140 results on '"Christopher L. Smith"'
Search Results
2. Association of Interstage Monitoring Era and Likelihood of Hemodynamic Compromise at Intervention for Recoarctation Following the Norwood Operation
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Ari J. Gartenberg, Oluwatimilehin Okunowo, Yoav Dori, Christopher L. Smith, J. William Gaynor, Christopher E. Mascio, Jonathan J. Rome, Matthew J. Gillespie, Andrew C. Glatz, and Michael L. O'Byrne
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aortic recoarctation ,congenital heart disease ,hypoplastic left heart syndrome ,interventional cardiology ,single ventricle ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
Background Intensive monitoring has been associated with a lower death rate between the Norwood operation and superior cavopulmonary connection, possibly due to early identification and effective treatment of residual anatomic lesions like recoarctation before lasting harm occurs. Methods and Results Neonates undergoing a Norwood operation and receiving interstage care at a single center between January 1, 2005, and September 18, 2020, were studied. In those with recoarctation, we evaluated association of era ([1] preinterstage monitoring, [2] a transitional phase, [3] current era) and likelihood of hemodynamic compromise (progression to moderate or greater ventricular dysfunction/atrioventricular valve regurgitation, initiation/escalation of vasoactive/respiratory support, cardiac arrest preceding catheterization, or interstage death with recoarctation on autopsy). We also analyzed whether era was associated with technical success of transcatheter recoarctation interventions, major adverse events, and transplant‐free survival. A total of 483 subjects were studied, with 22% (n=106) treated for recoarctation during the interstage period. Number of catheterizations per Norwood increased (P=0.005) over the interstage eras, with no significant change in the proportion of subjects with recoarctation (P=0.36). In parallel, there was a lower likelihood of hemodynamic compromise in subjects with recoarctation that was not statistically significant (P=0.06), with a significant difference in the proportion with ventricular dysfunction at intervention (P=0.002). Rates of technical success, procedural major adverse events, and transplant‐free survival did not differ (P>0.05). Conclusions Periods with interstage monitoring were associated with increased referral for catheterization but also reduced likelihood of ventricular dysfunction (and a suggestion of lower likelihood of hemodynamic compromise) in subjects with recoarctation. Further study is needed to guide optimal interstage care of this vulnerable population.
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- 2023
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3. TESS Giants Transiting Giants. VI. Newly Discovered Hot Jupiters Provide Evidence for Efficient Obliquity Damping after the Main Sequence
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Nicholas Saunders, Samuel K. Grunblatt, Ashley Chontos, Fei Dai, Daniel Huber, Jingwen Zhang, Guđmundur Stefánsson, Jennifer L. van Saders, Joshua N. Winn, Daniel Hey, Andrew W. Howard, Benjamin Fulton, Howard Isaacson, Corey Beard, Steven Giacalone, Judah Van Zandt, Joseph M. Akana Murphey, Malena Rice, Sarah Blunt, Emma Turtelboom, Paul A. Dalba, Jack Lubin, Casey Brinkman, Emma M. Louden, Emma Page, Cristilyn N. Watkins, Karen A. Collins, Chris Stockdale, Thiam-Guan Tan, Richard P. Schwarz, Bob Massey, Steve B. Howell, Andrew Vanderburg, George R. Ricker, Jon M. Jenkins, Sara Seager, Jessie L. Christiansen, Tansu Daylan, Ben Falk, Max Brodheim, Steven R. Gibson, Grant M. Hill, Bradford Holden, Aaron Householder, Stephen Kaye, Russ R. Laher, Kyle Lanclos, Erik A. Petigura, Arpita Roy, Ryan A. Rubenzahl, Christian Schwab, Abby P. Shaum, Martin M. Sirk, Christopher L. Smith, Josh Walawender, and Sherry Yeh
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Exoplanet astronomy ,Exoplanet dynamics ,Exoplanet detection methods ,Exoplanet evolution ,Exoplanet migration ,Exoplanets ,Astronomy ,QB1-991 - Abstract
The degree of alignment between a star’s spin axis and the orbital plane of its planets (the stellar obliquity) is related to interesting and poorly understood processes that occur during planet formation and evolution. Hot Jupiters orbiting hot stars (≳6250 K) display a wide range of obliquities, while similar planets orbiting cool stars are preferentially aligned. Tidal dissipation is expected to be more rapid in stars with thick convective envelopes, potentially explaining this trend. Evolved stars provide an opportunity to test the damping hypothesis, particularly stars that were hot on the main sequence and have since cooled and developed deep convective envelopes. We present the first systematic study of the obliquities of hot Jupiters orbiting subgiants that recently developed convective envelopes using Rossiter–McLaughlin observations. Our sample includes two newly discovered systems in the Giants Transiting Giants survey (TOI-6029 b, TOI-4379 b). We find that the orbits of hot Jupiters orbiting subgiants that have cooled below ∼6250 K are aligned or nearly aligned with the spin axis of their host stars, indicating rapid tidal realignment after the emergence of a stellar convective envelope. We place an upper limit for the timescale of realignment for hot Jupiters orbiting subgiants at ∼500 Myr. Comparison with a simplified tidal evolution model shows that obliquity damping needs to be ∼4 orders of magnitude more efficient than orbital period decay to damp the obliquity without destroying the planet, which is consistent with recent predictions for tidal dissipation from inertial waves excited by hot Jupiters on misaligned orbits.
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- 2024
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4. Lymphatic disorders caused by mosaic, activating KRAS variants respond to MEK inhibition
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Sarah E. Sheppard, Michael E. March, Christoph Seiler, Leticia S. Matsuoka, Sophia E. Kim, Charlly Kao, Adam I. Rubin, Mark R. Battig, Nahla Khalek, Erica Schindewolf, Nora O’Connor, Erin Pinto, Jessica R.C. Priestley, Victoria R. Sanders, Rojeen Niazi, Arupa Ganguly, Cuiping Hou, Diana Slater, Ilona J. Frieden, Thy Huynh, Joseph T. Shieh, Ian D. Krantz, Jessenia C. Guerrero, Lea F. Surrey, David M. Biko, Pablo Laje, Leslie Castelo-Soccio, Taizo A. Nakano, Kristen Snyder, Christopher L. Smith, Dong Li, Yoav Dori, and Hakon Hakonarson
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Cardiology ,Genetics ,Medicine - Abstract
Central conducting lymphatic anomaly (CCLA) due to congenital maldevelopment of the lymphatics can result in debilitating and life-threatening disease with limited treatment options. We identified 4 individuals with CCLA, lymphedema, and microcystic lymphatic malformation due to pathogenic, mosaic variants in KRAS. To determine the functional impact of these variants and identify a targeted therapy for these individuals, we used primary human dermal lymphatic endothelial cells (HDLECs) and zebrafish larvae to model the lymphatic dysplasia. Expression of the p.Gly12Asp and p.Gly13Asp variants in HDLECs in a 2‑dimensional (2D) model and 3D organoid model led to increased ERK phosphorylation, demonstrating these variants activate the RAS/MAPK pathway. Expression of activating KRAS variants in the venous and lymphatic endothelium in zebrafish resulted in lymphatic dysplasia and edema similar to the individuals in the study. Treatment with MEK inhibition significantly reduced the phenotypes in both the organoid and the zebrafish model systems. In conclusion, we present the molecular characterization of the observed lymphatic anomalies due to pathogenic, somatic, activating KRAS variants in humans. Our preclinical studies suggest that MEK inhibition should be studied in future clinical trials for CCLA due to activating KRAS pathogenic variants.
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- 2023
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5. Lymphatic Disorders in Patients With Single Ventricle Heart Disease
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Yoav Dori and Christopher L. Smith
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lymphatics ,protein-losing enteropathy (PLE) ,plastic bronchitis ,chylothorax ,DCMRL ,lymphangiography ,Pediatrics ,RJ1-570 - Abstract
Lymphatic abnormalities in patients with single ventricle physiology can lead to early Fontan failure and severe Fontan complications, such as protein-losing enteropathy (PLE), plastic bronchitis (PB), chylothorax, and edema. Recent developments in lymphatic imaging and interventions have shed new light on the lymphatic dysfunction in this patient population and the role of the lymphatic circulation in PLE, PB, and chylothorax. In this study, we reviewed some of the latest developments in this field and discuss new treatment options for these patients.
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- 2022
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6. Spontaneous contractions of the human thoracic duct—Important for securing lymphatic return during positive pressure ventilation?
