Ibuprofen-induced multiorgan malformation during embryogenesis in Xenopus laevis (FETAX).

Ibuprofen, one of the most commonly prescribed nonsteroidal anti-inflammatory drugs, has not been fully assessed for embryonic toxicity in vertebrates. Here, we systematically assessed the embryotoxicity of ibuprofen in Xenopus laevis at various concentrations during embryogenesis. Embryos were treated with different concentrations of ibuprofen, ranging from 8 to 64 mg/L, at 23 °C for 96 h, and examined daily and evaluated at 72 hpf. Lethal or teratogenic effects were documented. For histological analysis, paraffin embedded embryos were transversely sectioned at a thickness of 10-µm and stained with hematoxylin and eosin. Total RNA was isolated from embryos at stages 6, 12, 22 and 36, and real-time quantitative PCR was performed. Ibuprofen-treated embryos showed delayed or failed dorsal lip formation and its closure at the beginning of gastrulation. This resulted in herniation of the endodermal mass after gastrulation under high concentrations of ibuprofen-treated embryos. Underdeveloped intestines with stage and/or intestinal malrotation, distorted microcephaly, and hypoplastic heart, lungs, and pronephric tubules were observed in ibuprofen-treated embryos. Cephalic, cardiac, and truncal edema were also observed in them. The severity of the deformities was observed in a concentration-dependent manner. The teratogenic index was 2.28. These gross and histological disruptions correlated well with the altered expression of each organ marker gene. In conclusion, ibuprofen induced delayed and disrupted gastrulation in the early developmental stage and multiorgan malformation later in the organogenesis stage of Xenopus laevis embryos.

Helicobacter pylori Empirical and Tailored Eradication Therapy and Factors Influencing Eradication Rate: a 4-Year Single-Center Study.

BACKGROUND: The Helicobacter pylori eradication rate with standard triple therapy (STT) is continuously decreasing due to clarithromycin resistance. This study aimed to investigate the eradication rate of empirical and tailored therapy and explore various factors affecting this eradication rate using clarithromycin resistance test data for the last 4 years at a single institution in Daegu. METHODS: From August 2018 to July 2021, a total of 1,395 patients diagnosed with H. pylori infection based on rapid urea testing and histology at Keimyung University Dongsan Hospital were retrospectively examined. Participants were classified into the empirical and tailored therapy groups according to the results of the clarithromycin resistance test using the polymerase chain reaction. RESULTS: The overall eradication rate of empirical STT was 72.8%, and the eradication rate by year was 71.6% in 2018, 77.4% in 2019, 70.3% in 2020, and 70.6% in 2021; the differences were not statistically significant (p = 0.173). No significant difference was noted in the eradication rate according to gender, age, type of proton pump inhibitors, and use of probiotics. Significant differences were noted in the eradication rate according to the treat-ment period: 69.7% in the 7-day, 67.3% in the 10-day, and 81.4% in the 14-day group (p = 0.001). The eradication rate with STT was 87.4% in the non-resistant group. In the case of clarithromycin resistance, treatment was mainly with bismuth quadruple therapy (BQT), and the eradication rate was 86.1%. The eradication rate was higher with administration of BQT for 10 days or 14 days than for administration of BQT for 7 days, but with no statistical significance (p = 0.364). CONCLUSIONS: Extending the treatment period of STT helped in improving the eradication rate, and tailored therapy through clarithromycin resistance testing showed superior results when compared to empirical therapy.

Consistency of Helicobacter pylori eradication rates of first-line concomitant and sequential therapies in Korea: A nationwide multicenter retrospective study for the last 10 years.

BACKGROUND: Eradication rate of standard triple therapy for H. pylori has declined to unacceptable level, and alternative regimens such as concomitant and sequential therapy have been introduced. We aimed to assess the consistency of eradication rates of concomitant and sequential therapies as for the first-line H. pylori eradication in Korea. METHODS: A nationwide multicenter retrospective study was conducted including 18 medical centers from January 2008 to December 2017. We included 3,800 adults who had test to confirm H. pylori eradication within 1 year after concomitant or sequential therapy. RESULTS: Concomitant and sequential therapy were prescribed for 2508 and 1292 patients, respectively. The overall eradication rate of concomitant therapy was significantly higher than that of sequential therapy (91.8% vs. 86.1%, p < .001). In time trend analysis, the eradication rates of concomitant therapy were 90.2%, 88.2%, 92.1%, 94.3%, 91.1%, and 93.4% for each year from 2012 to 2017 with an increasing trend (p = .0146), while those of ST showed no significant trend (p = .0873). Among 263 patients with second-line therapy, bismuth quadruple therapy showed significantly higher eradication rate than quinolone-based triple therapy (73.9% vs. 51.5% in ITT analysis, p = .001; 82.7% vs. 63.0% in PP analysis, p = .002). CONCLUSION: Concomitant therapy is the best regimen for the first-line H. pylori eradication showing consistently higher eradication rate with an increasing trend for the last 10 years in Korea. Bismuth quadruple therapy should be considered for second-line therapy after eradication failure using non-bismuth quadruple therapy.

