Medical Specialties Commons^™

Handwashing Results In Incomplete Nicotine Removal From Fingers Of Individuals Who Smoke: A Randomized Controlled Experiment, Thomas F Northrup, Angela L Stotts, Robert Suchting, Amir M Khan, Michelle R Klawans, Charles Green, Eunha Hoh, Melbourne F Hovell, Georg E Matt, Penelope J E Quintana

Faculty, Staff and Student Publications

Objective: Tobacco residue, also known as third-hand smoke (THS), contains toxicants and lingers in dust and on surfaces and clothes. THS also remains on hands of individuals who smoke, with potential transfer to infants during visitation while infants are hospitalized in neonatal intensive care units (NICUs), raising concerns (e.g., hindered respiratory development) for vulnerable infants. Previously unexplored, this study tested handwashing (HW) and sanitization efficacy for finger-nicotine removal in a sample of adults who smoked and were visiting infants in an NICU.

Study design: A cross-sectional sample was recruited to complete an interview, carbon monoxide breath samples, and three nicotine …

Is Loss Of P53 A Driver Of Ductal Carcinoma In Situ Progression?, Rhiannon L Morrissey, Alastair M Thompson, Guillermina Lozano

Faculty, Staff and Student Publications

Ductal carcinoma in situ (DCIS) is a non-obligate precursor of invasive carcinoma. Multiple studies have shown that DCIS lesions typically possess a driver mutation associated with cancer development. Mutation in the TP53 tumour suppressor gene is present in 15-30% of pure DCIS lesions and in ~30% of invasive breast cancers. Mutations in TP53 are significantly associated with high-grade DCIS, the most likely form of DCIS to progress to invasive carcinoma. In this review, we summarise published evidence on the prevalence of mutant TP53 in DCIS (including all DCIS subtypes), discuss the availability of mouse models for the study of DCIS …

Rad Regulation Of Cav12 Channels Controls Cardiac Fight-Or-Flight Response, Arianne Papa, Sergey I Zakharov, Alexander N Katchman, Jared S Kushner, Bi-Xing Chen, Lin Yang, Guoxia Liu, Alejandro Sanchez Jimenez, Robyn J Eisert, Gary A Bradshaw, Wen Dun, Shah R Ali, Aaron Rodriques, Karen Zhou, Veli Topkara, Mu Yang, John P Morrow, Emily J Tsai, Arthur Karlin, Elaine Wan, Marian Kalocsay, Geoffrey S Pitt, Henry M Colecraft, Manu Ben-Johny, Steven O Marx

Faculty, Staff and Student Publications

Fight-or-flight responses involve β-adrenergic-induced increases in heart rate and contractile force. In the present study, we uncover the primary mechanism underlying the heart's innate contractile reserve. We show that four protein kinase A (PKA)-phosphorylated residues in Rad, a calcium channel inhibitor, are crucial for controlling basal calcium current and essential for β-adrenergic augmentation of calcium influx in cardiomyocytes. Even with intact PKA signaling to other proteins modulating calcium handling, preventing adrenergic activation of calcium channels in Rad-phosphosite-mutant mice (4SA-Rad) has profound physiological effects: reduced heart rate with increased pauses, reduced basal contractility, near-complete attenuation of β-adrenergic contractile response and diminished …

Prognostic Significance Of Preoperative And Postoperative Ca 19–9 Normalization In Pancreatic Adenocarcinoma Treated With Neoadjuvant Therapy Or Surgery First, Timothy P Diperi, Timothy E Newhook, Laura R Prakash, Naruhiko Ikoma, Jessica E Maxwell, Michael P Kim, Jeffrey E Lee, Matthew H G Katz, Ching-Wei D Tzeng

Faculty, Staff and Student Publications

BACKGROUND: Normal(ization) of serum carbohydrate 19-9 (CA19-9) before/after surgery has not been compared in patients with pancreatic adenocarcinoma (PDAC) treated with neoadjuvant therapy (NT) versus surgery-first (SF).

