Digital Commons Network^™

The Role Of The Immune System In Lung Transplantation: Towards Improved Long-Term Results, Ramsey R. Hachem

Open Access Publications

Over the past 35 years, lung transplantation has evolved from an experimental treatment to the treatment of choice for patients with end-stage lung disease. Beyond the immediate period after lung transplantation, rejection and infection are the leading causes of death. The risk of rejection after lung transplantation is generally higher than after other solid organ transplants, and this necessitates more intensive immunosuppression. However, this more intensive treatment does not reduce the risk of rejection sufficiently, and rejection is one of the most common complications after transplantation. There are multiple forms of rejection including acute cellular rejection, antibody-mediated rejection, and chronic …

Omnipresence Of Inflammasome Activities In Inflammatory Bone Diseases, Yael Alippe, Gabriel Mbalaviele

Open Access Publications

The inflammasomes are intracellular protein complexes that are assembled in response to a variety of perturbations including infections and injuries. Failure of the inflammasomes to rapidly clear the insults or restore tissue homeostasis can result in chronic inflammation. Recurring inflammation is also provoked by mutations that cause the constitutive assembly of the components of these protein platforms. Evidence suggests that chronic inflammation is a shared mechanism in bone loss associated with aging, dysregulated metabolism, autoinflammatory, and autoimmune diseases. Mechanistically, inflammatory mediators promote bone resorption while suppressing bone formation, an imbalance which over time leads to bone loss and increased fracture …

Relation Between Central Venous, Peripheral Venous And Arterial Lactate Levels In Patients With Sepsis In The Emergency Department, Dimitrios Velissaris, Vasileios Karamouzos, Nikolaos Dimitrios Pantzaris, Ourania Kyriakopoulou, Charalampos Gogos, Menelaos Karanikolas

Open Access Publications

Background: Sepsis and multi-organ failure remain a major clinical problem with high morbidity and mortality worldwide. Lactate measurement remains part of the initial assessment and management of patients with sepsis. Although arterial blood is most commonly used for lactate measurement, there is increasing use of peripheral venous lactate for initial assessment and for monitoring of response to treatment in patients with sepsis. The aim of this study was to evaluate the relation between lactate levels measured from central line, peripheral vein and arterial line in patients treated for sepsis in the emergency department (ED).

Methods: This prospective study enrolled 31 …

Steady-State Activation And Modulation Of The Synaptic-Type Α1Β2Γ2l Gabaa Receptor By Combinations Of Physiological And Clinical Ligands, Allison L Germann, Spencer R Pierce, Thomas C Senneff, Ariel B Burbridge, Joe Henry Steinbach, Gustav Akk

Open Access Publications

The synaptic α1β2γ2 GABA

Lessons Learned From Hurricane Maria In Puerto Rico: Practical Measures To Mitigate The Impact Of A Catastrophic Natural Disaster On Radiation Oncology Patients, Hiram A Gay, James A Kavanaugh, Jeff Bradley, Et Al

Open Access Publications

PURPOSE: Although the wind, rain, and flooding of Hurricane Maria in Puerto Rico abated shortly after its landfall on September 20, 2017, the disruption of the electrical, communications, transportation, and medical infrastructure of the island was unprecedented in scope and caused lasting harm for many months afterward. A compilation of recommendations from radiation oncologists who were in Puerto Rico during the disaster, and from a panel of American Society for Radiation Oncology (ASTRO) cancer experts was created.

METHODS AND MATERIALS: Radiation oncologists throughout Puerto Rico collaborated and improvised to continue treating patients in the immediate aftermath of the storm and …

Exome Sequencing Of Abcb5 Identifies Recurrent Melanoma Mutations That Result In Increased Proliferative And Invasive Capacities, Géraldine Sana, James P Madigan, Jared J Gartner, Marie Fourrez, Jimmy Lin, Nouar Qutob, Jitendra Narayan, Suneet Shukla, Suresh V Ambudkar, Di Xia, Steven A Rosenberg, Michael M Gottesman, Yardena Samuels, Jean-Pierre Gillet

Open Access Publications

ABCB5 is an ABC transporter that was shown to confer low-level multidrug resistance in cancer. In this study, we show that ABCB5 was mutated in 13.75% of the 640 melanoma samples analyzed. Besides nonsense mutations, two mutation hotspots were found in the ABCB5 protein, in the drug-binding pocket and the nucleotide-binding domains. Four mutations, which are representative of the mutation pattern, were selected. ATPase assays showed that these mutations resulted in a decrease in basal ATP hydrolysis by ABCB5. To select informative melanoma cell lines, mutational profiles of the clinical samples were further analyzed. This study showed mutations in the …

