (875 patients) to find out factors affecting BAE route selection in patients with OGIB. A total of 603 BAE procedures in 512 patients were investigated: there were 392 (65.0%) bidirectional and 211 (35.0%) unidirectional procedures. Overt OGIB was more frequent in the latter group ( = 0.024). Computed tomography (CT) was more frequently performed in the unidirectional group ( < 0.001). Capsule endoscopy and a small bowel barium study were performed more frequently in the bidirectional group ( < 0.001 and = 0.039, respectively). Multivariate analysis showed that occult OGIB, capsule endoscopy and a small bowel barium study were independently associated with use of the bidirectional approach ( = 0.011, = 0.013 and = 0.046, respectively). Conversely, CT was associated with use of the unidirectional approach ( < 0.001). Conclusion: CT can aid the selection of an optimal insertion route in OGIB patients. However, capsule endoscopy and small bowel barium study are unhelpful.
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http://dx.doi.org/10.3390/diagnostics11101860DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8535013PMC
October 2021

Efficacy and safety of split-dose bowel preparation with 1 L polyethylene glycol and ascorbate compared with 2 L polyethylene glycol and ascorbate in a Korean population: a phase IV, multicenter, randomized, endoscopist-blinded study.

Gastrointest Endosc 2021 Oct 12. Epub 2021 Oct 12.

Department of Internal Medicine, Korea University Anam Hospital, Korea University College of Medicine, Seoul, Korea.

Background And Aims: The 1-L polyethylene glycol (PEG)-based bowel preparation agent NER1006 (Plenvu; Norgine, Harefield, UK) has shown high cleansing efficacy and tolerability in clinical trials in Europe and North America. However, no clinical trials have yet been reported in Asia. Therefore, the aim of this study was to evaluate the efficacy and safety of 1L PEG-based bowel preparation with Plenvu compared with 2L PEG plus ascorbate bowel preparation in a Korean population.

Methods: In this multicenter, endoscopist-blinded, randomized study, patients at 9 hospitals in South Korea undergoing colonoscopy received either Plenvu or 2L PEG + ascorbate (2L PEG) with a split dose. The primary endpoint was overall bowel cleansing success (Boston Bowel Preparation Scale [BBPS] score ≥2 for all segments of the colon). Secondary endpoints were high-quality bowel cleansing success (overall, BBPS score = 9; segmental colon, BPPS score = 3), polyp detection rate (PDR), and adenoma detection rate (ADR).

Results: Of 360 included patients, cleansing efficacy was analyzed in 346 (Plenvu, 174; 2L PEG, 172). The Plenvu group showed noninferior bowel cleansing success rates compared with 2L PEG (93.10% vs 91.86%; difference, 1.24%; 1-sided 97.5% lower confidence limit, -4.31%; P < .0001; P = .661). The Plenvu group had higher high-quality bowel cleansing success rates for overall and right-sided colon segments than the 2L PEG group (49.43% vs 37.79% [P = .029] and 60.92% vs 48.84% [P = .024], respectively). The PDR was greater with Plenvu than with 2L PEG (48.85% vs 37.79%, P = .038). However, ADR did not differ between the 2 groups (24.71% vs 20.35%, P = .331). Although treatment-emergent adverse events (TEAEs) were slightly higher in the Plenvu group than in the 2L PEG group (65.71% vs 52.91%, P = .015), most TEAEs were mild (85.55%) and most patients recovered without any management (99.23%).

Conclusions: Plenvu showed noninferior overall bowel cleansing success rates comparable with 2L PEG but greater high-quality bowel cleansing in overall and right-sided colon, which might help improve the PDR in the Asian population. (Clinical trial registration number: KCT0005894.).
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http://dx.doi.org/10.1016/j.gie.2021.09.041DOI Listing
October 2021

Clinical Course of Hepatitis B Viral Infection in Patients Undergoing Anti-Tumor Necrosis Factor α Therapy for Inflammatory Bowel Disease.

Gut Liver 2021 Oct 1. Epub 2021 Oct 1.

Department of Internal Medicine, Toho University Sakura Medical Center, Sakura, Japan.

Background/aims: Little is known about the clinical course of hepatitis B virus (HBV)-infected patients undergoing anti-tumor necrosis factor α (TNF-α) therapy for inflammatory bowel disease (IBD). We aimed to investigate the clinical course of HBV infection and IBD and to analyze liver dysfunction risks in patients undergoing anti-TNF-α therapy.

Methods: This retrospective multinational study involved multiple centers in Korea, China, Taiwan, and Japan. We enrolled IBD patients with chronic or resolved HBV infection, who received anti-TNF-α therapy. The patients' medical records were reviewed, and data were collected using a web-based case report form.

Results: Overall, 191 patients (77 ulcerative colitis and 114 Crohn's disease) were included, 28.3% of whom received prophylactic antivirals. During a median follow-up duration of 32.4 months, 7.3% of patients experienced liver dysfunction due to HBV reactivation. Among patients with chronic HBV infection, the proportion experiencing liver dysfunction was significantly higher in the non-prophylaxis group (26% vs 8%, p=0.02). Liver dysfunction occurred in one patient with resolved HBV infection. Antiviral prophylaxis was independently associated with an 84% reduction in liver dysfunction risk in patients with chronic HBV infection (odds ratio, 0.16; 95% confidence interval, 0.04 to 0.66; p=0.01). The clinical course of IBD was not associated with liver dysfunction or the administration of antiviral prophylaxis.

Conclusions: Liver dysfunction due to HBV reactivation can occur in HBV-infected IBD patients treated with anti-TNF-α agents. Careful monitoring is needed in these patients, and antivirals should be administered, especially to those with chronic HBV infection.
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http://dx.doi.org/10.5009/gnl210081DOI Listing
October 2021

Occult Blood in Feces Is Associated with Increased Risk of Psoriasis.

Dermatology 2021 Sep 16:1-8. Epub 2021 Sep 16.

Department of Dermatology, Yeouido St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.

Background: The fecal immunochemistry test (FIT) has been proposed as a surrogate marker of intestinal inflammation. Psoriasis is a chronic inflammatory skin disease that is linked to underlying systemic inflammatory conditions, including inflammatory bowel disease.

Methods: We investigated the association between occult blood in feces and the risk of psoriasis using data from the National Health Insurance System. This study was conducted involving 1,395,147 individuals who underwent health examinations from January 2009 to December 2012 and were followed up until the end of 2017.