METHODS: Characteristics for patients with PDAC who underwent resection from July 2011 to October 2018 were collected. Patients with pre-/postoperative CA19-9, bilirubin/dL, and initial CA19-9 > 1 U/ml were included. Overall survival (OS) and recurrence-free survival (RFS) were compared by pre-/postoperative CA19-9.

RESULTS: In patients receiving NT, normal pre/postoperative CA19-9 ("NT

CONCLUSIONS: While a normal(ized) postoperative CA19-9 may result in similar survival as preoperative normal(ization), postoperative normalization failed to occur in nearly 30% of …

Optical Molecular Imaging And Theranostics In Neurological Diseases Based On Aggregation-Induced Emission Luminogens, Peili Cen, Youyou Zhou, Chunyi Cui, Yen Wei, Zhen Cheng, Shuizhu Wu, Hong Zhang, Mei Tian

Faculty, Staff and Student Publications

Optical molecular imaging and image-guided theranostics benefit from special and specific imaging agents, for which aggregation-induced emission luminogens (AIEgens) have been regarded as good candidates in many biomedical applications. They display a large Stokes shift, high quantum yield, good biocompatibility, and resistance to photobleaching. Neurological diseases are becoming a substantial burden on individuals and society that affect over 50 million people worldwide. It is urgently needed to explore in more detail the brain structure and function, learn more about pathological processes of neurological diseases, and develop more efficient approaches for theranostics. Many AIEgens have been successfully designed, synthesized, and further …

Validation Of Cancer-Type-Dependent Benefit From Immune Checkpoint Blockade In Tmb-H Tumors Identified By The Foundationone Cdx Assay, D J Mcgrail, P G Pilié, N U Rashid, L Voorwerk, M Slagter, M Kok, E Jonasch, M Khasraw, A B Heimberger, N T Ueno, R Ferrarotto, J T Chang, S-Y Lin

Faculty, Staff and Student Publications

No abstract provided.

An Optimized Bioassay For Screening Combined Anticoronaviral Compounds For Efficacy Against Feline Infectious Peritonitis Virus With Pharmacokinetic Analyses Of Gs-441524, Remdesivir, And Molnupiravir In Cats, Sarah Cook, Luke Wittenburg, Victoria C Yan, Jacob H Theil, Diego Castillo, Krystle L Reagan, Sonyia Williams, Cong-Dat Pham, Chun Li, Florian L Muller, Brian G Murphy

Faculty, Staff and Student Publications

Feline infectious peritonitis (FIP) is a fatal disease of cats that currently lacks licensed and affordable vaccines or antiviral therapeutics. The disease has a spectrum of clinical presentations including an effusive ("wet") form and non-effusive ("dry") form, both of which may be complicated by neurologic or ocular involvement. The feline coronavirus (FCoV) biotype, termed feline infectious peritonitis virus (FIPV), is the etiologic agent of FIP. The objective of this study was to determine and compare the in vitro antiviral efficacies of the viral protease inhibitors GC376 and nirmatrelvir and the nucleoside analogs remdesivir (RDV), GS-441524, molnupiravir (MPV; EIDD-2801), and β-D-N

Acetyl-Coenzyme A Synthetase 2 Potentiates Macropinocytosis And Muscle Wasting Through Metabolic Reprogramming In Pancreatic Cancer, Zhijun Zhou, Yu Ren, Jingxuan Yang, Mingyang Liu, Xiuhui Shi, Wenyi Luo, Kar-Ming Fung, Chao Xu, Michael S Bronze, Yuqing Zhang, Courtney W Houchen, Min Li

Faculty, Staff and Student Publications

BACKGROUND & AIMS: Rapid deconditioning, also called cachexia, and metabolic reprogramming are two hallmarks of pancreatic cancer. Acetyl-coenzyme A synthetase short-chain family member 2 (ACSS2) is an acetyl-enzyme A synthetase that contributes to lipid synthesis and epigenetic reprogramming. However, the role of ACSS2 on the nonselective macropinocytosis and cancer cachexia in pancreatic cancer remains elusive. In this study, we demonstrate that ACSS2 potentiates macropinocytosis and muscle wasting through metabolic reprogramming in pancreatic cancer.

