Efficacy, tolerability, and safety of oral sulfate tablet versus 2 L-polyethylene glycol/ascorbate for bowel preparation in older patients: prospective, multicenter, investigator single-blinded, randomized study.

BACKGROUND: We compared the efficacy, tolerability, and safety of oral sulfate tablets (OST, which contains simethicone) and 2 L-polyethylene glycol/ascorbate (2 L-PEG/Asc) with a split-dosing regimen in older individuals aged ≥ 70 years who underwent scheduled colonoscopy. METHODS: This prospective, randomized, investigator-blinded, multicenter study was conducted between June 2022 and October 2023. Participants aged ≥ 70 years were randomized at a ratio of 1:1 to the OST or 2 L-PEG/Asc groups. RESULTS: In total, 254 patients were evaluated using a modified full analysis set. Successful overall bowel preparation was excellent and similar between the OST and 2 L-PEG/Asc groups for the Boston Bowel Preparation Scale (BBPS) (96.5% vs. 96.6%) and Harefield Cleansing Scale (HCS) (96.5% vs. 97.4%). The overall high-quality preparation rate was higher in the OST group than in the 2 L-PEG/Asc group (BBPS: 55.7% vs. 28.4%, P < 0.001; HCS: 66.1% vs. 38.8%, P < 0.001). The overall adenoma detection rate (54.8% vs. 35.3, P = 0.003) was superior in the OST group compared to the 2 L-PEG/Asc group. Tolerability scores, including overall satisfaction, were generally higher in the OST group than in the 2 L-PEG/Asc group. The incidence of major solicited adverse events was comparable between the two groups (55.7% vs. 68.1, P = 0.051), and there were no clinically significant changes in the serum laboratory profiles on the day of or 7 days after colonoscopy. CONCLUSIONS: OST is an effective and safe low-volume agent for colonoscopy, with better tolerance than 2 L-PEG/Asc, in older individuals aged ≥ 70 years.

Impact of COVID-19 Pandemic on Performance of Gastrointestinal Endoscopy.

Background/Aims: Non-time-sensitive gastrointestinal endoscopy was deferred because of the risk of exposure to coronavirus disease 2019 (COVID-19), but no population-based studies have quantified the adverse impact on gastrointestinal procedures. This study examined the impact of the COVID-19 pandemic on the performance of esophagogastroduodenoscopy (EGD), colonoscopy, ERCP, and abdominal ultrasonography (US) in South Korea. Methods: This nationwide, population-based study compared the claim data of EGD, colonoscopy, ERCP, and abdominal US in 2020 and 2021 (COVID-19 era) with those in 2019 (before the COVID-19 era). Results: During the first year (2020) of the COVID-19 pandemic, the annual claim data of EGD and colonoscopy were reduced by 6.3% and 6.9%, respectively, but those of ERCP and abdominal US were increased by 1.0% and 2.9%, compared to those in 2019. During the first surge (March and April 2020) of COVID-19, the monthly claim data of EGD, colonoscopy, ERCP, and abdominal US were reduced by 28.8%, 43.8%, 5.1%, and 21.6%, respectively, in March 2020, and also reduced by 17.2%, 32.8%, 4.4%, and 9.5%, respectively, in April 2020, compared to those in March and April 2019. During March and April 2020, the monthly claims of ERCP, compared with those in 2019, declined less significantly than those of EGD and colonoscopy (both p<0.001). Conclusions: The claims of EGD and colonoscopy were reduced more significantly than those of ERCP and abdominal US during the COVID-19 pandemic because ERCPs are time-sensitive procedures and abdominal USs are non-aerosolized procedures.

Enrichment of Activated Fibroblasts as a Potential Biomarker for a Non-Durable Response to Anti-Tumor Necrosis Factor Therapy in Patients with Crohn's Disease.

