Digital Commons Network^™

Avacincaptad Pegol For Geographic Atrophy Secondary To Age-Related Macular Degeneration: Two-Year Efficacy And Safety Results From The Gather2 Phase 3 Trial, Arshad M Khanani, Carl J Danzig, Jeffrey S Heier, Glenn J Jaffe, Peter K Kaiser, David R Lally, Sunil S Patel, Lejla Vajzovic, Christina Y Weng, Hersh Patel, Julie Clark, Dhaval Desai, Don Luo, Erin Henry, Frank G Holz

Faculty, Staff and Students Publications

Purpose: Avacincaptad pegol (ACP) is a pegylated RNA aptamer that inhibits complement C5. The efficacy and safety of ACP 2 mg was investigated in GATHER2, with positive year 1 results published. Herein, 2-year results are reported.

Design: Phase 3, randomized, sham-controlled study (ClinicalTrials.gov identifier, NCT04435366).

Participants: Patients with non-center point-involving geographic atrophy (GA).

Methods: Eligible patients were randomized 1:1 to receive monthly ACP 2 mg (n = 225) or sham (n = 222) for 1 year. At month 12, patients who received ACP 2 mg were randomized again 1:1 to dosing every month (EM; n = 96) or every …

Variability In The Orthopaedic Residency Trainee Trauma Surgical Experience, Todd Phillips, Benjamin Fiedler, Joshua T Morrow, Zbigniew Gugala, Melvyn Harrington, Douglas R Dirschl

Faculty, Staff and Students Publications

Background: The aim of this study was to analyze fracture fixation case logs from residents training at a level 1 trauma center to assess variability across residents' surgical experiences within a single residency program. The authors hypothesize that notable variability exists between residents' surgical experiences in fracture care.

Methods: A retrospective case series was conducted at a single, urban residency program with a level 1 trauma center. Completed case logs were collected from program graduates from 2022 to 2024. All surgical cases involving fracture fixation at the level 1 trauma center were included for analysis. The anatomic region of the …

Empiric Azithromycin Alters The Upper Respiratory Microbiome And Resistome Without Anti-Inflammatory Benefit In Covid-19, Abigail Glascock, Cole Maguire, Hoang Van Phan, Emily C Lydon, Joanna Schaenman, Carolyn S Calfee, Esther Melamed, John Greenland, David B Corry, Farrah Kheradmand, Lindsey R Baden, Rafick Sekaly, Grace A Mccomsey, Elias K Haddad, Charles B Cairns, Linda N Geng, Bali Pulendran, Ana Fernandez-Sesma, Viviana Simon, Jordan P Metcalf, Nelson I Agudelo Higuita, William B Messer, Mark M Davis, Kari C Nadeau, Monica Kraft, Christian Bime, David J Erle, Mark A Atkinson, Scott C Brakenridge, Lauren I R Ehrlich, Ruth R Montgomery, Albert C Shaw, Catherine L Hough, David A Hafler, Alison D Augustine, Patrice M Becker, Bjoern Peters, Al Ozonoff, Annmarie Hoch, Seunghee Kim-Schulze, Florian Krammer, Steven Bosinger, Walter Eckalbar, Matthew C Altman, Michael Wilson, Leying Guan, Holden Maecker, Hanno Steen, Impacc Network, Joann Diray-Arce, Nadine Rouphael, Steven H Kleinstein, Naresh Doni Jayavelu, Elaine F Reed, Ofer Levy, Victoria T Chu, Charles R Langelier

Faculty, Staff and Students Publications

Azithromycin is a widely used antibiotic and was frequently used to treat hospitalized patients during the COVID-19 pandemic. The impact of empiric azithromycin use on the respiratory microbiome in patients with viral respiratory infections is unclear. Here we used longitudinal metatranscriptomics on nasal swabs from a prospective multicentre cohort of 1,164 patients hospitalized for COVID-19. We compared the upper respiratory microbiome, resistome and systemic immune response in patients treated with azithromycin (n = 366) with those who received no antibiotics (n = 474) or other antibiotics (n = 324). We found that azithromycin altered microbiome composition and increased the expression …

Feasibility Of A Large Language Model Chatbot To Support Parental Understanding In The Picu, R Brandon Hunter, Satid Thammasitboon, Sreya Rahman, Sriya Kakarla, Pamela Petersen, Shelley Kumar, Thomas Rappold, Sanjiv Mehta

Faculty, Staff and Students Publications

Objectives: To evaluate the feasibility of a large language model (LLM)-based chatbot for answering parental questions in the PICU and inform design of a randomized controlled trial (RCT).

