Korean clinical practice guidelines on biologics for moderate to severe Crohn’s disease

Crohn’s disease (CD) is a relapsing and progressive condition characterized by diarrhea, abdominal pain, weight loss, and hematochezia that results in serious complications such as perforations, fistulas, and abscesses. Various medications, interventions, and surgical treatments have been used to treat CD. The Korean guidelines for CD management were distributed in 2012 and revised in 2017 by the Inflammatory Bowel Disease (IBD) Research Group of the Korean Association for the Study of Intestinal Diseases. Substantial progress in mucosal immunologic research has elucidated the pathophysiology of IBD, leading to development of biological agents for treatment of CD. The first developed biologic agent, tumor necrosis factor-α agents, were shown to be efficacious in CD, heralding a new era in management of CD. Subsequently, vedolizumab, a monoclonal antibody against integrin α4β7, and ustekinumab, a human monoclonal antibody that inhibits the common p40 subunit of interleukin-12 and interleukin-23, were both approved for clinical use and are efficacious and safe for both induction and maintenance of remission in moderate-to-severe CD patients. Moreover, a recent study showed the non-inferiority of CT-P13, an infliximab biosimilar, compared with infliximab in CD patients. The third Korean guidelines for CD management provide updated information regarding treatment of moderate-to-severe CD patients with biologic agents.

Korean Guidelines for Postpolypectomy Colonoscopic Surveillance: 2022 revised edition

Colonoscopic polypectomy is effective in decreasing the incidence and mortality of colorectal cancer (CRC). Premalignant polyps discovered during colonoscopy are associated with the risk of metachronous advanced neoplasia. Postpolypectomy surveillance is the most important method for managing advanced metachronous neoplasia. A more efficient and evidence-based guideline for postpolypectomy surveillance is required because of the limited medical resources and concerns regarding colonoscopy complications. In these consensus guidelines, an analytic approach was used to address all reliable evidence to interpret the predictors of CRC or advanced neoplasia during surveillance colonoscopy. The key recommendations state that the high-risk findings for metachronous CRC following polypectomy are as follows: adenoma ≥10 mm in size; 3 to 5 (or more) adenomas; tubulovillous or villous adenoma; adenoma containing high-grade dysplasia; traditional serrated adenoma; sessile serrated lesion containing any grade of dysplasia; serrated polyp of at least 10 mm in size; and 3 to 5 (or more) sessile serrated lesions. More studies are needed to fully comprehend the patients who are most likely to benefit from surveillance colonoscopy and the ideal surveillance interval to prevent metachronous CRC.

Colonoscopic Screening and Risk of All-Cause and Colorectal Cancer Mortality in Young and Older Individuals / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#The incidence of early-onset colorectal cancer (CRC) and associated mortality have been increasing. However, the potential benefits of CRC screening are largely unknown in young individuals. We aimed to evaluate the effect of CRC screening with colonoscopy on all-cause and CRC mortality among young (aged < 45 years) and older (aged ≥ 45 years) individuals. @*Materials and Methods@#This cohort study included 528,046 Korean adults free of cancer at baseline who underwent a comprehensive health examination. The colonoscopic screening group was defined as those who reported undergoing colonoscopy for CRC screening. Mortality follow-up until December 31, 2019 was ascertained based on nationwide death certificate data from the Korea National Statistical Office. @*Results@#Colonoscopic screening was associated with a lower risk of all-cause mortality in both young and older individuals. Multivariable-adjusted time-dependent hazard ratios (95% confidence intervals) for all-cause mortality comparing ever- to never-screening were 0.86 (0.75-0.99) for young individuals and 0.71 (0.65-0.78) for older individuals. Colonoscopic screenings were also associated with a reduced risk of CRC mortality without significant interaction by age, although this association was significant only among participants aged ≥ 45 years, with corresponding time-dependent hazard ratios of 0.47 (0.15-1.44) for young individuals and 0.52 (0.31-0.87) for those aged ≥ 45 years. @*Conclusion@#Colonoscopic CRC screening decreased all-cause mortality among both young and older individuals, while significantly decreased CRC mortality was observed only in those aged ≥ 45 years. Screening initiation at an earlier age warrants more rigorous confirmatory studies.

