Glioma grading using multiparametric MRI: head-to-head comparison among dynamic susceptibility contrast, dynamic contrast-enhancement, diffusion-weighted images, and MR spectroscopy.

PURPOSE: To assess the diagnostic accuracy of dynamic susceptibility contrast, dynamic contrast-enhancement, MR spectroscopy (MRS), and diffusion-weighted imaging for differentiating high-grade (HGGs) from low-grade gliomas (LGGs). METHODS: Seventy-two patients (16 LGGs, 56 HGGs) with pathologically confirmed gliomas were retrospectively included. From three-dimensionally segmented tumor, histogram analyses of relative cerebral blood volume (rCBV), volume transfer constant (Ktrans), and apparent diffusion coefficient (ADC) were performed. Choline-to-creatinine ratio (Cho/Cr) was calculated using MRS. Logistic regression analyses were performed to differentiate HGGs (grade ≥ 3) from LGGs (grade ≤ 2). Areas under the receiver operating characteristics curves (AUC) were plotted. Subgroup analysis was performed between IDH-wildtype glioblastomas and IDH-mutant astrocytomas. Pairwise Spearman's correlation coefficients (ρ) were computed. RESULTS: HGGs had higher 95th percentile rCBV, Ktrans and Cho/Cr (P < 0.01) than LGGs. AUC of 95th percentiles of rCBV and Ktrans were 0.79 (95% CI, 0.67-0.91) and 0.74 (95% CI, 0.59-0.88), respectively. AUC of 5th percentile of ADC was 0.63 (95% CI, 0.48-0.79), and that of Cho/Cr was 0.67 (95% CI, 0.52-0.81). IDH-wildtype glioblastomas and IDH-mutant astrocytomas showed significantly different 95th percentile rCBV (P = 0.04) and Ktrans (P < 0.01), with Ktrans showing the highest AUC (0.73, 95% CI 0.57-0.89) in IDH status prediction. Moderate correlations were observed between 95th percentile rCBV and Ktrans (ρ = 0.47), Cho/Cr (ρ = 0.40), and 5th percentile ADC (ρ = -0.36) (all P < 0.01). CONCLUSIONS: The 95th percentile rCBV may be most helpful in discriminating HGGs from LGGs. The 95th percentile Ktrans may aid predicting IDH status of diffuse gliomas.

Adherence to Mediterranean Diet and Depressive Symptomatology Among Boston Area Puerto Ricans.

BACKGROUND: Higher Mediterranean diet (MeD) adherence has been linked with lower depressive symptomatology, but research examining this association is limited, especially among Latinos, including mainland U.S. Puerto Ricans. Hence, we examined cross-sectional and longitudinal associations between MeD adherence and self-reported depressive symptomatology in Boston area Puerto Rican adults. METHODS: The Center for Epidemiologic Studies Depression Scale (CES-D) was used to evaluate depressive symptoms. Adherence to MeD was assessed at all 3 visits. We used multivariable linear regression for baseline cross-sectional analysis, and linear mixed effects modeling over 3 waves of follow-up for longitudinal analysis. We also assessed whether baseline MeD adherence affected 5y CES-D trajectory. We conducted sensitivity analyses among participants without diabetes, and among participants with complete MeD and CES-D measures at all visits. RESULTS: MeD adherence was significantly associated with CES-D score at baseline (ß = -2.0, 95% confidence interval [CI] -4.0, -0.04 for highest vs lowest tertile, p trend = .04) and across 3 waves (ß = -1.9, 95% CI = -3.0, -0.8 for highest vs lowest tertile, p trend = .0005). Results were similar in analyses restricted to participants without diabetes, as well as among participants with complete CES-D and MeD scores at all visits. CONCLUSIONS: While CES-D score was consistently lower in those with higher MeD adherence over 5 years of follow up, no relationship between baseline MeD adherence and 5y CES-D trajectory was observed.