Sleep disorders in patients with functional dyspepsia: A multicenter study from the Korean Society of Neurogastroenterology and Motility.

BACKGROUND AND AIM: The few studies concerning the association between sleep disorders and functional dyspepsia (FD) have yielded inconsistent results. We compared the prevalence of sleep disorders in patients with FD and healthy controls, and evaluated whether FD was independently associated with sleep disorders, and the risk factors for sleep disorders in patients with FD. METHODS: This prospective, multicenter, cross-sectional study was conducted from August 2014 to December 2017 at 12 hospitals in South Korea. The inclusion criterion was the presence of FD (for ≥18 years) according to the Rome III criteria. Healthy controls were recruited from among patients who visited the Health Examination Center for check-ups. RESULTS: In total, 526 subjects were prospectively enrolled in this study (201 with FD and 325 healthy controls). The prevalence of sleep disorders was significantly higher among the patients with FD than among the healthy controls (41.8% vs 18.8%, P = 0.000). In a multivariate analysis, FD (odds ratio [OR] = 1.851; 95% confidence interval [CI] 1.194-2.870; P = 0.006), female sex (OR = 1.672; 95% CI 1.063-2.628; P = 0.026), and anxiety (OR = 3.325; 95% CI 2.140-5.166; P = 0.000) were independent risk factors for sleep disorders in the overall cohorts. In patients with FD only, low body mass index, heartburn, and anxiety were independent risk factors for sleep disorders in a further multivariate analysis. CONCLUSION: Sleep disorders were common in patients with FD. FD was significantly associated with sleep disorders in our patient population, irrespective of the presence of heartburn or psychiatric disorders.

Primary and secondary antibiotic resistance of Helicobacter pylori in Korea from 2003 to 2018.

BACKGROUND: Antimicrobial resistance of Helicobacter pylori (H pylori) affects the efficacy of eradication therapy. The aim of this study was to estimate the prevalence of primary and secondary resistance of H pylori isolates to antibiotics in Korea. METHODS: The present study was performed from 2003 to 2018. Primary resistance was evaluated in 591 patients without any history of eradication and secondary resistance in 149 patients from whom Helicobacter pylori was cultured after failure of eradication. A minimal inhibitory concentration test was performed for amoxicillin, clarithromycin, metronidazole, tetracycline, levofloxacin, and rifabutin using the agar dilution method. RESULTS: An increase in the primary resistance rate was found in clarithromycin (P < .001), metronidazole (P < .001), and both levofloxacin (P < .001) during the study period. The primary resistance rates of amoxicillin and tetracycline were low and stable during the study period. The secondary resistance rate significantly increased in metronidazole and levofloxacin (P = .022 and .039, respectively). CONCLUSIONS: The primary and secondary resistance rates of clarithromycin, metronidazole, and levofloxacin for Helicobacter pylori in Korea were high and increased over time. However, the primary and secondary resistance rates of amoxicillin and tetracycline were low and stable over time. These results will help in selecting effective eradication regimens of H pylori in Korea in the future.

Long-term oncologic outcomes of laparoscopic versus open resection following stent insertion for obstructing colon cancer: a multi-center retrospective study.

