Medical Specialties Commons^™

A Case Of Severe Anaphylactic Reaction After Administration Of Diagnostic-Dose Ferumoxytol In A Pediatric Patient, Fam Ekladious, David Saul

Jefferson Hospital Staff Papers and Presentations

We describe a case of anaphylaxis during administration of intravenous (IV) ferumoxytol as a magnetic resonance imaging (MRI) contrast agent in a 4-year-old patient with complicated past medical history including YARS genetic mutation with resultant liver failure and deceased donor liver transplantation, stage IV chronic kidney disease (CKD), and hypertension. The patient was noted to have labored breathing 4 min after initiation of ferumoxytol infusion and was subsequently rapidly intubated and returned to the intensive care unit (ICU) for monitoring. Anaphylactic reactions to therapeutic doses of ferumoxytol led to issuance of a black box warning by the FDA in 2015. …

Association Between Obstructive Sleep Apnea And Risk Of Benign Vocal Fold Lesions: A Nationwide 9-Year Follow-Up Cohort Study, Yong Tae Hong, Min Gu Kang, Min Gyu Lee, Sang Woo Yeom, Jong Seung Kim

Faculty, Staff and Student Publications

Since obstructive sleep apnea (OSA) affects various parts of the body, there has been little interest about the effect of OSA on voice. The objective of this study was to evaluate the risk of benign vocal fold lesions (BVFL) in OSA patients. This study used data from the National Health Insurance Service (NHIS) database. The study group was defined as the group diagnosed with OSA between 2008 and 2011. Non-OSA groups were selected based on propensity score (PS) matching. Incidence of BVFL among participants during the follow-up was analyzed. Cox proportional hazard regression analyses were performed to evaluate the association …

Elderly Mice With History Of Acetaminophen Intoxication Display Worsened Cognitive Impairment And Persistent Elevation Of Astrocyte And Microglia Burden, Celso S G Catumbela, Rodrigo Morales

Faculty, Staff and Student Publications

Acetaminophen (APAP) is a leading cause of acute liver failure. The effect of APAP metabolite's effects in the periphery are well characterized; however, associated consequences in the brain remain poorly understood. Animal studies on this subject are few and reveal that frequent APAP intake can trigger cerebral abnormalities that vary depending on the subject's age. Alarmingly, experimental efforts have yet to examine associated consequences in elderly hosts, who correspond to the highest risk of medication overload, impaired drug clearance, and cognitive deficits. Here, we interrogated the cerebral and peripheral pathology of elderly mice submitted to monthly episodes of APAP intoxication …

Electronic Patient-Reported Outcome-Based Symptom Management Versus Usual Care After Lung Cancer Surgery: Long-Term Results Of A Multicenter, Randomized, Controlled Trial, Wei Dai, Yaqin Wang, Jia Liao, Xing Wei, Zhen Dai, Wei Xu, Yangjun Liu, Xin Shelley Wang, Cecilia Pompili, Hongfan Yu, Yang Pu, Yuqian Zhao, Bangrong Cao, Qifeng Wang, Wenhong Feng, Yuanqiang Zhang, Fang Liu, Yuanle Deng, Jin Zhou, Juan Li, Shaohua Xie, Run Xiang, Xiang Wang, Bo Tian, Xiaozun Yang, Bin Hu, Xiaoqin Liu, Tianpeng Xie, Xiaojun Yang, Xiang Zhuang, Guibin Qiao, Qiang Li, Qiuling Shi

Faculty, Staff and Student Publications

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.We previously reported superior symptom control of electronic patient-reported outcome (ePRO)-based symptom management after lung cancer surgery for up to 1 month postdischarge. Here, we present the long-term results (1-12 months) of this multicenter, randomized trial, where …

Changes In Plasma Concentrations Of Per- And Polyfluoroalkyl Substances After Bariatric Surgery In Adolescents From The Teen-Longitudinal Assessment Of Bariatric Surgery (Teen-Labs) Study, Brittney O Baumert, Sandrah P Eckel, Jesse A Goodrich, Zhenjiang Li, Nikos Stratakis, Douglas I Walker, Yinqi Zhao, Fabian Christoph Fischer, Scott Bartell, Damaskini Valvi, Xiangping Lin, Zoe Coates Fuentes, Thomas Inge, Justin Ryder, Todd Jenkins, Rohit Kohli, Stephanie Sisley, Stavra Xanthakos, Sarah Rock, Michele A La Merrill, Rob Mcconnell, David V Conti, Lida Chatzi

