Purpose: Sepsis is one of the most common causes of death after surgery. Several conventional scoring systems have been developed to predict the outcome of sepsis; however, their predictive power is insufficient. The present study applies explainable machine-learning algorithms to improve the accuracy of predicting postoperative mortality in patients with sepsis caused by peritonitis. Methods: We performed a retrospective analysis of data from demographic, clinical, and laboratory analyses, including the delta neutrophil index (DNI), WBC and neutrophil counts, and CRP level. Laboratory data were measured before surgery, 12–36 hours after surgery, and 60–84 hours after surgery. The primary study output was the probability of mortality.The areas under the receiver operating characteristic curves (AUCs) of several machine-learning algorithms using the Sequential Organ Failure Assessment (SOFA) and Simplified Acute Physiology Score (SAPS) 3 models were compared.‘SHapley Additive exPlanations’ values were used to indicate the direction of the relationship between a variable and mortality. Results: The CatBoost model yielded the highest AUC (0.933) for mortality compared to SAPS3 and SOFA (0.860 and 0.867, respectively). Increased DNI on day 3, septic shock, use of norepinephrine therapy, and increased international normalized ratio on day 3 had the greatest impact on the model’s prediction of mortality. Conclusion Machine-learning algorithms increase the accuracy of predicting postoperative mortality in patients with sepsis caused by peritonitis.

Eosinophilic esophagitis (EoE) is a chronic, immune/antigen-mediated esophageal disease characterized by symptoms of esophageal dysfunction and eosinophil-predominant inflammation. The diagnostic criteria for EoE have changed with our growing knowledge over the past two decades. Esophageal eosinophilia, which responds histologically to a proton pump inhibitor (PPI) is not a distinct disease but a subset of EoE. An endoscopic scoring system that relies on the assessment of exudates, rings, edema, furrows, and strictures is a useful tool for assessing endoscopic severity. PPIs are regarded as safe and effective first-line treatments for EoE. Oral topical corticosteroids or dietary therapy are also options for first-line treatment. Endoscopic dilation is effective for relieving the dysphagia symptoms of a patient with an esophageal stricture.

Background/Aims: Compared with Western countries, chronic lymphocytic leukemia (CLL) rarely occurs in Asia and has different clinical characteristics. Thus, we aimed to evaluate the clinical characteristics, treatment outcomes, and prognostic significance of Korean patients with CLL. Methods: We retrospectively analyzed 90 patients with CLL who had received chemotherapy at 6 centers in Korea between 2000 and 2012. Results: Compared with Western patients with CLL, Korean patients with CLL express lambda (42.0%) and atypical markers such as CD22 and FMC7 (76.7% and 40.0%, respectively) more frequently. First-line chemotherapy regimens included chlorambucil (n = 43), fludarabine and cyclophosphamide (FC) (n = 20), fludarabine (n = 13), rituximab-FC (n = 4). The remaining patients were treated with other various regimens (n = 10). The 5-year overall survival (OS) and progression-free survival (PFS) rates were 79.3% and 28.1%, respectively. Multivariate analyses showed that hyperleukocytosis (≥ 100 × 103/μL), extranodal involvement, and the Binet C stage were significant negative prognostic factors for OS (hazard ratio [HR] 4.75, p = 0.039; HR 21.6, p = 0.002; and HR 4.35, p = 0.034, respectively). Cytogenetic abnormalities including complex karyotypes (≥ 3), del(11q), and del(17) had a significantly adverse impact on both OS and PFS (p < 0.001 and p = 0.010, respectively). Conclusions Initial hyperleukocytosis, extranodal involvement, complex karyotype, del(17) and del(11q) need to be considered in the risk stratification system for CLL.