METHODS: Clinical significance of ACSS2 was analyzed using samples from patients with pancreatic cancer. ACSS2-knockout cells were established using the clustered regularly interspaced short palindromic repeats-associated protein …

Exploiting Dna Replication Stress As A Therapeutic Strategy For Breast Cancer, Jing Zhang, Doug W Chan, Shiaw-Yih Lin

Faculty, Staff and Student Publications

Proliferating cells rely on DNA replication to ensure accurate genome duplication. Cancer cells, including breast cancer cells, exhibit elevated replication stress (RS) due to the uncontrolled oncogenic activation, loss of key tumor suppressors, and defects in the DNA repair machinery. This intrinsic vulnerability provides a great opportunity for therapeutic exploitation. An increasing number of drug candidates targeting RS in breast cancer are demonstrating promising efficacy in preclinical and early clinical trials. However, unresolved challenges lie in balancing the toxicity of these drugs while maintaining clinical efficacy. Furthermore, biomarkers of RS are urgently required to guide patient selection. In this review, …

Risk Factors For The Development Of Retinopathy In Prediabetes And Type 2 Diabetes: The Diabetes Prevention Program Experience, Neil H White, Qing Pan, William C Knowler, Emily B Schroeder, Dana Dabelea, Emily Y Chew, Barbara Blodi, Ronald B Goldberg, Xavier Pi-Sunyer, Christine Darwin, Mathias Schlögl, David M Nathan

Faculty, Staff and Student Publications

OBJECTIVE: To determine glycemic and nonglycemic risk factors that contribute to the presence of diabetic retinopathy (DR) before and after the onset of type 2 diabetes (T2D).

RESEARCH DESIGN AND METHODS: During the Diabetes Prevention Program (DPP) and DPP Outcome Study (DPPOS), we performed fundus photography over time in adults at high risk for developing T2D, including after they developed diabetes. Fundus photographs were graded using the Early Treatment Diabetic Retinopathy Study (ETDRS) grading system, with DR defined as typical lesions of DR (microaneurysms, exudates, hemorrhage, or worse) in either eye.

RESULTS: By DPPOS year 16 (∼20 years after random …

A Blood-Based Metabolite Panel For Distinguishing Ovarian Cancer From Benign Pelvic Masses, Ehsan Irajizad, Chae Y Han, Joseph Celestino, Ranran Wu, Eunice Murage, Rachelle Spencer, Jennifer B Dennison, Jody Vykoukal, James P Long, Kim Anh Do, Charles Drescher, Karen Lu, Zhen Lu, Robert C Bast, Sam Hanash, Johannes F Fahrmann

Faculty, Staff and Student Publications

PURPOSE: To assess the contributions of circulating metabolites for improving upon the performance of the risk of ovarian malignancy algorithm (ROMA) for risk prediction of ovarian cancer among women with ovarian cysts.

EXPERIMENTAL DESIGN: Metabolomic profiling was performed on an initial set of sera from 101 serous and nonserous ovarian cancer cases and 134 individuals with benign pelvic masses (BPM). Using a deep learning model, a panel consisting of seven cancer-related metabolites [diacetylspermine, diacetylspermidine, N-(3-acetamidopropyl)pyrrolidin-2-one, N-acetylneuraminate, N-acetyl-mannosamine, N-acetyl-lactosamine, and hydroxyisobutyric acid] was developed for distinguishing early-stage ovarian cancer from BPM. The performance of the metabolite panel was evaluated in an …

Nab-Paclitaxel, Capecitabine, And Radiation Therapy After Induction Chemotherapy In Treating Patients With Locally Advanced And Borderline Resectable Pancreatic Cancer: Phase 1 Trial And Imaging-Based Biomarker Validation, Eugene J Koay, Mohamed Zaid, Maureen Aliru, Polycarpe Bagereka, Arie Van Wieren, Maria Jovie Rodriguez, Galia Jacobson, Robert A Wolff, Michael Overman, Gauri Varadhachary, Shubham Pant, Huamin Wang, Ching-Wei Tzeng, Naruhiko Ikoma, Michael Kim, Jeffrey E Lee, Matthew Hg Katz, Eric Tamm, Priya Bhosale, Cullen M Taniguchi, Emma B Holliday, Grace L Smith, Ethan B Ludmir, Bruce D Minsky, Christopher H Crane, Albert C Koong, Prajnan Das, Xuemei Wang, Milind Javle, Sunil Krishnan