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Benjamin Kelly, Christopher L. Smith, Madhumitha Saravanan, Yoav Dori, and Vibeke E. Hjortdal
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congenital heart defects ,lymphatic contractions ,lymphatic intervention ,lymphatic physiology ,positive pressure ventilation ,Physiology ,QP1-981 - Abstract
Abstract The thoracic duct is responsible for the circulatory return of most lymphatic fluid. The return is a well‐timed synergy between the pressure in the thoracic duct, venous pressure at the thoracic duct outlet, and intrathoracic pressures during respiration. However, little is known about the forces determining thoracic duct pressure and how these respond to mechanical ventilation. We aimed to assess human thoracic duct pressure and identify elements affecting it during positive pressure ventilation and a brief ventilatory pause. The study examined pressures of 35 patients with severe congenital heart defects undergoing lymphatic interventions. Thoracic duct pressure and central venous pressure were measured in 25 patients during mechanical ventilation and in ten patients during both ventilation and a short pause in ventilation. TD contractions, mechanical ventilation, and arterial pulsations influenced the thoracic duct pressure. The mean pressure of the thoracic duct was 16 ± 5 mmHg. The frequency of the contractions was 5 ± 1 min−1 resulting in an average increase in pressure of 4 ± 4 mmHg. During mechanical ventilation, the thoracic duct pressure correlated closely to the central venous pressure. TD contractions were able to increase thoracic duct pressure by 25%. With thoracic duct pressure correlating closely to the central venous pressure, this intrinsic force may be an important factor in securing a successful return of lymphatic fluid. Future studies are needed to examine the return of lymphatic fluid and the function of the thoracic duct in the absence of both lymphatic complications and mechanical ventilation.
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- 2022
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7. Intrahepatic Dynamic Contrast‐Enhanced Magnetic Resonance Lymphangiography: Potential Imaging Signature for Protein‐Losing Enteropathy in Congenital Heart Disease
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Bethan A. Lemley, Dave M. Biko, Aaron G. Dewitt, Andrew C. Glatz, David J. Goldberg, Madhumitha Saravanan, Michael L. O’Byrne, Erin Pinto, Chitra Ravishankar, Jonathan J. Rome, Christopher L. Smith, and Yoav Dori
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magnetic resonance lymphangiography ,protein‐losing enteropathy ,single ventricle heart defects ,total cavopulmonary connection ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
Background Protein‐losing enteropathy (PLE) is a significant cause of morbidity and mortality in congenital heart disease patients with single ventricle physiology. Intrahepatic dynamic contrast‐enhanced magnetic resonance lymphangiography (IH‐DCMRL) is a novel diagnostic technique that may be useful in characterizing pathologic abdominal lymphatic flow in the congenital heart disease population and in diagnosing PLE. The objective of this study was to characterize differences in IH‐DCMRL findings in patients with single ventricle congenital heart disease with and without PLE. Methods and Results This was a single‐center retrospective study of IH‐DCMRL findings and clinical data in 41 consecutive patients, 20 with PLE and 21 without PLE, with single ventricle physiology referred for lymphatic evaluation. There were 3 distinct duodenal imaging patterns by IH‐DCMRL: (1) enhancement of the duodenal wall with leakage into the lumen, (2) enhancement of the duodenal wall without leakage into the lumen, and (3) no duodenal involvement. Patients with PLE were more likely to have duodenal involvement on IH‐DCMRL than patients without PLE (P
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- 2021
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8. Prevalence and Cause of Early Fontan Complications: Does the Lymphatic Circulation Play a Role?
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Reena M. Ghosh, Heather M. Griffis, Andrew C. Glatz, Jonathan J. Rome, Christopher L. Smith, Matthew J. Gillespie, Kevin K. Whitehead, Michael L. O'Byrne, David M. Biko, Chitra Ravishankar, Aaron G. Dewitt, and Yoav Dori
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cardiovascular magnetic resonance imaging ,congenital heart disease ,Fontan procedure ,lymph ,morbidity/mortality ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
Background Recent studies suggest that lymphatic congestion plays a role in development of late Fontan complications, such as protein‐losing enteropathy. However, the role of the lymphatic circulation in early post‐Fontan outcomes is not well defined. Methods and Results This was a retrospective, single‐center study of patients undergoing first‐time Fontan completion from 2012 to 2017. The primary outcome was early Fontan complication ≤6 months after surgery, a composite of death, Fontan takedown, extracorporeal membrane oxygenation, chest tube drainage >14 days, cardiac catheterization, readmission, or transplant. Complication causes were assigned to 1 of 4 groups: (1) Fontan circuit obstruction, (2) ventricular dysfunction or atrioventricular valve regurgitation, (3) persistent pleural effusions in the absence of Fontan obstruction or ventricular dysfunction, and (4) chylothorax or plastic bronchitis. T2‐weighted magnetic resonance imaging sequences were used to assess for lymphatic perfusion abnormality. The cohort consisted of 238 patients. Fifty‐eight (24%) developed early complications: 20 of 58 (34.5%) in group 1, 8 of 58 (14%) in group 2, 18 of 58 (31%) in group 3, and 12 of 58 (20%) in group 4. Preoperative T2 imaging was available for 126 (53%) patients. Patients with high‐grade lymphatic abnormalities had 6 times greater odds of developing early complications (P=0.001). Conclusions There is substantial morbidity in the early post‐Fontan period. Half of those who developed early complications had lymphatic failure or persistent effusions unrelated to structural or functional abnormalities. Preoperative T2 imaging demonstrated that patients with higher‐grade lymphatic perfusion abnormalities were significantly more likely to develop early complications. This has implications for risk stratification and optimization of patients before Fontan palliation.
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- 2020
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9. Academic, Clinical, and Psychosocial Profiles for High Ability Individuals with Obsessive Compulsive Disorder
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Brandon LeBeau, Megan Foley-Nicpon, Alissa F. Doobay, Katherine Schabilion, Christopher L. Smith, Amanda J. Berns, and Susan G. Assouline
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How mental health disorders such as obsessive compulsive disorder (OCD) manifest in high ability youth has received little empirical attention, and differentiating OCD from other diagnoses like autism spectrum disorder (ASD) can be challenging. The purpose of this study was to examine clinical profiles among OCD, ASD, or no diagnosis for those of high ability and not high ability. Results indicated those with high ability only tended to obtain higher ability and achievement scores than those with a co-occurring disability. Youth in the high ability/OCD and high ability/ASD groups had lower working memory and processing speed scores than the high ability alone group, but also had frequent comorbid attention-deficit hyperactivity disorder diagnoses. The high ability/OCD and high ability/ASD groups were the most divergent on the anxiety and atypicality Behavioral and Emotional Screening System (BASC) subtests, but an anxiety disorder was often comorbid with OCD.
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- 2024
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10. The Scintillating Grid Illusion is Enhanced by Binocular Viewing
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Jenny C. A. Read, Joseph H. Robson, Christopher L. Smith, and Andrew D. Lucas
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Psychology ,BF1-990 - Abstract
The scintillating grid illusion is an intriguing stimulus consisting of a grey grid on a black background, with white discs at the grid intersections. Most viewers perceive illusory “scintillating” black discs within the physical white discs, especially at non-fixated locations. Here, we report for the first time that this scintillation percept is stronger when the stimulus is viewed binocularly than when it is presented to only one eye. Further experiments indicate that this is not simply because two monocular percepts combine linearly, but involves a specifically cyclopean contribution (Schrauf & Spillmann, 2000). However, the scintillation percept does not depend on the absolute disparity of the stimulus relative to the screen. In an intriguing twist, although the basic illusion shows more scintillation when viewed binocularly, when the illusion is weakened by shifting the discs away from the grid intersections, scintillation becomes stronger with monocular viewing.
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- 2012
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11. Novel Utilization of Ultrasound Enhancing Agents in Complex Congenital Heart Disease Following Superior Cavopulmonary Connection
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Kasey J. Chaszczewski, Jarett R. Linder, Matthew J. Campbell, Michael Convery, Yan Wang, Christopher L. Smith, Benjamin W. Kozyak, and Michael D. Quartermain
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Radiology, Nuclear Medicine and imaging ,Cardiology and Cardiovascular Medicine - Published
- 2023
12. Predicting Exploitation of Disclosed Software Vulnerabilities Using Open-source Data.
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Benjamin L. Bullough, Anna K. Yanchenko, Christopher L. Smith, and Joseph R. Zipkin
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- 2017
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13. 'The Great Retirement Boom': The Pandemic-Era Surge in Retirements and Implications for Future Labor Force Participation
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Joshua Montes, Christopher L. Smith, and Juliana Dajon
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As of October 2022, the retired share of the U.S. population was nearly 1½ percentage points above its pre-pandemic level (after adjusting for updated population controls to the Current Population Survey), accounting for nearly all of the shortfall in the labor force participation rate. In this paper, we analyze the pandemic-era rise in retirements using a model that accounts for pre-pandemic trends in retirement, the cyclicality of retirement, and other factors. We show that: more than half of the increase in the retired share are “excess retirements” that would likely not have occurred in the absence of the pandemic; excess retirements have been concentrated among cohorts age 65 and older at the start of the pandemic; excess retirements have been largest among the college-educated and whites; and excess retirements reflect in part that worker transitions from the labor force to retirement remain elevated. We also show that failing to account for updated population controls to the Current Population Survey leads to an underestimate of the rise in the retired share over the last few years. We use a cohort-based framework to argue that looking forward, unless the pandemic has permanently affected retirement behavior, excess retirements should eventually fade as those who retired early during the pandemic reach ages when they would have normally retired. Even as excess retirements fade, the retired share will remain well above its pre-pandemic level, reflecting population aging.