BACKGROUND: This study compared oncologic outcomes between open and laparoscopic surgery following self-expanding metallic stents insertion for obstructing colon cancer. METHODS: This retrospective study included 50 patients who underwent open surgery and 44 patients who underwent laparoscopic surgery for obstructing left-sided colon cancer at four tertiary referral hospitals between June 2005 and December 2013. RESULTS: The median follow-up periods were 48 months and 47 months in the open and laparoscopic groups, respectively. The median operative time, time to soft diet, and length of stay were comparable between the groups. Four cases converted to open surgery (9.1%) in the laparoscopic group. The morbidity within 30 days after surgery was comparable between the groups (OR 0.931; 95% CI 0.357-2.426; p = 0.884). The proximal and distal resection margins, the histologic grade of tumor, TNM stage, median tumor size, and presence of lymphovascular invasion did not differ significantly between the groups. The 5-year overall survival (OS) rates of the open and laparoscopic groups were 67.1% and 71.7% (HR 1.028, 95% CI 0.491-2.15, p = 0.942) and the 5-year disease-free survival (DFS) rates were 55.8% and 61.5% (HR 0.982; 95% CI 0.522-1.847; p = 0.955), respectively. The recurrence pattern did not differ between the groups. Multivariate analysis showed that sex (p = 0.027), nodal stage (p = 0.043), and the proportion of patients receiving postoperative adjuvant chemotherapy (p = 0.002) were independent prognostic factors for OS. The proportion of patients receiving postoperative adjuvant chemotherapy (p = 0.017) was an independent prognostic factor for DFS. CONCLUSIONS: Laparoscopic resection following stent insertion for obstructing colon cancer can be performed safely, with long-term oncologic outcomes comparable with those of open surgery.

Positive Association Between Helicobacter pylori Infection and Metabolic Syndrome in a Korean Population: A Multicenter Nationwide Study.

BACKGROUND AND AIM: Helicobacter pylori (H. pylori) infection causes extra-gastrointestinal as well as gastric diseases. This analytical cross-sectional study was performed to investigate the association between H. pylori infection and metabolic syndrome in a Korean population. METHODS: Anthropometric and metabolic data, as well as anti-H. pylori IgG antibodies, were measured in 21,106 subjects who participated in a health checkup between January 2016 and June 2017. The classification of metabolic syndrome followed the revised National Cholesterol Education Program criteria. RESULTS: After excluding subjects with a history of H. pylori eradication therapy, or gastric symptoms, the seropositivity of H. pylori was 43.2% in 15,195 subjects. H. pylori-positive participants had significantly higher body mass index (BMI), waist circumference, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and lower high-density lipoprotein (HDL-C) than did seronegative participants (P < 0.05). After adjusting for confounders, high TC, low HDL-C, and high LDL-C were associated with H. pylori seropositivity. Finally, the prevalence of metabolic syndrome was higher in H. pylori-seropositive subjects than in negative ones (27.2% vs. 21.0%, P < 0.05), and H. pylori seropositivity increased the likelihood of metabolic syndrome (OR 1.19, 95% CI 1.09-1.31, P < 0.001) after adjusting for sex, age, BMI, smoking, residence, household income, and education level. However, the association between H. pylori seropositivity and metabolic syndrome disappeared in those ≥ 65 years old. CONCLUSIONS: H. pylori infection plays an independent role in the pathogenesis of metabolic syndrome in Koreans under 65 years old.

Usefulness of OLGA and OLGIM system not only for intestinal type but also for diffuse type of gastric cancer, and no interaction among the gastric cancer risk factors.

BACKGROUND: The operative link on gastric atrophy (OLGA) and operative link on gastric intestinal metaplasia (OLGIM) stages have been suggested for risk estimation of gastric cancer (GC). However, usefulness of OLGA/OLGIM systems in diffuse type of GC was not investigated so far. The aims of this study were to evaluate the OLGA/OLGIM systems in estimating the GC risk according to Lauren's classification and to investigate the interaction among the risk factors. MATERIALS AND METHODS: The OLGA/OLGIM stages were evaluated in 1398 (765 control and 633 GC patients) who were prospectively enrolled in the Seoul National University Bundang Hospital. Synergistic interaction among the risk factors for GC was calculated using an additive model. RESULTS: Among 387 intestinal-type GC patients, 71 (18.3%) were high-risk OLGA stages (III, IV) and 113 (29.2%) were high-risk OLGIM stages (III, IV). Of the 246 patients with diffuse-type GC, 36 (14.6%) were high-risk OLGA stages and 39 (15.9%) were high-risk OLGIM stages. Multivariable analysis revealed family history of GC, Helicobacter pylori infection, high-risk OLGA stages, and high-risk OLGIM stages as independent risk factors for GC regardless of histologic type (odds ratios [ORs] 1.78, 1.94, 2.63, and 3.18, respectively). There was no significant risk modification among the H. pylori infection, family history of GC, and high-risk OLGA/OLGIM stages. CONCLUSION: High-risk OLGA/OLGIM stages are important prediction markers for GC regardless of H. pylori infection or family history of GC not only for the intestinal type but also for diffuse-type GC.

