Digital Commons Network^™

Multifocal, Multiphenotypic Tumours Arising From An Mtor Mutation Acquired In Early Embryogenesis, Clarissa N Pacyna, Madhanagopal Anandapadamanaban, Kevin W Loudon, Iain M Hay, Olga Perisic, Ruoyan Li, Matthew Byrne, Laura Allen, Kirsty Roberts, Yvette Hooks, Anne Y Warren, Grant D Stewart, Menna R Clatworthy, Sarah A Teichmann, Sam Behjati, Peter J Campbell, Roger L Williams, Thomas J Mitchell

Faculty, Staff and Student Publications

Embryogenesis is a vulnerable time. Mutations in developmental cells can result in the wide dissemination of cells predisposed to disease within mature organs. We characterised the evolutionary history of four synchronous renal tumours from a 14-year-old girl using whole genome sequencing alongside single cell and bulk transcriptomic sequencing. Phylogenetic reconstruction timed the origin of all tumours to a multipotent embryonic cell committed to the right kidney, around 4 weeks post-conception. Biochemical and structural analysis of their shared MTOR mutation, absent from normal tissues, demonstrates enhanced protein flexibility, enabling a FAT domain hinge to dramatically increase activity of mTORC1 and mTORC2. …

Lower Intensity Therapy With Cladribine/Low Dose Cytarabine/Venetoclax In Older Patients With Acute Myeloid Leukemia Compares Favorably With Intensive Chemotherapy Among Patients Undergoing Allogeneic Stem Cell Transplantation, Jayastu Senapati, Hagop M Kantarjian, Alexandre Bazinet, Patrick Reville, Nicholas J Short, Naval Daver, Gautam Borthakur, Alex Bataller, Elias Jabbour, Courtney Dinardo, Fadi Haddad, Koji Sasaki, Uday Popat, Betul Oran, Amin M Alousi, Sanam Loghavi, Elizabeth Shpall, Guillermo Garcia-Manero, Farhad Ravandi, Tapan M Kadia

Faculty, Staff and Student Publications

Background: Allogeneic stem cell transplantation (SCT) remains the best consolidative modality in most patients with acute myeloid leukemia (AML). Along with factors directly pertaining to SCT, pretransplantation disease control, performance status, and prior treatment-related complications are important factors that affect posttransplantation survival outcomes.

Methods: The authors compared the survival outcomes of patients ≥60 years of age treated on the phase 2 clinical trial of venetoclax (Ven) added to cladribine (CLAD) and low dose cytarabine (LDAC) alternating with azacitidine (CLAD/LDAC/Ven arm) (NCT03586609) who underwent allogeneic SCT in first remission to a retrospective cohort of patients ≥60 years of age …

Downregulation Of Uba1 Expression In Myelodysplastic Neoplasm, Yue Wei, Hong Zheng, Ziyi Li, Pamela Pennington Lockyer, Faezeh Darbaniyan, Rashmi Kanagal-Shamanna, Hui Yang, Danielle Hammond, Guillermo Garcia-Manero

Faculty, Staff and Student Publications

No abstract provided.

Subsyndromes And Symptom Clusters: Multilevel Factor Analysis Of Behavioral And Psychological Symptoms Of Dementia With Intensive Longitudinal Data, Carolyn E Z Pickering, Vicki Winstead, Mustafa Yildiz, Danny Wang, Maria Yefimova, Andrew M Pickering

Faculty, Staff and Student Publications

Introduction: Behavioral and psychological symptoms in dementia (BPSD) are dynamic phenomena with a high amount of intraindividual variability. We applied a multilevel framework to identify subsyndromes (between-person factors) that represent clinically relevant profiles of BPSD and identify symptom clusters (within-person factors) that represent contextually driven daily symptom experiences.

Methods: This study used an intensive longitudinal design in which 68 co-residing family caregivers to persons living with dementia were recruited to proxy report on their care recipient's daily symptom experiences of 23 different BPSD for eight consecutive days (n = 443 diaries). A multilevel exploratory/confirmatory factor analysis was used to account …

