Medical Specialties Commons^™

Mass Transport Model Of Radiation Response: Calibration And Application To Chemoradiation For Pancreatic Cancer, Charles X Wang, Dalia Elganainy, Mohamed M Zaid, Joseph D Butner, Anshuman Agrawal, Sara Nizzero, Bruce D Minsky, Emma B Holliday, Cullen M Taniguchi, Grace L Smith, Albert C Koong, Joseph M Herman, Prajnan Das, Anirban Maitra, Huamin Wang, Robert A Wolff, Matthew H G Katz, Christopher H Crane, Vittorio Cristini, Eugene J Koay

Faculty, Staff and Student Publications

PURPOSE: The benefit of radiation therapy for pancreatic ductal adenocarcinoma (PDAC) remains unclear. We hypothesized that a new mechanistic mathematical model of chemotherapy and radiation response could predict clinical outcomes a priori, using a previously described baseline measurement of perfusion from computed tomography scans, normalized area under the enhancement curve (nAUC).

METHODS AND MATERIALS: We simplified an existing mass transport model that predicted cancer cell death by replacing previously unknown variables with averaged direct measurements from randomly selected pathologic sections of untreated PDAC. This allowed using nAUC as the sole model input to approximate tumor perfusion. We then compared the …

Informed Consent For Placebo-Controlled Trials: Do Ethics And Science Conflict?, Hope A Feldman, James A Feldman, Charles C Miller, Garrett Walsh, Jon E Tyson

Faculty, Staff and Student Publications

The use of a placebo has been considered the best method for controlling bias in a prospective randomized clinical trial and provides the most rigorous test of treatment efficacy for evaluating a medical therapy. Placebos commonly produce clinically important effects particularly in studies where the primary outcomes are subjective. Yet the potential beneficial or harmful effects of placebos are often not addressed in designing a clinical trial, calculating the sample size, seeking consent, or interpreting clinical trial results. In this manuscript, we use an actual study to indicate three approaches that might be considered in seeking informed consent for placebo-controlled …

Repeatability And Reproducibility Assessment Of The Apparent Diffusion Coefficient In The Prostate: A Trial Of The Ecog-Acrin Research Group (Acrin 6701), Michael A Boss, Bradley S Snyder, Eunhee Kim, Dena Flamini, Sarah Englander, Karthik M Sundaram, Naveen Gumpeni, Suzanne L Palmer, Haesun Choi, Adam T Froemming, Thorsten Persigehl, Matthew S Davenport, Dariya Malyarenko, Thomas L Chenevert, Mark A Rosen

Faculty, Staff and Student Publications

Background: Uncertainty regarding the reproducibility of the apparent diffusion coefficient (ADC) hampers the use of quantitative diffusion-weighted imaging (DWI) in evaluation of the prostate with magnetic resonance imaging MRI. The quantitative imaging biomarkers alliance (QIBA) profile for quantitative DWI claims a within-subject coefficient of variation (wCV) for prostate lesion ADC of 0.17. Improved understanding of ADC reproducibility would aid the use of quantitative diffusion in prostate MRI evaluation.

Purpose: Evaluation of the repeatability (same-day) and reproducibility (multi-day) of whole-prostate and focal-lesion ADC assessment in a multi-site setting.

Study type: Prospective multi-institutional.

Subjects: Twenty-nine males, ages 53 to 80 (median 63) …

Predominantly Persistent Intraretinal Fluid In The Comparison Of Age-Related Macular Degeneration Treatments Trials, Jason Q Core, Maxwell Pistilli, Peiying Hua, Ebenezer Daniel, Juan E Grunwald, Cynthia A Toth, Glenn J Jaffe, Daniel F Martin, Maureen G Maguire, Gui-Shuang Ying, Comparison Of Age-Related Macular Degeneration Treatments Trials (Catt) Research Group

Faculty, Staff and Student Publications

PURPOSE: To describe predominantly persistent intraretinal fluid (PP-IRF) and its association with visual acuity (VA) and retinal anatomic findings at long-term follow-up in eyes treated with pro re nata (PRN) ranibizumab or bevacizumab for neovascular age-related macular degeneration.

DESIGN: Cohort within a randomized clinical trial.

PARTICIPANTS: Participants in the Comparison of Age-related Macular Degeneration Treatments Trials (CATT) assigned to PRN treatment.