Design: Prospective single-arm feasibility study conducted from August 2024 to December 2024.

Setting: Quaternary PICU.

Subjects: Fourteen parents of children admitted to the PICU.

Interventions: Parents engaged in 10-minute sessions with a HIPAA-compliant GPT-4o- (Generative Pretrained Transformer 4o, OpenAI, San Francisco, CA) based chatbot prompted with patient-specific electronic health record (EHR) data.

Measurements and main results: Feasibility was assessed through four criteria: parental engagement and satisfaction, provider perceptions, accuracy and safety, and …

Body Mass Index And Survival In Children Receiving Extracorporeal Membrane Oxygenation, Pilar Anton-Martin, Keith Baxelbaum, Shilpa Vellore, Erika O'Neil, Vinai Modem, Sameer Thadani

Faculty, Staff and Students Publications

Importance: Underweight and obesity represent opposite ends of the nutritional risk spectrum that negatively affect children's health worldwide. Both conditions have been associated with increased mortality in pediatric patients receiving extracorporeal membrane oxygenation (ECMO) support.

Objective: To investigate the association of underweight and obesity status with pediatric ECMO outcomes using body mass index (BMI) z scores.

Design, setting, and participants: This retrospective cohort analysis used data from the Extracorporeal Life Support Organization (ELSO) database from January 1, 2019, to December 31, 2023. Participants included all pediatric patients from international ECMO centers aged 29 days to 18 years who received ECMO …

Driveline Infections Among Patients Supported With Left Ventricular Assist Devices: A Single Center Sixteen-Year Longitudinal Profile, Anh Nguyen, Alexis Shafii, Gabriel Loor, Andrew Civitello, O Howard Frazier, Todd Rosengart, Kenneth Liao

Faculty, Staff and Students Publications

Background: Left ventricular assist device (LVAD) driveline infections significantly impact patient outcomes. This study aimed to identify their risk factors.

Methods: We analyzed LVAD data from our institutional Intermacs database (January 1, 2008-December 31, 2023), combining primary implants and pump exchanges. Patient characteristics were summarized as frequencies for categorical variables and median (IQR) for continuous variables. The nature of repeated infection events was handled by the Andersen-Gill method within a multivariable Cox proportional hazards model for cause-specific hazard of driveline infections, accounting for death and heart transplant as competing risks.

Results: Our cohort included 1026 LVAD implants. Median patient age …

Glp1-Ra And Sglt2-I: Implementation And Insulin Deescalation Strategies, Arthi Palani, Sagar Patel, Shriya Patel, Shivani Srivastava, Jay Patel, Salman Salehin, Yochai Birnbaum, Joseph Allencherril

Faculty, Staff and Students Publications

Purpose of review: This review will summarize the most contemporary trials for glucagon-like peptide 1 receptor agonists (GLP1-RA) and sodium-glucose cotransporter 2 inhibitors (SGLT2-i) and present guidance on management and recommendations on adjunctive tapering of insulin in patients with insulin-dependent diabetes mellitus, which we term "de-insulinization."

Recent findings: GLP1-RA and SGLT2-i are the principal classes of diabetes medications evidencing cardiovascular benefit. However, there is limited consensus on how to effectively prescribe and maintain these medications for patients on other glucose-lowering therapy, especially insulin. Patients with type 2 diabetes and cardiovascular disease should be started on either a GLP-1RA, SGLT-i, or …

Long-Term Outcomes Of Left Bundle-Branch Pacing Vs Biventricular Pacing In Heart Failure: The Heartsync-Lbbp Randomized Clinical Trial, Xueying Chen, Xi Liu, Ruogu Li, Zhongkai Wang, Yixiu Liang, Lei Zhang, Wei Wang, Jin Bai, Jingfeng Wang, Shengmei Qin, Weiwei Zhang, Tianbao Yao, Dong Huang, Ting Chen, Xianxian Zhao, Dening Liao, Jingbo Li, Jialiang Mao, Mihail G Chelu, Yangang Su, Kenneth A Ellenbogen, Junbo Ge

Faculty, Staff and Students Publications

Importance: Left bundle-branch pacing (LBBP) has been proposed as an alternative to biventricular pacing (BiVP) for patients with heart failure with left bundle-branch block (LBBB). However, robust clinical evidence from randomized clinical trials is lacking.