Impact Of Race And Ethnicity On Outcomes After Umbilical Cord Blood Transplantation, Karen Ballen, Tao Wang, Naya He, Jennifer M Knight, Sanghee Hong, Haydar Frangoul, Leo F Verdonck, Amir Steinberg, Miguel A Diaz, C Fred Lemaistre, Sherif M Badawy, Jeffrey J Pu, Hasan Hashem, Bipin Savani, Akshay Sharma, Hillard M Lazarus, Muhammad Bilal Abid, Jason Tay, Hemalatha G Rangarajan, Tamila Kindwall-Keller, Cesar O Freytes, Amer Beitinjaneh, Lena E Winestone, Usama Gergis, Nosha Farhadfar, Neel S Bhatt, Raquel M Schears, David Gómez-Almaguer, Mahmoud Aljurf, Vaibhav Agrawal, Yachiyo Kuwatsuka, Sachiko Seo, David I Marks, Leslie Lehmann, William A Wood, Shahrukh Hashmi, Wael Saber

Faculty, Staff and Student Publications

Background: Umbilical cord blood transplant (UCBT) improves access to transplant for patients lacking a fully matched donor. Previous Center for International Blood and Marrow Transplant Research (CIBMTR) showed that Black patients had a lower overall survival (OS) than White patients following single UCBT. The current study draws on a larger modern cohort and compares outcomes among White, Latinx, Black, and Asian patients.

Objective: To compare outcomes by social determinants of health.

Study design: We designed a retrospective study using CIBMTR data. US patients were between ages 1 and 80; 983 received single and 1529 double UCBT as reported to CIBMTR, …

Prognostic Scores For Ursodeoxycholic Acid-Treated Patients Predict Graft Loss And Mortality In Recurrent Primary Biliary Cholangitis After Liver Transplantation, Aldo J Montano-Loza, Ellina Lytvyak, Gideon Hirschfield, Bettina E Hansen, Maryam Ebadi, Thierry Berney, Christian Toso, Giulia Magini, Alejandra Villamil, Frederik Nevens, Natalie Van Den Ende, Albert Pares, Pablo Ruiz, Débora Terrabuio, Palak J Trivedi, Nadir Abbas, Maria Francesca Donato, Lei Yu, Charles Landis, Jérôme Dumortier, Jessica Katharine Dyson, Adriaan J Van Der Meer, Rozanne De Veer, Mark Pedersen, Marlyn Mayo, Michael P Manns, Richard Taubert, Theresa Kirchner, Luca S Belli, Chiara Mazzarelli, Guido Stirnimann, Annarosa Floreani, Nora Cazzagon, Francesco Paolo Russo, Patrizia Burra, Udi Zigmound, Inbal Houri, Marco Carbone, Giacomo Mulinacci, Stefano Fagiuoli, Daniel Stephan Pratt, Alan Bonder, Thomas D Schiano, Brandy Haydel, Ansgar Lohse, Christoph Schramm, Darius Rüther, Stefania Casu, Xavier Verhelst, Benedetta Terziroli Beretta-Piccoli, Mercedes Robles, Andrew L Mason, Christophe Corpechot, Global Pbc Study Group

Faculty, Staff and Student Publications

Background & aims: Recurrent primary biliary cholangitis (rPBC) develops in approximately 30% of patients and negatively impacts graft and overall patient survival after liver transplantation (LT). There is a lack of data regarding the response rate to ursodeoxycholic acid (UDCA) in rPBC. We evaluated a large, international, multi-center cohort to assess the performance of PBC scores in predicting the risk of graft and overall survival after LT in patients with rPBC.

Methods: A total of 332 patients with rPBC after LT were evaluated from 28 centers across Europe, North and South America. The median age at the time of rPBC …

Diffusion Tensor Imaging For Characterizing Changes In Triple-Negative Breast Cancer During Neoadjuvant Systemic Therapy, Benjamin C Musall, David E Rauch, Rania M M Mohamed, Bikash Panthi, Medine Boge, Rosalind P Candelaria, Huiqin Chen, Mary S Guirguis, Kelly K Hunt, Lei Huo, Ken-Pin Hwang, Anil Korkut, Jennifer K Litton, Tanya W Moseley, Sanaz Pashapoor, Miral M Patel, Brandy J Reed, Marion E Scoggins, Jong Bum Son, Debu Tripathy, Vicente Valero, Peng Wei, Jason B White, Gary J Whitman, Zhan Xu, Wei T Yang, Clinton Yam, Beatriz E Adrada, Jingfei Ma

Faculty, Staff and Student Publications

Background: Assessment of treatment response in triple-negative breast cancer (TNBC) may guide individualized care for improved patient outcomes. Diffusion tensor imaging (DTI) measures tissue anisotropy and could be useful for characterizing changes in the tumors and adjacent fibroglandular tissue (FGT) of TNBC patients undergoing neoadjuvant systemic treatment (NAST).