Second-look endoscopy findings after endoscopic submucosal dissection for colorectal epithelial neoplasms

Background/Aims@#Although second-look endoscopy (SLE) is frequently performed after gastric endoscopic submucosal dissection (ESD) to prevent bleeding, no studies have reported SLE findings after colorectal ESD. This study aimed to investigate SLE findings and their role in preventing delayed bleeding after colorectal ESD. @*Methods@#Post-ESD ulcer appearances were divided into coagulation (with or without remnant minor vessels) and clip closure groups. SLE findings were categorized according to the Forrest classification (high-risk ulcer stigma [type I and IIa] and low-risk ulcer stigma [type IIb, IIc, III, or clip closure]), and risk factors for high-risk ulcer stigma were analyzed. @*Results@#Among the 375 cases investigated, SLEs were performed in 171 (45.6%) patients. The incidences of high-risk ulcer stigma and low-risk stigma were 5.3% (9/171) and 94.7% (162/171), respectively. During SLE, endoscopic hemostasis was performed more frequently in the high-risk ulcer stigma group than in the lowrisk ulcer stigma group (44.4% [4/9] vs. 1.9% [3/162], respectively; p < 0.001), but most of the endoscopic hemostasis in the high-risk ulcer stigma group (3/4, 75.0%) were prophylactic hemostasis. Post-ESD delayed bleeding occurred in three (0.8%) patients belonging to the SLE group, of which, one patient was from the high-risk stigma group and two were from the low-risk stigma group. @*Conclusions@#The incidence of high-risk ulcer stigma during SLE was low, and delayed bleeding occurred in, both, high-risk and low-risk groups of SLE. SLEs performed after colorectal ESD may not be effective in preventing delayed bleeding, and further prospective studies are needed to evaluate the efficacy of SLE in post-colorectal ESD.

Application of deep learning to predict advanced neoplasia using big clinical data in colorectal cancer screening of asymptomatic adults

Background/Aims@#We aimed to develop a deep learning model for the prediction of the risk of advanced colorectal neoplasia (ACRN) in asymptomatic adults, based on which colorectal cancer screening could be customized. @*Methods@#We collected data on 26 clinical and laboratory parameters, including age, sex, smoking status, body mass index, complete blood count, blood chemistry, and tumor marker, from 70,336 first-time colonoscopy screening recipients. For reference, we used a logistic regression (LR) model with nine variables manually selected from the 26 variables. A deep neural network (DNN) model was developed using all 26 variables. The area under the receiver operating characteristic curve (AUC), sensitivity, and specificity of the models were compared in a randomly split validation group. @*Results@#In comparison with the LR model (AUC, 0.724; 95% confidence interval [CI], 0.684 to 0.765), the DNN model (AUC, 0.760; 95% CI, 0.724 to 0.795) demonstrated significantly improved performance with respect to the prediction of ACRN (p < 0.001). At a sensitivity of 90%, the specificity significantly increased with the application of the DNN model (41.0%) in comparison with the LR model (26.5%) (p < 0.001), indicating that the colonoscopy workload required to detect the same number of ACRNs could be reduced by 20%. @*Conclusions@#The application of DNN to big clinical data could significantly improve the prediction of ACRNs in comparison with the LR model, potentially realizing further customization by utilizing large quantities and various types of biomedical information.

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

Background/Aims@#Our study aimed to evaluate the long-term outcomes and risk factors forrelapse 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 56months 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 Coxanalysis 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.