Classification of dental caries pattern in 12-year-old Korean adolescents by multivariate analysis / 대한구강보건학회지

Objectives@#The purpose of this study was to analyze the pattern of dental caries in 12-year-old Korean adolescents through multivariate analysis. @*Methods@#This study used raw data from the 2015 Korea Children’s Oral Health Survey. The study participants were 12-year-old adolescents. A total of 27,291 people participated in the questionnaire and oral test. The statistical analysis methods used were multidimensional scaling, cluster analysis, and factor analysis. @*Results@#The result was derived after analyzing the dental caries pattern of teeth and tooth surface by multi-dimensional scaling method, cluster analysis method, and factor analysis. Morphologically homologous teeth were gathered to form clusters. Caries occurrence showed a more similar caries experience pattern when the types of tooth surfaces, such as occlusal and occlusal surfaces, were the same than when they were different. @*Conclusions@#Epidemiological data on the pattern of dental caries in 12-year-old adolescents can be used as basic data to create evidence-based dental caries management plans.

The application of the health belief model in oral health-related dietary behavior / 대한구강보건학회지

Objectives@#This study aimed to investigate the relationship between oral health beliefs and oral health-related dietary behavior. @*Methods@#The participants of this cross-sectional study were 728 middle school students living in Jeonju who were selected through convenience sampling. For the survey, self-administered questionnaires were completed in individual settings. The analysis model was the oral health belief model, and the analysis method was path analysis. @*Results@#Among oral health beliefs, perceived susceptibility, perceived severity, perceived barriers, and self-efficacy were found to be correlated with the oral health-related dietary behavior index. Multiple regression analysis showed that factors affecting the oral health-related dietary behavior index were gender (female), perceived susceptibility, perceived severity, perceived barriers, and self-efficacy. Path analysis showed that variables that significantly impact the oral health-related dietary behavior index are perceived susceptibility, perceived benefits, perceived barriers, and likelihood of action. The factor with the greatest impact was perceived barrier; the lower the barrier, the higher the level of dietary behavior undertaken to prevent dental caries. @*Conclusions@#Oral health beliefs are related to oral health-related dietary behavior. Since perceived barriers had the greatest correlation with oral health-related dietary behavior, measures must be taken to help remove the barriers.

Effect of oral health-related self efficacy and social support on oral health-related quality of life among adolescents / 대한구강보건학회지

Objectives@#This study aimed to examine the effects of oral health-related self efficacy and social support on oral health-related quality of life, and analyze the related factors. @*Methods@#A cross-sectional study was carried out on 979 high school students living in Iksan. Data were collected from January 15 to 30, 2014. Individual self-administered surveys were conducted through the sampling method. The contents of the survey were the characteristics of the subjects, oral health-related self efficacy (OHSE), social support related to oral health (OHSS), and quality of life related to oral health (QHRQoL). A survey tool designed by the author was used to measure OHSE and OHSS. QHRQoL used Child Oral Health Impact Profile-Short Form 19 (COHIP-SF 19) for examination. The statistical analysis methods used were mean difference, correlation, and multiple regression analyses. @*Results@#QHRQol was correlated with OHSE, but not OHSS. Per the multivariate analysis, factors that affected QHRQoL were gender, mother’s education level, academic stress, and OHSE; OHSS did not have any effect. @*Conclusions@#It was found that OHSE influenced QHRQoL. Therefore, it is necessary to develop education programs that can enhance OHSE.