Results: The incidence of psoriasis (per 1,000 person-years) was 3.76 versus 4.14 (FIT-negative versus FIT-positive group) during a median follow-up of 6.68 years. In the multivariable-adjusted model, the hazard ratios for psoriasis were 1.03 for one positive FIT result, 1.12 for two positive FIT results, and 1.34 for three positive FIT results compared with negative FIT results.

Conclusion: The risk of psoriasis was significantly increased in patients with positive FIT results compared to the FIT-negative population.
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http://dx.doi.org/10.1159/000518625DOI Listing
September 2021

Deep learning model for diagnosing gastric mucosal lesions using endoscopic images: development, validation, and method comparison.

Gastrointest Endosc 2021 Sep 4. Epub 2021 Sep 4.

Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea.

Background And Aims: Endoscopic differential diagnoses of gastric mucosal lesions (benign gastric ulcer, early gastric cancer [EGC], and advanced gastric cancer) remain challenging. We aimed to develop and validate convolutional neural network-based artificial intelligence (AI) models: lesion detection, differential diagnosis (AI-DDx), and invasion depth (AI-ID; pT1a vs pT1b among EGC) models.

Methods: This study included 1366 consecutive patients with gastric mucosal lesions from 2 referral centers in Korea. One representative endoscopic image from each patient was used. Histologic diagnoses were set as the criterion standard. Performance of the AI-DDx (training/internal/external validation set, 1009/112/245) and AI-ID (training/internal/external validation set, 620/68/155) was compared with visual diagnoses by independent endoscopists (stratified by novice [<1 year of experience], intermediate [2-3 years of experience], and expert [>5 years of experience]) and EUS results, respectively.

Results: The AI-DDx showed good diagnostic performance for both internal (area under the receiver operating characteristic curve [AUROC] = .86) and external validation (AUROC = .86). The performance of the AI-DDx was better than that of novice (AUROC = .82, P = .01) and intermediate endoscopists (AUROC = .84, P = .02) but was comparable with experts (AUROC = .89, P = .12) in the external validation set. The AI-ID showed a fair performance in both internal (AUROC = .78) and external validation sets (AUROC = .73), which were significantly better than EUS results performed by experts (internal validation, AUROC = .62; external validation, AUROC = .56; both P < .001).

Conclusions: The AI-DDx was comparable with experts and outperformed novice and intermediate endoscopists for the differential diagnosis of gastric mucosal lesions. The AI-ID performed better than EUS for evaluation of invasion depth.
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http://dx.doi.org/10.1016/j.gie.2021.08.022DOI Listing
September 2021

Clinical features and long-term outcomes of pediatric-onset inflammatory bowel disease in a population-based cohort in the Songpa-Kangdong district of Seoul, Korea.

J Crohns Colitis 2021 Jul 26. Epub 2021 Jul 26.

Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.

Background And Aims: The long-term outcomes of pediatric-onset inflammatory bowel disease (pIBD) in non-Caucasian populations are unknown. We, therefore, evaluated and compared the clinical features and long-term outcomes of pIBD with those of adult-onset IBD (aIBD) using a population-based cohort in the Songpa-Kangdong district of Seoul, Korea.

Methods: Clinical characteristics and prognoses were compared between the two groups: pIBD (defined as <18 years of age at diagnosis) and aIBD (18-59 years of age at diagnosis).

Results: We identified 131 patients with pIBD (48 ulcerative colitis [UC], 83 Crohn's disease [CD]) and 1192 patients with aIBD (866 UC, 326 CD) during 1986-2015. An extensive colitis at diagnosis was more prevalent in pUC than in aUC (45.8% vs. 22.3%, P<0.001), and the overall exposure to corticosteroids, thiopurines, and anti-tumor necrosis factor agents was higher in pUC than in aUC (P<0.001). The cumulative risk of colectomy was higher in pUC than in aUC during a median follow-up of 125.0 and 112.1 months, respectively (8.9% vs. 1.8% at 10 years after diagnosis, P=0.030). Ileocolonic location and inflammatory behavior at diagnosis were more common in pCD than in aCD; however, patients with pCD and aCD did not differ regarding treatment or disease course during a median follow-up of 137.2 and 120.9 months, respectively.

Conclusion: Our study showed clear differences between pIBD and aIBD, especially in UC. pUC presents with more extensive diseases and may have a more severe disease course, as suggested by an earlier time to administering medications and performing colectomy.
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http://dx.doi.org/10.1093/ecco-jcc/jjab132DOI Listing
July 2021

Clinical outcomes and predictors of response for adalimumab in patients with moderately to severely active ulcerative colitis: a KASID prospective multicenter cohort study.

Intest Res 2021 Jul 23. Epub 2021 Jul 23.

Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul, Korea.

Background/aims: This study assessed the efficacy and safety of adalimumab (ADA) and explored predictors of response in Korean patients with ulcerative colitis (UC).

Methods: A prospective, observational, multicenter study was conducted over 56 weeks in adult patients with moderately to severely active UC who received ADA. Clinical response, remission, and mucosal healing were assessed using the Mayo score.

Results: A total of 146 patients were enrolled from 17 academic hospitals. Clinical response rates were 52.1% and 37.7% and clinical remission rates were 24.0% and 22.0% at weeks 8 and 56, respectively. Mucosal healing rates were 39.0% and 30.1% at weeks 8 and 56, respectively. Prior use of anti-tumor necrosis factor-α (anti-TNF-α) did not affect clinical and endoscopic responses. The ADA drug level was significantly higher in patients with better outcomes at week 8 (P<0.05). In patients with lower endoscopic activity, higher body mass index, and higher serum albumin levels at baseline, the clinical response rate was higher at week 8. In patients with lower Mayo scores and C-reactive protein levels, clinical responses, and mucosal healing at week 8, the clinical response rate was higher at week 56. Serious adverse drug reactions were identified in 2.8% of patients.

Conclusions: ADA is effective and safe for induction and maintenance in Korean patients with UC, regardless of prior anti-TNF-α therapy. The ADA drug level is associated with the efficacy of induction therapy. Patients with better short-term outcomes were predictive of those with an improved long-term response.
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http://dx.doi.org/10.5217/ir.2021.00049DOI Listing
July 2021

Changes in the Long-term Prognosis of Crohn's Disease between 1986 and 2015: The Population-Based Songpa-Kangdong Inflammatory Bowel Disease Cohort Study.