Metabolically Healthy Obesity Is Associated with an Increased Risk of Colorectal Adenoma Occurrence Diagnosed by Surveillance Colonoscopy

Background/Aims@#The risk of recurrence of colorectal adenoma among obese individuals without metabolic abnormalities or in those with metabolically healthy obesity is largely unexplored.Therefore, we longitudinally investigated the risk of adenoma occurrence in individuals undergoing surveillance colonoscopy according to metabolic status and obesity. @*Methods@#This retrospective cohort study included 16,872 Korean adults who underwent their first screening colonoscopy between 2003 and 2012 and who then underwent follow-up colonoscopy until 2017. Participants were categorized into a metabolically healthy nonobese group (reference group), a metabolically healthy obese group, a metabolically abnormal nonobese group, and a metabolically abnormal obese group. Hazard ratios (HRs) for adenoma recurrence compared to the reference group were calculated in each group. @*Results@#During a median follow-up duration of 47.3 months (interquartile range, 35.6 to 58.9 months), 3,673 (21.8%) and 292 (1.73%) participants developed adenoma and advanced adenoma, respectively. When age, sex, smoking, alcohol consumption, family history of colorectal cancer, and baseline adenoma risk were adjusted, the risk of adenoma recurrence was increased in metabolically healthy obese individuals (HR, 1.33; 95% confidence interval [CI], 1.12 to 1.57) and metabolically abnormal obese individuals (HR, 1.18; 95% CI, 1.08 to 1.30) but not in metabolically abnormal nonobese individuals (HR, 1.03; 95% CI, 0.94 to 1.13). @*Conclusions@#In this study, metabolically healthy obese individuals and metabolically abnormal obese individuals exhibited increased risks of occurrence of colorectal adenoma diagnosed by surveillance colonoscopy. This finding implies that obesity itself, even without metabolic abnormalities, is associated with an increased risk of adenoma recurrence.

Fetal Abdominal Obesity Detected At 24 to 28 Weeks of Gestation Persists Until Delivery Despite Management of Gestational Diabetes Mellitus

Background@#Fetal abdominal obesity (FAO) has been reported to be affected at gestational diabetes mellitus (GDM) diagnosis at 24 to 28 weeks of gestation in older and/or obese women. This study investigated whether the management of GDM improves FAO in GDM subjects near term. @*Methods@#Medical records of 7,099 singleton pregnant women delivering at CHA Gangnam Medical Center were reviewed retrospectively. GDM was diagnosed by 100-g oral glucose tolerance test after 50-g glucose challenge test based on Carpenter–Coustan criteria. GDM subjects were divided into four study groups according to maternal age and obesity. FAO was defined as ≥90th percentile of fetal abdominal overgrowth ratios (FAORs) of the ultrasonographically estimated gestational age (GA) of abdominal circumference per actual GA by the last menstruation period, biparietal diameter, or femur length, respectively. @*Results@#As compared with normal glucose tolerance (NGT) subjects near term, FAORs and odds ratio for FAO were significantly higher in old and/or obese women with GDM but not in young and nonobese women with GDM. For fetuses of GDM subjects with FAO at the time of GDM diagnosis, the odds ratio for exhibiting FAO near term and being large for GA at birth were 7.87 (95% confidence interval [CI], 4.38 to 14.15) and 10.96 (95% CI, 5.58 to 20.53) compared with fetuses of NGT subjects without FAO at GDM diagnosis. @*Conclusion@#Despite treatment, FAO detected at the time of GDM diagnosis persisted until delivery. Early diagnosis and treatment might be necessary to prevent near term FAO in high-risk older and/or obese women.

Second-look endoscopy findings after endoscopic submucosal dissection for colorectal epithelial neoplasms

Background/Aims@#Although second-look endoscopy (SLE) is frequently performed after gastric endoscopic submucosal dissection (ESD) to prevent bleeding, no studies have reported SLE findings after colorectal ESD. This study aimed to investigate SLE findings and their role in preventing delayed bleeding after colorectal ESD. @*Methods@#Post-ESD ulcer appearances were divided into coagulation (with or without remnant minor vessels) and clip closure groups. SLE findings were categorized according to the Forrest classification (high-risk ulcer stigma [type I and IIa] and low-risk ulcer stigma [type IIb, IIc, III, or clip closure]), and risk factors for high-risk ulcer stigma were analyzed. @*Results@#Among the 375 cases investigated, SLEs were performed in 171 (45.6%) patients. The incidences of high-risk ulcer stigma and low-risk stigma were 5.3% (9/171) and 94.7% (162/171), respectively. During SLE, endoscopic hemostasis was performed more frequently in the high-risk ulcer stigma group than in the lowrisk ulcer stigma group (44.4% [4/9] vs. 1.9% [3/162], respectively; p < 0.001), but most of the endoscopic hemostasis in the high-risk ulcer stigma group (3/4, 75.0%) were prophylactic hemostasis. Post-ESD delayed bleeding occurred in three (0.8%) patients belonging to the SLE group, of which, one patient was from the high-risk stigma group and two were from the low-risk stigma group. @*Conclusions@#The incidence of high-risk ulcer stigma during SLE was low, and delayed bleeding occurred in, both, high-risk and low-risk groups of SLE. SLEs performed after colorectal ESD may not be effective in preventing delayed bleeding, and further prospective studies are needed to evaluate the efficacy of SLE in post-colorectal ESD.

