Internal Medicine Commons^™

Regional Hemodynamic Characterization Of The Thoracic Aorta Using 4d Flow Mri: A Single-Center Pilot Study, John H. Major

Summer Research Program Abstracts

No abstract provided.

Breast Cancer-Derived Extracellular Vesicle Mir-425-5p (Mir-425) Promotes Brain Metastasis Via Activating Astrocytes Through The Novel Mir-425-Znf24-Ccl8 Signaling Axis, Grace L Wong, Munazza S Khan, Sara Manore, Shivani Bindal, Ravi Singh, Hui-Wen Lo

Faculty, Staff and Student Publications

Mechanisms underlying breast cancer brain metastasis (BCBM) are still not well understood. Here, we identified that BCBM patient serum contained extracellular vesicles (EVs) with high levels of microRNAs (miRNAs)-107 and -425. Levels of miR-107 and miR-425 were elevated in brain metastases, and the elevation was associated with poor patient prognoses. Ectopic expression of miR-107 and miR-425 promoted mammospheres; however, the inhibition of miR-425, but not miR-107, suppressed breast cancer mammosphere formation. We further observed that EVs from miR-425-overexpressing breast cancer cells strongly activated astrocytes whereas their inhibitors abrogated the effect. Conditioned media from miR-425-activated astrocytes promoted mammospheres. To elucidate how …

Optimizing Electrode Placement And Information Capacity For Local Field Potentials In Cortex, Jace A Willis, Christopher E Wright, Ruoqian Zhu, Yilan Ruan, Joshua Stallings, Amada M Abrego, Takfarinas Medani, Promit Moitra, Arjun Ramakrishnan, Charles E Schroeder, Anand A Joshi, Nitin Tandon, Richard M Leahy, John C Mosher, John P Seymour

Faculty, Staff and Student Publications

Recent neurosurgery advancements include improved stereotactic targeting and increased density and specificity of electrophysiological evaluation. This study introduces a subject-specific, in silico modeling tool for optimizing electrode placement and maximizing coverage with a variety of devices. The basis for optimization is the Shannon-Hartley information capacity of field potentials derived from dipolar sources. The approach integrates subject-specific MRI data with finite element modeling (FEM) used to simulate the sensitivity of subdural and intracortical devices. Sensitivity maps, or lead fields, from these models enable the comparison of different electrode placements, contact sizes, contact configurations, and substrate properties, which are often overlooked factors. …

A Community-Informed Survey Identifying Research Priorities For Sex Chromosome Aneuploidies, Matthew Fein

Summer Research Program Abstracts

No abstract provided.

Alterations In Cardiovascular Parameters In 5xfad Murine Model, Andrea G Marshall, Dominique Stephens, Kit Neikirk, Sepiso K Masenga, Bryanna Shao, Amber Crabtree, Zer Vue, Heather K Beasley, Edgar Garza-Lopez, Estevão Scudese, Benjamin I Rodriguez, Han Le, Steven Damo, George E Taffet, Okwute M Ochayi, Ronald Mcmillan, Jeremiah M Afolabi, Vernat Exil, Ashton Oliver, Vineeta Sharma, Pamela Martin, Amadou Gaye, Chanel Harris, Briar Tomeau, Lacara Bell, Markis Hamilton, Taneisha Gillyard, Railyn Webster, Marcus Jackson, Prem Prakash, Shanilah Frierson, Chandravanu Dash, Margaret Mungai, Annet Kirabo, Jennifer A Gaddy, Nelson Wandira, Antentor Hinton, Anilkumar K Reddy

Faculty, Staff and Students Publications

Alzheimer's Disease (AD) is a global health issue, affecting over 6 million people in the United States, with that number expected to increase as the population ages. As a neurodegenerative disorder that affects memory and cognitive functions, it is well established that AD is associated with cardiovascular risk factors beyond only cerebral decline. In this study, we measured hemodynamic parameters related to cardiovascular and cerebrovascular function in 5xFAD mice with AD and their littermates. Specifically, we measured cardiovascular pulse wave velocity parameters, a marker of arterial stiffness and cardiovascular risk, and cerebrovascular pulse wave velocity, a novel technique to measure …

