Background: Worldwide, sepsis is the leading cause of death in hospitals. If mortality rates in patients with sepsis can be predicted early, medical resources can be allocated efficiently. We constructed machine learning (ML) models to predict the mortality of patients with sepsis in a hospital emergency department. Methods: This study prospectively collected nationwide data from an ongoing multicenter cohort of patients with sepsis identified in the emergency department. Patients were enrolled from 19 hospitals between September 2019 and December 2020. For acquired data from 3,657 survivors and 1,455 deaths, six ML models (logistic regression, support vector machine, random forest, extreme gradient boosting [XGBoost], light gradient boosting machine, and categorical boosting [CatBoost]) were constructed using fivefold cross-validation to predict mortality. Through these models, 44 clinical variables measured on the day of admission were compared with six sequential organ failure assessment (SOFA) components (PaO 2 /FIO 2 [PF], platelets (PLT), bilirubin, cardiovascular, Glasgow Coma Scale score, and creatinine).The confidence interval (CI) was obtained by performing 10,000 repeated measurements via random sampling of the test dataset. All results were explained and interpreted using Shapley’s additive explanations (SHAP). Results: Of the 5,112 participants, CatBoost exhibited the highest area under the curve (AUC) of 0.800 (95% CI, 0.756–0.840) using clinical variables. Using the SOFA components for the same patient, XGBoost exhibited the highest AUC of 0.678 (95% CI, 0.626–0.730). As interpreted by SHAP, albumin, lactate, blood urea nitrogen, and international normalization ratio were determined to significantly affect the results. Additionally, PF and PLTs in the SOFA component significantly influenced the prediction results. Conclusion Newly established ML-based models achieved good prediction of mortality in patients with sepsis. Using several clinical variables acquired at the baseline can provide more accurate results for early predictions than using SOFA components. Additionally, the impact of each variable was identified.

Interleukin-1 receptor-associated kinase 4 (IRAK4) is a pivotal enzyme in the Toll-like receptor (TLR)/MYD88 dependent signaling pathway, which is highly activated in rheumatoid arthritis tissues and activated B cell-like diffuse large B-cell lymphoma (ABC-DLBCL). Inflammatory responses followed by IRAK4 activation promote B-cell proliferation and aggressiveness of lymphoma. Moreover, proviral integration site for Moloney murine leukemia virus 1 (PIM1) functions as an anti-apoptotic kinase in propagation of ABC-DLBCL with ibrutinib resistance. We developed a dual IRAK4/PIM1 inhibitor KIC-0101 that potently suppresses the NF-κB pathway and proinflammatory cytokine induction in vitro and in vivo. In rheumatoid arthritis mouse models, treatment with KIC-0101 significantly ameliorated cartilage damage and inflammation. KIC-0101 inhibited the nuclear translocation of NF-κB and activation of JAK/STAT pathway in ABC-DLBCLs. In addition, KIC-0101 exhibited an anti-tumor effect on ibrutinib-resistant cells by synergistic dual suppression of TLR/MYD88-mediated NF-κB pathway and PIM1 kinase. Our results suggest that KIC-0101 is a promising drug candidate for autoimmune diseases and ibrutinib-resistant B-cell lymphomas.

Colonic interposition is the main procedure used in esophageal reconstruction. We report a rare case of simultaneous treatment of an anastomotic site stricture and a neoplasm in the interpositioned colon. A 69-year-old female visited our outpatient clinic with symptoms of progressive dysphagia for 1 year. At the age of 30 years, the patient underwent esophagectomy with retrosternal colonic interposition because of severe esophageal burns after chemical ingestion. Upper gastrointestinal endoscopy revealed stricture at the anastomosis site and a 10-mm flat elevated high-grade dysplasia in the interpositioned colon. First, through-the-scope balloon dilatation was performed for strictures. However, stenosis was observed during the second upper gastrointestinal endoscopy session.Therefore, a second session of through-the-scope balloon dilatation was performed, and simultaneously, endoscopic submucosal dissection was also successfully performed. After 2 months of follow-up, stenosis persisted; consequently, balloon dilatation was performed. No recurrence of neoplasm was confirmed endoscopically. Through-the-scope balloon dilatation of the stricture site and simultaneous endoscopic submucosal dissection of the neoplasm in the interpositioned colon were successfully performed.