We investigated whether the response to anti-tumor necrosis factor (anti-TNF) treatment varied according to inflammatory tissue characteristics in Crohn's disease (CD). Bulk RNA sequencing (RNA-seq) data were obtained from inflamed and non-inflamed tissues from 170 patients with CD. The samples were clustered based on gene expression profiles using principal coordinate analysis (PCA). Cellular heterogeneity was inferred using CiberSortx, with bulk RNA-seq data. The PCA results displayed two clusters of CD-inflamed samples: one close to (Inflamed_1) and the other far away (Inflamed_2) from the non-inflamed samples. Inflamed_1 was rich in anti-TNF durable responders (DRs), and Inflamed_2 was enriched in non-durable responders (NDRs). The CiberSortx results showed that the cell fraction of activated fibroblasts was six times higher in Inflamed_2 than in Inflamed_1. Validation with public gene expression datasets (GSE16879) revealed that the activated fibroblasts were enriched in NDRs over Next, we used DRs by 1.9 times pre-treatment and 7.5 times after treatment. Fibroblast activation protein (FAP) was overexpressed in the Inflamed_2 and was also overexpressed in the NDRs in both the RISK and GSE16879 datasets. The activation of fibroblasts may play a role in resistance to anti-TNF therapy. Characterizing fibroblasts in inflamed tissues at diagnosis may help to identify patients who are likely to respond to anti-TNF therapy.

Single-Cell Network-Based Drug Repositioning for Discovery of Therapies against Anti-Tumour Necrosis Factor-Resistant Crohn's Disease.

Primary and secondary non-response affects approximately 50% of patients with Crohn's disease treated with anti-tumour necrosis factor (TNF) monoclonal antibodies. To date, very little single cell research exists regarding drug repurposing in Crohn's disease. We aimed to elucidate the cellular phenomena underlying resistance to anti-TNF therapy in patients with Crohn's disease and to identify potential drug candidates for these patients. Single-cell transcriptome analyses were performed using data (GSE134809) from the Gene Expression Omnibus and Library of Integrated Network-Based Cellular Signatures L1000 Project. Data aligned to the Genome Reference Consortium Human Build 38 reference genome using the Cell Ranger software were processed using the Seurat package. To capture significant functional terms, gene ontology functional enrichment analysis was performed on the marker genes. For biological analysis, 93,893 cells were retained (median 20,163 genes). Through marker genes, seven major cell lineages were identified: B-cells, T-cells, natural killer cells, monocytes, endothelial cells, epithelial cells, and tissue stem cells. In the anti-TNF-resistant samples, the top 10 differentially expressed genes were HLA-DQB-1, IGHG1, RPS23, RPL7A, ARID5B, LTB, STAT1, NAMPT, COTL1, ISG20, IGHA1, IGKC, and JCHAIN, which were robustly distributed in all cell lineages, mainly in B-cells. Through molecular function analyses, we found that the biological functions of both monocyte and T-cell groups mainly involved immune-mediated functions. According to multi-cluster drug repurposing prediction, vorinostat is the top drug candidate for patients with anti-TNF-refractory Crohn's disease. Differences in cell populations and immune-related activity within tissues may influence the responsiveness of Crohn's disease to anti-TNF agents. Vorinostat may serve as a promising novel therapy for anti-TNF-resistant Crohn's disease.

Interobserver Variation of Bowel Preparation for Colonoscopy.

BACKGROUD/AIMS: Several bowel preparation scales have been developed, but they are variably validated to guide clinical practice. The aim of this study was to assess the interobserver reliability between internal and external endoscopists using the Harefield Cleaning Scale (HCS). METHODS: Data was collected from a study evaluating the efficacy of oral sulfate tablets in patients undergoing colonoscopy. The assessments of bowel cleansing were carried out by four internal endoscopists at the time of the procedure, and colonoscopy video recordings were reviewed independently by three external endoscopists. Interobserver reliability was quantified using Cohen's Kappa coefficient, and scores and grades of each segment were compared between internal and external endoscopist groups. RESULTS: Among 83 colonoscopy videos, interobserver reliability yielded a fair agreement between internal and external endoscopists, with a Cohen's Kappa coefficient of 0.39 (95% CI 0.08-0.70). Successful overall preparation rates (100% vs 98.8%) and high-quality preparation rates (88% vs 94%) were excellent and comparable between the two groups. In contrast, one case of unsuccessful cleansing (grade C) was documented, only in the external group. In addition, the interobserver reliability between internal and external endoscopists comparing each segmental score yielded a slight agreement in the descending colon (0.11, 95% CI - 0.02 to 0.23) and sigmoid colon (0.04, 95% CI - 0.18 to 0.26). DISCUSSION: Interobserver reliability between internal and external endoscopists using the HCS was fair. However, the HCS may be limited as a reliable scale for assessing bowel preparation quality in the left colon, where liquid is mainly retained in the left lateral position.