Emergency Department-Initiated Palliative Care Screening Among Older Adults: A Systematic Review And Meta-Analysis Protocol, Dimitri E Lin, Satheesh Gunaga, Fabrice I Mowbray, Eric D Isaacs, Daniel Markwalter, Naomi George, Alison E Hay, Rita Manfredi, Erica Westlake, Murtaza Akhter, Jason K Bowman, Naomi Rebollo-Lee, Brian Gacioch, Alexander D Ginsburg, Justin Kenneth Brooten, Sarah Pajka, Katie Selman, Paul Bain, Joshua J Davis, Shan Liu, Kei Ouchi

Faculty, Staff and Students Publications

Introduction: The rapidly growing population of older adults (individuals aged 65 years and older) presents a new set of challenges for healthcare providers in the emergency department (ED), given the prevalence of severe and life-threatening conditions among this group, such as chronic cancer, Alzheimer's disease/dementia and congestive heart failure. ED encounters often represent a critical point in an older patient's trajectory of care and can thus be an important opportunity for various interventions such as palliative care consultation. Therefore, identifying those who will benefit most from palliative care is of high importance, especially in determining the course of future treatment. …

Efficacy Of Erdafitinib Before Or After Enfortumab Vedotin In Fgfr3-Altered Advanced Urothelial Cancer: Analysis Of The Unite Collaborative Study, Cindy Y Jiang, Hyunsoo Hwang, Ilana Y Epstein, Dimitra Rafailia Bakaloudi, Rafee Talukder, Amy K Taylor, Amanda Nizam, Tanya Jindal, Michael J Glover, Ali Raza Khaki, Pedro C Barata, Charles B Nguyen, Eugene Oh, Nancy B Davis, Hannah Mabey, Christopher J Hoimes, Sean T Evans, Bashar Abuqayas, Emily Lemke, Irene Tsung, Wei Qiao, Deepak Kilari, Yousef Zakharia, Mehmet A Bilen, Matthew I Milowsky, Sumit A Shah, Shilpa Gupta, Hamid Emamekhoo, Joaquim Bellmunt, Ajjai S Alva, Petros Grivas, Pavlos Msaouel, Vadim S Koshkin, Matthew T Campbell, Omar Alhalabi

Faculty, Staff and Students Publications

Background: Erdafitinib is approved for locally advanced/metastatic urothelial cancer (LA/mUC). As enfortumab vedotin (EV) plus pembrolizumab enters frontline management, outcomes with erdafitinib pre- and post-EV are clinically relevant but not specifically evaluated in clinical trials.

Methods: UNITE is a multi-institutional retrospective study of patients with LA/mUC treated with novel targeted agents. All patients with FGFR3 alterations treated with EV only, erdafitinib then EV (Erda->EV), and EV then erdafitinib (EV->Erda) were included. Sequential treatment with EV and Erda was not required. Primary endpoints were observed response rates (ORR) and progression-free survival (PFS); secondary endpoint was overall survival (OS).

Results: …

Treatment-Related Adverse Events And Associated Outcomes In Patients With Advanced Urothelial Carcinoma Treated With Enfortumab Vedotin: Analysis Of The Unite Study, Amanda Nizam, Charles B Nguyen, Jinju Li, Emily C Zabor, Pavlos Msaouel, Cindy Y Jiang, Omar Alhalabi, Eugene Oh, Matthew P Davidsohn, Ilana B Epstein, Dimitra Rafailia Bakaloudi, Rafee Talukder, Tanya Jindal, Amy K Taylor, Michael J Glover, Ali Raza Khaki, Emily Lemke, Hannah Mabey, Bashar Abuqayas, Albert Jang, Jason R Brown, Sean T Evans, Cameron Pywell, Arnab Basu, Mehmet A Bilen, Pedro C Barata, Yousef Zakharia, Matthew I Milowsky, Deepak Kilari, Christopher J Hoimes, Sumit A Shah, Hamid Emamekhoo, Nancy B Davis, Shilpa Gupta, Petros Grivas, Joaquim Bellmunt, Matthew T Campbell, Ajjai S Alva, Vadim S Koshkin

Faculty, Staff and Students Publications

Introduction: Enfortumab vedotin-ejfv (EV), an antibody-drug conjugate approved for advanced urothelial carcinoma (aUC), has limited real-world safety data and no validated predictive biomarkers. Retrospective studies suggest higher objective response rates (ORR) among patients developing EV-related dermatologic toxicities, but survival implications remain unclear. This analysis assessed the safety of EV monotherapy and the impact of dermatologic and neurologic toxicities on efficacy outcomes in a multi-institutional cohort.

