Objectives: . The impacts of ventilation tube (VT) type and effusion composition on the VT extrusion rate and complications in children with otitis media remain unclear. This part II study evaluated the factors affecting the extrusion rate, recurrence rate, and complications of VT insertion. Methods: . A prospective study was conducted between June 2014 and December 2016 (the EVENT study [analysis of the effectiveness of ventilation tube insertion in pediatric patients with chronic otitis media]), with follow-up data collected until the end of 2017. Patients aged <15 years diagnosed with otitis media with effusion who received VT insertion were recruited at 15 tertiary hospitals. The primary outcomes were time to extrusion of VT, time to effusion recurrence, and complications. Results: . Data from 401 patients were analyzed. After excluding the results of long-lasting tubes (Paparella type II and T-tubes), silicone tubes (Paparella type I) exhibited a significantly longer extended time to extrusion (mean, 400 days) than titanium tubes (collar-button-type 1.0 mm: mean, 312 days; P<0.001). VT material (hazard ratio [HR], 2.117, 95% confidence interval [CI], 1.254–3.572; P=0.005), age (HR, 3.949; 95% CI, 1.239–12.590; P=0.02), and effusion composition (P=0.005) were significantly associated with the time to recurrence of middle ear effusion. Ears with purulent (mean, 567 days) and glue-like (mean, 588 days) effusions exhibited a shorter time to recurrence than ears with serous (mean, 846 days) or mucoid (mean, 925 days) effusions. The revision VT rates during follow-up were 3.5%, 15.5%, 10.4%, and 38.9% in ears with serous, mucoid, glue-like, and purulent effusions, respectively (P<0.001). The revision surgery rates were higher among patients aged <7 years than among those aged ≥7 years. Conclusion . Silicone tubes (Paparella type I) were less prone to early extrusion than titanium 1.0 mm tubes. VT type, patient age, and effusion composition affected the time to recurrence of effusion.

Background: The microencapsulation is an ideal solution to overcome immune rejection without immunosuppressive treatment. Poor biocompatibility and small molecular antigens secreted from encapsulated islets induce fibrosis infiltration. Therefore, the aims of this study were to improve the biocompatibility of microcapsules by dexamethasone coating and to verify its effect after xenogeneic transplantation in a streptozotocin-induced diabetes mice. Methods: Dexamethasone 21-phosphate (Dexa) was dissolved in 1% chitosan and was cross-linked with the alginate microcapsule surface. Insulin secretion and viability assays were performed 14 days after microencapsulation. Dexa-containing chitosan-coated alginate (Dexa-chitosan) or alginate microencapsulated porcine islets were transplanted into diabetic mice. The fibrosis infiltration score was calculated from the harvested microcapsules. The harvested microcapsules were stained with trichrome and for insulin and macrophages. Results: No significant differences in glucose-stimulated insulin secretion and islet viability were noted among naked, alginate, and Dexa-chitosan microencapsulated islets. After transplantation of microencapsulated porcine islets, nonfasting blood glucose were normalized in both the Dexa-chitosan and alginate groups until 231 days. The average glucose after transplantation were lower in the Dexa-chitosan group than the alginate group. Pericapsular fibrosis and inflammatory cell infiltration of microcapsules were significantly reduced in Dexa-chitosan compared with alginate microcapsules. Dithizone and insulin were positive in Dexa-chitosan capsules. Although fibrosis and macrophage infiltration was noted on the surface, some alginate microcapsules were stained with insulin. Conclusion Dexa coating on microcapsules significantly suppressed the fibrotic reaction on the capsule surface after transplantation of xenogenic islets containing microcapsules without any harmful effects on the function and survival of the islets.