Gut Liver 2021 Jun 22. Epub 2021 Jun 22.

Department of Gastroenterology and Inflammatory Bowel Disease Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.

Background/aims: The long-term course of Crohn's disease (CD) has never been evaluated in non-Caucasian population-based cohorts. The aim of the present study was to evaluate the longterm prognosis of Korean CD patients in the well-defined population-based Songpa-Kangdong inflammatory bowel disease cohort.

Methods: Outcomes of disease and their predictors were evaluated for 418 patients diagnosed with CD between 1986 and 2015.

Results: During a median of 123 months, systemic corticosteroids, thiopurines, and anti-tumor necrosis factor (TNF) agents were administered to 58.6%, 81.3%, and 37.1% of patients, respectively. Over time, the cumulative probability of starting corticosteroids significantly decreased (p=0.001), whereas that of starting thiopurines and anti-TNFs significantly increased (both p<0.001). The cumulative probability of behavioral progression was 54.5% at 20 years, and it significantly decreased during the anti-TNF era. Intestinal resection was required for 113 patients (27.0%). The cumulative probabilities of intestinal resection at 1, 5, 10, 20, and 25 years after CD diagnosis were 12.7%, 16.5%, 23.8%, 45.1%, and 51.2%, respectively. Multivariable Cox regression analysis identified stricturing behavior at diagnosis (adjusted hazard ratio [aHR], 2.70; 95% confidence interval [CI], 1.55 to 4.71), penetrating behavior at diagnosis (aHR, 11.15; 95% CI, 6.91 to 17.97), and diagnosis of CD during the anti-TNF era (aHR, 0.51; 95% CI, 0.35 to 0.76) as independently associated with intestinal resection. The standardized mortality ratio among CD patients was 1.36 (95% CI, 0.59 to 2.68).

Conclusions: The long-term prognosis of Korean patients with CD is at least as good as that of Western CD patients, as indicated by the low intestinal resection rate. Moreover, behavioral progression and intestinal resection rates have decreased over the past 3 decades.
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http://dx.doi.org/10.5009/gnl210044DOI Listing
June 2021

Long-term Outcomes after the Discontinuation of Anti-Tumor Necrosis Factor-α Therapy in Patients with Inflammatory Bowel Disease under Clinical Remission: A Korean Association for the Study of Intestinal Disease Multicenter Study.

Gut Liver 2021 09;15(5):752-762

Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul, Korea.

Background/aims: Our study aimed to evaluate the long-term outcomes and risk factors for relapse after anti-tumor necrosis factor (TNF)-α cessation in inflammatory bowel disease (IBD) patients because they are not well established.

Methods: A retrospective multicenter cohort study was conducted involving patients with Crohn's disease (CD) or ulcerative colitis (UC) from 10 referral hospitals in Korea who discontinued firstline anti-TNF therapy after achieving clinical remission.

Results: A total of 109 IBD patients (71 CD and 38 UC) with a median follow-up duration of 56 months were analyzed. The cumulative relapse rates at 1, 3, and 5 years were 11.3%, 46.7%, and 62.5% for CD patients and 28.9%, 45.3%, and 60.9% for UC patients. Multivariable Cox analysis revealed that discontinuation owing to the clinician's decision was associated with lower risk of relapse (vs patient's preference: hazard ratio [HR], 0.13; 95% confidence interval [CI], 0.04 to 0.48; p=0.002) and adalimumab use was associated with higher risk of relapse (vs infliximab: HR, 4.42; 95% CI, 1.24 to 17.74; p=0.022) in CD patients. Mucosal healing was associated with lower risk of relapse (vs nonmucosal healing: HR, 0.12; 95% CI, 0.02 to 0.83; p=0.031) in UC patients. Anti-TNF re-induction was provided to 52 patients, and a response was obtained in 50 patients. However, 25 of them discontinued retreatment owing to a loss of response (n=15), the patient's preference (n=6), and other factors (n=4).

Conclusions: More than 60% of IBD patients in remission under anti-TNF therapy relapsed within 5 years of treatment cessation. Anti-TNF re-induction was effective. However, half of the patients discontinued anti-TNF therapy, and 50% of these patients discontinued treatment owing to loss of response.
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http://dx.doi.org/10.5009/gnl20233DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8444111PMC
September 2021

Proteinuria Is Associated with the Development of Crohn's Disease: A Nationwide Population-Based Study.

J Clin Med 2021 Feb 16;10(4). Epub 2021 Feb 16.

Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul 03080, Korea.

Background And Aims: The impact of proteinuria and its severity on the incidence of inflammatory bowel disease (IBD) has not yet been studied. We aimed to determine the association between proteinuria measured by urine dipstick tests and the development of IBD.

Methods: This nationwide population-based study was conducted using the Korean National Health Insurance Service (NHIS) database. A total of 9,917,400 people aged 20 years or older who had undergone a national health examination conducted by the NHIS in 2009 were followed up until 2017. The study population was classified into four groups-negative, trace, 1+, and ≥ 2+-according to the degree of proteinuria measured by the urine dipstick test. The primary endpoint was newly diagnosed IBD, Crohn's disease (CD), or ulcerative colitis (UC) during the follow-up period.

Results: Compared with the dipstick-negative group, the incidence of CD significantly increased according to the degree of proteinuria (adjusted hazard ratio [aHR] with 95% confidence interval [CI], 1.01 [0.703-1.451], 1.515 [1.058-2.162], and 2.053 [1.301-3.24] in the trace, 1+, and ≥ 2+ dipstick groups, respectively; for trend 0.007). However, there was no significant difference in the incidence of UC according to the degree of proteinuria (aHR with 95% CI, 1.12 [0.949-1.323], 0.947 [0.764-1.174], and 1.009 [0.741-1.373] in the trace, 1+, and ≥ 2+ dipstick groups, respectively; for trend 0.722). In the subgroup analysis, dipstick-positive proteinuria independently increased the incidence of CD regardless of the subgroup. However, dipstick-positive proteinuria was associated with the risk of UC in those with diabetes mellitus and not in those without diabetes mellitus (aHR, 1.527 vs. 0.846; interaction -value 0.004). The risk of CD was increased or decreased according to proteinuria changes but not associated with the risk of UC.

