Background/Aims: Fexuprazan, a novel potassium-competitive acid blocker, was developed for treating acid-related disorders. Pharmacokinetic and pharmacodynamic properties of fexuprazan, unlike those of proton pump inhibitors, are independent of food effect. This study aims to evaluate differences in efficacy and safety of fexuprazan in patients with erosive esophagitis (EE) according to the timing of dosing. Methods: In this multicenter, open-label noninferiority study, patients who had typical reflux symptoms with endoscopically confirmed EE were randomized 1:1 to receive fexuprazan 40 mg daily 30 minutes before or after meal. Treatment was completed after 2 weeks or 4 weeks when healing was endoscopically confirmed. The primary endpoint was the proportion of patients with healed EE confirmed by endoscopy up to week 4. Safety endpoints included treatment-emergent adverse events (TEAEs). Results: In the prior-to-meal group (n = 89) and after-meal group (n = 86), 4-week EE healing rates were 98.77% and 100.00% (difference, 0.01%; 95% CI, –0.01% to 0.04%) and 2-week EE healing rates were 95.77% and 97.14% (difference, 0.01%; 95% CI, –0.05% to 0.07%), respectively. TEAEs were 9.78% and 8.70% in the prior-to-meal group and the after-meal group, respectively. Conclusions Non-inferiority analysis revealed that taking fexuprazan after meal was non-inferior to taking fexuprazan before meals in patients with EE. The frequency of adverse events was similar between the 2 study groups. The drug is safe and effective for healing EE regardless of the timing of dosing.

Background/Aims: Fexuprazan, a novel potassium-competitive acid blocker, was developed for treating acid-related disorders. Pharmacokinetic and pharmacodynamic properties of fexuprazan, unlike those of proton pump inhibitors, are independent of food effect. This study aims to evaluate differences in efficacy and safety of fexuprazan in patients with erosive esophagitis (EE) according to the timing of dosing. Methods: In this multicenter, open-label noninferiority study, patients who had typical reflux symptoms with endoscopically confirmed EE were randomized 1:1 to receive fexuprazan 40 mg daily 30 minutes before or after meal. Treatment was completed after 2 weeks or 4 weeks when healing was endoscopically confirmed. The primary endpoint was the proportion of patients with healed EE confirmed by endoscopy up to week 4. Safety endpoints included treatment-emergent adverse events (TEAEs). Results: In the prior-to-meal group (n = 89) and after-meal group (n = 86), 4-week EE healing rates were 98.77% and 100.00% (difference, 0.01%; 95% CI, –0.01% to 0.04%) and 2-week EE healing rates were 95.77% and 97.14% (difference, 0.01%; 95% CI, –0.05% to 0.07%), respectively. TEAEs were 9.78% and 8.70% in the prior-to-meal group and the after-meal group, respectively. Conclusions Non-inferiority analysis revealed that taking fexuprazan after meal was non-inferior to taking fexuprazan before meals in patients with EE. The frequency of adverse events was similar between the 2 study groups. The drug is safe and effective for healing EE regardless of the timing of dosing.

Background/Aims: Fexuprazan, a novel potassium-competitive acid blocker, was developed for treating acid-related disorders. Pharmacokinetic and pharmacodynamic properties of fexuprazan, unlike those of proton pump inhibitors, are independent of food effect. This study aims to evaluate differences in efficacy and safety of fexuprazan in patients with erosive esophagitis (EE) according to the timing of dosing. Methods: In this multicenter, open-label noninferiority study, patients who had typical reflux symptoms with endoscopically confirmed EE were randomized 1:1 to receive fexuprazan 40 mg daily 30 minutes before or after meal. Treatment was completed after 2 weeks or 4 weeks when healing was endoscopically confirmed. The primary endpoint was the proportion of patients with healed EE confirmed by endoscopy up to week 4. Safety endpoints included treatment-emergent adverse events (TEAEs). Results: In the prior-to-meal group (n = 89) and after-meal group (n = 86), 4-week EE healing rates were 98.77% and 100.00% (difference, 0.01%; 95% CI, –0.01% to 0.04%) and 2-week EE healing rates were 95.77% and 97.14% (difference, 0.01%; 95% CI, –0.05% to 0.07%), respectively. TEAEs were 9.78% and 8.70% in the prior-to-meal group and the after-meal group, respectively. Conclusions Non-inferiority analysis revealed that taking fexuprazan after meal was non-inferior to taking fexuprazan before meals in patients with EE. The frequency of adverse events was similar between the 2 study groups. The drug is safe and effective for healing EE regardless of the timing of dosing.