Faculty, Staff and Students Publications

Exposure to per- and poly-fluoroalkyl substances (PFAS) is ubiquitous due to their persistence in the environment and in humans. Extreme weight loss has been shown to influence concentrations of circulating persistent organic pollutants (POPs). Using data from the multi-center perspective Teen-Longitudinal Assessment of Bariatric Surgery (Teen-LABS) cohort, we investigated changes in plasma-PFAS in adolescents after bariatric surgery. Adolescents (Mean age = 17.1 years, SD = 1.5 years) undergoing bariatric surgery were enrolled in the Teen-LABS study. Plasma-PFAS were measured at the time of surgery and then 6-, 12-, and 36 months post-surgery. Linear mixed effect models were used to evaluate …

Microglial P2y6 Calcium Signaling Promotes Phagocytosis And Shapes Neuroimmune Responses In Epileptogenesis, Anthony D Umpierre, Bohan Li, Katayoun Ayasoufi, Whitney L Simon, Shunyi Zhao, Manling Xie, Grace Thyen, Benjamin Hur, Jiaying Zheng, Yue Liang, Dale B Bosco, Mark A Maynes, Zhaofa Wu, Xinzhu Yu, Jaeyun Sung, Aaron J Johnson, Yulong Li, Long-Jun Wu

Faculty, Staff and Student Publications

Microglial calcium signaling is rare in a baseline state but strongly engaged during early epilepsy development. The mechanism(s) governing microglial calcium signaling are not known. By developing an in vivo uridine diphosphate (UDP) fluorescent sensor, GRABUDP1.0, we discovered that UDP release is a conserved response to seizures and excitotoxicity across brain regions. UDP can signal through the microglial-enriched P2Y6 receptor to increase calcium activity during epileptogenesis. P2Y6 calcium activity is associated with lysosome biogenesis and enhanced production of NF-κB-related cytokines. In the hippocampus, knockout of the P2Y6 receptor prevents microglia from fully engulfing neurons. Attenuating microglial calcium signaling through calcium …

Repeat Controlled Human Plasmodium Falciparum Infections Delay Bloodstream Patency And Reduce Symptoms, Patricia Ferrer, Andrea A Berry, Allison N Bucsan, Surendra K Prajapati, Karthik Krishnan, Michelle C Barbeau, David M Rickert, Sandra Mendoza Guerrero, Miho Usui, Yonas Abebe, Asha Patil, Sumana Chakravarty, Peter F Billingsley, Faith Pa'ahana-Brown, Kathy Strauss, Biraj Shrestha, Effie Nomicos, Gregory A Deye, B Kim Lee Sim, Stephen L Hoffman, Kim C Williamson, Kirsten E Lyke

Faculty, Staff and Student Publications

Resistance to clinical malaria takes years to develop even in hyperendemic regions and sterilizing immunity has rarely been observed. To evaluate the maturation of the host response against controlled repeat exposures to P. falciparum (Pf) NF54 strain-infected mosquitoes, we systematically monitored malaria-naïve participants through an initial exposure to uninfected mosquitoes and 4 subsequent homologous exposures to Pf-infected mosquitoes over 21 months (n = 8 males) (ClinicalTrials.gov# NCT03014258). The primary outcome was to determine whether protective immunity against parasite infection develops following repeat CHMI and the secondary outcomes were to track the clinical signs and symptoms of malaria and anti-Pf antibody …