Prevalence and risk factors for upper gastrointestinal diseases in health check-up subjects: a nationwide multicenter study in Korea.

OBJECTIVES: The prevalence of upper gastrointestinal disease is expected to change following advances in socioeconomic status and improved hygiene in Korea. The aim of this study was to investigate the recent trends in upper gastrointestinal diseases based on endoscopic findings and Helicobacter pylori (H. pylori) seroprevalence in subjects undergoing health check-up at tertiary centers in Korea. METHODS: A multicenter cross-sectional study was conducted at nine healthcare centers between September 2016 and June 2017. The subjects were evaluated using questionnaires, upper endoscopy and H. pylori serology tests. The results were compared with previous data in our study group obtained from eight tertiary healthcare centers in 2011 (n = 4023). RESULTS: In total, we prospectively enrolled 2504 subjects undergoing health check-up. The prevalence of reflux esophagitis (RE) was 9.7%, which showed an increasing but insignificant trend since 2011 (8.8%). The prevalence of active and healing-stage benign gastric ulcer and duodenal ulcer (DU) was 1.6% and 1.2%, respectively, which confirmed a significant decrease since 2011 (4.1%; p < .001 and 2.2%; p = .005, respectively). The prevalence of gastric cancer was 0.5%, representing an increasing trend since 2011 (0.12%; p = .003). H. pylori seroprevalence was 51.3%, which significantly decreased from 2011 (59.8%; p < .001). In multivariate analysis, H. pylori seropositivity was a significant risk factor for DU (p < .001), whereas a significant protective factor against RE (p < .001). CONCLUSIONS: The significant decrease of H. pylori seroprevalence in the past five years altered the incidence of upper gastrointestinal disease.

Procalcitonin as a Decision-Supporting Marker of Urgent Biliary Decompression in Acute Cholangitis.

BACKGROUND AND AIM: This study aimed to evaluate the association of serum procalcitonin (PCT) at hospital presentation with disease severity and clinical deterioration to septic shock in acute cholangitis. METHODS: This study included consecutive patients with a diagnosis of acute cholangitis who presented to the emergency department and underwent biliary drainage. PCT and blood culture tests were conducted at the time of initial presentation. Patients were categorized into three groups based on disease severity. White blood cell count, levels of C-reactive protein and PCT were compared regarding the following: cholangitis severity, blood culture positivity, and clinical deterioration to septic shock. RESULTS: A total of 204 consecutive patients were enrolled, with grade I severity in 39 (19.1%), grade II in 139 (68.1%), and grade III in 26 (12.7%). The numbers of patients with blood culture positivity and clinical deterioration were 6 (15.4%) and 1 (2.6%) in grade I, 45 (32.4%) and 4 (2.9%) in grade II, and 14 (53.8%) and 1 (5.6%) in grade III cholangitis, respectively. Only PCT was significantly associated with blood culture positivity (3.25 vs 0.62 ng/mL; P = 0.001) and clinical deterioration (9.11 vs 0.89 ng/mL; P = 0.040). The cutoff value of PCT for clinical deterioration to septic shock among patients with grade I and II was 3.77 ng/mL (sensitivity of 80.0% and specificity of 74.0%). CONCLUSION: PCT could be a promising marker of clinical deterioration to septic shock in acute cholangitis. Therefore, PCT might be used as a decision-supporting biomarker for urgent biliary decompression.

Comparison of the efficacy of culture-based tailored therapy for Helicobacter pylori eradication with that of the traditional second-line rescue therapy in Korean patients: a prospective single tertiary center study.

