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: We aimed to analyze the impact of concomitant Maze procedure on the clinical and rhythm outcomes, and echocardiographic parameters in tricuspid repair for patients with severe tricuspid regurgitation (TR) and persistent atrial fibrillation (AF). Methods: Patients who had severe TR and persistent AF and underwent tricuspid valve (TV) repair were included in the study. Both primary TR and secondary TR were included in the current study. The study population was stratified according to Maze procedure. The primary outcome was major adverse cardiovascular and cerebrovascular event (MACCE) at 15 years postsurgery. Propensity-score matching analyses was performed to adjust baseline differences. Results: Three hundred seventy-one patients who underwent tricuspid repair for severe TR and persistent AF from 1994 to 2021 were included, and 198 patients (53.4%) underwent concomitant Maze procedure. The maze group showed 10-year sinus rhythm (SR) restoration rate of 55%. In the matched cohort, the maze group showed a lower cumulative incidence of cardiac death (4.6% vs. 14.4%, P = 0.131), readmission for heart failure (8.1% vs. 22.2%, P = 0.073), and MACCE (21.1% vs. 42.1%, P = 0.029) at 15 years compared to the non-maze group. Left atrial (LA) diameter significantly decreased in the maze group at 5 years (53.3 vs. 59.6 mm, P < 0.001) after surgery compared to preoperative level, and there was a significant difference in the change of LA diameter over time between the two groups (P = 0.013). Conclusion The Maze procedure during TV repair in patients with severe TR and persistent AF showed acceptable SR rates and lower MACCE rates compared to those without the procedure, while also promoting LA reverse remodeling.

Background: Mandibular split fractures, in which the fracture occurs exclusively in the posterior wall, are uncommon. This study aimed to enhance clinicians’ understanding of mandibular split fractures and offer insights for future research. Methods: This study included six patients who visited our hospital between January 2020 and June 2023 and were diagnosed with mandibular split fractures. We retrospectively collected data from patients’ medical records on their age, sex, symptoms, mechanism, impact site, associated injuries, and treatment method, as well as the location, pattern, and number of fractures observed on computed tomography (CT) and panoramic images. The frequency of split fractures among all mandibular fractures was calculated. Results: The six patients included three men (50%) and three women (50%), ranging in age from 20 to 71 years (mean age, 49.8 years). The split fractures were located in the symphysis in one patient (16.7%), symphysis to parasymphysis in two patients (33.3%), parasymphysis in one patient (16.7%), and parasymphysis to the body in two patients (33.3%). Four patients (66.7%) had condylar head fractures, while two patients (33.3%) had single split fractures. The mechanism of trauma was a slip-down incident in four cases (66.7%), while two cases (33.3%) were caused by motorcycle traffic accidents. Four patients (67%) underwent intermaxillary fixation, while two patients (33%) improved with conservative treatment. Split fractures were diagnosed in all six patients on CT, whereas the fracture line was not clearly visible on panoramic images. Mandibular split fractures accounted for 5.6% of all mandibular fractures. Conclusion This study provides insights into the clinical characteristics of rare mandibular split fractures and the diagnostic imaging findings. Furthermore, CT scans and three-dimensional image synthesis-instead of panoramic images-may be essential for accurately diagnosing mandibular fractures, including mandibular split fractures, in the future.

Pyogenic liver abscess (PLA) can be caused by bacteria entering the liver via the portal vein or primary bacteremia, or it can be cryptogenic. Recently, Klebsiella pneumoniae has been increasingly found as a PLA pathogen. PLA due to this bacterium often leads to formation of extrahepatic abscesses. The treatment of choice is dual therapy with insertion of percutaneous catheter drainage and antibiotic therapy. We report 2 cases of PLA due to K. pneumoniae in immunocompetent children. We successfully treated patient 1 with percutaneous catheter drainage for 18 days and 6-week course of antibiotic therapy. Patient 2 was treated with percutaneous needle aspiration and antibiotic therapy for the same period. In both patients, the PLAs showed the ultrasound-confirmed resolutions after the dual therapy.
Abscess ; Anti-Bacterial Agents ; Bacteremia ; Bacteria ; Catheters ; Child ; Drainage ; Humans ; Immunocompetence ; Klebsiella pneumoniae ; Klebsiella ; Liver ; Liver Abscess, Pyogenic ; Needles ; Pneumonia ; Portal Vein

BACKGROUND: The 24-hour mean blood pressure (mBP) is the best predictor of organ damage; however, it is not easily applicable in clinical practice. The APrODiTe study suggested that systolic blood pressure (SBP) values at 7:00 AM and 9:30 PM were associated with the 24-hour mSBP in patients with chronic kidney disease (CKD). We investigated the association of the SBP values at these time-points with the renal outcomes in patients with diabetic CKD during 1-year follow-up. METHODS: Ninety-six patients with diabetic CKD were included at 1-year follow-up. The renal outcomes were an increase in the random urine protein/creatinine ratio or estimated glomerular filtration rate (eGFR) deterioration, which means a decrease in eGFR ≥5 mL/min/1.73 m² compared to the baseline values. RESULTS: The baseline SBP values at 7:00 AM, and 9:30 PM, and the 24-hour mSBP were 135.6±24.9 mmHg, 141.7±25.6 mmHg, and 136.4±20.7 mmHg, respectively. The SBP values measured at the same time-points after 1 year were similar to those at baseline. The SBP at 7:00 AM was significantly associated with eGFR deterioration in the univariate and multivariate analyses (odds ratio [OR]: 1.032; 95% confidence interval [CI]: 1.006–1.059; p=0.016). The SBP at 7:00AM and 24-hour mSBP did not show a concordant association with sustained proteinuria in the linear and logistic analyses. In the subgroup analysis, the association between the SBP at 7:00 AM and eGFR deterioration persisted in patients with CKD stage 3–5 (OR: 1.041; 95% CI: 1.010–1.073; p=0.010). CONCLUSION The SBP at 7:00 AM, in addition to the 24-hour mSBP, is also associated with eGFR deterioration in patients with diabetic CKD, particularly in those with CKD stage 3–5.