Purpose: To evaluate the potential of DTI parameters for prediction of treatment response in TNBC patients undergoing NAST.

Study type: Prospective.

Population: Eighty-six women (average age: 51 ± 11 years) with biopsy-proven clinical stage I-III TNBC who underwent NAST followed by definitive surgery. 47% of patients (40/86) had pathologic complete response (pCR). …

Menin Inhibitors In Pediatric Acute Leukemia: A Comprehensive Review And Recommendations To Accelerate Progress In Collaboration With Adult Leukemia And The International Community, Branko Cuglievan, Hagop Kantarjian, Jeffrey E Rubnitz, Todd M Cooper, C Michel Zwaan, Jessica A Pollard, Courtney D Dinardo, Tapan M Kadia, Erin Guest, Nicholas J Short, David Mccall, Naval Daver, Cesar Nunez, Fadi G Haddad, Miriam Garcia, Kapil N Bhalla, Abhishek Maiti, Samanta Catueno, Warren Fiskus, Bing Z Carter, Amber Gibson, Michael Roth, Sajad Khazal, Priti Tewari, Hussein A Abbas, Wallace Bourgeois, Michael Andreeff, Neerav N Shukla, Danh D Truong, Jeremy Connors, Joseph A Ludwig, Janine Stutterheim, Elisabeth Salzer, Kristian L Juul-Dam, Koji Sasaki, Kris M Mahadeo, Sarah K Tasian, Gautam Borthakur, Samantha Dickson, Nitin Jain, Elias Jabbour, Soheil Meshinchi, Guillermo Garcia-Manero, Farhad Ravandi, Eytan M Stein, E Anders Kolb, Ghayas C Issa

Faculty, Staff and Student Publications

Aberrant expression of HOX and MEIS1 family genes, as seen in KMT2A-rearranged, NUP98-rearranged, or NPM1-mutated leukemias leads to arrested differentiation and leukemia development. HOX family genes are essential gatekeepers of physiologic hematopoiesis, and their expression is regulated by the interaction between KMT2A and menin. Menin inhibitors block this interaction, downregulate the abnormal expression of MEIS1 and other transcription factors and thereby release the differentiation block. Menin inhibitors show significant clinical efficacy against KMT2A-rearranged and NPM1-mutated acute leukemias, with promising potential to address unmet needs in various pediatric leukemia subtypes. In this collaborative initiative, pediatric and adult hematologists/oncologists, and stem cell …

Targeting Multiple Receptor Tyrosine Kinases With Sitravatinib: A Phase 1b Study In Advanced Renal Cell Carcinoma And Castrate-Resistant Prostate Cancer, Shubham Pant, Byoung Chul Cho, Christos E Kyriakopoulos, Alexander Spira, Nizar Tannir, Theresa L Werner, Xiaohong Yan, Saskia Neuteboom, Richard Chao, Sanjay Goel

Faculty, Staff and Student Publications

Sitravatinib (MGCD516) is an oral inhibitor of several closely related oncogenic tyrosine kinase receptors that include VEGFR-2 (vascular endothelial growth factor receptor-2), AXL, and MET (mesenchymal-epithelial transition). The safety and antitumor activity of sitravatinib are reported in patients from two histologic cohorts (anti-angiogenesis-refractory clear cell renal cell carcinoma [RCC] and castrate-resistant prostate cancer [CRPC] with bone metastases) who participated in a Phase 1/1b study. The patients were enrolled using a 3-stage design that was based on observed objective responses. Objective response rate (ORR) was the primary endpoint. Duration of response, progression-free survival (PFS), overall survival (OS), and safety were also …

Extent Of Resection Thresholds In Molecular Subgroups Of Newly Diagnosed Isocitrate Dehydrogenase-Wildtype Glioblastoma, Antonio Dono, Ping Zhu, Takeshi Takayasu, Octavio Arevalo, Roy Riascos, Nitin Tandon, Leomar Y Ballester, Yoshua Esquenazi

Faculty, Staff and Student Publications

Background and objectives: Maximizing the extent of resection (EOR) improves outcomes in glioblastoma (GBM). However, previous GBM studies have not addressed the EOR impact in molecular subgroups beyond IDH1/IDH2 status. In the current article, we evaluate whether EOR confers a benefit in all GBM subtypes or only in particular molecular subgroups.