Objective: To evaluate the long-term clinical outcomes of LBBP and BiVP.

Design, setting, and participants: This multicenter, prospective, randomized clinical trial enrolled 200 patients at 6 centers in China with a left ventricular ejection fraction (LVEF) of 35% or less and LBBB from October 2020 to March 2022. This study was took place from October 2020 to September 2024. These data were analyzed September 2024 …

Novel Variants Identified In Families With Snx27 -Related Neurodevelopmental Disorder, Aiding In Characterizing Its Genotypic And Phenotypic Spectrum, Tayyaba Shan, Abrar Hussain, Anushree Acharya, Mulazim Hussain, Yumei Li, Hafiz Muhammad Jafar Hussain, Kiran Afshan, Suzanne M Leal, Rui Chen, Asif Mir, Isabelle Schrauwen, Sabika Firasat

Faculty, Staff and Students Publications

Background:

Sorting Nexin 27 (SNX27), a key regulator of synaptic receptor trafficking and endosomal recycling, has been implicated in maintaining synaptic homeostasis and cognitive function. To date, variants in SNX27 have been reported in a small number of patients across three publications with severe neurodevelopmental phenotypes. However, the genetic and functional landscape of SNX27-related disorders remains poorly understood, and further evidence is needed to confirm its association with disease and to better delineate the associated phenotype.

Methods and Results:

Two unrelated Pakistani families with a total of five affected individuals segregating a neurodevelopmental disorder were investigated via exome …

Non-Invasive Intracranial Pressure Estimation In The Intensive Care Unit: Narrative Review Of Methods And Clinical Applications, Edoardo Picetti, Daniele Guerino Biasucci, Elisa Gouvea Bogossian, Sérgio Brasil, Danilo Cardim, Marek Czosnyka, Daniel A Godoy, Gregory W J Hawryluk, Mohammad I Hirzallah, Frank A Rasulo, Carla Bittencourt Rynkowski, Andres M Rubiano, Fabio Silvio Taccone, Chiara Robba

Faculty, Staff and Students Publications

Despite invasive methods are the gold standard for intracranial pressure (ICP) measurement, several non-invasive techniques (nICP) have been proposed as surrogate, although their use remains insufficiently recognized in clinical practice. These include transcranial Doppler blood flow velocity  assessment (arterial or venous), optic nerve sheath diameter (ONSD), automated pupillometry, measurement of skull expansion and compliance, brain imaging, double-depth ophthalmic artery blood flow velocity, and ultrasound time-of-flight. The main limitations of all indirect methods are calibration and zeroing, which constrain the absolute accuracy of non-invasive ICP monitoring. For transcranial Doppler-based methods, the 95% limits of agreement are approximately ± 7-15 mmHg, while …

Efficient In Vivo Pharmacological Inhibition Of Δfosb, An Ap-1 Transcription Factor, In The Brain, Sean Mcneme, Anil Kumar, Yun Young Yim, Brandon W Hughes, Corey St Romain, Yi Li, Ashwani Kumar, Qichao Bao, Molly Estill, Shanghua Fan, Nadeen Takatka, Earnest P Chen, Matthew Rivera, Haiying Chen, Alfred J Robison, Mischa Machius, Stephen J Haggarty, Jeannie Chin, Eric J Nestler, Jia Zhou, Gabby Rudenko

Faculty, Staff and Students Publications

ΔFOSB, an unusually stable member of the AP-1 family of transcription factors, mediates long-term maladaptations that play a key role in the pathogenesis of drug addiction, cognitive decline, dyskinesia, and several other chronic neurological and psychiatric conditions. We have recently identified that 2-phenoxybenzenesulfonic acid-containing compounds disrupt the binding of ΔFOSB to DNA in vitro in cell-based assays, and one such compound, JPC0661, disrupts ΔFOSB binding to genomic DNA in vivo in the mouse brain with partial efficiency. JPC0661 binds to a groove outside of the DNA-binding cleft of the ΔFOSB/JUND bZIP heterodimer in a cocrystal structure. Here, we generated a …

