Background: We aimed to evaluate whether composite blood biomarkers including aldo-keto reductase family 1 member B10 (AKR1B10) and cytokeratin 18 (CK-18; a nonalcoholic steatohepatitis [NASH] marker) have clinically applicable performance for the diagnosis of NASH, advanced liver fibrosis, and high-risk NASH (NASH+significant fibrosis). Methods: A total of 116 subjects including healthy control subjects and patients with biopsy-proven nonalcoholic fatty liver disease (NAFLD) were analyzed to assess composite blood-based and imaging-based biomarkers either singly or in combination. Results: A composite blood biomarker comprised of AKR1B10, CK-18, aspartate aminotransferase (AST), and alanine aminotransferase (ALT) showed excellent performance for the diagnosis of, NASH, advanced fibrosis, and high-risk NASH, with area under the receiver operating characteristic curve values of 0.934 (95% confidence interval [CI], 0.888 to 0.981), 0.902 (95% CI, 0.832 to 0.971), and 0.918 (95% CI, 0.862 to 0.974), respectively. However, the performance of this blood composite biomarker was inferior to that various magnetic resonance (MR)-based composite biomarkers, such as proton density fat fraction/MR elastography- liver stiffness measurement (MRE-LSM)/ALT/AST for NASH, MRE-LSM+fibrosis-4 index for advanced fibrosis, and the known MR imaging-AST (MAST) score for high-risk NASH. Conclusion Our blood composite biomarker can be useful to distinguish progressive forms of NAFLD as an initial noninvasive test when MR-based tools are not available.

Background/Aims: Patients with active cancer frequently develop venous thromboembolism (VTE). However, there is little data about VTE in patients with advanced cholangiocarcinoma (CCA). Therefore, we investigated the clinical significance of VTE in patients with advanced CCA. Methods: We analyzed the data of a total of 332 unresectable CCA patients diagnosed between 2010 and 2020 in this retrospective study. We investigated the incidence and risk factors for VTE, and its effect on survival in patients with advanced CCA. Results: During a median follow-up of 11.6 months, 118 patients (35.5%) developed VTE. The cumulative incidence of VTE was 22.4% (95% confidence interval [CI], 0.18 to 0.27) at 3 months and 32.8% (95% CI, 0.27 to 0.38) at 12 months. Major vessel invasion was an independent risk factor for VTE (hazard ratio, 2.88; 95% CI, 1.92 to 4.31; p<0.001). Patients who developed VTE during follow-up had shorter overall survival than patients who did not (11.50 months vs 15.83 months, p=0.005). In multivariable analysis, VTE (hazard ratio, 1.58; 95% CI, 1.23 to 2.02;p<0.001) was associated with poor overall survival. Conclusions Major vessel invasion is related to the occurrence of VTE in advanced CCA. The development of VTE significantly decreases the overall survival and is an important unfavorable prognostic factor for survival.

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.

Background/Aims: The combinatorial effects of prophylactic methods for postendoscopic retrograde cholangiopancreatography pancreatitis (PEP) in patients with risk factors remain unclear. In this network meta-analysis, we compared the efficacy of various prophylactic strategies to decrease the risk of PEP among patients with risk factors. Methods: A systematic review was performed to identify randomized controlled trials from PubMed, Embase, and the Cochrane Library through July 2021. We used frequentist network meta-analysis to compare the rates of PEP among patients who received prophylactic treatments as follows: class A, rectal nonsteroidal anti-inflammatory drugs; class B, prophylactic pancreatic stent; class C, aggressive hydration; or control, no prophylaxis or active control. We selected those studies that included patients with risk factors for PEP. Results: We identified 19 trials, comprising 4,328 participants. Class ABC (odds ratio [OR], 0.08; 95% confidence interval [CI], 0.03 to 0.24), class AC (OR, 0.10; 95% CI, 0.02 to 0.47), class AB (OR, 0.12; 95% CI, 0.05 to 0.26), class BC (OR, 0.13; 95% CI, 0.04 to 0.41), class A (OR, 0.16; 95% CI, 0.05 to 0.50), and class B (OR, 0.26; 95% CI, 0.14 to 0.46), were associated with a reduced risk of PEP as compared to that of the control. The most effective prophylaxis was ABC (0.87), followed by AC (0.68), AB (0.65), BC (0.56), A (0.49), and B (0.24) according to P-score. Conclusions The results of this network meta-analysis suggest that the more prophylactic methods are employed, the better the outcomes. It appears that for patients with risk factors, we need to prevent PEP through the use of these well proven combination strategies.