Faculty, Staff and Student Publications

PURPOSE: Effective consolidative chemoradiation (CRT) regimens are lacking. In this phase 1 trial, we evaluated the safety and efficacy of nab-paclitaxel, capecitabine, and radiation therapy after induction chemotherapy in patients with locally advanced and borderline-resectable pancreatic cancer (LAPC and BRPC). Also, we evaluated a computed tomography (CT)-based biomarker of response.

METHODS AND MATERIALS: Eligible patients had pathologically confirmed pancreatic ductal adenocarcinoma, underwent computed tomography-imaging, received a diagnosis of LAPC or BRPC, and received induction chemotherapy. Standard 3 + 3 study design was used, with 3 escalating nab-paclitaxel dose levels (50, 75, and 100 mg/m

RESULTS: Twenty-three patients started and finished …

Targeted Temperature Management Using Esophageal Cooling, Cedar Morrow Anderson, Christopher Joseph, Rick Fisher, Donald Berry, J Brad Diestelhorst, Christine Kulstad, Marvin Wayne

Faculty, Staff and Student Publications

Although specific temperature targets are debated, targeted temperature management (TTM) is a common treatment for postcardiac arrest patients. However, consistently implementing a TTM protocol is challenging, especially in a community hospital. Often, the protocols described in the literature include labor- and cost-intensive methods that are not feasible or sustainable in many health care settings. Esophageal temperature management (ETM) is a TTM method that can be easily utilized alone or combined with surface methods. We sought to evaluate ETM in a cohort of patients treated with TTM after cardiac arrest. Chart reviews were conducted of all patients treated with ETM after …

Medication Complexity Among Older Adults With Heart Failure – How Can We Assess Better?, Min Ji Kwak, Monica Cheng, Parag Goyal, Dae Hyun Kim, Scott L Hummel, Abhijeet Dhoble, Ashish Deshmukh, Rajender Aparasu, Holly M Holmes

Faculty, Staff and Student Publications

Medical management of heart failure (HF) has evolved and has achieved significant survival benefits, resulting in highly complex medication regimens. Complex medication regimens create challenges for older adults, including nonadherence and increased adverse drug events, especially associated with cognitive impairment, physical limitations, or lack of social support. However, the association between medication complexity and patients' health outcomes among older adults with HF is unclear. The purpose of this review is to address how the complexity of HF medications has been assessed in the literature and what clinical outcomes are associated with medication regimen complexity in HF. Further, we aimed to …

The Effect Of Biologic Therapy For Immune-Mediated Inflammatory Diseases On Clinical Outcomes Of Covid-19 In The Greater Houston Area: A Retrospective Chart Review, Michela Tinelli, Raphael Wittenberg, Michelle Cornes, Robert W Aldridge, Michael Clark, Richard Byng, Graham Foster, James Fuller, Andrew Hayward, Nigel Hewett, Alan Kilmister, Jill Manthorpe, Joanne Neale, Elizabeth Biswell, Martin Whiteford

Faculty, Staff and Student Publications

There are long-standing concerns that people experiencing homelessness may not recover well if left unsupported after a hospital stay. This study reports on a study investigating the cost-effectiveness of three different 'in patient care coordination and discharge planning' configurations for adults experiencing homelessness who are discharged from hospitals in England. The first configuration provided a clinical and housing in-reach service during acute care and discharge coordination but with no 'step-down' care. The second configuration provided clinical and housing in-reach, discharge coordination and 'step-down' intermediate care. The third configuration consisted of housing support workers providing in-reach and discharge coordination as well …

Comparison Of Setup Accuracy And Efficiency Between The Klarity System And Bodyfix System For Spine Stereotactic Body Radiation Therapy, Enzhuo Quan, Shane P Krafft, Tina M Briere, Marissa J Vaccarelli, Amol J Ghia, Andrew J Bishop, Debra N Yeboa, Todd A Swanson, Eun Young Han

Faculty, Staff and Student Publications

BACKGROUND: Spine stereotactic body radiation therapy (SBRT) uses highly conformal dose distributions and sharp dose gradients to cover targets in proximity to the spinal cord or cauda equina, which requires precise patient positioning and immobilization to deliver safe treatments.