This study evaluated the correlation between serum uric acid level and the nutrients adequacy ratio (NAR) using data from the Korea National Health and Nutrition Examination Survey (KNHANES) 2016∼2019. This is a cross-sectional study in which 6,579 Korean male adults were divided into quartiles according to their uric acid levels. All analyses were performed with adjusted age. Uric acid decreased as the age increased from the age group 19∼29 years to 30∼49 years and then to 50∼64 years. Interquartile results of serum uric acid levels showed that increases in the serum uric acid levels were associated with decreases in LDL-cholesterol (P＜0.01), triglycerides (P＜0.001), body weight (P＜0.001), waist circumference (P＜0.001), body mass index (P＜0.001), systolic blood pressure (SBP) (P＜0.001), diastolic blood pressure (DBP) (P＜0.001). However, uric acid levels decreased with an increase in HDL cholesterol (P＜0.001). The analysis of the NARs according to the quartiles of serum uric acid levels in men showed that an increase in serum uric acid levels was associated with a decrease in the NAR levels of dietary fiber (P＜0.001), calcium (P＜0.001), and folic acid (P＜0.001).

Purpose: For liposarcoma (LPS), clinical course and proper treatment strategies have not been well-established. Recently, immune-checkpoint inhibitors have shown potential efficacy in LPS. We aimed to describe the clinical course of LPS and evaluate the clinical impact of programmed death-ligand 1 (PD-L1). Materials and Methods: We reviewed all consecutive patients (n=332) who underwent curative-intent surgery for localized LPS at Asan Medical Center between 1989 and 2017. PD-L1 testing was performed in well-differentiated and dedifferentiated LPS. Results: The median age was 56 years with males comprising 60.8%. Abdomen-pelvis (47.6%) and well-differentiated (37.7%) were the most frequent primary site and histologic subtype, respectively. During a median follow-up of 81.2 months, recurrence was observed in 135 (40.7%), and 86.7% (117/135) were loco-regional. Well-differentiated subtype (hazard ratio [HR], 0.38), abdomen-pelvis origin (HR, 2.43), tumor size larger than 5 cm (HR, 1.83), positive resection margin (HR, 2.58), and postoperative radiotherapy (HR, 0.36) were significantly related with recurrence-free survival as well as visceral involvement (HR, 1.84) and multifocality (HR, 3.79) in abdomen-pelvis LPS. PD-L1 was positive in 31.5% (23/73) and 51.3% (39/76) of well-differentiated and dedifferentiated LPS, respectively, but had no impact on survival outcomes. Conclusion Clinical course of LPS was heterogeneous according to histology and anatomic location. Clear resection margin was important to lower recurrence and postoperative radiotherapy might have additional benefit. A decent portion of well-differentiated and dedifferentiated LPS were positive for PD-L1, but its prognostic role was unclear. Further research is needed to determine clinical implications of PD-L1, especially for advanced-stage LPS with unmet needs for effective systemic treatment.

Limb-Girdle Muscular Dystrophy 2B (LGMD2B) presents with proximal and/or distal muscle weakness and markedly high creatine kinase level. It is caused by the loss of dysferlin due to mutations in the DYSF gene. Due to its similar clinical features as inflammatory myopathy, it is often difficult to distinguish between the two. We present a case of a 48-year-old male who developed progressive proximal muscle weakness, papulosquamous lesions on the knuckles, elevated levels of muscle enzymes, and electromyogram abnormalities. Based on the clinical presentation, the initial impression was dermatomyositis, yet it was refractory to immunosuppressive therapy. Subsequently, dysferlin immunostaining and genetic analysis led to the final diagnosis of LGMD2B. This case shows that LGMD2B can present with extramuscular symptoms mimicking inflammatory myopathy in later stages of life. Dysferlin immunostaining and/or genetic analysis of the DYSF gene are essential for its diagnosis.

Background: The indication of denosumab for osteoporosis was expanded from second-line to first-line therapy in 2019. The aim of this study was to evaluate the efficacy of denosumab as both first- and second-line therapy in postmenopausal women with osteoporosis and osteopenia with risk factors by using the Fracture Risk Assessment Tool (FRAX). Methods: We conducted a medication use evaluation of denosumab in 98 patients who had been treated three or more times for osteoporosis or osteopenia at Chungnam National University Hospital from July 1st , 2017 to January 31st , 2020. Risk factors were identified using quantitative Ngram analyses of FRAX estimations. Patient information, including menopause status and results of bone mineral density tests (Tscore), was obtained from electronic medical records. Results: Age, body mass index (BMI), prior medication use, and T-score were identified as risk factors and were included as variables in the evaluation of denosumab use. Since no significant differences were detected between groups, denosumab is likely effective regardless of age or BMI. In addition, no significant difference was detected in T-scores following denosumab treatment, between groups who took bisphosphonates and selective estrogen receptor modulators (SERMs) with denosumab as first-line therapy for postmenopausal osteoporosis. Denosumab may, therefore, be effective as second-line therapy. Conclusion Efficacy of denosumab was evaluated in postmenopausal women with osteoporosis.Denosumab may be used as first- and second-line therapy regardless of age, BMI, and prior use of bisphosphonates and SERMs.