Ins-17 Acts As A Nutrient Deprivation Signal To Mediate Adult Iis-Regulated Associative Behaviors In C. Elegans, Emily J Leptich, Priyadharshini Vijayakumar, Edward W Pietryk, Meredith I Williams, Rachana Rajupalem, Rachel N Arey

Faculty, Staff and Students Publications

Insulin/Insulin-like growth factor 1 (IGF-1) signaling (IIS) is a pleiotropic signaling pathway that functions across tissues to coordinate phenotypic changes in response to nutrient status. Thus, the ubiquity of the IIS pathway hinders efforts to elucidate the mechanisms driving specific IIS-related phenotypes. Previous research in the nematode worm C. elegans has demonstrated that loss of function of the IIS transmembrane receptor (IR) ortholog, DAF-2, results in a doubled lifespan and enhanced learning and memory behaviors in young and aged animals. However, these findings are the result of reducing DAF-2 receptor function rather than modulating ligand-receptor interactions. In the current study, …

The Association Between Physical Activity, Sedentary Time, And Sleep With Risk Of Hepatocellular Carcinoma In Patients With Cirrhosis, Samuel Ma, Yossef Alsabawi, Fasiha Kanwal, Hao Duong, Laith Elserag, Amit G Singal, Nicole E Rich, Saira Khaderi, Sumeet K Asrani, Hashem B El-Serag, Aaron P Thrift

Faculty, Staff and Students Publications

Background: The majority of hepatocellular carcinoma (HCC) cases arise in patients with cirrhosis, with known major risk factors of hepatitis B (HBV) or C (HCV) infection, metabolic dysfunction-associated steatotic liver disease (MASLD), and alcohol-associated liver disease (ALD). However, the impact of additional risk factors that act independently or jointly on the pathogenesis of HCC in cirrhosis patients is unknown. The aim of this study was to determine whether sleep, sedentariness, or physical activity levels play a role in the progression of cirrhosis to HCC.

Methods: We systematically collected data on sleep, sedentary time, and physical activity from the ongoing prospective …

Androgen Activity In The Male Embryonic Hindbrain Drives Lethal Pfa Ependymoma, Jiao Zhang, Winnie Ong, Alexandra Rasnitsyn, Ricardo Daniel Gonzalez, Rodrigo Lopez Gutierrez, Polina Balin, Amr Saadeldin, Xiaochong Wu, Maria C Vladoiu, Vicente Santa-Maria Lopez, Fernando Gonzalez-Salinas, Navneesh Yadav, Dinesh Mohanakrishnan, Kannan Boosi Narayana Rao, Raja Gopal Reddy Mooli, Hinda Najem, Sebastian Pacheco, Kaitlin Kharas, Cory Richman, David Przelicki, Evan Y Wang, Haipeng Su, Rachel Naomi Curry, Runze Yang, Michelle Masayo Kameda-Smith, Bryn Livingston, David Scott, Zaili Luo, Mingyang Xia, Namal Abeysundara, Anders W Erickson, Ncedile Mankahla, Lucas Zhongming Hu, Chu Pan, Raul Suarez, Ning Huang, Yihao Wu, Hao Wang, Tajana Douglas, Jonelle Pallota, Steven Hébert, Karen Ng, Krystin Mantione, Heather Whetstone, Hassaan Maan, Hussein Lakkis, Juyeun Lee, Sadeesh K Ramakrishnan, Yanxin Pei, Yujie Tang, Frank Y Lin, Guillermo Aldave, Marco Gallo, Robert M Friedlander, Faiyaz Notta, Laura K Donovan, Murali Chintagumpala, Bo Wang, Yun Li, Daniel D De Carvalho, Zhaolei Zhang, Ying Mao, Wei Hua, Charles Eberhart, Calixto-Hope G Lucas, Sriram Venneti, Poul H Sorensen, Alberto Delaidelli, Hao Li, Wenhao Zhou, Jason Kirk, Dean G Tang, Tao Jiang, Hailong Liu, Justin D Lathia, Hiromichi Suzuki, Jeremy N Rich, Lincoln D Stein, Nada Jabado, Vijay Ramaswamy, Q Richard Lu, Amy B Heimberger, Craig Daniels, Kulandaimanuvel Antony Michealraj, Claudia L Kleinman, Michael D Taylor

