Efficacy of early immunomodulator therapy on the outcomes of Crohn’s disease

BACKGROUND: The natural course of Crohn’s disease (CD), with continuing relapses and remissions, leads to irreversible intestinal damage. Early adoption of immunomodulator therapy has been proposed in order to address this; however, it is still uncertain whether early immunomodulator therapy could affect the natural course of the disease in real practice. We evaluated the efficacy of such therapy on the prognosis of newly diagnosed patients with CD. METHODS: This retrospective study included 168 patients who were newly diagnosed with CD and who started treatment at Severance Hospital, Seoul, Korea between January 2006 and March 2013. The short- and long-term outcomes were compared between patients treated with early immunomodulator therapy and those treated with conventional therapy. RESULTS: A Kaplan-Meier analysis identified that administration of immunomodulators within 6 months after diagnosis of CD was superior to conventional therapy in terms of clinical remission and corticosteroid-free remission rates (P=0.043 and P=0.035). However, P=0.827). Patients with a baseline elevated CRP level were more likely to relapse (P<0.005). Drug-related adverse events were more frequent in the early immunomodulator therapy group than in the conventional therapy group P=0.029). CONCLUSIONS: Early immunomodulator therapy was more effective than conventional therapy in inducing remission, but not in preventing relapse. Baseline high CRP level was a significant indicator of relapse

The current capacity and quality of colonoscopy in Korea

Background/Aims Little is known for the capacity and quality of colonoscopy, and adherence to colonoscopy surveillance guidelines in Korea. This study aimed to investigate the present and potential colonoscopic capacity, colonoscopic quality, and adherence to colonoscopy surveillance guidelines in Korea. Methods We surveyed representative endoscopists of 72 endoscopy units from June to August 2015, using a 36-item questionnaire regarding colonoscopic capacity, quality, and adherence to colonoscopy surveillance guidelines of each hospitals. Results Among the 62 respondents who answered the questionnaire, 51 respondents were analyzed after exclusion of 11 incomplete answers. Only 1 of 3 of endoscopy units can afford to perform additional colonoscopies in addition to current practice, and the potential maximum number of colonoscopies per week was only 42. The quality of colonoscopy was variable as reporting of quality indicators of colonoscopy were considerably variable (29.4%–94.1%) between endoscopy units. Furthermore, there are substantial gaps in the adherence to colonoscopy surveillance guidelines, as concordance rate for guideline recommendation was less than 50% in most scenarios. Conclusions The potential capacity and quality of colonoscopy in Korea was suboptimal. Considering suboptimal reporting of colonoscopic quality indicators and low adherence rate for colonoscopy surveillance guidelines, quality improvement of colonoscopy should be underlined in Korea

Caloric restriction of db/db mice reverts hepatic steatosis and body weight with divergent hepatic metabolism

Non-alcoholic fatty liver disease (NAFLD) is one of the most frequent causes of liver disease and its prevalence is a serious and growing clinical problem. Caloric restriction (CR) is commonly recommended for improvement of obesity-related diseases such as NAFLD. However, the effects of CR on hepatic metabolism remain unknown. We investigated the effects of CR on metabolic dysfunction in the liver of obese diabetic db/db mice. We found that CR of db/db mice reverted insulin resistance, hepatic steatosis, body weight and adiposity to those of db/m mice. H-NMR- and UPLC-QTOF-MS-based metabolite profiling data showed significant metabolic alterations related to lipogenesis, ketogenesis, and inflammation in db/db mice. Moreover, western blot analysis showed that lipogenesis pathway enzymes in the liver of db/db mice were reduced by CR. In addition, CR reversed ketogenesis pathway enzymes and the enhanced autophagy, mitochondrial biogenesis, collagen deposition and endoplasmic reticulum stress in db/db mice. In particular, hepatic inflammation-related proteins including lipocalin-2 in db/db mice were attenuated by CR. Hepatic metabolomic studies yielded multiple pathological mechanisms of NAFLD. Also, these findings showed that CR has a therapeutic effect by attenuating the deleterious effects of obesity and diabetes-induced multiple complications

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 &lt; 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

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&lt;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&lt;0.001), hospital visits (-15.4% vs. -7.9%, P&lt;0.001), CRC operations (-33.8% vs. -0.7%, P&lt;0.05), and colonoscopic polypectomies (-41.8% vs. -38.0%, P&lt;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

Application of Combined Analyses of Stable Isotopes and Stomach Contents for Understanding Ontogenetic Niche Shifts in Silver Croaker (Pennahia argentata)

Stable isotope analysis (SIA) and stomach content analysis (SCA) were conducted to understand ontogenetic niche shifts in silver croaker Pennahia argentata inhabiting the southern coastal waters of the Korean peninsula. Sampled P. argentata were classified into three groups based on their total length (TL; 60–80 mm TL, 80–120 mm TL, and 120–210 mm TL). Carbon isotope (δ13C) ratios were distinguishable, whereas nitrogen isotope (δ15N) ratios were not significantly different among size classes, and Standard Ellipse Area (SEA), estimated by δ13C and δ15N, was expanded with increasing TL from 0.2 ‰2 (60–80 mm TL) to 2.0 ‰2 (120–210 mm TL). SCA results showed variable contribution of dietary items to each size class. In particular, higher dietary contribution of Polychaeta to P. argentata of 80–120 mm TL than 120–210 mm TL mirrored variation in δ13C values of P. argentata in those size classes. Based on the combined analyses involving SIA and SCA, we concluded that P. argentata underwent ontogenetic niche shifts, particularly dietary shifts, with growth stages. Ontogenetic niche shifting is a representative survival strategy in fish, and, therefore, represents essential information for managing fisheries. The present study demonstrated applicability of combined SIA and SCA analyses, not only for dietary resource tracing, but also for ecological niche studies

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

Uncovering Novel Pre-Treatment Molecular Biomarkers for Anti-TNF Therapeutic Response in Patients with Crohn&rsquo;s Disease

Neutralising monoclonal antibodies for tumour necrosis factor (TNF) has been widely used to treat Crohn&rsquo;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

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