Materials and methods: UNITE is a multicenter, retrospective study across 16 US sites of patients with aUC treated with targeted agents, including EV. Primary endpoints were the incidence of EV treatment-related adverse events (TRAEs, any …

Peritoneal Immunosurgery: Immunotherapy Augmented Surgery For The Treatment Of Peritoneal Cancers, Ada I Ozcan, Arianexys Aquino López, Mary K Mckenna, Malcolm K Brenner, Alastair M Thompson

Faculty, Staff and Students Publications

Peritoneal malignancy often indicates disruptions in multiple physiological systems resulting from widespread cancer. The heterogenous origin and dynamic nature of peritoneal cancer make it difficult to treat with standard approaches that fit into guidelines. We describe how successful treatment should address the underlying pathology, the systemic response to surgical treatments and target the immune perturbations that facilitate the establishment and propagation of this multifaceted disease.

Social Disparities, Delirium Occurrence, And Related Outcomes Among Hospitalized Older Adults, Alan P Pan, Kathryn Agarwal, Thomas Potter, Karim Borei, Sara Nowakowski, Courtenay R Bruce, George E Taffet, Farhaan S Vahidy

Faculty, Staff and Students Publications

Background: Underlying socio-economic and health burden may variably impact delirium presentation among older adults. We characterized differences in patient factors related to social marginalization and studied their effects on delirium occurrence and hospital outcomes.

Methods: We conducted a 7-year retrospective analysis of older adults (aged ≥ 70 years) who systematically underwent screening for delirium at an 8-hospital healthcare system. Our primary exposure included patient characteristics related to demographics and social marginalization. Multivariable logistic regression models were built to identify factors associated with increased odds of delirium occurrence, either (1) present-on-admission (D-POA) or (2) hospital-acquired (HAD). Secondary outcomes included hospital length …

A Multi-Institutional Multi-Methods Analysis Of Jeopardy Systems In Academic Hospital Medicine, Kirsten N Kangelaris, Angela Keniston, Andrew D Auerbach, Gregory Bowling, Marisha Burden, Shradha A Kulkarni, Luci K Leykum, Anne S Linker, Matthew Sakumoto, Jeffrey Schnipper, Gopi Astik

Faculty, Staff and Students Publications

Background: Hospital medicine programs use backup ("jeopardy") systems to cover unexpected staffing gaps, but little is known about their structures or optimal practices.

Objectives: To describe jeopardy structures, assess clinician perceptions, and identify potential approaches across a broad sample of hospital medicine groups.

Methods: This multi-methods study, conducted within a national hospitalist consortium, used virtual focus groups and an email survey to (1) describe the presence and structure of jeopardy systems and (2) explore features perceived as fair, equitable, and tolerable. Rapid qualitative analysis identified major themes, while descriptive methods analyzed survey data.

Results: Twenty-five individuals participated in focus groups, …

Time-Frequency Fingerprint Analysis In Seeg Source-Space To Identify The Epileptogenic Zone, Yash Shashank Vakilna, Deniz Atilgan, Johnson Hampson, Chinmay Chinara, Takfarinas Medani, Richard M Leahy, Nuria Lacuey, Samden D Lhatoo, Sandipan Pati, John C Mosher, Jay R Gavvala

Faculty, Staff and Student Publications

This case study highlights the application of seizure fingerprint analysis in the source-space of stereo-EEG (SEEG) data to accurately localize the epileptogenic zone (EZ) in patients with complex cortical malformations. A 25-year-old female with extensive bilateral perisylvian polymicrogyria (PMG) presented with intractable focal seizures. The source-level analysis performed in Brainstorm using the sLORETA imaging algorithm subsequently showed EZ fingerprint analysis. The patient underwent MR-guided laser interstitial thermal therapy (LITT), targeting the identified EZ, resulting in postoperative seizure freedom with minimal complications. Extending the analysis from the sensor-space to the source-space could further enhance surgical planning and improve outcomes in complex …