Assessing Organizational Supports For Evidence-Based Decision Making In Local Public Health Departments In The United States: Development And Psychometric Properties Of A New Measure, Stephanie Mazzucca, Renee G Parks, Rachel G Tabak, Peg Allen, Maureen Dobbins, Katherine A Stamatakis, Ross C Brownson

Open Access Publications

CONTEXT: Fostering evidence-based decision making (EBDM) within local public health departments and among local health department (LHD) practitioners is crucial for the successful translation of research into public health practice to prevent and control chronic disease.

OBJECTIVE: The purpose of this study was to identify organizational supports for EBDM within LHDs and determine psychometric properties of a measure of organizational supports for EBDM in LHDs.

DESIGN: Cross-sectional, observation study.

SETTING: Local public health departments in the United States.

PARTICIPANTS: Local health department practitioners (N = 376) across the United States participated in the study.

MAIN OUTCOME MEASURES: Local health department …

Four-Jointed Knock-Out Delays Renal Failure In An Adpkd Model With Kidney Injury, Chiara Formica, Hester Happé, Kimberley Am Veraar, Andrea Vortkamp, Marion Scharpfenecker, Helen Mcneill, Dorien Jm Peters

Open Access Publications

Autosomal Dominant Polycystic Kidney Disease is characterised by the development of fluid-filled cysts in the kidneys which lead to end-stage renal disease (ESRD). In the majority of cases, the disease is caused by a mutation in the Pkd1 gene. In a previous study, we demonstrated that renal injury can accelerate cyst formation in Pkd1 knock-out (KO) mice. In that study, we found that after injury four-jointed (Fjx1), an upstream regulator of planar cell polarity and the Hippo pathway, was aberrantly expressed in Pkd1 KO mice compared to WT. Therefore, we hypothesised a role for Fjx1 in injury/repair and cyst formation. …

Dhx33 Interacts With Ap-2Β To Regulate Bcl-2 Gene Expression And Promote Cancer Cell Survival, Jiuling Wang, Weimin Feng, Zhen Yuan, Jason D. Weber, Yandong Zhang

Open Access Publications

The RNA helicase DHX33 has been found to be overexpressed in human cancers, where it promotes cancer development. Previous reports have shown that DHX33 deficiency caused cancer cell apoptosis, but the underlying mechanism remains unknown. In this study, we discovered that DHX33 regulates Bcl-2 family protein expression. In multiple human cancer cell lines, DHX33 was found to stimulate the transcription of

Physical Therapy Management, Surgical Treatment, And Patient-Reported Outcomes Measures In A Prospective Observational Cohort Of Patients With Neurogenic Thoracic Outlet Syndrome, Joshua Balderman, Ahmmad A Abuirqeba, Lindsay Eichaker, Cassandra Pate, Jeanne A Earley, Michael M Bottros, Senthil N Jayarajan, Robert W Thompson

Open Access Publications

OBJECTIVE: To assess the results of physical therapy management and surgical treatment in a prospective observational cohort of patients with neurogenic thoracic outlet syndrome (NTOS) using patient-reported outcomes measures.

METHODS: Of 183 new patient referrals from July 1 to December 31, 2015, 150 (82%) met the established clinical diagnostic criteria for NTOS. All patients underwent an initial 6-week physical therapy trial. Those with symptom improvement continued physical therapy, and the remainder underwent surgery (supraclavicular decompression with or without pectoralis minor tenotomy). Pretreatment factors and 7 patient-reported outcomes measures were compared between the physical therapy and surgery groups using t-tests and …

An Open-Source, Automated Home-Cage Sipper Device For Monitoring Liquid Ingestive Behavior In Rodents, Elizabeth Godynyuk, Maya N Bluitt, Jessica R Tooley, Alexxai V Kravitz, Meaghan C Creed

Open Access Publications

Measuring ingestive behavior of liquids in rodents is commonly used in studies of reward, metabolism, and circadian biology. Common approaches for measuring liquid intake in real time include computer-tethered lickometers or video-based systems. Additionally, liquids can be measured or weighed to determine the amount consumed without real-time sensing. Here, we built a photobeam-based sipper device that has the following advantages over traditional methods: (1) it is battery powered and fits in vivarium caging to allow home-cage measurements; (2) it quantifies the intake of two different liquids simultaneously for preference studies; (3) it is low cost and easily constructed, enabling high-throughput …

