1.Identification of Preeclamptic Placenta in Whole Slide Images Using Artificial Intelligence Placenta Analysis
Young Mi JUNG ; Seyeon PARK ; Youngbin AHN ; Haeryoung KIM ; Eun Na KIM ; Hye Eun PARK ; Sun Min KIM ; Byoung Jae KIM ; Jeesun LEE ; Chan-Wook PARK ; Joong Shin PARK ; Jong Kwan JUN ; Young-Gon KIM ; Seung Mi LEE
Journal of Korean Medical Science 2024;39(39):e271-
		                        		
		                        			 Background:
		                        			Preeclampsia (PE) is a hypertensive pregnancy disorder linked to placental dysfunction, often involving pathological lesions like acute atherosis, decidual vasculopathy, accelerated villous maturation, and fibrinoid deposition. However, there is no gold standard for the pathological diagnosis of PE and this limits the ability of clinicians to distinguish between PE and non-PE pregnancies. Recent advances in computational pathology have provided the opportunity to automate pathological analysis for diagnosis, classification, prediction, and prediction of disease progression. In this study, we assessed whether computational pathology could be used to identify PE placentas. 
		                        		
		                        			Methods:
		                        			A total of 168 placental whole-slide images (WSIs) of patients from Seoul National University Hospital (comprising 84 PE cases and 84 normal controls) were used for model development and internal validation. For external validation of the model, 76 placental slides (including 38 PE cases and 38 normal controls) were obtained from the Boramae Medical Center (BMC). To establish standard criteria for diagnosing PE and distinguishing it from controls using placental WSIs, patch characteristics and quantification of terminal and intermediate villi were employed. In unsupervised learning, K-means clustering was conducted as a feature obtained through an Auto Encoder to extract the ratio of each cluster for each WSI. For supervised learning, quantitative assessments of the villi were obtained using a U-Net-based segmentation algorithm. The prediction model was developed using an ensemble method and was compared with a clinical feature model developed by using placental size features. 
		                        		
		                        			Results:
		                        			Using ensemble modeling, we developed a model to identify PE placentas.The model showed good performance (area under the precision-recall curve [AUPRC], 0.771; 95% confidence interval [CI], 0.752–0.790), with 77.3% of sensitivity and 71.1% of specificity, whereas the clinical feature model showed an AUPRC 0.713 (95% CI, 0.694–0.732) with 55.6% sensitivity and 86.8% specificity. External validation of the predictive model employing the BMC-derived set of placental slides also showed good discrimination (AUPRC, 0.725; 95% CI, 0.720–0.730). 
		                        		
		                        			Conclusion
		                        			The proposed computational pathology model demonstrated a strong ability to identify preeclamptic placentas. Computational pathology has the potential to improve the identification of PE placentas. 
		                        		
		                        		
		                        		
		                        	
2.Central Neurogenic Hyperventilation Following Ischemic Stroke in the Pons
Hyeo Seo MOON ; Byoung Wook HWANG ; Min A LEE ; Chang Ju LEE ; Ju Hye KIM ; Jun Hyeok PARK ; Seong Hwan AHN
Journal of the Korean Neurological Association 2024;42(3):245-247
		                        		
		                        			
		                        			 Central neurogenic hyperventilation (CNH) is a rare condition that characterized by an increase in the rate and depth of respiration to an extent that produces advanced respiratory alkalosis due to various central nervous disorder. The mechanism of CNH remains unclear. We reported a case of CNH in patients with progressive ischemic stroke in pons, including parabrachial nucleus, which is thought to have disrupted inhibitory impulses to the medullary respiratory center. 
		                        		
		                        		
		                        		
		                        	
3.The mediating role of the left ventricular mass index on the relationship between the fluid balance and left ventricular diastolic function in patients with chronic kidney disease
Byoung-Geun HAN ; Jun Young LEE ; Jae-Seok KIM ; Jae-Won YANG ; Sang Wook PARK
Kidney Research and Clinical Practice 2024;43(1):101-110
		                        		