Faculty, Staff and Students Publications

Posterior fossa type A (PFA) ependymoma is an unusual infantile brain tumour with few known somatic mutations, thought to be driven by epigenetic mechanisms1. PFA ependymoma has a markedly higher incidence and worse prognosis in male children than in female children2. The mechanisms that underlie these sex differences are at present unknown. Here we show that the cellular hierarchy of PFA ependymoma is less differentiated in male individuals than it is in female individuals. In the normal developing mouse hindbrain, male gliogenic progenitors are less differentiated than matched female sibling controls. To further parse the effects …

Robotic Single-Incision Laparoscopic Surgery For The Management Of Endometriosis: First Experience Via The Da Vinci Sp Platform, Qiannan Yang, Daniel Y Lovell, Xiaoming Guan

Faculty, Staff and Students Publications

Objective: To demonstrate the feasibility and mid-term outcomes of Robotic single-port single-incision laparoscopic surgery (RSP-SILS) for endometriosis management.

Methods: A retrospective analysis was conducted on 50 adult women with endometriosis who underwent RSP-SILS via the da Vinci SP platform between November 2023 and July 2025.

Results: Median total operative time was 142 min, robot dock time was 3 min, and robot console time was 99 min. Median estimated blood loss was 25 mL. No conversion occurred. Reported mid-term outcomes included 1 case each of pelvic haematoma, Clostridioides difficile colitis, and umbilical surgical site infection, as well as 3 cases of …

Methodological Progress Note: Logic Models, Molly J Horstman, Kyler M Godwin

Faculty and Staff Publications

Logic models are an accessible tool to organize the planning, management, and evaluation of programs across healthcare disciplines. This methodological progress note describes the five standard components of a logic model (Inputs, Activities, Outputs, Outcomes, and Impact) and provides guidance for developing a logic model. Logic models offer a visual representation of the work and theory of a program and should be created with input from all interested parties. Logic models are living tools that need to be revised as programs evolve and new information becomes available.

Kidney Disease And Heart Failure: Recent Advances And Current Challenges: Conclusions From A Kidney Disease: Improving Global Outcomes (Kdigo) Controversies Conference, Carolyn S P Lam, Biykem Bozkurt, David Z I Cherney, Justin A Ezekowitz, Meg J Jardine, Sadiya S Khan, Magdalena Madero, Mark J Sarnak, Jozine M Ter Maaten, Michael Cheung, Jennifer M King, Morgan E Grams, Michel Jadoul, Nisha Bansal

Faculty, Staff and Students Publications

Heart failure (HF) and chronic kidney disease (CKD) frequently coexist, which elevates the risks of hospitalization, disease progression, and death. Despite advances in treating each condition independently, many challenges remain in diagnosing and managing them in combination. In March 2024, Kidney Disease: Improving Global Outcomes (KDIGO) held the Controversies Conference on Kidney Disease and Heart Failure: Recent Advances and Current Challenges. Discussions highlighted the complex, bidirectional relationship between HF and CKD, including shared risk factors and overlapping pathophysiology as well as nuances in interpreting biomarkers such as natriuretic peptides and serum creatinine. Sodium-glucose cotransporter-2 inhibitors, renin-angiotensin-aldosterone system inhibitors, and emerging …

Ethical Controversies In Organ Procurement: A National Survey On Public Perceptions Of Thoracoabdominal Normothermic Regional Perfusion, Trevor M Bibler, Jill Oliver Robinson, Adam Omelianchuk, Tariq Nisar, Savitri Fedson, Ariel N Levchenko, Amy L Mcguire

Center for Medical Ethics and Health Policy Staff Publications

Thoracoabdominal normothermic regional perfusion (TA-NRP) would likely expand the quantity and quality of organs procured after controlled circulatory death donation in the United States, yet its ethical permissibility remains contested. We surveyed a representative sample of US adults (n = 975) with the goal of assessing their perspectives on the ethical permissibility of TA-NRP. After reading a neutral description of TA-NRP, participants judged its permissibility, reviewed 5 critic and 5 supporter arguments (in random order), and chose which argument they found most convincing. Multivariable logistic regression examined predictors of agreeing with critics. Before exposure to the arguments, 51.5% stated that …