Tyk2 Promotes Malignant Peripheral Nerve Sheath Tumor Progression Through Inhibition Of Cell Death, Wenjing Qin, Abigail Godec, Xiaochun Zhang, Cuige Zhu, Jieya Shao, Yu Tao, Xianzhang Bu, Angela C Hirbe

Open Access Publications

BACKGROUND: Malignant peripheral nerve sheath tumors (MPNSTs) are aggressive sarcomas that arise most commonly in the setting of the Neurofibromatosis Type 1 (NF1) cancer predisposition syndrome. Despite aggressive multimodality therapy, outcomes are dismal and most patients die within 5 years of diagnosis. Prior genomic studies in our laboratory identified tyrosine kinase 2 (TYK2) as a frequently mutated gene in MPNST. Herein, we explored the function of TYK2 in MPNST pathogenesis.

METHODS: Immunohistochemistry was utilized to examine expression of TYK2 in MPNSTs and other sarcomas. To establish a role for TYK2 in MPNST pathogenesis, murine and human TYK2 knockdown and knockout …

Mrd Response In Relapsed/Refractory Fl After Obinutuzumab Plus Bendamustine Or Bendamustine Alone In The Gadolin Trial, Christiane Pott, Laurie H Sehn, David Belada, John Gribben, Eva Hoster, Brad Kahl, Britta Kehden, Emmanuelle Nicolas-Virelizier, Nathalie Spielewoy, Guenter Fingerle-Rowson, Chris Harbron, Kirsten Mundt, Elisabeth Wassner-Fritsch, Bruce D Cheson

Open Access Publications

We report assessment of minimal residual disease (MRD) status and its association with outcome in rituximab-refractory follicular lymphoma (FL) in the randomized GADOLIN trial (NCT01059630). Patients received obinutuzumab (G) plus bendamustine (Benda) induction followed by G maintenance, or Benda induction alone. Patients with a clonal marker (t[14;18] translocation and/or immunoglobulin heavy or light chain rearrangement) detected at study screening were assessed for MRD at mid-induction (MI), end of induction (EOI), and every 6-24 months post-EOI/discontinuation by real-time quantitative PCR. At MI, 41/52 (79%) patients receiving G-Benda were MRD-negative vs. 17/36 (47%) patients receiving Benda alone (p = 0.0029). At EOI, …

Best Practices For Bioinformatic Characterization Of Neoantigens For Clinical Utility, Megan M Richters, Huiming Xia, Katie M Campbell, William E Gillanders, Obi L Griffith, Malachi Griffith

Open Access Publications

Neoantigens are newly formed peptides created from somatic mutations that are capable of inducing tumor-specific T cell recognition. Recently, researchers and clinicians have leveraged next generation sequencing technologies to identify neoantigens and to create personalized immunotherapies for cancer treatment. To create a personalized cancer vaccine, neoantigens must be computationally predicted from matched tumor-normal sequencing data, and then ranked according to their predicted capability in stimulating a T cell response. This candidate neoantigen prediction process involves multiple steps, including somatic mutation identification, HLA typing, peptide processing, and peptide-MHC binding prediction. The general workflow has been utilized for many preclinical and clinical …

Comparative Genomics Of Antibiotic-Resistant Uropathogens Implicates Three Routes For Recurrence Of Urinary Tract Infections, Robert Thänert, Kimberly A Reske, Tiffany Hink, Meghan A Wallace, Bin Wang, Drew J Schwartz, Sondra Seiler, Candice Cass, Carey-Ann D. Burnham, Erik R Dubberke, Jennie H Kwon, Gautam Dantas

Open Access Publications

The rise of antimicrobial resistance in uropathogens has complicated the management of urinary tract infections (UTIs), particularly in patients who are afflicted by recurrent episodes of UTIs. Antimicrobial-resistant (AR) uropathogens persistently colonizing individuals at asymptomatic time points have been implicated in the pathophysiology of UTIs. The dynamics of uropathogen persistence following the resolution of symptomatic disease are, however, mostly unclear. To further our understanding, we determined longitudinal AR uropathogen carriage and clonal persistence of uropathogenic

Decipher Identifies Men With Otherwise Clinically Favorable-Intermediate Risk Disease Who May Not Be Good Candidates For Active Surveillance, Annika Herlemann, Hyun Kim, Et Al

Open Access Publications

BACKGROUND: We aimed to validate Decipher to predict adverse pathology (AP) at radical prostatectomy (RP) in men with National Comprehensive Cancer Network (NCCN) favorable-intermediate risk (F-IR) prostate cancer (PCa), and to better select F-IR candidates for active surveillance (AS).