Methods: A retrospective cohort of newly diagnosed GBM isocitrate dehydrogenase (IDH)-wildtype undergoing resection were prospectively included in a database (n = 138). EOR and residual tumor volume (RTV) were quantified with semiautomated software. Formalin-fixed paraffin-embedded tumor tissues were analyzed by targeted next-generation sequencing. The association between recurrent genomic alterations …

Imageable Radioembolization Microspheres For Treatment Of Unresectable Hepatocellular Carcinoma: Interim Results From A First-In-Human Trial, Robert J Abraham, Aravind Arepally, David Liu, Robert Lewandowski, S Cheenu Kappadath, Amit Verma, David Dobrowski, Andrew Holden

Faculty, Staff and Student Publications

Purpose: To determine 6-month interim safety, effectiveness, and multimodal imageability of imageable glass microsphere yttrium-90 (90Y) radioembolization for unresectable hepatocellular carcinoma (HCC) in a first-in-human trial.

Materials and methods: Imageable microspheres (Eye90 Microspheres; ABK Biomedical, Halifax, Nova Scotia, Canada), a U.S. Food and Drug Administration (FDA) Breakthrough-Designated Device consisting of glass radiopaque 90Y microspheres visible on computed tomography (CT) and single photon emission CT (SPECT), were used to treat 6 subjects with unresectable HCC. Patients underwent selective (≤2 segments) treatment in a prospective open-label pilot trial. Key inclusion criteria included liver-only HCC, performance status ≤1, total lesion diameter ≤9 cm, …

Columbia-1: A Randomised Study Of Durvalumab Plus Oleclumab In Combination With Chemotherapy And Bevacizumab In Metastatic Microsatellite-Stable Colorectal Cancer, Neil H Segal, Jeanne Tie, Scott Kopetz, Michel Ducreux, Eric Chen, Rodrigo Dienstmann, Antoine Hollebecque, Matthew J Reilley, Elena Elez, Jan Cosaert, Jason Cain, Yee Soo-Hoo, Nicola Hewson, Zachary A Cooper, Rakesh Kumar, Josep Tabernero

Faculty, Staff and Student Publications

Background: To determine whether the addition of durvalumab (anti-PD-L1) and oleclumab (anti-CD73) to standard-of-care treatment (FOLFOX and bevacizumab) enhances the anti-tumour effect in patients with metastatic colorectal cancer (mCRC).

Methods: COLUMBIA-1 (NCT04068610) was a Phase Ib (feasibility; Part 1)/Phase II (randomised; Part 2) trial in patients with treatment-naïve microsatellite stable mCRC. Patients in Part 2 were randomised to receive standard-of-care (control arm) or standard-of-care plus durvalumab and oleclumab (experimental arm). Primary objectives included safety and efficacy.

Results: Seven patients were enrolled in Part 1 and 52 in Part 2 (n = 26 in each arm). Grade ≥3 treatment-emergent …

Optical Genome Mapping Improves The Accuracy Of Classification, Risk Stratification, And Personalized Treatment Strategies For Patients With Acute Myeloid Leukemia, Sanam Loghavi, Qing Wei, Farhad Ravandi, Andres E Quesada, Mark J Routbort, Shimin Hu, Gokce A Toruner, Sa A Wang, Wei Wang, Roberto N Miranda, Shaoying Li, Jie Xu, Courtney D Dinardo, Naval Daver, Tapan M Kadia, Ghayas C Issa, Hagop M Kantarjian, L Jeffrey Medeiros, Guilin Tang

Faculty, Staff and Student Publications

Cytogenomic characterization is crucial for the classification and risk stratification of acute myeloid leukemia (AML), thereby facilitating therapeutic decision-making. We examined the clinical utility of optical genome mapping (OGM) in 159 AML patients (103 newly diagnosed and 56 refractory/relapsed), all of whom also underwent chromosomal banding analysis (CBA), fluorescence in situ hybridization, and targeted next-generation sequencing. OGM detected nearly all clinically relevant cytogenetic abnormalities that SCG identified with >99% sensitivity, provided the clonal burden was above 20%. OGM identified additional cytogenomic aberrations and/or provided information on fusion genes in 77 (48%) patients, including eight patients with normal karyotypes and four …

Identification Of Molecular Signatures In Epicardial Adipose Tissue In Heart Failure With Preserved Ejection Fraction, Shan He, Lei Zhao, Jianjun Zhang, Xinchun Yang, Huagang Zhu

Faculty, Staff and Student Publications

AIMS: The molecular signatures in epicardial adipose tissue (EAT) that contribute to the pathogenesis of heart failure with preserved ejection fraction (HFpEF) are poorly characterized. In this study, we sought to elucidate molecular signatures including genetic transcripts and long non-coding RNAs (lncRNAs) in EAT that might modulate HFpEF development.