Background: and Purpose: We investigated the correlation between the deep distribution of white matter hyperintensity (WMH) (dWMH: WMH in deep and corticomedullary areas, with minimal periventricular WMH) and a positive agitated saline contrast echocardiography result. Methods: We retrospectively recruited participants with comprehensive dementia evaluations, an agitated saline study, and brain imaging. The participants were classified into two groups according to WMH-distributions: dWMH and dpWMH (mainly periventricular WMH with or without deep WMH.) We hypothesized that dWMH is more likely associated with embolism, whereas dpWMH is associated with small-vessel diseases. We compared the clinical characteristics, WMH-distributions, and positive rate of agitated saline studies between the two groups. Results: Among 90 participants, 27 and 12 met the dWMH and dpWMH criteria, respectively. The dWMH-group was younger (62.2±7.5 vs. 78.9±7.3, p<0.001) and had a lower prevalence of hypertension (29.6% vs. 75%, p=0.008), diabetes mellitus (3.7% vs.25%, p=0.043), and hyperlipidemia (33.3% vs. 83.3%, p=0.043) than the dpWMH-group. Regarding deep white matter lesions, the number of small lesions (<3 mm) was higher in the dWMH-group(10.9±9.7) than in the dpWMH-group (3.1±6.4) (p=0.008), and WMH was predominantly distributed in the border-zones and corticomedullary areas. Most importantly, the positive agitated saline study rate was higher in the dWMH-group than in the dpWMH-group (81.5% vs. 33.3%, p=0.003). Conclusions The dWMH-group with younger participants had fewer cardiovascular risk factors, showed more border-zone-distributions, and had a higher agitated saline test positivity rate than the dpWMH-group, indicating that corticomedullary or deep WMHdistribution with minimal periventricular WMH suggests embolic etiologies.

Background/Aims: Prokinetics such as mosapride citrate CR (conventional-release; Gasmotin) are commonly used in functional dyspepsia (FD). This study aims to evaluate the efficacy and safety of once-a-day mosapride citrate SR (DWJ1252), a sustained-release formulation of mosapride citrate, compared with mosapride citrate CR 3 times a day, in patients with FD. Methods: In this multicenter, randomized, double-blind, active-controlled, non-inferiority study, 119 patients with FD (by the Rome III criteria, 60 for mosapride citrate SR and 59 for mosapride citrate CR) were randomly allocated to mosapride citrate SR once daily or mosapride citrate CR thrice daily for 4 weeks in 16 medical institutions. Primary end point was the change in gastrointestinal symptom (GIS) score from baseline, assessed by GIS questionnaires on 5-point Likert scale after 4-week treatment. Secondary end points and safety profiles were also analyzed. Results: The study included 51 and 49 subjects in the mosapride citrate SR and mosapride citrate CR groups, respectively. GIS scores at week 4 were significantly reduced in both groups (mean ± SD: − 10.04 ± 4.45 and − 10.86 ± 5.53 in the mosapride citrate SR and mosapride citrate CR groups, respectively; P < 0.001), and the GIS changes from baseline did not differ between the 2 groups (difference, 0.82 point; 95% CI, − 1.17, 2.81; P = 0.643). Changes in GIS at weeks 2 and 4 and quality of life at week 4, and the improvement rates of global assessments at weeks 2 and 4, did not differ between the groups. Adverse events were similar in the 2 groups, and there were no serious adverse events. Conclusion In patients with FD, mosapride citrate SR once daily is as effective as mosapride citrate CR thrice daily, with a similar safety profile.

Purpose: We evaluated the association of body composition with long-term oncologic outcomes innon-metastatic rectal cancer patients. Materials and Methods: We included 1,384 patients with stage(y)0-III rectal cancer treated at Asan Medical Centerbetween January 2005 and December 2012. Body composition at diagnosis was measuredusing abdomino-pelvic computed tomography (CT). Sarcopenia, visceral obesity (VO), andsarcopenic obesity (SO) were defined using CT measured parameters such as skeletal muscleindex (total abdominal muscle area, TAMA), visceral fat area (VFA), and VFA/TAMA. Inflammatorystatus was defined as a neutrophil-lymphocyte ratio of ! 3. Obesity was categorizedby body mass index (! 25 kg/m2). Results: Among the 1,384 patients, 944 (68.2%) had sarcopenia and 307 (22.2%) had SO. The5-year overall survival (OS) rate was significantly lower in sarcopenic patients (no sarcopeniavs. sarcopenia; 84% vs. 78%, p=0.003) but the 5-year recurrence-free survival (RFS) ratewas not different (77.3% vs. 77.9% p=0.957). Patients with SO showed lower 5-year OS(79.1% vs. 75.5% p=0.02) but no difference in 5-year RFS (p=0.957). Sarcopenia, SO, VO,and obesity were not associated with RFS. However, obesity, SO, age, sex, inflammatorystatus, and tumor stage were confirmed as independent factors associated with OS on multivariateanalysis. In subgroup analysis, association of SO with OS was more prominent inpatients with (y)p stage 0-2 and no inflammatory status. Conclusion The presence of SO and a low body mass index at diagnosis are negatively associated withOS in non-metastatic rectal cancer patients.