Conclusion: Proteinuria, measured by the dipstick test, is strongly associated with the development of CD.
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http://dx.doi.org/10.3390/jcm10040799DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7920471PMC
February 2021

Development of a Clinical and Genetic Prediction Model for Early Intestinal Resection in Patients with Crohn's Disease: Results from the IMPACT Study.

J Clin Med 2021 Feb 7;10(4). Epub 2021 Feb 7.

Division of Gastroenterology, Department of Internal Medicine and Gastrointestinal Cancer Center, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul 03181, Korea.

Early intestinal resection in patients with Crohn's disease (CD) is necessary due to a severe and complicating disease course. Herein, we aim to predict which patients with CD need early intestinal resection within 3 years of diagnosis, according to a tree-based machine learning technique. The single-nucleotide polymorphism (SNP) genotype data for 337 CD patients recruited from 15 hospitals were typed using the Korea Biobank Array. For external validation, an additional 126 CD patients were genotyped. The predictive model was trained using the 102 candidate SNPs and seven sets of clinical information (age, sex, cigarette smoking, disease location, disease behavior, upper gastrointestinal involvement, and perianal disease) by employing a tree-based machine learning method (CatBoost). The importance of each feature was measured using the Shapley Additive Explanations (SHAP) model. The final model comprised two clinical parameters (age and disease behavior) and four SNPs (rs28785174, rs60532570, rs13056955, and rs7660164). The combined clinical-genetic model predicted early surgery more accurately than a clinical-only model in both internal (area under the receiver operating characteristic (AUROC), 0.878 vs. 0.782; = 51; < 0.001) and external validation (AUROC, 0.836 vs. 0.805; = 126; < 0.001). Identification of genetic polymorphisms and clinical features enhanced the prediction of early intestinal resection in patients with CD.
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http://dx.doi.org/10.3390/jcm10040633DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7915022PMC
February 2021

Prostaglandin E receptor PTGER4-expressing macrophages promote intestinal epithelial barrier regeneration upon inflammation.

Gut 2021 Dec 7;70(12):2249-2260. Epub 2021 Feb 7.

Department of Microbiology and Immunology and Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Republic of Korea

Objective: Dysfunctional resolution of intestinal inflammation and altered mucosal healing are essential features in the pathogenesis of inflammatory bowel disease (IBD). Intestinal macrophages are vital in the process of inflammation resolution, but the mechanisms underlying their mucosal healing capacity remain elusive.

Design: We investigated the role of the prostaglandin E (PGE) receptor PTGER4 on the differentiation of intestinal macrophages in patients with IBD and mouse models of intestinal inflammation. We studied mucosal healing and intestinal epithelial barrier regeneration in Csf1r-iCre Ptger4 mice during dextran sulfate sodium (DSS)-induced colitis. The effect of PTGER4 macrophage secreted molecules was investigated on epithelial organoid differentiation.

Results: Here, we describe a subset of PTGER4-expressing intestinal macrophages with mucosal healing properties both in humans and mice. Csf1r-iCre Ptger4 mice showed defective mucosal healing and epithelial barrier regeneration in a model of DSS colitis. Mechanistically, an increased mucosal level of PGE triggers chemokine (C-X-C motif) ligand 1 (CXCL1) secretion in monocyte-derived PTGER4 macrophages via mitogen-activated protein kinases (MAPKs). CXCL1 drives epithelial cell differentiation and proliferation from regenerating crypts during colitis. Specific therapeutic targeting of macrophages with liposomes loaded with an MAPK agonist augmented the production of CXCL1 in vivo in conditional macrophage PTGER4-deficient mice, restoring their defective epithelial regeneration and favouring mucosal healing.

Conclusion: PTGER4 intestinal macrophages are essential for supporting the intestinal stem cell niche and regeneration of the injured epithelium. Our results pave the way for the development of a new class of therapeutic targets to promote macrophage healing functions and favour remission in patients with IBD.
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http://dx.doi.org/10.1136/gutjnl-2020-322146DOI Listing
December 2021

Incidence of Psoriasis in Patients with Inflammatory Bowel Disease: A Nationwide Population-Based Matched Cohort Study.

Dermatology 2021 8;237(3):330-337. Epub 2021 Feb 8.

Department of Internal Medicine, Liver Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.

Background: Emerging data suggest that inflammatory bowel disease (IBD) and psoriasis are associated, sharing common genetic predispositions and immunological mechanisms. However, concrete data on psoriasis risk in IBD patients compared to the general population are limited.

Objective: We investigated the risk of developing psoriasis in IBD patients compared to controls without IBD.

Methods: Using the Korean National Health Insurance Database, patients diagnosed with Crohn's disease (CD) or ulcerative colitis (UC) between 2005 and 2008 were age- and sex-matched 1:4 to non-IBD subjects from 2003 to 2018. IBD patients were defined by combining the International Classification of Diseases 10th revision code and at least one prescription of IBD-specific medications. Disease phenotypes, including psoriasis severity and psoriatic arthritis, were also identified. We investigated newly diagnosed psoriasis from 2009 to 2018. Incidence rates and risk of psoriasis were assessed with multivariate Cox regression models. Subgroup analyses for age and sex, and sensitivity analysis involving tumor necrosis factor (TNF) inhibitor-naïve patients were performed.

Results: During nearly a decade of follow-up, 20,152 IBD patients were identified (14,619 [72.54%] UC and 5,533 [27.46%] CD). Among them, 439 patients were newly diagnosed with psoriasis (incidence rate of 217.68 per 100,000 person-years and 228.62 per 100,000 person-years for UC and CD, respectively). The psoriasis risk was higher in IBD patients than in the matched controls (adjusted hazard ratio, aHR, 2.95, 95% confidence interval, CI, 2.60-3.33). Moreover, IBD patients aged <30 years were at an increased risk (aHR 3.35, 95% CI 2.58-4.35), a trend that was unchanged across all psoriasis phenotypes. Sensitivity analysis of TNF inhibitor-naïve patients revealed consistent results.

Conclusions: IBD patients were more likely to develop psoriasis compared to non-IBD subjects, including younger patients at an elevated risk regardless of TNF inhibitor use. This advocates the interplay between IBD and psoriasis; thus, inspection of cutaneous manifestation and dermatological consultation may be helpful in IBD patients at risk.
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http://dx.doi.org/10.1159/000514030DOI Listing
November 2021

Risk of gastrointestinal cancer in patients with an elevated level of gamma-glutamyltransferase: A nationwide population-based study.