METHODS: The presence of intraretinal fluid (IRF) on OCT scans was assessed at baseline and monthly follow-up visits by Duke OCT Reading Center. Predominantly persistent intraretinal fluid through week 12, year 1, and year 2 was defined as the …

Idh1 Pr132h Ctdna And D-2-Hydroxyglutarate As Csf Biomarkers In Patients With Idh-Mutant Gliomas, Yoko Fujita, Luis Nunez-Rubiano, Antonio Dono, Allison Bellman, Mauli Shah, Juan C Rodriguez, Vasanta Putluri, Abu Hena Mostafa Kamal, Nagireddy Putluri, Roy F Riascos, Jay-Jiguang Zhu, Yoshua Esquenazi, Leomar Y Ballester

Faculty, Staff and Student Publications

INTRODUCTION: We aimed to evaluate IDH1 p.R132H mutation and 2-hydroxyglutarate (2HG) in cerebrospinal fluid (CSF) as biomarkers for patients with IDH-mutant gliomas.

METHODS: CSF was collected from patients with infiltrating glioma, and 2HG levels were measured by liquid chromatography-mass spectrometry. IDH1 p.R132H mutant allele frequency (MAF) in CSF-ctDNA was measured by digital droplet PCR (ddPCR). Tumor volume was measured from standard-of-care magnetic resonance images.

RESULTS: The study included 48 patients, 6 with IDH-mutant and 42 with IDH-wildtype gliomas, and 57 samples, 9 from the patients with IDH-mutant and 48 from the patients with IDH-wildtype gliomas. ctDNA was detected in 7 …

High Prevalence Of Osteopathy In Chronic Pancreatitis: A Cross-Sectional Analysis From The Proceed Study, Phil A Hart, Dhiraj Yadav, Liang Li, Savi Appana, William Fisher, Evan Fogel, Chris E Forsmark, Walter G Park, Stephen Pandol, Mark D Topazian, Stephen K Van Den Eden, Santhi Swaroop Vege, David Bradley, Jose Serrano, Darwin L Conwell, Consortium For The Study Of Chronic Pancreatitis, Diabetes, And Pancreatic Cancer (Cpdpc)

Faculty, Staff and Student Publications

osteopenia). However, existing literature is mostly limited to retrospective or administrative studies that have not clearly defined the prevalence and risk factors. Our aim was to identify patient- and disease-related associations with osteopathy in a prospective cohort study of CP.

Methods: We studied 282 subjects with definitive CP enrolled in the PROCEED study who had a baseline dual-energy X-ray absorptiometry (DXA) scan. Osteopenia and osteoporosis were defined using the lowest T-scores. Clinical data were collected using standardized case report forms. Comparisons were performed with a multivariate logistic regression model with forward selection to identify risk factors for osteopathy.

Results: The …

Integrated Relationship Of Nasopharyngeal Airway Host Response And Microbiome Associates With Bronchiolitis Severity, Michimasa Fujiogi, Yoshihiko Raita, Marcos Pérez-Losada, Robert J Freishtat, Juan C Celedón, Jonathan M Mansbach, Pedro A Piedra, Zhaozhong Zhu, Carlos A Camargo, Kohei Hasegawa

Faculty, Staff and Students Publications

Bronchiolitis is a leading cause of infant hospitalizations but its immunopathology remains poorly understood. Here we present data from 244 infants hospitalized with bronchiolitis in a multicenter prospective study, assessing the host response (transcriptome), microbial composition, and microbial function (metatranscriptome) in the nasopharyngeal airway, and associate them with disease severity. We investigate individual associations with disease severity identify host response, microbial taxonomical, and microbial functional modules by network analyses. We also determine the integrated relationship of these modules with severity. Several modules are significantly associated with risks of positive pressure ventilation use, including the host-type I interferon, neutrophil/interleukin-1, T cell …

The Value Of In Vivo Reflectance Confocal Microscopy As An Assessment Tool In Chemotherapy-Induced Peripheral Neuropathy: A Pilot Study, Sabrina R Ramnarine, Patrick M Dougherty, Roman Rolke, Linda J Williams, Christi Alessi-Fox, Andrew J Coleman, Caterina Longo, Lesley A Colvin, Marie T Fallon

Faculty, Staff and Student Publications

Background: There is a lack of standardized objective and reliable assessment tools for chemotherapy-induced peripheral neuropathy (CIPN). In vivo reflectance confocal microscopy (RCM) imaging offers a non-invasive method to identify peripheral neuropathy markers, namely Meissner's corpuscles (MC). This study investigated the feasibility and value of RCM in CIPN.