Real World Predictors Of Response And 24-Month Survival In High-Grade Tp53-Mutated Myeloid Neoplasms, Amandeep Kaur, Alexandra E Rojek, Emily Symes, Mariam T Nawas, Anand A Patel, Jay L Patel, Payal Sojitra, Barina Aqil, Madina Sukhanova, Megan E Mcnerney, Leo P Wu, Aibek Akmatbekov, Jeremy Segal, Melissa Y Tjota, Sandeep Gurbuxani, Jason X Cheng, Su-Yeon Yeon, Harini V Ravisankar, Carrie Fitzpatrick, Angela Lager, Michael W Drazer, Caner Saygin, Pankhuri Wanjari, Panagiotis Katsonis, Olivier Lichtarge, Jane E Churpek, Sharmila B Ghosh, Ami B Patel, Madhu P Menon, Daniel A Arber, Peng Wang, Girish Venkataraman

Faculty, Staff and Students Publications

Current therapies for high-grade TP53-mutated myeloid neoplasms (≥10% blasts) do not offer a meaningful survival benefit except allogeneic stem cell transplantation in the minority who achieve a complete response to first line therapy (CR1). To identify reliable pre-therapy predictors of complete response to first-line therapy (CR1) and outcomes, we assembled a cohort of 242 individuals with TP53-mutated myeloid neoplasms and ≥10% blasts with well-annotated clinical, molecular and pathology data. Key outcomes examined were CR1 & 24-month survival (OS24). In this elderly cohort (median age 68.2 years) with 74.0% receiving frontline non-intensive regimens (hypomethylating agents +/- venetoclax), the overall cohort CR1 …

The Ifitm5 Mutation In Osteogenesis Imperfecta Type V Is Associated With An Erk/Sox9-Dependent Osteoprogenitor Differentiation Defect, Ronit Marom, I-Wen Song, Emily C Busse, Megan E Washington, Ava S Berrier, Vittoria C Rossi, Laura Ortinau, Youngjae Jeong, Ming-Ming Jiang, Brian C Dawson, Mary Adeyeye, Carolina Leynes, Caressa D Lietman, Bridget M Stroup, Dominyka Batkovskyte, Mahim Jain, Yuqing Chen, Racel Cela, Alexis Castellon, Alyssa A Tran, Isabel Lorenzo, D Nicole Meyers, Shixia Huang, Alicia Turner, Vinitha Shenava, Maegen Wallace, Eric Orwoll, Dongsu Park, Catherine G Ambrose, Sandesh Cs Nagamani, Jason D Heaney, Brendan H Lee

Faculty, Staff and Students Publications

Osteogenesis imperfecta (OI) type V is the second most common form of OI, distinguished by hyperplastic callus formation and calcification of the interosseous membranes, in addition to the bone fragility. It is caused by a recurrent, dominant pathogenic variant (c.-14C>T) in interferon-induced transmembrane protein 5 (IFITM5). Here, we generated a conditional Rosa26-knockin mouse model to study the mechanistic consequences of the recurrent mutation. Expression of the mutant Ifitm5 in osteo-chondroprogenitor or chondrogenic cells resulted in low bone mass and growth retardation. Mutant limbs showed impaired endochondral ossification, cartilage overgrowth, and abnormal growth plate architecture. The cartilage phenotype correlates with …

Efficacy And Safety Of Esmethadone (Rel-1017) In Patients With Major Depressive Disorder And Inadequate Response To Standard Antidepressants: A Phase 3 Randomized Controlled Trial, Maurizio Fava, Stephen M Stahl, Luca Pani, Sara De Martin, Andrew J Cutler, Vladimir Maletic, Charles W Gorodetzky, Frank J Vocci, Frank L Sapienza, Thomas R Kosten, Cornelia Kröger, Paggard Champasa, Cedric O'Gorman, Clotilde Guidetti, Andrea Alimonti, Stefano Comai, Andrea Mattarei, Franco Folli, David Bushnell, Sergio Traversa, Charles E Inturrisi, Paolo L Manfredi, Marco Pappagallo

Faculty, Staff and Students Publications

No abstract provided.