Background: The indication of denosumab for osteoporosis was expanded from second-line to first-line therapy in 2019. The aim of this study was to evaluate the efficacy of denosumab as both first- and second-line therapy in postmenopausal women with osteoporosis and osteopenia with risk factors by using the Fracture Risk Assessment Tool (FRAX). Methods: We conducted a medication use evaluation of denosumab in 98 patients who had been treated three or more times for osteoporosis or osteopenia at Chungnam National University Hospital from July 1st , 2017 to January 31st , 2020. Risk factors were identified using quantitative Ngram analyses of FRAX estimations. Patient information, including menopause status and results of bone mineral density tests (Tscore), was obtained from electronic medical records. Results: Age, body mass index (BMI), prior medication use, and T-score were identified as risk factors and were included as variables in the evaluation of denosumab use. Since no significant differences were detected between groups, denosumab is likely effective regardless of age or BMI. In addition, no significant difference was detected in T-scores following denosumab treatment, between groups who took bisphosphonates and selective estrogen receptor modulators (SERMs) with denosumab as first-line therapy for postmenopausal osteoporosis. Denosumab may, therefore, be effective as second-line therapy. Conclusion Efficacy of denosumab was evaluated in postmenopausal women with osteoporosis.Denosumab may be used as first- and second-line therapy regardless of age, BMI, and prior use of bisphosphonates and SERMs.

PURPOSE: The diagnostic criteria of gastric intraepithelial neoplasia (IEN) are controversial across the world. We investigated how many discrepancies occur in the pathologic diagnosis of IEN and early gastric carcinoma in endoscopic submucosal dissection (ESD) specimens, and evaluated the reasons of the discordance. MATERIALS AND METHODS: We retrospectively reviewed 1,202 ESD specimens that were originally diagnosed as gastric IEN and early carcinoma at 12 institutions. RESULTS: The final consensus diagnosis of carcinoma were 756 cases, which were originally 692 carcinomas (91.5%), 43 high-grade dysplasias (5.7%), 20 low-grade dysplasias (2.6%), and 1 others (0.1%), respectively. High- and low-grade dysplasia were finally made in 63 and 342 cases, respectively. The diagnostic concordance with the consensus diagnosis was the highest for carcinoma (91.5%), followed by low-grade dysplasia (86.3%), others (63.4%) and high-grade dysplasia (50.8%). The general kappa value was 0.83, indicating excellent concordance. The kappa values of individual institutions ranged from 0.74 to 1 and correlated with the proportion of carcinoma cases. The cases revised to a final diagnosis of carcinoma exhibited both architectural abnormalities and cytologic atypia. The main differential points between low- and high-grade dysplasias were the glandular distribution and glandular shape. Additional features such as the glandular axis, surface maturation, nuclear stratification and nuclear polarity were also important. CONCLUSION: The overall concordance of the diagnosis of gastric IEN and early carcinoma in ESD specimens was excellent. It correlated with the proportion of carcinoma cases, demonstrating that the diagnostic criteria for carcinoma are more reproducible than those for dysplasia.
Consensus ; Diagnosis ; Retrospective Studies ; Stomach Neoplasms

BACKGROUND/AIMS: Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) and brushing cytology are used worldwide to diagnose pancreatic and biliary malignant tumors. Liquid-based cytology (LBC) has been developed and it is currently used to overcome the limitations of conventional smears (CS). In this study, the authors aimed to compare the diagnostic value of the CellPrepPlus (CP; Biodyne) LBC method with CS in samples obtained using EUS-FNA and brushing cytology. METHODS: This study prospectively enrolled 75 patients with pancreatic or biliary lesions from June 2012 to October 2013. For cytological analyses, including inadequate specimens, benign and atypical were further classified into benign, and suspicious and malignant were subcategorized as malignant. Sensitivity, specificity, accuracy, and positive predictive values (PPV) and negative predictive values (NPV) were evaluated. RESULTS: In the EUS-FNA based cytological analysis of pancreatic specimens, CP had a sensitivity of 60.7%; specificity, 100%; accuracy, 77.1%; PPV, 100%; and NPV, 64.5%. CS had a sensitivity of 85.7%; specificity, 100%; accuracy, 91.7%; PPV, 100%; and NPV, 83.3%. In the brushing cytology based analysis of biliary specimens, CP had sensitivity of 53.1%; specificity, 100%; accuracy, 54.5%; PPV, 100%; and NPV, 6.3%. CS had a sensitivity of 78.1%; specificity, 100%; accuracy, 78.8%; PPV, 100%; and NPV, 12.5%. CONCLUSIONS: Our study found that CP had a lower sensitivity because of low cellularity compared with CS. Therefore, CP (LBC) has a lower diagnostic accuracy for pancreatic EUS-FNA based and biliary brush cytology based analyses compared with CS.
Endoscopic Ultrasound-Guided Fine Needle Aspiration ; Humans ; Methods ; Prospective Studies ; Sensitivity and Specificity