		                        			
		                        			 The pathophysiological mechanism of cardiovascular disease in patients with chronic kidney disease (CKD) is complicated. Mediation analysis is an important statistical tool for gaining insight into the complex mechanisms of exposure-outcome effects. We investigated the potential mediating role of the left ventricular mass index (LVMI) on the association between fluid balance (overhydration/extracellular water, OH/ECW) and left ventricular diastolic function (E/e´ ratio) in patients with CKD not yet on dialysis. Methods: Bioimpedance spectroscopy, echocardiography, and laboratory evaluations were performed on 425 consecutive patients on the same day. The patients were classified into two groups according to the estimated glomerular filtration rate corresponding to CKD stages 3 and 5. Mediation analysis was performed using the PROCESS macro and bootstrapping methods. Results: OH/ECW and LVMI were positively correlated with the E/e´ ratio in both the CKD stages 3 and five groups. In CKD stage 5, there was a statistically significant association between OH/ECW and LVMI, whereas no correlation was observed in CKD stage 3. In the mediation analysis, LVMI positively mediated the relationship between OH/ECW and E/e´ ratio when controlling for confounders in patients with CKD stage 5 (B = 2.602; Boot 95% confidence interval, 1.313–4.076). Conclusion: In our analysis, the indirect effect of mediators was significant in patients with advanced CKD. Therefore, our study suggests that further research on several other risk factors may be needed to determine the underlying mechanisms of association between the associated factors in all CKD stages. 
		                        		
		                        		
		                        		
		                        	
4.Feasibility of the Threshold-Based Quantification of Myocardial Fibrosis on Cardiac CT as a Prognostic Marker in Nonischemic Dilated Cardiomyopathy
Na Young KIM ; Dong Jin IM ; Yoo Jin HONG ; Byoung Wook CHOI ; Seok-Min KANG ; Jong-Chan YOUN ; Hye-Jeong LEE
Korean Journal of Radiology 2024;25(6):540-549
		                        		
		                        			 Objective:
		                        			This study investigated the feasibility and prognostic relevance of threshold-based quantification of myocardial delayed enhancement (MDE) on CT in patients with nonischemic dilated cardiomyopathy (NIDCM). 
		                        		
		                        			Materials and Methods:
		                        			Forty-three patients with NIDCM (59.3 ± 17.1 years; 21 male) were included in the study and underwent cardiac CT and MRI. MDE was quantified manually and with a threshold-based quantification method using cutoffs of 2, 3, and 4 standard deviations (SDs) on three sets of CT images (100 kVp, 120 kVp, and 70 keV). Interobserver agreement in MDE quantification was assessed using the intraclass correlation coefficient (ICC). Agreement between CT and MRI was evaluated using the Bland-Altman method and the concordance correlation coefficient (CCC). Patients were followed up for the subsequent occurrence of the primary composite outcome, including cardiac death, heart transplantation, heart failure hospitalization, or appropriate use of an implantable cardioverter-defibrillator. The Kaplan–Meier method was used to estimate event-free survival according to MDE levels. 
		                        		
		                        			Results:
		                        			Late gadolinium enhancement (LGE) was observed in 29 patients (67%, 29/43), and the mean LGE found with the 5-SD threshold was 4.1% ± 3.6%. The 4-SD threshold on 70-keV CT showed excellent interobserver agreement (ICC = 0.810) and the highest concordance with MRI (CCC = 0.803). This method also yielded the smallest bias with the narrowest range of 95% limits of agreement compared to MRI (bias, -0.119%; 95% limits of agreement, -4.216% to 3.978%). During a median follow-up of 1625 days (interquartile range, 712–1430 days), 10 patients (23%, 10/43) experienced the primary composite outcome. Event-free survival significantly differed between risk subgroups divided by the optimal MDE cutoff of 4.3% (log-rank P = 0.005). 
		                        		
		                        			Conclusion
		                        			The 4-SD threshold on 70-keV monochromatic CT yielded results comparable to those of MRI for quantifying MDE as a marker of myocardial fibrosis, which showed prognostic value in patients with NIDCM. 
		                        		
		                        		
		                        		
		                        	
5.Efficacy and safety of sofosbuvir–velpatasvir and sofosbuvir–velpatasvir–voxilaprevir for hepatitis C in Korea: a Phase 3b study
Jeong HEO ; Yoon Jun KIM ; Sung Wook LEE ; Youn-Jae LEE ; Ki Tae YOON ; Kwan Soo BYUN ; Yong Jin JUNG ; Won Young TAK ; Sook-Hyang JEONG ; Kyung Min KWON ; Vithika SURI ; Peiwen WU ; Byoung Kuk JANG ; Byung Seok LEE ; Ju-Yeon CHO ; Jeong Won JANG ; Soo Hyun YANG ; Seung Woon PAIK ; Hyung Joon KIM ; Jung Hyun KWON ; Neung Hwa PARK ; Ju Hyun KIM ; In Hee KIM ; Sang Hoon AHN ; Young-Suk LIM
The Korean Journal of Internal Medicine 2023;38(4):504-513
		                        		