This clinical practice position statement, a product of the Fatty Liver Research Group of the Korean Diabetes Association, proposes recommendations for the diagnosis, progression and/or severity assessment, management, and follow-up of non-alcoholic fatty liver disease (NAFLD) in patients with type 2 diabetes mellitus (T2DM). Patients with both T2DM and NAFLD have an increased risk of non-alcoholic steatohepatitis (NASH) and fibrosis and a higher risk of cardiovascular diseases and diabetic complications compared to those without NAFLD. With regards to the evaluation of patients with T2DM and NAFLD, ultrasonography-based stepwise approaches using noninvasive biomarker models such as fibrosis-4 or the NAFLD fibrosis score as well as imaging studies such as vibration-controlled transient elastography with controlled attenuation parameter or magnetic resonance imaging-proton density fat fraction are recommended. After the diagnosis of NAFLD, the stage of fibrosis needs to be assessed appropriately. For management, weight reduction achieved by lifestyle modification has proven beneficial and is recommended in combination with antidiabetic agent(s). Evidence that some antidiabetic agents improve NAFLD/NASH with fibrosis in patients with T2DM is emerging. However, there are currently no definite pharmacologic treatments for NAFLD in patients with T2DM. For specific cases, bariatric surgery may be an option if indicated.

PURPOSE: Despite medical and surgical treatments, some cases of nasal polyps (NP) exhibit recidivism. However, the endotype of refractory chronic rhinosinusitis with NP (CRSwNP) remains unclear. Therefore, the objective of this study was to characterize the immunological profile of refractory CRSwNP. METHODS: The control (n =23), primary NP group (pNP, n =70) and refractory NP group (rNP, n =86) were enrolled in this study. Patients who underwent revision surgeries due to failed maximal medical treatment after primary surgery were defined as the rNP group. A total of 18 inflammatory markers were investigated in nasal tissues using multiplex cytokine assay or enzyme-linked immunosorbent assay. RESULTS: The clinical characteristics of rNP included more extensive disease and worse clinical course after surgery. Additionally, rNP subjects showed higher infection rate (mucopurulence and culture-positive rate), more frequent use of antibiotics and suffered from symptomatic bacterial infection, increased asthma morbidity compared to pNP. Cytokine profile analysis showed that levels of Th17-associated mediators (myeloperoxidase, interleukin (IL)-8, IL-17A and IL-23), B-cell activating factor (BAFF) and Th1 cytokine (interferon-γ) were up-regulated in rNP compared to controls and pNP. Human neutrophil elastase-positive cells were also enhanced in rNP compared with pNP. Upregulation of Th17/Th1mediators and BAFF were observed in rNP, regardless of tissue eosinophilia or asthmatic comorbidity. Interestingly, eosinophilic markers, such as eosinophil cationic protein and C-C motif chemokine ligand 24, were up-regulated in asthmatic rNP compared to pNP and controls. Levels of anti-dsDNA immunoglobulin (Ig) G and IgA were up-regulated in rNP and highest in asthmatic eosinophilic rNP among subtypes of rNP. CONCLUSIONS: Our results suggest that Th17/Th1-associated mediators and BAFF may play a role and be a potential therapeutic target in refractory CRSwNP. Additionally, eosinophilic markers and autoantibodies may contribute to refractoriness in asthmatic rNP.
Anti-Bacterial Agents ; Asthma ; Autoantibodies ; B-Cell Activating Factor ; Bacterial Infections ; Comorbidity ; Enzyme-Linked Immunosorbent Assay ; Eosinophil Cationic Protein ; Eosinophilia ; Eosinophils ; Humans ; Immunoglobulin A ; Immunoglobulins ; Interleukin-17 ; Interleukins ; Nasal Polyps ; Neutrophils ; Sinusitis ; Th17 Cells ; Up-Regulation

OBJECTIVES: The aim of this multicenter registry study was to investigate the effectiveness of ventilation tube insertion and the microbiology of otitis media with effusion (OME) in children. This part I study was conducted to evaluate the microbiological profile of children with OME who needed ventilation tube insertion. METHODS: Patients < 15 years old who were diagnosed as having OME and received ventilation tube insertion were prospectively enrolled in 16 tertiary hospitals from June 2014 to December 2016. After excluding patients with missing data, the data of 397 patients were analyzed among a total of 433 enrolled patients. The clinical symptoms, findings of the tympanic membrane, hearing level, and microbiological findings were collected. RESULTS: In 103 patients (25.9%), antibiotics were used within 3 weeks before surgery. Ventilation tube insertion was performed in a total of 710 ears (626 in both ears in 313 patients, 55 in the left ear only, and 29 in the right ear only). Culture of middle ear effusion was done in at least one ear in 221 patients (55.7%), and in a total of 346 ears. Only 46 ears (13.3%) showed positive results in middle ear effusion culture. Haemophilus influenzae (17.3%, followed by coagulase-negative Staphylococcus and Staphylococcus auricularis) was the most common bacteria detected. CONCLUSION: H. influenzae was the most commonly found bacteria in middle ear effusion. Relatively low rates of culture positivity were noted in middle ear effusion of patients with OME in Korea.
Anti-Bacterial Agents ; Bacteria ; Child ; Ear ; Ear, Middle* ; Haemophilus influenzae ; Hearing ; Humans ; Influenza, Human ; Korea ; Middle Ear Ventilation ; Otitis Media with Effusion* ; Otitis Media* ; Otitis* ; Prospective Studies ; Staphylococcus ; Tertiary Care Centers ; Tympanic Membrane ; Ventilation*

