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Unusual Cause of Severe Tricuspid Regurgitation: Tricuspid Leaflet Annular Tear Following Remote Motor Vehicle Accident [Case Report]

Bamira, Daniel G; Dwivedi, Aeshita; Bhatla, Puneet; Halpern, Dan; Vainrib, Alan F; Kim, Eugene; Zias, Elias; Saric, Muhamed
Tricuspid regurgitation (TR) is an uncommon and underdiagnosed complication of blunt chest trauma. Typical mechanisms include torn chordae, papillary muscle rupture, and radial leaflet tear. We describe an unusual case of traumatic TR due to circumferential avulsion of the anterior tricuspid leaflet from the tricuspid annulus and the crucial role of multimodality imaging in its diagnosis and treatment. (Level of Difficulty: Intermediate.).
PMID: 34317128
ISSN: 2666-0849
CID: 4949442

Isl1 Regulation of Nkx2.1 in the Early Foregut Epithelium Is Required for Trachea-Esophageal Separation and Lung Lobation

Kim, Eugene; Jiang, Ming; Huang, Huachao; Zhang, Yongchun; Tjota, Natalie; Gao, Xia; Robert, Jacques; Gilmore, Nikesha; Gan, Lin; Que, Jianwen
The esophagus and trachea arise from the dorsal and ventral aspects of the anterior foregut, respectively. Abnormal trachea-esophageal separation leads to the common birth defect esophageal atresia with or without trachea-esophageal fistula (EA/TEF). Yet the underlying cellular mechanisms remain unknown. Here, we combine Xenopus and mouse genetic models to identify that the transcription factor Isl1 orchestrates trachea-esophageal separation through modulating a specific epithelial progenitor cell population (midline epithelial cells [MECs], Isl1+ Nkx2.1+ Sox2+) located at the dorsal-ventral boundary of the foregut. Lineage tracing experiments show that MECs contribute to both tracheal and esophageal epithelium, and Isl1 is required for Nkx2.1 transcription in MECs. Deletion of the chromosomal region spanning the ISL1 gene has been found in patients with abnormal trachea-esophageal separation. Our studies thus provide definitive evidence that ISL1 is a critical player in the process of foregut morphogenesis, acting in a small progenitor population of boundary cells.
PMID: 31813798
ISSN: 1878-1551
CID: 4250122

T2-weighted MRI-derived textural features reflect prostate cancer aggressiveness: preliminary results

Nketiah, Gabriel; Elschot, Mattijs; Kim, Eugene; Teruel, Jose R; Scheenen, Tom W; Bathen, Tone F; Selnæs, Kirsten M
PURPOSE/OBJECTIVE:To evaluate the diagnostic relevance of T2-weighted (T2W) MRI-derived textural features relative to quantitative physiological parameters derived from diffusion-weighted (DW) and dynamic contrast-enhanced (DCE) MRI in Gleason score (GS) 3+4 and 4+3 prostate cancers. MATERIALS AND METHODS/METHODS:) were calculated from index tumours delineated on the T2W, DW, and DCE images, respectively. The association between the textural features and prostatectomy GS and the MRI-derived parameters, and the utility of the parameters in differentiating between GS 3+4 and 4+3 prostate cancers were assessed statistically. RESULTS:. The combined texture-MRI parameters yielded higher classification accuracy (91%) than the individual parameter sets. CONCLUSION/CONCLUSIONS:T2W MRI-derived textural features could serve as potential diagnostic markers, sensitive to the pathological differences in prostate cancers. KEY POINTS/CONCLUSIONS:• T2W MRI-derived textural features correlate significantly with Gleason score and ADC. • T2W MRI-derived textural features differentiate Gleason score 3+4 from 4+3 cancers. • T2W image textural features could augment tumour characterization.
PMID: 27975146
ISSN: 1432-1084
CID: 4004162

The Transcription Factor Early B-cell Factor 1 is Critical for Proper Formation of the Cardiac Ventricular Conduction System [Meeting Abstract]

Kim, Eugene; Shekhar, Akshay; Zhang, Jie; Liu, Fang-Yu; Young, Wilson; Fishman, Glenn I
ISSN: 1524-4571
CID: 2411402

Lipomatous Atrial Septal Hypertrophy: A Review of Its Anatomy, Pathophysiology, Multimodality Imaging, and Relevance to Percutaneous Interventions

Laura, Diana M; Donnino, Robert; Kim, Eugene E; Benenstein, Ricardo; Freedberg, Robin S; Saric, Muhamed
Lipomatous atrial septal hypertrophy (LASH) is a histologically benign cardiac lesion characterized by excessive fat deposition in the region of the interatrial septum that spares the fossa ovalis. The etiology of LASH remains unclear, though it may be associated with advanced age and obesity. Because of the sparing of the fossa ovalis, LASH has a pathognomonic dumbbell shape. LASH may be mistaken for various tumors of the interatrial septum. Histologically, LASH is composed of both mature and brown (fetal) adipose tissue, but the role of brown adipose tissue remains unclear. In interventional procedures requiring access to the left atrium, LASH may interfere with transseptal puncture, as traversing the thickened area can reduce the maneuverability of catheters and devices. This may cause the needle to enter the epicardial space, causing dangerous pericardial effusions. LASH was once considered a contraindication to percutaneous device closure of atrial septal defects because of an associated increased risk for incorrect device deployment. However, careful attention to preprocedural imaging and procedural intracardiac echocardiography enable interventional cardiologists to perform procedures in patients with LASH without serious complications. In this review article, the authors describe anatomic and functional aspects of LASH, with emphasis on their roles in percutaneous interventions.
PMID: 27288088
ISSN: 1097-6795
CID: 2136702