Application of deep learning to predict advanced neoplasia using big clinical data in colorectal cancer screening of asymptomatic adults

Background/Aims@#We aimed to develop a deep learning model for the prediction of the risk of advanced colorectal neoplasia (ACRN) in asymptomatic adults, based on which colorectal cancer screening could be customized. @*Methods@#We collected data on 26 clinical and laboratory parameters, including age, sex, smoking status, body mass index, complete blood count, blood chemistry, and tumor marker, from 70,336 first-time colonoscopy screening recipients. For reference, we used a logistic regression (LR) model with nine variables manually selected from the 26 variables. A deep neural network (DNN) model was developed using all 26 variables. The area under the receiver operating characteristic curve (AUC), sensitivity, and specificity of the models were compared in a randomly split validation group. @*Results@#In comparison with the LR model (AUC, 0.724; 95% confidence interval [CI], 0.684 to 0.765), the DNN model (AUC, 0.760; 95% CI, 0.724 to 0.795) demonstrated significantly improved performance with respect to the prediction of ACRN (p < 0.001). At a sensitivity of 90%, the specificity significantly increased with the application of the DNN model (41.0%) in comparison with the LR model (26.5%) (p < 0.001), indicating that the colonoscopy workload required to detect the same number of ACRNs could be reduced by 20%. @*Conclusions@#The application of DNN to big clinical data could significantly improve the prediction of ACRNs in comparison with the LR model, potentially realizing further customization by utilizing large quantities and various types of biomedical information.

Deep Neural Network-Based Prediction of the Risk of Advanced Colorectal Neoplasia

Background/Aims@#Risk prediction models using a deep neural network (DNN) have not been reported to predict the risk of advanced colorectal neoplasia (ACRN). The aim of this study was to compare DNN models with simple clinical score models to predict the risk of ACRN in colorectal cancer screening. @*Methods@#Databases of screening colonoscopy from Kangbuk Samsung Hospital (n=121,794) and Kyung Hee University Hospital at Gangdong (n=3,728) were used to develop DNN-based prediction models. Two DNN models, the Asian-Pacific Colorectal Screening (APCS) model and the Korean Colorectal Screening (KCS) model, were developed and compared with two simple score models using logistic regression methods to predict the risk of ACRN. The areas under the receiver operating characteristic curves (AUCs) of the models were compared in internal and external validation databases. @*Results@#In the internal validation set, the AUCs of DNN model 1 and the APCS score model were 0.713 and 0.662 (p0.1). @*Conclusions@#Simple score models for the risk prediction of ACRN are as useful as DNN-based models when input variables are limited. However, further studies on this issue are warranted to predict the risk of ACRN in colorectal cancer screening because DNN-based models are currently under improvement.

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

Background/Aims@#Our study aimed to evaluate the long-term outcomes and risk factors forrelapse 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 56months 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 Coxanalysis 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.