Objective: To intraindividually compare hepatocellular carcinoma (HCC) washout between MRIs using hepatobiliary agent (HBA) and extracellular agent (ECA). Materials and Methods: This study included 114 prospectively enrolled patients with chronic liver disease (mean age, 55 ± 9 years; 94 men) who underwent both HBA-MRI and ECA-MRI before surgical resection for HCC between November 2016 and May 2019. For 114 HCCs, the lesion-to-liver visual signal intensity ratio (SIR) using a 5-point scale (-2 to +2) was evaluated in each phase. Washout was defined as negative visual SIR with temporal reduction of visual SIR from the arterial phase. Illusional washout (IW) was defined as a visual SIR of 0 with an enhancing capsule. The frequency of washout and MRI sensitivity for HCC using LR-5 or its modifications were compared between HBA-MRI and ECA-MRI. Subgroup analysis was performed according to lesion size (< 20 mm or ≥ 20 mm). Results: The frequency of portal venous phase (PP) washout with HBA-MRI was comparable to that of delayed phase (DP) washout with ECA-MRI (77.2% [88/114] vs. 68.4% [78/114]; p = 0.134). The frequencies were also comparable when IW was allowed (79.8% [91/114] for HBA-MRI vs. 81.6% [93/114] for ECA-MRI; p = 0.845). The sensitivities for HCC of LR-5 (using PP or DP washout) were comparable between HBA-MRI and ECA-MRI (78.1% [89/114] vs. 73.7% [84/114]; p = 0.458). In HCCs < 20 mm, the sensitivity of LR-5 was higher on HBA-MRI than on ECA-MRI (70.8% [34/48] vs. 50.0% [24/48]; p = 0.034). The sensitivity was similar to each other if IW was added to LR-5 (72.9% [35/48] for HBA-MRI vs. 70.8% [34/48] for ECA-MRI; p > 0.999). Conclusion Extracellular phase washout for HCC diagnosis was comparable between MRIs with both contrast agents, except for tumors < 20 mm. Adding IW could improve the sensitivity for HCC on ECA-MRI in tumors < 20 mm.

Background: Several noninvasive tools are available for the assessment of nonalcoholic fatty liver disease (NAFLD) including clinical and blood biomarkers, transient elastography (TE), and magnetic resonance imaging (MRI) techniques, such as proton density fat fraction (MRI-PDFF) and magnetic resonance elastography (MRE). In the present study, we aimed to evaluate whether magnetic resonance (MR)-based examinations better discriminate the pathophysiologic features and fibrosis progression in NAFLD than other noninvasive methods. Methods: A total of 133 subjects (31 healthy volunteers and 102 patients with NAFLD) were subjected to clinical and noninvasive NAFLD evaluation, with additional liver biopsy in some patients (n=54). Results: MRI-PDFF correlated far better with hepatic fat measured by MR spectroscopy (r=0.978, P<0.001) than with the TE controlled attenuation parameter (CAP) (r=0.727, P<0.001). In addition, MRI-PDFF showed stronger correlations with various pathophysiologic parameters for cellular injury, glucose and lipid metabolism, and inflammation, than the TE-CAP. The MRI-PDFF and TE-CAP cutoff levels associated with abnormal elevation of serum alanine aminotransferase were 9.9% and 270 dB/m, respectively. The MRE liver stiffness measurement (LSM) showed stronger correlations with liver enzymes, platelets, complement component 3, several clinical fibrosis scores, and the enhanced liver fibrosis (ELF) score than the TE-LSM. In an analysis of only biopsied patients, MRE performed better in discriminating advanced fibrosis with a cutoff value of 3.9 kPa than the TE (cutoff 8.1 kPa) and ELF test (cutoff 9.2 kPa). Conclusion Our results suggest that MRI-based assessment of NAFLD is the best non-invasive tool that captures the histologic, pathophysiologic and metabolic features of the disease.

PURPOSE: Patients' gender, which can be one of the most important determinants of traumatic brain injury (TBI) outcomes, is also likely to interact with many other outcome variables of TBI. This multicenter descriptive study investigated gender differences in epidemiological, clinical, treatment, mortality, and variable characteristics in adult TBI patients. METHODS: The selection criteria were defined as patients who had been diagnosed with TBI and were admitted to the hospital between January 1, 2016 and December 31, 2018. A total of 4468 adult TBI patients were enrolled at eight University Hospitals. Based on the list of enrolled patients, the medical records of the patients were reviewed and they were registered online at each hospital. The registered patients were classified into three groups according to the Glasgow coma scale (GCS) score: mild (13-15), moderate (9-12), and severe (3-8), and the differences between men and women in each group were investigated. The risk factors of moderated and severe TBI compared to mild TBI were also investigated. RESULTS: The study included 3075 men and 1393 women and the proportion of total males was 68.8%. Among all the TBI patients, there were significant differences between men and women in age, past history, and GCS score. While the mild and severe TBI groups showed significant differences in age, past history, and clinical symptoms, the moderate TBI group showed significant differences in age, past history, cause of justice, and diagnosis. CONCLUSION To the best of our knowledge, this multicenter study is the first to focus on gender differences of adult patients with TBI in Korea. This study shows significant differences between men and women in many aspects of adult TBI. Therefore, gender differences should be strongly considered in TBI studies.
Adult ; Brain Injuries ; Brain Injuries, Traumatic/epidemiology* ; Female ; Glasgow Coma Scale ; Humans ; Male ; Prospective Studies ; Sex Factors