PLoS One 2021 5;16(2):e0245052. Epub 2021 Feb 5.

Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea.

Emerging evidence that an elevated serum gamma-glutamyltransferase (GGT) level is associated with an increased risk of gastrointestinal cancer, but still controversial. The aim of this study to assess the relationship between GGT level and risk of gastrointestinal cancer, and the contribution of the interaction of hyperglycemia with elevated GGT level to the incidence of gastrointestinal cancer by the stratified analysis. A total of 8,120,665 Koreans who received medical checkups in 2009 were included. Subjects were classified according to the quartile of GGT level for women and men. The incidence rates of gastrointestinal cancer for each group were analyzed using Cox proportional hazards models. During follow-up, 129,853 cases of gastrointestinal cancer newly occurred (esophagus, 3,792; stomach, 57,932; and colorectal, 68,789 cases). The highest GGT quartile group showed an increased risk of gastrointestinal cancer (esophagus, hazard ratio = 2.408 [95% confidence interval, 2.184-2.654]; stomach, 1.121 [1.093-1.149]; and colorectal, 1.185 [1.158-1.211]). The risk increased significantly with the rise in GGT quartile level, regardless of the site of cancer. The stratified analysis according to glycemic status showed that the effect of elevated GGT was predominant in the risk of esophageal cancer. The effect of elevated GGT further increased the risk of stomach and colorectal cancers in diabetic patients. An elevated level of GGT was associated with an increased risk of gastrointestinal cancer, regardless of the site of cancer. The effect of the increase in GGT level on the risk of gastrointestinal cancer depended on the type of cancer and glycemic status.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0245052PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7864398PMC
July 2021

Clinical Outcomes and Response Predictors of Vedolizumab Induction Treatment for Korean Patients With Inflammatory Bowel Diseases Who Failed Anti-TNF Therapy: A KASID Prospective Multicenter Cohort Study.

Inflamm Bowel Dis 2021 11;27(12):1931-1941

Department of Gastroenterology and Inflammatory Bowel Disease Center, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea.

Background: We investigated the real-life effectiveness and safety of vedolizumab (VDZ) induction therapy among Korean patients with Crohn disease (CD) or ulcerative colitis (UC) for whom anti-tumor necrosis factor therapy previously failed.

Methods: Adult patients who started VDZ induction therapy at 16 centers were prospectively enrolled in the Korean VDZ nationwide registry. The coprimary outcomes were clinical remission, defined as a Crohn's Disease Activity Index score <150 points and a partial Mayo score ≤2 points with a combined rectal bleeding and stool frequency subscore ≤1 point at week 14 and endoscopic remission defined as a Mayo endoscopic subscore ≤1 point. We also analyzed predictors of clinical remission.

Results: Between August 2017 and November 2019, a total of 158 patients (80 with CD and 78 with UC) received VDZ induction therapy. Clinical remission rates among patients with CD and patients with UC were 44.1% and 44.0%, respectively. Among patients with UC, the endoscopic remission rate was 32.4%. Clinical response and remission rates showed increasing trends during induction therapy. Multivariable analysis revealed that clinical response at week 6 was the only predictor of clinical remission at week 14 for both patients with CD and patients with UC. Among patients who experienced 1 or more adverse events (n = 71; 44.9%), disease exacerbation (n = 28; 17.7%) was the most common adverse event.

Conclusions: Among Korean patients with CD or UC for whom anti-tumor necrosis factor therapy failed, VDZ induction therapy was effective and safe. The early clinical response was associated with clinical remission after VDZ induction therapy.
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http://dx.doi.org/10.1093/ibd/izaa361DOI Listing
November 2021

Clinical Characteristics and Long-term Prognosis of Elderly-Onset Ulcerative Colitis in a Population-Based Cohort in the Songpa-Kangdong District of Seoul, Korea.

Gut Liver 2021 09;15(5):742-751

Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.

Background/aims: We aimed to evaluate the clinical characteristics and long-term prognosis of elderly-onset ulcerative colitis (EOUC) in Korean patients over a 30-year period using a wellestablished population-based cohort in the Songpa-Kangdong district of Seoul, Korea.

Methods: Clinical characteristics and prognosis were compared between two groups: EOUC, defined as UC diagnosed in individuals aged ≥60 years and non-EOUC (N-EOUC), defined as UC diagnosed in individuals aged 18 to 59 years.

Results: We identified 99 patients with EOUC (10.3%) and 866 patients with N-EOUC (89.7%) between 1986 and 2015. During the median follow-up of 104.5 months, the overall exposure to medications was comparable between patients with EOUC and N-EOUC (p=0.091 for corticosteroids, p=0.794 for thiopurines, and p=0.095 for anti-tumor necrosis factor agents). The cumulative risks of disease outcomes were also comparable between patients with EOUC and N-EOUC (22.4% vs 30.4% for proximal disease extension [p=0.351], 11.9% vs 18.1% for hospitalization [p=0.240], and 2.3% vs 1.8% for colectomy [p=0.977]) at 10 years after diagnosis. Multivariate Cox regression analysis revealed that corticosteroid use at diagnosis was an independent predictor of proximal disease extension (hazard ratio [HR], 6.216; 95% confidence interval [CI], 1.314 to 28.826) and hospitalization (HR, 11.241; 95% CI, 3.027 to 41.742) in patients with EOUC.

Conclusions: In this population-based study from Korea, the pattern of medication use seemed comparable between the EOUC and N-EOUC groups. Moreover, patients with EOUC and those with N-EOUC have a similar disease course in terms of proximal disease extension, hospitalization, and colectomy.
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http://dx.doi.org/10.5009/gnl20289DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8444105PMC
September 2021

Clinical Features of Intra-Abdominal Abscess and Intestinal Free-Wall Perforation in Korean Patients with Crohn's Disease: Results from the CONNECT Study.

J Clin Med 2020 Dec 31;10(1). Epub 2020 Dec 31.

Department of Internal Medicine, Hanyang University College of Medicine, Guri 11923, Korea.