		                        			
		                        			 Despite the availability of direct-acting antivirals (DAAs) for chronic hepatitis C virus (HCV) infection in Korea, need remains for pangenotypic regimens that can be used in the presence of hepatic impairment, comorbidities, or prior treatment failure. We investigated the efficacy and safety of sofosbuvir–velpatasvir and sofosbuvir–velpatasvir–voxilaprevir for 12 weeks in HCV-infected Korean adults. Methods: This Phase 3b, multicenter, open-label study included 2 cohorts. In Cohort 1, participants with HCV genotype 1 or 2 and who were treatment-naive or treatment-experienced with interferon-based treatments, received sofosbuvir–velpatasvir 400/100 mg/day. In Cohort 2, HCV genotype 1 infected individuals who previously received an NS5A inhibitor-containing regimen ≥ 4 weeks received sofosbuvir–velpatasvir–voxilaprevir 400/100/100 mg/day. Decompensated cirrhosis was an exclusion criterion. The primary endpoint was SVR12, defined as HCV RNA < 15 IU/mL 12 weeks following treatment. Results: Of 53 participants receiving sofosbuvir–velpatasvir, 52 (98.1%) achieved SVR12. The single participant who did not achieve SVR12 experienced an asymptomatic Grade 3 ASL/ALT elevation on day 15 and discontinued treatment. The event resolved without intervention. All 33 participants (100%) treated with sofosbuvir–velpatasvir–voxilaprevir achieved SVR 12. Overall, sofosbuvir–velpatasvir and sofosbuvir–velpatasvir–voxilaprevir were safe and well tolerated. Three participants (5.6%) in Cohort 1 and 1 participant (3.0%) in Cohort 2 had serious adverse events, but none were considered treatment-related. No deaths or grade 4 laboratory abnormalities were reported. Conclusions: Treatment with sofosbuvir–velpatasvir or sofosbuvir–velpatasvir–voxilaprevir was safe and resulted in high SVR12 rates in Korean HCV patients. 
		                        		
		                        		
		                        		
		                        	
7.The Etiology of Acute Stroke with Experience of Repeated Upper Extremity Deep Vein Thrombosis
Chang Ju LEE ; Dong Kun LEE ; Min A LEE ; Byoung Wook HWANG ; Ju Hye KIM ; Hyeo Seo MOON ; Sung-Chul LIM ; Seong Hwan AHN
Journal of the Korean Neurological Association 2023;41(1):52-55
		                        		
		                        			
		                        			 In stroke patients, upper extremity deep vein thrombosis (UEDVT) is uncommon compared with lower extremity. Unlike the blood stasis in lower extremity, UEDVT has been developed by secondary cause. We reported a case of stroke patient with repeated UEDVT, presenting superficial venous congestion, who was finally diagnosed with pulmonary adenocarcinoma. The cause of stroke was non-bacterial thromboembolism formed at the mitral valve. Our case shows that unexpected UEDVT should be closely evaluated for higher coagulable status such as a malignancy. 
		                        		
		                        		
		                        		
		                        	
8.The Effect of Vanishing Twin on Firstand Second-Trimester Maternal Serum Markers and Nuchal Translucency: A Multicenter Prospective Cohort Study
Se Jin LEE ; You Jung HAN ; Minhyoung KIM ; Jae-Yoon SHIM ; Mi-Young LEE ; Soo-young OH ; JoonHo LEE ; Soo Hyun KIM ; Dong Hyun CHA ; Geum Joon CHO ; Han-Sung KWON ; Byoung Jae KIM ; Mi Hye PARK ; Hee Young CHO ; Hyun Sun KO ; Ji Hye BAE ; Chan-Wook PARK ; Joong Shin PARK ; Jong Kwan JUN ; Sohee OH ; Da Rae LEE ; Hyun Mee RYU ; Seung Mi LEE
Journal of Korean Medical Science 2023;38(38):e300-
		                        		
		                        			 Background:
		                        			The purpose of this study was to evaluate the effect of vanishing twin (VT) on maternal serum marker concentrations and nuchal translucency (NT). 
		                        		
		                        			Methods:
		                        			This is a secondary analysis of a multicenter prospective cohort study in 12 institutions. Serum concentrations of pregnancy-associated plasma protein-A in the first trimester and alpha-fetoprotein (AFP), total human chorionic gonadotrophin, unconjugated estriol, and inhibin A in the second trimester were measured, and NT was measured between 10 and 14 weeks of gestation. 
		                        		
		                        			Results:
		                        			Among 6,793 pregnant women, 5,381 women were measured for serum markers in the first or second trimester, including 65 cases in the VT group and 5,316 cases in the normal singleton group. The cases in the VT group had a higher median multiple of the median value of AFP and inhibin A than the normal singleton group. The values of other serum markers and NT were not different between the two groups. After the permutation test with adjustment,AFP and inhibin A remained significant differences. The frequency of abnormally increased AFP was also higher in the VT group than in the normal singleton group. 
		                        		
		                        			Conclusion
		                        			VT can be considered as an adjustment factor for risk assessment in the secondtrimester serum screening test. 
		                        		