BACKGROUND/AIMS: To evaluate the efficacy and safety of a controlled release, once-daily formulation of mosapride (UI05MSP015CT) in patients with functional dyspepsia (FD). METHODS: Patients with FD were randomly assigned (1:1) to receive either UI05MSP015CT (15 mg once a day, study group) or mosapride (5 mg three times a day, control group) and corresponding placebo for 4 weeks. The primary endpoint was a change in the gastrointestinal symptom score (GIS) evaluated at enrollment and after 4 weeks. Secondary endpoints were changes in the Nepean Dyspepsia Index-Korean version (NDI-K), rate of satisfactory symptom relief, and rate of adverse events. RESULTS: A total of 138 patients were enrolled (female, 73.9%; mean age, 44.0±15.4 years). After excluding patients who violated the study protocol, 59 and 58 patients from the study and control groups, respectively, were included in the per-protocol analysis. No difference was observed in drug compliance between the control and study groups (97.07%±4.52% vs 96.85%±6.05%, p=0.870). Changes in GIS scores were 9.69±6.44 and 10.01±5.92 in the study and control groups. The mean difference in GIS change between groups was 0.33 (95% confidence interval, 1.75 to 2.41), demonstrating non-inferiority of UI-05MSP015CT (p=0.755). The rate of satisfactory symptom relief was not different between the study and control groups (39.0% vs 56.9%, p=0.053). No differences in change in NDI-K score (14.3 vs 16.9, p=0.263) or rates of adverse events (12.9% vs. 4.4%, p=0.062) were observed between the study and control groups. CONCLUSIONS: Once-daily mosapride is not inferior to conventional mosapride in efficacy and is safe in patients with FD.
Compliance ; Dyspepsia* ; Humans

This study compared the efficacy of DA-9601 (Dong-A ST Co., Seoul, Korea) and its new formulation, DA-5204 (Dong-A ST Co.), for treating erosive gastritis. This phase III, randomized, multicenter, double-blind, non-inferiority trial randomly assigned 434 patients with endoscopically proven gastric mucosal erosions into two groups: DA-9601 3 times daily or DA-5,204 twice daily for 2 weeks. The final analysis included 421 patients (DA-5204, 209; DA-9601, 212). The primary endpoint (rate of effective gastric erosion healing) and secondary endpoints (cure rate of endoscopic erosion and gastrointestinal [GI] symptom relief) were assessed using endoscopy after the treatment. Drug-related adverse events (AEs), including GI symptoms, were also compared. At week 2, gastric healing rates with DA-5204 and DA-9601 were 42.1% (88/209) and 42.5% (90/212), respectively. The difference between the groups was −0.4% (95% confidence interval, −9.8% to 9.1%), which was above the non-inferiority margin of −14%. The cure rate of gastric erosion in both groups was 37.3%. The improvement rates of GI symptoms with DA-5204 and DA-9601 were 40.4% and 40.8%, respectively. There were no statistically significant differences between the two groups in both secondary endpoints. AEs were reported in 18 (8.4%) patients in the DA-5204 group and 19 (8.8%) in the DA-9601 group. Rates of AE were not different between the two groups. No serious AE or adverse drug reaction (ADR) occurred. These results demonstrate the non-inferiority of DA-5204 compared to DA-9601. DA-5204 is as effective as DA-9601 in the treatment of erosive gastritis. Registered randomized clinical trial at ClinicalTrials.gov (NCT02282670)
Artemisia ; Double-Blind Method ; Drug-Related Side Effects and Adverse Reactions ; Endoscopy ; Gastritis* ; Humans ; Seoul

