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: 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.

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.

Objectives: Periodontitis is the most common chronic disease that causes tooth loss and is related to systemic diseases such as cardiovascular dis-ease and diabetes. An objective indicator of the current activity of periodontitis is necessary. Soluble forms of the receptor for advanced glycation endproducts (sRAGE) are markers that reflect the status of inflammatory diseases. In this study, the relationship between sRAGE and periodontitis was analyzed to determine whether it can be used to diagnose the current state of periodontitis. Patients and Methods: Eighty-four patients without any systemic diseases were diagnosed with periodontitis using three classifications of periodontitis. Demographics and oral examination data such as plaque index (PI), bleeding on probing (BOP) index, and probing pocket depth (PPD) were analyzed according to each classification. In addition, correlation and partial correlation between sRAGE and the values indicating periodontitis were analyzed. Results: In each classification, the level of sRAGE tended to decrease if periodontitis was present or severe, but this change was not statistically significant. sRAGE and periodontitis-related variables exhibited a weak correlation, among which the BOP index showed a relatively strong negative cor-relation (ρ=–0.20). Based on this, on analyzing the correlation between the BOP index and sRAGE in the group with more severe periodontitis (PPD≥5 mm group, severe group of AAP/CDC [American Academy of Periodontology/Centers for Disease Control and Prevention], periodontitis group of López), the correlation further increased (ρ=–0.23, –0.40, –0.50). Partial correlation analysis of the sRAGE and BOP index showed a stronger negative correlation (ρ=–0.36, –0.55, –0.45). Conclusion sRAGE demonstrated a tendency to decrease upon increased severity of periodontitis according to the classifications used. Above all, the correlation with the BOP index, which reflects the current state of periodontitis, was higher in the group with severe periodontitis. This indicates that the current status of periodontitis can be diagnosed through sRAGE.

The Korea National Health and Nutrition Examination Survey (KNHANES) was initiated in 1998 to provide evidence for the development and evaluation of health policies and programs. The Korea Disease Control and Prevention Agency is responsible for the KNHANES and has conducted it as a series of surveys. Over the past 20 years, efforts to produce accurate, timely, and nationwide health statistics have been refined by establishing a continuous annual survey system with full-time field staff, incrementally expanding survey components, collaborating with relevant academic societies for quality control, and revising the survey methods. Additionally, the utility of the collected data was increased by linking the KNHANES data with related data from other government agencies or institutions and making the overall data publicly available on the official website of KNHANES (https://knhanes.kdca.go.kr). Additional long-term plans are being developed, including plans to continue producing nationwide health indicators and invigorating the utilization of the KNHANES data.