Metabolically Healthy Obesity Is Associated with an Increased Risk of Colorectal Adenoma Occurrence Diagnosed by Surveillance Colonoscopy

Background/Aims@#The risk of recurrence of colorectal adenoma among obese individuals without metabolic abnormalities or in those with metabolically healthy obesity is largely unexplored.Therefore, we longitudinally investigated the risk of adenoma occurrence in individuals undergoing surveillance colonoscopy according to metabolic status and obesity. @*Methods@#This retrospective cohort study included 16,872 Korean adults who underwent their first screening colonoscopy between 2003 and 2012 and who then underwent follow-up colonoscopy until 2017. Participants were categorized into a metabolically healthy nonobese group (reference group), a metabolically healthy obese group, a metabolically abnormal nonobese group, and a metabolically abnormal obese group. Hazard ratios (HRs) for adenoma recurrence compared to the reference group were calculated in each group. @*Results@#During a median follow-up duration of 47.3 months (interquartile range, 35.6 to 58.9 months), 3,673 (21.8%) and 292 (1.73%) participants developed adenoma and advanced adenoma, respectively. When age, sex, smoking, alcohol consumption, family history of colorectal cancer, and baseline adenoma risk were adjusted, the risk of adenoma recurrence was increased in metabolically healthy obese individuals (HR, 1.33; 95% confidence interval [CI], 1.12 to 1.57) and metabolically abnormal obese individuals (HR, 1.18; 95% CI, 1.08 to 1.30) but not in metabolically abnormal nonobese individuals (HR, 1.03; 95% CI, 0.94 to 1.13). @*Conclusions@#In this study, metabolically healthy obese individuals and metabolically abnormal obese individuals exhibited increased risks of occurrence of colorectal adenoma diagnosed by surveillance colonoscopy. This finding implies that obesity itself, even without metabolic abnormalities, is associated with an increased risk of adenoma recurrence.

Fetal Abdominal Obesity Detected At 24 to 28 Weeks of Gestation Persists Until Delivery Despite Management of Gestational Diabetes Mellitus

Background@#Fetal abdominal obesity (FAO) has been reported to be affected at gestational diabetes mellitus (GDM) diagnosis at 24 to 28 weeks of gestation in older and/or obese women. This study investigated whether the management of GDM improves FAO in GDM subjects near term. @*Methods@#Medical records of 7,099 singleton pregnant women delivering at CHA Gangnam Medical Center were reviewed retrospectively. GDM was diagnosed by 100-g oral glucose tolerance test after 50-g glucose challenge test based on Carpenter–Coustan criteria. GDM subjects were divided into four study groups according to maternal age and obesity. FAO was defined as ≥90th percentile of fetal abdominal overgrowth ratios (FAORs) of the ultrasonographically estimated gestational age (GA) of abdominal circumference per actual GA by the last menstruation period, biparietal diameter, or femur length, respectively. @*Results@#As compared with normal glucose tolerance (NGT) subjects near term, FAORs and odds ratio for FAO were significantly higher in old and/or obese women with GDM but not in young and nonobese women with GDM. For fetuses of GDM subjects with FAO at the time of GDM diagnosis, the odds ratio for exhibiting FAO near term and being large for GA at birth were 7.87 (95% confidence interval [CI], 4.38 to 14.15) and 10.96 (95% CI, 5.58 to 20.53) compared with fetuses of NGT subjects without FAO at GDM diagnosis. @*Conclusion@#Despite treatment, FAO detected at the time of GDM diagnosis persisted until delivery. Early diagnosis and treatment might be necessary to prevent near term FAO in high-risk older and/or obese women.

Prevention and management of viral hepatitis in inflammatory bowel disease: a clinical practice guideline by the Korean Association for the Study of Intestinal Diseases

The treatment of inflammatory bowel disease (IBD) has been revolutionized for the last 10 years by the increasing use of immunomodulators and biologics. With immunosuppression of this kind, opportunistic infection is an important safety concern for patients with IBD. In particular, viral hepatitis is determined by the interaction between the virus and the host’s immunity, and the risk of reactivation increases if immunity is compromised by immunosuppression therapy. Parts of Asia, including Korea, still show intermediate endemicity for the hepatitis A virus and hepatitis B virus compared with the United States and Western Europe. Thus, members of IBD research group of the Korean Association for the Study of Intestinal Diseases have produced a guideline on the prevention and management of viral hepatitis in IBD.