Patients and methods: Reflectance confocal microscopy was performed on the fingertip to evaluate MC density in 45 healthy controls and 9 patients with cancer (prior, during, and post-chemotherapy). Quantification was completed by 2 reviewers (one blinded), with maximum MC count/3 × 3 mm image reported. Quantitative Sensory Testing (QST; thermal and mechanical …

Association Of Changes In Antithrombin Activity Over Time With Responsiveness To Enoxaparin Prophylaxis And Risk Of Trauma-Related Venous Thromboembolism, Laura E Vincent, Michael M Talanker, Dakota D Butler, Xu Zhang, Jeanette M Podbielski, Yao-Wei W Wang, Amber Chen-Goodspeed, Selina L Hernandez Gonzalez, Erin E Fox, Bryan A Cotton, Charles E Wade, Jessica C Cardenas

Faculty, Staff and Student Publications

Importance: Venous thromboembolism (VTE) affects 2% to 20% of recovering trauma patients, despite aggressive prophylaxis with enoxaparin. Antithrombin is a primary circulating anticoagulant and crucial component of enoxaparin thromboprophylaxis. Approximately 20% of trauma patients present with antithrombin deficiency (antithrombin activity < 80%).

Objective: To examine time-dependent changes in antithrombin activity, responsiveness to enoxaparin, as measured by anti-factor Xa (anti-FXa) levels, and incidence of VTE after severe trauma and to assess the association of ex vivo antithrombin supplementation with patients' sensitivity to enoxaparin prophylaxis.

Design, setting, and participants: This single-center, prospective cohort study was performed at a level 1 trauma center between January …

Venetoclax Combined With Flag-Ida Induction And Consolidation In Newly Diagnosed Acute Myeloid Leukemia, Courtney D Dinardo, Curtis A Lachowiez, Koichi Takahashi, Sanam Loghavi, Tapan Kadia, Naval Daver, Lianchun Xiao, Maria Adeoti, Nicholas J Short, Koji Sasaki, Sa A Wang, Gautam Borthakur, Ghayas Issa, Abhishek Maiti, Yesid Alvarado, Naveen Pemmaraju, Guillermo Montalban Bravo, Lucia Masarova, Musa Yilmaz, Nitin Jain, Michael Andreeff, Guillermo Garcia-Manero, Steven Kornblau, Farhad Ravandi, Elias Jabbour, Marina Y Konopleva, Hagop M Kantarjian

Faculty, Staff and Student Publications

Multi-agent induction chemotherapy (IC) improves response rates in younger patients with acute myeloid leukemia (AML); however, relapse remains the principal cause of treatment failure. Improved induction regimens are needed. A prospective single-center phase Ib/II study evaluating fludarabine, cytarabine, G-CSF, and idarubicin combined with venetoclax (FLAG-IDA + VEN) in patients with newly diagnosed (ND) or relapsed/refractory AML. The primary efficacy endpoint was assessment of overall activity (overall response rate [ORR]: complete remission [CR] + CR with partial hematologic recovery [CRh] + CR with incomplete hematologic recovery [CRi] + morphologic leukemia free state + partial response). Secondary objectives included additional assessments of …

The Geriatric Nutritional Risk Index As A Predictor Of Complications In Geriatric Trauma Patients: Author Reply In Response To: “The Admission Serum Level Of Albumin Cannot Thoroughly Represent The Nutritional Status Of Trauma Patients”, Heather R Kregel, Patrick B Murphy, Mina Attia, David E Meyer, Rachel S Morris, Ezenwa C Onyema, Sasha D Adams, Charles E Wade, John A Harvin, Lillian S Kao, Thaddeus J Puzio

Faculty, Staff and Student Publications

BACKGROUND: Malnutrition is associated with increased morbidity and mortality after trauma. The Geriatric Nutritional Risk Index (GNRI) is a validated scoring system used to predict the risk of complications related to malnutrition in nontrauma patients. We hypothesized that GNRI is predictive of worse outcomes in geriatric trauma patients.