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- 2022
14. Occlusion Pressure of the Thoracic Duct in Fontan Patients With Lymphatic Failure: Does Dilatation Challenge Contractility?
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Jill J. Savla, Benjamin Kelly, Emil Krogh, Christopher L. Smith, Ganesh Krishnamurthy, Andrew C. Glatz, Aaron G. DeWitt, Erin M. Pinto, Chitra Ravishankar, Matthew J. Gillespie, Michael L. O’Byrne, Fernando A. Escobar, Jonathan J. Rome, Vibeke Hjortdal, and Yoav Dori
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Lymphatic Vessels/diagnostic imaging ,Lymphatic System ,Pediatrics, Perinatology and Child Health ,Humans ,Surgery ,General Medicine ,Cardiology and Cardiovascular Medicine ,Dilatation ,Thoracic Duct ,Retrospective Studies ,Lymphatic Vessels ,Dilatation, Pathologic - Abstract
Background The Fontan circulation challenges the lymphatic system. Increasing production of lymphatic fluid and impeding lymphatic return, increased venous pressure may cause lymphatic dilatation and decrease lymphatic contractility. In-vitro studies have reported a lymphatic diameter-tension curve, with increasing passive stretch affecting the intrinsic contractile properties of each thoracic duct segment. We aimed to describe thoracic duct occlusion pressure and asses if thoracic duct dilation impairs contractility in individuals with a Fontan circulation and lymphatic failure. Methods Central venous pressure and thoracic duct measurements were retrospectively collected from 31 individuals with a Fontan circulation. Thoracic duct occlusion pressure was assessed during a period of external manual compression and used as an indicator of lymphatic vessel contractility. Measurements of pressure were correlated with measurements of the thoracic duct diameter in images obtained by dynamic contrast-enhanced MR lymphangiography. Results The average central venous pressure and average pressure of the thoracic duct were 17 mm Hg. During manual occlusion, the thoracic duct pressure significantly increased to 32 mm Hg. The average thoracic duct diameter was 3.3 mm. Thoracic duct diameter correlated closely with the central venous pressure. The rise in pressure following manual occlusion showed an inverse correlation with the diameter of the thoracic duct. Conclusion Higher central venous pressures are associated with increasing diameters of the thoracic duct. When challenged by manual occlusion, dilated thoracic ducts display a decreased ability to increase pressure. Dilatation and a resulting decreased contractility may partly explain the challenged lymphatic system in individuals with a Fontan circulation.
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- 2022
15. Lymphatic anomalies in congenital heart disease
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Karen I. Ramirez-Suarez, Luis Octavio Tierradentro-García, David M. Biko, Hansel J. Otero, Ammie M. White, Yoav Dori, Christopher L. Smith, Seth Vatsky, and Jordan B. Rapp
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Pediatrics, Perinatology and Child Health ,Radiology, Nuclear Medicine and imaging - Published
- 2022
16. Pathogenic variants in PIK3CA are associated with clinical phenotypes of kaposiform lymphangiomatosis, generalized lymphatic anomaly, and central conducting lymphatic anomaly
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Jeremy M. Grenier, Alexandra J. Borst, Sarah E. Sheppard, Kristen M. Snyder, Dong Li, Lea F. Surrey, Alyaa Al‐Ibraheemi, David R. Weber, James R. Treat, Christopher L. Smith, Pablo Laje, Yoav Dori, Denise M. Adams, Michael Acord, and Abhay S. Srinivasan
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Oncology ,Pediatrics, Perinatology and Child Health ,Hematology - Published
- 2023
17. Understanding the next circulation: lymphatics and what the future holds
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Catherine E. Tomasulo, Yoav Dori, and Christopher L. Smith
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Cardiology and Cardiovascular Medicine - Published
- 2023
18. Data from Mesenchymal Stem Cells from Human Fat Engineered to Secrete BMP4 Are Nononcogenic, Suppress Brain Cancer, and Prolong Survival
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Alfredo Quinones-Hinojosa, Andre Levchenko, Hugo Guerrero-Cazares, Christopher L. Smith, Hao Zhang, David A. Chesler, Kaisorn L. Chaichana, Colette Aprhys, Mingxin Zhu, Joanna Y. Wang, Sussan J. Salas, Olindi Wijesekera, and Qian Li
- Abstract
Purpose: Glioblastoma is the most common adult primary malignant intracranial cancer. It is associated with poor outcomes because of its invasiveness and resistance to multimodal therapies. Human adipose-derived mesenchymal stem cells (hAMSC) are a potential treatment because of their tumor tropism, ease of isolation, and ability to be engineered. In addition, bone morphogenetic protein 4 (BMP4) has tumor-suppressive effects on glioblastoma and glioblastoma brain tumor–initiating cells (BTIC), but is difficult to deliver to brain tumors. We sought to engineer BMP4-secreting hAMSCs (hAMSCs-BMP4) and evaluate their therapeutic potential on glioblastoma.Experimental Design: The reciprocal effects of hAMSCs on primary human BTIC proliferation, differentiation, and migration were evaluated in vitro. The safety of hAMSC use was evaluated in vivo by intracranial coinjections of hAMSCs and BTICs in nude mice. The therapeutic effects of hAMSCs and hAMSCs-BMP4 on the proliferation and migration of glioblastoma cells as well as the differentiation of BTICs, and survival of glioblastoma-bearing mice were evaluated by intracardiac injection of these cells into an in vivo intracranial glioblastoma murine model.Results: hAMSCs-BMP4 targeted both the glioblastoma tumor bulk and migratory glioblastoma cells, as well as induced differentiation of BTICs, decreased proliferation, and reduced the migratory capacity of glioblastomas in vitro and in vivo. In addition, hAMSCs-BMP4 significantly prolonged survival in a murine model of glioblastoma. We also demonstrate that the use of hAMSCs in vivo is safe.Conclusions: Both unmodified and engineered hAMSCs are nononcogenic and effective against glioblastoma, and hAMSCs-BMP4 are a promising cell-based treatment option for glioblastoma. Clin Cancer Res; 20(9); 2375–87. ©2014 AACR.
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- 2023
19. Supplemental Figure 4 from Mesenchymal Stem Cells from Human Fat Engineered to Secrete BMP4 Are Nononcogenic, Suppress Brain Cancer, and Prolong Survival
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Alfredo Quinones-Hinojosa, Andre Levchenko, Hugo Guerrero-Cazares, Christopher L. Smith, Hao Zhang, David A. Chesler, Kaisorn L. Chaichana, Colette Aprhys, Mingxin Zhu, Joanna Y. Wang, Sussan J. Salas, Olindi Wijesekera, and Qian Li
- Abstract
Supplementary SFig. 4. hAMSCs retain proliferation capacity when exposed to BTIC-CM in vitro.
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- 2023
20. Supplemental Materials and Methods from Mesenchymal Stem Cells from Human Fat Engineered to Secrete BMP4 Are Nononcogenic, Suppress Brain Cancer, and Prolong Survival
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Alfredo Quinones-Hinojosa, Andre Levchenko, Hugo Guerrero-Cazares, Christopher L. Smith, Hao Zhang, David A. Chesler, Kaisorn L. Chaichana, Colette Aprhys, Mingxin Zhu, Joanna Y. Wang, Sussan J. Salas, Olindi Wijesekera, and Qian Li
- Abstract
Supplemental Materials and Methods from Mesenchymal Stem Cells from Human Fat Engineered to Secrete BMP4 Are Nononcogenic, Suppress Brain Cancer, and Prolong Survival
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- 2023
21. Supplemental Figure 3 from Mesenchymal Stem Cells from Human Fat Engineered to Secrete BMP4 Are Nononcogenic, Suppress Brain Cancer, and Prolong Survival
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Alfredo Quinones-Hinojosa, Andre Levchenko, Hugo Guerrero-Cazares, Christopher L. Smith, Hao Zhang, David A. Chesler, Kaisorn L. Chaichana, Colette Aprhys, Mingxin Zhu, Joanna Y. Wang, Sussan J. Salas, Olindi Wijesekera, and Qian Li
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Supplementary SFig. 3. hAMSCs-BMP4 promote differentiation of BTICs in vitro.
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- 2023
22. Supplementary Figure Legends from Mesenchymal Stem Cells from Human Fat Engineered to Secrete BMP4 Are Nononcogenic, Suppress Brain Cancer, and Prolong Survival
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Alfredo Quinones-Hinojosa, Andre Levchenko, Hugo Guerrero-Cazares, Christopher L. Smith, Hao Zhang, David A. Chesler, Kaisorn L. Chaichana, Colette Aprhys, Mingxin Zhu, Joanna Y. Wang, Sussan J. Salas, Olindi Wijesekera, and Qian Li
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Supplementary Figure Legends
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- 2023
23. Supplemental Figure 5 from Mesenchymal Stem Cells from Human Fat Engineered to Secrete BMP4 Are Nononcogenic, Suppress Brain Cancer, and Prolong Survival
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Alfredo Quinones-Hinojosa, Andre Levchenko, Hugo Guerrero-Cazares, Christopher L. Smith, Hao Zhang, David A. Chesler, Kaisorn L. Chaichana, Colette Aprhys, Mingxin Zhu, Joanna Y. Wang, Sussan J. Salas, Olindi Wijesekera, and Qian Li
- Abstract
Supplemental SFig. 5. hAMSCs do not form tumors in vivo.
