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.

Contribution of Personality Traits,Psychological Factors, and Health-Related Qualityof Life to Medication Adherence in Patientswith Rheumatoid Arthritis

Purpose@#This study sought to investigate the associations between personality traits and medication adherence and to identifypredictors of good medication adherence in rheumatoid arthritis (RA) patients. @*Materials and Methods@#A total of 207 RA patients using disease-modifying anti-rheumatic drugs were invited for an interviewand questionnaire study. Medication adherence was measured using the Compliance Questionnaire for Rheumatology (CQR).Personality traits were analyzed with the five-factor model of the Korean version of the Big Five Inventory 10. Psychological factorswere assessed with the Patient Health Questionnaire-9, Generalized Anxiety Disorder-7, and British Columbia Cognitive Inventory.Health-related Quality of Life (HRQoL) and functional disability were evaluated with the EuroQoL-5 dimension questionnaireand Health Assessment Questionnaire. Multivariate logistic regression analyses were performed to investigate predictorsof good medication adherence. @*Results@#Nonadherence to medication was reported by 66.7%. The number of daily prescribed pills was higher in the medicationadherence group than in the nonadherence group. Concomitant oral glucocorticoid doses were associated with medication adherence.A high level of conscientiousness and diabetes mellitus comorbidity were associated with better medication adherence[odds ratio (OR), 2.11; 95% confidence interval (CI), 1.01–4.38 and OR, 3.00; 95% CI, 1.12–8.07, respectively]. There were no significantdifferences in psychological factors or HRQoL between medication adherence and nonadherence groups. @*Conclusion@#The personality trait of conscientiousness was associated with medication adherence among the five personalitytraits evaluated. Patients with diabetes mellitus also showed higher medication adherence than those without this comorbidity.

A Rare Case of Overlap Syndrome with Diffuse Systemic Sclerosis, Rheumatoid Arthritis, and Cutaneous Sarcoidosis

Overlap syndrome is defined as a disease entity that satisfies the classification criteria of at least two connective tissue diseases occurring concurrently or separately in a single patient. Here, we report a rare case of a 59-year-old woman with diffuse systemic sclerosis with lung involvement-rheumatoid arthritis overlap syndrome accompanied by cutaneous sarcoidosis. Although there is no consensus for the optimal treatment of overlap syndrome to date, this case of co-existing rheumatoid arthritis and systemic sclerosis with interstitial lung disease successfully responded to abatacept.

Overview of Deep Learning in Gastrointestinal Endoscopy

Artificial intelligence is likely to perform several roles currently performed by humans, and the adoption of artificial intelligence-based medicine in gastroenterology practice is expected in the near future. Medical image-based diagnoses, such as pathology, radiology, and endoscopy, are expected to be the first in the medical field to be affected by artificial intelligence. A convolutional neural network, a kind of deep-learning method with multilayer perceptrons designed to use minimal preprocessing, was recently reported as being highly beneficial in the field of endoscopy, including esophagogastroduodenoscopy, colonoscopy, and capsule endoscopy. A convolutional neural network-based diagnostic program was challenged to recognize anatomical locations in esophagogastroduodenoscopy images, Helicobacter pylori infection, and gastric cancer for esophagogastroduodenoscopy; to detect and classify colorectal polyps; to recognize celiac disease and hookworm; and to perform small intestine motility characterization of capsule endoscopy images. Artificial intelligence is expected to help endoscopists provide a more accurate diagnosis by automatically detecting and classifying lesions; therefore, it is essential that endoscopists focus on this novel technology. In this review, we describe the effects of artificial intelligence on gastroenterology with a special focus on automatic diagnosis, based on endoscopic findings.