Association between oral health status and school loss in adolescents / 대한구강보건학회지

Objectives@#This study aimed to investigate the association between school loss due to dental disease and oral health status in adolescents. @*Methods@#The study participants were 881 adolescents (453 middle and 428 high school students).Data were collected through a self-administered survey and oral examination. Chi-square test and t-test were used to analyze the association between school loss due to dental disease and oral health status, and multiple logistic regression was used to analyze the factors influencing school loss. @*Results@#Dental caries was the leading cause of school loss. School loss due to dental disease was more prevalent in the group with a higher number of carious teeth than in the group without dental caries. According to bivariate analysis, school loss due to dental disease was associated with toothache, gingival bleeding, maxillofacial trauma, and caries. When controlling demographic variables, gingival bleeding, maxillofacial trauma, and dental caries were associated with school absence.Moreover, maxillofacial trauma was associated with school absence period up to 1 year. @*Conclusions@#Therefore, oral health status and school loss of adolescents are associated, and the importance of oral health in adolescents should be emphasized.

Dental caries incidence in permanent teeth of 12-year-old children in Korea / 대한구강보건학회지

Objectives@#The objective of this study was to analyze dental caries incidence in the permanent teeth of 12-year-old children. @*Methods@#This study used the raw data from the 2015 Korean children’s oral health survey. Participants of the research were 12-year-old children in their first year of middle school. A total of 27,291 people participated in the questionnaire and oral examination. Statistical analysis was performed using complex samples frequency analysis and contingency coefficient phi (φ). @*Results@#Dental caries predominately developed symmetrically with a higher tendency for left-right symmetry than for maxillary-mandibular symmetry in the mouth. The incidence of dental caries between adjacent teeth had a statistically significant correlation and was highest in the first and second premolars. @*Conclusions@#Information on symmetry in the development of dental caries and the association of dental caries incidence between adjacent teeth of 12-year-old children should be actively utilized when establishing evidence-based dental caries management plans.

Clinical and Radiological Features of Korean Patients With Anti-HMGCR Myopathy

Background@#and Purpose To understand the characteristics of Korean patients with anti-3-hydroxy-3-methylglutaryl-coenxyme A reductase (HMGCR) myopathy, we measured antiHMGCR antibodies and analyzed the clinical, radiological, and pathological features of patients with anti-HMGCR myopathy. @*Methods@#We measured titers of anti-HMGCR antibodies in the sera of 99 patients with inflammatory myopathy, 36 patients with genetic myopathy, and 63 healthy subjects using an enzyme-linked immunosorbent assay. We tested 16 myositis-specific autoantibodies (MSAs) in all patients with anti-HMGCR myopathy. @*Results@#Positivity for the anti-HMGCR antibody was observed in 17 (4 males and 13 females) of 99 patients with inflammatory myopathy. The median age at symptom onset was 60 years.Ten (59%) of the patients with anti-HMGCR positivity had taken statins. The titer of antiHMGCR antibodies was significantly higher in the statin-naïve group (median=230 U/mL, interquartile range=170–443 U/mL) than in the statin-exposed group (median=178 U/mL, interquartile range=105–210 U/mL, p=0.045). The most common symptom was proximal muscle weakness in 15 patients (88%), followed by myalgia in 9 (53%), neck weakness in 4 (24%), dysphagia in 3 (18%), and skin lesions in 2 (12%). The median titer of anti-HMGCR antibody was 202 U/mL. We found eight different MSAs in nine (53%) patients. The median disease duration from symptom onset to diagnosis was significantly shorter in the MSA-positive group than in the MSA-negative group (p=0.027). @*Conclusions@#Our study was the first to measure anti-HMGCR antibodies in inflammatory myopathy. It has provided new findings, including the suggestion of the coexistence of other MSAs in Korean patients.

Effects of Exhaustive Exercise on Inflammatory, Apoptotic, and Antioxidative Signaling Pathways in Human Peripheral Blood Mononuclear Cells