Longitudinal Meta-Cohort Study Protocol Using Systems Biology To Identify Vaccine Safety Biomarkers, Joann Diray-Arce, Ana C Chang, Sara Moradipoor, Donato Amodio, Bruce Carleton, Wan-Chun Chang, Nigel W Crawford, Meagan Karoly, Annmarie Hoch, Kerry Mcenaney, Tahir S Kafil, Mahitha Donthireddy, Sarah K Steltz, Simon D Van Haren, Asimenia Angelidou, Kinga K Smolen, Hanno Steen, Jessica Lasky-Su, Huyen Tran, Peter Liu, C Buddy Creech, Clare L Cutland, Helen Petousis-Harris, Ishac Nazy, Rae S M Yeung, Sonali Kochhar, Steve Black, Nicholas Wood, Dale Nordenberg, Paolo Palma, Inna G Ovsyannikova, Richard B Kennedy, Gregory A Poland, Al Ozonoff, Robert T Chen, Ofer Levy, Karina A Top, International Network Of Special Immunization Services (Insis) Members

Faculty, Staff and Students Publications

The International Network of Special Immunization Services (INSIS) was established to investigate the causes and risk factors of rare adverse events following immunizations (AEFIs) and develop immunization strategies for mitigating or preventing risk for individuals with prior AEFIs or at risk of AEFIs. INSIS integrates clinical data with multi-omic technologies (e.g., transcriptomics, proteomics, metabolomics) through a global consortium of clinical networks, leading immunology, pharmacogenomics teams to uncover the molecular mechanisms behind AEFIs. The network ensures accurate and standardized data collection and analysis through rigorous data management and quality assurance processes. INSIS also implements harmonized case definitions and protocols for collecting …

A 65-Year-Old Man With Cough, Hypercalcemia, And Diffuse Opacities, Philip K Angelides, Oriana Salamo, Sujith V Cherian, Eduardo Yepez Guevara, Carlos A Jimenez, Saadia A Faiz

Faculty, Staff and Student Publications

Respiratory infections in patients with cancer are common. A low threshold for bronchoscopy with bronchoalveolar lavage (BAL) should be maintained in immunocompromised patients with pulmonary opacities on chest imaging to evaluate for opportunistic infections. In those with unresolving symptoms, transbronchial biopsies may add significant diagnostic value. Concomitant hypercalcemia in patients with cancer is typically related to underlying malignant disease. However, in those with persistent respiratory symptoms or atypical infiltrates then granulomatous inflammatory diseases should be considered. Diagnosing histoplasmosis in immunocompromised patients can be difficult. Antigen testing is often more sensitive, but tissue biopsy or culture may be needed. We describe …

An Electronic Trigger To Detect Telemedicine-Related Diagnostic Errors, Daniel R Murphy, Himabindu Kadiyala, Li Wei, Hardeep Singh

Faculty, Staff and Students Publications

Introduction

Methods

Congestion And Sinonasal Illness In Outer Space: A Study On The International Space Station, Faizaan Khan, Koyal Ansingkar, Roshan Dongre, Zain Mehdi, Aatin K Dhanda, Kayla Powell, Tariq Syed, Samuel E Razmi, Isuru Somawardana, Jeffrey T Vrabec, David Hilmers, Omar G Ahmed, Masayoshi Takashima

Faculty, Staff and Students Publications

Objectives: This study aims to characterize quantitative data pertaining to sinonasal symptoms and their related medication use aboard the International Space Station (ISS). A secondary focus involves correlating these findings with mission parameters such as extravehicular activity (EVA) participation and mission duration.

Methods: This retrospective cohort study was conducted utilizing data requested from the National Aeronautics and Space Administration (NASA) Lifetime Surveillance of Astronaut Health (LSAH) program.

Results: Of 71 de-identified ISS astronauts beginning with Expedition 1 in the year 2000 through 62 in 2019, there were 754 logged medical events; 60 astronauts reported any type of sinonasal medical event …

1d Thermoembolization Model Using Ct Imaging Data For Porcine Liver, Rohan Amare, Danielle Stolley, Steve Parrish, Megan Jacobsen, Rick R Layman, Chimamanda Santos, Beatrice Riviere, Natalie Fowlkes, David Fuentes, Erik Cressman

Faculty, Staff and Student Publications

Innovative therapies such as thermoembolization are expected to play an important role in improving care for patients with diseases such as hepatocellular carcinoma. Thermoembolization is a minimally invasive strategy that combines thermal ablation and embolization in a single procedure. This approach exploits an exothermic chemical reaction that occurs when an acid chloride is delivered via an endovascular route. However, comprehension of the complexities of the biophysics of thermoembolization is challenging. Mathematical models can aid in understanding such complex processes and assisting clinicians in making informed decisions. In this study, we used a Hagen-Poiseuille 1D blood flow model to predict the …

