Efficacy comparison of 7- and 14-day P-CAB based bismuth-containing quadruple regimen with PPI based bismuth-containing quadruple regimen for Helicobacter pylori infection: rationale and design of an open-label, multicenter, randomized controlled trial.

BACKGROUND: Owing to its strong acid inhibition, potassium-competitive acid blocker (P-CAB) based regimens for Helicobacter pylori (H. pylori) eradication are expected to offer clinical advantages over proton pump inhibitor (PPI) based regimens. This study aims to compare the efficacy and adverse effects of a 7-day and a 14-day P-CAB-based bismuth-containing quadruple regimen (PC-BMT) with those of a 14-day PPI-based bismuth-containing quadruple regimen (P-BMT) in patients with high clarithromycin resistance. METHODS: This randomized multicenter controlled clinical trial will be performed at five teaching hospitals in Korea. Patients with H. pylori infection who are naive to treatment will be randomized into one of three regimens: 7-day or 14-day PC-BMT (tegoprazan 50 mg BID, bismuth subcitrate 300 mg QID, metronidazole 500 mg TID, and tetracycline 500 mg QID) or 14-day P-BMT. The eradication rate, treatment-related adverse events, and drug compliance will be evaluated and compared among the three groups. Antibiotic resistance testing by culture will be conducted during the trial, and these data will be used to interpret the results. A total of 366 patients will be randomized to receive 7-day PC-BMT (n = 122), 14-day PC-BMT (n = 122), or 14-day P-BMT (n = 122). The H. pylori eradication rates in the PC-BMT and P-BMT groups will be compared using intention-to-treat and per-protocol analyses. DISCUSSION: This study will demonstrate that the 7-day or 14-day PC-BMT is well tolerated and achieve similar eradication rates to those of 14-day P-BMT. Additionally, the 7-day PC-BMT will show fewer treatment-related adverse effects and higher drug compliance, owing to its reduced treatment duration. TRIAL REGISTRATION: Korean Clinical Research Information Service registry, KCT0007444. Registered on 28 June 2022, https://cris.nih.go.kr/cris/index/index.do .

The Diagnostic Performance of Linked Color Imaging Compared to White Light Imaging in Endoscopic Diagnosis of Helicobacter pylori Infection: A Systematic Review and Meta-Analysis.

Background/Aims: Recognizing Helicobacter pylori infection during endoscopy is important because it can lead to the performance of confirmatory testing. Linked color imaging (LCI) is an image enhancement technique that can improve the detection of gastrointestinal lesions. The purpose of this study was to compare LCI to conventional white light imaging (WLI) in the endoscopic diagnosis of H. pylori infection. Methods: We conducted a comprehensive literature search using PubMed, Embase, and the Cochrane Library. All studies evaluating the diagnostic performance of LCI or WLI in the endoscopic diagnosis of H. pylori were eligible. Studies on magnifying endoscopy, chromoendoscopy, and artificial intelligence were excluded. Results: Thirty-four studies were included in this meta-analysis, of which 32 reported the performance of WLI and eight reported the performance of LCI in diagnosing H. pylori infection. The pooled sensitivity and specificity of WLI in the diagnosis of H. pylori infection were 0.528 (95% confidence interval [CI], 0.517 to 0.540) and 0.821 (95% CI, 0.811 to 0.830), respectively. The pooled sensitivity and specificity of LCI in the diagnosis of H. pylori were 0.816 (95% CI, 0.790 to 0.841) and 0.868 (95% CI, 0.850 to 0.884), respectively. The pooled diagnostic odds ratios of WLI and LCI were 15.447 (95% CI, 8.225 to 29.013) and 31.838 (95% CI, 15.576 to 65.078), respectively. The areas under the summary receiver operating characteristic curves of WLI and LCI were 0.870 and 0.911, respectively. Conclusions: LCI showed higher sensitivity in the endoscopic diagnosis of H. pylori infection than standard WLI.