In Crohn's disease (CD), intra-abdominal abscess (IA) and intestinal free-wall perforation (IP) have a common mechanism of transmural inflammation; however, their manifestation is different. This study aimed to investigate differences in the clinical features between IA and IP in Korean patients with Crohn's disease. : A retrospective cohort study. Thirty university hospitals and two local hospitals in Korea. Patients who were diagnosed with CD between July 1982 and December 2008 were enrolled. Clinical characteristics of IA and IP. : Among 1286 patients with CD, 147 (11.4%) had IA and 83 (6.5%) had IP. IA patients were younger than those of IP (24.2 ± 8.6 vs. 30.4 ± 11.1 years, = 0.001). Location and behavior were significantly different between IA and IP ( = 0.035 and 0.021). In multivariate analyses, perianal fistula was not associated with increased risk of IA and IP, while intestinal stricture was associated with increased risk of IA (OR: 2.72, < 0.0001) and IP (OR: 2.76, < 0.0001). In subgroup analyses, 55 (36.5%) IA patients were diagnosed at the diagnosis of CD, and 92 (63.5%) during follow-up of CD, while 47 (56.6%) IP patients were diagnosed at the diagnosis of CD, and 36 (43.3%) during follow-up of CD. There are several differences in the clinical features of IA and IP in Korean patients with CD. The development mechanism is considered as identical, but further investigation should be needed for clinical implication.
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http://dx.doi.org/10.3390/jcm10010116DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7794699PMC
December 2020

Occult Blood in Feces Is Associated With an Increased Risk of Ischemic Stroke and Myocardial Infarction: A Nationwide Population Study.

J Am Heart Assoc 2021 01 29;10(1):e017783. Epub 2020 Dec 29.

Department of Internal Medicine Liver Research InstituteSeoul National University College of Medicine Seoul Republic of Korea.

Background Although occult hemoglobin in feces is universally valued as a screening tool for colorectal cancer (CRC), only few studies investigated the clinical meaning of fecal immunochemical test (FIT) in other diseases. We evaluated the clinical utility of FIT in patients with cardiovascular diseases (namely, ischemic stroke and myocardial infarction [MI]). Methods and Results Using the National Health Insurance database, participants (aged >50 years) with CRC screening records from 2009 to 2012 were screened and followed up. Subjects with a history of cardiovascular diseases and CRC were excluded. Ischemic stroke, MI, and other comorbidities were defined by (), codes. Age, sex, smoking, alcohol consumption, regular exercise, diabetes mellitus, hypertension, dyslipidemia, and body mass index were adjusted in a multivariate analysis. A total of 6 277 446 subjects were eligible for analysis. During the mean 6.79 years of follow-up, 168 570 participants developed ischemic stroke, 105 983 developed MI, and 11 253 deaths were observed. A multivariate-adjusted model revealed that the risk of ischemic stroke was higher in the FIT-positive population (adjusted hazard ratio [HR], 1.09; 95% CI, 1.07-1.11). Similarly, FIT-positive subjects were at an increased risk of MI (adjusted HR, 1.09; 95% CI, 1.06-1.12). Moreover, increased all-cause mortality was observed in the FIT-positive population (adjusted HR, 1.15; 95% CI, 1.07-1.23). The increased risk remained consistent in the stratified analysis on anemia and CRC status. Conclusions Positive FIT findings were associated with ischemic stroke, MI, and mortality. Occult blood in feces may offer more clinical information than its well-known conventional role in CRC screening.
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http://dx.doi.org/10.1161/JAHA.120.017783DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7955497PMC
January 2021

Increasing changes in visceral adiposity is associated with higher risk for colorectal adenoma: Multilevel analysis in a prospective cohort.

J Gastroenterol Hepatol 2021 Jul 6;36(7):1836-1842. Epub 2021 Jan 6.

Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea.

Background And Aim: While many studies demonstrated an association between visceral adiposity and colorectal adenoma (CRA), the effect of longitudinal changes in body fat composition on CRA is unclear. We investigated the longitudinal association between changes in visceral adiposity and CRA occurrence.

Methods: Between 2006 and 2018, 732 (62.8%) of the 1165 subjects in a prospective cohort voluntarily underwent follow-up abdominal fat computed tomography and colonoscopy. We defined incident and recurrent CRA as adenoma detected at follow-up colonoscopy from negative and positive adenoma at baseline colonoscopy, respectively. Multilevel survival analysis examined the longitudinal association between changes in visceral fat and CRA.

Results: During a median follow-up of 7.4 years, 400 (54.6%) subjects developed CRA. In multivariable analysis, increasing changes in visceral adipose tissue (VAT) area were associated with higher risk of incident adenoma (hazard ratio [HR] 1.21, 95% confidence interval [CI] 1.00-1.46 for change per 10 cm increase; HR 1.79, 95% CI 1.08-2.97 for highest vs lowest quartile, P values for trend = 0.045). Likewise, increasing changes in VAT area were independently associated with a higher risk of recurrent adenoma (HR 1.35, 95% CI 1.13-1.62 for change per 10 cm increase; HR 1.62, 95% CI 1.04-2.52 for highest vs lowest quartile, P values for trend = 0.001). Changes in subcutaneous adipose tissue area were not independently associated with CRA.

Conclusion: Increasing changes in VAT area were longitudinally associated with a higher risk of incident and recurrent CRA, independent of risk factors, suggesting that visceral adiposity may be an important target in CRA prevention.
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http://dx.doi.org/10.1111/jgh.15364DOI Listing
July 2021

Toll-like receptor 4 regulates intestinal fibrosis via cytokine expression and epithelial-mesenchymal transition.

Sci Rep 2020 11 16;10(1):19867. Epub 2020 Nov 16.

Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea.

Intestinal fibrosis induced by chronic and recurrent colitis, which is exacerbated by bowel stenosis, stricture, and obstruction, is challenging to treat. Toll-like receptor 4 (TLR4) stimulates innate and acquired immunity in response to specific microbial components, but the role of TLR4 in intestinal fibrosis is largely unknown. We investigated its role in intestinal fibrosis using not only a murine fibrosis model but also human myofibroblasts and intestinal epithelial cells. Colon fibrosis was induced in TLR4-deficient (TLR4) mice and its wild-type counterparts with 3% dextran sulfate sodium. Absence of TLR4 gene attenuated chronic inflammation and colonic macrophages infiltration; intestinal fibrosis and collagen deposition were suppressed. Also, the production of tumor necrosis factor-α, interleukin-12p40, and transforming growth factor-β was reduced in TLR4-deficient peritoneal macrophages. TLR4 was silenced in CCD-18Co cells by small interfering RNA (siRNA), and matrix metalloproteinase-1, tissue inhibitor of metalloproteinase, and collagen α1 expression was evaluated. Role of TLR4 in epithelial-mesenchymal transition (EMT) was evaluated in HCT116 cells. Suppression of TLR4 transcription by siRNAs affected myofibroblasts activity, collagen synthesis, and EMT in the human cancer cell line. Thus, we suggest that TLR4 can be an essential mediator in intestinal chronic inflammation and fibrosis, indicating that TLR4 signaling is a potential therapeutic target for intestinal fibrosis.
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http://dx.doi.org/10.1038/s41598-020-76880-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7670421PMC
November 2020

Periodontitis combined with smoking increases risk of the ulcerative colitis: A national cohort study.