Comparison of a novel mini-oral sulfate tablet and the conventional oral sulfate tablet in bowel preparation for colonoscopy: a prospective, randomized, investigator-blinded, multicenter, non-inferior, phase 3 trial.

BACKGROUND AND AIMS: The use of conventional oral sulfate tablets (OSTs) has gained popularity; nonetheless, they may be not only inconvenient to swallow but also difficult to dissolve. A novel mini-OST has recently been developed to enhance compliance with conventional OST use. This study aimed to compare the efficacy, tolerability, and safety between mini-OST and conventional OST. METHODS: This was a prospective, randomized, investigator-blinded, multicenter, and non-inferior phase 3 trial conducted between September 2022 and December 2022. The efficacy, safety, and tolerability were compared between mini-OST and conventional OST. RESULTS: Exactly 83 patients were evaluated based on a full analysis set (FAS), whereas 82 patients were evaluated as a per-protocol set (PPS). With respect to the efficacy of preparation, successful and high-quality preparation was excellent in the mini-OST and conventional OST groups on both FAS and PPS analyses, without significant differences between the two groups. On the FAS analysis, the satisfaction and tolerability scores were high in both groups, without significant differences. The first bowel movement after taking the investigational product occurred 30 min earlier in the mini-OST group than in the OST group. Mild, moderate, and severe adverse events (AEs) were comparable between the two groups; however, any AEs were more common in the mini-OST group than in the conventional OST group overall. CONCLUSIONS: Compared with conventional OST, the novel mini-OST preparation showed similar efficacy, tolerability, and safety, including mild eight solicited AEs and moderate-to-severe AEs. Clinical trial registration NCT05670470.

Impact of the COVID-19 Pandemic on Esophagogastroduodenoscopy and Gastric Cancer Claims in South Korea: A Nationwide, Population-Based Study.

PURPOSE: There has been little information about the impact of coronavirus disease 2019 (COVID-19) pandemic on esophagogastroduodenoscopy (EGD) and gastric cancer claims. This study aimed to measure the impact of COVID-19 pandemic on EGD and gastric cancer claims in South Korea. MATERIALS AND METHODS: This nationwide, population-based study compared the claims data of EGD, gastric cancer, early gastric cancer (EGC), advanced gastric cancer (AGC) and gastric cancer operation in 2020 and 2021 (COVID-19 era) to those in 2019 (before COVID-19 pandemic). RESULTS: The annual claims of EGD, gastric cancer, EGC, and AGC were reduced by 6.3%, 5.0%, 4.7%, and 3.6% in 2020 and by 2.2%, 1.0%, 0.6%, and 1.9% in 2021, respectively, compared to 2019. The amount of annual claims of gastric cancer operation was reduced by 8.8% in 2020, but increased by 0.9% in 2021, compared to those in 2019. The monthly claims of EGD, gastric cancer, EGC, AGC, and gastric cancer operation were mainly reduced in the first epidemic wave of COVID-19, but decreased in the 2nd to 4th epidemic wave. Compared to 2019, the monthly claim of EGD, gastric cancer, EGC, AGC, and gastric cancer operation were reduced by 28.8%, 14.3%, 18.1%, 9.2%, and 5.8% in March 2020 and by 17.2%, 10.8%, 10.3%, 7.2%, and 35.4% in April 2020, respectively. CONCLUSION: Negative impact of the COVID-19 pandemic on EGD, gastric cancer, EGC, AGC, and gastric cancer operation was worst during the first surge of COVID-19, but decreased in the 2nd to 4th epidemic wave of the disease in 2020 and 2021.