Role of linked color imaging for upper gastrointestinal disease: present and future.

Techniques for upper gastrointestinal endoscopy are advancing to facilitate lesion detection and improve prognosis. However, most early tumors in the upper gastrointestinal tract exhibit subtle color changes or morphological features that are difficult to detect using white light imaging. Linked color imaging (LCI) has been developed to overcome these shortcomings; it expands or reduces color information to clarify color differences, thereby facilitating the detection and observation of lesions. This article summarizes the characteristics of LCI and advances in LCI-related research in the upper gastrointestinal tract field.

Effects of prior antibiotic use on clarithromycin resistance in Helicobacter pylori.

BACKGROUND: Macrolide antibiotics are widely used to treat various infections such as pneumonia and sinusitis, and previous exposure to macrolides is presumed to be a risk factor for standard triple therapy failure in Helicobacter pylori (H. pylori) eradication. We aimed to determine whether previous use of macrolide antibiotics could affect clarithromycin resistance of H. pylori. MATERIALS AND METHODS: From the Korea National Health Insurance Service (NHIS2021-1-775) database, a total of 46,160 patients who were tested for clarithromycin resistance of H. pylori from 2016 to 2019 in Korea were identified. Their history of antibiotics in the past 10 years and history of respiratory comorbidity in the past 1 year were investigated. RESULTS: Clarithromycin resistance rate of H. pylori in Korea was 16.2%. A multivariate analysis revealed that female sex (OR: 1.472, p < .001), age > 50 years (OR: 1.340, p < .001), previous use of macrolide antibiotics (clarithromycin, OR: 2.902, p < .001; azithromycin, OR: 1.930, p < .001; erythromycin, OR: 2.060, p = .001; roxithromycin, OR: 2.022, p < .001), and history of respiratory comorbidity (sinusitis, OR: 1.271, p < .001; laryngopharyngitis, OR: 1.135, p = .032; bronchitis, OR: 1.245, p = .001; pneumonia, OR: 1.335, p = .026) were independent risk factors of clarithromycin resistance in H. pylori. CONCLUSIONS: The use of macrolide antibiotics and a recent diagnosis of respiratory disease might increase clarithromycin resistance of H. pylori.

Outcomes of the Conventional versus Pocket-Creation Method for Endoscopic Submucosal Dissection of Gastric Body Tumors Using a Dual Knife: A Retrospective Study.

Background/Aims: Various endoscopic submucosal dissection (ESD) methods for gastric tumors have been tried. However, no studies have yet compared results according to the ESD method for gastric body tumors using a dual knife. The objective of this study was to compare outcomes of two ESD methods for gastric body tumors: the pocket-creation method and conventional method. Methods: Patients who underwent ESD for a gastric body tumor were retrospectively reviewed. Patients were divided into two groups according to the ESD method: the conventional method (group I) and pocket-creation method (group II). Characteristics of patients and tumors, hospitalization period, incidence of complications, resection margin status, incidence of surgical operation, procedure time, and laboratory findings were investigated. Results: Of the total of 100 patients, 52 belonged to group I and 48 to group II. All tumors were successfully resected en bloc. Resection margin involvement was found in six (11.5%) of group I and six (12.5%) of group II. Complications were observed in seven (13.5%; major complication five, minor two) of group I and eight (16.7%; major two, minor six) of group II. There were no significant differences in ESD outcomes such as hospitalization period, incidence of complications, resection margin status, incidence of surgical operation, procedure time, or inflammatory response after ESD between the two groups. Conclusions: Both methods are suitable for treating gastric body tumors with adequate treatment success rates and comparable complication rates.

Cancer risk in patients with Peutz-Jeghers syndrome in Korea: a retrospective multi-center study.