METHODS: This was a single-center retrospective study of trauma patients 65 years or older admitted in 2019. Geriatric Nutritional Risk Index was calculated based on admission albumin level and ratio of actual body weight to ideal body weight. Groups were defined as major risk (GNRI98). The primary outcome was mortality. Secondary outcomes …

Tp53-Altered Chronic Lymphocytic Leukemia Treated With Firstline Bruton’S Tyrosine Kinase Inhibitor-Based Therapy: A Retrospective Analysis, Hua-Jay J Cherng, Raamis Khwaja, Rashmi Kanagal-Shamanna, Guilin Tang, Jan Burger, Philip Thompson, Alessandra Ferrajoli, Zeev Estrov, Koji Sasaki, Deepa Sampath, Xuemei Wang, Hagop Kantarjian, Michael Keating, William G Wierda, Nitin Jain

Faculty, Staff and Student Publications

Long-term follow up of prospective studies has shown that continuous Bruton's tyrosine kinase inhibitor (BTKi) therapy leads to durable remissions in previously untreated patients with TP53-altered chronic lymphocytic leukemia (CLL); however, it is unknown how variant allele frequency (VAF) of TP53 mutation (TP53-m) or percentage of cells with deletion of chromosome 17p [del(17p)] influences efficacy of firstline BTKi. We performed a retrospective analysis of 130 patients with CLL with baseline del(17p) and/or TP53-m treated with BTKi with or without the BCL2 inhibitor venetoclax (VEN) and with or without CD20 antibody in the firstline setting. A total of 104/130 (80%) patients …

Microbiome Dynamics During Chemoradiation Therapy For Anal Cancer, Daniel Lin, Molly B El Alam, Joseph Abi Jaoude, Ramez Kouzy, Jae L Phan, Jacob H Elnaggar, Brianna Resendiz, Andrea Y Delgado Medrano, Erica J Lynn, Nicholas D Nguyen, Sonal S Noticewala, Geena G Mathew, Emma B Holliday, Bruce D Minsky, Prajnan Das, Van K Morris, Cathy Eng, Melissa P Mezzari, Joseph F Petrosino, Nadim J Ajami, Ann H Klopp, Cullen M Taniguchi, Lauren E Colbert

Faculty, Staff and Student Publications

Purpose: Patients with localized squamous cell carcinoma of the anus (SCCA) who experience treatment toxicity or recurrences have few therapeutic options. Investigation into the microbiome's influence on treatment toxicity and its potential use as a predictive biomarker could improve these patients' outcomes. Our study presents the first longitudinal characterization of the SCCA tumor microbiome and its associations with treatment-related toxicities.

Methods and materials: This prospective cohort study included patients with nonmetastatic SCCA receiving standard-of-care chemoradiation therapy. Anorectal swabs of the tumor site were collected before, during, and after treatment. Patient-reported quality-of-life metrics were collected at similar time points. 16S rRNA …

Clinical Activity Of Mitogen-Activated Protein Kinase-Targeted Therapies In Patients With Non-V600 Braf-Mutant Tumors, Matthew Dankner, Yifan Wang, Rouhi Fazelzad, Benny Johnson, Caroline A Nebhan, Ibiayi Dagogo-Jack, Nathaniel J Myall, Georg Richtig, Jillian W P Bracht, Marco Gerlinger, Eiji Shinozaki, Takayuki Yoshino, Daisuke Kotani, Jason R Fangusaro, Oliver Gautschi, Julien Mazieres, Jeffrey A Sosman, Scott Kopetz, Vivek Subbiah, Michael A Davies, Anna L Groover, Ryan J Sullivan, Keith T Flaherty, Douglas B Johnson, Andrea Benedetti, David W Cescon, Anna Spreafico, George Zogopoulos, April A N Rose

Faculty, Staff and Student Publications

Purpose: Non-V600 mutations comprise approximately 35% of all BRAF mutations in cancer. Many of these mutations have been identified as oncogenic drivers and can be classified into three classes according to molecular characteristics. Consensus treatment strategies for class 2 and 3 BRAF mutations have not yet been established.

Methods: We performed a systematic review and meta-analysis with published reports of individual patients with cancer harboring class 2 or 3 BRAF mutations from 2010 to 2021, to assess treatment outcomes with US Food and Drug Administration-approved mitogen-activated protein kinase (MAPK) pathway targeted therapy (MAPK TT) according to BRAF class, cancer type, …

Echocardiographic Predictors Of Symptomatic Cardiotoxicity Among Patients Undergoing Chemotherapy: A Systematic Review And Meta-Analysis, Muhammad Umer Siddiqui, Youssef Yaacoub, Heidi-Anne Hanson, Joey Junarta, Ahmed K Pasha, Mahek Shah

Division of Internal Medicine Faculty Papers & Presentations

BACKGROUND: Chemotherapeutic agents have been associated with cardiotoxicity; thus, they require close monitoring. Several echocardiographic variables have been investigated as early predictors of symptomatic cardiotoxicity in patients undergoing chemotherapy.

OBJECTIVE: To identify if global longitudinal strain (GLS) is a better predictor of symptomatic cardiotoxicity compared to left ventricular ejection fraction (LVEF) in patients receiving chemotherapy.