METHODS: RNA sequencing (RNA-seq) was performed to identify differentially expressed lncRNAs and mRNAs in EAT samples from patients with HFpEF (n = 5) and without HF (control, n = 5) who underwent coronary artery bypass grafting. The sequencing results were validated using quantitative real-time PCR (qRT-PCR). Bioinformatics analysis (Gene Ontology and …

Interest In And Willingness To Use Prep: A Cross-Sectional Study Of Individuals With Problematic Substance Use Residing In A High Hiv Prevalence Jurisdiction, Angela M Heads, Constanza De Dios, Kaixuan An, Jin H Yoon, Robert Suchting, Adrienne Gilmore-Thomas, Joy M Schmitz

Faculty, Staff and Student Publications

Although it is an effective HIV prevention method, pre-exposure prophylaxis (PrEP) is underutilized in the Southern US. Many people who use drugs (PWUD) have increased susceptibility to HIV which could be lessened by using PrEP. Potential barriers to PrEP use include lack of awareness of PrEP, low knowledge about HIV prevention, low self-efficacy for HIV prevention, inaccurate risk perceptions, and anticipated stigma. The current study examined predisposing, enabling, and reinforcing factors that may predict interest in PrEP. The purpose of the current study was to explore factors associated with interest in and willingness to use daily oral and long acting …

Targeting The Epidermal Growth Factor Receptor Pathway In Chemotherapy-Resistant Triple-Negative Breast Cancer: A Phase Ii Study, Clinton Yam, Miral Patel, Holly A Hill, Ryan Sun, Roland L Bassett, Elisabeth Kong, Senthil Damodaran, Kimberly B Koenig, Sausan Abouharb, Sadia Saleem, Ajit K Bisen, Rashmi K Murthy, David L Ramirez, Gaiane M Rauch, Beatriz E Adrada, Rosalind P Candelaria, Xiaoping Wang, Elizabeth A Mittendorf, Alastair M Thompson, Jason B White, Elizabeth E Ravenberg, Alyson R Clayborn, Qing-Qing Ding, Daniel J Booser, Oluchi Oke, Abenaa M Brewster, Gabriel N Hortobagyi, Nuhad K Ibrahim, Jennifer K Litton, Vicente Valero, Banu K Arun, Debu Tripathy, Jeffrey T Chang, Ken Chen, Anil Korkut, Stacy L Moulder, Lei Huo, Bora Lim, Naoto T Ueno

Faculty, Staff and Student Publications

Purpose: Epidermal growth factor receptor (EGFR) pathway activation causes chemotherapy resistance, and inhibition of the EGFR pathway sensitizes triple-negative breast cancer (TNBC) cells to chemotherapy in preclinical models. Given the high prevalence of EGFR overexpression in TNBC, we conducted a single-arm phase II study of panitumumab (anti-EGFR monoclonal antibody), carboplatin, and paclitaxel as the second phase of neoadjuvant therapy (NAT) in patients with doxorubicin and cyclophosphamide (AC)-resistant TNBC (NCT02593175).

Patients and methods: Patients with early-stage, AC-resistant TNBC, defined as disease progression or ≤80% reduction in tumor volume after four cycles of AC, were eligible for this study and …

Long Covid Among Undocumented Latino Immigrant Populations In The Emergency Department, Karen P Reyes, Zubaid Rafique, Brian Chinnock, Vijaya Arun Kumar, Michael Gottlieb, Kristin L Rising, Robert M Rodriguez

Faculty, Staff and Students Publications

This cross-sectional study assesses the understanding of and access to care for long COVID symptoms among undocumented Latino immigrants in US emergency departments (EDs).

Dsm-5 Criterion-A-Based Trauma Types In Service Members And Veterans Seeking Treatment For Posttraumatic Stress Disorder, Natasha Benfer, Breanna Grunthal, Katherine A Dondanville, Stacey Young-Mccaughan, Abby Blankenship, Chadi G Abdallah, Sudie E Back, Julianne Flanagan, Edna B Foa, Peter T Fox, John H Krystal, Brian P Marx, Donald D Mcgeary, Carmen P Mclean, Kristi E Pruiksma, Patricia A Resick, John D Roache, Paulo Shiroma, Denise M Sloan, Daniel J Taylor, Jennifer Schuster Wachen, Argelio L López-Roca, Karin L Nicholson, Richard P Schobitz, Christian C Schrader, Allah-Fard M Sharrieff, Jeffrey S Yarvis, Jim Mintz, Terence M Keane, Alan L Peterson, Brett T Litz