Altered Mitochondrial Functions and Morphologies in Epithelial Cells Are Associated With Pathogenesis of Chronic Rhinosinusitis With Nasal Polyps

Purpose@#Chronic rhinosinusitis with nasal polyps (CRSwNP) is a complex inflammatory disease of the nasal and paranasal sinus mucosa. The disease is associated with mitochondrial dysfunction, structural changes in the mitochondria, and reactive oxygen species (ROS) generation. This study investigated whether there are functional and morphological changes in the mitochondria in the epithelial cells of nasal polyps (NPs) and Staphylococcus aureus enterotoxin B (SEB)-stimulated nasal epithelial cells. @*Methods@#In all, 30 patients with CRSwNP and 15 healthy subjects were enrolled. Mitochondrial ROS (mtROS) and changes in mitochondrial functions and structures were investigated in the uncinate tissue (UT) of healthy controls, the UT or NPs of CRSwNP patients, and human nasal epithelial cells with or without SEB stimulation. @*Results@#Oxidative phosphorylation complexes showed various responses following SEB stimulation in the nasal epithelial cells, and their expressions were significantly higher in the NPs of patients with CRSwNP than in the UT of controls. Generation of mtROS was increased following SEB exposure in nasal epithelial cells and was reduced by pretreatment with MitoTEMPO, which is used as an mtROS scavenger. In the tissues, mtROS was significantly increased in the NPs of CRSwNP patients compared to the UT of controls or CRSwNP patients. The expressions of fusion- and fission-related molecules were also significantly higher in SEB-exposed nasal epithelial cells than in non-exposed cells. In tissues, the expression of fission (fission mediator protein 1)- and fusion (membrane and mitofusin-1, and optic atrophy protein 1)-related molecules was significantly higher in the NPs of CRSwNP patients than in UT of controls or CRSwNP patients. Transmission electron microscopy revealed elongated mitochondria in SEB-exposed nasal epithelial cells and epithelial cells of NPs. @*Conclusions@#Production of mtROS, disrupted mitochondrial function, and structural changes in nasal epithelial cells might be involved in the pathogenesis of CRSwNP.

Altered Mitochondrial Functions and Morphologies in Epithelial Cells Are Associated With Pathogenesis of Chronic Rhinosinusitis With Nasal Polyps

Purpose@#Chronic rhinosinusitis with nasal polyps (CRSwNP) is a complex inflammatory disease of the nasal and paranasal sinus mucosa. The disease is associated with mitochondrial dysfunction, structural changes in the mitochondria, and reactive oxygen species (ROS) generation. This study investigated whether there are functional and morphological changes in the mitochondria in the epithelial cells of nasal polyps (NPs) and Staphylococcus aureus enterotoxin B (SEB)-stimulated nasal epithelial cells. @*Methods@#In all, 30 patients with CRSwNP and 15 healthy subjects were enrolled. Mitochondrial ROS (mtROS) and changes in mitochondrial functions and structures were investigated in the uncinate tissue (UT) of healthy controls, the UT or NPs of CRSwNP patients, and human nasal epithelial cells with or without SEB stimulation. @*Results@#Oxidative phosphorylation complexes showed various responses following SEB stimulation in the nasal epithelial cells, and their expressions were significantly higher in the NPs of patients with CRSwNP than in the UT of controls. Generation of mtROS was increased following SEB exposure in nasal epithelial cells and was reduced by pretreatment with MitoTEMPO, which is used as an mtROS scavenger. In the tissues, mtROS was significantly increased in the NPs of CRSwNP patients compared to the UT of controls or CRSwNP patients. The expressions of fusion- and fission-related molecules were also significantly higher in SEB-exposed nasal epithelial cells than in non-exposed cells. In tissues, the expression of fission (fission mediator protein 1)- and fusion (membrane and mitofusin-1, and optic atrophy protein 1)-related molecules was significantly higher in the NPs of CRSwNP patients than in UT of controls or CRSwNP patients. Transmission electron microscopy revealed elongated mitochondria in SEB-exposed nasal epithelial cells and epithelial cells of NPs. @*Conclusions@#Production of mtROS, disrupted mitochondrial function, and structural changes in nasal epithelial cells might be involved in the pathogenesis of CRSwNP.