The thioredoxin (Trx) system plays critical roles in regulating intracellular redox levels and defending organisms against oxidative stress. Recent studies indicated that Trx reductase (TrxR) was overexpressed in various types of human cancer cells indicating that the Trx-TrxR system may be a potential target for anti-cancer drug development. This study investigated the synergistic effect of auranofin, a TrxR-specific inhibitor, on sulforaphane-mediated apoptotic cell death using Hep3B cells. The results showed that sulforaphane significantly enhanced auranofin-induced apoptosis by inhibiting TrxR activity and cell proliferation compared to either single treatment. The synergistic effect of sulforaphane and auranofin on apoptosis was evidenced by an increased annexin-V-positive cells and Sub-G1 cells. The induction of apoptosis by the combined treatment caused the loss of mitochondrial membrane potential (ΔΨm) and upregulation of Bax. In addition, the proteolytic activities of caspases (-3, -8, and -9) and the degradation of poly (ADP-ribose) polymerase, a substrate protein of activated caspase-3, were also higher in the combined treatment. Moreover, combined treatment induced excessive generation of reactive oxygen species (ROS). However, treatment with N-acetyl-L-cysteine, a ROS scavenger, reduced combined treatment-induced ROS production and apoptosis. Thereby, these results deduce that ROS played a pivotal role in apoptosis induced by auranofin and sulforaphane. Furthermore, apoptosis induced by auranofin and sulforaphane was significantly increased through inhibition of the phosphoinositide 3-kinase (PI3K)/Akt pathway. Taken together, the present study demonstrated that down-regulation of TrxR activity contributed to the synergistic effect of auranofin and sulforaphane on apoptosis through ROS production and inhibition of PI3K/Akt signaling pathway.

PURPOSE: We conducted a randomized, multicenter, phase III trial to compare S-1 plus docetaxel (DS) with S-1 plus cisplatin (SP) as adjuvant chemotherapy for stage III gastric cancer patients. MATERIALS AND METHODS: Stage III gastric cancer patients who had received curative gastrectomy with D2 lymphadenectomy were randomized into equal groups to receive adjuvant chemotherapy of eight cycles of DS (S-1 70 mg/m2/day on days 1-14 plus docetaxel 35 mg/m2on days 1 and 8) every 3 weeks or SP (S-1 70 mg/m2/day on days 1-14 plus cisplatin 60 mg/m2on day 1) every 3 weeks. The primary endpoint was 3-year disease-free survival (DFS) rate. RESULTS: Between November 2010 and July 2013, 153 patients (75 patients to DS and 78 patients to SP) were enrolled from 8 institutions in Korea. After the capecitabine plus oxaliplatin was approved based on the CLASSIC study, itwas decided to close the study early. With a median follow-up duration of 56.9 months, the 3-year DFS rate between two groups was not significantly different (49.14% in DS group vs. 52.5% in SP group). The most common grade 3-4 adverse event was neutropenia (42.7% in DS and 38.5% in SP, p=0.351). SP group had more grade 3-4 anemia (1.3% vs. 11.5%, p=0.037), whereas grade 3-4 hand-foot syndrome (4.1% vs. 0%, p=0.025) and mucositis (10.7% vs. 2.6%, p=0.001) were more common in DS group. Fifty-one patients (68%) in DS group and 52 (66.7%) in SP group finished planned treatment. CONCLUSION: Our findings suggest that SP or DS is an effective and tolerable option for patients with curatively resected stage III gastric cancer.
Anemia ; Capecitabine ; Chemotherapy, Adjuvant* ; Cisplatin ; Disease-Free Survival ; Follow-Up Studies ; Gastrectomy ; Hand-Foot Syndrome ; Humans ; Korea ; Lymph Node Excision ; Mucositis ; Neutropenia ; Stomach Neoplasms*

PURPOSE: Identification of biomarkers to predict recurrence risk is essential to improve adjuvant treatment strategies in stage II/III gastric cancer patients. This study evaluated biomarkers for predicting survival after surgical resection. MATERIALS AND METHODS: This post-hoc analysis evaluated patients from the CLASSIC trial who underwent D2 gastrectomywith orwithout adjuvant chemotherapy (capecitabine plus oxaliplatin) at the Yonsei Cancer Center. Tumor expressions of thymidylate synthase (TS), excision repair cross-complementation group 1 (ERCC1), and programmed death-ligand 1 (PD-L1) were evaluated by immunohistochemical (IHC) staining to determine their predictive values. RESULTS: Among 139 patients, IHC analysis revealed high tumor expression of TS (n=22, 15.8%), ERCC1 (n=23, 16.5%), and PD-L1 (n=42, 30.2%) in the subset of patients. Among all patients, high TS expression tended to predict poor disease-free survival (DFS; hazard ratio [HR], 1.80; p=0.053), whereas PD-L1 positivity was associated with favorable DFS (HR, 0.33; p=0.001) and overall survival (OS; HR, 0.38; p=0.009) in multivariate Cox analysis. In the subgroup analysis, poor DFS was independently predicted by high TS expression (HR, 2.51; p=0.022) in the adjuvant chemotherapy subgroup (n=66). High PD-L1 expression was associated with favorable DFS (HR, 0.25; p=0.011) and OS (HR, 0.22; p=0.015) only in the surgery-alone subgroup (n=73). The prognostic impact of high ERCC1 expression was not significant in the multivariate Cox analysis. CONCLUSION: This study shows that high TS expression is a predictive factor for worse outcomes on capecitabine plus oxaliplatin adjuvant chemotherapy, whereas PD-L1 expression is a favorable prognostic factor in locally advanced gastric cancer patients.
Biomarkers ; Capecitabine ; Chemotherapy, Adjuvant ; Disease-Free Survival ; DNA Repair ; Humans ; Immunohistochemistry ; Prognosis ; Prospective Studies ; Recurrence ; Stomach Neoplasms ; Thymidylate Synthase