Faculty, Staff and Students Publications

Objective: In posttraumatic stress disorder (PTSD), the assumption of the equipotentiality of traumas ignores potentially unique contexts and consequences of different traumas. Accordingly, Stein et al. (2012) developed a reliable typing scheme in which assessors categorized descriptions of traumatic events into six "types": life threat to self (LTS), life threat to other, aftermath of violence (AV), traumatic loss, moral injury by self (MIS), and moral injury by other (MIO). We extended this research by validating the typing scheme using participant endorsements of type, rather than assesor-based types. We examined the concordance of participant and assesor types, frequency, and validity …

Association Of Aortic Valve Calcium With Dementia And Stroke: The Multi-Ethnic Study Of Atherosclerosis, Natalie Marrero, Kunal Jha, Timothy M Hughes, Alexander C Razavi, Jelani K Grant, Ellen Boakye, Khalil Anchouche, Omar Dzaye, Matthew J Budoff, Jerome I Rotter, Xiuqing Guo, Jie Yao, Alexis C Wood, Roger S Blumenthal, Erin D Michos, George Thanassoulis, Wendy S Post, Michael J Blaha, Chinwe Ibeh, Seamus P Whelton

Faculty, Staff and Students Publications

Background and aims: Calcific aortic valve disease is associated with increased thrombin formation, platelet activation, decreased fibrinolysis, and subclinical brain infarcts. We examined the long-term association of aortic valve calcification (AVC) with newly diagnosed dementia and incident stroke in the Multi-Ethnic Study of Atherosclerosis (MESA).

Methods: AVC was measured using non-contrast cardiac CT at Visit 1. We examined AVC as a continuous (log-transformed) and categorical variable (0, 1-99, 100-299, ≥300). Newly diagnosed dementia was adjudicated using International Classification of Disease codes. Stroke was adjudicated from medical records. We calculated absolute event rates (per 1000 person-years) and multivariable adjusted Cox proportional …

A Virtual Breakthrough Series Collaborative For Missed Test Results: A Stepped-Wedge Cluster-Randomized Clinical Trial, Lisa Zubkoff, Andrew J Zimolzak, Ashley N D Meyer, Jennifer Sloane, Umber Shahid, Traber Giardina, Sahar A Memon, Taylor M Scott, Daniel R Murphy, Hardeep Singh

Faculty, Staff and Students Publications

IMPORTANCE: Missed test results, defined as test results not followed up within an appropriate time frame, are common and lead to delays in diagnosis and treatment.

OBJECTIVE: To evaluate the effect of a quality improvement collaborative, the Virtual Breakthrough Series (VBTS), on the follow-up rate of 2 types of test results prone to being missed: chest imaging suspicious for lung cancer and laboratory findings suggestive of colorectal cancer.

DESIGN, SETTING, AND PARTICIPANTS: This stepped-wedge cluster-randomized clinical trial was conducted between February 2020 and March 2022 at 12 Department of Veterans Affairs (VA) medical centers, with a predefined 3-cohort roll-out. Each …

Discordance Between Aptt And Anti-Xa In Monitoring Heparin Anticoagulation In Mechanical Circulatory Support, Song Li, Ang Li, Jennifer A Beckman, Christopher Kim, Marian A Granich, John Mondin, Daniel E Sabath, David A Garcia, Claudius Mahr

Faculty, Staff and Students Publications

AIMS: It is unclear whether activated partial thromboplastin time (aPTT) or anti-Xa is more accurate for monitoring heparin anticoagulation in mechanical circulatory support (MCS) patients. This study investigates the relationship between aPTT and anti-Xa in MCS patients and identifies predictors of discordance.