Knowledge and Viewpoints on Biosimilar Monoclonal Antibodies among Asian Physicians: Comparison with European Physicians / 대한소화기학회지

BACKGROUND/AIMS: Current knowledge and viewpoints regarding biosimilars among physicians in Asia are unknown, even though these were investigated by European Crohn's and Colitis Organization (ECCO) members in 2013 and 2015. Thus, this study conducted a multinational survey to assess the awareness of biosimilar monoclonal antibodies among Asian physicians.METHODS: A 17-question multiple-choice anonymous web survey was conducted with the logistic support of the Asian Organization of Crohn's and Colitis (AOCC). Randomly selected AOCC members were invited by e-mail to participate between February 24, 2017 and March 26, 2017.RESULTS: In total, 151 physicians from eight Asian countries responded to the survey. Most of the participants were gastroenterologists (96.6%), and 77.5% had cared for inflammatory bowel diseases (IBD) patients for more than 5 years. The majority of the respondents (66.2%) were aware that a biosimilar is similar but not equivalent to the originator. The majority of respondents (77.5%) considered cost saving to be the main advantage of biosimilars, but a high percentage of respondents (38.4%) were concerned about a different immunogenicity from that of the originator (92.4% and 27.1% respectively in ECCO 2015). Only 19.2% considered that the originator and biosimilars were interchangeable, and only 6.0% felt very confident in the use of biosimilars (44.4% and 28.8% respectively in ECCO 2015).CONCLUSIONS: Asian gastroenterologists in 2017 are generally well informed about biosimilars. On the other hand, compared to the ECCO members surveyed in 2015, Asian gastroenterologists had more concerns and less confidence about the use of biosimilars in clinical practice. Thus, IBD-specific data on the comparison of the efficacy, safety, and immunogenicity in Asian patients are needed.

Adherence to Asacol once daily versus divided regimen for maintenance therapy in ulcerative colitis: a prospective, multicenter, randomized study

BACKGROUND/AIMS: A once-daily (OD) regimen of 5-aminosalicylic acid (5-ASA) was easier to comply with than a divided daily (DD) regimen, and that treatment efficacy for ulcerative colitis (UC) was not affected by the dosing regimen. This study evaluated treatment adherence of OD and DD dosing in the Korean UC patients. METHODS: This study was a prospective, multicenter, randomized trial. UC patients were enrolled who have been in remission for more than 3 months. Patients were randomly assigned to the OD or DD group in a 1:1 ratio. The primary endpoint was adherence rate measured by tablet counts and self-reported adherence rate at 3, 6, 9, and 12 months. The relapse rate was measured at 1 year. RESULTS: Data from the 180 patients who were randomized were analyzed. Both self-reported adherence rate and adherence rate measured by tablet counts were not different at every points, including 1 year. The patients' satisfaction of the OD group was higher than that of the DD group (P<0.001). At 1 year, 91.2% and 95.5% of patients in the OD group and DD group had maintained clinical remission, respectively (P=0.37). CONCLUSIONS: The adherence rates were not different between the OD group and DD group. The patients' satisfaction was higher in the OD group than in the DD group. 5-ASA OD dosing might have the same effect as DD for the maintenance of UC remission.

A case of life-threatening intraoperative diffuse alveolar hemorrhage during a femur fracture operation with suspected fat embolism: A case report

Diffuse alveolar hemorrhage (DAH) is a rare manifestation of trauma or long bone fracture. A relationship between fat embolism and DAH has been reported. A 73-year-old female developed sudden cardiac arrest during a femur fracture operation. Cardiopulmonary resuscitation (CPR) was repeated for about 130 minutes. During CPR, blood was detected in the endotracheal tube. Diffuse patch ground glass opacity appearance and increased pulmonary artery with bulging of interventricular septum toward the left ventricle were detected on a chest computed tomography scan. After full supportive care including ventilator therapy, the patient's condition became stabilized and she was extubated after 7 days. We report a case of DAH in the course of a suspected fat embolism during femur fracture operation. Although DAH is a rare manifestation of fat embolism, early diagnosis and aggressive treatment likely can decrease morbidity and mortality.