World J Gastroenterol 2020 Oct;26(37):5661-5672

Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul 03080, South Korea.

Background: Periodontitis is a chronic inflammation of periodontal tissues. The effect of periodontitis on the development of inflammatory bowel disease (IBD) remains unclear.

Aim: To assessed the risk of IBD among patients with periodontitis, and the risk factors for IBD related to periodontitis.

Methods: A nationwide population-based cohort study was performed using claims data from the Korean National Healthcare Insurance Service. In total, 9950548 individuals aged ≥ 20 years who underwent national health screening in 2009 were included. Newly diagnosed IBD [Crohn's disease (CD), ulcerative colitis (UC)] using the International Classification of Disease 10 revision and rare intractable disease codes, was compared between the periodontitis and non-periodontitis groups until 2017.

Results: A total of 1092825 individuals (11.0%) had periodontitis. Periodontitis was significantly associated with older age, male gender, higher body mass index, quitting smoking, not drinking alcohol, and regular exercise. The mean age was 51.4 ± 12.9 years in the periodontitis group and 46.6 ± 14.2 years in the non-periodontitis group ( < 0.01), respectively. The mean body mass index was 23.9 ± 3.1 and 23.7 ± 3.2 in the periodontitis and non-periodontitis groups, respectively ( < 0.01). Men were 604307 (55.3%) and 4844383 (54.7%) in the periodontitis and non-periodontitis groups, respectively. The mean follow-up duration was 7.26 years. Individuals with periodontitis had a significantly higher risk of UC than those without periodontitis [adjusted hazard ratio: 1.091; 95% confidence interval (CI): 1.008-1.182], but not CD (adjusted hazard ratio: 0.879; 95% confidence interval: 0.731-1.057). The risks for UC were significant in the subgroups of age ≥ 65 years, male gender, alcohol drinker, current smoker, and reduced physical activity. Current smokers aged ≥ 65 years with periodontitis were at a 1.9-fold increased risk of UC than non-smokers aged ≥ 65 years without periodontitis.

Conclusion: Periodontitis was significantly associated with the risk of developing UC, but not CD, particularly in current smokers aged ≥ 65 years.
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http://dx.doi.org/10.3748/wjg.v26.i37.5661DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7545388PMC
October 2020

Ferroelectric Switching in Trilayer AlO/HfZrO/AlO Structure.

Micromachines (Basel) 2020 Sep 30;11(10). Epub 2020 Sep 30.

ICT Creative Research Laboratory, Electronics and Telecommunications Research Institute, Daejeon 34129, Korea.

Since ferroelectricity has been observed in simple binary oxide material systems, it has attracted great interest in semiconductor research fields such as advanced logic transistors, non-volatile memories, and neuromorphic devices. The location in which the ferroelectric devices are implemented depends on the specific application, so the process constraints required for device fabrication may be different. In this study, we investigate the ferroelectric characteristics of Zr doped HfO layers treated at high temperatures. A single HfZrO layer deposited by sputtering exhibits polarization switching after annealing at a temperature of 850 °C. However, the achieved ferroelectric properties are vulnerable to voltage stress and higher annealing temperature, resulting in switching instability. Therefore, we introduce an ultrathin 1-nm-thick AlO layer at both interfaces of the HfZrO. The trilayer AlO/HfZrO/AlO structure allows switching parameters such as remnant and saturation polarizations to be immune to sweeping voltage and pulse cycling. Our results reveal that the trilayer not only makes the ferroelectric phase involved in the switching free from pinning, but also preserves the phase even at high annealing temperature. Simultaneously, the ferroelectric switching can be improved by preventing leakage charge.
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http://dx.doi.org/10.3390/mi11100910DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7600860PMC
September 2020

Anemia is associated with the risk of Crohn's disease, not ulcerative colitis: A nationwide population-based cohort study.

PLoS One 2020 8;15(9):e0238244. Epub 2020 Sep 8.

Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, South Korea.

Anemia is a common manifestation of inflammatory bowel disease (IBD), but it remains unclear whether anemia is associated with the development of IBD. We assessed the risk of developing IBD in anemic patients, and stratified the results with respect to their hemoglobin concentrations. A population-based study was conducted using the National Healthcare Insurance Service database in South Korea. We included individuals over 20 years' old who participated in the national health screening program in 2009 (n = 9,962,064). Anemia was defined as a hemoglobin level less than 13 g/dL in men and less than 12 g/dL in women. We compared the rate of newly diagnosed IBD in anemic patients and non-anemic individuals. Newly diagnosed IBD was identified using both the ICD-10 medical code and specialized V codes for rare intractable diseases in South Korea. During the mean follow-up period of 7.3 years, the incidences of CD and UC in anemic patients were 2.89 and 6.88 per 100,000 person-years, respectively. The risk of CD was significantly higher in anemic patients than in non-anemic individuals [adjusted hazard ratio (aHR), 2.084; 95% confidence interval (CI), 1.769-2.455]. The risk of CD development was inversely proportional to the hemoglobin concentration. A J-curve relationship was observed between age and the risk of CD in anemic patients. The risk of CD in male anemic patients was significantly higher than that in female anemic patients (aHR, 1.432 vs. 1.240, respectively). By contrast, there was no statistically significant difference in the risk of developing UC in anemic and non-anemic individuals (aHR, 0.972; 95% CI, 0.880-1.073). This work indicates that anemia is related to the development of CD, and this risk was inversely proportional to the hemoglobin concentration.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0238244PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7478647PMC
October 2020

Long-term outcomes of infliximab in a real-world multicenter cohort of patients with acute severe ulcerative colitis.