BACKGROUND/AIMS: There have been little research on the cancer risks of patients with Peutz-Jeghers syndrome (PJS) in Korea. We aimed to investigate the clinical features of PJS patients and their cancer incidence rate. METHODS: Patients with PJS from nine medical centers were enrolled. In those patients diagnosed with cancer, data obtained included the date of cancer diagnosis, the tumor location, and the cancer stage. The cumulative risks of gastrointestinal cancers and extra-gastrointestinal cancers were calculated using the Kaplan-Meier method. RESULTS: A total of 96 PJS patients were included. The median age at diagnosis of PJS was 23.4 years. Cancer developed in 21 of the 96 patients (21.9%). The age of PJS diagnosis was widely distributed (0.9 to 72.4 years). The most common cancers were gastrointestinal cancer (n = 12) followed by breast cancer (n = 6). The cumulative lifetime cancer risk was calculated to be 62.1% at age 60. The cumulative lifetime gastrointestinal cancer risk was 47.1% at age 70. The cumulative lifetime extra- gastrointestinal cancer risk was 40.3% at age 60. CONCLUSION: PJS onset may occur at any age and the risks of gastrointestinal and extra-gastrointestinal cancer are high. Thorough surveillance of PJS patients for malignancies is vital.

Randomised clinical trial: comparison of tegoprazan and lansoprazole as maintenance therapy for healed mild erosive oesophagitis.

BACKGROUND: Tegoprazan is a novel potassium-competitive acid blocker used to treat acid-related disorders. AIM: To compare tegoprazan 25 mg with lansoprazole 15 mg as maintenance therapy in healed erosive oesophagitis (EE) METHODS: In this phase 3, double-blind, multi-centre study, patients with endoscopically confirmed healed EE were randomised 1:1 to receive tegoprazan 25 mg or lansoprazole 15 mg once daily for up to 24 weeks. The primary efficacy endpoint was the endoscopic remission rate after 24 weeks. The secondary efficacy endpoint was the endoscopic remission rate after 12 weeks. Safety endpoints included adverse events, clinical laboratory results and serum gastrin and pepsinogen I/II levels. RESULTS: We randomised patients to tegoprazan 25 mg (n = 174) or lansoprazole 15 mg (n = 177). Most had mild EE (Los Angeles (LA) grade A: 57.3%, LA grade B: 37.3%). The endoscopic remission rate after 24 weeks was 90.6% with tegoprazan and 89.5% with lansoprazole. Tegoprazan was not inferior to lansoprazole for maintaining endoscopic remission at 24 weeks and 12 weeks. In subgroup analysis, tegoprazan 25 mg showed no significant difference in maintenance rate according to LA grade (p = 0.47). The maintenance effect of tegoprazan was consistent in CYP2C19 extensive metabolisers (p = 0.76). Increases in serum gastrin were not higher in tegoprazan-treated than lansoprazole-treated patients. CONCLUSIONS: Tegoprazan 25 mg was non-inferior to lansoprazole 15 mg in maintenance of healing of mild EE. In this study, tegoprazan had a similar safety profile to lansoprazole.

Underwater Versus Conventional Endoscopic Mucosal Resection for Superficial Non-ampullary Duodenal Epithelial Tumors: A Systematic Review and Meta-Analysis.

BACKGROUND/AIMS: Duodenal underwater endoscopic mucosal resection (UEMR) has been suggested as a feasible treatment option for superficial non-ampullary duodenal epithelial tumors (SNADETs). However, its efficacy and safety have not been fully established yet. Thus, the objective of this systematic review and meta-analysis was to determine the efficacy and safety of UEMR as compared with conventional endoscopic mucosal resection (CEMR) in the treatment of SNADETs. METHODS: We conducted a comprehensive literature search in PubMed, EMBASE, the Cochrane Library. Studies comparing CEMR and UEMR for the resection of SNADET were included. Outcomes included en-bloc and complete resection rates, adverse events, and procedure time. RESULTS: A total of six studies with 2454 lesions were included in the quantitative synthesis. En-bloc and complete resection rates were not significantly different between UEMR and CEMR (OR for en-bloc resection: 0.997 [95% CI 0.439-2.266]; OR for complete resection: 0.960 [95% CI 0.628-1.468]). There was no significant risk difference for perforation (risk difference: - 0.002; 95% CI - 0.009 to 0.005) or delayed bleeding (risk difference: - 0.001; 95% CI - 0.014 to 0.011). Procedure time was significantly shorter in the UEMR (standardized mean difference: - 1.294; 95% CI - 2.461 to - 0.127). The risk of recurrence was not significantly different between UEMR and CEMR (risk difference: 0.001; 95% CI - 0.041 to 0.044). CONCLUSION: Although our results did not show any superiority of UEMR over CEMR in the treatment of SNADETs, UEMR showed equivalent efficacy and safety as compared with CEMR and was associated with a shorter procedure time.