METHODS: In all, 647 patients diagnosed with NCCN very low/low risk (VL/LR) or F-IR prostate cancer were identified from a multi-institutional PCa biopsy database; all underwent RP with complete postoperative clinicopathological information and Decipher genomic risk scores. The performance of all risk assessment tools was evaluated using logistic regression model for the endpoint of AP, defined as grade group 3-5, pT3b …

Obstructive Sleep Apnoea, Positive Airway Pressure Treatment And Postoperative Delirium: Protocol For A Retrospective Observational Study, Christopher R King, Krisztina E Escallier, Yo-El S Ju, Nan Lin, Ben Julian Palanca, Sherry Lynn Mckinnon, Michael Simon Avidan

Open Access Publications

INTRODUCTION: Obstructive sleep apnoea (OSA) is common among older surgical patients, and delirium is a frequent and serious postoperative complication. Emerging evidence suggests that OSA increases the risk for postoperative delirium. We hypothesise that OSA is an independent risk factor for postoperative delirium, and that in patients with OSA, perioperative adherence to positive airway pressure (PAP) therapy decreases the incidence of postoperative delirium and its sequelae. The proposed retrospective cohort analysis study will use existing datasets to: (i) describe and compare the incidence of postoperative delirium in surgical patients based on OSA diagnosis and treatment with PAP; (ii) assess whether …

Sensorimotor Coding Of Vermal Granule Neurons In The Developing Mammalian Cerebellum, Kelly H. Markwalter, Yue Yang, Timothy E. Holy, Azad Bonni

Open Access Publications

The vermal cerebellum is a hub of sensorimotor integration critical for postural control and locomotion, but the nature and developmental organization of afferent information to this region have remained poorly understood

Mucosal Infection Rewires Tnfɑ Signaling Dynamics To Skew Susceptibility To Recurrence, Lu Yu, Valerie P. O'Brien, Jonathan Livny, Denise Dorsey, Nirmalya Bandyopadhyay, Marco Colonna, Michael G. Caparon, Elisha D.O. Roberson, Scott J. Hultgren, Thomas Hannan

Open Access Publications

A mucosal infectious disease episode can render the host either more or less susceptible to recurrent infection, but the specific mechanisms that tip the balance remain unclear. We investigated this question in a mouse model of recurrent urinary tract infection and found that a prior bladder infection resulted in an earlier onset of tumor necrosis factor-alpha (TNFɑ)-mediated bladder inflammation upon subsequent bacterial challenge, relative to age-matched naive mice. However, the duration of TNFɑ signaling activation differed according to whether the first infection was chronic (Sensitized) or self-limiting (Resolved). TNFɑ depletion studies revealed that transient early-phase TNFɑ signaling in Resolved mice …

Noroviruses Subvert The Core Stress Granule Component G3bp1 To Promote Viral Vpg-Dependent Translation, Myra Hosmillo, Jia Lu, Michael R. Mcallaster, James B. Eaglesham, Xinjie Wang, Edward Emmott, Patricia Domingues, Yasmin Chaudhry, Tim J. Fitzmaurice, Matthew K.H. Tung, Marc Dominik Panas, Gerald Mcinerney, Nicolas Locker, Craig B. Wilen, Ian G. Goodfellow

Open Access Publications

Knowledge of the host factors required for norovirus replication has been hindered by the challenges associated with culturing human noroviruses. We have combined proteomic analysis of the viral translation and replication complexes with a CRISPR screen, to identify host factors required for norovirus infection. The core stress granule component G3BP1 was identified as a host factor essential for efficient human and murine norovirus infection, demonstrating a conserved function across the

A Single-Nuclei Rna Sequencing Study Of Mendelian And Sporadic Ad In The Human Brain, Jorge L Del-Aguila, Zeran Li, Umber Dube, Kathie A Mihindukulasuriya, John P Budde, Maria Victoria Fernandez, Laura Ibanez, Joseph Bradley, Fengxian Wang, Kristy Bergmann, Richard Davenport, John C Morris, David M Holtzman, Richard J Perrin, Bruno A Benitez, Joseph Dougherty, Carlos Cruchaga, Oscar Harari

Open Access Publications

BACKGROUND: Alzheimer's disease (AD) is the most common form of dementia. This neurodegenerative disorder is associated with neuronal death and gliosis heavily impacting the cerebral cortex. AD has a substantial but heterogeneous genetic component, presenting both Mendelian and complex genetic architectures. Using bulk RNA-seq from the parietal lobes and deconvolution methods, we previously reported that brains exhibiting different AD genetic architecture exhibit different cellular proportions. Here, we sought to directly investigate AD brain changes in cell proportion and gene expression using single-cell resolution.