Intest Res 2021 Jul 18;19(3):323-331. Epub 2020 Aug 18.

Center for Crohn's and Colitis, Department of Gastroenterology, Kyung Hee University Hospital, Kyung Hee University College of Medicine, Seoul, Korea.

Background/aims: Infliximab (IFX) has proven effective as rescue therapy in steroid-refractory acute severe ulcerative colitis (ASUC), however, the long-term real-world data are scarce. Our study aimed to assess the long-term treatment outcomes of IFX in a real-life cohort.

Methods: We established a multicenter retrospective cohort of hospitalized patients with ASUC, who met Truelove and Witt's criteria and received intravenous corticosteroid (IVCS) or IFX during index hospitalization between 2006 and 2016 in 5 university hospitals in Korea. The cohort was systematically followed up until colectomy, death or last follow-up visit.

Results: A total of 296 patients were followed up for a mean of 68.9 ± 44.0 months. During index hospitalization, 49 patients were treated with IFX; as rescue therapy for IVCS failure in 37 and as first-line medical therapy for ASUC in 12. All patients treated with IFX avoided colectomy during index hospitalization. The cumulative rates of rehospitalization and colectomy were 20.4% and 6.1% at 3 months and 39.6% and 18.8% at the end of follow-up, respectively. Patients treated with IFX presented with significantly shorter colectomy-free survival than IVCS responders (P= 0.04, log-rank test). Both cytomegalovirus colitis and Clostridioides difficile infection (CDI) were the significant predictors of colectomy in the overall study cohort (hazard ratios of 6.57 and 4.61, respectively). There were no fatalities.

Conclusions: Our real-world cohort study demonstrated that IFX is an effective therapeutic option in Korean patients with ASUC, irrespective of IFX indication. Aggressive vigilance for cytomegalovirus colitis and CDI is warranted for hospitalized patients with ASUC.
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http://dx.doi.org/10.5217/ir.2020.00039DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8322032PMC
July 2021

Atopic Diseases Are Associated With Development of Inflammatory Bowel Diseases in Korea: A Nationwide Population-based Study.

Clin Gastroenterol Hepatol 2021 10 23;19(10):2072-2081.e6. Epub 2020 Jul 23.

Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.

Background & Aims: The association between atopic diseases and inflammatory bowel diseases (IBD) is unclear. We conducted a nationwide population-based study in Korea to investigate the effect of atopic diseases on the development of IBD.

Methods: A total of 9,923,521 participants, who received a medical check-up in 2009, were included and followed through 2017. The presence of any atopic diseases, including atopic dermatitis (AD), allergic rhinitis (AR), and asthma, was evaluated. Patients who developed IBD, including Crohn's disease (CD) and ulcerative colitis (UC), were identified using claims data from National Health Insurance; the association between atopic diseases and the risk of IBD was evaluated using Cox proportional hazard models, and presented as adjusted hazard ratios (aHRs) with 95% CIs.

Results: During a mean follow-up period of 7.3 years, 1419 patients (0.014%) developed CD and 5897 patients (0.059%) developed UC. The incidences of CD (per 100,000 person-years) were 3.756, 2.248, and 2.346 in patients with AD, AR, or asthma, respectively. The incidences of UC were 11.952, 9.818, and 9.358 in patients with AD, AR, or asthma, respectively. Multivariable analysis revealed that the aHRs for incident CD in patients with AD, AR, or asthma were 2.02, 1.33, and 1.60 (95% CIs, 1.118-3.663, 1.149-1.529, and 1.193-2.136, respectively) compared with controls. The risks of incident UC in patients with AD, AR, or asthma were 1.51, 1.32, and 1.29 (95% CIs, 1.082-2.104, 1.229-1.410, and 1.115-1.491, respectively) compared with controls. Moreover, an increase in the number of atopic diseases gradually increased the risk for CD and UC; for 1 or 2 or more atopic diseases, the aHRs for CD were 1.35 and 1.65 (95% CIs, 1.171-1.560 and 1.146-2.376), and the aHRs for UC were 1.30 and 1.49 (95% CIs, 1.211-1.392 and 1.249-1.774), respectively.

Conclusions: Based on a nationwide population-based study in Korea, patients with any atopic disease, including AD, AR, or asthma, have an increased risk for CD and UC. The risk for IBD increases with the increase in the number of atopic diseases.
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http://dx.doi.org/10.1016/j.cgh.2020.07.049DOI Listing
October 2021

Exploiting defective RRAM array as synapses of HTM spatial pooler with boost-factor adjustment scheme for defect-tolerant neuromorphic systems.

Sci Rep 2020 07 16;10(1):11703. Epub 2020 Jul 16.

ICT Creative Research Laboratory, Electronics and Telecommunications Research Institute, Daejeon, 34129, South Korea.

A crossbar array architecture employing resistive switching memory (RRAM) as a synaptic element accelerates vector-matrix multiplication in a parallel fashion, enabling energy-efficient pattern recognition. To implement the function of the synapse in the RRAM, multilevel resistance states are required. More importantly, a large on/off ratio of the RRAM should be preferentially obtained to ensure a reasonable margin between each state taking into account the inevitable variability caused by the inherent switching mechanism. The on/off ratio is basically adjusted in two ways by modulating measurement conditions such as compliance current or voltage pulses modulation. The latter technique is not only more suitable for practical systems, but also can achieve multiple states in low current range. However, at the expense of applying a high negative voltage aimed at enlarging the on/off ratio, a breakdown of the RRAM occurs unexpectedly. This stuck-at-short fault of the RRAM adversely affects the recognition process based on reading and judging each column current changed by the multiplication of the input voltage and resistance of the RRAM in the array, degrading the accuracy. To address this challenge, we introduce a boost-factor adjustment technique as a fault-tolerant scheme based on simple circuitry that eliminates the additional process to identify specific locations of the failed RRAMs in the array. Spectre circuit simulation is performed to verify the effect of the scheme on Modified National Institute of Standards and Technology dataset using convolutional neural networks in non-ideal crossbar arrays, where experimentally observed imperfective RRAMs are configured. Our results show that the recognition accuracy can be maintained similar to the ideal case because the interruption of the failure is suppressed by the scheme.
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http://dx.doi.org/10.1038/s41598-020-68547-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7367284PMC
July 2020
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