The association between specific IgE antibodies to component allergens and allergic symptoms on dog and cat exposure among Korean pet exhibition participants.

Background: Component resolved diagnostics (CRD) in dog and cat allergy is not sufficiently investigated, especially regarding new components such as Can f 4, Can f 6, and Fel d 7. The purpose of this study is to evaluate the potential role of CRD with new components in predicting allergic symptoms on dog and cat exposure. Methods: Among 552 Korean adults who participated in a pet exhibition and completed questionnaires regarding exposure to dog or cat and allergic symptoms, 522 were venipunctured for measurement of IgE and IgG4 antibody concentration against dog and cat dander extract and underwent skin prick test (SPT). In 238 individuals who were sensitized for both dog and cat dander extract, the dog IgE components (Can f 1-6) and the cat components (Fel d 1/2/4/7) were analyzed. Results: An increasing number of sensitizing components was associated with the likelihood of having any allergic symptoms (P < 0.001 for dog and P < 0.01 for cat), and those of asthma (P < 0.01 for dog and P < 0.05 for cat) and rhinoconjunctivitis (P < 0.001 for dog and P < 0.05 for cat). Pairwise correlation of IgE levels was r = 0.56 (P < 0.001) for Can f 6 and Fel d 4, r = 0.74 (P < 0.001) for Can f 1 and Fel d 7 and r = 0.84 (P < 0.001) for Can f 3 and Fel d 2. Conclusions: Polysensitization to dog and cat allergen components is associated with high likelihood of having allergic symptoms during exposure to dogs and cats. Cross-reactivity between dog and cat allergen components is also identified. CRD has a potential in fine-tuning prediction for allergic symptoms on dog and cat exposure.

Indication, Location of the Lesion, Diagnostic Yield, and Therapeutic Yield of Double-Balloon Enteroscopy: Seventeen Years of Experience.

Double-balloon enteroscopy (DBE) has become one of the standard methods in the diagnosis and treatment of small bowel (SB) disease. However, previous studies for DBE have limitations due to heterogeneity of indications and operators. The aim was to investigate the indication, location of the lesion, diagnostic yield, and therapeutic yield of DBE based on long-term data from a single operator. A retrospective study was performed by reviewing medical records of subjects who had received DBE at our unit in the past 17 years. Overall diagnostic yield was 78.7% (210/267). The diagnostic yield for obscure gastrointestinal bleeding (OGIB) was 68.3% (84/123). The diagnostic yield for OGIB was significantly lower (p < 0.001) than that for other indications. Therapeutic yield was 24.7% (66/267). Complications occurred in 7 (2.6%). Crohn's disease, intestinal tuberculosis, nonsteroidal anti-inflammatory drug enteropathy, and diverticular lesions were mainly found in the ileum. Vascular lesions, non-specific inflammation, and neoplastic lesions were found more frequently in the jejunum. DBE is an excellent and safe endoscopic method for the diagnosis and treatment of SB lesions. DBE has a lower diagnostic rate for OGIB than for other indications. The location where a lesion is commonly found depends on the type of the lesion.

Effectiveness and Safety of Codeine and Levodropropizine in Patients With Chronic Cough.

