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Background/Aims@#The major histocompatibility class II (MHC II) transactivator, known as CIITA, is induced by Interferon gamma (IFN-γ) and plays a well-established role in regulating the expression of class II MHC molecules in antigen-presenting cells. @*Methods@#Primary human hepatocytes (PHH) were isolated via therapeutic hepatectomy from two donors. The hepatocellular carcinoma (HCC) cell lines HepG2 and Huh7 were used for the mechanistic study, and HBV infection was performed in HepG2-NTCP cells. HBV DNA replication intermediates and secreted antigen levels were measured using Southern blotting and ELISA, respectively. @*Results@#We identified a non-canonical function of CIITA in the inhibition of hepatitis B virus (HBV) replication in both HCC cells and patient-derived PHH. Notably, in vivo experiments demonstrated that HBV DNA and secreted antigen levels were significantly decreased in mice injected with the CIITA construct. Mechanistically, CIITA inhibited HBV transcription and replication by suppressing the activity of HBV-specific enhancers/promoters. Indeed, CIITA exerts antiviral activity in hepatocytes through ERK1/2-mediated down-regulation of the expression of hepatocyte nuclear factor 1α (HNF1α) and HNF4α, which are essential factors for virus replication. In addition, silencing of CIITA significantly abolished the IFN-γ-mediated anti-HBV activity, suggesting that CIITA mediates the anti-HBV activity of IFN-γ to some extent. HBV X protein (HBx) counteracts the antiviral activity of CIITA via direct binding and impairing its function. @*Conclusions@#Our findings reveal a novel antiviral mechanism of CIITA that involves the modulation of the ERK pathway to restrict HBV transcription. Additionally, our results suggest the possibility of a new immune avoidance mechanism involving HBx.
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Background and Objectives@#Pathophysiological changes of right ventricle (RV) after repair of tetralogy of Fallot (TOF) are coupled with a highly compliant low-pressure pulmonary artery (PA) system. This study aimed to determine whether pulmonary vascular function was associated with RV parameters and exercise capacity, and its impact on RV remodeling after pulmonary valve replacement. @*Methods@#In a total of 48 patients over 18 years of age with repaired TOF, pulmonary arterial elastance (Ea), RV volume data, and RV-PA coupling ratio were calculated and analyzed in relation to exercise capacity. @*Results@#Patients with a low Ea showed a more severe pulmonary regurgitation volume index, greater RV end-diastolic volume index, and greater effective RV stroke volume (p=0.039, p=0.013, and p=0.011, respectively). Patients with a high Ea had lower exercise capacity than those with a low Ea (peak oxygen consumption [peak VO2 ] rate: 25.8±7.7 vs. 34.3±5.5 mL/kg/min, respectively, p=0.003), while peak VO2 was inversely correlated with Ea and mean PA pressure (p=0.004 and p=0.004, respectively). In the univariate analysis, a higher preoperative RV end-diastolic volume index and RV end-systolic volume index, left ventricular end-systolic volume index, and higher RV-PA coupling ratio were risk factors for suboptimal outcomes. Preoperative RV volume and RV-PA coupling ratio reflecting the adaptive PA system response are important factors in optimal postoperative results. @*Conclusions@#We found that PA vascular dysfunction, presenting as elevated Ea in TOF, may contribute to exercise intolerance. However, Ea was inversely correlated with pulmonary regurgitation (PR) severity, which may prevent PR, RV dilatation, and left ventricular dilatation in the absence of significant pulmonary stenosis.
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Sudden death during or after percutaneous coronary intervention (PCI) could be led to potential medicolegal disputes. This study aimed to investigate the clinical and postmortem findings in PCI-related deaths-focusing on the current statusto inform preventive strategies against these fatalities. Forty-three cases were retrieved from the National Forensic Service's postmortem records between 2015 and 2021, and the corresponding postmortem findings and clinical information were analyzed. The analyses revealed a relatively consistent annual incidence of PCI-related deaths. Immediate deaths during or shortly after PCI occurred in 17 cases (39.5%), and delayed PCI-related deaths after discharge from the hospital occurred in 26 cases (60.5%). The causes of PCI-related deaths in the postmortem cases were categorized into four groups: PCI complications (11 cases, 26%), acute myocardial infarction (23 cases, 53%), ischemic heart disease (8 cases, 19%), and others (1 case, 2%). Postmortem examinations played a critical role in determining the cause of death and obtaining medical evidence, including pathological findings of the heart as well as those of coronary artery and stent insertion. Our findings suggest that a detailed examination of the heart, coronary arteries, stent status, and atherosclerosis in PCI-related deaths could help provide more accurate information as medical evidence and prevent/resolve potential medicolegal issues. Further, this could advance our understanding of PCI-related deaths and inform future preventive strategies.