METHODS AND RESULTS: aPTT and anti-Xa were simultaneously measured in a prospective cohort of MCS patients receiving unfractionated heparin at a tertiary academic medical centre. Therapeutic aPTT and anti-Xa levels were 60-100 s and 0.3-0.7 IU/mL, respectively, and concordance was defined as both levels being subtherapeutic, therapeutic, or supratherapeutic. To identify predictors of discordance, both a machine learning …

Outcomes In Solid Organ Transplant Recipients Receiving Organs From A Donor With Fusarium Solani Species Complex Meningitis, Isabel S Griffin, Dallas J Smith, Pallavi Annambhotla, Jeremy A W Gold, Luis Ostrosky-Zeichner, Carol A Kauffman, Lalitha Gade, Anastasia Litvintseva, Daniel Zp Friedman, Angie G Nishio Lucar, Tarina C Parpia, Joshua Lieberman, Janet Bujan, Julie Corkrean, Mukul K Divatia, Kevin Grimes, Jiejian Lin, Constance Mobley, Mary R Schwartz, Bashar Hannawi, Anne Malilay, Anne O'Boye, Jeffrey Lysne, Mrinalini Venkata Subramani, Hayley Heckmann, Venice Servellita, Charles Chiu, Sridhar V Basavaraju

Faculty, Staff and Student Publications

Background: Five organs (heart, right lung, liver, right, and left kidneys) from a deceased patient were transplanted into five recipients in four US states; the deceased patient was identified as part of a healthcare-associated fungal meningitis outbreak among patients who underwent epidural anesthesia in Matamoros, Mexico.

Methods: After transplant surgeries occurred, Fusarium solani species complex, a fungal pathogen with a high case-mortality rate, was identified in cerebrospinal fluid from the organ donor by metagenomic next-generation sequencing (mNGS) and fungal-specific polymerase chain reaction and in plasma by mNGS.

Results: Four of five transplant recipients received recommended voriconazole prophylaxis; four were monitored …

Technical Pitfalls For Fenestrated-Branched Endovascular Aortic Repair Following Petticoat, Aidin Baghbani-Oskouei, Emanuel R Tenorio, Marina Dias-Neto, Andrea Vacirca, Aleem K Mirza, Naveed Saqib, Bernardo C Mendes, Laura Ocasio, Thanila A Macedo, Gustavo S Oderich

Faculty, Staff and Student Publications

Purpose: The Provisional Extension to Induce Complete Attachment Technique (PETTICOAT) uses a bare-metal stent to scaffold the true lumen in patients with acute or subacute aortic dissections. While it is designed to facilitate remodeling, some patients with chronic post-dissection thoracoabdominal aortic aneurysms (TAAAs) require repair. This study describes the technical pitfalls of fenestrated-branched endovascular aortic repair (FB-EVAR) in patients who underwent prior PETTICOAT repair.

Technique: We report 3 patients with extent II TAAAs who had prior bare-metal dissection stents treated by FB-EVAR. Two patients required maneuvers to reroute the aortic guidewire, which was initially placed in-between stent struts. This was …

Percutaneous Sacral Screw Fixation Alone Sufficient For Mildly Displaced U-Type Sacral Fractures With Preserved Osseous Fixation Pathways, Augustine M Saiz, Patrick J Kellam, Adeet Amin, Zachary Arambula, Abhi Rashiwala, Joshua L Gary, Stephen J Warner, Milton Routt, Jonathan G Eastman

Faculty, Staff and Student Publications

Purpose: To describe U-type sacral fracture characteristics amenable to percutaneous sacral screw fixation.

Methods: U-type sacral fractures were identified from a trauma registry at a level 1 trauma center from 2014 to 2020. Patient demographics, injury mechanism, fracture characteristics, and fixation construct were retrospectively retrieved. Associations between fracture pattern and surgical fixation were identified.

Results: 82 U-type sacral fractures were reviewed. Six treated with lumbopelvic fixation (LPF) and 76 were treated with percutaneous sacral screws (PSS) alone. Patients receiving LBF had greater sacral fracture displacement in coronal, sagittal, and axial planes compared to patients receiving PSS alone (P < 0.05), negating osseous fixation pathways. All patients went onto sacral union and there were no implant failures or unplanned reoperations for either group.

Conclusion: If …

Ketamine For Acute Pain After Trauma: A Pragmatic, Randomized Clinical Trial, James M Klugh, Thaddeus J Puzio, Michael W Wandling, Chelsea J Guy-Frank, Charles Green, Paulina B Sergot, Samuel J Prater, Julius Balogh, Christopher T Stephens, Charles E Wade, Lillian S Kao, John A Harvin

Faculty, Staff and Student Publications

Background: Non-narcotic intravenous medications may be a beneficial adjunct to oral multimodal pain regimens (MMPRs) which reduce but do not eliminate opioid exposure and prescribing after trauma. We hypothesized that the addition of a subdissociative ketamine infusion (KI) to a standardized oral MMPR reduces inpatient opioid exposure.