Objective: To evaluate the prognostic implications of preoperative magnetic resonance imaging (MRI) features of hepatocellular carcinoma (HCC) with a focus on those with targetoid appearance based on the Liver Imaging Reporting and Data System (LI-RADS), as well as known microvascular invasion (MVI) features. Materials and Methods: This retrospective study included 242 patients (190 male; mean age, 57.1 years) who underwent surgical resection of a single HCC (≤ 5 cm) as well as preoperative gadoxetic acid-enhanced MRI between January 2012 and March 2015. LI-RADS category was assigned, and the LR-M category was further classified into two groups according to rim arterial-phase hyperenhancement (APHE). The imaging features associated with MVI were also assessed. The overall survival (OS), recurrence-free survival (RFS), and their associated factors were evaluated. Results: Among the 242 HCCs, 190 (78.5%), 25 (10.3%), and 27 (11.2%) were classified as LR-4/5, LR-M with rim APHE, and LR-M without rim APHE, respectively. LR-M with rim APHE (vs. LR-4/5; hazard ratio [HR] for OS, 5.48 [p = 0.002]; HR for RFS, 2.09 [p = 0.042]) and tumor size (per cm increase; HR for OS, 6.04 [p = 0.009]; HR for RFS, 1.77 [p = 0.014]) but not MVI imaging features (p > 0.05) were independent factors associated with OS and RFS. Compared to the 5-year OS and RFS rates in the LR-4/5 group (93.9% and 66.8%, respectively), the LR-M with rim APHE group had significantly lower rates (68.0% and 45.8%, respectively, both p < 0.05), while the LR-M without rim APHE group did not significantly differ in the survival rates (91.3% and 80.2%, respectively, both p > 0.05). Conclusion Further classification of LR-M according to the presence of rim APHE may help predict the postoperative prognosis of patients with a single HCC.

Objective: To intraindividually compare hepatocellular carcinoma (HCC) washout between MRIs using hepatobiliary agent (HBA) and extracellular agent (ECA). Materials and Methods: This study included 114 prospectively enrolled patients with chronic liver disease (mean age, 55 ± 9 years; 94 men) who underwent both HBA-MRI and ECA-MRI before surgical resection for HCC between November 2016 and May 2019. For 114 HCCs, the lesion-to-liver visual signal intensity ratio (SIR) using a 5-point scale (-2 to +2) was evaluated in each phase. Washout was defined as negative visual SIR with temporal reduction of visual SIR from the arterial phase. Illusional washout (IW) was defined as a visual SIR of 0 with an enhancing capsule. The frequency of washout and MRI sensitivity for HCC using LR-5 or its modifications were compared between HBA-MRI and ECA-MRI. Subgroup analysis was performed according to lesion size (< 20 mm or ≥ 20 mm). Results: The frequency of portal venous phase (PP) washout with HBA-MRI was comparable to that of delayed phase (DP) washout with ECA-MRI (77.2% [88/114] vs. 68.4% [78/114]; p = 0.134). The frequencies were also comparable when IW was allowed (79.8% [91/114] for HBA-MRI vs. 81.6% [93/114] for ECA-MRI; p = 0.845). The sensitivities for HCC of LR-5 (using PP or DP washout) were comparable between HBA-MRI and ECA-MRI (78.1% [89/114] vs. 73.7% [84/114]; p = 0.458). In HCCs < 20 mm, the sensitivity of LR-5 was higher on HBA-MRI than on ECA-MRI (70.8% [34/48] vs. 50.0% [24/48]; p = 0.034). The sensitivity was similar to each other if IW was added to LR-5 (72.9% [35/48] for HBA-MRI vs. 70.8% [34/48] for ECA-MRI; p > 0.999). Conclusion Extracellular phase washout for HCC diagnosis was comparable between MRIs with both contrast agents, except for tumors < 20 mm. Adding IW could improve the sensitivity for HCC on ECA-MRI in tumors < 20 mm.