AIMS: Given some limitations with the BodyFIX system in our practice, we sought to evaluate the accuracy and efficiency of the Klarity SBRT patient immobilization system in comparison to the BodyFIX system.

METHODS: Twenty-three patients with 26 metastatic spinal lesions (78 fractions) were enrolled in this prospective observational study with one of two systems - BodyFIX (n = 11) or Klarity …

Inhibition Of Cyclin Dependent Kinase 4/6 Overcomes Primary Resistance To Programmed Cell Death 1 Blockade In Malignant Mesothelioma, Hee-Jin Jang, Cynthia Y Truong, Eric M Lo, Hudson M Holmes, Daniela Ramos, Maheshwari Ramineni, Ju-Seog Lee, Daniel Y Wang, Massimo Pietropaolo, R Taylor Ripley, Bryan M Burt, Hyun-Sung Lee

Faculty, Staff and Student Publications

BACKGROUND: Despite the profound number of malignant pleural mesothelioma (MPM) patients now treated with programmed cell death 1 (PD-1) blockade, insight into the underpinnings of rational therapeutic strategies to treat resistance to checkpoint immunotherapy remains unrealized. Our objective was to develop a novel therapeutic approach to overcome primary resistance to PD-1 blockade in MPM.

METHODS: We generated a transcriptome signature of resistance to PD-1 blockade in MPM patients treated with nivolumab (4 responders and 4 nonresponders). We used The Cancer Genome Atlas MPM cohort (n = 73) to determine what genomic alterations were associated with the resistance signature. We tested …

Investigation Of Murine Host Sex As A Biological Variable In Epithelial Barrier Function And Muscle Contractility In Human Intestinal Organoids, Brooke T Beanland, Eoin P Mcneill, David J Sequeira, Hasen Xue, Noah F Shroyer, Allison L Speer

Faculty, Staff and Student Publications

Intestinal failure (IF) occurs when intestinal surface area or function is not sufficient to support digestion and nutrient absorption. Human intestinal organoid (HIO)-derived tissue-engineered intestine is a potential cure for IF. Research to date has demonstrated successful HIO transplantation (tHIO) into mice with significant in vivo maturation. An area lacking in the literature is exploration of murine host sex as a biological variable (SABV) in tHIO function. In this study, we investigate murine host SABV in tHIO epithelial barrier function and muscle contractility. HIOs were generated in vitro and transplanted into nonobese diabetic, severe combined immunodeficiency gamma chain deficient male …

Combined Regulatory T-Lymphocyte And Il-2 Treatment Is Safe, Tolerable, And Biologically Active For 1 Year In Persons With Amyotrophic Lateral Sclerosis, Jason R Thonhoff, James D Berry, Eric A Macklin, David R Beers, Patricia A Mendoza, Weihua Zhao, Aaron D Thome, Fabio Triolo, James J Moon, Sabrina Paganoni, Merit Cudkowicz, Stanley H Appel

Faculty, Staff and Student Publications

BACKGROUND AND OBJECTIVES: In a phase 1 amyotrophic lateral sclerosis (ALS) study, autologous infusions of expanded regulatory T-lymphocytes (Tregs) combined with subcutaneous interleukin (IL)-2 were safe and well tolerated. Treg suppressive function increased and disease progression stabilized during the study. The present study was conducted to confirm the reliability of these results.

