Background/Aims: Synchronous multiple gastric cancer (SMGC) accounts for approximately 6% to 14% of gastric cancer (GC) cases. This study aimed to identify risk factors for SMGC. Methods: A total of 14,603 patients diagnosed with GC were prospectively enrolled. Data including age, sex, body mass index, smoking, alcohol consumption, family history, p53 expression, microsatellite instability, cancer classification, lymph node metastasis, and treatment were collected. Risk factors were analyzed using logistic regression analysis between a single GC and SMGC. Results: The incidence of SMGC was 4.04%, and that of early GC (EGC) and advanced GC (AGC) was 5.43% and 3.11%, respectively. Patients with SMGC were older (65.33 years vs 61.75 years, p<0.001) and more likely to be male. Lymph node metastasis was found in 27% of patients with SMGC and 32% of patients with single GC. Multivariate analysis showed that SMGC was associated with sex (male odds ratio [OR], 1.669; 95% confidence interval [CI], 1.223 to 2.278; p=0.001), age (≥65 years OR, 1.532; 95% CI, 1.169 to 2.008; p=0.002), and EGC (OR, 1.929; 95% CI, 1.432 to 2.600; p<0.001). Survival rates were affected by Lauren classification, sex, tumor size, cancer type, distant metastasis, and venous invasion but were not related to the number of GCs. However, the survival rate of AGC with SMGC was very high. Conclusions SMGC had unique characteristics such as male sex, older age, and EGC, and the survival rate of AGC, in which the intestinal type was much more frequent, was very good (Trial registration number: NCT04973631).

Background: The pathogenesis and development of autoimmune diseases are associated with alteration of hormone levels. The effects of menopausal hormone therapy (MHT) on Behcet’s disease (BD) are unclear. Objective: We hypothesized that MHT would increase the risk of BD in postmenopausal women due to the central role of immunomodulation of estrogen and other sex hormones in autoimmune diseases. Methods: We analyzed data from the Korean National Health Insurance Service database and investigated the relationship between MHT and the risk of BD in postmenopausal women with BD. The study included 220,663 patients who received MHT and 1,170,566 who did not. The hazard ratio (HR) of BD was measured in all subjects.Statistical analyses were utilized with adjustments for possible confounding factors such as age, body mass index, smoking, alcohol consumption, physical activity, income, diabetes, hypertension, dyslipidemia, age at menarche (group), age at menopause (group), parity, breastfeeding, and oral contraceptive use. Results: After adjusting for confounding factors, the participants with a history of MHT had a higher risk of BD (MHT＜2 years, HR=1.459, 95% confidence interval [95% CI]=1.29∼1.649; MHT＞2 and ＜5 years, HR=1.512, 95% CI=1.265∼1.808; MHT≥5 years, HR=2.045, 95% CI=1.708∼2.447). Conclusion The findings demonstrate that MHT is associated with an increased risk of BD in postmenopausal women, indicating that estrogen plays an important role in the disease activity of BD. However, additional studies are needed to confirm these findings.

According to recent evidence, ferroptosis is a major cell death mechanism in the pathogenesis of kidney injury and fibrosis.Despite the renoprotective effects of classical ferroptosis inhibitors, therapeutic approaches targeting kidney ferroptosis remain limited. In this study, we assessed the renoprotective effects of melatonin and zileuton as a novel therapeutic strategy against ferroptosis-mediated kidney injury and fibrosis. First, we identified RSL3-induced ferroptosis in renal tubular epithelial HK-2 and HKC-8 cells. Lipid peroxidation and cell death induced by RSL3 were synergistically mitigated by the combination of melatonin and zileuton. Combination treatment significantly downregulated the expression of ferroptosis-associated proteins, 4-HNE and HO-1, and upregulated the expression of GPX4. The expression levels of p-AKT and p-mTOR also increased, in addition to that of NRF2 in renal tubular epithelial cells. When melatonin (20 mg/kg) and zileuton (20 mg/kg) were administered to a unilateral ureteral obstruction (UUO) mouse model, the combination significantly reduced tubular injury and fibrosis by decreasing the expression of profibrotic markers, such as α-SMA and fibronectin. More importantly, the combination ameliorated the increase in 4-HNE levels and decreased GPX4 expression in UUO mice. Overall, the combination of melatonin and zileuton was found to effectively ameliorate ferroptosis-related kidney injury by upregulating the AKT/mTOR/ NRF2 signaling pathway, suggesting a promising therapeutic strategy for protection against ferroptosis-mediated kidney injury and fibrosis.