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- 2023
24. Supplemental Figure 1 from Mesenchymal Stem Cells from Human Fat Engineered to Secrete BMP4 Are Nononcogenic, Suppress Brain Cancer, and Prolong Survival
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Alfredo Quinones-Hinojosa, Andre Levchenko, Hugo Guerrero-Cazares, Christopher L. Smith, Hao Zhang, David A. Chesler, Kaisorn L. Chaichana, Colette Aprhys, Mingxin Zhu, Joanna Y. Wang, Sussan J. Salas, Olindi Wijesekera, and Qian Li
- Abstract
Supplementary SFig. 1. hAMSCs-BMP4 decrease migration of BTICs in vitro.
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- 2023
25. Supplemental Figure 6 from Mesenchymal Stem Cells from Human Fat Engineered to Secrete BMP4 Are Nononcogenic, Suppress Brain Cancer, and Prolong Survival
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Alfredo Quinones-Hinojosa, Andre Levchenko, Hugo Guerrero-Cazares, Christopher L. Smith, Hao Zhang, David A. Chesler, Kaisorn L. Chaichana, Colette Aprhys, Mingxin Zhu, Joanna Y. Wang, Sussan J. Salas, Olindi Wijesekera, and Qian Li
- Abstract
Supplemental SFig. 6. hAMSCs-BMP4 decrease TNF-α and VEGF in tumor mass in vivo.
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- 2023
26. Genetics etiologies and genotype phenotype correlations in a cohort of individuals with central conducting lymphatic anomaly
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Mandi Liu, Christopher L. Smith, David M. Biko, Dong Li, Erin Pinto, Nora O’Connor, Cara Skraban, Elaine H. Zackai, Hakon Hakonarson, Yoav Dori, and Sarah E. Sheppard
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Genetics ,Genetics (clinical) - Published
- 2022
27. Lymphatic Disorders and Management in Patients With Congenital Heart Disease
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Jonathan M. Chen, Jonathan J. Rome, Christopher L. Smith, Catherine E. Tomasulo, Katsuhide Maeda, and Yoav Dori
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Heart Defects, Congenital ,Pulmonary and Respiratory Medicine ,medicine.medical_specialty ,Heart disease ,Plastic bronchitis ,Protein-Losing Enteropathies ,030204 cardiovascular system & hematology ,Lymphatic System ,03 medical and health sciences ,0302 clinical medicine ,Ascites ,Humans ,Medicine ,Enteropathy ,In patient ,Bronchitis ,Intensive care medicine ,Lymphatic Diseases ,business.industry ,fungi ,food and beverages ,Chylothorax ,medicine.disease ,Lymphatic system ,030228 respiratory system ,Surgery ,medicine.symptom ,Cardiology and Cardiovascular Medicine ,business ,Lymphatic Disorders - Abstract
Congenital heart disease can lead to notable lymphatic complications such as chylothorax, plastic bronchitis, protein-losing enteropathy, and ascites. Recent improvements in lymphatic imaging and the development of new lymphatic procedures can help alleviate symptoms and improve outcomes.
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- 2022
28. Dynamic contrast-enhanced MR lymphangiography: feasibility of using ferumoxytol in patients with chronic kidney disease
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Ensar Yekeler, Ganesh Krishnamurthy, Christopher L. Smith, Fernando A. Escobar, Erin Pinto, Jordan B. Rapp, Hansel J. Otero, Ammie M. White, Yoav Dori, and David M. Biko
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Radiology, Nuclear Medicine and imaging ,General Medicine - Published
- 2022
29. Kaposiform lymphangiomatosis: Diagnosis, pathogenesis, and treatment
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C. Griffin McDaniel, Denise M. Adams, Kimberley E. Steele, Adrienne M. Hammill, A. Carl Merrow, Janet L. Crane, Christopher L. Smith, Harry P. W. Kozakewich, and Timothy D. Le Cras
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Oncology ,Pediatrics, Perinatology and Child Health ,Hematology - Published
- 2023
30. Post-operative Chylothorax in Patients with Repaired Transposition of the Great Arteries
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Yoav Dori, Madhumitha Saravanan, Christopher L. Smith, David J. Goldberg, Erin Pinto, Jonathan J. Rome, Michael L. O'Byrne, Danish Vaiyani, Matthew J. Gillespie, Aaron G. DeWitt, and Chitra Ravishankar
- Subjects
medicine.medical_specialty ,business.industry ,Chylothorax ,Vascular surgery ,medicine.disease ,Thoracic duct ,Surgery ,Lymphatic disease ,Cardiac surgery ,Venous thrombosis ,medicine.anatomical_structure ,Great arteries ,Pediatrics, Perinatology and Child Health ,medicine ,Medical history ,Cardiology and Cardiovascular Medicine ,business - Abstract
Patients with dextro-transposition of the great arteries (d-TGA) require surgical repair as neonates. These patients are at risk for post-operative chylothorax. We sought to describe the presentation, imaging, and outcomes after intervention for patients with d-TGA with post-operative chylothorax. A retrospective chart review was performed in patients with repaired d-TGA who were referred from 1/1/2013 to 4/1/2020 for evaluation of chylothorax. Patient history, lymphatic imaging, and interventional data were collected. Impact of intervention on lymphatic drainage was evaluated with a student’s t-test. Eight patients met inclusion criteria for this study. Five patients had a history of central venous thrombus leading to thoracic duct outlet occlusion. Five patients underwent intervention, two were managed conservatively, and one was not a candidate for intervention. Chylothorax resolved in six patients. There was a significant difference in output from 7 days prior to first intervention (114 mL/kg/day) compared to 28 days following final intervention (27 mL/kg/day, p = 0.034). There were no procedural complications. Chylothorax in patients with repaired transposition of the great arteries is often amenable to intervention. Early surveillance and management of central venous thrombosis may reduce the burden of lymphatic disease in these patients.
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- 2021
31. A Hybrid Algorithm for Parameter Estimation (HAPE) for Dynamic Constant Power Loads
- Author
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Christopher L. Smith, James L. Kirtley, and Matthew Overlin
- Subjects
Control and Systems Engineering ,Computer science ,Control theory ,Estimation theory ,Amplifier ,Testbed ,Waveform ,Device under test ,Electrical and Electronic Engineering ,Stability (probability) ,Hybrid algorithm ,Voltage - Abstract
Low-inertia microgrids may easily have a single load that can make up most of the total load, thereby greatly affecting stability and power quality. Instead of a static load model, a dynamic constant power load (DCPL) model is considered here. Next, a hybrid algorithm for parameter estimation (HAPE) is introduced. In order to verify the load model and the HAPE, two experiments are conducted with different DCPLs using a power-hardware-in-the-loop (PHiL) testbed. The PHiL testbed consists of a real-time computer working with a programmable power amplifier in order to perturb the input voltage's amplitude and frequency. Each connected DCPL in two separate experiments serves as the device under test. Using the captured experimental data as a reference, the HAPE is then invoked. The resulting parameter estimates are used to define simulation models. Both resulting DCPL models are simulated to produce waveforms that closely resemble experimental waveforms. Finally, the HAPE's resulting parameter estimates are presented, and the performance of the HAPE is discussed.