All-Cause And Cause-Specific Mortality In Patients With Bipolar Ii Disorder, Chih-Wei Hsu, Yang-Chieh Brian Chen, Edward Chia-Cheng Lai, Andrew A Nierenberg, Michael Berk, Sheng-Yu Lee, Liang-Jen Wang, Mu-Hong Chen, Yao-Hsu Yang, Chih-Sung Liang, Andre F Carvalho

Children’s Nutrition Research Center Staff Publications

Importance: Whether bipolar II disorder (BD-II) is associated with increased long-term mortality remains uncertain because most studies have not distinguished BD-II from bipolar I disorder (BD-I).

Objective: To examine whether BD-II is associated with elevated all-cause and cause-specific mortality compared with population controls, unaffected siblings, and those with BD-I.

Design, setting, and participants: This population-based, retrospective cohort study used data from Taiwan's National Health Insurance Database from January 1, 2000, to December 31, 2022. Individuals 12 years or older with 2 or more psychiatrist-assigned BD-II diagnoses were individually matched to 4 controls without BD-II by sex and birthdate. Additional comparisons …

Weaning Drives Microbiome-Mediated Epigenetic Regulation To Shape Immune Memory In Mice, Li Yang, Robert C Peery, Shirui Zhou, Xiaomin Chen, Leah M Farmer, Fabiola Gutierrez, Stephanie Fowler, Lanjing Zhang, Julia M Salamat, Karen Riggins, Jiejun Shi, Lanlan Shen

Children’s Nutrition Research Center Staff Publications

During weaning, the transition to solid food diversifies the gut microbiome, triggering a programmed immune response critical for long-lasting mucosal immunity. Previous work showed that the gut microbiome mediates epigenetic development in intestinal stem cells (ISCs) during suckling, but what happens during weaning is unclear. Here, genome-wide profiling revealed that weaning-driven microbiome changes shape the DNA methylome and transcriptome of murine ISCs in an IFNγ-dependent manner. Specifically, we observe demethylation of enhancer elements essential for MHC class II genes, which results in a transcriptional memory that persists through differentiation into adulthood. IFNγ blockade, or low-dose penicillin to target Gram-positive bacteria, …

Dental Insurance Status Among Formerly Incarcerated Older Adults, Alexander Testa, Rafael Samper-Ternent, Dylan B Jackson, Kyle T Ganson, Vahed Maroufy, Jason M Nagata, Ana C Neumann

Faculty, Staff and Student Publications

Formerly incarcerated individuals have poorer oral health and less frequent dental care utilization than the general population. However, prior work has overlooked the relationship between prior incarceration and disparities in dental insurance coverage. Using data from the Health and Retirement Study (n = 11,638), findings from multiple logistic regression analyses demonstrate that formerly incarcerated older adults are significantly less likely to have dental insurance coverage (odds ratio [OR] = 0.745, 95% confidence interval [CI] = 0.608, 0.912). After accounting for the income-to-poverty ratio, this association was no longer statistically significant. Analyses using the Karlson-Holm-Breen method demonstrated that approximately 45% of …

Sexual Health And Relationship Education Needs Of People In Recovery For An Opioid Use Disorder, J Michael Wilkerson, Kathryn R Gallardo, I Niles Zoschke, Hannah L N Stewart, Serena A Rodriguez, Michael U Anosike, Jason Pullin, Sheryl A Mccurdy

Faculty, Staff and Student Publications

People in recovery with histories of sex and drug-linked behavior (SDB) have an increased risk of substance use recurrence. However, sexual health concerns remain largely unaddressed by recovery support services researchers and practitioners. The purpose of this analysis was to describe the sex and relationship concerns of people in recovery for an opioid use disorder living in level II and level III recovery homes. Recovery homes are sober living homes that the National Association for Recovery Residences classifies into four levels based on staffing and service provision. We interviewed 93 residents and thematically analyzed 92 of the resulting transcripts; one …