Background/Aims: There are few reports regarding mixed carcinoma, defined as a mixture of glandular and poorly cohesive components, in patients with gastric cancer (GC). The aim of this study was to evaluate the proportion and characteristics of mixed carcinoma in GC patients. Methods: A total of 7,215 patients diagnosed with GC at Seoul National University Bundang Hospital were enrolled from March 2011 to February 2020. GC was divided into four groups (wellmoderately differentiated GC, poorly differentiated GC, poorly cohesive carcinoma, and mixed carcinoma). The proportion of each GC type and the clinicopathological features were analyzed and divided into early GC and advanced GC. Results: The proportion of mixed carcinoma was 10.9% (n=787). In early GC, submucosal invasion was the most common in poorly differentiated (53.7%), and mixed carcinoma ranked second (41.1%). Mixed carcinoma showed the highest proportion of lymph node metastasis in early GC (23.0%) and advanced GC (78.3%). In advanced GC, the rate of distant metastasis was 3.6% and 3.9% in well-moderately differentiated GC and mixed carcinoma, respectively, lower than that in poorly differentiated GC (6.4%) and poorly cohesive carcinoma (5.7%), without statistical significance. Conclusions Mixed carcinoma was associated with lymph node metastasis compared to other histological GC subtypes. And it showed relatively common submucosal invasion in early GC, but the rates of venous invasion and distant metastasis were lower in advanced GC. Further research is needed to uncover the mechanism underlying these characteristics of mixed carcinoma (Trial registration number: NCT04973631).

Background/Aims: The incidence and prognosis of gastric cancer (GC) shows sex difference.This study aimed to evaluate the effect of body mass index (BMI) on GC survival depending on sex. Methods: The sex, age, location, histology, TNM stages, BMI, and survival were analyzed in GC patients from May 2003 to February 2020 at the Seoul National University Bundang Hospital. Results: Among 14,688 patients, there were twice as many males (66.6%) as females (33.4%).However, under age 40 years, females (8.6%) were more prevalent than males (3.1%). Cardia GC in males showed a U-shaped distribution for underweight (9.6%), normal (6.4%), overweight (6.1%), obesity (5.6%), and severe obesity (9.3%) but not in females (p=0.003). Females showed decreased proportion of diffuse-type GC regarding BMI (underweight [59.9%], normal [56.8%], overweight [49.5%], obesity [44.8%], and severe obesity [41.7%]), but males did not (p<0.001). Both sexes had the worst prognosis in the underweight group (p<0.001), and the higher BMI, the better prognosis in males, but not females. Sex differences in prognosis according to BMI tended to be more prominent in males than in females in subgroup analysis of TNM stages I, II, and III and the operative treatment group. Conclusions GC-specific survival was affected by BMI in a sex-dependent manner. These differences may be related to genetic, and environmental, hormonal factors; body composition; and muscle mass (Trial registration number: NCT04973631).

Purpose: This study aimed to examine the changes in stress, occupational stress, and subjective health problems of novice female nurses within the first 18 months of work. Methods: This was a longitudinal study conducted with a secondary data analysis based on the Shift Work Nurse’s Health and Turnover (SWNHT) study. The participants were 178 female novice nurses who participated in all 3 data collection activities (on the first day of orientation before ward placement [T0], 6 months after work [T1], and 18 months after work [T2]). The stress, occupational stress, 8 subjective health problems (upper musculoskeletal pain, leg/foot discomfort, depression, anxiety or emotional disorder, sleep disturbance, headache, gastrointestinal disorder, menstrual disorder, and others), and the greatest health problem during the study period were measured, respectively. Data were analyzed using SPSS 26.0 to obtain descriptive statistics. Results: The subjective health of novice female nurses were found to be poor at T1 compared to T0 on both physical (upper musculoskeletal pain, leg/foot discomfort, and sleep disturbance) and psychological health problems (depression and stress). However, the psychological health problems of the participants were alleviated at T2 whereas; physical health problems persisted until T2. Conclusion Novice nurses had poor health problems 6 months after work. Sleep disturbance and musculoskeletal pain persisted although other health problems such as depression and stress were alleviated over the period. Strategies to prevent and manage different health problems of novice female nurses at different work duration are urgently needed.

Purpose: Laparoscopic proximal gastrectomy with double-tract reconstruction (LPG-DTR) is a function-preserving procedure performed for treating upper early gastric cancer (EGC).However, few studies have compared the outcomes of LPG-DTR with those of laparoscopic total gastrectomy (LTG). This study aimed at comparing the short-term outcomes of LPGDTR between LTG and upper EGC. Materials and Methods: For upper-third EGC, a multicenter, prospective, randomized trial was performed to compare those who underwent LPG-DTR with those who underwent LTG. Short-term outcomes, including clinicopathologic results, morbidity, mortality, and postoperative courses, were evaluated using a full analysis set based on the intention-to-treat principle and the per-protocol set. Results: Of the patients, 138 who fulfilled the criteria were randomized to each group. One patient in the LPG-DTR group withdrew consent. Sixty-eight patients underwent LPGDTR and 69 underwent LTG. The operative time (LPG-DTR=219.4 minutes; LTG=201.8 minutes; P=0.085), estimated blood loss (LPG-DTR=76.0 mL; LTG=66.1 mL; P=0.413), and the morbidity rate (LPG-DTR=23.5%; LTG=17.4%; P=0.373) between the groups were not significantly different. No mortality occurred in either of the study groups. Two weeks post operation, the Visick scores for postprandial symptoms, including reflux symptoms, were not significantly different between the groups (P=0.749). Laboratory findings on postoperative day 5 were not significantly different between the groups. Conclusions The short-term outcomes of LPG-DTR for upper EGC were comparable to those of LTG.Trial Registration: ClinicalTrials.gov Identifier: NCT02892643