Investigations into the development of new therapeutic agents for lung inflammatory disorders have led to the discovery of plant-based alternatives. The rhizomes of Anemarrhena asphodeloides have a long history of use against lung inflammatory disorders in traditional herbal medicine. However, the therapeutic potential of this plant material in animal models of lung inflammation has yet to be evaluated. In the present study, we prepared the alcoholic extract and derived the saponin-enriched fraction from the rhizomes of A. asphodeloides and isolated timosaponin A-III, a major constituent. Lung inflammation was induced by intranasal administration of lipopolysaccharide (LPS) to mice, representing an animal model of acute lung injury (ALI). The alcoholic extract (50–200 mg/kg) inhibited the development of ALI. Especially, the oral administration of the saponin-enriched fraction (10–50 mg/kg) potently inhibited the lung inflammatory index. It reduced the total number of inflammatory cells in the bronchoalveolar lavage fluid (BALF). Histological changes in alveolar wall thickness and the number of infiltrated cells of the lung tissue also indicated that the saponin-enriched fraction strongly inhibited lung inflammation. Most importantly, the oral administration of timosaponin A-III at 25–50 mg/kg significantly inhibited the inflammatory markers observed in LPS-induced ALI mice. All these findings, for the first time, provide evidence supporting the effectiveness of A. asphodeloides and its major constituent, timosaponin A-III, in alleviating lung inflammation.
Acute Lung Injury ; Administration, Intranasal ; Administration, Oral ; Alcoholics ; Anemarrhena* ; Animals* ; Bronchoalveolar Lavage Fluid ; Herbal Medicine ; Humans ; Lung* ; Mice ; Models, Animal* ; Plants ; Pneumonia* ; Rhizome*

BACKGROUND: Woman kidney donors face obstetric complication risks after kidney donation, such as gestational hypertension and preeclampsia. Studies on childbirth-related complications among Asian women donors are scarce. METHODS: This retrospective cohort study included woman donors aged 45 years or younger at the time of kidney donation in a single tertiary hospital between 1985 and 2014. Pregnancy associated complications were investigated using medical records and telephone questionnaires for 426 pregnancies among 225 donors. Matched non-donor controls were selected by propensity score and the maternal and fetal outcomes were compared with those of donors. Primary outcomes were differences in maternal complications, and secondary outcomes were fetal outcomes in pregnancies of the donor and control groups. RESULTS: A total of 56 cases had post-donation pregnancies. The post-donation pregnancies group was younger at the time of donation and older at the time of delivery than the pre-donation pregnancies group, and there were no differences in primary outcomes between the groups except the proportion receiving cesarean section. Comparison of the complication risk between post-donation pregnancies and non-donor matched controls showed no significant differences in gestational hypertension, preeclampsia, or composite outcomes after propensity score matching including age at delivery, era at pregnancy, systolic blood pressure, body weight, and estimated glomerular filtration ratio (odds ratio, 0.63; 95% confidence interval, 0.19–2.14; P = 0.724). CONCLUSION: This study revealed that maternal and fetal outcomes between woman kidney donors and non-donor matched controls were comparable. Studies with general population pregnancy controls are warranted to compare pregnancy outcomes for donors.
Asian Continental Ancestry Group ; Blood Pressure ; Body Weight ; Cesarean Section ; Cohort Studies ; Female ; Filtration ; Humans ; Hypertension, Pregnancy-Induced ; Kidney* ; Medical Records ; Pre-Eclampsia ; Pregnancy Outcome ; Pregnancy* ; Propensity Score ; Retrospective Studies ; Telephone ; Tertiary Care Centers ; Tissue Donors*

Proteasomes are the primary degradation machinery for oxidatively damaged proteins that compose a class of misfolded protein substrates. Cellular levels of reactive oxygen species increase with age and this cellular propensity is particularly harmful when combined with the age-associated development of various human disorders including cancer, neurodegenerative disease and muscle atrophy. Proteasome activity is reportedly downregulated in these disease conditions. Herein, we report that docosahexaenoic acid (DHA), a major dietary omega-3 polyunsaturated fatty acid, mediates intermolecular protein cross-linkages through oxidation, and the resulting protein aggregates potently reduce proteasomal activity both in vitro and in cultured cells. Cellular models overexpressing aggregation-prone proteins such as tau showed significantly elevated levels of tau aggregates and total ubiquitin conjugates in the presence of DHA, thereby reflecting suppressed proteasome activity. Strong synergetic cytotoxicity was observed when the cells overexpressing tau were simultaneously treated with DHA. Antioxidant N-acetyl cysteine significantly desensitized the cells to DHA-induced oxidative stress. DHA significantly delayed the proteasomal degradation of muscle proteins in a cellular atrophy model. Thus, the results of our study identified DHA as a potent inducer of cellular protein aggregates that inhibit proteasome activity and potentially delay systemic muscle protein degradation in certain pathologic conditions.
Atrophy ; Cells, Cultured ; Cysteine ; Humans ; In Vitro Techniques* ; Muscle Fibers, Skeletal* ; Muscle Proteins ; Muscular Atrophy* ; Neurodegenerative Diseases ; Oxidative Stress ; Proteasome Endopeptidase Complex* ; Protein Aggregates* ; Reactive Oxygen Species ; Ubiquitin