Background and Objectives: Cardiac resynchronization therapy (CRT) is a treatment option for patients with heart failure and left ventricular (LV) dyssynchrony. However, one-third of CRT patients are non-responders. The objective of this study is to evaluate the feasibility of an in silico electromechanical heart model to predict CRT outcomes. Methods: The three-dimensional heart geometries of 11 patients (age, 64.0 ± 10.7 years, 4 men) with CRT were constructed from cardiac computed tomography images. The finite element method was used to simulate the electrical wave propagation and mechanics in the heart. We coupled cardiac electrical excitation and mechanical contraction with vascular hemodynamics using a lumped parameter model. We predicted the LV end-diastolic and end-systolic volumes and LV ejection fraction (LVEF) after CRT implantation using the in silico CRT simulation model. A CRT responder was defined as a patient with an absolute LVEF increase ≥ 5%. We compared the in silico CRT outcomes with the real CRT outcomes. Results: Two patients were in silico CRT responders, and those 2 patients were also real CRT responders. Nine patients were in silico CRT non-responders, 8 who were real CRT non-responders, and 1 who was a real CRT responder. The in silico CRT outcomes agreed with the real CRT outcomes in 10 of 11 patients. The positive and negative predictive values, accuracy, sensitivity, and specificity of the in silico CRT model were 100%, 88.9%, 90.9%, 66.7%, and 100%, respectively. Conclusion The in silico CRT simulation model is feasible for predicting real CRT outcomes.

Background: The exposome encompasses all factors people encounter through life, with the skin constantly exposed. While particulate matter (PM) and sleep deprivation are known to contribute to barrier dysfunction, their combined effects remain unclear. Objective: To evaluate the independent and combined effects of PM exposure and short-term sleep deprivation on skin barrier function. Methods: Forty healthy Korean women (aged 24–58 years) were enrolled in this study. Forearms were divided into 4 sites: control, PM exposure, sleep deprivation, and PM plus sleep deprivation. Parameters such as trans-epidermal water loss (TEWL), hydration, elasticity, roughness, and redness were measured at baseline and post-exposure. RNA sequencing and reverse transcription-polymerase chain reaction were conducted on tape-stripped skin samples. Results: PM exposure significantly increased TEWL (+25.59%, p<0.01), roughness (+21.9%, p<0.01), and redness (+13.7%, p<0.0001) while reducing elasticity (−3.98%, p<0.01). Sleep deprivation modestly reduced elasticity (−1.39%, p<0.05) without affecting other parameters.Combined PM and sleep deprivation did not further exacerbate barrier dysfunction compared to PM alone. RNA sequencing revealed reduced FLG and LORICRIN expression and upregulated endoplasmic reticulum (ER) stress markers (HSP90B1, CANX) in both PM and sleep deprivation conditions. Conclusion PM exposure impaired skin barrier function, while short-term sleep deprivation alone did not significantly affect the barrier, either independently or in combination with PM.However, it was observed that the sleep deprivation-only, while not directly causing barrier damage, induced changes in ER stress-related gene expression in tape-stripped skin samples, like the PM exposure-only. This suggests that such signaling pathways could potentially exacerbate skin barrier deterioration.

Background: Brugada syndrome (BrS) and arrhythmogenic cardiomyopathy (ACM) are inherited cardiac diseases that may predispose to ventricular arrhythmia. Although overlapping features between BrS and ACM have been demonstrated previously, it remains to be determined whether genetic testing for ACM-related genes is needed in BrS probands.MethodBased on a single-center, retrospective registry of BrS, we aimed to verify genetic profiles of BrS using a next-generation sequencing panel, and further analyzed genetic testing of ACM-related variants in Brugada phenotypes. Results: Among a total of 119 Brugada phenotypes, 114 patients (95.8%) were male and the mean age of onset was 43.6 years. Genetic variants were identified in 25 of the 42 patients who underwent genetic testing. Fifteen patients had BrS-related genotypes, including SCN5A in 6 patients, and non-SCN5A genes in 9 patients (SCN10A, HCN4, SCN3B, and KCNE3). Nineteen patients underwent additional genetic testing with cardiomyopathy panel, which revealed ACM-related genotypes (2 PKP2, 1 DSG2, 1 TMEM43, 1 JUP, and 1 DSP) present in 6 patients (31.5%). None of the patients had structural or electrocardiographic features that fulfilled the diagnostic criteria for ACM. Conclusions In clinical setting, ACM-related genes were identified in a significant proportion of Brugada phenotypes, supporting the argument that genetic testing of ACM overlapping is needed. Follow-up imaging studies should be considered to monitor if the disease progresses to ACM.

Background/Aims: Owing to the low prevalence of small-bowel adenocarcinoma (SBA), data on the impact of Crohn’s disease (CD) on the survival of patients with SBA are lacking. Therefore, we investigated this issue in this study. Methods: In this bicenter cohort study, patients with histologically confirmed SBA were retrospectively enrolled and classified into two groups: sporadic SBA and CD-associated SBA. Patients with duodenal SBA were excluded. Overall survival, disease-free survival, and factors associated with survival were analyzed. Results: Of 128 patients with SBA, 115 had sporadic SBA and 13 had CD-associated SBA. Ileal involvement and poorly differentiated tumors were more common in the CD-associated SBA group than in the sporadic SBA group (ileal involvement, 53.8% vs 22.6%; poor differentiation, 46.2% vs 14.8%; both p<0.05). In survival analysis, overall survival showed no statistical difference between the sporadic SBA and CD-associated SBA groups (p=0.370). However, when stratified by stage, the adjusted overall survival of the CD-associated SBA group was lower in patients with an advanced disease stage (p=0.029). Disease-free survival showed the same tendency, albeit without clinical significance (p=0.097). CD (hazard ratio [HR], 2.308; p=0.047), older age (≥65 yr) at SBA diagnosis (HR, 2.766; p=0.001), and stage III/IV disease (HR, 3.151; p<0.001) were factors associated with mortality. Conclusions The overall survival of patients with CD-associated SBA did not differ from that of patients with sporadic SBA. However, as CD is an independent risk factor for mortality, vigilant surveillance in high-risk patients may be crucial.