BACKGROUND AND OBJECTIVES: Preoperative identification of intimal tear site in acute type A dissection will help procedural planning. The objective of this study was to determine the key findings of computed tomography (CT)-based prediction for tear site and compare the accuracy between radiologists and surgeons. SUBJECTS AND METHODS: Multi-detector CT (MDCT) images from 50 patients who underwent surgical repair of type A aortic dissection were retrospectively reviewed by 4 cardiac surgeons with limited experience or by 3 radiologists specialized in cardiovascular imaging. Surgical findings of intimal tear site were used as references. RESULTS: In surgical findings, the locations of intimal tear that were identified in 43 patients included aorta (n=25), ascending with arch (n=7), and arch only (n=11). The rest were retrograde dissections from the tear of descending aorta. Key CT findings that were most frequently found were defect in the intimal flap shadow (30.0+/-4.0 patients/reviewer, accuracy 87.0+/-11.7%) and differential filling of false lumen by phase and location (9.4+/-2.9 patients/reviewer, 84.8+/-10.4%). Surgeons predicted tear site (75.0+/-7.7% vs. 86.7+/-1.2%, p=0.055) and specified flap defect (80.5+/-10.3% vs. 95.7+/-7.4%, p=0.073) with lower accuracy than radiologists. CONCLUSIONS: With MDCT imaging, well-educated surgeons could be accurate in three fourths of cases. There was room for improvement through experience. Considering the substantial possibility of inaccuracy, critical decisions on CT images should be made through thorough reviewing by as many experienced radiologists and surgeons as possible.
Aorta ; Aorta, Thoracic ; Humans ; Retrospective Studies ; Tears*

PURPOSE: We investigated the prevalence and risk factors of allergic rhinitis (AR), nationwide in random children and adolescents of Korea. METHODS: A modified International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire survey was done in 1,820 children from elementary, middle, and high school nationwide in Korea. The subjects were selected by the stratifying sampling method by school grade and five regions. Current AR was defined as having AR symptoms during the last 12 months with a history of physician-diagnosed AR. Skin prick tests for 18 common allergens were performed. RESULTS: The number of males was 945, and that of females was 875. The mean age of the patients was 12.61+/-3.40 years. The prevalence of current AR and atopic current AR were 29.0% and 18.7%, respectively. Risk factors for current AR were male (adjusted odds ratio [aOR], 1.486; 95% confidence interval [CI], 1.189-1.856), family history of paternal AR (aOR, 3.208; 95% CI, 2.460-4.182), family history of maternal AR (aOR, 3.138; 95% CI, 2.446-4.025), antibiotic use in infancy (aOR, 1.547; 95% CI, 1.228-1.949), mold exposure during infancy (aOR, 1.416; 95% CI, 1.103-1.819), mold exposure during the last 12 months (aOR, 1.285; 95% CI, 1.012-1.630), and sensitization on skin prick tests (aOR, 2.596; 95% CI, 2.055-3.279). Risk factors for atopic current AR were the same as those of current AR, whereas breast-milk feeding (aOR, 0.720; 95% CI, 0.530-0.976) was a protective factor. Sensitized allergens as risk factors for current AR were Dermatophagoides pteronyssinus, Dermatophagoides farina, ragweed, mugwort, oak, alder, birch, Japanese hop, cat, and dog. CONCLUSION: The prevalences of current AR and atopic current AR were 29.0% and 18.7%, respectively. Male, sex parental AR, antibiotic use in infancy, mold exposure during the last 12 months, mold exposure during infancy, and atopic sensitization were risk factors for current AR. Breast-milk feeding was a protective factor for atopic current AR. Aeroallergen sensitization was an important risk factor for AR.
Adolescent ; Allergens ; Alnus ; Ambrosia ; Animals ; Artemisia ; Asian Continental Ancestry Group ; Asthma ; Betula ; Cats ; Child ; Dermatophagoides pteronyssinus ; Dogs ; Female ; Fungi ; Humans ; Humulus ; Hypersensitivity ; Korea ; Male ; Odds Ratio ; Parents ; Prevalence* ; Pyroglyphidae ; Rhinitis* ; Risk Factors* ; Skin

