Objective: To evaluate the diagnostic performance of the “probable hepatocellular carcinoma (HCC)” category in the Korean Liver Cancer Association-National Cancer Center (KLCA-NCC) v2022 guidelines. Materials and Methods: This multicenter retrospective study included patients at risk of HCC who underwent gadoxetic acid-enhanced MRI between January 2015 and June 2018; a subgroup of these patients also underwent liver CT. Eligible patients had at least one non-cystic lesion (≥10 mm) with a reference standard. Four radiologists interpreted the images independently and the results were pooled. The performance of “definite HCC” and “probable HCC” together and “probable HCC” alone were compared between v2018 and v2022. Results: A total of 2,237 patients (1,666 men; mean age, 59 ± 11 years) with 2,445 lesions were included. In v2022, 1.5% (143/9,780) of the lesions were additionally categorized as “probable HCC” by four reviewers on MRI; among these, 104 lesions were not HCCs. Focal nodular hyperplasia (FNH) or FNH-like nodules constituted 90.4% (94/104) of the false positives. When “definite HCC” and “probable HCC” were combined, v2022 showed higher sensitivity (83.7% [5,670/6,776] vs. 83.1% [5,631/6,776]) but lower specificity (77.1% [2,316/3,004] vs. 80.6% [2,420/3,004]) than v2018 (P < 0.001). For “probable HCC” alone, v2022 showed a lower positive predictive value (PPV) than v2018 (64.1% [373/582] vs. 76.1% [334/439], P < 0.001). In v2022, lesions with non-rim arterial-phase hyperenhancement (APHE) showed a lower PPV than those without APHE (42.3% [91/215] vs. 76.8% [282/367], P < 0.001). In the CT subgroup (n = 1,590), 1.6% (99/6,360) of the lesions were reassessed as “probable HCC,” and its PPV was 83.8% (83/99) in v2022 whereas no lesions were classified as “probable HCC” under v2018. Conclusion The revised “probable HCC” category in the KLCA-NCC v2022 aligns with updates in the diagnostic flow, demonstrating acceptable performance on MRI and CT. Notably, FNH or FNH-like nodules can be misclassified as “probable HCC” when MRI is used.

Background: Sodium-glucose cotransporter 2 (SGLT-2) inhibitors are currently used to treat patients with diabetes. Previous studies have demonstrated that treatment with SGLT-2 inhibitors is accompanied by altered metabolic phenotypes. However, it has not been investigated whether the hypothalamic circuit participates in the development of the compensatory metabolic phenotypes triggered by the treatment with SGLT-2 inhibitors. Methods: Mice were fed a standard diet or high-fat diet and treated with dapagliflozin, an SGLT-2 inhibitor. Food intake and energy expenditure were observed using indirect calorimetry system. The activity of hypothalamic neurons in response to dapagliflozin treatment was evaluated by immunohistochemistry with c-Fos antibody. Quantitative real-time polymerase chain reaction was performed to determine gene expression patterns in the hypothalamus of dapagliflozin-treated mice. Results: Dapagliflozin-treated mice displayed enhanced food intake and reduced energy expenditure. Altered neuronal activities were observed in multiple hypothalamic nuclei in association with appetite regulation. Additionally, we found elevated immunosignals of agouti-related peptide neurons in the paraventricular nucleus of the hypothalamus. Conclusion This study suggests the functional involvement of the hypothalamus in the development of the compensatory metabolic phenotypes induced by SGLT-2 inhibitor treatment.

Carbohydrate-restricted diets and intermittent fasting (IF) have been rapidly gaining interest among the general population and patients with cardiometabolic disease, such as overweight or obesity, diabetes, and hypertension. However, there are limited expert recommendations for these dietary regimens. This study aimed to evaluate the level of scientific evidence on the benefits and harms of carbohydrate-restricted diets and IF to make responsible recommendations. A meta-analysis and systematic literature review of 66 articles on 50 randomized controlled trials (RCTs) of carbohydrate-restricted diets and 10 articles on eight RCTs of IF was performed. Based on the analysis, the following recommendations are suggested. In adults with overweight or obesity, a moderately-low carbohydrate or low carbohydrate diet (mLCD) can be considered as a dietary regimen for weight reduction. In adults with type 2 diabetes mellitus, mLCD can be considered as a dietary regimen for improving glycemic control and reducing body weight. In contrast, a very-low carbohydrate diet (VLCD) and IF are recommended against in patients with diabetes. Furthermore, no recommendations are suggested for VLCD and IF in adults with overweight or obesity, and carbohydrate-restricted diets and IF in patients with hypertension. Here, we describe the results of our analysis and the evidence for these recommendations.