- Published
- 2021
32. Effect of positive pressure ventilation on lymphatic flow in pediatric patients
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Sarah Khan, Christopher L. Smith, Erin M. Pinto, Dalal K. Taha, Kathleen A. Gibbs, Samuel A. Rosenblatt, and Yoav Dori
- Subjects
Pediatrics, Perinatology and Child Health ,Obstetrics and Gynecology - Published
- 2022
33. Alternative Evaluation of the Right Axillary Lymphatic Pathway by Using Dynamic Contrast-enhanced MR Lymphangiography
- Author
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Michael Simon, Yoav Dori, Christopher L. Smith, David M. Biko, Lea F. Surrey, Denise M. Adams, Ganesh Krishnamurthy, and Jordan B. Rapp
- Subjects
Case Report ,Radiology, Nuclear Medicine and imaging - Abstract
The lymphatic system plays an integral part in fluid homeostasis. Disturbances in lymphatic pathways are congenital, posttraumatic, or posttreatment related, such as after Fontan palliation. Lymphatic pathway evaluation is challenging because of the difficulty in introducing contrast material into the lymphatics. Intranodal, intramesenteric, and intrahepatic dynamic contrast-enhanced MR lymphangiography (DCMRL) offer better visualization of major lymphatic pathways. However, these techniques exclude pathways outside the central conduction system, preventing the visualization of abnormalities and, thus, administration of treatment. The authors describe alternative imaging of an axillary pathway via DCMRL in a patient with a symptomatic chylous effusion not previously assessed with current techniques. Keywords: Lymphatic, MR–Dynamic Contrast Enhanced, Pediatrics, Thorax, Pleura Supplemental material is available for this article. © RSNA, 2022
- Published
- 2022
34. Liver lymphatic anatomy and role in systemic lymphatic disease
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Madhumitha Saravanan, Matthew J. Gillespie, Mandi Liu, Aaron G. DeWitt, Andrew C. Glatz, David M. Biko, Christopher L. Smith, Jefferson N. Brownell, Ganesh Krishnamurthy, Michael L. O'Byrne, Fernando Escobar, Chitra Ravishankar, Yoav Dori, Erin Pinto, Jonathan J. Rome, and Petar Mamula
- Subjects
medicine.medical_specialty ,030204 cardiovascular system & hematology ,Chylothorax ,030218 nuclear medicine & medical imaging ,03 medical and health sciences ,0302 clinical medicine ,Ascites ,Lymphatic diseases ,medicine ,Humans ,Radiology, Nuclear Medicine and imaging ,Lymphatic Vessels ,Retrospective Studies ,Neuroradiology ,medicine.diagnostic_test ,business.industry ,Protein losing enteropathy ,Lymphography ,Interventional radiology ,Retrospective cohort study ,General Medicine ,medicine.disease ,Lymphatic disease ,Lymphatic system ,Liver ,Paediatric ,Radiology ,medicine.symptom ,business - Abstract
ObjectivesTo characterize hepatic to systemic lymphatic connections in patients with systemic lymphatic disease using intra-hepatic lymphangiography and to compare outcomes after lymphatic intervention.MethodsIn this retrospective study, patients with intra-hepatic lymphangiography from May 2014 – April 2019 at our institution were included. Imaging review was performed and hepatic lymphatic connections and flow patterns were characterized. Clinical data were reviewed and comparisons between patients undergoing lymphatic intervention with or without abnormal hepatic lymphatics were performed.ResultsDuring the study period, 105 patients underwent intra-hepatic lymphangiography. Primary clinical presentation included ascites (19/105), chylothorax (27/105), plastic bronchitis (PB) (17/105), and protein losing enteropathy (PLE) (42/105). Five categories of hepatic lymphatic connections and flow patterns were identified (%): normal (25%, 26/105), hepatoperitoneal (12%, 13/105), hepatopulmonary (10.5%, 11/105), hepatomesenteric (7.5%, 8/105), and hepatoduodenal (41%, 43/105) with four patients having more than one abnormal pattern. A comparison between clinical presentation and imaging category revealed an increased likelihood of having ascites with hepatoperitoneal (p< .0001), chylothorax/PB with hepatopulmonary (p= .01), and PLE with hepatoduodenal (p< .001) connections. Seventy-six patients had a lymphatic intervention, 24% with normal, and 76% with abnormal liver lymphatics. There was no difference in length of hospital stay or mortality between the two groups, but there was a prolonged time to symptom resolution (p= .006) and persistent symptoms after 6 months (5% vs 44%,p= .002) in the group with abnormal liver lymphatics.ConclusionWe identified five liver lymphatic imaging categories with a substantial correlation to presenting lymphatic disease. Abnormal imaging patterns correlated with increased morbidity. Evaluation of liver lymphatics should be considered in patients with a systemic lymphatic disease if central lymphatic imaging is normal.Key Points•We identified five liver lymphatic imaging patterns: normal, hepatoperitoneal, hepatomesenteric, hepatopulmonary, and hepatoduodenal.•Imaging patterns were correlated with disease presentation (normal – chylothorax/PB, hepatoperitoneal – ascites/chylothorax, hepatopulmonary – chylothorax/PB, hepatoduodenal – PLE).•Abnormal imaging patterns correlated with increased morbidity.
- Published
- 2021
35. State-of-the-art imaging for lymphatic evaluation in children
- Author
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Karen I. Ramirez-Suarez, Luis Octavio Tierradentro-Garcia, Joseph A. Stern, Yoav Dori, Fernando A. Escobar, Hansel J. Otero, Jordan B. Rapp, Christopher L. Smith, Ganesh Krishnamurthy, and David M. Biko
- Subjects
Pediatrics, Perinatology and Child Health ,Radiology, Nuclear Medicine and imaging - Published
- 2022
36. Transcatheter Thoracic Duct Decompression for Multicompartment Lymphatic Failure After Fontan Palliation
- Author
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Christopher L. Smith, Yoav Dori, Michael L. O’Byrne, Andrew C. Glatz, Matthew J. Gillespie, and Jonathan J. Rome
- Subjects
Adult ,Decompression ,Heart Defects, Congenital ,Adolescent ,Protein-Losing Enteropathies ,Fontan Procedure ,Thoracic Duct ,Young Adult ,Postoperative Complications ,Treatment Outcome ,Child, Preschool ,Humans ,Bronchitis ,Child ,Cardiology and Cardiovascular Medicine ,Plastics - Abstract
Background: Lymphatic embolization therapy has proven effective for Fontan failure from plastic bronchitis or protein-losing enteropathy but not when multiple lymphatic compartments are involved; furthermore, embolization does not alter the underlying pathophysiology of lymphatic dysfunction. A technique for transcatheter thoracic duct decompression (TDD), rerouting the thoracic duct to the pulmonary venous atrium to treat multicompartment lymphatic failure is described and early outcomes presented. Methods: Initially covered stents were used to channel the innominate vein flow inside of the cavopulmonary pathway into the pulmonary venous atrium. A modified approach was developed where covered stents redirected innominate vein directly to the left atrium via an extravascular course. Baseline and follow-up data on all patients undergoing TDD were reviewed. Results: Twelve patients underwent TDD between March 2018 and February 2021 at a median age of 12 (range: 2–22) years. Lymphatic failure occurred in median of 3 compartments per patient (protein-losing enteropathy, ascites, pleural effusions, plastic bronchitis); 10 patients had lymphatic embolizations before TDD. TDD method was intra-Fontan tunnel in 4, direct approach in 7, and other in 1. There were no major procedural complications; 6 patients underwent subsequent procedures, most commonly to treat endoleaks. Lymphatic failure resolved in 6 patients, improved in 2, and was unchanged in 4 at 6 (range: 1–20) months follow-up. One patient died after TDD from Fontan failure. Conclusions: TDD is a promising new treatment for the failing Fontan physiology from multicompartment lymphatic failure. Additional work is needed to refine the technique and define optimal candidates.
- Published
- 2022
37. Dynamic contrast-enhanced magnetic resonance lymphangiography
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Karen I Ramirez-Suarez, Yoav Dori, Luis Octavio Tierradentro-García, Christopher L. Smith, Fernando Escobar, Ganesh Krishnamurthy, Hansel J. Otero, Jordan B Rapp, and David M. Biko
- Subjects
medicine.medical_specialty ,medicine.diagnostic_test ,business.industry ,Chylothorax ,Magnetic resonance imaging ,Lymphatic flow ,medicine.disease ,030218 nuclear medicine & medical imaging ,03 medical and health sciences ,0302 clinical medicine ,Lymphatic system ,Lymphedema ,Pediatrics, Perinatology and Child Health ,Chylopericardium ,Medicine ,Radiology, Nuclear Medicine and imaging ,Enteropathy ,Radiology ,business ,030217 neurology & neurosurgery ,Neuroradiology - Abstract
Lymphatic flow disorders include a broad spectrum of abnormalities that can originate in the lymphatic or the venous system. The development of these disorders is multifactorial and is most commonly associated with congenital heart diseases and palliative surgeries that these patients undergo. Central lymphatic disorders might be secondary to traumatic leaks, lymphatic overproduction, conduction abnormalities or lymphedema, and they can progress to perfusion anomalies. Several imaging modalities have been used to visualize the lymphatic system. However, the imaging of central lymphatic flow has always been challenging. Dynamic contrast-enhanced magnetic resonance lymphangiography (DCMRL) allows for visualization of central lymphatic flow disorders and has been recently applied for the assessment of plastic bronchitis, protein-losing enteropathy, chylothorax and chylopericardium, among other lymphatic disorders. The hepatic and mesenteric accesses are innovative and promising techniques for better identification and understanding of these abnormalities. The main objectives of this review are to discuss the physiology and anatomy of the lymphatic system and review the current uses of DCMRL in the diagnosis and management of lymphatic flow disorders.