Methods: Eligible adult trauma patients admitted to the intermediate or intensive care unit were randomized upon admission to our institutional MMPR per usual care (UC) or UC plus subdissociative KI for 24 hours to 72 hours after arrival. The primary outcome was morphine milligram equivalents per day (MME/d) and secondary outcomes included total …

Response To Letter To The Editor Concerning The Article "The Clinical And Economic Impact Of Extended Battery Longevity Of A Substernal Extravascular Implantable Cardioverter Defibrillator"., Bradley P Knight, Nicolas Clémenty, Anish Amin, Ulrika Maria Birgersdotter-Green, Henri Roukoz, Reece Holbrook, Jaimie Manlucu

Heart and Vascular Articles

No abstract provided.

Feasibility Of Interdisciplinary Evaluation In Non-Arthritic Hip Pain: A Randomized Trial, Sarah Depp, Lindsey Brown, Catherine Quatman-Yates, Randi Foraker, Emily S Patterson, W Kelton Vasileff, Stephanie Di Stasi

2020-Current year OA Pubs

BACKGROUND: Physical therapy and orthopaedic surgery are two common treatments for non-arthritic hip pain. Interdisciplinary evaluation across these disciplines may produce a more supportive treatment-planning process; however, the feasibility of such an evaluation remains unknown.

HYPOTHESIS OBJECTIVE: To assess the feasibility of an interdisciplinary evaluation with an orthopaedic surgeon and physical therapist for non-arthritic hip pain.

STUDY DESIGN: Observational feasibility study of a randomized controlled trial.

METHODS: Participants were randomized to an interdisciplinary (surgeon + physical therapist) or standard (surgeon) evaluation in a hip preservation clinic. Recruitment rate was recorded. Retention rate was calculated for all variables of interest. Enrollment …

Discovery Of Genomic And Transcriptomic Pleiotropy Between Kidney Function And Soluble Receptor For Advanced Glycation End Products Using Correlated Meta-Analyses: The Long Life Family Study, Mary F Feitosa, Shiow J Lin, Sandeep Acharya, Bharat Thyagarajan, Mary K Wojczynski, Allison L Kuipers, Alexander Kulminski, Kaare Christensen, Joseph M Zmuda, Michael R Brent, Michael A Province

2020-Current year OA Pubs

Patients with chronic kidney disease (CKD) have increased oxidative stress and chronic inflammation, which may escalate the production of advanced glycation end-products (AGEs). High soluble receptor for AGE (sRAGE) and low estimated glomerular filtration rate (eGFR) levels are associated with CKD and aging. We evaluated whether eGFR calculated from creatinine and cystatin C share pleiotropic genetic factors with sRAGE. We employed whole-genome sequencing and correlated meta-analyses on combined genome-wide association study (GWAS) p-values in 4182 individuals (age range: 24-110) from the Long Life Family Study (LLFS). We also conducted transcriptome-wide association studies (TWAS) on whole blood in a subset of …

15-Gene Expression Profile And Prame As Integrated Prognostic Test For Uveal Melanoma: First Report Of Collaborative Ocular Oncology Group Study No. 2 (Coog2.1), J William Harbour, Kisha D Piggott, Et Al.

2020-Current year OA Pubs

PURPOSEValidated and accurate prognostic testing is critical for precision medicine in uveal melanoma (UM). Our aims were to (1) prospectively validate an integrated prognostic classifier combining a 15-gene expression profile (15-GEP) and

Post-Transplant Cyclophosphamide-Based Graft-Versus-Host Disease Prophylaxis Attenuates Disparity In Outcomes Between Use Of Matched Or Mismatched Unrelated Donors, Brian C Shaffer, Ramzi Abboud, Et Al.

2020-Current year OA Pubs

PURPOSEAccess to allogeneic hematopoietic cell transplantation (HCT) remains limited among persons of non-European ancestry if human leukocyte antigen (HLA) matching is required. We evaluated whether post-transplant cyclophosphamide (PTCy)-based graft-versus-host disease (GVHD) prophylaxis improved HCT outcomes with HLA-matched unrelated donor (MUD) and mismatched unrelated donor (MMUD) HCT when compared with calcineurin inhibitor (CNI)-based prophylaxis.METHODSThree-year overall survival (OS) and GVHD-free, relapse-free survival (GRFS) were compared between adult recipients undergoing initial MUD or single HLA locus MMUD HCT with either PTCy- or CNI-based prophylaxis who were reported to the Center for International Blood and Marrow Transplant Research between 2017 and 2021.RESULTSIncluded were 10,025 …