Implementation Mapping To Guide Adoption Of A Semi-Structured Intraoperative Anesthesia Handoff Tool, Aubrey Samost-Williams, Reed Richter, Naveen Vanga, Spandana Mandaloju, Adlai Arandela, Srikanth Sridhar, Eric J Thomas

Faculty, Staff and Student Publications

There frequently exists a gap between known best practices and real-world methods. Closing this gap involves thoughtful implementation, typically involving multiple implementation strategies. Implementation mapping is a technique that links the innovation being implemented with potential barriers to implementation and connects these barriers to the strategies that form the implementation plan. This study demonstrates the application of implementation mapping to guide the adoption of the Epic Health Systems Intraoperative Anesthesia Handoff Report. The objective is to create a comprehensive implementation plan tailored to the anticipated challenges of the local environment. There are five steps in implementation mapping: (1) performing a …

Pharmacogenetics Of Plasma Dolutegravir Exposure During 1-Month Rifapentine/Isoniazid Treatment Of Latent Tuberculosis, Nia Covington, Anne F Luetkemeyer, Marjorie Z Imperial, Rodney Dawson, Yoninah Cramer, Sue Rosenkranz, Susan Swindells, Irina Gelmanova, Anchalee Avihingsanon, Roberto C Arduino, Wadzanai Samaneka, Kelly E Dooley, Rada Savic, Anthony T Podany, David W Haas

Faculty, Staff and Student Publications

In Advancing Clinical Therapeutics Globally protocol A5372, a pharmacokinetic study of dolutegravir with 1-month of daily rifapentine/isoniazid, twice-daily dolutegravir offset the induction effects of rifapentine on plasma dolutegravir trough concentrations (C trough ). Here, we characterize the impact on dolutegravir C trough of UGT1A1 , AADAC , and NAT2 polymorphisms that affect dolutegravir, rifapentine, and isoniazid, respectively. People with HIV receiving dolutegravir-based antiretroviral therapy with an indication to treat latent tuberculosis underwent pharmacokinetic sampling during dolutegravir 50 mg once daily alone, and on day 28 of dolutegravir 50 mg twice daily with rifapentine/isoniazid. Multivariable linear regression models characterized genetic associations …

Eye Catching, Alec B Rezigh, Anand D Jagannath, Austin C Rezigh, Ann Marie Kumfer, Stephanie V Sherman

Faculty, Staff and Students Publications

A 55 year-old man with type 2 diabetes mellitus presented to the emergency department with subacute nausea, vomiting, and abdominal pain. He was found to have epididymitis and hyperglycemia that improved with antibiotics and supportive care. However, he was also discovered to have significant acute kidney injury and chronic, relapsing-remitting bouts of eye pain and redness, confirmed to be uveitis on ophthalmologic evaluation. Despite completing an appropriate course of antibiotics, his pyuria and kidney injury persisted. An extensive infectious, autoimmune, and malignancy work-up was negative. As such, renal biopsy was pursued and revealed findings consistent with tubulointerstitial nephritis. With a …

When The Right Ventricle Fails After Left Ventricular Assist Device Implantation: Prediction Tools, Recognition Strategies, And Support Options, Juan Jose Rodriguez Arias, James Schurr, Phyllis Billia, Joyce W. Wald

Journal of Shock and Hemodynamics

The incidence of right heart failure (RHF) during durable left ventricular assist device (LVAD) surgery ranges from 9% to 42%, depending on the definition. RHF can be divided into three peri-implantation categories: early acute, early, and late. Despite many available risk models, predicting RHF before durable LVAD implantation has been difficult. Preemptive right-sided temporary mechanical circulatory support can improve outcomes; however, if intraoperative RHF is not suspected, early recognition and appropriate intervention after surgery are important.