In the present study, we investigated the effects of exhaustive exercise and recovery on inflammatory, pro-apoptotic, and anti-oxidative responses in human peripheral blood mononuclear cells (PBMCs). Sixteen volunteers participated in a guided physical activity program in which they were subjected to progressive exercise on the treadmill until they were exhausted followed by an 1-hour recovery period. Isolated human PBMCs were collected before exercise, immediately after exercise, and after 1-hour recovery. Exhaustive exercise induced expression of heme oxygenase-1 and glutamate cysteine ligase catalytic subunit and activation of NF-κB and NF-E2 related factor 2 (Nrf2). Apoptosis, as measured by activity and cleavage of caspase-3 and its substrate PARP also significantly increased. However, induction of redox signaling and the pro-apoptotic response fully returned to the baseline level during the 1-hour recovery period. On the other hand, COX-2 expression was continuously elevated after exercise cessation throughout the 1-hour recovery period. Taking all these findings into account, we conclude that exhaustive exercise transiently induces Nrf2-mediated antioxidant gene expression and eliminates damaged cells through apoptosis as part of an adaptive cytoprotective response against oxidative and inflammatory stress.

Resting heart rate and cardiovascular outcomes in patients with non‑paroxysmal atrial fibrillation: CODE‑AF registry

Background@#The prognostic significance of resting heart rate and its therapeutic target in atrial fibrillation (AF) is uncertain. We sought to investigate the relationship between resting heart rate and cardiovascular outcomes in patients with non-paroxysmal AF (non-PAF). @*Methods@#In this propensity score-weighted, multi-center prospective cohort study, 3217 patients with non-PAF were analyzed. Patients were categorized according to the baseline resting heart rate and cardiovascular outcomes were accessed for a median follow-up of 30 months. The primary outcome was a composite of cardiovascular death, heart failure hospitalization, and myocardial infarction/critical limb ischemia. @*Results@#Freedom from primary outcome was longest among patients with resting heart rate 80–99 beats per minute (bpm) whereas shortest among those with ≤ 59 bpm (weighted log rank, p = 0.008). Compared with heart rate ≥ 100 bpm, resting heart rate 80–99 and 60–79 bpm was associated with reduced risk of primary outcome (weighted hazard ratio [WHR] 0.52, 95% confidence interval [CI] 0.32–0.84, p = 0.008 and WHR 0.58, 95% CI 0.37–0.92, p = 0.021 for heart rate 80–99 and 60–79 bpm, respectively). Using weighted restricted cubic spline curves, there was a U-shaped association between the resting heart rate and primary outcome with reduced risk of primary outcome in heart rate range of 68–99 bpm. This association was maintained regardless of atrioventricular node (AVN) blocker use or persistent/permanent AF (p for interaction 0.767 for AVN blocker use and 0.720 for AF type). @*Conclusion@#Resting heart rate was associated with cardiovascular outcomes in patients with non-PAF and those with resting heart rate between 68 and 99 bpm had lower risk of adverse cardiovascular events regardless of AVN blocker use or persistent/permanent AF.

Association between alcohol consumption and subclinical atrial fibrillation

Background@#It has become important to identify and manage risk factors for subclinical atrial fibrillation (AF) with an increase in its detection rate. Thus, this research aimed to investigate whether alcohol consumption contrib‑ utes to the development of subclinical AF. @*Methods@#This prospective study enrolled 467 patients without AF from a multicenter pacemaker registry. The incidence of subclinical AF (episodes of atrial rate > 220 beats per minute without symptoms) was compared between alcohol-drinking and non-drinking groups. @*Results@#During followup (median 18 months), the incidence and risk of long-duration atrial high-rate episodes (AHRE) ≥ 24 h were increased in the alcohol group compared to the non-alcohol group [5.47 vs. 2.10 per 100 personyears, adjusted hazard ratio (HR), 2.83; 95% confidence interval (CI), 1.14–7.04; P = 0.03]. After propensity score match‑ ing, the incidence and risk of long-duration AHRE were higher in the alcohol group (6.97 vs. 1.27 per 100 personyears, adjusted HR, 7.84; 95% CI, 1.21–50.93; P = 0.03). The mean burden of long-duration subclinical AF was higher in the alcohol group than in the non-alcohol group (0.18 vs. 1.61% during follow-up, P = 0.08). @*Conclusion@#Alcohol consumption was associated with an increased risk of subclinical AF. Long-duration AHRE inci‑ dence and AHRE burden were higher in alcohol drinkers than in non-drinkers.