METHODS: MEDLINE, Scopus, and Cochrane Central Register of Controlled Trials were searched from inception through December 2020. Adults who developed symptomatic cardiotoxicity (New York Heart Association [NYHA] Class III-IV heart failure, cardiac arrest, or cardiac death) after undergoing chemotherapy with pre- and postchemotherapy echocardiographic measures …

Pilot Phase Results Of A Prospective, Randomized Controlled Trial Of Narrowband Ultraviolet B Phototherapy In Hospitalized Covid-19 Patients, Frank H Lau, Catherine E Powell, Giacomo Adonecchi, Denise M Danos, Andrew R Dinardo, Robert J Chugden, Peter Wolf, Carmen F Castilla

Faculty, Staff and Students Publications

COVID-19 morbidity and mortality are driven by poor immune regulation. Narrowband ultraviolet B (NB-UVB) phototherapy is standard of care in a number of immune-dysregulated diseases. To assess the efficacy of NB-UVB phototherapy for improving COVID-19 outcomes in high-risk, hospitalized, we developed the Adaptive Photo-Protection Trial. This is a multi-center, prospective, double-blinded, randomized, placebo-controlled trial. The pilot phase results are reported here. Consecutive patients admitted with a positive COVID-19 PCR were screened for eligibility. Enrolled subjects were computer randomized 1:1 to NB-UVB or placebo phototherapy. Subjects were treated daily with escalating doses on 27% of their body surface area for up …

Maternal Obesity, Pregnancy Weight Gain, And Birth Weight And Risk Of Colorectal Cancer, Caitlin C Murphy, Piera M Cirillo, Nickilou Y Krigbaum, Amit G Singal, Minjae Lee, Timothy Zaki, Ezra Burstein, Barbara A Cohn

Faculty, Staff and Student Publications

Objective: Colorectal cancer (CRC) is a leading cause of cancer-related death worldwide. Obesity is a well-established risk factor for CRC, and fetal or developmental origins of obesity may underlie its effect on cancer in adulthood. We examined associations of maternal obesity, pregnancy weight gain, and birth weight and CRC in adult offspring.

Design: The Child Health and Development Studies is a prospective cohort of women receiving prenatal care between 1959 and 1966 in Oakland, California (N=18 751 live births among 14 507 mothers). Clinical information was abstracted from mothers' medical records 6 months prior to pregnancy through delivery. Diagnoses of …

Minimal Clinically Important Differences Of Promis Pf In Ankle Fracture Patients, Luke Myhre, Patrick Kellam, Graham Dekeyser, Haojia Li, Yue Zhang, Amy M Cizik, Justin Haller

Faculty, Staff and Student Publications

BACKGROUND: Evaluating the minimal clinically important differences (MCIDs) in patient-reported outcome scores is essential for use of clinical outcomes data. The purpose of the current study was to calculate MCID of Patient Reported Outcome Information System Physical Function (PROMIS PF) scores for ankle fracture patients.

METHODS: All patients who underwent operative fixation for ankle fractures at a single level 1 trauma center were identified by

RESULTS: A total of 331 patients were included in the distribution-based analysis, and 195 patients were included in the anchor-based analysis. Mean age was 45.3 years (SD 17.5), and 59.4% of participants were female. MCID …

A Pilot Study To Determine The Incidence, Type, And Severity Of Non-Routine Events In Neonates Undergoing Gastrostomy Tube Placement, Daniel J France, Emma Schremp, Evan B Rhodes, Jason Slagle, Sarah Moroz, Peter H Grubb, Leon D Hatch, Matthew Shotwell, Amanda Lorinc, Jamie Robinson, Marlee Crankshaw, Timothy Newman, Matthew B Weinger, Martin L Blakely

Faculty, Staff and Student Publications

BACKGROUND: Non-routine events (NRE) are defined as any suboptimal occurrences in a process being measured in the opinion of the reporter and comes from the field of human factors engineering. These typically occur well up-stream of an adverse event and NRE measurement has not been applied to the complex context of neonatal surgery. We sought to apply this novel safety event measurement methodology to neonates in the NICU undergoing gastrostomy tube placement.