OBJECTIVE: The effectiveness of Helicobacter pylori therapies has declined with an increase in antibiotic resistance. To overcome this problem, the efficacy of tailored H. pylori eradication therapy based on antimicrobial susceptibility testing was compared with that of empirical second-line rescue regimens. MATERIAL AND METHODS: Patients who had persistent H. pylori infection after the first eradication were recommended to undergo culture for determining the minimal inhibitory concentration (MIC) via gastroscopy, which increased the cost by 300%. Fourteen-day esomeprazole, tripotassium dicitrate bismuthate, metronidazole and tetracycline (EBMT) therapy or esomeprazole, moxifloxacin and amoxicillin (MEA) therapy was performed according to the results of antibiotic susceptibility testing. In case of refusal to undergo culture, the participants were treated with either 14-day empirical EBMT or MEA regimen for second eradication after explaining the complexity, side effects and costs associated with each regimen. This trial was registered at ClinicalTrials.Gov (NCT 02349685). RESULTS: In the 219 patients included, the intention to treat (ITT) and per protocol (PP) eradication rates was 75.3% and 79.8% in the 14-day EBMT group (n = 89), 70.8% and 72.4% in the 14-day MEA group (n = 89) and 87.8% and 100.0% in the 14-day tailored therapy group (n = 41), respectively. Based on the PP analysis, the 14-day tailored therapy group showed a significantly higher eradication rate than the 14-day EBMT or MEA group (both p ≤ 0.001). CONCLUSIONS: Tailored therapy based on H. pylori culture and MIC test could be an option as a second-line eradication regimen in the presence of high level of antimicrobial resistance.

Comparison of sequential therapy and amoxicillin/tetracycline containing bismuth quadruple therapy for the first-line eradication of Helicobacter pylori: a prospective, multi-center, randomized clinical trial.

BACKGROUND: The <80 % Helicobacter pylori eradication rate with sequential therapy is unsatisfactory. Modified bismuth quadruple therapy, replacing metronidazole with amoxicillin, could be promising because H. pylori resistance to tetracycline or to amoxicillin is relatively low. A 14-day modified bismuth quadruple protocol as first-line H. pylori treatment was compared with 10-day sequential therapy. METHODS: In total, 390 H. pylori-infected subjects participated in the randomized clinical trial: 10-day sequential therapy (40 mg pantoprazole plus 1 g amoxicillin twice a day for 5 days, then 40 mg pantoprazole and 500 mg clarithromycin twice a day and 500 mg metronidazole three times a day for 5 days) or 14-day modified bismuth quadruple therapy (40 mg pantoprazole, 600 mg bismuth subcitrate, 1 g tetracycline, and 1 g amoxicillin, twice a day). (13)C-urea breath test, rapid urease testing, or histology was performed to check for eradication. RESULTS: Intention-to-treat (ITT) eradication rates of 10-day sequential and 14-day quadruple therapy were 74.6 % and 68.7 %, respectively, and the per-protocol (PP) rates were 84.2 and 76.5 %, respectively. The eradication rate was higher in the sequential therapy group, but neither the ITT nor the PP analyses had a significant difference (P = 0.240 and P = 0.099, respectively). However, the adverse events were significantly lower in the modified bismuth quadruple therapy group than the sequential therapy group (36.9 vs. 47.7 %, P = 0.040). CONCLUSIONS: Ten-day sequential therapy appears to be more effective despite frequent adverse events. However, both 10-day SQT and 14-day PBAT did not reach the excellent eradication rates that exceed 90 %. Additional trials are needed to identify a more satisfactory first-line eradication therapy. TRIAL REGISTRATION: ClinicalTrials.gov ( NCT02159976 ); Registration date: 2014-06-03, CRIS ( KCT0001176 ); Registration date: 2014-07-23.

The Diagnostic Validity of Citric Acid-Free, High Dose (13)C-Urea Breath Test After Helicobacter pylori Eradication in Korea.

BACKGROUND: The (13)C-urea breath test ((13)C-UBT) is a noninvasive method for diagnosing Helicobacter pylori (H. pylori) infection. The aims of this study were to evaluate the diagnostic validity of the (13)C-UBT cutoff value and to identify influencing clinical factors responsible for aberrant results. METHODS: (13)C-UBT (UBiTkit; Otsuka Pharmaceutical, cutoff value: 2.5‰) results in the range 2.0‰ to 10.0‰ after H. pylori eradication therapy were compared with the results of endoscopic biopsy results of the antrum and body. Factors considered to affect test results adversely were analyzed. RESULTS: Among patients with a positive (13)C-UBT result (2.5‰ to 10.0‰, n = 223) or a negative (13)C-UBT result (2.0‰ to < 2.5‰, n = 66) after H. pylori eradication, 73 patients (34.0%) were false positive, and one (1.5%) was false negative as determined by endoscopic biopsy. The sensitivity, specificity, false-positive rate, and false-negative rate for a cutoff value of 2.5‰ were 99.3%, 47.1%, 52.9%, and 0.7%, respectively, and positive and negative predictive values of the (13)C-UBT were 67.3% and 98.5%, respectively. Multivariate analysis showed that a history of two or more previous H. pylori eradication therapies (OR = 2.455, 95%CI = 1.299-4.641) and moderate to severe gastric intestinal metaplasia (OR = 3.359, 95%CI = 1.572-7.178) were associated with a false-positive (13)C-UBT result. CONCLUSION: The (13)C-UBT cutoff value currently used has poor specificity for confirming H. pylori status after eradication, and this lack of specificity is exacerbated in patients that have undergone multiple prior eradication therapies and in patients with moderate to severe gastric intestinal metaplasia. In addition, the citric-free (13)C-UBT would increase a false-positive (13)C-UBT result.