The elderly population are more vulnerable for the management of colorectal cancer during the COVID-19 pandemic: a nationwide, population-based study.

BACKGROUND/AIMS: The impact of coronavirus disease 2019 (COVID-19) on the management of colorectal cancer (CRC) may worse in elderly population, as almost all COVID-19 deaths occurred in the elderly patients. This study aimed to evaluate the impact of COVID-19 on CRC management in the elderly population. METHODS: The numbers of patients who underwent colonoscopy, who visited hospitals or operated for CRC in 2020 and 2021 (COVID-19 era) were compared with those in 2019, according to 3 age groups (≥70 years, 50-69 years, and ≤49 years), based on the nationwide, population-based database (2019-2021) in South Korea. RESULTS: The annual volumes of colonoscopy and hospital visits for CRC in 2020 were more significantly declined in the old age group than in the young age group (both P<0.001). In addition, the annual volume of patients operated for CRC numerically more declined in old age group than in young age group. During the first surge of COVID-19 (March and April 2020), old age patients showed statistically significant declines for the monthly number of colonoscopies (-46.5% vs. -39.3%, P<0.001), hospital visits (-15.4% vs. -7.9%, P<0.001), CRC operations (-33.8% vs. -0.7%, P<0.05), and colonoscopic polypectomies (-41.8% vs. -38.0%, P<0.001) than young age patients, compared with those of same months in 2019. CONCLUSIONS: Elderly population are more vulnerable for the management of CRC during the COVID-19 pandemic. Therefore, the elderly population are more carefully cared for in the management of CRC during the next pandemic.

Clinical and pathological characteristics of early-onset colorectal cancer in South Korea.

Background: Early-onset colorectal cancer (EOCRC) may differ by race and ethnicity, and recently South Korea has witnessed a surge in cases. We aimed to evaluate the clinical and pathological features of patients with EOCRC, and to determine the predictors of overall survival. Methods: In this retrospective study, EOCRC was defined as CRC diagnosed in patients aged < 50 years, and late-onset CRC was defined as CRC diagnosed in those over 75 years of age. The clinical and pathological characteristics of patients with EOCRC were compared with late-onset CRC. We also used multivariable Cox proportional hazard models to find predictors of overall survival in patients with EOCRC. Results: The proportion of early-onset CRC was 9.1% of 518 patients with CRC, and the clinical and pathological characteristics were similar between early-onset (n = 47) and late-onset CRC (n = 134). However, EOCRC had a preponderance for distal tumor location (70.2% vs. 50.7%, P = 0.02) and T1-2 stage disease (23.4% vs. 11.2%, P = 0.04), compared with those of late-onset CRC. Using multivariable Cox proportional hazard models, only vascular invasion (hazard ratio = 8.75, 95% confidence interval 1.139‒67.197) was found to be a risk factor for overall survival (P = 0.04) for patients with CRC. Conclusion: EOCRC had preponderance for distal tumor location and early T-stage disease, compared with late-onset CRC. Considering the increasing incidence of EOCRC, more studies on clinical and pathological characteristics of EOCRC may be warranted.

Neutrophil to lymphocyte ratio can predict overall survival in patients with stage II to III colorectal cancer.