A resorbable barrier membrane is commonly used for the repair of perforated sinus membranes during sinus lifting surgeries. However, repairing largescale perforations poses challenges for clinicians as the protection and isolation of graft material remain uncertain. With this technique, we aimed to prevent graft material loss and subsequent sinus-related complications using intra-sinus rigid fixation of the resorbable barrier membrane in cases with a large perforation of the sinus membrane.

Background and Objectives: Inherited arrhythmia (IA) is a more common cause of sudden cardiac death in Asian population, but little is known about the genetic background of Asian IA probands. We aimed to investigate the clinical characteristics and analyze the genetic underpinnings of IA in a Korean cohort. Methods: This study was conducted in a multicenter cohort of the Korean IA Registry from 2014 to 2017. Genetic testing was performed using a next-generation sequencing panel including 174 causative genes of cardiovascular disease. Results: Among the 265 IA probands, idiopathic ventricular fibrillation (IVF) and Brugada Syndrome (BrS) was the most prevalent diseases (96 and 95 cases respectively), followed by long QT syndrome (LQTS, n=54). Two-hundred-sixteen probands underwent genetic testing, and 69 probands (31.9%) were detected with genetic variant, with yield of pathogenic or likely pathogenic variant as 6.4%. Left ventricular ejection fraction was significantly lower in genotype positive probands (54.7±11.3 vs. 59.3±9.2%, p=0.005). IVF probands showed highest yield of positive genotype (54.0%), followed by LQTS (23.8%), and BrS (19.5%). Conclusions There were significant differences in clinical characteristics and genetic yields among BrS, LQTS, and IVF. Genetic testing did not provide better yield for BrS and LQTS. On the other hand, in IVF, genetic testing using multiple gene panel might enable the molecular diagnosis of concealed genotype, which may alter future clinical diagnosis and management strategies.

Background/Aims: Biofeedback therapy is widely used to treat patients with chronic constipation, especially those with dyssynergic defecation. Yet, the utility of high-resolution manometry with novel parameters in the prediction of biofeedback response has not been reported. Thus, we constructed a model for predicting biofeedback therapy responders by applying the concept of integrated pressurized volume in patients undergoing high-resolution anorectal manometry. Methods: Seventy-one female patients (age: 48-68 years) with dyssynergic defecation who underwent initial high-resolution anorectal manometry and subsequent biofeedback therapy were enrolled. The manometry profiles were used to calculate the 3-dimensional integrated pressurized volumes by multiplying the distance, time, and amplitude during simulated evacuation. Partial least squares regression was performed to generate a predictive model for responders to biofeedback therapy by using the integrated pressurized volume parameters. Results: Fifty-five (77.5%) patients responded to biofeedback therapy. The responders and non-responders did not show significant differences in the conventional manometric parameters. The partial least squares regression model used a linear combination of eight integrated pressurized volume parameters and generated an area under the curve of 0.84 (95% confidence interval: 0.76-0.95, P < 0.01), with 85.5% sensitivity and 62.1% specificity. Conclusions Integrated pressurized volume parameters were better than conventional parameters in predicting the responsiveness to biofeedback therapy, and the combination of these parameters and partial least squares regression was particularly promising. Integrated pressurized volume parameters can more effectively explain the physiology of the anorectal canal compared with conventional parameters.

Background: Cardiac resynchronization therapy (CRT) is an effective treatment option for patients with heart failure (HF) and left ventricular (LV) dyssynchrony. However, the problem of some patients not responding to CRT remains unresolved. This study aimed to propose a novel in silico method for CRT simulation. Methods: Three-dimensional heart geometry was constructed from computed tomography images. The finite ele‑ ment method was used to elucidate the electric wave propagation in the heart. The electric excitation and mechani‑ cal contraction were coupled with vascular hemodynamics by the lumped parameter model. The model parameters for three-dimensional (3D) heart and vascular mechanics were estimated by matching computed variables with measured physiological parameters. CRT effects were simulated in a patient with HF and left bundle branch block (LBBB). LV end-diastolic (LVEDV) and end-systolic volumes (LVESV), LV ejection fraction (LVEF), and CRT responsiveness measured from the in silico simulation model were compared with those from clinical observation. A CRT responder was defined as absolute increase in LVEF ≥ 5% or relative increase in LVEF ≥ 15%. Results: A 68-year-old female with nonischemic HF and LBBB was retrospectively included. The in silico CRT simu‑ lation modeling revealed that changes in LVEDV, LVESV, and LVEF by CRT were from 174 to 173 mL, 116 to 104 mL, and 33 to 40%, respectively. Absolute and relative ΔLVEF were 7% and 18%, respectively, signifying a CRT responder.In clinical observation, echocardiography showed that changes in LVEDV, LVESV, and LVEF by CRT were from 162 to 119 mL, 114 to 69 mL, and 29 to 42%, respectively. Absolute and relative ΔLVESV were 13% and 31%, respectively, also signifying a CRT responder. CRT responsiveness from the in silico CRT simulation model was concordant with that in the clinical observation. Conclusion This in silico CRT simulation method is a feasible technique to screen for CRT non-responders in patients with HF and LBBB.

Female ; Forced Expiratory Volume ; Humans ; Linear Models ; Lung ; Male ; Radiography, Thoracic ; Spirometry ; Vital Capacity