METHODS: Participants with ALS underwent leukapheresis, and their Tregs were isolated and expanded in a current Good Manufacturing Practice facility. Seven participants were randomly assigned in a 1:1 ratio to receive Treg infusions (1 × 10

RESULTS: The Treg/IL-2 treatments were safe and well tolerated, and Treg suppressive …

Differential Integrated Stress Response And Asparagine Production Drive Symbiosis And Therapy Resistance Of Pancreatic Adenocarcinoma Cells, Christopher J Halbrook, Galloway Thurston, Seth Boyer, Cecily Anaraki, Jennifer A Jiménez, Amy Mccarthy, Nina G Steele, Samuel A Kerk, Hanna S Hong, Lin Lin, Fiona V Law, Catherine Felton, Lorenzo Scipioni, Peter Sajjakulnukit, Anthony Andren, Alica K Beutel, Rima Singh, Barbara S Nelson, Fran Van Den Bergh, Abigail S Krall, Peter J Mullen, Li Zhang, Sandeep Batra, Jennifer P Morton, Ben Z Stanger, Heather R Christofk, Michelle A Digman, Daniel A Beard, Andrea Viale, Ji Zhang, Howard C Crawford, Marina Pasca Di Magliano, Claus Jorgensen, Costas A Lyssiotis

Faculty, Staff and Student Publications

The pancreatic tumor microenvironment drives deregulated nutrient availability. Accordingly, pancreatic cancer cells require metabolic adaptations to survive and proliferate. Pancreatic cancer subtypes have been characterized by transcriptional and functional differences, with subtypes reported to exist within the same tumor. However, it remains unclear if this diversity extends to metabolic programming. Here, using metabolomic profiling and functional interrogation of metabolic dependencies, we identify two distinct metabolic subclasses among neoplastic populations within individual human and mouse tumors. Furthermore, these populations are poised for metabolic cross-talk, and in examining this, we find an unexpected role for asparagine supporting proliferation during limited respiration. Constitutive …

The Equilibrium Of Tumor Suppression: Dubs As Active Regulators Of Pten, Audrey Christine, Mi Kyung Park, Su Jung Song, Min Sup Song

Faculty, Staff and Student Publications

PTEN is among the most commonly lost or mutated tumor suppressor genes in human cancer. PTEN, a bona fide lipid phosphatase that antagonizes the highly oncogenic PI3K-AKT-mTOR pathway, is considered a major dose-dependent tumor suppressor. Although PTEN function can be compromised by genetic mutations in inherited syndromes and cancers, posttranslational modifications of PTEN may also play key roles in the dynamic regulation of its function. Notably, deregulated ubiquitination and deubiquitination lead to detrimental impacts on PTEN levels and subcellular partitioning, promoting tumorigenesis. While PTEN can be targeted by HECT-type E3 ubiquitin ligases for nuclear import and proteasomal degradation, studies have …

Molecular Mechanisms Of Resistance To Kinase Inhibitors And Redifferentiation In Thyroid Cancers, Marie-Claude Hofmann, Muthusamy Kunnimalaiyaan, Jennifer R Wang, Naifa L Busaidy, Steven I Sherman, Stephen Y Lai, Mark Zafereo, Maria E Cabanillas

Faculty, Staff and Student Publications

Protein kinases play critical roles in cell survival, proliferation and motility. Their dysregulation is therefore a common feature in the pathogenesis of a number of solid tumors, including thyroid cancers. Inhibiting activated protein kinases has revolutionized thyroid cancer therapy, offering a promising strategy in treating tumors refractory to radioactive iodine treatment or cytotoxic chemotherapies. However, despite satisfactory early responses, these drugs are not curative and most patients inevitably progress due to drug resistance. This review summarizes up-to-date knowledge on various mechanisms that thyroid cancer cells develop to bypass protein kinase inhibition and outlines strategies that are being explored to overcome …

A Semi-Mechanistic Dose-Finding Design In Oncology Using Pharmacokinetic/Pharmacodynamic Modeling, Xiao Su, Yisheng Li, Peter Müller, Chia-Wei Hsu, Haitao Pan, Kim-Anh Do