Long-term Outcomes of Endoscopic Intraductal Radiofrequency Ablation for Ampullary Adenoma with Intraductal Extension after Endoscopic Snare Papillectomy

Background/Aims@#There are limitations in treating ampullary adenomas with intraductal extension using conventional endoscopic modalities. Endoscopic intraductal radiofrequency ablation (ID-RFA) may be useful for treating intraductal (common bile duct [CBD] and/or pancreatic duct [PD]) extensions of ampullary adenomas, but long-term data are lacking. We thus evaluated the long-term outcomes of endoscopic ID-RFA for managing ampullary adenomas with intraductal extension. @*Methods@#Prospectively collected endoscopic ID-RFA database at Asan Medical Center was reviewed to identify consecutive patients with ampullary adenoma who underwent ID-RFA for intraductal extension between January 2018 and August 2021. Technical success, short-term and long-term clinical success, and adverse events were evaluated. @*Results@#A total of 29 patients (14 CBD, 1 PD, and 14 CBD and PD) were analyzed. All patients had undergone endoscopic snare papillectomy prior to ID-RFA. A median of one session of IDRFA (range, 1 to 3) for residual or relapsed intraductal extension of ampullary adenoma were successfully performed (technical success=100%). Both biliary and pancreatic stenting were routinely performed after ID-RFA to prevent ductal stricture. After a median follow-up of 776 days (interquartile range, 470 to 984 days), the short-term and long-term clinical success rates were 93% and 76%, respectively. Seven patients experienced procedural adverse events and three patients developed ductal strictures. @*Conclusions@#Endoscopic ID-RFA showed good long-term outcomes in treating residual or relapsed ampullary adenomas with intraductal extension. Repeated ID-RFA may be considered as an option for managing recurrence. Further studies are needed to standardize the procedure.

Beneficial Effects of a Curcumin Derivative and Transforming Growth Factor-β Receptor I Inhibitor Combination on Nonalcoholic Steatohepatitis

Background@#Curcumin 2005-8 (Cur5-8), a derivative of curcumin, improves fatty liver disease via AMP-activated protein kinase activation and autophagy regulation. EW-7197 (vactosertib) is a small molecule inhibitor of transforming growth factor β (TGF-β) receptor I and may scavenge reactive oxygen species and ameliorate fibrosis through the SMAD2/3 canonical pathway. This study aimed to determine whether co-administering these two drugs having different mechanisms is beneficial. @*Methods@#Hepatocellular fibrosis was induced in mouse hepatocytes (alpha mouse liver 12 [AML12]) and human hepatic stellate cells (LX-2) using TGF-β (2 ng/mL). The cells were then treated with Cur5-8 (1 μM), EW-7197 (0.5 μM), or both. In animal experiments were also conducted during which, methionine-choline deficient diet, Cur5-8 (100 mg/kg), and EW-7197 (20 mg/kg) were administered orally to 8-week-old C57BL/6J mice for 6 weeks. @*Results@#TGF-β-induced cell morphological changes were improved by EW-7197, and lipid accumulation was restored on the administration of EW-7197 in combination with Cur5-8. In a nonalcoholic steatohepatitis (NASH)-induced mouse model, 6 weeks of EW-7197 and Cur5-8 co-administration alleviated liver fibrosis and improved the nonalcoholic fatty liver disease (NAFLD) activity score. @*Conclusion@#Co-administering Cur5-8 and EW-7197 to NASH-induced mice and fibrotic hepatocytes reduced liver fibrosis and steatohepatitis while maintaining the advantages of both drugs. This is the first study to show the effect of the drug combination against NASH and NAFLD. Similar effects in other animal models will confirm its potential as a new therapeutic agent.