Diffusion-weighted MRI for early detection and characterization of prostate cancer in the transgenic adenocarcinoma of the mouse prostate model

Hill, Deborah K; Kim, Eugene; Teruel, Jose R; Jamin, Yann; Widerøe, Marius; Søgaard, Caroline D; Størkersen, Øystein; Rodrigues, Daniel N; Heindl, Andreas; Yuan, Yinyin; Bathen, Tone F; Moestue, Siver A
PURPOSE/OBJECTIVE:To improve early diagnosis of prostate cancer to aid clinical decision-making. Diffusion-weighted magnetic resonance imaging (DW-MRI) is sensitive to water diffusion throughout tissues, which correlates with Gleason score, a histological measure of prostate cancer aggressiveness. In this study the ability of DW-MRI to detect prostate cancer onset and development was evaluated in transgenic adenocarcinoma of the mouse prostate (TRAMP) mice. MATERIALS AND METHODS/METHODS:T2 -weighted and DW-MRI were acquired using a 7T MR scanner, 200 mm bore diameter; 10 TRAMP and 6 C57BL/6 control mice were scanned every 4 weeks from 8 weeks of age until sacrifice at 28-30 weeks. After sacrifice, the genitourinary tract was excised and sectioned for histological analysis. Histology slides registered with DW-MR images allowed for validation of DW-MR images and the apparent diffusion coefficient (ADC) as tools for cancer detection and disease stratification. An automated early assessment tool based on ADC threshold values was developed to aid cancer detection and progression monitoring. RESULTS:The ADC differentiated between control prostate ((1.86 ± 0.20) × 10(-3) mm(2) /s) and normal TRAMP prostate ((1.38 ± 0.10) × 10(-3) mm(2) /s) (P = 0.0001), between TRAMP prostate and well-differentiated cancer ((0.93 ± 0.18) × 10(-3) mm(2) /s) (P = 0.0006), and between well-differentiated cancer and poorly differentiated cancer ((0.63 ± 0.06) × 10(-3) mm(2) /s) (P = 0.02). CONCLUSION/CONCLUSIONS:DW-MRI is a tool for early detection of cancer, and discrimination between cancer stages in the TRAMP model. The incorporation of DW-MRI-based prostate cancer stratification and monitoring could increase the accuracy of preclinical trials using TRAMP mice.
PMID: 26559017
ISSN: 1522-2586
CID: 4004142

Experience from the ACE study in treating peripheral vessel embolization using large-volume Ruby coils [Meeting Abstract]

Teigen, C; Moyle, H; Patel, R; Fischman, A; Kim, E; Baxter, B; Quarfordt, S; Heck, D; Klucznik, R; Diaz, O; Reeves, A; Abraham, M; Madarang, E; Zwiebel, B; Brant-Zawadzki, M; Peck, W; Nguyen, B; Whitaker, L; Gailloud, P; Hagino, R; Liu, K; Moskovitz, J D; Luong, E; Lai, J; Kuo, S S; Hak, S S; Nguyen, N; Bose, A; Sit, S P
Purpose: The Penumbra RubyTM Coil system is a generation of novel large-volume platinum detachable coils designed for arterial and venous embolization in the peripheral vasculature. Recent literature describes the impact of packing density on the stability of recanalization.1 Herein, initial data from the multicenter Aneurysm Coiling Efficiency (ACE) registry aims to validate the system's safety and efficacy in relation to high packing density and sustainable occlusion in the periphery. Material and Methods: Patients were treated at 13 centers using the Ruby Coil system between March 2012 and January 2015. Data compiled from the first 68 cases included 7 splenic, 11 renal, 3 mesenteric, 1 iliac, and 1 hepatic artery aneurysms; 7 AVMs; 6 fistulae; 4 varices; and 28 vessel sacrifices. Results: For aneurysms only, median number of coils placed was 6 and mean packing density was 28% (N=40). Post-treatment distribution of Raymond occlusion scores were Class I (91.3%), II (4.3%), and III (4.3%). At 6 months, scores were Class I (92.9%) and II (7.1%). For vessel sacrifices, all 28 had successful coil embolization. Median number of coils placed was 2.5, and mean fluoroscopy time was 21 min. Thirteen patients with 6-month follow-up demonstrated stable or ongoing occlusion. For all 68 patients, no procedural SAEs were recorded. Follow-up is ongoing. Conclusion: Using Ruby resulted in a high mean packing density and complete post-procedure occlusion, which remained stable at the 6-month follow-up. 1JVIR 2013;24:1798
ISSN: 0174-1551
CID: 1839872