Fate of Abstracts Presented at the Korean College of Rheumatology Annual Scientific Meetings

OBJECTIVE: To evaluate the fate of abstracts presented at scientific meetings of the Korean College of Rheumatology (KCR). METHODS: This study examined the abstracts presented at annual meetings of the KCR from 2005 to 2014. Only original studies were selected, excluding case reports. A manual search was conducted using PubMed, KoreaMed, Cochrane Library, and Embase to track the published articles. The abstracts were considered to have been published if the authors, title, study design, and results were the same for a published article. In addition, they were considered published if the author and the study design matched, even if the results of the abstract and the results of the published articles were not identical. RESULTS: A total of 928 abstracts from 2005 to 2014 were analyzed. Of the 928 abstracts, 468 (50.43%) abstracts were published in a peer-reviewed journal and the mean time to publication was 19 months. Of the 468 abstracts, 414 were published in a science citation index extended (SCI[E]) journal, and 54 were published in non-SCI(E) journals. The proportion of SCI(E) articles increased annually. The average impact factor for the SCI(E) journals was 2.93. In subgroup analysis, the abstracts that were awarded the best oral or best poster presentation were more likely to be published as full-length articles with a higher impact factor than the abstracts not awarded. CONCLUSION: Half of the abstracts presented in the KCR annual meetings were published in a peer-reviewed journal. Approximately 90% of the articles were published in a SCI(E) journal.

Quality Indicators and Outcome Measures of Endoscopy in the National Cancer Screening Program

PURPOSE: Quality indicators of the National Endoscopy Quality Improvement Program (NEQIP) and outcome measures of endoscopy in the National Cancer Screening Program (NCSP) in Korea are not clear. We evaluated the quality indicators of the revised NEQIP and outcome measures of endoscopy at different types of healthcare facilities participating in the NCSP. MATERIALS AND METHODS: This study was conducted between March and August 2018 in primary, secondary, and tertiary healthcare facilities that perform endoscopy as a part of the NCSP. Representative endoscopists completed a questionnaire for quality indicators of the NEQIP and provided data on outcome measures for endoscopy. RESULTS: Quality indicators of the NEQIP were mostly acceptable. However, the quality indicators for annual volume of esophagogastroduodenoscopy (EGD) and colonoscopy, training for endoscopy quality improvement by endoscopy nursing staff, colonoscopy reports, documentation of pathologic lesions, quality of endoscopy reprocessing areas, and completion of endoscopy reprocessing education programs were suboptimal. For outcome measures of EGD, the number of photo-documentations and total procedure time were higher at tertiary healthcare facilities than at other facilities (p<0.001 and p=0.023, respectively). For the outcome measures of colonoscopy, colonoscopy completion rate and waiting times for colonoscopy were significantly higher at tertiary healthcare facilities than at other facilities (both p<0.001). CONCLUSION: Outcome measures of endoscopy should be included as quality indicators of NCSP. However, universal outcome measures for all types of healthcare facilities should be established because performance levels of some outcome measures differ among individual healthcare facility types.

Revision of Quality Indicators for the Endoscopy Quality Improvement Program of the National Cancer Screening Program in Korea

Gastroscopy and colonoscopy are widely used for the early diagnosis of stomach and colorectal cancer. The present revision integrates recent data regarding previous quality indicators and novel indicators suggested for gastroscopy and colonoscopy procedures for the National Cancer Screening Program in Korea. The new indicators, developed by the Quality Improvement Committee of the Korean Society for Gastrointestinal Endoscopy, vary in the level of supporting evidence, and most are based solely on expert opinion. Updated indicators validated by clinical research were prioritized, but were chosen by expert consensus when such studies were absent. The resultant quality indicators were graded according to the levels of consensus and recommendations. The updated indicators will provide a relevant guideline for high-quality endoscopy. The future direction of quality indicator development should include relevant outcome measures and an evidence-based approach to support proposed performance targets.

Revision of Quality Indicators for the Endoscopy Quality Improvement Program of the National Cancer Screening Program in Korea / 대한소화기학회지

Gastroscopy and colonoscopy are widely used for the early diagnosis of stomach and colorectal cancer. The present revision integrates recent data regarding previous quality indicators and novel indicators suggested for gastroscopy and colonoscopy procedures for the National Cancer Screening Program in Korea. The new indicators, developed by the Quality Improvement Committee of the Korean Society for Gastrointestinal Endoscopy, vary in the level of supporting evidence, and most are based solely on expert opinion. Updated indicators validated by clinical research were prioritized, but were chosen by expert consensus when such studies were absent. The resultant quality indicators were graded according to the levels of consensus and recommendations. The updated indicators will provide a relevant guideline for high-quality endoscopy. The future direction of quality indicator development should include relevant outcome measures and an evidence-based approach to support proposed performance targets.