METHODS: A prospective pilot study was conducted between November 2016 and August 2020 in the Level IV NICU and the pediatric operating rooms of an urban academic children's …

Urgent Cytoreduction For Newly Diagnosed Acute Myeloid Leukemia Patients Allows Acquisition Of Pretreatment Genomic Data And Enrollment On Investigational Clinical Trials, Kunhwa Kim, Marina Konopleva, Courtney D Dinardo, Gautam Borthakur, Sanam Loghavi, Guilin Tang, Naval Daver, Naveen Pemmaraju, Elias Jabbour, Caitlin R Rausch, Musa Yilmaz, Koji Sasaki, Nicholas J Short, Nitin Jain, Mark Brandt, Sherry Pierce, Guillermo Garcia-Manero, Farhad Ravandi, Hagop Kantarjian, Tapan M Kadia

Faculty, Staff and Student Publications

Newly diagnosed acute myeloid leukemia is often deemed a medical emergency, requiring urgent treatment. This is in contradiction with the need for accurate cytogenetic and molecular data, which is not immediately available, to select optimal therapy. We hypothesized that cytoreduction with hydroxyurea or cytarabine would enable urgent disease control and provide a bridge to clinical trial enrollment. We analyzed three prospective frontline clinical trials that allowed the use of cytoreduction before treatment initiation. Among 274 patients with a median age of 62 (range, 18-89), there was no significant difference in short- and long-term outcome and safety among patients who did …

Impact Of Gap Distance Between Fenestration And Aortic Wall On Target Artery Instability Following Fenestrated-Branched Endovascular Aortic Repair, Jesse Chait, Emanuel R Tenorio, Bernardo C Mendes, Guilherme B Barbosa Lima, Giulianna B Marcondes, Joshua Wong, Thanila A Macedo, Randall R De Martino, Gustavo S Oderich

Faculty, Staff and Student Publications

Objective: Target artery (TA) instability has been the most frequent indication for secondary intervention after fenestrated and branched endovascular aortic repair (FB-EVAR) of pararenal and thoracoabdominal aortic aneurysms (TAAAs). The aim of the present study was to evaluate the effect of the gap distance between the endograft reinforced fenestration and TA origin at the aortic wall (fenestration gap [FG]) on target-related outcomes after FB-EVAR.

Methods: The clinical data and imaging studies of 430 patients enrolled in a prospective, nonrandomized study to evaluate FB-EVAR using manufactured stent grafts were reviewed. Of the 430 patients, 340 (79%) had had more than one …

Gut Microbiome Alterations Associated With Diabetes In Mexican Americans In South Texas, Suet-Ying Kwan, Caroline M Sabotta, Aron Joon, Peng Wei, Lauren E Petty, Jennifer E Below, Xiaogang Wu, Jianhua Zhang, Robert R Jenq, Ernest T Hawk, Joseph B Mccormick, Susan P Fisher-Hoch, Laura Beretta

Faculty, Staff and Student Publications

Mexican Americans have a high prevalence of diabetes and burden of diabetes-related complications, highlighting the need for novel preventive strategies and noninvasive predictors of diabetes risk tailored to this population. Changes in the gut microbiome have the potential to predict diabetes. Here, we aimed to identify alterations in the gut microbiome associated with diabetes in the high-risk population of Mexican Americans in South Texas. Stool samples were collected from 216 subjects from the population-based Cameron County Hispanic Cohort. Among them, 75 had type 2 diabetes. Taxonomic and functional profiling of the stool samples were assessed by 16S and shotgun metagenomic …

Exploratory Investigation Of The Plasma Proteome Associated With The Endotheliopathy Of Trauma, Joseph D Krocker, Kyung Hyun Lee, Hanne H Henriksen, Yao-Wei Willa Wang, Erwin M Schoof, Sigurdur T Karvelsson, Óttar Rolfsson, Pär I Johansson, Claudia Pedroza, Charles E Wade

Faculty, Staff and Student Publications

Background: The endotheliopathy of trauma (EoT) is associated with increased mortality following injury. Herein, we describe the plasma proteome related to EoT in order to provide insight into the role of the endothelium within the systemic response to trauma.

Methods: 99 subjects requiring the highest level of trauma activation were included in the study. Enzyme-linked immunosorbent assays of endothelial and catecholamine biomarkers were performed on admission plasma samples, as well as untargeted proteome quantification utilizing high-performance liquid chromatography and tandem mass spectrometry.

Results: Plasma endothelial and catecholamine biomarker abundance was elevated in EoT. Patients with EoT (n = 62) …

Soy Diferente: A Qualitative Study On The Perceptions Of Recovery Following Traumatic Brain Injury Among Spanish-Speaking Us Immigrants, Monique R Pappadis, Angelle M Sander, Margaret A Struchen, Diana M Kurtz

Faculty, Staff and Students Publications

PURPOSE: To explore the impact of traumatic brain injury (TBI) on the quality of life (QoL) and self-concept of Spanish-speaking U.S. Hispanic immigrants with TBI.