		                        		
		                        		
		                        	
9.Chemotherapy-Related Cardiac Dysfunction:Quantitative Cardiac Magnetic Resonance Image Parameters and Their Prognostic Implications
Jinhee KIM ; Yoo Jin HONG ; Kyunghwa HAN ; Jin Young KIM ; Hye-Jeong LEE ; Jin HUR ; Young Jin KIM ; Byoung Wook CHOI
Korean Journal of Radiology 2023;24(9):838-848
		                        		
		                        			 Objective:
		                        			To quantitatively analyze the cardiac magnetic resonance imaging (CMR) characteristics of chemotherapy-related cardiac dysfunction (CTRCD) and explore their prognostic value for major adverse cardiovascular events (MACE). 
		                        		
		                        			Materials and Methods:
		                        			A total of 145 patients (male:female = 76:69, mean age = 63.0 years) with cancer and heart failure who underwent CMR between January 2015 and January 2021 were included. CMR was performed using a 3T scanner (Siemens). Biventricular functions, native T1 T2, extracellular volume fraction (ECV) values, and late gadolinium enhancement (LGE) of the left ventricle (LV) were compared between those with and without CTRCD. These were compared between patients with mild-to-moderate CTRCD and those with severe CTRCD. Cox proportional hazard regression analysis was used to evaluate the association between the CMR parameters and MACE occurrence during follow-up in the CTRCD patients. 
		                        		
		                        			Results:
		                        			Among 145 patients, 61 had CTRCD and 84 did not have CTRCD. Native T1, ECV, and T2 were significantly higher in the CTRCD group (1336.9 ms, 32.5%, and 44.7 ms, respectively) than those in the non-CTRCD group (1303.4 ms, 30.5%, and 42.0 ms, respectively; P = 0.013, 0.010, and < 0.001, respectively). They were not significantly different between patients with mild-to-moderate and severe CTRCD. Indexed LV mass was significantly smaller in the CTRCD group (65.0 g/m2 vs. 78.9 g/m2 ; P < 0.001). According to the multivariable Cox regression analysis, T2 (hazard ratio [HR]: 1.14, 95% confidence interval [CI]: 1.01–1.27; P = 0.028) and quantified LGE (HR: 1.07, 95% CI: 1.01–1.13; P = 0.021) were independently associated with MACE in the CTRCD patients. 
		                        		
		                        			Conclusion
		                        			Quantitative parameters from CMR have the potential to evaluate myocardial changes in CTRCD. Increased T2 with reduced LV mass was demonstrated in CTRCD patients even before the development of severe cardiac dysfunction. T2 and quantified LGE may be independent prognostic factors for MACE in patients with CTRCD. 
		                        		
		                        		
		                        		
		                        	
10.Rescue Endovascular Treatment to Prevent Neurological Deterioration in Acute Symptomatic Bilateral Vertebral Artery Occlusion
Byoung Wook HWANG ; Min A LEE ; Sang Woo HA ; Jae Ho KIM ; Hak Sung KIM ; Seong Hwan AHN
Neurointervention 2023;18(3):182-189
		                        		
		                        			
		                        			 Bilateral vertebral artery occlusive disease has been considered as a favorable condition with good collaterals. However, the prognosis of acute ischemic stroke secondary to symptomatic bilateral vertebral artery occlusion (BVAO) and endovascular treatment (EVT) has rarely been reported. We retrospectively selected patients with acute ischemic stroke admitted for symptomatic BVAO between January 2020 and February 2023. All patients with ischemic stroke were evaluated for ischemic lesion and arterial status using brain imaging and angiography. The prognosis of acute stroke with symptomatic BVAO was compared between EVT and conventional treatment. Outcomes were evaluated using modified Rankin Scale (mRS) score at 3 months follow-up. Within the study period, 17 of 2,655 acute ischemic stroke patients were diagnosed with ischemic stroke with symptomatic BVAO. The median age of these patients was 70 (interquartile range 44–89) years, and 13 (76%) were male. Seven patients received emergent EVT with stenting and 10 patients received conventional medical treatment only. Nine of 10 patients with conventional treatment had in-hospital stroke progression and developed new ischemic lesions in the pons and midbrain. Five patients with fetal and hypoplastic posterior communicating artery presented bilateral cerebral peduncular lesions. At 3 months follow-up, 6 patients (35%) had favorable outcomes (mRS 0–2), of which 5 were treated with vertebral artery stenting and 1 received conventional treatment. Ischemic stroke in patients with acute symptomatic BVAO is uncommon. However, stroke progression is common, and the prognosis of most patients is poor. Rescue management such as EVT might be considered for symptomatic BVAO. 
		                        		
		                        		
		                        		
		                        	
            
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