Is Urinary Tumor Necrosis Factor-like Weak Inducer of Apoptosis a Biomarker of Lupus Nephritis?

No abstract available.

Metabolomics Approach to Explore the Effects of Rebamipide on Inflammatory Arthritis Using Ultra Performance Liquid Chromatography/Quadrupole Time-of-Flight Mass Spectrometry

OBJECTIVE: Rebampide is a gastroprotective agent used to treat gastritis. It possesses anti-inflammatory and anti-arthritis effects, but the mechanisms of these effects are not well understood. The objective of this study was to explore mechanisms underlying the therapeutic effects of rebamipide in inflammatory arthritis. METHODS: Collagen-induced arthritis (CIA) was induced in DBA/1J mice. DBA/1J mice were immunized with chicken type II collagen, then treated intraperitoneally with rebamipide (10 mg/kg or 30 mg/kg) or vehicle (10% carboxymethylcellulose solution) alone. Seven weeks later, plasma samples were collected. Plasma metabolic profiles were analyzed using ultra performance liquid chromatography/quadrupole time-of-flight mass spectrometry-based metabolomics study and metabolite biomarkers were identified through multivariate data analysis. RESULTS: Low dose rebamipide treatment reduced the clinical arthritis score compared with vehicle treatment, whereas high dose rebamipide in CIA aggravated arthritis severity. Based on multivariate analysis, 17 metabolites were identified. The plasma levels of metabolites associated with fatty acids and phospholipid metabolism were significantly lower with rebamipide treatment than with vehicle. The levels of 15-deoxy-Δ¹²,¹⁴ prostaglandin J2 and thromboxane B3 decreased only in high dose-treated groups. Certain peptide molecules, including enterostatin (VPDPR) enterostatin and bradykinin dramatically increased in rebamipide-treated groups at both doses. Additionally, corticosterone increased in the low dose-treated group and decreased in the high dose-treated group. CONCLUSION: Metabolomics analysis revealed the anti-inflammatory effects of rebamipide and suggested the potential of the drug repositioning in metabolism- and lipid-associated diseases.

Endogenous Cushing's Syndrome in a Patient with Systemic Lupus Erythematosus

Systemic lupus erythematosus is an autoimmune disease for which glucocorticoids are the mainstay of treatment. Cushing's syndrome is caused by glucocorticoid excess, which can be either exogenous or endogenous. Although iatrogenic Cushing's syndrome is the most common form, especially in patients undergoing glucocorticoid treatment, endogenous glucocorticoid excess should be considered because it has a different treatment strategy. We describe a 51-year old woman with a longstanding history of SLE. She was treated with steroid and cytoxan pulse therapy and plasmapheresis. Her lupus activity had been stable for 7 years with low-dose glucocorticoid treatment. She showed excessive weight gain, easy bruising, moon facies, truncal obesity, acne, and menstrual disorder. Given her history of long-term steroid therapy, iatrogenic Cushing's syndrome was considered the most likely diagnosis; however, worsening features of Cushing's syndrome with a minimal dose of glucocorticoid led us to diagnose endogenous Cushing's syndrome due to a left adrenal adenoma. The patient underwent laparoscopic left adrenalectomy. Her SLE was controlled with transient low-dose glucocorticoid treatment, and her lupus activity remained stable without glucocorticoid treatment. This is the first reported case of concomitant endogenous Cushing's syndrome in a patient with preexisting SLE in Korea. This case shows the importance of differential diagnosis including exogenous Cushing's syndrome and endogenous Cushing's syndrome in autoimmune disease patients with glucocorticoid therapy.