Maldi Imaging Mass Spectrometry Visualizes The Distribution Of Antidepressant Duloxetine And Its Major Metabolites In Mouse Brain, Liver, Kidney, And Spleen Tissues, Saleh M Khalil, Xuan Qin, John M Hakenjos, Jian Wang, Zhaoyong Hu, Xinli Liu, Jin Wang, Mirjana Maletic-Savatic, Kevin R Mackenzie, Martin M Matzuk, Feng Li

Faculty, Staff and Student Publications

Imaging mass spectrometry (IMS) is a powerful tool for mapping the spatial distribution of unlabeled drugs and metabolites that may find application in assessing drug delivery, explaining drug efficacy, and identifying potential toxicity. This study focuses on determining the spatial distribution of the antidepressant duloxetine, which is widely prescribed despite common adverse effects (liver injury, constant headaches) whose mechanisms are not fully understood. We used high-resolution IMS with matrix-assisted laser desorption/ionization to examine the distribution of duloxetine and its major metabolites in four mouse organs where it may contribute to efficacy or toxicity: brain, liver, kidney, and spleen. In none …

Prevalence And Relevant Factors Of Nocturia And Its Impact On Sleep Quality In Chinese University Students, Yakai Liu, Zhenwei Zhang, Huijie Hu, Xiangfei He, Pengchao Xu, Qifeng Dou, Cuiping Song, Huiqing Zhang, Israel Franco, Konstantinos Kamperis, Søren Rittig, Jianguo Wen

Faculty, Staff and Student Publications

The purpose of this study was to investigate the prevalence and relevant factors of nocturia and its impact on sleep quality in university students in Mainland China. A large-scale survey was conducted on 14,000 university students from 3 universities in Henan province, China by using an anonymous questionnaire. The questionnaire collected the information from the past six months. The relationships between the prevalence of nocturia and its relevant factors were evaluated. A total of 13,874 questionnaires were collected and 13,104 qualified for statistical analysis. A total of 659 students suffered from clinically relevant nocturia (CRN) (4.56% in male and 5.34% …

Spatiotemporal Analysis Of Hpv Vaccination And Associated Neighborhood-Level Disparities In Texas-An Ecological Study, Ryan Ramphul, Abigail S Zamorano, Saswati Upadhyay, Manali Desai, Cici Bauer

Faculty, Staff and Student Publications

BACKGROUND: HPV is responsible for most cervical, oropharyngeal, anal, vaginal, and vulvar cancers. The HPV vaccine has decreased cervical cancer incidence, but only 49% of Texas adolescents have initiated the vaccine. Texas shows great variation in HPV vaccination rates. We used geospatial analysis to identify areas with high and low vaccination rates and explored differences in neighborhood characteristics.

METHODS: Using Anselin's Local Moran's I statistic, we conducted an ecological analysis of hot and cold spots of adolescent HPV vaccination coverage in Texas from 2017 to 2021. Next, we utilized a Mann-Whitney U test to compare neighborhood characteristics of vaccination coverage …

Developmental Milestones And Daily Living Skills In Individuals With Angelman Syndrome, Anjali Sadhwani, Sonya Powers, Anne Wheeler, Hillary Miller, Sarah Nelson Potter, Sarika U Peters, Carlos A Bacino, Steven A Skinner, Logan K Wink, Craig A Erickson, Lynne M Bird, Wen-Hann Tan

Faculty, Staff and Students Publications

BACKGROUND: Angelman syndrome (AS) is a neurodevelopmental disorder associated with severe global developmental delay. However, the ages at which different developmental skills are achieved in these individuals remain unclear. We seek to determine the probability and the age of acquisition of specific developmental milestones and daily living skills in individuals with AS across the different molecular subtypes, viz. class I deletion, class II deletion, uniparental disomy, imprinting defect, and UBE3A variants.

METHODS: Caregivers participating in a longitudinal multicenter Angelman Syndrome Natural History Study completed a questionnaire regarding the age at which their children achieved specific developmental milestones and daily living …

Persistent Gram-Negative Bloodstream Infection Increases The Risk Of Recurrent Bloodstream Infection With The Same Species, Paa Kwesi Ankrah, Andrew Bock, Felicia Ruffin, Blake M Hanson, Cesar A Arias, Stacey A Maskarinec, Joshua Parsons, Vance G Fowler, Joshua T Thaden

Faculty, Staff and Student Publications

The association between persistent gram-negative bloodstream infection (GN-BSI), or ongoing positive cultures, and recurrent GN-BSI has not been investigated. Among 992 adults, persistent GN-BSI was associated with increased recurrent GN-BSI with the same bacterial species and strain (6% vs 2%; P = .04). Persistent GN-BSI may be a marker of complicated infection.