Forward Genetic Screen In Zebrafish Identifies New Fungal Regulators That Limit Host-Protective Candida-Innate Immune Interaction, Bailey A Blair, Emma Bragdon, Gursimran Dhillon, Nnamdi Baker, Lena Stasiak, Mya Muthig, Pedro Miramon, Michael C Lorenz, Robert T Wheeler

Faculty, Staff and Student Publications

Candida is one of the most frequent causes of bloodstream infections, and our first line of defense against these invasive infections is the innate immune system. The early immune response is critical in controlling Candida albicans infection, but C. albicans has several strategies to evade host immune attack. Phagocytosis of C. albicans blocks hyphal growth, limiting host damage and virulence, but how C. albicans limits early recruitment and phagocytosis in vertebrate infection is poorly understood. To study innate immune evasion by intravital imaging, we utilized the transparent larval zebrafish infection model to screen 131 C. albicans mutants for altered …

Clerkship Students' Use Of Clinical Reasoning Concepts After A Pre-Clinical Reasoning Course, Shradha A Kulkarni, Gurpreet Dhaliwal, Arianne Teherani, Denise M Connor

Faculty, Staff and Students Publications

Background: Many medical schools have incorporated clinical reasoning (CR) courses into their pre-clinical curricula to address the quality and safety issue of diagnostic error. It is unknown how students use concepts and practices from pre-clinical CR courses once in clerkships.

Objective: We sought to understand how students utilize CR concepts from a pre-clinical course during clerkships and to identify facilitators and barriers to the use of reasoning concepts.

Design: We used structured interviews to gain insight into medical students' experiences with CR concepts in clerkships.

Participants: We interviewed 16 students who had completed a pre-clinical CR course and subsequently completed …

Maternal Dysbiosis Produces Long-Lasting Behavioral Changes In Offspring, Jacob Hudobenko, Claudia M Di Gesù, Patrick R Mooz, Joseph Petrosino, Nagireddy Putluri, Bhanu P Ganesh, Kristen Rebeles, Frank W Blixt, Venugopal R Venna, Louise D Mccullough

Faculty, Staff and Student Publications

Advanced maternal age (AMA) is defined as a pregnancy in a woman older than 35 years of age. AMA increases the risk for both maternal and neonatal complications, including miscarriage and stillbirth. AMA has also been linked to neurodevelopmental and neuropsychiatric disorders in the offspring. Recent studies have found that age-associated compositional shifts in the gut microbiota contribute to altered microbial metabolism and enhanced inflammation in the host. We investigated the specific contribution of the maternal microbiome on pregnancy outcomes and offspring behavior by recolonizing young female mice with aged female microbiome prior to pregnancy. We discovered that pre-pregnancy colonization …

Clinicians’ Perspectives Concerning Treatment Initiation And Escalation Strategies For Digital Ulcers In Patients With Systemic Sclerosis, Giulia Campanaro, Giulia Bandini, Alessia Alunno, Stefano Di Donato, Begonya Alcacer-Pitarch, Ilaria Galetti, Barbara Ruaro, Silvia Bellando Randone, Alberto Moggi Pignone, Marco Matucci-Cerinic, Zsuzsanna H Mcmahan, Michael Hughes

Faculty, Staff and Student Publications

Objectives: Digital ulcers (DUs) are a major cause of pain and disability in systemic sclerosis (SSc) patients and remain a major treatment challenge. Our aim was to explore clinicians' perspectives towards treatment initiation and escalation, akin to a 'Treat to Target' (T2T) strategy.

Methods: SSc clinicians were invited to participate in an online survey.

Results: A total of 173 responses (75% rheumatologists) were obtained from 33 countries. When initiating a change in oral drug therapy for SSc-DUs, most (80%) respondents would consider adding new medication to existing treatment, and 50% would increase existing treatment dose. Time to assess the impact …

Can Endothelin-1 Help Address The Diagnostic And Prognostic Challenges In Multimorbid Acute Heart Failure Patients?, Bianca-Ana Dmour, Minerva Codruta Badescu, Cristina Tuchiluș, Corina Maria Cianga, Daniela Constantinescu, Nicoleta Dima, Ștefania Teodora Duca, Awad Dmour, Alexandru Dan Costache, Maria-Ruxandra Cepoi, Adrian Crișan, Sabina Andreea Leancă, Cătălin Loghin, Ionela-Lăcrămioara Șerban, Irina Iuliana Costache-Enache

Faculty, Staff and Student Publications

The management of acute heart failure (AHF) is becoming increasingly complex, especially in patients with multiple comorbidities. Endothelin-1 (ET-1), a vasoconstrictive peptide, is an important mediator of neurohormonal activation, endothelial dysfunction, and cardiac remodeling-key processes involved in the pathogenesis of AHF. The aim of our study was to evaluate the diagnostic and prognostic performance of ET-1 in multimorbid AHF patients, compared to established markers such as amino terminal pro B-type natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin I (hs-cTnI). We conducted a single-center prospective study including 76 patients; 54 with AHF and 22 serving as controls. Upon admission, all patients …