Background: The primary objectives of mandibular surgery are to achieve optimal occlusion, low sensory disturbance, and adequate fixation with early movement. In-depth knowledge of the mandibular structure is required to achieve these goals. This study used computed tomography (CT) to evaluate the mandibular cortical thickness and cancellous space according to age and sex. Methods: We enrolled 230 consecutive patients, aged 20 to 50 years, who underwent CT scanning. The cortex and cancellous space centered around the inferior alveolar nerve (IAN) canal were measured at two specific locations: the lingula and second molar region. Statistical analysis of differences according to increasing age and sex was performed. Results: The t-test revealed that the cancellous space and cortical thickness differed significantly with respect to the threshold of 35 years of age. Both cortical thickness and cancellous space in the molar region were negatively correlated with age. Meanwhile, both cortical thickness and cancellous space in the lingula region showed a positive correlation with age. With respect to sex, significant differences in the cancellous space at the molar region and the cortical thickness at the lingula were observed. However, no further statistically significant differences were observed in other variables with respect to sex. The sum of each measurement on the mandibular body reflected the safe distance from the surface of the outer cortex to the IAN canal. The safe distances also showed statistically significant differences between those above and below 35 years of age. Conclusion Knowledge of the anatomical structure of the mandible and of changes in bone structure is crucial to ensure optimal surgical outcomes and avoid damage to the IAN. CT examination is useful to identify changes in the bone structure, and these should be taken into account in the planning of surgery for older patients.

Background: We performed a prospective survey on the adverse reactions following the first dose of two types of vaccines against coronavirus disease 2019 (COVID-19) in healthcare workers (HCWs) in South Korea. Methods: HCWs at a tertiary referral hospital in Seoul, South Korea, received a chimpanzee adenovirus-vectored vaccine (ChAdOx1 nCoV-19) or an mRNA-based vaccine (BNT162b2) between March 5 and March 26, 2021. The HCWs were asked to report adverse reactions through a mobile self-report questionnaire for three days after vaccination. Results: A total of 7,625 HCWs received the first dose of ChAdOx1 or BNT162b2 vaccine during the study period. Of them, 5,866 (76.9%) HCWs (ChAdOx1, n = 5,589 [95.3%];BNT162b2, n = 277 [4.7%]) participated at least once in the survey, of whom 77% were female and 86% were younger than 50 years. The overall adverse reaction rate was 93% in the ChAdOx1 group and 80% in the BNT162b2 group (P < 0.001). Both local and systemic reactions were more commonly reported in the ChAdOx1 group, and the difference was larger in systemic reactions such as fever and fatigue. In the ChAdOx1 group, the incidence of adverse reactions was significantly higher in females and those in the younger age groups, while the BNT162b2 group showed such difference according to age. Conclusion In our prospective survey, vaccine-associated adverse reactions were more commonly reported in the ChAdOx1 group than in the BNT162b2 group. Females and younger age groups experienced vaccine-associated adverse reactions more frequently.

Background: We performed a prospective survey on the adverse reactions following the first dose of two types of vaccines against coronavirus disease 2019 (COVID-19) in healthcare workers (HCWs) in South Korea. Methods: HCWs at a tertiary referral hospital in Seoul, South Korea, received a chimpanzee adenovirus-vectored vaccine (ChAdOx1 nCoV-19) or an mRNA-based vaccine (BNT162b2) between March 5 and March 26, 2021. The HCWs were asked to report adverse reactions through a mobile self-report questionnaire for three days after vaccination. Results: A total of 7,625 HCWs received the first dose of ChAdOx1 or BNT162b2 vaccine during the study period. Of them, 5,866 (76.9%) HCWs (ChAdOx1, n = 5,589 [95.3%];BNT162b2, n = 277 [4.7%]) participated at least once in the survey, of whom 77% were female and 86% were younger than 50 years. The overall adverse reaction rate was 93% in the ChAdOx1 group and 80% in the BNT162b2 group (P < 0.001). Both local and systemic reactions were more commonly reported in the ChAdOx1 group, and the difference was larger in systemic reactions such as fever and fatigue. In the ChAdOx1 group, the incidence of adverse reactions was significantly higher in females and those in the younger age groups, while the BNT162b2 group showed such difference according to age. Conclusion In our prospective survey, vaccine-associated adverse reactions were more commonly reported in the ChAdOx1 group than in the BNT162b2 group. Females and younger age groups experienced vaccine-associated adverse reactions more frequently.