A comparison between 15-day sequential, 10-day sequential and proton pump inhibitor-based triple therapy for Helicobacter pylori infection in Korea.

OBJECTIVE: The eradication rate of 10-day sequential therapy for Helicobacter pylori (H. pylori) infection was not satisfactory in Korea, probably due to antibiotic resistance. To compare the treatment efficacy of 15-day and 10-day sequential therapy of conventional 7-day proton pump inhibitor (PPI) triple therapy for the treatment of H. pylori infection. METHODS: A total of 332 patients with H. pylori infection were randomly assigned to receive either 7-day PPI triple therapy, 10-day sequential therapy or 15-day sequential therapy. Eradication rate, drug compliance, and adverse events were compared among the three regimens. RESULTS: The eradication rates by intention-to-treat analysis were 64.3% (95% CI: 55.5-73.2; 74 of 115 patients), 72.1% (95% CI: 63.6-80.5; 80 of 111 patients), and 80.2% (95% CI: 72.5-87.9; 85 of 106 patients) in the 7-day PPI triple, 10-day and 15-day sequential therapy groups, respectively (p = 0.032). The eradication rates by per-protocol analysis were 68.5% (95% CI: 59.6-77.4; 74 of 108 patients), 78.4% (95% CI: 70.3-86.5; 80 of 102 patients), and 89.5% (95% CI: 83.2-95.8; 85 of 95 patients) in the 7-day PPI triple, 10-day and 15-day sequential therapy groups, respectively (p = 0.001). There were no statistically significant differences between the three eradication therapy groups in regard to drug compliance and adverse events. CONCLUSION: The 15-day sequential therapy demonstrated improved eradication efficacy compared with 7-day PPI triple and 10-day sequential therapy in Korea.

Protective effects of garlic extract, PMK-S005, against nonsteroidal anti-inflammatory drugs-induced acute gastric damage in rats.

BACKGROUND: PMK-S005 is synthetic s-allyl-L-cysteine (SAC), a sulfur-containing amino acid, which was initially isolated from garlic. The antioxidant and anti-inflammation activities of SAC have been demonstrated in diverse experimental animal models. AIMS: The purpose of this study was to investigate the gastroprotective effects of PMK-S005 against NSAIDs-induced acute gastric damage in rats. METHODS: Eight-week SD rats were pretreated with PMK-S005 (1, 5, or 10 mg/kg) or rebamipide (50 mg/kg) 1 h before administration of NSAIDs including aspirin (200 mg/kg), diclofenac (80 mg/kg), and indomethacin (40 mg/kg). After 4 h, the gross ulcer index, histological index, and gastric mucus level were determined. Myeloperoxidase (MPO), TNF-α, IL-1ß, PGE2, and LTB4 levels were estimated in the gastric mucosal tissue by ELISA. Protein expressions of cPLA2, COX-1, and COX-2 were assessed by Western blot analysis. RESULTS: Pretreatment with PMK-S005 significantly attenuated the NSAIDs-induced gastric damage and increased the gastric mucus level. In addition, PMK-S005 attenuated increases in MPO, TNF-α, and IL-1ß production. The expressions of cPLA2 and COX-2 induced by NSAIDs were decreased by PMK-S005 pretreatment. PMK-S005 did not cause suppression of PGE2 synthesis induced by NSAIDs, but LTB4 production was significantly suppressed by PMK-S005. The effects of PMK-S005 were consistently maximized at a concentration of 5 mg/kg, which were frequently superior to those of rebamipide. CONCLUSIONS: These results strongly suggest that PMK-S005 can be a useful gastroprotective agent against acute gastric mucosal damage by suppressing proinflammatory cytokines, down-regulating cPLA2, COX-2 and LTB4 expression, and increasing the synthesis of mucus.