BACKGROUND/AIMS: Therapies of functional dyspepsia (FD) are limited. DA-9701 is a novel prokinetic agent formulated with Pharbitis semen and Corydalis Tuber. We aimed to assess the efficacy of DA-9701 compared with itopride in FD patients. METHODS: Patients with FD randomly received either itopride 50 mg or DA-9701 30 mg t.i.d after a 2-week baseline period. After 4 weeks of treatment, 2 primary efficacy endpoints were analyzed: the change from baseline in composite score of the 8 dyspeptic symptoms and the overall treatment effect. Impact on patients' quality of life was assessed using the Nepean Dyspepsia Index (NDI) questionnaire. RESULTS: We randomly assigned 464 patients with 455 having outcome data. The difference of the composite score change of the 8 symptoms between the 2 groups was 0.62, indicating that DA-9701 was not inferior to itopride. The overall treatment effect response rate was not different between the groups. When responder was defined as > or = 5 of the 7 Likert scale, responder rates were 37% of DA-9701 and 36% of itopride group. Patients receiving DA-9701 experienced similar mean percentage of days with adequate relief during the 4-week treatment period compared with those receiving itopride (56.8% vs 59.1%). Both drugs increased the NDI score of 5 domains without any difference in change of the NDI score between the groups. The safety profile of both drugs was comparable. CONCLUSIONS: DA-9701 significantly improves symptoms in patients with FD. DA-9701 showed non-inferior efficacy to itopride with comparable safety.
Corydalis ; Dyspepsia* ; Humans ; Quality of Life ; Surveys and Questionnaires ; Semen

Helicobacter pylori, a gram-negative bacterium, is a causative agent of gastroduodenal diseases of human. Human immune system produces harmful reactive oxygen species to kill this bacterium that locates the microaerophilic mucous layer. H. pylori harbors various antioxidant enzymes including SodB, KatA and AhpC to protect the oxygen toxicity. We removed the catalase gene (katA) from H. pylori 26695 genome, and the change of profile of the gene expression of the mutant was analyzed by high resolution 2-DE followed by matrix assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS), tandem MS and microarray analysis. Eleven and 37 genes were upregulated and downregulated in the mutant respectively, either transcriptionally or translationally. Expression level of pfr and hp1588 that were decreased on protein level in the mutant was confirmed by RT-PCR analysis.
Catalase ; Gene Expression ; Genome ; Helicobacter pylori* ; Humans ; Immune System ; Mass Spectrometry ; Microarray Analysis ; Oxygen ; Proteome* ; Reactive Oxygen Species

Helicobacter pylori, a causative agent of gastroduodenal diseases, is a Gram-negative microaerophilic bacterium. Although H. pylori locates in the microaerophilic mucous layer, the bacteria would come into contact harmful reactive oxygen species generated by host immune system. It has been reported that H. pylori harbors various defense mechanisms which can protect bacterial cells from oxygen exposure. The change of the gene expression profile of sodB-negative isogenic mutant of H. pylori 26695 was analyzed by high resolution 2-DE followed by matrix assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) and tandem MS and microarray analysis. Eighteen genes and 41 genes were upregulated and downregulated respectively, either transcriptionally or translationally. Expression levels of three genes including trxB, yxjE and ribE that were changed both on a mRNA level and on a protein level were confirmed by RT-PCR analysis. However, change of expression levels of other major antioxidants such as KatA, AhpC and NapA were not detected, which means Sod is regulated by different way from that of KatA and AhpC. Mutant study of other antioxidant proteins may give us better understanding for the regulation of stress response in H. pylori.
Antioxidants ; Bacteria ; Defense Mechanisms ; Gene Expression* ; Helicobacter pylori ; Helicobacter* ; Immune System ; Mass Spectrometry ; Microarray Analysis ; Oxygen ; Reactive Oxygen Species ; Ribes ; RNA, Messenger ; Superoxide Dismutase* ; Superoxides* ; Transcriptome