BACKGROUND: This study aimed to investigate sternal healing over time and the incidence of poor sternal healing in patients undergoing coronary artery bypass graft (CABG) surgery using bilateral internal thoracic arteries. MATERIALS AND METHODS: This study enrolled 197 patients who underwent isolated CABG using skeletonized bilateral internal thoracic arteries (sBITA) from 2006 through 2009. Postoperative computed tomography (CT) angiography was performed on all patients at monthly intervals for three to six months after surgery. In 108 patients, an additional CT study was performed 24 to 48 months after surgery. The axial CT images were used to score sternal fusion at the manubrium, the upper sternum, and the lower sternum. These scores were added to evaluate overall healing: a score of 0 to 1 reflected poor healing, a score of 2 to 4 was defined as fair healing, and a score of 5 to 6 indicated complete healing. Medical records were also retrospectively reviewed to identify perioperative variables associated with poor early sternal healing. RESULTS: Three to six months after surgery, the average total score of sternal healing was 2.07+/-1.52 and 68 patients (34.5%) showed poor healing. Poor healing was most frequently found in the manubrium, which was scored as zero in 72.6% of patients. In multivariate analysis, the factors associated with poor early healing were shorter post-surgery time, older age, diabetes mellitus, and postoperative renal dysfunction. In later CT images, the average sternal healing score improved to 5.88+/-0.38 and complete healing was observed in 98.2% of patients. CONCLUSION: Complete sternal healing takes more than three months after a median sternotomy for CABG using sBITA. Healing is most delayed in the manubrium.
Angiography ; Coronary Artery Bypass* ; Diabetes Mellitus ; Humans ; Incidence ; Mammary Arteries* ; Manubrium ; Medical Records ; Multivariate Analysis ; Retrospective Studies ; Skeleton ; Sternotomy ; Sternum ; Transplants ; Wound Healing

BACKGROUND: The balance of the risks and the benefits of cardiac surgery in the elderly remains a major concern. We evaluated the early and mid-term clinical results of patients aged over 75 years who underwent major cardiovascular surgery. METHODS: Two hundred and fifty-one consecutive patients, who underwent cardiac surgery at Seoul National University Bundang Hospital between July 2003 and June 2011, were included in this study (mean age, 78.7+/-3.4 years; male:female=130:121). Elective surgery was performed in 112 patients, urgent in 90, and emergency in 49. RESULTS: Early mortality was 12.7% (32/251). Follow-up completion was 100%, and the mean follow-up duration was 2.8+/-2.2 years. Late mortality was 24.2% (53/219). There were 283 readmissions in a total of 109 patients after discharge. However, the reason for readmission was related more to non-cardiac factors (71.3%) than to cardiac factors. The overall survival estimates were 79.2% at the 1-year follow-up and 58.4% at the 5-year follow-up. Patients who underwent elective surgery had a lower early mortality rate (elective, 4.5%; urgent, 13.3%; emergency, 30.6%) and better overall survival rate than those that underwent urgent or emergency surgery (p <0.001). CONCLUSION: The timing of cardiac surgery was found to be an independent risk factor for early and late mortality. Thus, earlier referral and intervention may improve operative results. Further, comprehensive coordinated postoperative care is needed for other comorbid problems in aged patients.
Aged ; Cardiac Surgical Procedures ; Emergencies ; Follow-Up Studies ; Humans ; Mortality ; Postoperative Care ; Referral and Consultation ; Risk Factors ; Seoul ; Survival Rate ; Thoracic Surgery