- Published
- 2021
38. O-3 | Identification and Percutaneous Embolization of Abnormal Hepatopulmonary Lymphatic Connections
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Mudit Gupta, Catherine E. Tomasulo, Brooke Ford, Abhay S. Srinivasan, Ganesh Krishnamurthy, Fernando Escobar, Yoav Dori, and Christopher L. Smith
- Published
- 2023
39. Outcomes of Operator-Directed Sedation and Anesthesiologist Care in the Pediatric/Congenital Catheterization Laboratory
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Kevin F. Kennedy, Marisa E. Millenson, Christopher L. Smith, James M. Steven, Kevin D. Hill, Yoav Dori, Matthew J. Gillespie, Andrew C. Glatz, Reid C. Chamberlain, Jonathan J. Rome, and Michael L. O'Byrne
- Subjects
medicine.medical_specialty ,Framingham Risk Score ,business.industry ,Sedation ,medicine.medical_treatment ,Health services research ,Retrospective cohort study ,030204 cardiovascular system & hematology ,03 medical and health sciences ,0302 clinical medicine ,Case mix index ,Emergency medicine ,medicine ,030212 general & internal medicine ,Outcomes research ,medicine.symptom ,Cardiology and Cardiovascular Medicine ,Adverse effect ,business ,Cardiac catheterization - Abstract
Objectives The objective of this study was to assess contemporary use of operator directed sedation (ODS) and anesthesiologist care (AC) in the pediatric/congenital cardiac catheterization laboratory (PCCL), specifically evaluating whether the use of operator-directed sedation was associated with increased risk of major adverse events. Background The safety of ODS relative to AC during PCCL procedures has been questioned. Methods A multicenter, retrospective cohort study was performed studying procedures habitually performed with ODS or AC at IMPACT (Improving Adult and Congenital Treatment) registry hospitals using ODS for ≥5% of cases. The risks for major adverse events (MAE) for ODS and AC cases were compared, adjusted for case mix. Current recommendations were evaluated by comparing the ratio of observed to expected MAE for cases in which ODS was inappropriate (inconsistent with those guidelines) with those for similar risk AC cases, as well as those in which ODS or AC was appropriate. Results Of the hospitals submitting data to IMPACT, 28 of 101 met inclusion criteria. Of the 7,042 cases performed using ODS at these centers, 88% would be inappropriate. Use of ODS was associated with lower likelihood of MAE both in observed results (p Conclusions Across a range of hospitals, ODS was used safely and with improved efficiency. Clinical judgment better identified cases in which ODS could be used than pre-procedural risk score. This should inform future guidelines for the use of ODS and AC in the catheterization laboratory
- Published
- 2021
40. Pediatric/Congenital Cardiac Catheterization Quality
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Jonathan J. Rome, Ivor B Asztalos, Michael L. O'Byrne, Jing Huang, Matthew J. Gillespie, Yoav Dori, Christopher L. Smith, and Andrew C. Glatz
- Subjects
medicine.medical_specialty ,Quality management ,business.industry ,medicine.medical_treatment ,media_common.quotation_subject ,Disease ,030204 cardiovascular system & hematology ,03 medical and health sciences ,Patient safety ,0302 clinical medicine ,Catheterization procedure ,Heart catheterization ,Medicine ,Quality (business) ,Medical physics ,030212 general & internal medicine ,Metric (unit) ,Cardiology and Cardiovascular Medicine ,business ,Cardiac catheterization ,media_common - Abstract
Objectives The aim of this study was to enumerate and categorize quality metrics relevant to the pediatric/congenital cardiac catheterization laboratory (PCCL). Background Diagnostic and interventional catheterization procedures are an increasingly important part of the care of young patients with cardiac disease. Measurement of the performance of PCCL programs in a stringent and consistent fashion is a crucial step toward improving outcomes. To the best of our knowledge, a systematic evaluation of current quality metrics in PCCL has not been performed previously. Methods Potential metrics were evaluated by: 1) a systematic review of peer-reviewed research; 2) a review of metrics from organizations interested in quality improvement, patient safety, and/or PCCL programs; and 3) a survey of U.S. PCCL cardiologists. Collected metrics were grouped on 2 dimensions: 1) Institute of Medicine domains; and 2) the Donabedian structure/process/outcome framework. Survey responses were dichotomized between favorable and unfavorable responses and then compared within and between categories. Results In the systematic review, 6 metrics were identified (from 9 publications), all focused on safety either as an outcome (adverse events [AEs], mortality, and failure to rescue along with radiation exposure) or as a structure (procedure volume or operator experience). Four organizations measure quality metrics of PCCL programs, of which only 1 publicly reports data. For the survey, 229 cardiologists from 118 hospital programs responded (66% of individuals and 72% of hospital programs). The highest favorable ratings were for safety metrics (p Conclusions There is a limited number of PCCL quality metrics, primarily focused on safety. Confidence in current risk adjustment methodology is low. The knowledge gaps identified should guide future research in the development of new quality metrics.
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- 2020
41. Pathogenic variants in
- Author
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Alicia B, Byrne, Pascal, Brouillard, Drew L, Sutton, Jan, Kazenwadel, Saba, Montazaribarforoushi, Genevieve A, Secker, Anna, Oszmiana, Milena, Babic, Kelly L, Betterman, Peter J, Brautigan, Melissa, White, Sandra G, Piltz, Paul Q, Thomas, Christopher N, Hahn, Matthias, Rath, Ute, Felbor, G Christoph, Korenke, Christopher L, Smith, Kathleen H, Wood, Sarah E, Sheppard, Denise M, Adams, Ariana, Kariminejad, Raphael, Helaers, Laurence M, Boon, Nicole, Revencu, Lynette, Moore, Christopher, Barnett, Eric, Haan, Peer, Arts, Miikka, Vikkula, Hamish S, Scott, and Natasha L, Harvey
- Subjects
Mice ,Myogenic Regulatory Factors ,Pregnancy ,Hydrops Fetalis ,Animals ,Endothelial Cells ,Humans ,Female ,Lymphedema ,Chylothorax ,Lymphatic Vessels - Abstract
Central conducting lymphatic anomaly (CCLA), characterized by the dysfunction of core collecting lymphatic vessels including the thoracic duct and cisterna chyli, and presenting as chylothorax, pleural effusions, chylous ascites, and lymphedema, is a severe disorder often resulting in fetal or perinatal demise. Although pathogenic variants in RAS/mitogen activated protein kinase (MAPK) signaling pathway components have been documented in some patients with CCLA, the genetic etiology of the disorder remains uncharacterized in most cases. Here, we identified biallelic pathogenic variants in
- Published
- 2022
42. Imaging of fetal lymphangiectasias: prenatal and postnatal imaging findings
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Teresa Victoria, David M. Biko, Christopher L. Smith, Christian A. Barrera, Ganesh Krishnamurthy, Fernando Escobar, and Julie S. Moldenhauer
- Subjects
medicine.medical_specialty ,Modalities ,Modality (human–computer interaction) ,medicine.diagnostic_test ,business.industry ,Ultrasound ,Magnetic resonance imaging ,Lymphangiectasia ,medicine.disease ,030218 nuclear medicine & medical imaging ,Lymphatic disease ,03 medical and health sciences ,0302 clinical medicine ,Lymphatic system ,030225 pediatrics ,Pediatrics, Perinatology and Child Health ,medicine ,Radiology, Nuclear Medicine and imaging ,Radiology ,business ,Neuroradiology - Abstract
Lymphangiectasias are lymphatic malformations characterized by the abnormal dilation and morphology of the lymphatic channels. The classification and treatment of these disorders can be challenging given the limited amount of literature available in children. Various imaging modalities are used to confirm suspected diagnosis, plan the most appropriate treatment, and estimate a prognosis. Prenatal evaluation is performed using both prenatal US imaging and fetal MRI. These modalities are paramount for appropriate parental counseling and planning of perinatal care. During the neonatal period, chest US imaging is a useful modality to evaluate pulmonary lymphangiectasia because other modalities such as conventional radiography and CT display nonspecific findings. Finally, the recent breakthroughs in lymphatic imaging with MRI have allowed us to better classify lymphatic disorders. Dynamic contrast-enhanced lymphangiography, conventional lymphangiography and percutaneous lymphatic procedures offer static and dynamic evaluation of the central conducting lymphatics in children, with excellent spatial resolution and the possibility to provide treatment. The purpose of this review is to discuss the normal and abnormal development of the fetal lymphatic system and how to best depict it by imaging during the prenatal and postnatal life.
- Published
- 2020
43. Use of Contrast-Enhanced Ultrasound to Determine Thoracic Duct Patency
- Author
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Mandi Liu, Erin Pinto, Jonathan J. Rome, Molly Shipman, David M. Biko, Hansel J. Otero, Erika J. Mejia, Yoav Dori, Aaron G. DeWitt, and Christopher L. Smith
- Subjects
Male ,Percutaneous ,Adolescent ,Contrast Media ,Article ,Thoracic duct ,Thoracic Duct ,030218 nuclear medicine & medical imaging ,03 medical and health sciences ,0302 clinical medicine ,Predictive Value of Tests ,Humans ,Medicine ,Radiology, Nuclear Medicine and imaging ,Child ,Lymphatic Diseases ,Retrospective Studies ,Ultrasonography ,business.industry ,Ultrasound ,Infant ,medicine.anatomical_structure ,Child, Preschool ,030220 oncology & carcinogenesis ,Contrast injection ,Predictive value of tests ,Feasibility Studies ,Female ,Cardiology and Cardiovascular Medicine ,business ,Nuclear medicine ,Contrast-enhanced ultrasound - Abstract
The aim of this study was to determine the feasibility of using contrast-enhanced ultrasound (CEUS) evaluation to determine thoracic duct (TD) outlet patency. Nine patients referred for lymphatic imaging and intervention underwent percutaneous intranodal ultrasound contrast injection and conventional lymphangiography (CL). Eight of 9 patients had a patent TD by CEUS and CL. One patient did not have a patent TD. There was 100% agreement between CEUS and CL. These results suggest that CEUS is an imaging modality that might be as accurate as CL in determining TD patency.