Robo2 Variants Associated With Atrial Septal Defect Define A Novel Regulatory Element, Seong Won Kim, Michael Parfenov, Laura Rodriguez-Murillo, David A Conner, Arun Sharma, Inga Peter, Feng Xiao, Olivia Layton, Angela Tai, Tarsha Ward, Lauren K Wasson, Joshua M Gorham, Erica Mazaika, Valentina N Lagomarsino, Tracy L Young-Pearse, Elizabeth Goldmuntz, Hiroko Wakimoto, A J Agopian, David M Mckean, Steven R Depalma, William T Pu, Christine E Seidman, Bruce D Gelb, Jonathan G Seidman

Faculty, Staff and Student Publications

Background: Atrial septal defects (ASDs) are a prevalent type of congenital heart disease. Previous GWAS (Genome-Wide Association Studies) have identified common variants associated with ASDs, though their mechanisms remain unknown. We aimed to expand insights into the architecture of common variants associated with ASD risk and elucidate functional mechanisms.

Methods: We conducted a GWAS using isolated ASD cases and healthy controls and replicated findings in an independent cohort. We examined epigenetic marks within this ASD locus in human induced pluripotent stem cell-derived cardiomyocytes and fetal human hearts. We characterized the consequences of deletions introduced by CRISPR-Cas9 mutagenesis of human induced …

The All-Payer Claims Database After The Gobeille Supreme Court Decision: Assessing The Impact On Fatal Opioid-Related Overdose Research, Jack Cordes, Cici Bauer, Dana Bernson, Marc R Larochelle, Wenjun Li, Jiahao Cao, Olaf Dammann, Thomas J Stopka

Faculty, Staff and Student Publications

Objective: To determine the consequences of the Gobeille v. Liberty Mutual Supreme Court decision on the representativeness of the Massachusetts all-payer claims database (APCD). The loss of individuals captured in the APCD may vary demographically, geographically, and in the capture of fatal opioid-related overdose (OOD).

Data sources and study setting: We used 2013-2021 data from the Massachusetts Public Health Data Warehouse (PHD), which links person-level APCD records to other datasets. The APCD includes commercially-insured health claims mandatorily reported pre-Gobeille. Post-Gobeille, reporting from self-insured plans, a subset of commercially-insured plans, became voluntary.

Study design: In a repeated cross-sectional design, we compared …

Transfusion In Transit: A Decade Of Prehospital Blood Transfusion In Pediatric Trauma, Krysta M Sutyak, Eunise C Chen, Lea Mock, Rudolfo Cabrera, Jeannette M Joly, Kuojen Tsao, Bryan A Cotton, David E Meyer, Charles S Cox, Kevin P Lally, Natalie A Drucker

The Brown Foundation: Institute of Molecular Medicine

Background: Prehospital blood transfusion improves mortality in adults, with limited evidence in children. This study describes prehospital blood transfusion in pediatric trauma patients and the impact on shock index, pediatric adjusted (SIPA).

Methods: This study is a retrospective cohort study of trauma patients younger than 18 years who received blood transfusions during helicopter transport to a Level 1 pediatric trauma center from 2011 to 2023. Primary outcome was change in SIPA at time of emergency department (ED) arrival with prehospital transfusion. Secondary subgroup analysis was performed based on transport origin.

Results: Of 137 patients, 58% (80 of 137 patients) were …

Natural Language Generation In Healthcare: A Review Of Methods And Applications, Mengxian Lyu, Xiaohan Li, Ziyi Chen, Jinqian Pan, Cheng Peng, Sankalp Talankar, Yonghui Wu

Faculty, Staff and Student Publications

Objective: This study presents a systematic review of natural language generation (NLG) methods and applications in the medical domain, providing quantitative and qualitative analyses to answer four key research questions regarding methods, evaluation, applications, and challenges of NLG in healthcare.

Methods: We searched PubMed, ACM Digital Library, Web of Science, Science Direct, Scopus, Embase, and ACL Anthology for NLG-related studies in healthcare from 2018 to 2024. Out of 3,988 research articles, 113 met the inclusion criteria and were analyzed across data modality, model architecture, evaluation metrics, and application domain.

