Background: and Purpose We delineated the association between otolithic dysfunction and blood pressure (BP) variability. Methods: We prospectively recruited 145 consecutive patients (age=71 [59–79] years, median [interquartile range]; 76 females) with orthostatic intolerance between December 2021 and December 2023 at a tertiary hospital in South Korea. Each patient underwent evaluations of cervical and ocular vestibular-evoked myogenic potentials (oVEMPs), 24-h noninvasive ambulatory BP monitoring (ABPM), and a head-up tilt-table test using the Finometer device. As measures of BP variability, the standard deviations (SDs) of the systolic BP (SBP SD) and the diastolic BP were calculated based on serial ABPM recordings. Patients were divided into those with orthostatic hypotension (OH, n=68) and those with a normal head-up tilt-table test despite orthostatic intolerance (NOI, n=77) groups. Results: A multivariable logistic regression analysis showed that OH was associated with bilateral oVEMP abnormalities (p=0.021), SBP SD (p=0.012), and female sex (p=0.004). SBP SD was higher in patients with OH than in those with NOI (p<0.001), and was not correlated with n1–p1 amplitude (p=0.491) or normalized p13–n23 amplitude (p=0.193) in patients with OH.The sensitivity and specificity for differentiating OH from NOI were 72.1% and 67.5%, respectively, at a cutoff value of 12.7 mm Hg for SBP SD, with an area under the receiver operating characteristic curve of 0.73. Conclusions Bilaterally deficient oVEMP responses may be associated with OH regardless of 24-h BP variability, reflecting the integrity of the otolith-autonomic reflex during orthostasis. Alternatively, 24-h BP variability is predominantly regulated by the baroreflex, which also participates in securing orthostatic tolerance complementary to the vestibulo-autonomic reflex.

Background: and Purpose We delineated the association between otolithic dysfunction and blood pressure (BP) variability. Methods: We prospectively recruited 145 consecutive patients (age=71 [59–79] years, median [interquartile range]; 76 females) with orthostatic intolerance between December 2021 and December 2023 at a tertiary hospital in South Korea. Each patient underwent evaluations of cervical and ocular vestibular-evoked myogenic potentials (oVEMPs), 24-h noninvasive ambulatory BP monitoring (ABPM), and a head-up tilt-table test using the Finometer device. As measures of BP variability, the standard deviations (SDs) of the systolic BP (SBP SD) and the diastolic BP were calculated based on serial ABPM recordings. Patients were divided into those with orthostatic hypotension (OH, n=68) and those with a normal head-up tilt-table test despite orthostatic intolerance (NOI, n=77) groups. Results: A multivariable logistic regression analysis showed that OH was associated with bilateral oVEMP abnormalities (p=0.021), SBP SD (p=0.012), and female sex (p=0.004). SBP SD was higher in patients with OH than in those with NOI (p<0.001), and was not correlated with n1–p1 amplitude (p=0.491) or normalized p13–n23 amplitude (p=0.193) in patients with OH.The sensitivity and specificity for differentiating OH from NOI were 72.1% and 67.5%, respectively, at a cutoff value of 12.7 mm Hg for SBP SD, with an area under the receiver operating characteristic curve of 0.73. Conclusions Bilaterally deficient oVEMP responses may be associated with OH regardless of 24-h BP variability, reflecting the integrity of the otolith-autonomic reflex during orthostasis. Alternatively, 24-h BP variability is predominantly regulated by the baroreflex, which also participates in securing orthostatic tolerance complementary to the vestibulo-autonomic reflex.