Faculty, Staff and Student Publications

While a number of phase I dose-finding designs in oncology exist, the commonly used ones are either algorithmic or empirical model-based. We propose a new framework for modeling the dose-response relationship, by systematically incorporating the pharmacokinetic (PK) data collected in the trial and the hypothesized mechanisms of the drug effects, via dynamic PK/PD modeling, as well as modeling of the relationship between a latent cumulative pharmacologic effect and a binary toxicity outcome. This modeling framework naturally incorporates the information on the impact of dose, schedule and method of administration (e.g., drug formulation and route of administration) on toxicity. The resulting …

Development And Validation Of A Population-Based Anatomical Colorectal Model For Radiation Dosimetry In Late Effects Studies Of Survivors Of Childhood Cancer, Constance A Owens, Bastien Rigaud, Ethan B Ludmir, Aashish C Gupta, Suman Shrestha, Arnold C Paulino, Susan A Smith, Christine B Peterson, Stephen F Kry, Choonsik Lee, Tara O Henderson, Gregory T Armstrong, Kristy K Brock, Rebecca M Howell

Faculty, Staff and Student Publications

Purpose: The purposes of this study were to develop and integrate a colorectal model that incorporates anatomical variations of pediatric patients into the age-scalable MD Anderson Late Effects (MDA-LE) computational phantom, and validate the model for pediatric radiation therapy (RT) dose reconstructions.

Methods: Colorectal contours were manually derived from whole-body non-contrast computed tomography (CT) scans of 114 pediatric patients (age range: 2.1-21.6 years, 74 males, 40 females). One contour was used for an anatomical template, 103 for training and 10 for testing. Training contours were used to create a colorectal principal component analysis (PCA)-based statistical shape model (SSM) to extract …

Molecular Map Of Chronic Lymphocytic Leukemia And Its Impact On Outcome, Binyamin A Knisbacher, Ziao Lin, Cynthia K Hahn, Ferran Nadeu, Martí Duran-Ferrer, Kristen E Stevenson, Eugen Tausch, Julio Delgado, Alex Barbera-Mourelle, Amaro Taylor-Weiner, Pablo Bousquets-Muñoz, Ander Diaz-Navarro, Andrew Dunford, Shankara Anand, Helene Kretzmer, Jesus Gutierrez-Abril, Sara López-Tamargo, Stacey M Fernandes, Clare Sun, Mariela Sivina, Laura Z Rassenti, Christof Schneider, Shuqiang Li, Laxmi Parida, Alexander Meissner, François Aguet, Jan A Burger, Adrian Wiestner, Thomas J Kipps, Jennifer R Brown, Michael Hallek, Chip Stewart, Donna S Neuberg, José I Martín-Subero, Xose S Puente, Stephan Stilgenbauer, Catherine J Wu, Elias Campo, Gad Getz

Faculty, Staff and Student Publications

Recent advances in cancer characterization have consistently revealed marked heterogeneity, impeding the completion of integrated molecular and clinical maps for each malignancy. Here, we focus on chronic lymphocytic leukemia (CLL), a B cell neoplasm with variable natural history that is conventionally categorized into two subtypes distinguished by extent of somatic mutations in the heavy-chain variable region of immunoglobulin genes (IGHV). To build the 'CLL map,' we integrated genomic, transcriptomic and epigenomic data from 1,148 patients. We identified 202 candidate genetic drivers of CLL (109 new) and refined the characterization of IGHV subtypes, which revealed distinct genomic landscapes and leukemogenic trajectories. …

Comparison Of Pulmonary Function Changes Between Patients Receiving Neoadjuvant Chemotherapy And Chemoradiotherapy Prior To Minimally Invasive Esophagectomy: A Randomized And Controlled Trial, Xiaosang Chen, Mingjun Du, Han Tang, Hao Wang, Yong Fang, Miao Lin, Jun Yin, Lijie Tan, Yaxing Shen

Faculty, Staff and Student Publications

PURPOSE: Adequate pulmonary function is important for patients undergoing surgical resection of esophageal cancer, especially those that received neoadjuvant therapy. However, it is unknown if pre-operative radiation affects pulmonary function differently compared to chemotherapy. The purpose of this study was to compare changes in pulmonary function between patients undergoing minimally invasive esophagectomy (MIE) who received neoadjuvant chemotherapy or chemoradiotherapy.