Results and conclusion: NLG in healthcare has grown substantially, with annual …

Traumatic Brain Injury And Risk Of Early-Onset Dementia: A Population-Based Cohort Study, Aishwarya Saravanan, Katherine Giorgio, Natalia Lakomski, Andrea L C Schneider, Barbara A Olson-Bullis, Behnam Sabayan, James S Pankow, Paul S De Vries, Kristine Yaffe, Alexa Beiser, Abbas Dehghan, Elizabeth A Peterson, Rachel Zmora, John J Stephen, Denise Scholtens, Maxwell Mansolf, Lenore J Launer, Richard F Maclehose, Pamela L Lutsey, Norrina B Allen, Sanaz Sedaghat

Faculty, Staff and Student Publications

Introduction: We investigated the association between traumatic brain injury (TBI) and incidence of early-onset dementia (EOD) versus late-onset dementia (LOD).

Methods: We included 501,710 UK Biobank participants (average age 56.5). Over a median 13.6 years of follow-up, 836 developed EOD (before 65) and 8947 developed LOD (after 65). We estimated hazard ratios (HRs) for TBI's association with EOD and LOD using Cox proportional hazard models with TBI as a time-varying exposure and coefficient.

Results: TBI was associated with higher risk of both EOD (HR: 4.06 [95% confidence interval: 3.13, 5.26]) and LOD (HR: 2.51 [2.31, 2.72]. Among participants included in …

Continuous Versus Bolus Norepinephrine Administration To Treat Hypotension After Induction Of General Anaesthesia In Low-To-Moderate Risk Noncardiac Surgery Patients: A Randomised Trial, Kristen K Thomsen, Finn Külls, Christina Vokuhl, Linda Krause, Dominik Müller, Max Bossemeyer, Mirja Wegge, Alina Kröker, Alina Bergholz, Christian Zöllner, Daniel I Sessler, Bernd Saugel

Faculty, Staff and Student Publications

Background: Hypotension after induction of general anaesthesia (postinduction hypotension) is common in patients undergoing noncardiac surgery and frequently requires treatment with vasopressors such as norepinephrine. We tested the hypothesis that giving norepinephrine continuously using a syringe infusion pump, compared with giving it as repeated manual boluses, reduces postinduction hypotension within 15 min after starting induction of general anaesthesia in low-to-moderate risk noncardiac surgery patients.

Methods: Patients undergoing elective noncardiac surgery were randomised to either continuous norepinephrine infusion or manual bolus norepinephrine administration intravenously during induction of general anaesthesia. In both groups, norepinephrine was administered through a peripheral venous catheter. Blood …

Predicting Ventilation From Single Breathing Phase Non-Contrast Ct Using Swin Transformers, Yi-Kuan Liu, Hsu-Ting Kuo, Alaa Melek, Richard Castillo, Yevgeniy Vinogradskiy, Lili Zhao, Girish Nair, Edward Castillo

Department of Radiation Oncology Faculty Papers

BACKGROUND: Pulmonary ventilation imaging enables functional avoidance radiotherapy treatment plans by quantifying regional lung function. However, current clinical standards, such as 99𝑚Tc-based single-photon emission computed tomography (SPECT), rely on radioactive tracers, which can introduce imaging deposition artifacts. CT ventilation imaging (CTVI) methods based on both physical models and deep learning approaches currently require multiple CT images as input, such as the inhale/exhale phases of a 4DCT. While the theoretical foundation of physics-based CTVI is built on multi-phase information, the feasibility of single-phase deep learning CTV models has not been determined.

PURPOSE: While deep learning methods have predicted SPECT ventilation from …

Computed Tomography For Four-Dimensional Dose Calculation: Effect Of Detector Array Length, Inhwan Yeo, Qianyi Xu

Department of Radiation Oncology Faculty Papers

PURPOSE: Four-dimensional computed tomography (4DCT) is susceptible to a geometrical error when respiration changes upon patient shift. 4DCT using 16-cm detector arrays, not needing the shift, has been shown to improve geometrical accuracy, compared with a conventional 4DCT (4-cm array), albeit with some Hounsfield unit discrepancies. The 4DCTs were validated for 4D planning.

MATERIALS AND METHODS: A lung-mimicking phantom containing a spherical target with ten respiratory traces and three tumor-shaped targets with their traces was respectively imaged when, to each of the ten-positions/phases, the lung was moved (1) step-wisely by helical scan at each movement (ground truth; 4DCT_GT), …