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- 2020
44. Neonatal lymphatic flow disorders: impact of lymphatic imaging and interventions on outcomes
- Author
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Mandi Liu, Erin Pinto, Chitra Ravishankar, Catherine Williams, Jonathan J. Rome, Yoav Dori, Aaron G. DeWitt, Andrew C. Glatz, Dalal Taha, Christopher L. Smith, Huayan Zhang, Ganesh Krishnamurthy, Fernando Escobar, David M. Biko, and Heather Griffis
- Subjects
medicine.medical_specialty ,business.industry ,medicine.medical_treatment ,Obstetrics and Gynecology ,Chylothorax ,Retrospective cohort study ,medicine.disease ,Anasarca ,Thoracic duct ,Surgery ,03 medical and health sciences ,0302 clinical medicine ,medicine.anatomical_structure ,Lymphatic system ,030225 pediatrics ,Pediatrics, Perinatology and Child Health ,Ascites ,Medicine ,030212 general & internal medicine ,Embolization ,medicine.symptom ,business ,Neonatal Disorder - Abstract
Neonatal chylothorax (NCTx) and central lymphatic flow disorder (CLFD) are historically challenging neonatal disorders with high morbidity and mortality. METHODS We conducted a retrospective study of 35 neonates with pulmonary lymphatic abnormalities at our institution who underwent lymphatic evaluation between December 2015 and September 2018. Patients with only pulmonary lymphatic perfusion syndrome were classified as NCTx and those with multiple flow abnormalities were classified as CLFD. Demographics, clinical characteristics, and outcomes were compared using t-tests/Wilcoxon rank sum tests and Fisher's exact tests. RESULTS All 35 patients had intranodal MR lymphangiography and 14 (40%) also had conventional fluoroscopic lymphangiography. Fifteen (42.8%) patients were diagnosed with NCTx and 20 (57.1%) were diagnosed with CLFD. Thirty-four (97.1%) patients had pleural effusions. None of the NCTx group had ascites, anasarca, or dermal backflow compared to 17 (85%) (p
- Published
- 2020
45. Intramesenteric dynamic contrast pediatric MR lymphangiography: initial experience and comparison with intranodal and intrahepatic MR lymphangiography
- Author
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Aaron G. DeWitt, Christopher L. Smith, Abhay Srinivasan, Ganesh Krishnamurthy, David M. Biko, Yoav Dori, and Fernando Escobar
- Subjects
Male ,medicine.medical_specialty ,Leak ,Adolescent ,Contrast Media ,Gadolinium ,030218 nuclear medicine & medical imaging ,Lymphatic System ,03 medical and health sciences ,0302 clinical medicine ,Ascites ,Image Processing, Computer-Assisted ,Humans ,Medicine ,Radiology, Nuclear Medicine and imaging ,Child ,Lymphatic Diseases ,Lymphatic Vessels ,Retrospective Studies ,Neuroradiology ,medicine.diagnostic_test ,business.industry ,Lymph duct ,Protein losing enteropathy ,Angiography ,Infant ,Lymphography ,Magnetic resonance imaging ,Interventional radiology ,General Medicine ,medicine.disease ,Magnetic Resonance Imaging ,Lymphatic system ,Child, Preschool ,030220 oncology & carcinogenesis ,Female ,Lymph Nodes ,Radiology ,medicine.symptom ,business - Abstract
To report on our initial experience with intramesenteric (IM) dynamic contrast magnetic resonance lymphangiography (DCMRL) for evaluation of the lymphatics in patients with concern for mesenteric lymphatic flow disorders and to compare IM-DCMRL with intrahepatic (IH) and intranodal (IN) DCMRL. This is a retrospective review of imaging findings in 15 consecutive patients who presented with protein losing enteropathy (PLE) and/or ascites undergoing IM-DCMRL, IH-DCMRL, and IN-DCMRL. The IM-DCMRL technique involves the injection of a gadolinium contrast agent into the mesenteric lymphatic ducts or lymph nodes followed by imaging of the abdomen and chest with dynamic time-resolved MR lymphangiography. IM-DCMRL was successfully performed in 14/15 (93%) of the patients. When comparing IN-DCMRL with IM-DCMRL, there was a significant difference in the visualization of dermal backflow (p = 0.014), duodenal perfusion (p = 0.003), duodenal leak (p = 0.014), and peritoneal leak (p = 0.003). IM-DCMRL demonstrated peritoneal leak in 7 patients in contrast to IH-DCMRL which demonstrated leak in 4 patients and IN-DCMRL which did not demonstrate any peritoneal leaks. Duodenal leaks were seen by IH-DCMRL in 9 patients versus 5 with IM-DCMRL and none with IN-DCMRL. In one patient with congenital PLE, the three modalities showed different disconnected flow patterns with duodenal leak only seen by IM-DCMRL. There were no short-term complications from the procedures. IM-DCMRL is a feasible imaging technique for evaluation of the mesenteric lymphatics. In certain mesenteric lymphatic flow abnormalities, such as PLE and ascites, this imaging may be helpful for diagnosis and the planning of interventions and warrants further studies. • Intramesenteric dynamic contrast magnetic resonance lymphangiography (IM-DCMRL) is a new imaging technique to evaluate mesenteric lymphatic flow disorders such as ascites. • IM-DCMRL is able to image lymphatic leaks in patients with ascites and protein losing enteropathy not seen with intranodal (IN-DCMRL) imaging.
- Published
- 2020
46. Incidence and fate of device‐related left pulmonary artery stenosis and aortic coarctation in small infants undergoing transcatheter patent ductus arteriosus closure
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Jonathan J. Rome, Michael L. O'Byrne, Taylor Demkin, Catherine E. Tomasulo, Andrew C. Glatz, Christopher L. Smith, Matthew J. Gillespie, Yoav Dori, and David Munson
- Subjects
Male ,Cardiac Catheterization ,medicine.medical_specialty ,Time Factors ,Percutaneous ,Septal Occluder Device ,030204 cardiovascular system & hematology ,Aortic Coarctation ,03 medical and health sciences ,0302 clinical medicine ,Risk Factors ,medicine.artery ,Internal medicine ,Ductus arteriosus ,medicine ,Birth Weight ,Humans ,Stenosis, Pulmonary Artery ,Radiology, Nuclear Medicine and imaging ,030212 general & internal medicine ,Ductus Arteriosus, Patent ,Retrospective Studies ,business.industry ,Ductus arteriosus closure ,Incidence ,Incidence (epidemiology) ,Age Factors ,Infant, Newborn ,Infant ,Retrospective cohort study ,General Medicine ,Left pulmonary artery ,Infant, Low Birth Weight ,medicine.disease ,Stenosis ,Treatment Outcome ,medicine.anatomical_structure ,Descending aorta ,Cardiology ,Female ,Cardiology and Cardiovascular Medicine ,business - Abstract
Objectives To evaluate short- and middle-term outcomes after transcatheter patent ductus arteriosus (TC-PDA) closure in small infants, specifically device-related left pulmonary artery (LPA) stenosis and aortic coarctation, risk factors, and changes over time. Background Recent studies have demonstrated successful transcatheter PDA (TC-PDA) closure in small infants. LPA stenosis and aortic coarctation have been seen after TC-PDA, but it is not clear whether device-related LPA/aortic obstruction persists. Methods A single-center retrospective study of infants ≤4 kg who underwent TC-PDA closure from February 1, 2007 to September 1, 2018 was performed, evaluating the incidence and risk factors for LPA stenosis and coarctation. Results Forty-four patients underwent successful TC-PDA with Amplatzer Vascular Plug II (AVPII; n = 30), Amplatzer Duct Occluder II-Additional Sizes (n = 10), Amplatzer Duct Occluder I (n = 3), and coil-filled AVPI (n = 1) devices, all via an antegrade approach. Median birthweight and procedural weight were 890 g (range: 490-3,250) and 2.8 kg (range: 1.2-4.0), respectively. Median follow-up was 0.7 years (range: 2 days-7 years). Thirty-eight patients had post-procedure echocardiograms assessing LPA/aortic obstruction. Of those, 17 had LPA flow acceleration/stenosis (≥1.5 m/s), which improved or resolved in all patients with available follow-up; 3 developed mild coarctation (>2 m/s), which improved in the two with more than short-term follow-up; 4 developed mild flow acceleration (1.5-2 m/s) in the descending aorta, which resolved in three and increased in one (2.4 m/s). Flow acceleration in the LPA was associated with younger procedural age, larger PDA minimal diameter, and placement of a device other than the AVPII. There was no device-related mortality or need for reintervention. Conclusion TC-PDA in small infants is effective, without significant complications. Device-related LPA/aortic obstruction can improve with time/growth.