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Background/Aims@#The association between symptomatic knee osteoarthritis (OA) and higher cardiovascular disease (CVD) mortality is established; however, findings from studies that utilized regression analysis were limited, attributed to the strong association between OA and metabolic risk factors. This study aimed to evaluate the association between knee OA and mortality through propensity score matching. @*Methods@#This was a cohort study including Korean National Health and Nutrition Examination Survey (2010–2013) participants aged ≥ 50 years. By linking the survey data to cause of death data (through 2019) from Statistics Korea, mortality and cause-specific mortality data were obtained. Radiographic knee OA (ROA) was defined as bilateral Kellgren–Lawrence grade ≥ 2. Propensity score matching (1:1) was conducted between asymptomatic ROA, knee pain, and symptomatic ROA groups and normal groups, balancing the confounding factors. Time to death was analyzed using Cox proportional hazard modeling. @*Results@#A higher CVD mortality was observed in the symptomatic ROA group, but not in others; the risk estimates were asymptomatic ROA (hazard ratio [HR] 1.12; 95% confidence interval [CI] 0.77–1.65), knee pain (HR 0.61; 95% CI 0.27–1.38), and symptomatic ROA (HR 1.39; 95% CI 0.89–2.17). No association was found between the all-cause/cancer mortality and other groups. @*Conclusions@#When propensity score matching controls metabolic risk factor imbalances, the association between symptomatic knee OA and higher CVD mortality was weaker compared to results of prior studies that used regression adjustment. The results may be more precise estimates of the total risk of knee OA for mortality in Koreans.
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Background and Objectives@#Protein-losing enteropathy (PLE) is a devastating complication after the Fontan operation. This study aimed to investigate the clinical characteristics, treatment response, and outcomes of Fontan-associated PLE. @*Methods@#We reviewed the medical records of 38 patients with Fontan-associated PLE from 1992 to 2018 in 2 institutions in Korea. @*Results@#PLE occurred in 4.6% of the total 832 patients after the Fontan operation. After a mean period of 7.7 years after Fontan operation, PLE was diagnosed at a mean age of 11.6years. The mean follow-up period was 8.9 years. The survival rates were 81.6% at 5 years and 76.5% at 10 years. In the multivariate analysis, New York Heart Association Functional classification III or IV (p=0.002), low aortic oxygen saturation (<90%) (p=0.003), and ventricular dysfunction (p=0.032) at the time of PLE diagnosis were found as predictors of mortality. PLE was resolved in 10 of the 38 patients after treatment. Among medical managements, an initial heparin response was associated with survival (p=0.043). Heparin treatment resulted in resolution in 4 patients. We found no evidence on pulmonary vasodilator therapy alone. PLE was also resolved after surgical Fontan fenestration (2/6), aortopulmonary collateral ligation (1/1), and transplantation (1/1). @*Conclusions@#The survival rate of patients with Fontan-associated PLE has improved with the advancement of conservative care. Although there is no definitive method, some treatments led to the resolution of PLE in one-fourth of the patients. Further investigations are needed to develop the best prevention and therapeutic strategies for PLE.
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Purpose@#Although chronotropic incompetence (CI) is common in patients with complex congenital heart disease (CHD) and is associated with adverse cardiovascular outcomes, few data are available regarding modifiable predictors of CI in this escalating patient population. We tested the hypothesis that higher levels of physical activity (PA) are associated with a lower prevalence of CI in patients with complex CHD and evaluated the receiver operating characteristic curve to identify the PA level that best predicted CI. @*Methods@#We evaluated 111 adolescents with complex CHD. CI was defined as the failure to achieve 80% of the chronotropic response index during peak cardiopulmonary exercise test. Self-reported habitual activity was obtained using a global PA questionnaire. @*Results@#CI was identified in 45 of the 111 cases (40.5%). After adjusting for potential confounding variables, the high PA group demonstrated a lower odds ratio for having CI (odds ratios, 0.25; 95% confidence interval, 0.06‒0.99) compared with the low PA group. The most accurate cut-point for PA to predict the prevalence of CI was 15 metabolic equivalents (METs)-hours/week (areas under the curve, 0.71; 95% confidence interval, 0.61‒0.81; sensitivity, 71%; specificity, 69%). @*Conclusion@#Our findings demonstrate that higher levels of PA are associated with a lower prevalence of CI, independent of potential confounders, and that 15 METs-hours/week of PA provides a cut-point for accurately predicting the presence of CI in adolescents with complex CHD.