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

Two separate studies were conducted to establish bioequivalence (BE) for two doses of atorvastatin/metformin sustained-release (SR) fixed dose combination (FDC) versus the same dosage of the individual component (IC) tablets in healthy male subjects under fed conditions (study 1, BE of atorvastatin/metformin SR 20/500 mg FDC; study 2, BE of atorvastatin/metformin SR 20/750 mg FDC). Each study was a randomized, open-label, single oral dose, two-way crossover design. Serial blood samples were collected pre-dose and up to 36 hours post-dose for atorvastatin and 24 hours for metformin. Plasma concentrations of atorvastatin, 2-OH atorvastatin and metformin were analyzed using a validated liquid chromatography tandem mass-spectrometry. A non-compartmental analysis was used to calculate pharmacokinetic (PK) variables and analysis of variance was performed on the lognormal-transformed PK variables. A total of 75 subjects completed the study 1 (36 subjects) and study 2 (39 subjects). The 90% confidence intervals for the adjusted geometric mean ratio of Cmax and the AUC0-t were within the predefined 0.80 to 1.25 range. The number of subjects reporting at least one adverse event following FDC treatments was comparable to that following IC treatments. The two treatments were well tolerated. Therefore, atorvastatin/metformin SR 20/500 mg and 20/750 mg FDC tablets are expected to be used as alternatives to IC tablets to decrease the pill burden and increase patient compliance.
Atorvastatin Calcium* ; Chromatography, Liquid ; Cross-Over Studies* ; Humans ; Male* ; Metformin* ; Patient Compliance ; Pharmacokinetics* ; Plasma ; Tablets* ; Therapeutic Equivalency

Enteropathy-associated T-cell lymphoma (EATL) is a rare extranodal T-cell lymphoma arising from the intestine. Two types of EATL have been reported. In contrast to the classic EATL type I, EATL type II occurs sporadically, is unrelated to celiac disease, and comprises 10% to 20% of all EATL cases. A total of five cases of EATL type II were diagnosed at our clinic from January 2009 to September 2012. Four of the five patients were diagnosed with the help of endoscopy. Among the four patients, two of the cases involved both the small and large intestines, whereas in the other two patients, EATL was limited to the small intestine. Common endoscopic findings included innumerable fine granularities (also called mosaic mucosal patterns) and diffuse thickening of the mucosa with a semicircular shallow ulceration in the lesions of the small bowel. In contrast, the endoscopic findings of the colon were nonspecific and could not distinguish EATL type II from other diseases. There are only few published reports regarding the representative endoscopic findings of EATL. Here, we present the clinical and endoscopic findings of four cases of EATL type II diagnosed by endoscopy.
Aged ; Celiac Disease/complications ; *Colonoscopy ; Enteropathy-Associated T-Cell Lymphoma/etiology/*pathology ; Female ; Humans ; Intestinal Mucosa/pathology ; Intestine, Large/pathology ; Intestine, Small/pathology ; Male ; Middle Aged

BACKGROUND/AIMS: The effect of proton pump inhibitors (PPI) in Asian functional dyspepsia (FD) patients has not been well established as in Western countries. DA-9701, a novel prokinetic agent, stimulates gastric emptying and modulates visceral hypersensitivity in vivo and in human studies. This study was conducted to compare the efficacy of DA-9701 with a conventional PPI in mono or combination therapy in patients with FD. METHODS: In this double-blind, randomized, non-inferiority trial, 389 patients diagnosed with FD using Rome III criteria were allocated among 3 groups: 30-mg DA-9701 t.i.d (means 3 times a day), 40-mg pantoprazole, and 30-mg DA-9701 t.i.d + 40-mg pantoprazole. The primary efficacy end-point was a global assessment of the patient binary response or response on a 5-Likert scale after 4 weeks. RESULTS: The global symptomatic improvement was 60.5% in the DA-9701 group, 65.6% in the pantoprazole group, and 63.5% in the DA-9701 + pantoprazole group using a 5-Likert scale at week 4 with no significant difference among 3 groups (P = 0.685). Symptom improvement measured by binary outcome was significantly achieved in each of the 3 groups, but not different among groups. Patients in all treatment groups reported significant improvement in the response rate and symptoms according to FD subtypes and dyspepsia-related quality of life (P < 0.001), but there were no significant differences among the 3 groups. CONCLUSIONS: DA-9701 improves global and individual symptoms and increases dyspepsia-specific quality of life in patients with FD. The efficacy of DA-9701 monotherapy is comparable with pantoprazole and there is no additive effect with combination of DA-9701 and pantoprazole in patients with FD.
Asian Continental Ancestry Group ; Dyspepsia* ; Gastric Emptying ; Humans ; Hypersensitivity ; Proton Pump Inhibitors ; Quality of Life