Cardiac Magnetic Resonance In The Assessment Of The Anomalous Right Coronary Artery Originating From The Left Sinus Of Valsalva, Alberto Cipriani, Mauro Lo Rito, Silvia Pica, Monica De Gaspari, Ilaria Rigato, Martina Perazzolo Marra, Giorgio De Conti, Simone Corradin, Raffaella Motta, Valeria Pergola, Francesco Secchi, Massimo Lombardi, Barbara Bauce, Alessandro Zorzi, Gaetano Thiene, Cristina Basso, Silvana Molossi, Massimo Antonio Padalino, Domenico Corrado

Faculty, Staff and Students Publications

No abstract provided.

Viral And Host Factors Are Associated With Mortality In Hospitalized Patients With Covid-19, Neil R Aggarwal, Jacquie Nordwall, Dominique L Braun, Lucy Chung, Jordan Coslet, Tatyana Der, Nnakelu Eriobu, Adit A Ginde, Awori J Hayanga, Helene Highbarger, Mark Holodniy, Juan P Horcajada, Mamta K Jain, Kami Kim, Sylvain Laverdure, Jens Lundgren, Ven Natarajan, Hien H Nguyen, Sarah L Pett, Andrew Phillips, Garyphallia Poulakou, David A Price, Philip Robinson, Angela J Rogers, Uriel Sandkovsky, Katy Shaw-Saliba, Jeffrey M Sturek, Barbara W Trautner, Michael Waters, Cavan Reilly

Faculty, Staff and Students Publications

BACKGROUND: Persistent mortality in adults hospitalized due to acute COVID-19 justifies pursuit of disease mechanisms and potential therapies. The aim was to evaluate which virus and host response factors were associated with mortality risk among participants in Therapeutics for Inpatients with COVID-19 (TICO/ACTIV-3) trials.

METHODS: A secondary analysis of 2625 adults hospitalized for acute SARS-CoV-2 infection randomized to 1 of 5 antiviral products or matched placebo in 114 centers on 4 continents. Uniform, site-level collection of participant baseline clinical variables was performed. Research laboratories assayed baseline upper respiratory swabs for SARS-CoV-2 viral RNA and plasma for anti-SARS-CoV-2 antibodies, SARS-CoV-2 nucleocapsid …

Ikzf1 And Ubr4 Gene Variants Drive Autoimmunity And Th2 Polarization In Igg4-Related Disease, Qingxiang Liu, Yanyan Zheng, Ines Sturmlechner, Abhinav Jain, Maryam Own, Qiankun Yang, Huimin Zhang, Filippo Pinto E Vairo, Karen Cerosaletti, Jane H Buckner, Kenneth J Warrington, Matthew J Koster, Cornelia M Weyand, Jörg J Goronzy

Faculty, Staff and Student Publications

IgG4-related disease (IgG4-RD) is a systemic immune-mediated fibroinflammatory disease whose pathomechanisms remain poorly understood. Here, we identified gene variants in familial IgG4-RD and determined their functional consequences. All 3 affected members of the family shared variants of the transcription factor IKAROS, encoded by IKZF1, and the E3 ubiquitin ligase UBR4. The IKAROS variant increased binding to the FYN promoter, resulting in higher transcription of FYN in T cells. The UBR4 variant prevented the lysosomal degradation of the phosphatase CD45. In the presence of elevated FYN, CD45 functioned as a positive regulatory loop, lowering the threshold for T cell activation. Consequently, …

Durable Objective Response To Lurbinectedin In Small Cell Bladder Cancer With Tp53 Mutation: A Molecular-Directed Strategy, Mohammad Jad Moussa, Jaanki Khandelwal, Nathaniel R Wilson, Sagar A Naik, Vivek Subbiah, Matthew T Campbell, Pavlos Msaouel, Parminder Singh, Omar Alhalabi