METHODS: Between March 2017 and March 2018, esophageal cancer patients requiring neoadjuvant therapy were prospectively enrolled and randomly assigned to receive chemotherapy (CT) or chemoradiotherapy (CRT) before MIE. All patients received pulmonary function testing before and after the neoadjuvant therapy. Changes …

“Racing-Stripe” Modification Of Radial Forearm Free Flap: Technique And Experience (704 Consecutive Cases), Emmanuel G Melissinos, Erik S Marques

Faculty, Staff and Student Publications

The radial forearm fasciocutaneous free flap (RFFF) has proven to be a versatile and reliable tool for the reconstructive microsurgeon when addressing soft-tissue defects. A significant drawback of the traditional RFFF is related to donor site morbidity and wound healing complications, especially when coverage of sizable defects is planned. The authors describe the "racing-stripe" modification of the RFFF (RS-RFFF) that involves harvesting a large segment of the deep forearm fascia with a narrow strip of skin overlying the radial vessels, thus allowing primary closure of the donor site.

METHODS: Retrospective chart review was conducted of a single surgeon's (E.G.M.) experience …

Flow Cytometry Immunophenotypic Features Of Pure Erythroid Leukemia And The Distinction From Reactive Erythroid Precursors, Hong Fang, Sa A Wang, M James You, Shimin Hu, Roberto N Miranda, Zhenya Tang, Pei Lin, Jeffrey L Jorgensen, Jie Xu, Beenu Thakral, Ellen J Schlette, Siba El Hussein, Carlos Bueso-Ramos, L Jeffrey Medeiros, Wei Wang

Faculty, Staff and Student Publications

BACKGROUND: The immunophenotype of pure erythroid leukemia (PEL) as determined by flow cytometry immunophenotypic analysis is not well characterized. The immunophenotypic difference between PEL and reactive conditions is under-explored.

METHODS: We assessed and compared the immunophenotype of 24 PEL cases and 28 reactive cases containing early erythroid precursors by flow cytometry.

RESULTS: The neoplastic erythroid cells in all PEL cases were positive for CD36 and CD71. CD45 was also positive in all cases, but the expression level was often dimmer than granulocytes. CD117 expression ranged from partial to uniform, and CD235a was often only positive in the CD117-dim to negative …

Exploration Of The Minimum Necessary Fviii Level At Different Physical Activity Levels In Pediatric Patients With Hemophilia A, Di Ai, Kun Huang, Gang Li, Yingzi Zhen, Xinyi Wu, Ningning Zhang, Aihua Huo, Zhenping Chen, Runhui Wu

Faculty, Staff and Student Publications

BACKGROUND: Physical activity can increase joint stability and reduce the risk of injury in hemophilia patients. There is limited clinical data on target trough FVIII levels during physical activity in hemophilia A patients. Hence, this study aimed to explore the target trough FVIII level required to avoid bleeding during different physical activities in hemophilia A patients.

METHODS: Patients with severe or moderate hemophilia A, who underwent pharmacokinetics (PK) tests at our center were enrolled in this study. Physical activities and clinical information such as bleeding were recorded. The FVIII level during physical activity was calculated by the WAPPS-Hemo.

RESULTS: A …

Aortic Root Dissection Due To An Automated Fastener Device, Ismael A Salas De Armas, L Maximilian Buja, Manish K Patel, Jayeshkumar Patel, Mehmet H Akay, Emre Gok, Igor D Gregoric

Faculty, Staff and Student Publications

Minimally invasive aortic valve replacement through a right thoracotomy is frequently performed in patients with aortic valve disease. The Cor-Knot Device (LSI Solutions) is an automated fastener that secures valve sutures. This case report is for a patient who developed postcardiotomy shock during a minimally invasive aortic valve surgery. The patient was found to have an aortic root dissection involving 90% of the aortic root circumference, including bilateral coronary ostia. The autopsy revealed that the aortic damage could be explained by a direct aortic intimal tear from the distal tip of the device shaft. The device was most likely not …