The neutrophil-to-lymphocyte ratio (NLR) is a prognostic inflammatory marker in colorectal cancer (CRC), however, little is known for its prognostic role in stage II to III CRC patients underwent curative resection. This study was aimed to investigate prognostic role of NLR in stage II to III CRC patients underwent surgery. Medical records of 1378 newly diagnosed CRC patients between June 2006 and March 2020 were reviewed. Data were collected by using electronic medical record software. Survival rate were analyzed using the Kaplan-Meier method. The cutoff values of NLR in stage II to III CRC patients were defined by maximally selected log-rank statistics. Multivariable cox proportional-hazard models were performed to find risk factors associated with overall survival (OS) in stage II to III CRC patients underwent surgery. Among 1378 CRC patients enrolled, 910 patients underwent surgery. In entire surgical cohort, age, body mass index (BMI), CEA, carbohydrate antigen 19-9 (CA 19-9), lymphatic invasion, NLR, and albumin-to-globulin ratio (AGR) were found to be risk factors associated with OS (all P < .05). In stage II to III CRC patients underwent curative resection (n = 623), age, BMI, lymphatic invasion, AGR, and NLR were found to be risk factors associated with OS (all P < .05). In the multivariable analysis, CA 19-9 and lymphatic invasion were independent risk factors for OS in entire surgical cohort. In the multivariable analysis for the stage II to III CRC patients, age, BMI, lymphatic invasion and NLR (Hazard ratio = 2.41, 95% confidential interval [CI]: 1.04-5.595, P = .041) were independent risk factors for OS. NLR can be used as a clinically simple and useful parameter for predicting OS in stage II to III CRC patients undergoing curative resection, however, its optimal cutoff value should be further evaluated.

Chasm between Public Perceptions and Epidemiological Data on Colorectal Cancer.

Background/Aims: Only a few studies have examined perceptions of the incidence and prognosis of colorectal cancer (CRC) in the general Korean population. The aim of this study was to determine public perceptions of the lifetime incidence rate and survival of CRC. Methods: All adults older than 50 years who visited the Kyung Hee University Hospital at Gangdong were invited to participate in this survey for 5 months in 2021. During the study period, eligible individuals participated in this survey through a link or quick response code on a poster posted in the hospital, which was linked to a web-based questionnaire. The questionnaire used for this survey included demographic and socioeconomic data, perceptions of CRC, and awareness of the CRC incidence and 5-year survival rate. Results: Among 203 respondents, 196 answers were analyzed after the exclusion of seven incomplete answers. In our survey, half of the respondents (49.5%) answered the expected lifetime incidence rate of CRC as 0% to 4.9%. Koreans perceived CRC as a more fatal disease than epidemiological data, as 70.9% of the respondents expected the 5-year survival rate of CRC to be less than 70% for the general population. However, Koreans perceived stage IV CRC as a less fatal disease than epidemiological data, because only 20.9% of the respondents expected the 5-year survival rate of stage IV CRC to be less than 10% for general population. Conclusions: Koreans recognized CRC as a more common and fatal disease than actual epidemiological data of CRC. Therefore, more efforts should be made to provide more correct information on CRC for better decision-making and communication.

The Prognostic Utilities of DNA Mismatch Repair Status and KRAS and BRAF Mutation in Korean Colorectal Cancer Patients: The KASID Multicenter Study.

INTRODUCTION: KRAS, BRAF, and DNA mismatch repair (MMR) mutations aid clinical decision-making for colorectal cancer (CRC) patients. To ensure accurate predictions, the prognostic utilities of these biomarkers and their combinations must be individualized for patients with various TNM stages. METHODS: Here, we retrospectively analyzed the clinicopathological features of 904 Korean CRC patients who underwent CRC surgery in three teaching hospitals from 2011 to 2013; we also assessed the prognostic utilities of KRAS, BRAF, and MMR mutations in these patients. RESULTS: The overall frequencies of KRAS and BRAF mutations were 35.8% and 3.2%, respectively. Sixty-nine patients (7.6%) lacking expression of ≥1 MMR protein were considered MMR protein deficient (MMR-D); the remaining patients were considered MMR protein intact. KRAS mutations constituted an independent risk factor for shorter overall survival (OS) in TNM stage I-IV and stage III patients. BRAF mutations were associated with shorter OS in TNM stage I-IV patients. MMR-D status was strongly positive prognostic in TNM stage I-II patients. DISCUSSION/CONCLUSION: To our knowledge, this is the first multicenter study to explore the prognostic utilities of KRAS, BRAF, and MMR statuses in Korean CRC patients. Various combinations of KRAS, BRAF, and DNA MMR mutations serve as genetic signatures that affect tumor behavior; they are prognostic in CRC patients.