STX0119 Ameliorates Arthritis in SKG Mice via Inhibiting T Helper 17

Rheumatoid arthritis (RA) is an autoimmune disease with chronic and excessive inflammation. Upregulation of interleukin (IL)-17 is involved in the pathogenesis of RA. STX0119 is a specific inhibitor of signal transducer and activator of transcription 3 (STAT3) as a potential target for the treatment of RA. STAT3 is a member of DNA-binding molecules that regulates the expression of proinflammatory cytokines involved in the pathogenesis of RA. The objective of this study was to determine whether STX0119 could inhibit STAT3 and IL-17. We demonstrated that STX0119 decreased T helper (Th) 17 differentiation and IL-17 expression in vitro. STX0119 also improved the severity of zymosan induced arthritis and reduced joint inflammation. STX0119 reduced the proliferation of Th17 and phosphorylated STAT3 expression while increasing Treg differentiation and phosphorylated STAT5 expression. Moreover, STX0119 decreased the expression of IL-6 and -17 but not IL-10. These findings suggest that STX0119 can be used to treat autoimmune RA through inhibiting the activation of STAT3.

Gastrointestinal Risk Factors and Non-steroidal Anti-inflammatory Drugs Use in Rheumatoid Arthritis and Osteoarthritis Patients in Korea

OBJECTIVE: The aim of this study was to examine and compare the gastrointestinal (GI) risk factors and treatment patterns of rheumatoid arthritis (RA) and osteoarthritis (OA) patients in Korea. METHODS: This was a cross-sectional, observational study on RA and OA patients taking non-steroidal anti-inflammatory drugs (NSAIDs) for at least 1 month. A total of 1,896 patients (981 RA patients, 915 OA patients) were recruited from 20 university hospitals. Data were collected through medical records and patient surveys. GI risk factors included age, prolonged (over 3 months) or high-dose use of NSAIDs, alcohol drinking, smoking, use of aspirin, anticoagulants or glucocorticoids, comorbidities, and history of Helicobacter pylori infection or other GI complications. Treatment patterns were classified according to groups using, selective cyclooxygenase (COX)-2 inhibitors+/-gastro-protective agents, non-selective COX-2 inhibitors+proton pump inhibitor, or non-selective COX-2 inhibitors+/-other gastro-protective agents. RESULTS: GI risk factors were highly present in both RA and OA patients. The proportion of prolonged use of NSAIDs, smoking, and glucocorticoid use were higher in RA patients (p<0.001). The proportion of comorbidities and use of aspirin were higher in OA patients (p<0.001). The remaining GI risk factors were present in similar proportions in both groups. Use of selective COX-2 inhibitors or gastro-protective agents was higher in RA patients. CONCLUSION: Prolonged use of NSAIDs and concomitant glucocorticoid use were higher in RA patients, while comorbidities and concomitant aspirin use were predominant in OA patients. These results will provide insights for use in development of future guidelines for proper selection of NSAIDs and effective prevention of GI complications in arthritis patients.

Mikulicz's Disease with Progressively Transformed Germinal Centers-type Immunoglobulin G4-related Lymphadenopathy Mimicking Sjogren's Syndrome

Immunoglobulin G4-related disease (IgG4-RD) is a systemic disease, and lymphadenopathy is frequently observed in these patients. Among the 5 subtypes of IgG4-related lymphadenopathy, progressively transformed germinal centers (PTGC)-type IgG4-related lymphadenopathy possesses a unique characteristic that differentiates it from the other 4 subtypes. Here, we report on a rare case of PTGC-type IgG4-related lymphadenopathy accompanying Mikulicz's disease. A 39-year-old female complained of a left cervical mass and bilateral upper eyelid hypertrophy. The serum level of IgG4 was elevated, and computed tomography showed enlargement of the bilateral lacrimal and submandibular glands and left cervical lymph node. Excisional biopsy of a submandibular gland and cervical lymph node was performed, and the histopathologic findings revealed Mikulicz's disease accompanied by PTGC-type IgG4-related lymphadenopathy. After treatment of the patient with oral prednisolone and azathioprine, the patient's appearance improved. To the best of our knowledge, no case of PTGC-type IgG4-related lymphadenopathy has been previously reported in Korea.