Arthroscopic transosseous anchorless rotator cuff repair reduces bone defects related to peri-implant cyst formation: a comparison with conventional suture anchors using propensity score matching

Background@#The transosseous anchorless repair (ToR) technique was recently introduced to avoid suture anchor-related problems. While favorable outcomes of the ToR technique have been reported, no previous studies on peri-implant cyst formation with the ToR technique exist. Therefore, this study compared the clinical outcomes and prevalence of peri-implant cyst formation between the ToR technique and the conventional transosseous equivalent technique using suture anchors (SA). @*Methods@#Cases with arthroscopic rotator cuff repair (ARCR) between 2016 and 2018 treated with the double-row suture bridge technique were retrospectively reviewed. Patients were divided into ToR and SA groups. To compare clinical outcomes, 19 ToR and 57 SA cases without intraoperative implant failure were selected using propensity score matching (PSM). While intraoperative implant failure rate was analyzed before PSM, retear rate, peri-implant cyst formation rate, and functional outcomes were compared after PSM. @*Results@#The intraoperative implant failure rate (ToR, 8% vs. SA, 15.3%) and retear rate (ToR, 5.3% vs. SA, 19.3%) did not differ between the two groups (all P>0.05). However, peri-implant cysts were not observed in the ToR group, while they were observed in 16.7% of the SA group (P=0.008). Postoperative functional outcomes were not significantly different between the two groups (all P>0.05). @*Conclusions@#The ToR technique produced comparable clinical outcomes to conventional techniques. Considering the prospect of potential additional surgeries, the absence of peri-implant cyst formation might be an advantage of ToR. Furthermore, ToR might reduce the medical costs related to suture anchors and, thereby, could be a useful option for ARCR.Level of evidence: III.

Altered Functional Connectivity of the Nucleus Accumbens and Amygdala in Cyber Addiction: A Resting State Functional Magnetic Resonance Imaging Study

Objective@#Cyber addiction, which is more vulnerable in adolescents, is defined as the excessive use of computers and the Internet that causes serious psychological, social, and physical problems. In this study, we investigated the resting-state functional connectivity (rsFC) in adolescents with cyber addiction. @*Methods@#We collected and analyzed resting-state functional neuroimaging data of 20 patients with cyber addiction, aged 13−18 years, and 27 healthy controls. Based on previous studies, the seed regions included the dorsolateral prefrontal cortex, medial orbitofrontal cortex, lateral orbitofrontal cortex, dorsal anterior cingulate cortex, insula, hippocampus, amygdala, nucleus accumbens, and the ventral tegmental area. Seed-to-voxel analyses were performed to investigate the differences between patients and healthy controls. A correlation analysis between rsFC and cyber addiction severity was also performed. @*Results@#Patients with cyber addiction showed the following characteristics: increased positive rsFC between the left insular−right middle temporal gyrus; increased positive rsFC between the right hippocampus−right precentral gyrus;increased positive rsFC between the right amygdala−right precentral gyrus and right parietal operculum cortex; increased negative rsFC between the left nucleus accumbens−right cerebellum crus II and right cerebellum VI. @*Conclusion@#Adolescents with cyber addiction show altered functional connectivity during the resting state. The findings of this study may help us better understand the neuropathology of cyber addiction in adolescents.