BACKGROUND: Recent progress in chronic cough management includes controlling cough triggers and hypersensitivity using antitussives. Therefore, we investigated the effects and safety outcomes of antitussives, codeine and levodropropizine, in patients with chronic cough. METHODS: We conducted an open-label, randomized comparative trial with newly referred patients with chronic cough. Patients were orally administered codeine (60 mg/day) and levodropropizine (180 mg/day) for 2 weeks. Cough severity, including the visual analog scale (VAS), Cough Symptom Score (CSS), Leicester Cough Questionnaire (LCQ), and safety for each treatment were assessed. The primary outcome was VAS score changes before and after 2 weeks of treatment. RESULTS: Among the 88 participants, 45 and 43 in the codeine and levodropropizine groups, respectively, were included in the analysis. Changes in the VAS score were higher in the codeine group than in the levodropropizine group (35.11 ± 20.74 vs. 19.77 ± 24.83, P = 0.002). Patients administered codeine also had improved CSS (2.96 ± 2.35 vs. 1.26 ± 1.89, P < 0.001) and LCQ (3.28 ± 3.36 vs. 1.61 ± 3.53, P = 0.025) than those administered levodropropizine. Treatment-related adverse events, including drowsiness, constipation, and headaches, were more frequent in the codeine group than in the levodropropizine group. However, no significant differences existed in the adverse events leading to discontinuation. CONCLUSION: Codeine is an effective and generally well-tolerated antitussive for chronic cough. However, it may induce side effects in some patients. Individual responses and adverse events should be carefully monitored when codeine is used to treat chronic cough.

Recent Advances in Allergen-Specific Immunotherapy in Humans: A Systematic Review.

Allergen-specific immunotherapy (AIT) is presumed to modulate the natural course of allergic disease by inducing immune tolerance. However, conventional AITs, such as subcutaneous immunotherapy and sublingual immunotherapy, require long treatment durations and often provoke local or systemic hypersensitivity reactions. Therefore, only <5% of allergy patients receive AIT as second-line therapy. Novel administration routes, such as intralymphatic, intradermal and epicutaneous immunotherapies, and synthetic recombinant allergen preparations have been evaluated to overcome these limitations. We will review the updated views of diverse AIT methods, and discuss the limitations and opportunities of the AITs for the treatment of allergic diseases in humans.

Bismuth-Based Quadruple Therapy versus Metronidazole-Intensified Triple Therapy as a First-Line Treatment for Clarithromycin-Resistant Helicobacter pylori Infection: A Multicenter Randomized Controlled Trial.

Background/Aims: Clarithromycin resistance is a main factor for treatment failure in the context of Helicobacter pylori infection. However, the treatment regimen for clarithromycin-resistant H. pylori infection has not yet been determined. We aimed to compare the efficacy and cost-effectiveness of 14-day bismuth-based quadruple therapy versus 14-day metronidazole-intensified triple therapy for clarithromycin-resistant H. pylori infection with genotypic resistance. Methods: This was a multicenter, randomized, controlled trial. A total of 782 patients with H. pylori infection examined using sequencing-based clarithromycin resistance point mutation tests were recruited between December 2018 and October 2020 in four institutions in Korea. Patients with significant point mutations (A2142G, A2142C, A2143G, A2143C, and A2144G) were randomly assigned to receive either 14-day bismuth-based quadruple therapy (n=102) or 14-day metronidazole-intensified triple therapy (n=99). Results: The overall genotypic clarithromycin resistance rate was 25.7% according to the sequencing method. The eradication rate of 14-day bismuth-based quadruple therapy was not significantly different in the intention-to-treat analysis (80.4% vs 69.7%, p=0.079), but was significantly higher than that of 14-day metronidazole-intensified triple therapy in the per-protocol analysis (95.1% vs 76.4%, p=0.001). There were no significant differences in the incidence of side effects. In addition, the 14-day bismuth-based quadruple therapy was more cost-effective than the 14-day metronidazole-intensified triple therapy. Conclusions: Fourteen-day bismuth-based quadruple therapy showed comparable efficacy with 14-day metronidazole-intensified triple therapy, and it was more cost-effective in the context of clarithromycin-resistant H. pylori infection.