METHODS: We generated unsorted single-nuclei RNA sequencing data from brain tissue. We leveraged the tissue donated from …

Toxoplasma Gondii Infection Drives Conversion Of Nk Cells Into Ilc1-Like Cells, Eugene Park, Swapneel Patel, Qiuling Wang, Prabhakar Andhey, Konstantin Zaitsev, Sophia Porter, Maxwell Hershey, Michael Bern, Beatrice Plougastel-Douglas, Patrick Collins, Marco Colonna, Kenneth M. Murphy, Eugene Oltz, Maxim Artyomov, L David Sibley, Wayne M. Yokoyama

Open Access Publications

Innate lymphoid cells (ILCs) were originally classified based on their cytokine profiles, placing natural killer (NK) cells and ILC1s together, but recent studies support their separation into different lineages at steady-state. However, tumors may induce NK cell conversion into ILC1-like cells that are limited to the tumor microenvironment and whether this conversion occurs beyond this environment remains unknown. Here, we describe

How Genomics Can Be Used To Understand Host Susceptibility To Enteric Infection, Aiding In The Development Of Vaccines And Immunotherapeutic Interventions, Lynda Mottram, Subhra Chakraborty, Eric Cox, James Fleckenstein

Open Access Publications

Thanks to the modern sequencing era, the extent to which infectious disease imposes selective pressures on the worldwide human population is being revealed. This is aiding our understanding of the underlying immunological and host mechanistic defenses against these pathogens, as well as potentially assisting in the development of vaccines and therapeutics to control them. As a consequence, the workshop "How genomics can be used to understand host susceptibility to enteric infection, aiding in the development of vaccines and immunotherapeutic interventions" at the VASE 2018 meeting, aimed to discuss how genomics and related tools could be used to assist Shigella and …

Association Of Baseline Inflammatory Biomarkers With Cancer Mortality In The Regards Cohort, Tomi Akinyemiju, Justin X. Moore, Maria Pisu, Michael Goodman, Virginia J. Howard, Monika Safford, Susan C. Gilchrist, Mary Cushman, Leann Long, Suzanne E. Judd

Open Access Publications

This study examines the association between inflammatory biomarkers and risk of cancer mortality by race. Data were obtained from 1,856 participants in the prospective REGARDS cohort who were cancer-free at baseline, and analyzed in relation to cancer mortality prospectively. Biomarkers were log-transformed and categorized into tertiles due to non-normal distributions, and Cox proportional hazard regression models were utilized to compute hazard ratios with 95% confidence intervals using robust sandwich methods. Individuals in the highest tertile of IL-6 had over a 12-fold increased risk of cancer mortality (HR: 12.97, 95% CI: 3.46-48.63); those in the highest tertile of IL-8 had over …

Sleep Disturbances In Wolfram Syndrome, Amy Licis, Gabriel Davis, Sarah A Eisenstein, Heather M Lugar, Tamara Hershey

Open Access Publications

BACKGROUND: Wolfram syndrome is a rare disorder associated with diabetes mellitus, diabetes insipidus, optic nerve atrophy, hearing and vision loss, and neurodegeneration. Sleep complaints are common but have not been studied with objective measures. Our goal was to assess rates of sleep apnea and objective and self-reported measures of sleep quality, and to determine the relationship of sleep pathology to other clinical variables in Wolfram syndrome patients.

METHODS: Genetically confirmed Wolfram syndrome patients were evaluated at the 2015 and 2016 Washington University Wolfram Syndrome Research Clinics. Patients wore an actigraphy device and a type III ambulatory sleep study device and …

Host And Viral Mechanisms Of Congenital Zika Syndrome, Brooke Liang, José Paulo Guida, Maria Laura Costa Do Nascimento, Indira U Mysorekar

Open Access Publications

In 2015-2016, in the Americas, and especially in northeast Brazil, a significant number of cases of microcephaly and other congenital brain abnormalities were linked with an outbreak of Zika virus (ZIKV) infection in pregnant women. While maternal symptoms of ZIKV are generally mild and self-limiting, clinical presentation in fetuses and newborns infected is extensive and includes microcephaly, decreased cortical development, atrophy and hypoplasia of the cerebellum and cerebellar vermis, arthrogryposis, and polyhydramnios. The term congenital ZIKV syndrome (CZS) was introduced to describe the range of findings associated with maternal-fetal ZIKV transmission. ZIKV is primarily transmitted by