The Common and Unique Pattern of Microbiome Profiles among Saliva, Tissue, and Stool Samples in Patients with Crohn's Disease.

This study aimed to elucidate common and unique microbiome patterns in saliva, intestinal tissue biopsy, and stool samples from patients with Crohn's disease (CD). Saliva, tissue, and stool samples from patients with CD were prospectively collected. Quantitative and phylogenetic analyses of 16s rRNA sequencing data were performed with bioinformatical pipelines. A total of 30 patients were enrolled in this study. The composition of major microbial taxa was similar between tissue and stool samples. A total of 11 of the 20 most abundant microbiota were found in both samples. The microbial community in saliva was significantly distinct from that in tissue and stool. The major species of microbiota and their composition also differed significantly from those of tissue and stool samples. However, Streptococcus and Prevotella are common genera in saliva, tissue, and stool microbiome. The abundance of Streptococcus, Pantoea, and Actinomyces from the saliva sample group were significantly different, varying with the location of the inflammation. Saliva has a distinct microbial community compared with tissues and stools in patients with CD. Prevotella and Streptococcus, which are commonly observed in saliva, stool, and tissue, can be considered a potential biomarker related to the diagnosis or prognosis of CD.

Development of a Machine Learning Model to Predict Non-Durable Response to Anti-TNF Therapy in Crohn's Disease Using Transcriptome Imputed from Genotypes.

Almost half of patients show no primary or secondary response to monoclonal anti-tumor necrosis factor α (anti-TNF) antibody treatment for inflammatory bowel disease (IBD). Thus, the exact mechanisms of a non-durable response (NDR) remain inadequately defined. We used our genome-wide genotype data to impute expression values as features in training machine learning models to predict a NDR. Blood samples from various IBD cohorts were used for genotyping with the Korea Biobank Array. A total of 234 patients with Crohn's disease (CD) who received their first anti-TNF therapy were enrolled. The expression profiles of 6294 genes in whole-blood tissue imputed from the genotype data were combined with clinical parameters to train a logistic model to predict the NDR. The top two and three most significant features were genetic features (DPY19L3, GSTT1, and NUCB1), not clinical features. The logistic regression of the NDR vs. DR status in our cohort by the imputed expression levels showed that the ß coefficients were positive for DPY19L3 and GSTT1, and negative for NUCB1, concordant with the known eQTL information. Machine learning models using imputed gene expression features effectively predicted NDR to anti-TNF agents in patients with CD.

Quality indicators in colonoscopy: the chasm between ideal and reality.

Continuous measurement of quality indicators (QIs) should be a routine part of colonoscopy, as a wide variation still exists in the performance and quality levels of colonoscopy in Korea. Among the many QIs of colonoscopy, the adenoma detection rate, average withdrawal time, bowel preparation adequacy, and cecal intubation rate should be monitored in daily clinical practice to improve the quality of the procedure. The adenoma detection rate is the best indicator of the quality of colonoscopy; however, it has many limitations for universal use in daily practice. With the development of natural language processing, the adenoma detection rate is expected to become more effective and useful. It is important that colonoscopists do not strictly and mechanically maintain an average withdrawal time of 6 minutes but instead perform careful colonoscopy to maximally expose the colonic mucosa with a withdrawal time of at least 6 minutes. To achieve adequate bowel preparation, documentation of bowel preparation with the Boston Bowel Preparation Scale (BBPS) should be a routine part of colonoscopy. When colonoscopists routinely followed the bowel preparation protocols, ≥85% of outpatient screening colonoscopies had a BBPS score of ≥6. In addition, the cecal intubation rate should be ≥95% of all screening colonoscopies. The first step in improving colonoscopy quality in Korea is to apply these key performance measurements in clinical practice.

Gastrointestinal and non-gastrointestinal complication rates associated with diagnostic esophagogastroduodenoscopy under sedation.