Trajectories Of Forced Vital Capacity In Patients With Systemic Sclerosis-Associated Interstitial Lung Disease, Oliver Distler, Madelon C Vonk, Arata Azuma, Maureen D Mayes, Dinesh Khanna, Kristin B Highland, Gerrit Toenges, Margarida Alves, Yannick Allanore

Faculty, Staff and Student Publications

We used data from the SENSCIS and SENSCIS-ON trials to assess decline in forced vital capacity (FVC) in patients with systemic sclerosis-associated interstitial lung disease (SSc-ILD) who received long-term treatment with nintedanib and the effect of switching patients from placebo to nintedanib. In the SENSCIS trial, patients were randomised to receive nintedanib or placebo until the last patient reached week 52 but for ≤ 100 weeks. In SENSCIS-ON, the extension to SENSCIS, all patients received open-label nintedanib. Per protocol, the off-treatment period between these trials was ≤ 12 weeks. We assessed the trajectory of FVC in patients who received nintedanib …

Non-Canonical Splice Variants In Thoracic Aortic Dissection Cases And Marfan Syndrome With Negative Genetic Testing, David R Murdock, Dong-Chuan Guo, John S Depaolo, Ulrike Schwarze, Xue-Yan Duan, Alana C Cecchi, Isabella C Marin, Yingying Tang, Jessica X Chong, Michael J Bamshad, Kathleen A Leppig, Peter H Byers, Scott M Damrauer, Dianna M Milewicz

Faculty, Staff and Student Publications

Individuals with heritable thoracic aortic disease (HTAD) face a high risk of deadly aortic dissections, but genetic testing identifies causative variants in only a minority of cases. We explored the contribution of non-canonical splice variants (NCVAS) to thoracic aortic disease (TAD) using SpliceAI and sequencing data from diverse cohorts, including 551 early-onset sporadic dissection cases and 437 HTAD probands with exome sequencing, 57 HTAD pedigrees with whole genome sequencing, and select sporadic cases with clinical panel testing. NCVAS were identified in syndromic HTAD genes such as FBN1, SMAD3, and COL3A1, including intronic variants in FBN1 in two Marfan syndrome (MFS) …

Precision Phenotyping For Curating Research Cohorts Of Patients With Unexplained Post-Acute Sequelae Of Covid-19, Alaleh Azhir, Jonas Hügel, Jiazi Tian, Jingya Cheng, Ingrid V Bassett, Douglas S Bell, Elmer V Bernstam, Maha R Farhat, Darren W Henderson, Emily S Lau, Michele Morris, Yevgeniy R Semenov, Virginia A Triant, Shyam Visweswaran, Zachary H Strasser, Jeffrey G Klann, Shawn N Murphy, Hossein Estiri

Faculty, Staff and Student Publications

BACKGROUND: Scalable identification of patients with post-acute sequelae of COVID-19 (PASC) is challenging due to a lack of reproducible precision phenotyping algorithms, which has led to suboptimal accuracy, demographic biases, and underestimation of the PASC.

METHODS: In a retrospective case-control study, we developed a precision phenotyping algorithm for identifying cohorts of patients with PASC. We used longitudinal electronic health records data from over 295,000 patients from 14 hospitals and 20 community health centers in Massachusetts. The algorithm employs an attention mechanism to simultaneously exclude sequelae that prior conditions can explain and include infection-associated chronic conditions. We performed independent chart reviews …

Meta-Analysis On Sex Differences In Mortality And Neurodevelopment In Congenital Heart Defects, Alyssa K Crain, Zhia N Lim, Chloe J Sarfatis, Magela Arias, Travis Holder, Alvaro G Moreira, Antonio F Corno, Tina O Findley

Faculty, Staff and Student Publications

Given the increasing survival rates among congenital heart disease (CHD) patients and the growing emphasis on their quality of life, there is a need to comprehensively assess the impact of surgical interventions on neurodevelopmental outcomes. With increasing awareness in sex-related disparities in CHD, there is a need to explore potential differences in surgical mortality and neurodevelopmental outcomes between male and female patients. In this systematic review, we adhered to PRISMA guidelines and PROSPERO registration (#CRD42021225610). Articles published from 2015 to 2021 were searched using MeSH descriptors in three major databases (MEDLINE Ovid, Elsevier Embase, and Cochrane Library). Study selection criteria …