Factors affecting first-line triple therapy of Helicobacter pylori including CYP2C19 genotype and antibiotic resistance.

BACKGROUND: Emerging evidence shows that the eradication rate of proton pump inhibitor (PPI)-based triple therapy for the first-line treatment of Helicobacter pylori (H. pylori) has decreased. AIMS: To clarify the trend of eradication rate of PPI-based triple therapy and to assess the related factors in Korea during the past decade. METHODS: We prospectively prescribed the triple regimen for seven days (PPI + amoxicillin 1.0 g + clarithromycin 500 mg, twice a day) from March 2003 to May 2013 in 2,202 H. pylori-positive patients. Antibiotic susceptibility tests were performed by the agar dilution method, and the CYP2C19 genotype was determined by the PCR method. RESULTS: In the past decade, the annual eradication rate showed a decreasing trend in intention-to-treat and per-protocol analyses (P = 0.001, both). The antibiotic resistance was increased to amoxicillin (7.2-17.2%, P = 0.003) and clarithromycin (23.2-37.3%, P = 0.010) during the study period. The poor metabolizer genotype of CYP2C19 showed a high eradication rate compared to the extensive metabolizer (86.8 vs. 78.2%, P = 0.035). In addition, age ≥ 50 years, female gender, BMI < 25 kg/m(2), amoxicillin and/or clarithromycin resistance were associated with treatment failure on univariate analysis. However, on multivariate analysis, clarithromycin resistance was the only significant factor for treatment failure (OR, 12.76; 95% CI, 5.58-29.18; P < 0.001). CONCLUSIONS: An increase in clarithromycin resistance has led to decreased eradication rate of first-line triple therapy, and; hence, a new strategy is needed to improve the eradication rate of H. pylori.

Identifying Novel Subtypes of Functional Gastrointestinal Disorder by Analyzing Nonlinear Structure in Integrative Biopsychosocial Questionnaire Data.

Background/Objectives: Given the limited success in treating functional gastrointestinal disorders (FGIDs) through conventional methods, there is a pressing need for tailored treatments that account for the heterogeneity and biopsychosocial factors associated with FGIDs. Here, we considered the potential of novel subtypes of FGIDs based on biopsychosocial information. Methods: We collected data from 198 FGID patients utilizing an integrative approach that included the traditional Korean medicine diagnosis questionnaire for digestive symptoms (KM), as well as the 36-item Short Form Health Survey (SF-36), alongside the conventional Rome-criteria-based Korean Bowel Disease Questionnaire (K-BDQ). Multivariate analyses were conducted to assess whether KM or SF-36 provided additional information beyond the K-BDQ and its statistical relevance to symptom severity. Questions related to symptom severity were selected using an extremely randomized trees (ERT) regressor to develop an integrative questionnaire. For the identification of novel subtypes, Uniform Manifold Approximation and Projection and spectral clustering were used for nonlinear dimensionality reduction and clustering, respectively. The validity of the clusters was assessed using certain metrics, such as trustworthiness, silhouette coefficient, and accordance rate. An ERT classifier was employed to further validate the clustered result. Results: The multivariate analyses revealed that SF-36 and KM supplemented the psychosocial aspects lacking in K-BDQ. Through the application of nonlinear clustering using the integrative questionnaire data, four subtypes of FGID were identified: mild, severe, mind-symptom predominance, and body-symptom predominance. Conclusions: The identification of these subtypes offers a framework for personalized treatment strategies, thus potentially enhancing therapeutic outcomes by tailoring interventions to the unique biopsychosocial profiles of FGID patients.

Masculinity, Rather Than Biological Sex, Is Associated With Psychological Comorbidities in Patients With Irritable Bowel Syndrome.