Faculty, Staff and Student Publications

Small cell bladder cancer (SCBC) is a rare and aggressive disease, often treated with platinum/etoposide-based chemotherapy. Key molecular drivers include the inactivation of onco-suppressor genes (TP53, RB1) and amplifications in proto-oncogenes (MYC). We report a patient with SCBC who achieved an objective and prolonged response to lurbinectedin, which has been approved for metastatic small cell lung cancer, after developing disease progression on cisplatin/etoposide and nivolumab/ipilimumab. A genomic analysis of a metastatic biopsy prior to lurbinectedin initiation revealed a TP53 mutation and amplification of the cell cycle regulators E2F3 and MYCL. A repeat biopsy following …

Mycoplasmoides Genitalium Nucleic Acid Semi-Quantitation And Molecular Macrolide Resistance Detection Via Automated Assays: Gender And Specimen Source Considerations, Erik Munson, Josephine Moore, Trinity Krueger, Amanda Zapp, Stephen C Lavey, Kimber L Munson, Irene A Stafford, Brian Mustanski

Faculty, Staff and Student Publications

A laboratory-developed test (LDT) using analyte-specific reagents has been optimized on a commercial platform to detect macrolide resistance-associated mutations (MRM) in 23S rRNA from Mycoplasmoides genitalium from primary clinical specimens. In this study, MRM-LDT was applied to a multi-specimen source study set. One thousand four hundred ninety-five primary specimens testing positive for M. genitalium by commercial transcription-mediated amplification (TMA) were initially titered by the TMA assay using serial 10-fold dilutions to semi-quantitate target nucleic acid burden. Primary specimens were then processed for MRM detection using the MRM-LDT. Findings were stratified by gender and specimen source. The mean log10 target nucleic …

History Of Suicidal Behavior And Clozapine Prescribing Among People With Schizophrenia In China: A Cohort Study, Yi Yin, Chen Lin, Lijing Wei, Jinghui Tong, Junchao Huang, Baopeng Tian, Shuping Tan, Zhiren Wang, Fude Yang, Yongsheng Tong, Song Chen, L Elliot Hong, Yunlong Tan

Faculty, Staff and Student Publications

BACKGROUND: Clozapine is an off-label drug used in most countries to prevent suicide in individuals with schizophrenia. However, few studies have reported real-world prescription practices. This study aimed to explore the association between a history of suicidal behavior and clozapine prescribing during eight weeks of hospitalization for individuals with early-stage schizophrenia.

METHODS: This observational cohort study used routine health data collected from a mental health hospital in Beijing, China. The study included 1057 inpatients who had schizophrenia onset within 3 years. History of suicidal behavior was coded from reviewing medical notes according to the Columbia Suicide Severity Rating Scale. Information …

Small-Molecule Inhibition Of Kras Through Conformational Selection, Bharti Manwani, Nivetha Brathaban, Abiya Baqai, Yashee Munshi, Hilda W Ahnstedt, Mengqi Zhang, Kajsa Arkelius, Ted Llera, Edilberto Amorim, Fanny M Elahi, Neel S Singhal

Faculty, Staff and Student Publications

L1CAM-positive extracellular vesicles (L1EV) are an emerging biomarker that may better reflect ongoing neuronal damage than other blood-based biomarkers. The physiological roles and regulation of L1EVs and their small RNA cargoes following stroke is unknown. We sought to characterize L1EV small RNAs following stroke and assess L1EV RNA signatures for diagnosing stroke using weighted gene co-expression network analysis and random forest (RF) machine learning algorithms. Interestingly, small RNA sequencing of plasma L1EVs from patients with stroke and control patients (n = 28) identified micro(mi)RNAs known to be enriched in the brain. Weighted gene co-expression network analysis (WGCNA) revealed small RNA …

Small Rna Signatures Of Acute Ischemic Stroke In L1cam Positive Extracellular Vesicles, Bharti Manwani, Nivetha Brathaban, Abiya Baqai, Yashee Munshi, Hilda W Ahnstedt, Mengqi Zhang, Kajsa Arkelius, Ted Llera, Edilberto Amorim, Fanny M Elahi, Neel S Singhal