ABSTRACT: Esophagogastroduodenoscopy (EGD) under sedation may result in gastrointestinal (GI) and non-GI complications. However, no previous studies have reported 30-day GI and non-GI complications after diagnostic EGD under sedation.We conducted a retrospective, observational study of 30-day GI and non-GI complication rates after outpatient diagnostic EGD under sedation in subjects ≥18 years between January 2012 and December 2017 based on a common data model database. Thirty-day complication rates were compared with EGD under sedation or not, type of sedation drugs (midazolam only vs midazolam/propofol) and age groups (18-64 year vs ≥65 year) for GI (bleeding and perforation) and non-GI complications (pneumonia, acute myocardial infarction, congestive heart failure and cerebral stroke).In total, 39,910 were performed with sedation (midazolam only, n = 16,033 and midazolam/propofol, n = 23,864) and 22,894 were performed without sedation. Elderly patients significantly favored EGD without sedation (P < .01). GI and non-GI complication rates were similar between EGD under sedation and without sedation (all P > .1) except for acute myocardial infarction rate, which was significantly higher in EGD without sedation than EGD under sedation (1.7/10,000 vs 0.3/10,000 persons, P = .043). All GI and non-GI complications were also similar between the midazolam/propofol and midazolam only groups as well as between young and old patients (all P > .1).Outpatient diagnostic EGD under sedation has an excellent safety profile. In addition, it can be safely performed with midazolam only or midazolam/propofol and in young and old patients.

Uncovering Novel Pre-Treatment Molecular Biomarkers for Anti-TNF Therapeutic Response in Patients with Crohn's Disease.

Neutralising monoclonal antibodies for tumour necrosis factor (TNF) has been widely used to treat Crohn's disease (CD) in clinical practice. However, differential individual response necessitates a therapeutic response assessment of anti-TNF agents in CD patients for optimizing therapeutic strategy. We aimed to predict anti-TNF therapy response in CD patients using transcriptome analyses. Transcriptome analyses were performed using data from the Gene Expression Omnibus, GeneCards, and Human Protein Atlas databases. The significantly mitigated biological functions associated with anti-TNF therapy resistance in CD patients encompassed immune pathways, including Interleukin-17 (IL-17) signaling, cytokine-cytokine receptor interaction, and rheumatoid arthritis. The scores of immune cell markers, including neutrophils, monocytes, and macrophages/monocytes were also significantly decreased in non-responders compared with that measured in anti-TNF therapy responders. The KAT2B gene, associated with IL-17 cytokine mediated neutrophil mobilization and activation, was significantly under-expressed in both tissue and peripheral blood mononuclear cells (PBMCs) in anti-TNF therapy-resistant CD patients. The reduced expression of several pro-inflammatory cytokines due to down-regulated IL-17 signaling, is suggestive of the primary non-response to anti-TNF agents in CD patients. Furthermore, the PBMC KAT2B gene signature may be a promising pre-treatment prognostic biomarker for anti-TNF drug response in CD patients.

Artificial intelligence-based measurement outperforms current methods for colorectal polyp size measurement.

OBJECTIVES: An accurate polyp size estimation during colonoscopy is crucial to determine the surveillance interval and predict the risk of malignant progression. However, there is a high degree of subjectivity in estimating polyp size among endoscopists in clinical practice. We aimed to assess the efficacy of a novel method that uses artificial intelligence (AI) to measure the size of colon polyps and compare it with current approaches. METHODS: Using the W-Net model for vessel segmentation and based on retinal image datasets (DRIVE, STARE, CHASE-DB, and HRF) and colonoscopy images, we developed the bifurcation-to-bifurcation (BtoB) distance measuring method and applied it to endoscopic images. Measurements were compared with those obtained by eight endoscopists (four expert and four trainees). Diagnostic ability and reliability were evaluated using Lin's concordance correlation coefficients (CCCs) and Bland-Altman analyses. RESULTS: For both experts and trainees, visually estimated sizes of the same polyp were significantly inconsistent depending on the camera view used (P < 0.001). Bland-Altman analyses showed that there was a trend toward underestimation of the sizes of the polyps in both groups, especially for polyps larger than 10 mm. The new technique was highly accurate and reliable in measuring the size of colon polyp (CCC, 0.961; confidence interval 0.926-0.979), clearly outperforming the visual estimation and open biopsy forceps methods. CONCLUSION: The new AI measurement method improved the accuracy and reliability of polyp size measurements in colonoscopy images. Incorporating AI might be particularly important to improve the efficiency of trainees at estimating polyp size during colonoscopy.