Analysis of Plasma Circulating Tumor DNA in Borderline Resectable Pancreatic Cancer Treated with Neoadjuvant Modified FOLFIRINOX: Clinical Relevance of DNA Damage Repair Gene Alteration Detection / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#There are no reliable biomarkers to guide treatment for patients with borderline resectable pancreatic cancer (BRPC) in the neoadjuvant setting. We used plasma circulating tumor DNA (ctDNA) sequencing to search biomarkers for patients with BRPC receiving neoadjuvant mFOLFIRINOX in our phase 2 clinical trial (NCT02749136). @*Materials and Methods@#Among the 44 patients enrolled in the trial, patients with plasma ctDNA sequencing at baseline or post-operation were included in this analysis. Plasma cell-free DNA isolation and sequencing were performed using the Guardant 360 assay. Detection of genomic alterations, including DNA damage repair (DDR) genes, were examined for correlations with survival. @*Results@#Among the 44 patients, 28 patients had ctDNA sequencing data qualified for the analysis and were included in this study. Among the 25 patients with baseline plasma ctDNA data, 10 patients (40%) had alterations of DDR genes detected at baseline, inclu-ding ATM, BRCA1, BRCA2 and MLH1, and showed significantly better progression-free survival than those without such DDR gene alterations detected (median, 26.6 vs. 13.5 months; log-rank p=0.004). Patients with somatic KRAS mutations detected at baseline (n=6) had significantly worse overall survival (median, 8.5 months vs. not applicable; log-rank p=0.003) than those without. Among 13 patients with post-operative plasma ctDNA data, eight patients (61.5%) had detectable somatic alterations. @*Conclusion@#Detection of DDR gene mutations from plasma ctDNA at baseline was associated with better survival outcomes of pati-ents with borderline resectable pancreatic ductal adenocarcinoma treated with neoadjuvant mFOLFIRINOX and may be a prognostic biomarker.

Survival Benefit of Adjuvant Chemotherapy in Patients with Pancreatic Ductal Adenocarcinoma Who Underwent Surgery Following Neoadjuvant FOLFIRINOX / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#The benefit of adjuvant chemotherapy following curative-intent surgery in pancreatic ductal adenocarcinoma (PDAC) patients who had received neoadjuvant FOLFIRINOX is unclear. This study aimed to assess the survival benefit of adjuvant chemotherapy in this patient population. @*Materials and Methods@#This retrospective study included 218 patients with localized non-metastatic PDAC who received neoadjuvant FOLFIRINOX and underwent curative-intent surgery (R0 or R1) between January 2017 and December 2020. The association of adjuvant chemotherapy with disease-free survival (DFS) and overall survival (OS) was evaluated in overall patients and in the propensity score matched (PSM) cohort. Subgroup analysis was conducted according to the pathology-proven lymph node status. @*Results@#Adjuvant chemotherapy was administered to 149 patients (68.3%). In the overall cohort, the adjuvant chemotherapy group had significantly improved DFS and OS compared to the observation group (DFS: median, 13.8 months [95% confidence interval (CI), 11.0 to 19.1] vs. 8.2 months [95% CI, 6.5 to 12.0]; p < 0.001; and OS: median, 38.0 months [95% CI, 32.2 to not assessable] vs. 25.7 months [95% CI, 18.3 to not assessable]; p=0.005). In the PSM cohort of 57 matched pairs of patients, DFS and OS were better in the adjuvant chemotherapy group than in the observation group (p < 0.001 and p=0.038, respectively). In the multivariate analysis, adjuvant chemotherapy was a significant favorable prognostic factor (vs. observation; DFS: hazard ratio [HR], 0.51 [95% CI, 0.36 to 0.71; p < 0.001]; OS: HR, 0.45 [95% CI, 0.29 to 0.71; p < 0.001]). @*Conclusion@#Among PDAC patients who underwent surgery following neoadjuvant FOLFIRINOX, adjuvant chemotherapy may be associated with improved survival. Randomized studies should be conducted to validate this finding.

Prognostic significance of programmed cell death-ligand 1 expression on immune cells and epithelialmesenchymal transition expression in patients with hepatocellular carcinoma