Background/Aims: Irritable bowel syndrome (IBS) generally shows sex differences, and psychiatric comorbidities play an important role in its pathogenesis. We aim to measure the levels of gender roles and investigate their relationship with psychiatric factors in patients with IBS versus healthy controls. Methods: Patients diagnosed with IBS by Rome III and whose colonoscopy findings were normal were enrolled at multiple sites in Korea. The participants completed the Korean Sex Role Inventory-Short Form (KSRI-SF) to assess masculinity and femininity, the stress questionnaire, the Hospital Anxiety Depression Scale (HADS), and the 36-item Short Form Health Survey questionnaire to assess the quality of life (QOL). Results: In total, 102 patients with IBS (male:female = 35:67; mean age 42.6 ± 16.7 years) and 55 controls (male:female = 20:35; mean age 42.4 ± 11.1 years) were recruited. IBS patients had higher stress (9.69 ± 8.23 vs 4.56 ± 8.31, P < 0.001) and HADS scores (16.12 ± 7.17 vs 10.22 ± 5.74, P < 0.001) than the control group, but showed no significant difference in KSRI-SF scores. No significant differences in HADS and KSRI-SF scores were found between males and females. However, IBS patients whose symptoms worsened due to stress and patients with anxiety or depression had significantly lower masculinity. QOL was poorer in IBS patients than in controls. In stepwise multivariate analyses, the anxiety score, depression score, and the degree of daily life disturbance, not masculinity, were associated with the QOL of IBS patients. Conclusions: IBS patients had higher stress, more psychiatric comorbidities, and lower QOL than controls. Low masculinity, rather than sex, was associated with stress and psychological comorbidities, which deteriorated the QOL in IBS patients.

Prevalence and predictive value of sarcopenia in hospitalized patients with ischemic colitis.

Ischemic colitis (IC) and sarcopenia are associated with aging and multiple comorbidities. We aimed to investigate the prevalence and predictive role of sarcopenia in patients with IC. We retrospectively analyzed 225 hospitalized patients (median age, 72 years; women, 67.1%; severe IC, 34.2%) who were diagnosed with IC between January 2007 and February 2022. Sarcopenia was defined as the skeletal muscle index at the third lumbar vertebra determined by computed tomography. It was present in 49.3% (n = 111) of the patients and was significantly associated with severe IC compared to those without sarcopenia (48.6% vs. 20.2%, P < 0.001). Sarcopenia was associated with extended hospitalization (median: 8 vs. 6 days, P < 0.001) and fasting periods (4 vs. 3 days, P = 0.004), as well as prolonged antibiotic use (9 vs. 7 days, P = 0.039). Sarcopenia was linked to a higher risk of surgery or mortality (9.0% vs. 0%, P = 0.001) and independently predicted this outcome (odds ratio [OR], 11.17; 95% confidence interval [CI], 1.24‒1467.65, P = 0.027). It was prevalent among hospitalized patients with IC, potentially indicating severe IC and a worse prognosis. This underscores the importance of meticulous monitoring, immediate medical intervention, and timely surgical consideration.

Clinical Trial: Efficacy of Mosapride Controlled-release and Nortriptyline in Patients With Functional Dyspepsia: A Multicenter, Double-placebo, Double-blinded, Randomized Controlled, Parallel Clinical Study.

Background/Aims: Prokinetic agents and neuromodulators are among the treatment options for functional dyspepsia (FD), but their comparative efficacy is unclear. We aimed to compare the efficacy of mosapride controlled-release (CR) and nortriptyline in patients with FD after 4 weeks of treatment. Methods: Participants with FD were randomly assigned (1:1) to receive mosapride CR (mosapride CR 15 mg and nortriptyline placebo) or nortriptyline (mosapride CR placebo and nortriptyline 10 mg) in double-placebo, double-blinded, randomized controlled, parallel clinical study. The primary endpoint was defined as the proportion of patients with overall dyspepsia improvement after 4 weeks treatment. The secondary endpoints were changes in individual symptom scores, anxiety, depression, and quality of life. Results: One hundred nine participants were recruited and assessed for eligibility, and 54 in the mosapride CR group and 50 in the nortriptyline group were included in the modified intention-to-treat protocol. The rate of overall dyspepsia improvement was similar between groups (53.7% vs 54.0%, P = 0.976). There was no difference in the efficacy of mosapride CR and nortriptyline in a subgroup analysis by FD subtype (59.3% vs 52.5% in postprandial distress syndrome, P = 0.615; 44.4% vs 40.0% in epigastric pain syndrome, P = > 0.999; 50.0% vs 59.1% in overlap, P = 0.565; respectively). Both treatments significantly improved anxiety, depression, and quality of life from baseline. Conclusion: Mosapride CR and nortriptyline showed similar efficacy in patients with FD regardless of the subtype. Both treatments could be equally helpful for improving quality of life and psychological well-being while also relieving dyspepsia.