MATERIALS AND METHODS: A prospective, qualitative study conducted in a county level I trauma center and community. Semi-structured interviews on QoL and self-concept following TBI were conducted with 24 Spanish-speaking U.S. Hispanic immigrants with TBI living in the community at least 6 months following injury.

RESULTS: Perceived facilitators of QoL included faith, hopefulness in recovery, empathy for others, and support from others. Perceived barriers to QoL mentioned were symptoms/consequences of injury, employment/financial changes, loss of …

Comprehensive Quantitative Evaluation Of Variability In Magnetic Resonance-Guided Delineation Of Oropharyngeal Gross Tumor Volumes And High-Risk Clinical Target Volumes: An R-Ideal Stage 0 Prospective Study, Carlos E Cardenas, Sanne E Blinde, Abdallah S R Mohamed, Sweet Ping Ng, Cornelis Raaijmakers, Marielle Philippens, Alexis Kotte, Abrahim A Al-Mamgani, Irene Karam, David J Thomson, Jared Robbins, Kate Newbold, Clifton D Fuller, Chris Terhaard

Faculty, Staff and Student Publications

Purpose: Tumor and target volume manual delineation remains a challenging task in head and neck cancer radiation therapy. The purpose of this study was to conduct a multi-institutional evaluation of manual delineations of gross tumor volume (GTV), high-risk clinical target volume (CTV), parotids, and submandibular glands on treatment simulation magnetic resonance scans of patients with oropharyngeal cancer.

Methods and materials: We retrospectively collected pretreatment T1-weighted, T1-weighted with gadolinium contrast, and T2-weighted magnetic resonance imaging scans for 4 patients with oropharyngeal cancer under an institution review board-approved protocol. We provided the scans to 26 radiation oncologists from 7 international cancer centers …

Assessment Of Clinical Response Following Atezolizumab And Bevacizumab Treatment In Patients With Neuroendocrine Tumors: A Nonrandomized Clinical Trial, Daniel M Halperin, Suyu Liu, Arvind Dasari, David Fogelman, Priya Bhosale, Armeen Mahvash, Jeannelyn S Estrella, Laura Rubin, Ajaykumar C Morani, Mark Knafl, Tim A Overeem, Szu-Chin Fu, Luisa M Solis, Edwin Parra Cuentas, Anuj Verma, Hong-Lei Chen, Swati Gite, Priya Subashchandrabose, Shannon Dervin, Katja Schulze, Walter C Darbonne, Cindy Yun, Ignacio I Wistuba, P Andrew Futreal, Scott E Woodman, James C Yao

Faculty, Staff and Student Publications

Importance: Therapies for patients with advanced well-differentiated neuroendocrine tumors (NETs) have expanded but remain inadequate, with patients dying of disease despite recent advances in NET therapy. While patients with other cancers have seen long-term disease control and tumor regression with the application of immunotherapies, initial prospective studies of single-agent programmed cell death 1 inhibitors in NET have been disappointing.

Objective: To evaluate the response rate following treatment with the combination of the vascular endothelial growth factor inhibitor bevacizumab with the programmed cell death 1 ligand 1 inhibitor atezolizumab in patients with advanced NETs.

Design, setting, and participants: This single-arm, open-label …

Cardiovascular Outcomes In Aortopathy: Gentac Registry Of Genetically Triggered Aortic Aneurysms And Related Conditions, Kathryn W Holmes, Sheila Markwardt, Kim A Eagle, Richard B Devereux, Jonathan W Weinsaft, Federico M Asch, Scott A Lemaire, Cheryl L Maslen, Howard K Song, Dianna M Milewicz, Siddharth K Prakash, Dongchuan Guo, Shaine A Morris, Reed E Pyeritz, Rita C Milewski, William J Ravekes, H C Dietz, Ralph V Shohet, Michael Silberbach, Mary J Roman

Faculty, Staff and Student Publications

BACKGROUND: The GenTAC (Genetically Triggered Thoracic Aortic Aneurysm and Cardiovascular Conditions) Registry enrolled patients with genetic aortopathies between 2007 and 2016.

OBJECTIVES: The purpose of this study was to compare age distribution and probability of elective surgery for proximal aortic aneurysm, any dissection surgery, and cardiovascular mortality among aortopathy etiologies.