Background: and Purpose We delineated the association between otolithic dysfunction and blood pressure (BP) variability. Methods: We prospectively recruited 145 consecutive patients (age=71 [59–79] years, median [interquartile range]; 76 females) with orthostatic intolerance between December 2021 and December 2023 at a tertiary hospital in South Korea. Each patient underwent evaluations of cervical and ocular vestibular-evoked myogenic potentials (oVEMPs), 24-h noninvasive ambulatory BP monitoring (ABPM), and a head-up tilt-table test using the Finometer device. As measures of BP variability, the standard deviations (SDs) of the systolic BP (SBP SD) and the diastolic BP were calculated based on serial ABPM recordings. Patients were divided into those with orthostatic hypotension (OH, n=68) and those with a normal head-up tilt-table test despite orthostatic intolerance (NOI, n=77) groups. Results: A multivariable logistic regression analysis showed that OH was associated with bilateral oVEMP abnormalities (p=0.021), SBP SD (p=0.012), and female sex (p=0.004). SBP SD was higher in patients with OH than in those with NOI (p<0.001), and was not correlated with n1–p1 amplitude (p=0.491) or normalized p13–n23 amplitude (p=0.193) in patients with OH.The sensitivity and specificity for differentiating OH from NOI were 72.1% and 67.5%, respectively, at a cutoff value of 12.7 mm Hg for SBP SD, with an area under the receiver operating characteristic curve of 0.73. Conclusions Bilaterally deficient oVEMP responses may be associated with OH regardless of 24-h BP variability, reflecting the integrity of the otolith-autonomic reflex during orthostasis. Alternatively, 24-h BP variability is predominantly regulated by the baroreflex, which also participates in securing orthostatic tolerance complementary to the vestibulo-autonomic reflex.

Background and Objectives: Early diastolic mitral annular tissue (e’) velocity is a commonly used marker of left ventricular (LV) diastolic function. This study aimed to investigate the prognostic implications of e’ velocity in patients with mitral regurgitation (MR). Methods: This retrospective cohort study included 1,536 consecutive patients aged <65 years with moderate or severe chronic primary MR diagnosed between 2009 and 2018. The primary and secondary outcomes were all-cause and cardiovascular mortality, respectively.According to the current guidelines, the cut-off value of e’ velocity was defined as 7 cm/s. Results: A total of 404 individuals were enrolled (median age, 51.0 years; 64.1% male; 47.8% severe MR). During a median 6.0-year follow-up, there were 40 all-cause mortality and 16 cardiovascular deaths. Multivariate analysis revealed a significant association between e’ velocity and all-cause death (adjusted hazard ratio [aHR], 0.770; 95% confidence interval [CI], 0.634–0.935; p=0.008) and cardiovascular death (aHR, 0.690; 95% CI, 0.477–0.998;p=0.049). Abnormal e’ velocity (≤7 cm/s) independently predicted all-cause death (aHR, 2.467; 95% CI, 1.170–5.200; p=0.018) and cardiovascular death (aHR, 5.021; 95% CI, 1.189–21.211; p=0.028), regardless of symptoms, LV dimension and ejection fraction. Subgroup analysis according to sex, MR severity, mitral valve replacement/repair, and symptoms, showed no significant interactions. Including e’ velocity in the 10-year risk score improved reclassification for mortality (net reclassification improvement [NRI], 0.154; 95% CI, 0.308– 0.910; p<0.001) and cardiovascular death (NRI, 1.018; 95% CI, 0.680–1.356; p<0.001). Conclusions In patients aged <65 years with primary MR, e’ velocity served as an independent predictor of all-cause and cardiovascular deaths.

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.

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.

Background: This study investigates the long-term efficacy and safety of evogliptin add-on therapy in patients with inadequately controlled type 2 diabetes mellitus (T2DM) previously received dapagliflozin and metformin (DAPA/MET) combination. Methods: In this multicenter randomized placebo-controlled phase 3 trial, patients with glycosylated hemoglobin (HbA1c) levels 7.0% to 10.5% (n=283) previously used DAPA 10 mg plus MET (≥1,000 mg) were randomly assigned to the evogliptin 5 mg once daily or placebo group (1:1). The primary endpoint was the difference in the HbA1c level from baseline at week 24, and exploratory endpoints included the efficacy and safety of evogliptin over 52 weeks (trial registration: ClinicalTrials.gov NCT04170998). Results: Evogliptin add-on to DAPA/MET therapy was superior in HbA1c reduction compared to placebo at weeks 24 and 52 (least square [LS] mean difference, –0.65% and –0.55%; 95% confidence interval [CI], –0.79 to –0.51 and –0.71 to –0.39; P<0.0001). The proportion of patients achieving HbA1c <7% was higher in the triple combination group at week 52 (32.14% vs. 8.51% in placebo; odds ratio, 5.62; P<0.0001). Evogliptin significantly reduced the fasting glucose levels and mean daily glucose levels with improvement in homeostatic model assessment of β-cell function (LS mean difference, 9.04; 95% CI, 1.86 to 16.21; P=0.0138). Adverse events were similar between the groups, and no serious adverse drug reactions were reported in the evogliptin group. Conclusion Long-term triple combination with evogliptin added to DAPA/MET showed superior HbA1c reduction and glycemic control compared to placebo at 52 weeks and was well tolerated.