Faculty, Staff and Student Publications

L1CAM-positive extracellular vesicles (L1EV) are an emerging biomarker that may better reflect ongoing neuronal damage than other blood-based biomarkers. The physiological roles and regulation of L1EVs and their small RNA cargoes following stroke is unknown. We sought to characterize L1EV small RNAs following stroke and assess L1EV RNA signatures for diagnosing stroke using weighted gene co-expression network analysis and random forest (RF) machine learning algorithms. Interestingly, small RNA sequencing of plasma L1EVs from patients with stroke and control patients (n = 28) identified micro(mi)RNAs known to be enriched in the brain. Weighted gene co-expression network analysis (WGCNA) revealed small RNA …

Meningioma Transcriptomic Landscape Demonstrates Novel Subtypes With Regional Associated Biology And Patient Outcome, H Nayanga Thirimanne, Damian Almiron-Bonnin, Nicholas Nuechterlein, Sonali Arora, Matt Jensen, Carolina A Parada, Chengxiang Qiu, Frank Szulzewsky, Collin W English, William C Chen, Philipp Sievers, Farshad Nassiri, Justin Z Wang, Tiemo J Klisch, Kenneth D Aldape, Akash J Patel, Patrick J Cimino, Gelareh Zadeh, Felix Sahm, David R Raleigh, Jay Shendure, Manuel Ferreira, Eric C Holland

Faculty, Staff and Students Publications

Meningiomas, although mostly benign, can be recurrent and fatal. World Health Organization (WHO) grading of the tumor does not always identify high-risk meningioma, and better characterizations of their aggressive biology are needed. To approach this problem, we combined 13 bulk RNA sequencing (RNA-seq) datasets to create a dimension-reduced reference landscape of 1,298 meningiomas. The clinical and genomic metadata effectively correlated with landscape regions, which led to the identification of meningioma subtypes with specific biological signatures. The time to recurrence also correlated with the map location. Further, we developed an algorithm that maps new patients onto this landscape, where the nearest …

Therapy-Related Chronic Myelomonocytic Leukemia Does Not Have The High-Risk Features Of A Therapy-Related Neoplasm, Alex Bataller, Georgina Gener-Ricos, Emmanuel Almanza-Huante, Kelly S Chien, Samuel Urrutia, Alexandre Bazinet, Juan Jose Rodriguez-Sevilla, Danielle Hammond, Koji Sasaki, Koichi Takahashi, Courtney D Dinardo, Farhad Ravandi, Gautam Borthakur, Tapan M Kadia, Rashmi Kanagal-Shamanna, Hagop M Kantarjian, Guillermo Garcia-Manero, Guillermo Montalban-Bravo

Faculty, Staff and Student Publications

Therapy-related myeloid neoplasms (t-MNs) arise after exposure to cytotoxic therapies and are associated with high-risk genetic features and poor outcomes. We analyzed a cohort of patients with therapy-related chronic myelomonocytic leukemia (tCMML; n = 71) and compared its features to that of de novo CMML (dnCMML; n = 461). Median time from cytotoxic therapy to tCMML diagnosis was 6.5 years. Compared with dnCMML, chromosome-7 abnormalities (4% vs 13%; P = .005) but not complex karyotype (3% vs 7%; P = .15), were more frequent in tCMML. tCMML was characterized by higher TP53 mutation frequency (4% vs 12%; P = .04) …

Morbidity And Mortality Following Hiatal Hernia Repair In Geriatric Patients: A Multicenter Research Network Study, Sunjay S. Kumar, Martina Rama, Scott Koeneman, Sami Tannouri, Talar Tatarian, Francesco Palazzo

Department of Surgery Faculty Papers

BACKGROUND: Hiatal hernia is a common surgical pathology. Such hernias can be found incidentally and patients may opt for an initial nonoperative approach though many will pursue surgery after symptom progression. Data on the effects of age on the outcomes of hiatal hernia repair may help inform this decision-making process.

METHODS: The TriNetX database was queried for all adult patients undergoing hiatal hernia repair from 2000 to 2023. Patients were divided into elective and emergent cohorts on the basis of diagnosis codes indicating obstruction or gangrene. Patients aged 80-89 were compared against those aged 65-79 in unadjusted analysis. Logistic regression …

Echocardiogram By Apical-Subcostal Protocol In Prone Position During Invasive Mechanical Ventilation In Cardiovascular Intensive Care Unit, César Del Castillo, Fernando Verdugo, Franco Appiani, Francisca Yáñez, Camila Bontá, Carlos Torres-Herrera, Angela Garcia, Zorba Blázquez-Bermejo, Javier Castrodeza, Daniel Requena, Andreina Rodríguez, Arquimedes Silvio, Agustín Gatica, Arnulfo Begazo, Mario Alfaro

Faculty, Staff and Students Publications

AIMS: To evaluate the feasibility of a transthoracic echocardiogram using an apical-subcostal protocol in invasive mechanical ventilation (IMV) and prone position.