Risk of malignancy in kidney transplant recipients: a nationwide population-based cohort study.

BACKGROUND: Post-transplant malignancy is major morbidity complicated in kidney transplantation (KT). In Korea, a few studies have investigated the sex- and age-dependent risk for post-transplant malignancy among KT recipients on a large scale. METHODS: We utilized a national health insurance database in Korea to investigate the relative risk of post-transplant malignancy in 12,634 KT recipients between 2007 and 2017. The same number of patients with acute appendicitis was included as a control group. The relative risk of malignancy was estimated using a multivariable-adjusted Cox model, and interaction analysis was performed to investigate age- and sex-predominant patterns. RESULTS: KT recipients had an overall 1.8-fold higher risk for post-transplant malignancy with an increased risk for 14 of 29 cancer types, among which Kaposi's sarcoma, non-Hodgkin's lymphoma, kidney, uterus, and bladder/urinary tract cancers were most prominent. Although the overall risk for post-transplant malignancy was similar between male and female KT recipients, head and neck cancer had a higher risk among male KT recipients, whereas non-Hodgkin's lymphoma and bladder/urinary tract cancer had a higher risk among female KT recipients. Overall, the young (< 50 years) KT recipients had a higher risk for post-transplant malignancy than older ones (≥ 50 years), whose pattern was most prominent in non-Hodgkin's lymphoma. In contrast, breast and nonmelanoma skin cancer showed a higher risk among older KT recipients. CONCLUSION: KT recipients had an increased risk for a wide range of cancer types, some of which showed differential risk patterns with age and sex. Our result suggests that focused screening for predominant post-transplant malignancies may be an effective strategy for selected KT recipients.

Improving the tolerability and safety of 1-L polyethylene glycol plus low-dose ascorbic acid for bowel preparation in a healthy population: a randomized multicenter clinical trial.

BACKGROUND AND AIMS: One-liter polyethylene glycol plus ascorbic acid (PEG-ASC) improves patient tolerability, but some patients still show low tolerability to a relatively high content of ASC. This study aimed to improve the tolerability and safety of 1-L PEG with low-dose ASC in comparison with standard 1-L and 2-L PEG-ASC. METHODS: This was a randomized, controlled, double-blinded, multicenter, noninferiority trial involving 215 healthy adults who underwent colonoscopy from June 2020 to January 2021. Efficacy, tolerability, and safety were compared among 1-L PEG with low-dose ASC (50% lower ASC concentration in group A and 25% lower ASC concentration in groups B and C) and standard 1-L and 2-L PEG-ASC with all split regimens. RESULTS: One-liter PEG with low-dose ASC (groups A-C) had similar bowel cleansing efficacies according to the Harefield Cleansing Scale and Boston Bowel Preparation Scale, without negative clinical performance, compared with standard 1-L and 2-L PEG-ASC preparation (all P > .1). One-liter PEG with low-dose ASC had better tolerability compared with 2-L PEG-ASC and less residual fluid retention in the stomach compared with 1-L PEG-ASC, proportional to the amount of ASC. No significant differences were found in the incidences of overall adverse events, mild adverse events, or death or in the occurrence of gastroduodenal erosion or ulcer in upper endoscopy. CONCLUSIONS: One-liter PEG with low-dose ASC (25%-50% reduction in dose) for bowel cleansing showed similar efficacy and safety compared with standard 1-L or 2-L PEG-ASC, better tolerability compared with 2-L PEG-ASC, and less residual gastric fluid retention compared with standard 1-L PEG-ASC. (Clinical trial registration number: KCT0005490.).