Comparison of Two pMDIs in Adult Asthmatics: A Randomized Double-Blind Double-Dummy Clinical Trial.

BACKGROUND: Only a few studies directly compared the therapeutic efficacy and safety of two pressurized metered-dose inhalers (pMDIs) in asthma. We analyzed the asthma treatment outcomes, safety, and patient preferences using formoterol/beclomethasone (FORM/BDP), a pMDI with extra-fine particles, compared with formoterol/budesonide (FORM/BUD), another pMDI with non-extra-fine particles. METHODS: In this randomized, double-blind, double-dummy parallel group study, 40 adult asthmatics were randomized to FORM/BDP group (n=18; active FORM/BDP and placebo FORM/BUD) or FORM/BUD group (n=22; active FORM/BUD and placebo FORM/BDP). During the two visits (baseline and end of 8-week treatment), subjects were asked to answer questionnaires including asthma control test (ACT), asthma control questionnaires (ACQ), and Quality of Life Questionnaire for Adult Korean Asthmatics (QLQAKA). Lung function, compliance with inhaler, and inhaler-handling skills were also assessed. RESULTS: Ten subjects in the FORM/BDP group and 14 in the FORM/BUD group completed follow-up visits. ACT, ACQ, QLQAKA (a primary outcome), and adverse events did not differ between two groups. We found that the increase in forced expiratory volume in 1 second/forced vital capacity and forced expiratory flow at 25% to 75% of the pulmonary volume in the FORM/BDP group was higher than in the FORM/BUD group. Regarding preference, subjects responded that the flume velocity of FORM/BDP was higher, but more adequate than that of FORM/BUD. They also answered that FORM/BDP reached the trachea and bronchus and irritated them significantly more than FORM/BUD. CONCLUSION: The use of pMDI with extra-fine particles may relieve small airway obstruction more than the one with non-extra-fine particles despite no significant differences in overall treatment outcomes. Some asthmatics have a misconception about the adequacy of high flume velocity of pMDIs.

Prevalence and diagnostic values of laboratory animal allergy among research personnel.

BACKGROUND: Laboratory animal allergy (LAA) has not been sufficiently investigated, although LAA is a relatively common work-related condition and important occupational hazard. OBJECTIVE: This study aimed to evaluate the prevalence of LAA and analyze the diagnostic value of serum specific IgE (sIgE) using the skin prick test (SPT) as a comparative standard. METHODS: Korean laboratory animal researchers who attended an annual symposium were requested to answer questionnaires regarding demographic characteristics, laboratory animal exposure, and symptoms related to laboratory animal exposure. A total of 213 participants underwent a SPT with mouse and rat epithelial allergen extract. We measured sIgE against rodent urine, epithelium, and serum allergens from 63 participants. SPT outcome served as the comparison method. RESULTS: Among 223 participants, 213 had direct/indirect exposure to mice or rats, and 30% and 14% of them complained of allergic symptoms after exposure to mouse and rat, respectively. Sensitization rates were 28% for mouse epithelium and 23% for rat epithelium. Compared to a positive SPT with wheal ≥ 3 mm, presence of sIgE against rodent allergens showed a higher positive predictive value of 87-91% at a cut-off level of 0.35 KUA/L. Agreement between SPT and sIgE test was determined to be fair to moderate. CONCLUSIONS: Sensitization and allergy to mouse and rat were prevalent among laboratory personnel in Korea. When evaluating cases of potential LAA, the sIgE test can provide added diagnostic value if the skin test is positive. Careful interpretation of two tests is required to accurately diagnose LAA.