Isolation and Characterization of ESC-Derived Cardiac Purkinje Cells

Maass, Karen; Shekhar, Akshay; Lu, Jia; Kang, Guoxin; See, Fiona; Kim, Eugene; Delgado, Camila; Shen, Steven; Cohen, Lisa; Fishman, Glenn I
The cardiac Purkinje fiber network is comprised of highly specialized cardiomyocytes responsible for the synchronous excitation and contraction of the ventricles. Computational modeling, experimental animal studies and intracardiac electrical recordings from patients with heritable and acquired forms of heart disease suggest that Purkinje cells (PC) may also serve as critical triggers of life-threatening arrhythmias. Nonetheless, owing to the difficulty in isolating and studying this rare population of cells, the precise role of PC in arrhythmogenesis and the underlying molecular mechanisms responsible for their pro-arrhythmic behavior are not fully characterized. Conceptually, a stem cell-based model system might facilitate studies of PC-dependent arrhythmia mechanisms and serve as a platform to test novel therapeutics. Here, we describe the generation of murine embryonic stem cells (ESC) harboring pan-cardiomyocyte and PC-specific reporter genes. We demonstrate that the dual reporter gene strategy may be used to identify and isolate the rare ESC-derived PC (ESC-PC) from a mixed population of cardiogenic cells. ESC-PC display transcriptional signatures and functional properties, including action potentials, intracellular calcium cycling and chronotropic behavior comparable to endogenous PC. Our results suggest that stem-cell derived PC are a feasible new platform for studies of developmental biology, disease pathogenesis and screening for novel anti-arrhythmic therapies
PMID: 25524238
ISSN: 1066-5099
CID: 1411522

PCP4 regulates Purkinje cell excitability and cardiac rhythmicity

Kim, Eugene E; Shekhar, Akshay; Lu, Jia; Lin, Xianming; Liu, Fang-Yu; Zhang, Jie; Delmar, Mario; Fishman, Glenn I
Cardiac Purkinje cells are important triggers of ventricular arrhythmias associated with heritable and acquired syndromes; however, the mechanisms responsible for this proarrhythmic behavior are incompletely understood. Here, through transcriptional profiling of genetically labeled cardiomyocytes, we identified expression of Purkinje cell protein-4 (Pcp4), a putative regulator of calmodulin and Ca2+/calmodulin-dependent kinase II (CaMKII) signaling, exclusively within the His-Purkinje network. Using Pcp4-null mice and acquired cardiomyopathy models, we determined that reduced expression of PCP4 is associated with CaMKII activation, abnormal electrophysiology, dysregulated intracellular calcium handling, and proarrhythmic behavior in isolated Purkinje cells. Pcp4-null mice also displayed profound autonomic dysregulation and arrhythmic behavior in vivo. Together, these results demonstrate that PCP4 regulates cardiac excitability through both Purkinje cell-autonomous and central mechanisms and identify this modulator of CaMKII signaling as a potential arrhythmia-susceptibility candidate.
PMID: 25295538
ISSN: 0021-9738
CID: 1299982

The Role of Multimodality Imaging in Percutaneous Left Atrial Appendage Suture Ligation with the LARIAT Device

Laura, Diana M; Chinitz, Larry A; Aizer, Anthony; Holmes, Douglas S; Benenstein, Ricardo; Freedberg, Robin S; Kim, Eugene E; Saric, Muhamed
Atrial fibrillation (AF), the most common cardiac arrhythmia, is a significant cause of embolic stroke. Although systemic anticoagulation is the primary strategy for preventing the thromboembolic complications of AF, anticoagulants carry major bleeding risks, and many patients have contraindications to their use. Because thromboembolism typically arises from a clot in the left atrial appendage (LAA), local therapeutic alternatives to systemic anticoagulation involving surgical or percutaneous exclusion of the LAA have been developed. Surgical exclusion of the LAA is typically performed only as an adjunct to other cardiac surgeries, thus limiting the number of eligible patients. Furthermore, surgical exclusion of the LAA is frequently incomplete, and thromboembolism may still occur. Percutaneous LAA exclusion includes two approaches: transseptal delivery of an occlusion device to the LAA and epicardial suture ligation of the LAA, the LARIAT procedure. In the LARIAT procedure, a pretied snare is placed around the epicardial surface of the LAA orifice via pericardial access. Proper snare placement is achieved with epicardial and endocardial magnet-tipped guidewires. The endocardial wire is advanced transvenously to the LAA apex after transseptal puncture. The epicardial wire, introduced into the pericardial space, achieves end-to-end union with the endocardial wire at the LAA apex. The snare is then placed over the LAA, tightened, and sutured. On the basis of early clinical experience, the LARIAT procedure has a high success rate of LAA exclusion with low risk for complications. The authors describe the indispensable role of real-time transesophageal echocardiography in the guidance of LAA epicardial suture ligation with the LARIAT device.
PMID: 24874974
ISSN: 0894-7317
CID: 1018862