Background/Aims: This study aimed to examine the independent and synergistic association of aerobic physical activity and resistance exercise with nonalcoholic fatty liver disease (NAFLD) using a nationwide representative database. Methods: This was a cross-sectional study using data from the Korea National Health and Nutritional Examination Survey between 2007 and 2010. Multiple logistic regression models were used to examine the independent and synergistic (additive interaction) associations of aerobic physical activity and resistance exercise with NAFLD after adjusting for multiple covariates. Results: The prevalence of NAFLD was 26.2% for men and 17.6% for women. In the fully adjusted multiple logistic regression model to examine the independent association of aerobic physical activity or resistance exercise with NAFLD, the odds ratios for NAFLD were significantly decreased in both men (p=0.03) and women (p<0.01) who had highly active aerobic physical activity. Regarding the frequency of resistance exercise, the odds ratio for NAFLD was decreased in men who did resistance exercise ≥5 days per week (p=0.04), but not in women (p=0.19). How-ever, when investigating the synergistic associations of aerobic physical activity and resistance exercise, the odds ratios for NAFLD significantly decreased when the frequency of both exercises increased together in both men (p for interaction <0.01) and women (p for interaction<0.01). Conclusions Combining aerobic physical activity and resistance exercise had a synergistic preventive association for NAFLD in Korean men and women.

Background: This longitudinal study examined risk factors for future suicidality among North Korean defectors (NKDs) living in South Korea. Methods: The subjects were 300 NKDs registered with a regional adaptation center (the Hana Center) in South Korea. Face-to-face interviews were conducted using the North Korean version of the World Health Organization’s Composite International Diagnostic Interview to diagnose mental disorders according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. Subjects were also asked about sociodemographic and clinical factors at baseline. At follow-up after three years, the NKDs (n = 172 respondents) were asked to participate in an online survey, responding to self-questionnaires about suicidality. Logistic regression analyses were used to explore associations between baseline variables and future suicidality among NKDs. Results: Thirty (17.4%) of the 172 survey respondents reported suicidality at follow-up. The presence of health problems over the past year, any prior suicidality at baseline, a higher score on a trauma-related scale, and a lower score on a resilience scale at baseline were associated with greater odds of suicidality at follow-up after adjusting for age, sex, and educational level. Of all mental disorder categories, major depressive disorder, dysthymia, agoraphobia, and social phobia were also associated with significantly increased odds of suicidality at follow-up after adjusting for age, sex, educational level, and prior suicidality at baseline. Conclusion Resilience, a previous history of suicidality, and the presence of lifetime depressive disorder and anxiety disorder should be given consideration in mental health support and suicide prevention in NKDs.

Objective: : We performed an expanded multi-ethnic meta-analysis to identify associations between inflammation-related loci with intracranial aneurysm (IA) susceptibility. This meta-analysis possesses increased statistical power as it is based on the most data ever evaluated. Methods: : We searched and reviewed relevant literature through electronic search engines up to August 2022. Overall estimates were calculated under the fixed- or random-effect models using pooled odds ratio (OR) and 95% confidence intervals (CIs). Subgroup analyses were performed according to ethnicity. Results: : Our meta-analysis enrolled 15 studies and involved 3070 patients and 5528 controls including European, Asian, Hispanic, and mixed ethnic populations. Of 17 inflammation-related variants, the rs1800796 locus (interleukin [IL]-6) showed the most significant genome-wide association with IA in East-Asian populations, including 1276 IA patients and 1322 controls (OR, 0.65; 95% CI, 0.56–0.75; p=3.24×10-9) under a fixed-effect model. However, this association was not observed in the European population (OR, 1.09; 95% CI, 0.80–1.47; p=0.5929). Three other variants, rs16944 (IL-1β), rs2195940 (IL-12B), and rs1800629 (tumor necrosis factor-α) showed a statistically nominal association with IA in both the overall, as well as East-Asian populations (0.01Conclusion : Our updated meta-analysis with increased statistical power highlights that rs1800796 which maps on the IL-6 gene is associated with IA, and in particular confers a protective effect against occurrence of IA in the East-Asian population.