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Purpose@#To evaluate the changes in eyelid parameters after the endonasal approach compared with transcaruncular medial wall decompression combined with the transconjunctival inferior wall decompression approach with inferomedial strut preservation. @*Methods@#In total, 71 patients with thyroid eye disease who underwent orbital decompression were retrospectively evaluated. The data collected included Hertel exophthalmometry, marginal reflex distance 1, marginal reflex distance 2, interpalpebral fissure, levator function test measures, and complications related to surgery. @*Results@#Proptosis reduction produced a statistically significant improvement across all decompression groups. Lower eyelid retraction produced a statistically significant improvement in the two-wall decompression groups but not in the one-wall decompression groups. No statistical difference was observed in the upper eyelid retraction and levator function after surgery across all decompression groups. In the post-hoc analysis, statistical improvement was not observed in the lower eyelid retraction between the endonasal and transcaruncular approach in the one-wall and two-wall decompression groups, although statistically significant exophthalmos reduction and improvement in the lower eyelid retraction was noted in the two-wall decompression subgroups compared with one-wall decompression subgroups. @*Conclusions@#Our study showed no differences in eyelid parameters between the endonasal and transcaruncular decompression approaches in one-wall and two-wall decompression. In the two-wall decompression group, proptosis reduction was greater with the endonasal approach than with the transcaruncular approach when the strut was preserved; however, it does not lead to a significant difference in the improvement of lower eyelid retraction.
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Atherectomy has become a promising treatment option for peripheral artery disease caused by diabetes mellitus or end-stage renal disease. Atherectomy refers to the removal of atheromatous tissue by mechanical method, resulting in an enlarged lumen of the treated blood vessel. Based on this method, the term is limited to the percutaneous minimally invasive approach, and there are currently two types of atherectomy devices available in Korea. The increased prevalence of atherectomy has led to the concept of “vascular preparation” and a new treatment concept of “leave nothing behind.” Various studies have proven the safety and effectiveness of atherectomy; however, there are some limitations. We need to remain focused on patient selection and subsequent large-scale research.
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Atherectomy has become a promising treatment option for peripheral artery disease caused by diabetes mellitus or end-stage renal disease. Atherectomy refers to the removal of atheromatous tissue by mechanical method, resulting in an enlarged lumen of the treated blood vessel. Based on this method, the term is limited to the percutaneous minimally invasive approach, and there are currently two types of atherectomy devices available in Korea. The increased prevalence of atherectomy has led to the concept of “vascular preparation” and a new treatment concept of “leave nothing behind.” Various studies have proven the safety and effectiveness of atherectomy; however, there are some limitations. We need to remain focused on patient selection and subsequent large-scale research.
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The objective of this study was to compare changes in the simplified disease activity index (SDAI) between biologic (b) and conventional (c) disease-modifying antirheumatic drugs (DMARD) users with seropositive rheumatoid arthritis (RA) in daily clinical practice. Methods: This was a nationwide multicenter observational study. Patients who had three or more active joint counts and abnormal inf lammatory marker in blood test were enrolled. The selection of DMARDs was determined by the attending rheumatologist. Clinical parameters, laboratory findings, and Health Assessment Questionnaire (HAQ) scores were obtained at baseline and at 6 and 12 months. Serial SDAI changes and clinical remission rate at 6 and 12 months were assessed. Results: A total of 850 patients participated in this study. The mean baseline SDAI score in bDMARD group was higher than that in cDMARD group (32.08 ± 12.98 vs 25.69 ± 10.97, p < 0.0001). Mean change of SDAI at 12 months was –19.0 in the bDMARD group and –12.6 in the cDMARD group (p < 0.0001). Clinical remission rates at 12 months in bDMARD and cDMARD groups were 15.4% and 14.6%, respectively. Patient global assessment and HAQ at 12 months were also significantly improved in both groups. Multivariate logistic regression showed that baseline HAQ score was the most notable factor associated with remission. Conclusions: There was a significant reduction in SDAI within 12 months after receiving DMARDs in Korean seropositive RA patients irrespective of bDMARD or cDMARD use in real-world practice. Clinical remission was achieved in those with lower baseline HAQ scores.