- Published
- 2020
47. Compression of the left mainstem bronchus by patent ductus arteriosus in neonates under consideration for ductal stenting
- Author
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David M. Biko, David Saul, Samuel B. Goldfarb, Michael L. O'Byrne, and Christopher L. Smith
- Subjects
Thorax ,Shunt placement ,congenital, hereditary, and neonatal diseases and abnormalities ,medicine.medical_specialty ,Clinical Decision-Making ,Bronchi ,030204 cardiovascular system & hematology ,03 medical and health sciences ,0302 clinical medicine ,Risk Factors ,Bronchial compression ,Ductus arteriosus ,Humans ,Medicine ,Radiology, Nuclear Medicine and imaging ,cardiovascular diseases ,030212 general & internal medicine ,Blalock-Taussig Procedure ,Ductus Arteriosus, Patent ,Bronchus ,business.industry ,Angioplasty ,Palliative Care ,Infant, Newborn ,General Medicine ,Surgery ,Airway Obstruction ,Stent placement ,Treatment Outcome ,medicine.anatomical_structure ,cardiovascular system ,Female ,Stents ,Cardiology and Cardiovascular Medicine ,business ,Airway - Abstract
Stent angioplasty of patent ductus arteriosus has been shown to be a viable alternative to operative shunt placement in cyanotic neonates. With broader implementation of this strategy, novel complications are bound to arise. We present a series of cases evaluated for ductal stent angioplasty in which a dilated and torturous ductus arteriosus compressed the left mainstem bronchus. After reviewing our recent experience with ductal stenting and isolated Blalock-Taussig shunts, our best estimate of the incidence of bronchial compression by the dilated ductus is 4.6% (3/64, 95% confidence interval 1.0-12.9%). Awareness of the airway and other nonvascular contents of the thorax is an important consideration prior to ductal stenting.
- Published
- 2020
48. Pathogenic variants in MDFIC cause recessive central conducting lymphatic anomaly with lymphedema
- Author
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Alicia B. Byrne, Pascal Brouillard, Drew L. Sutton, Jan Kazenwadel, Saba Montazaribarforoushi, Genevieve A. Secker, Anna Oszmiana, Milena Babic, Kelly L. Betterman, Peter J. Brautigan, Melissa White, Sandra G. Piltz, Paul Q. Thomas, Christopher N. Hahn, Matthias Rath, Ute Felbor, G. Christoph Korenke, Christopher L. Smith, Kathleen H. Wood, Sarah E. Sheppard, Denise M. Adams, Ariana Kariminejad, Raphael Helaers, Laurence M. Boon, Nicole Revencu, Lynette Moore, Christopher Barnett, Eric Haan, Peer Arts, Miikka Vikkula, Hamish S. Scott, Natasha L. Harvey, UCL - SSS/DDUV/GEHU - Génétique, UCL - SSS/IREC/SLUC - Pôle St.-Luc, UCL - (SLuc) Centre de génétique médicale UCL, UCL - (SLuc) Service de chirurgie plastique, Byrne, Alicia B, Brouillard, Pascal, Sutton, Drew L, Kazenwadel, Jan, Montazaribarforoush, Saba, Secker, Genevieve A, Oszmiana, Anna, Babic, Milena, Betterman, Kelly L, Brautigan, Peter J, Hahn, Christopher N, Arts, Peer, Scott, Hamish S, and Harvey, Natasha L
- Subjects
General Medicine - Abstract
Central conducting lymphatic anomaly (CCLA), characterized by the dysfunction of core collecting lymphatic vessels including the thoracic duct and cisterna chyli, and presenting as chylothorax, pleural effusions, chylous ascites, and lymphedema, is a severe disorder often resulting in fetal or perinatal demise. Although pathogenic variants in RAS/mitogen activated protein kinase (MAPK) signaling pathway components have been documented in some patients with CCLA, the genetic etiology of the disorder remains uncharacterized in most cases. Here, we identified biallelic pathogenic variants in MDFIC , encoding the MyoD family inhibitor domain containing protein, in seven individuals with CCLA from six independent families. Clinical manifestations of affected fetuses and children included nonimmune hydrops fetalis (NIHF), pleural and pericardial effusions, and lymphedema. Generation of a mouse model of human MDFIC truncation variants revealed that homozygous mutant mice died perinatally exhibiting chylothorax. The lymphatic vasculature of homozygous Mdfic mutant mice was profoundly mispatterned and exhibited major defects in lymphatic vessel valve development. Mechanistically, we determined that MDFIC controls collective cell migration, an important early event during the formation of lymphatic vessel valves, by regulating integrin β 1 activation and the interaction between lymphatic endothelial cells and their surrounding extracellular matrix. Our work identifies MDFIC variants underlying human lymphatic disease and reveals a crucial, previously unrecognized role for MDFIC in the lymphatic vasculature. Ultimately, understanding the genetic and mechanistic basis of CCLA will facilitate the development and implementation of new therapeutic approaches to effectively treat this complex disease.
- Published
- 2022
49. Dynamic contrast magnetic resonance lymphangiography localizes lymphatic leak to the duodenum in protein-losing enteropathy
- Author
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Yoav Dori, David M. Biko, Erin Pinto, David A. Piccoli, Christopher L. Smith, Pablo Laje, Petar Mamula, Jefferson N Brownell, Ganesh Krishnamurthy, Abhay Srinivasan, and Fernando Escobar
- Subjects
Constrictive pericarditis ,Leak ,medicine.medical_specialty ,Magnetic Resonance Spectroscopy ,Duodenum ,Protein-Losing Enteropathies ,Thoracic duct ,Article ,Lymphatic System ,medicine ,Humans ,Enteropathy ,Retrospective Studies ,medicine.diagnostic_test ,business.industry ,Protein losing enteropathy ,Gastroenterology ,Infant ,Lymphography ,Magnetic resonance imaging ,medicine.disease ,Lymphatic system ,medicine.anatomical_structure ,Pediatrics, Perinatology and Child Health ,Radiology ,business - Abstract
OBJECTIVES: Protein-losing enteropathy (PLE) is a disorder of intestinal lymphatic flow resulting in leakage of protein-rich lymph into the gut lumen. Our primary aim was to report the imaging findings of dynamic contrast magnetic resonance lymphangiography (DCMRL) in patients with PLE. Our secondary objective was to use these imaging findings to characterize lymphatic phenotypes. METHODS: Single-center retrospective cohort study of patients with PLE unrelated to single-ventricle circulation who underwent DCMRL. We report imaging findings of intranodal (IN), intrahepatic (IH), and intramesenteric (IM) access points for DCMRL. RESULTS: Nineteen patients 0.3–58 years of age (median 1.2 years) underwent 29 DCMRL studies. Primary intestinal lymphangiectasia (PIL) was the most common referring diagnosis (42%). Other etiologies included constrictive pericarditis, thoracic insufficiency syndrome, and genetic disorders. IN-DCMRL demonstrated a normal central lymphatic system in all patients with an intact thoracic duct and localized duodenal leak in one patient (1/19, 5%). IH-DCMRL detected a duodenal leak in 12/17 (71%), and IM-DCMRL detected duodenal leak in 5/6 (83%). Independent of etiology, lymphatic leak was only visualized in the duodenum. CONCLUSIONS: In patients with PLE, imaging via DCMRL reveals that leak is localized to the duodenum regardless of etiology. Comprehensive imaging evaluation with three access points can provide detailed information about the site of duodenal leak.
- Published
- 2022
50. Lymphatic anomalies in congenital heart disease
- Author
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Karen I, Ramirez-Suarez, Luis Octavio, Tierradentro-García, David M, Biko, Hansel J, Otero, Ammie M, White, Yoav, Dori, Christopher L, Smith, Seth, Vatsky, and Jordan B, Rapp
- Subjects
Heart Defects, Congenital ,Lymphatic System ,Lymphatic Abnormalities ,Humans ,Lymphography ,Child ,Chylothorax ,Magnetic Resonance Imaging - Abstract
Congenital heart disease can lead to various lymphatic complications including traumatic leaks, lymphatic overproduction, conduction abnormalities or lymphedema. Advancements in the imaging of central lymphatics and guided interventions have improved outcomes in these children. Dynamic contrast-enhanced magnetic resonance (MR) lymphangiography allows for the assessment of abnormal lymphatic drainage. This technique is preferred for evaluating lymphatic conditions such as plastic bronchitis, chylothorax, chyloptysis, chylopericardium, protein-losing enteropathy and chylous ascites, among other lymphatic disorders. In this review, we discuss lymphatic abnormalities encountered on MRI in children with congenital heart disease. We also briefly review treatment options.
- Published
- 2021
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