Immunoglobulin G4-Related Disease

Immunoglobulin G4-related disease (IgG4-RD) is an emerging immune-mediated fibro-inflammatory disorder which can involve any organ. The main characteristics of IgG4-RD are increased serum IgG4 concentration, abundant IgG4+ plasma cells in affected tissues, and painless swollen organs often without general symptoms. Typical pathology features of IgG4-RD are lymphoplasmacytic infiltration, dense storiform fibrosis, and obliterative pheblitis. The pathogenesis of IgG4-RD remains elusive, but involvement of excess production of type 2 T helper cells, regulatory T-cell cytokines, and B-cell activating factor in the development of IgG4-RD has been suggested. Diagnosis of IgG4-RD can be made on the basis of serological, imaging, particularly histopathological findings. Glucocorticoid is the first-line therapy for patients with multiple organ dysfunction and clinical symptoms. Drugs such as azathioprine, mycophenolate mofetil, methotrexate, and cyclophosphamide can be used as steroid-sparing agents. Rituximab is reported to be an effective therapy for treatment of IgG4-RD, even without concomitant glucocorticoid therapy. This review summarizes current concepts on pathophysiology, clinical manifestations, and treatment of IgG4-RD.

Ursodeoxycholic Acid Ameliorates Pain Severity and Cartilage Degeneration in Monosodium Iodoacetate-Induced Osteoarthritis in Rats

Osteoarthritis (OA) is a degenerative joint disease characterized by a progressive loss of cartilage. And, increased oxidative stress plays a relevant role in the pathogenesis of OA. Ursodeoxycholic acid (UDCA) is a used drug for liver diseases known for its free radical-scavenging property. The objectives of this study were to investigate the in vivo effects of UDCA on pain severity and cartilage degeneration using an experimental OA model and to explore its mode of actions. OA was induced in rats by intra-articular injection of monosodium iodoacetate (MIA) to the knee. Oral administration UDCA was initiated on the day of MIA injection. Limb nociception was assessed by measuring the paw withdrawal latency and threshold. Samples were analyzed macroscopically and histologically. Immunohistochemistry was used to investigate the expression of interleukin-1beta (IL-1beta), IL-6, nitrotyrosine and inducible nitric oxide synthase (iNOS) in knee joints. UDCA showed an antinociceptive property and attenuated cartilage degeneration. OA rats given oral UDCA significantly exhibited a decreased number of osteoclasts in subchondral bone legion compared with the vehicle-treated OA group. UDCA reduced the expression of IL-1beta, IL-6, nitrotyrosine and iNOS in articular cartilage. UDCA treatment significantly attenuated the mRNA expression of matrix metalloproteinase-3 (MMP-3), -13, and ADAMTS5 in IL-1beta-stimulated human OA chondrocytes. These results show the inhibitory effects of UDCA on pain production and cartilage degeneration in experimentally induced OA. The chondroprotective properties of UDCA were achieved by suppressing oxidative damage and inhibiting catabolic factors that are implicated in the pathogenesis of cartilage damage in OA.

Periarticular Osteoporosis Is a Prominent Feature in Early Rheumatoid Arthritis: Estimation Using Shaft to Periarticular Bone Mineral Density Ratio

We aimed to quantify periarticular osteoporosis and investigate its significance in 45 patients with rheumatoid arthritis (RA) and 106 controls. Dual-energy X-ray absorptiometry (DXA) was used to determine the ratio of shaft to periarticular bone mineral density (BMD) as an index of periarticular demineralization. Periarticular osteoporosis was measured by conventional radiography. The BMDs of shaft and periarticular regions in eight designated areas on proximal phalanges were quantified. Clinical variables were examined to identify risk factors for periarticular osteoporosis. The assessment of periarticular osteoporosis on X-ray images reached a moderate degree of interobserver agreement among four physicians (k = 0.47). For BMD quantification, we designed three types of mathematical formulae: the ratio of shaft to periarticular BMD, the mean of the ratios, and the ratio of the sums. These ratios were significantly higher in the patients with early RA (disease duration < or = 3 yr) than in controls (P < 0.01). The findings were not as distinctive in patients with established RA. Body mass index, cumulative dose of corticosteroid, and C-terminal telopeptide were correlated with BMD ratios. Conclusively, DXA-assisted localized quantification and BMD ratio calculations are feasible for assessing periarticular demineralization. Periarticular osteoporosis is a relatively distinctive feature of early RA.