METHODS: Prospective study of adults who required a prone position during IMV. A pillow was placed only under the left hemithorax in the prone position to elevate and ease the apical and subcostal windows. A critical care cardiologist (prone group) acquired and evaluated the images using the apical-subcostal protocol. Besides, we used ambulatory echocardiograms performed as a comparative group (supine group).

RESULTS: 86 patients were included, 43 in the prone and 43 in the supine. In the prone group, …

Folate As A Potential Treatment For Lethal Ventricular Arrhythmias In Tango2-Deficiency Disorder, Weiyi Xu, Yingqiong Cao, Sara B Stephens, Maria Jose Arredondo, Yifan Chen, William Perez, Liang Sun, Andy C Yu, Jean J Kim, Seema R Lalani, Na Li, Frank T Horrigan, Francisco Altamirano, Xander Ht Wehrens, Christina Y Miyake, Lilei Zhang

Faculty, Staff and Students Publications

TANGO2-deficiency disorder (TDD) is an autosomal-recessive genetic disease caused by biallelic loss-of-function variants in the TANGO2 gene. TDD-associated cardiac arrhythmias are recalcitrant to standard antiarrhythmic medications and constitute the leading cause of death. Disease modeling for TDD has been primarily carried out using human dermal fibroblast and, more recently, in Drosophila by multiple research groups. No human cardiomyocyte system has been reported, which greatly hinders the investigation and understanding of TDD-associated arrhythmias. Here, we established potentially novel patient-derived induced pluripotent stem cell differentiated cardiomyocyte (iPSC-CM) models that recapitulate key electrophysiological abnormalities in TDD. These electrophysiological abnormalities were rescued in iPSC-CMs …

Determining The Optimal Dosage Of Dexmedetomidine For Smooth Emergence In Older Patients Undergoing Spinal Surgery: A Study Of 44 Cases, Hyoeun Ahn, Yun Jeong Chae, Gyu Bin Choi, Min Gyu Lee, Ji Young Yoo

Faculty, Staff and Student Publications

BACKGROUND Emergence agitation, or delirium, occurs during early recovery from general anesthesia and involves disorientation, excitation, and uncontrolled physical movements. Dexmedetomidine is an alpha agonist that has sedative, anxiolytic, analgesic, and sympatholytic activities and is used as a continuous infusion to prevent emergence agitation. This study aimed to evaluate patients aged 65 years and older undergoing general anesthesia to determine the 90% effective dose (ED90) of dexmedetomidine continuous intraoperative infusion to prevent emergence agitation. MATERIAL AND METHODS We enrolled 44 patients aged 65 years and older undergoing spinal surgery under general anesthesia. Dexmedetomidine administration commenced 30 minutes before surgery completion, …

Vertebral Hu Value And The Pectoral Muscle Index Based On Chest Ct Can Be Used To Opportunistically Screen For Osteoporosis, Xiong-Yi Wang, Sheng Pan, Wei-Feng Liu, Yi-Ke Wang, Si-Min Yun, You-Jia Xu

Faculty, Staff and Student Publications

BACKGROUND: Existing studies have shown that computed tomography (CT) attenuation and skeletal muscle tissue are strongly associated with osteoporosis; however, few studies have examined whether vertebral HU values and the pectoral muscle index (PMI) measured at the level of the 4th thoracic vertebra (T4) are strongly associated with bone mineral density (BMD). In this study, we demonstrate that vertebral HU values and the PMI based on chest CT can be used to opportunistically screen for osteoporosis and reduce fracture risk through prompt treatment.

METHODS: We retrospectively evaluated 1000 patients who underwent chest CT and DXA scans from August 2020-2022. The …