METHODS: The GenTAC study had a retrospective/prospective design. Participants with bicuspid aortic valve (BAV) with aneurysm (n = 879), Marfan syndrome (MFS) (n = 861), nonsyndromic heritable thoracic aortic disease (nsHTAD) (n = 378), Turner syndrome (TS) (n = 298), vascular Ehlers-Danlos syndrome (vEDS) (n = 149), and Loeys-Dietz syndrome …

Rapid Molecular Diagnostics Of Tuberculosis Resistance By Targeted Stool Sequencing, Doctor B Sibandze, Alexander Kay, Viola Dreyer, Welile Sikhondze, Qiniso Dlamini, Andrew Dinardo, Godwin Mtetwa, Bhekumusa Lukhele, Debrah Vambe, Christoph Lange, Muyalo Glenn Dlamini, Tara Ness, Rojelio Mejia, Barbara Kalsdorf, Jan Heyckendorf, Martin Kuhns, Florian P Maurer, Sindisiwe Dlamini, Gugu Maphalala, Stefan Niemann, Anna Mandalakas

Faculty, Staff and Students Publications

BACKGROUND: Stool is an important diagnostic specimen for tuberculosis in populations who struggle to provide sputum, such as children or people living with HIV. However, the culture of Mycobacterium tuberculosis (M. tuberculosis) complex strains from stool perform poorly. This limits the opportunity for phenotypic drug resistance testing with this specimen. Therefore, reliable molecular methods are urgently needed for comprehensive drug resistance testing on stool specimens.

METHODS: We evaluated the performance of targeted next-generation sequencing (tNGS, Deeplex® Myc-TB) for the detection of mutations associated with M. tuberculosis complex drug resistance on DNA isolated from stool specimens provided by participants from a …

Hypomethylating Agent And Venetoclax With Flt3 Inhibitor “Triplet” Therapy In Older/Unfit Patients With Flt3 Mutated Aml, Musa Yilmaz, Hagop Kantarjian, Nicholas J Short, Patrick Reville, Marina Konopleva, Tapan Kadia, Courtney Dinardo, Gautam Borthakur, Naveen Pemmaraju, Abhishek Maiti, Elias Jabbour, Nitin Jain, Ghayas Issa, Koichi Takahashi, Koji Sasaki, Maro Ohanian, Sherry Pierce, Guillin Tang, Sanam Loghavi, Keyur Patel, Sa A Wang, Guillermo Garcia-Manero, Michael Andreeff, Farhad Ravandi, Naval Daver

Faculty, Staff and Student Publications

In older/unfit newly diagnosed patients with FLT3 mutated acute myeloid leukemia (AML), lower intensity chemotherapy (LIC) in combination with either a FLT3 inhibitor or with venetoclax results in poor overall survival (median 8 to 12.5 months). We performed a retrospective analysis of 87 newly diagnosed FLT3 mutated AML patients treated on triplet (LIC + FLT3 inhibitor + Venetoclax, [N = 27]) and doublet (LIC + FLT3 inhibitor, [N = 60]) regimens at our institution. Data were collected from prospective clinical trials in 75% (N = 65) and 25% (N = 22) who received the same treatment regimens outside of a …

Venetoclax Combined With Induction Chemotherapy In Patients With Newly Diagnosed Acute Myeloid Leukaemia: A Post-Hoc, Propensity Score-Matched, Cohort Study, Curtis A Lachowiez, Patrick K Reville, Hagop Kantarjian, Elias Jabbour, Gautam Borthakur, Naval Daver, Sanam Loghavi, Ken Furudate, Lianchun Xiao, Sherry Pierce, Nicholas J Short, Abhishek Maiti, Musa Yilmaz, Koji Sasaki, Koichi Takahashi, Marina Konopleva, Naveen Pemmaraju, Uday Popat, Elizabeth Shpall, Guillermo Garcia-Manero, Farhad Ravandi, Courtney D Dinardo, Tapan M Kadia

Faculty, Staff and Student Publications

Background: Venetoclax combined with intensive chemotherapy has been shown to be safe with promising activity in fit patients with newly diagnosed acute myeloid leukaemia. The aim of this study was to compare the activity of venetoclax plus intensive chemotherapy with intensive chemotherapy alone.

Methods: This was a post-hoc propensity score matched analysis of prospective clinical trials (NCT03214562, NCT02115295, and NCT01289457) in patients at The University of Texas MD Anderson Cancer Center, Texas, USA between March 29, 2010, and June 15, 2021. Eligible patients were aged 18 years and older, and had newly diagnosed acute myeloid leukaemia …