Circulating Serum Fatty Acid Synthase Is Elevated In Patients With Diabetes And Carotid Artery Stenosis And Is Ldl-Associated, Gayan S De Silva, Kshitij Desai, Malik Darwech, Uzma Naim, Xiaohua Jin, Sangeeta Adak, Nikolai Harroun, Luis A Sanchez, Clay F Semenkovich, Mohamed A Zayed

Open Access Publications

BACKGROUND AND AIMS: Diabetes is an independent risk factor for carotid artery stenosis (CAS). Fatty acid synthase (FAS), an essential de novo lipogenesis enzyme, has increased activity in the setting of diabetes that leads to altered lipid metabolism. Circulating FAS (cFAS) was recently observed in the blood of patients with hyperinsulinemia and cancer. We thought to evaluate the origin of cFAS and its role in diabetes-associated CAS.

METHODS: Patients with diabetes and no diabetes, undergoing carotid endarterectomy (CEA) for CAS, were prospectively enrolled for collection of plaque and fasting serum. FPLC was used to purify lipoprotein fractions, and ELISA was …

Analysis Of An Improved Cyanophora Paradoxa Genome Assembly, Dana C Price, Ursula W Goodenough, Robyn Roth, Jae-Hyeok Lee, Thamali Kariyawasam, Marek Mutwil, Camilla Ferrari, Fabio Facchinelli, Steven G Ball, Ugo Cenci, Cheong Xin Chan, Nicole E Wagner, Hwan Su Yoon, Andreas P M Weber, Debashish Bhattacharya

Open Access Publications

Glaucophyta are members of the Archaeplastida, the founding group of photosynthetic eukaryotes that also includes red algae (Rhodophyta), green algae, and plants (Viridiplantae). Here we present a high-quality assembly, built using long-read sequences, of the ca. 100 Mb nuclear genome of the model glaucophyte Cyanophora paradoxa. We also conducted a quick-freeze deep-etch electron microscopy (QFDEEM) analysis of C. paradoxa cells to investigate glaucophyte morphology in comparison to other organisms. Using the genome data, we generated a resolved 115-taxon eukaryotic tree of life that includes a well-supported, monophyletic Archaeplastida. Analysis of muroplast peptidoglycan (PG) ultrastructure using QFDEEM shows that PG is …

Novel Cell Adhesion/Migration Pathways Are Predictive Markers Of Hdac Inhibitor Resistance In Cutaneous T Cell Lymphoma, Jared M Andrews, Jennifer A Schmidt, Kenneth R Carson, Amy C Musiek, Neha Mehta-Shah, Jacqueline E Payton

Open Access Publications

BACKGROUND: Treatment for Cutaneous T Cell Lymphoma (CTCL) is generally not curative. Therefore, selecting therapy that is effective and tolerable is critical to clinical decision-making. Histone deacetylase inhibitors (HDACi), epigenetic modifier drugs, are commonly used but effective in only ~30% of patients. There are no predictive markers of HDACi response and the CTCL histone acetylation landscape remains unmapped. We sought to identify pre-treatment molecular markers of resistance in CTCL that progressed on HDACi therapy.

METHODS: Purified T cells from 39 pre/post-treatment peripheral blood samples and skin biopsies from 20 patients were subjected to RNA-seq and ChIP-seq for histone acetylation marks …

Pneumothorax Following Combination Chemotherapy With Bevacizumab: A Case Report And Review Of The Literature, Taha Alrifai, Raya Saba, Dana Rifai, Sarbagya Pandit, Kelley E Kozma

Open Access Publications

Bevacizumab (BV) is a humanized monoclonal antibody that inhibits angiogenesis by targeting vascular endothelial growth factor (VEGF). The addition of BV to combination chemotherapy has been shown to improve the outcomes in several malignancies, including colorectal carcinoma (CRC). However, the use of BV has been associated with adverse effects, including hypertension, hemorrhage, proteinuria, delayed wound healing and bowel perforation. Pneumothorax (PTX) as an adverse event associated with BV use has rarely been reported. We herein report the case of a 68-year-old female patient with a history of metastatic CRC treated with combination chemotherapy, including BV, who presented with complaints of …