Objectives: This paper aimed to use machine learning to identify a new group of factors predicting frailty in the elderly population by utilizing the existing frailty criteria as a basis, as well as to validate the obtained results. Methods: This study was conducted using data from the Korean Frailty and Aging Cohort Study (KFACS). The KFACS participants were classified as robust or frail based on Fried’s frailty phenotype and excluded if they did not properly answer the questions, resulting in 1,066 robust and 165 frail participants. We then selected influential features through feature selection and trained the model using support vector machine, random forest, and gradient boosting algorithms with the prepared dataset. Due to the imbalanced distribution in the dataset with a low sample size, holdout was applied with stratified 10-fold and cross-validation for estimating the model performance. The reliability of the constructed model was validated using an unseen test set. The model was then trained with hyperparameter optimization. Results: During the feature selection process, 27 features were identified as meaningful factors for frailty. The model was trained based on the selected features, and the weighted average F1-score reached 95.30% with the random forest algorithm. Conclusions The results of the study demonstrated the possibility of adopting machine learning to strengthen existing frailty criteria. As the method analyzes questionnaire responses in a short time, it can support higher volumes of data on participants’ health conditions and alert them regarding potential risks in advance.

Background: and PurposeThe first-line medications for the symptomatic treatment of rapid eye movement sleep behavior disorder (RBD) are clonazepam and melatonin taken at bedtime. We aimed to identify the association between depression and treatment response in patients with idiopathic RBD (iRBD). Methods: We reviewed the medical records of 123 consecutive patients (76 males; age, 66.0±7.7 years; and symptom duration, 4.1±4.0 years) with iRBD who were treated with clonazepam and/or melatonin. Clonazepam and melatonin were initially administered at 0.25–0.50 and 2 mg/day, respectively, at bedtime, and the doses were subsequently titrated according to the response of individual patients. Treatment response was defined according to the presence or absence of any improvement in dream-enacting behaviors or unpleasant dreams after treatment. Results: Forty (32.5%) patients were treated with clonazepam, 56 (45.5%) with melatonin, and 27 (22.0%) with combination therapy. The doses of clonazepam and melatonin at followup were 0.5±0.3 and 2.3±0.7 mg, respectively. Ninety-six (78.0%) patients reported improvement in their RBD symptoms during a mean follow-up period of 17.7 months. After adjusting for potential confounders, depression was significantly associated with a negative treatment response (odds ratio=3.76, 95% confidence interval=1.15–12.32, p=0.029). Conclusions We found that comorbid depression is significantly associated with a negative response to clonazepam and/or melatonin in patients with iRBD. Further research with larger numbers of patients is needed to verify our observations and to determine the clinical implications of comorbid depression in the pathophysiology of iRBD.

Allergic march is a part of a phase that occurs in a series of continuous steps in disease of pediatric patients, which proceeds from atopic dermatitis to asthma, and from asthma to allergic rhinitis. Recently, several hypotheses have been raised to explain the allergic march. Among them, the study of the hygiene theory related to microbiota, and the study on the role of innate cytokines which occurs in skin barrier damage are attracting attentions. If the interaction between the microbiota and the immune system occurs improperly, the activity of the regulatory T cell becomes insufficient and the immune-regulatory function is reduced, resulting in allergic diseases. Because of the skin barrier disruption, the innate cytokines are activated, thus resulting in Th2 inflammation reaction being increased. Considering this pathogenesis, blocking the linkage to pathogens is regarded to play an important role in preventing and treating allergic march.

Allergic march is a part of a phase that occurs in a series of continuous steps in disease of pediatric patients, which proceeds from atopic dermatitis to asthma, and from asthma to allergic rhinitis. Recently, several hypotheses have been raised to explain the allergic march. Among them, the study of the hygiene theory related to microbiota, and the study on the role of innate cytokines which occurs in skin barrier damage are attracting attentions. If the interaction between the microbiota and the immune system occurs improperly, the activity of the regulatory T cell becomes insufficient and the immune-regulatory function is reduced, resulting in allergic diseases. Because of the skin barrier disruption, the innate cytokines are activated, thus resulting in Th2 inflammation reaction being increased. Considering this pathogenesis, blocking the linkage to pathogens is regarded to play an important role in preventing and treating allergic march.
Asthma ; Attention ; Child ; Cytokines ; Dermatitis, Atopic ; Humans ; Hygiene ; Immune System ; Immunotherapy ; Inflammation ; Microbiota ; Rhinitis, Allergic ; Skin