In vivo action of IL-27: reciprocal regulation of Th17 and Treg cells in collagen-induced arthritis

Interleukin (IL)-27 is a novel cytokine of the IL-6/IL-12 family that has been reported to be involved in the pathogenesis of autoimmune diseases and has a pivotal role as both a pro- and anti-inflammatory cytokine. We investigated the in vivo effects of IL-27 on arthritis severity in a murine collagen-induced arthritis (CIA) model and its mechanism of action regarding control of regulatory T (Tregs) and IL-17-producing T helper 17 (Th17) cells. IL-27-Fc-treated CIA mice showed a lower severity of arthritis. IL-17 expression in the spleens was significantly decreased in IL-27-Fc-treated CIA mice compared with that in the CIA model. The Th17 population was decreased in the spleens of IL-27-Fc-treated CIA mice, whereas the CD4+CD25+Foxp3+ Treg population increased. In vitro studies revealed that IL-27 inhibited IL-17 production in murine CD4+ T cells, and the effect was associated with retinoic acid-related orphan receptor gammaT and signal transducer and activator of transcription 3 inhibition. In contrast, fluorescein isothiocyanate-labeled forkhead box P3 (Foxp3) and IL-10 were profoundly augmented by IL-27 treatment. Regarding the suppressive capacity of Treg cells, the proportions of CTLA-4+ (cytotoxic T-lymphocyte antigen 4), PD-1+ (programmed cell death protein 1) and GITR+ (glucocorticoid-induced tumor necrosis factor receptor) Tregs increased in the spleens of IL-27-Fc-treated CIA mice. Furthermore, in vitro differentiated Treg cells with IL-27 exerted a more suppressive capacity on T-cell proliferation. We found that IL-27 acts as a reciprocal regulator of the Th17 and Treg populations in CD4+ cells isolated from healthy human peripheral blood mononuclear cells (PBMCs), as well as from humans with rheumatoid arthritis (RA) PBMCs. Our study suggests that IL-27 has the potential to ameliorate overwhelming inflammation in patients with RA through a reciprocal regulation of Th17 and Treg cells.

Gastroprotective Effects of Grape Seed Proanthocyanidin Extracts against Nonsteroid Anti-Inflammatory Drug-Induced Gastric Injury in Rats

BACKGROUND/AIMS: To investigate the gastroprotective effects of grape seed proanthocyanidin extracts (GSPEs) against nonsteroid anti-inflammatory drug (NSAID)-induced gastric mucosal injury in rats. METHODS: Sprague-Dawley rats were randomly allocated to the normal control, indomethacin, low-dose GSPE, high-dose GSPE and misoprostol groups. All groups except the normal control group received pretreatment drugs for 6 consecutive days. On the 5th and 6th day, indomethacin was administered orally to all groups except for normal control group. The microscopic features of injury were analyzed. The levels of gastric mucosal glutathione, gastric mucosal prostaglandin E2 (PGE2), and proinflammatory cytokines were investigated. RESULTS: The total areas of ulceration in the GSPE and misoprostol groups were significantly decreased compared with the indomethacin group (p<0.05). However, a difference in ulcer formation among the drug treatment groups was not observed. Meanwhile, the glutathione levels in the high-dose GSPE group were higher than those of both the indomethacin and misoprostol groups (p<0.05) and were similar to those of the normal control group. Additionally, there was no difference among the groups in the levels of gastric mucosal PGE2 and proinflammatory cytokines. CONCLUSIONS: High-dose GSPE has a strong protective effect against NSAID-induced gastric mucosal injury, which may be associated with the antioxidant effects of GSPE.

The Therapeutic Efficacy of Apigenin in a Murine Model of Scleroderma

No abstract available.