Intralymphatic immunotherapy with tyrosine-adsorbed allergens: a double-blind, placebo-controlled trial.

BACKGROUND: Most previous studies used aluminum hydroxide-absorbed allergen extracts in evaluating the potential therapeutic roles of intralymphatic allergen-specific immunotherapy (ILAIT). In this study, we evaluated the therapeutic efficacy and safety of ILAIT with L-tyrosine-adsorbed allergen extracts of Dermatophagoides farinae, D. pteronyssinus, cat, dog, or mixtures thereof, in patients with allergic rhinitis induced by these allergens. METHODS: In this randomized, double-blind, placebo-controlled trial, study subjects received three intralymphatic injections of L-tyrosine-adsorbed allergen extracts (active group) or saline (placebo group) at 4-week intervals. RESULTS: Although ILAIT reduced daily medication use and skin reactivity to HDM and cat allergens at 4 months after treatment, overall symptom score on a visual analog scale (VAS), sinonasal outcome test-20 (SNOT-20), rhinoconjunctivitis quality of life questionnaire (RQLQ), daily symptom score (dSS), daily medication score (dMS), daily symptom medication score (dSMS), nasal reactivity to HDM allergen, and basophil activity to HDM, cat, and dog allergens at 4 months and 1 year after treatment were similar between the treatment and control groups. Intralymphatic injection was more painful than a venous puncture, and pain at the injection site was the most frequent local adverse event (12.8%); dyspnea and wheezing were the most common systemic adverse events (5.3%). CONCLUSIONS: ILAIT with L-tyrosine-adsorbed allergen extracts does not exhibit profound therapeutic efficacy in allergic rhinitis and can provoke moderate-to-severe systemic reactions and cause pain at the injection site. TRIAL REGISTRATION: clinicaltrials.gov: NCT02665754; date of registration: 28 January 2016.

Inter-observer variability of experts and trainees for the diagnosis of reflux esophagitis: Comparison of linked color imaging, blue laser imaging, and white light imaging.

OBJECTIVES: Diagnosis of reflux esophagitis according to the Los Angeles classification minimal change (LA-M) has a low inter-observer agreement. We aimed to investigate whether the inter-observer agreement of reflux esophagitis was better when expert endoscopists read the endoscopic images, or when the linked color imaging (LCI) or blue laser imaging (BLI)-bright mode was used. In addition, whether the inclusion of LA-M in the definition of reflux esophagitis affected the consistency of the diagnosis was investigated. METHODS: During upper endoscopy, endoscopic images of the gastroesophageal junction were taken using white light imaging (WLI), BLI-bright, and LCI modes. Four expert endoscopists and four trainees reviewed the images to diagnose reflux esophagitis according to the modified LA classification. RESULTS: The kappa values for the inter-observer variability for the diagnosis of reflux esophagitis were poor to fair among the experts (κ = â€Š0.22, 0.17, and 0.27 for WLI, BLI-bright, and LCI, respectively) and poor among the trainees (κ = â€Š0.18, 0.08, and 0.14 for WLI, BLI-bright, and LCI). The inter-observer variabilities for the diagnosis of reflux esophagitis excluding LA-M were fair to moderate (κ = â€Š0.42, 0.35, and 0.42 for WLI, BLI-bright, and LCI) among the expert endoscopists and moderate among the trainees (κ = 0.48, 0.43, and 0.51 for WLI, BLI-bright, and LCI). CONCLUSIONS: The inter-observer agreement for the diagnosis of reflux esophagitis was very low for both the expert endoscopists and the trainees, even using BLI-bright or LCI mode. However, when reflux esophagitis LA-M was excluded from the diagnosis of esophagitis, the degree of inter-observer agreement increased.

Diagnostic performance of artificial intelligence model for pneumonia from chest radiography.