Purpose@#Immune checkpoint inhibitors (ICIs) have been shown significant oncological improvements in several cancers.However, ICIs are still in their infancy in hepatocellular carcinoma (HCC). Programmed cell death-ligand 1 (PD-L1), tumorinfiltrating lymphocytes (TILs), and epithelial-mesenchymal transition (EMT) have been known as prognostic factors in HCC. Therefore, we have focused on identifying the molecular mechanisms between each marker to evaluate a predictive role. @*Methods@#Formalin-fixed paraffin-embedded samples were obtained from 166 patients with HCC who underwent surgery. The expression of PD-L1 and TILs and EMT marker were evaluated by immunohistochemical analysis. @*Results@#The multivariate analysis showed that TIL expression (hazard ratio [HR], 0.483; 95% confidence interval [CI], 0.269–0.866; P = 0.015) were independent prognostic factors for overall survival. The prognostic factors for disease-free survival were EMT marker expression (HR, 1.565; 95% CI, 1.019–2.403; P = 0.005). Patients with high expression of TILs had significantly better survival compared to patients with low expression (P = 0.023). Patients who were TIL+/EMT– showed a significantly better prognosis than those who were TIL–/EMT+ (P = 0.049). @*Conclusion@#This study demonstrates that PD-L1 expression of TILs is closely associated with EMT marker expression in HCC. Clinical investigations using anti–PD-1/PD-L1 inhibitors in patients with EMT-associated PD-L1 upregulation are warranted.

Hypersensitivity reactions to ibuprofen and acetaminophen: A report of case with literature review

The higher the use of nonsteroidal anti-inflammatory drugs (NSAIDs), the more reports of adverse drug reactions, especially in children than in adults. As patients with fever take several NSAIDs alternatively, suspected symptoms allergic to drugs with different chemical structures are also experienced in the clinical field. This is because it appears not only through immunological mechanisms but also through cross-intolerant reactions. Therefore, when hypersensitivity to one or more NSAIDs is present, it is important to distinguish between the 2 mechanisms for future treatment planning. Although it is difficult to distinguish between the 2 mechanisms by clinical history, drug provocation test with aspirin is helpful in diagnosis. A 4-year-old patient who had urticaria/angioedema and shortness of breath after taking ibuprofen and acetaminophen visited Kangwon National University Hospital for a treatment plan using antipyretics and/or analgegics forward. We propose a diagnosis and treatment protocol for such patients with a brief literature review.

Umbelliferone Ameliorates Hepatic Steatosis and Lipid-Induced ER Stress in High-Fat Diet-Induced Obese Mice

Purpose@#Among the characteristics of non-alcoholic fatty liver disease (NAFLD), hepatic steatosis is due to excessive fat accumulation and causes liver damage and lipotoxicity, which are associated with insulin resistance, endoplasmic reticulum (ER) stress, and apoptosis. Umbelliferone (UMB) has various powerful pharmacological properties, such as antioxidant, anti-hyperglycemic, anti-viral, and anti-inflammatory effects. However, the mechanism of action in hepatic steatosis and lipid-induced ER stress is still unclear. Thus, the efficacy of UMB in hepatic steatosis and palmitate (PA)-induced hepatocellular lipotoxicity was evaluated in the present study. @*Materials and Methods@#Male C57BL/6J mice (n=40) were divided into four groups: regular diet (RD), UMB-supplemented RD, high-fat diet (HFD), and UMB-supplemented HFD. All mice were fed orally for 12 weeks. In addition, the effects of UMB on lipotoxicity were investigated in AML12 cells treated with PA (250 μM) for 24 h; Western blot analysis was used to evaluate the changes in ER stress and apoptotic-associated proteins. @*Results@#Administration with UMB in HFD-fed mice reduced lipid accumulation and hepatic triglyceride (TG) as well as serum insulin and glucose levels. In AML12 cells, UMB treatment reduced lipid accumulation as indicated by decreases in the levels of lipogenesis markers, such as SREBP1, FAS, PPAR-γ, and ADRP. Furthermore, UMB reduced both oxidative stress and ER stress-related cellular apoptosis. @*Conclusion@#UMB supplementation ameliorated hepatic steatosis and improved insulin resistance by inhibiting lipid accumulation and regulating ER stress. These findings strongly suggest that UMB may be a potential therapeutic compound against NAFLD.