OBJECTIVE: The chest X-ray (CXR) is the most readily available and common imaging modality for the assessment of pneumonia. However, detecting pneumonia from chest radiography is a challenging task, even for experienced radiologists. An artificial intelligence (AI) model might help to diagnose pneumonia from CXR more quickly and accurately. We aim to develop an AI model for pneumonia from CXR images and to evaluate diagnostic performance with external dataset. METHODS: To train the pneumonia model, a total of 157,016 CXR images from the National Institutes of Health (NIH) and the Korean National Tuberculosis Association (KNTA) were used (normal vs. pneumonia = 120,722 vs.36,294). An ensemble model of two neural networks with DenseNet classifies each CXR image into pneumonia or not. To test the accuracy of the models, a separate external dataset of pneumonia CXR images (n = 212) from a tertiary university hospital (Gachon University Gil Medical Center GUGMC, Incheon, South Korea) was used; the diagnosis of pneumonia was based on both the chest CT findings and clinical information, and the performance evaluated using the area under the receiver operating characteristic curve (AUC). Moreover, we tested the change of the AI probability score for pneumonia using the follow-up CXR images (7 days after the diagnosis of pneumonia, n = 100). RESULTS: When the probability scores of the models that have a threshold of 0.5 for pneumonia, two models (models 1 and 4) having different pre-processing parameters on the histogram equalization distribution showed best AUC performances of 0.973 and 0.960, respectively. As expected, the ensemble model of these two models performed better than each of the classification models with 0.983 AUC. Furthermore, the AI probability score change for pneumonia showed a significant difference between improved cases and aggravated cases (Δ = -0.06 ± 0.14 vs. 0.06 ± 0.09, for 85 improved cases and 15 aggravated cases, respectively, P = 0.001) for CXR taken as a 7-day follow-up. CONCLUSIONS: The ensemble model combined two different classification models for pneumonia that performed at 0.983 AUC for an external test dataset from a completely different data source. Furthermore, AI probability scores showed significant changes between cases of different clinical prognosis, which suggest the possibility of increased efficiency and performance of the CXR reading at the diagnosis and follow-up evaluation for pneumonia.

Atorvastatin Induces FXR and CYP7A1 Activation as a Result of the Sequential Action of PPARγ/PGC-1α/HNF-4α in Hep3B Cells.

Backgrounds/Aims: PPARγ, farnesoid X receptor (FXR) and CYP7A1 are associated with solubility of bile. This study was performed to understand a mechanism and interactions of statin-induced PPARγ, PGC-1α and HNF-4α related to the statin-induced activation of FXR and CYP7A1, and verify whether the mevalonate pathway is involved in the mechanism. Methods: MTT assays were performed using cultured human Hep3B cells to determine the effect of atorvastatin on the cell proliferation. Expression levels of indicated proteins were measured using Western blotting assays by inhibiting the protein expression or not. Results: Atorvastatin increased expression of PPARγ, PGC-1α, HNF-4α, FXR, and CYP7A1 in Hep3B cells. PPARγ ligand of troglitazone upregulated the expression of PGC-1α, HNF-4α, FXR, and CYP7A1 in Hep3B cells. Silencing of PPARγ, PGC1α, and HNF4α using respective siRNA demonstrated that atorvastatin-induced FXR and CYP7A1 activation required sequential action of PPARγ /PGC-1α/HNF-4α. The silencing of PPARγ completely inhibited atorvastatin-induced PGC-1α expression, and the PGC1α silencing partially inhibited atorvastatin-induced PPARγ expression. The inhibition of HNF4α did not affect atorvastatin-induced PPARγ expression, but partially inhibited atorvastatin-induced PGC-1α expression. Besides, mevalonate completely reversed the effect of atorvastatin on PPARγ, PGC-1α, HNF-4α, FXR, and CYP7A1. Conclusions: Atorvastatin induces FXR and CYP7A1 activation as a result of sequential action of PPARγ/PGC-1α/HNF-4α in human hepatocytes. We propose that atorvastatin enhances solubility of cholesterol in bile by simultaneously activating of FXR and CYP7A1.