Unknown Rectal Lesions: A Case Of Severe Proctitis Secondary To Mpox In The Setting Of Concomitant Hiv, Syphilis, Hsv, And Chlamydia, Nicole Robertson Mph, James Crosby Do, Cynthia R. Young Md, Msc, Anne E. Sayers Md, Nicholas J. Van Sickles Md

ePublications of Emerging Medical Research Scholars

Introduction:

Mpox emerged as a public health crisis with limited research describing co-occurring HIV and sexually transmitted infections (STIs). We present a case of severe proctitis secondary to Mpox with concomitant HIV (Human Immunodeficiency Virus), syphilis, HSV (Herpes Simplex Virus), and chlamydia and review presentation, diagnosis, treatment, and prevention of Mpox with concurrent STIs.

Case Presentation:

34-year-old male living with HIV (LWH) presenting with worsening rectal pain, multiple anal papules, and fever. His laboratory workup revealed simultaneous positive results for orthopoxvirus, chlamydia, and HSV-1 PCR. We initiated tecovirimat due to rectal involvement and uncontrolled pain. He subsequently developed lesions on …

Promotion Of Early Recognition Of Depression To Improve Health Related Quality Of Life In Pediatric Oncology Patients, Jennifer Blankenship

DNP Projects

Background: Depression and anxiety are serious complications of cancer and deemed a challenging diagnosis due to the symptoms of depression mimicking common side effects of chemotherapy and radiation. Signs/symptoms frequently are underrecognized thus appropriate treatment is delayed, compromising the health-related quality of life (HRQOL) for pediatric oncology patients.

Purpose: Analyze existing physician and Advanced Practice Provider (APP) clinical practice regarding depression, via a pre- and post-survey and educational PowerPoint on the use of the Center for Epidemiological Studies Depression Scale for Children (CES-DC) to promote early recognition of depression.

Methods: A prospective, single-arm, study was completed in the Kentucky Children’s …

Effectiveness Of Point-Of-Care Ultrasound Education For Advanced Practice Providers, Nicole Brumfield

DNP Projects

Abstract

Background: Provider shortages and demands for inpatient providers have led to an increase in the utilization of Advanced Practice Providers (APPs). The increased use and specialization of APPs has brought attention to education and skills that have been instituted for other provider types but remains missing from the APP curricula. One such example is point-of-care ultrasound (POCUS) education. This technology and skill set have been shown to enhance clinical skills, confidence levels, and provide useful information for the provider to enhance clinical decision making for the patient.

Purpose: The purpose of this project was to evaluate the effectiveness of …

Relationship Between Preoperative Frailty And Postoperative Outcomes After Lvad Implantation, Katherine L. Wilhelm

DNP Projects

Abstract

Background: Frailty is common in many patients with advanced heart failure, including those who undergo left ventricular assist device (LVAD) implantation. Frailty has been associated with worse outcomes after other cardiac surgeries; however, little is known about the effect of frailty on postoperative outcomes after LVAD implant.

Purpose: The purpose of this project was to evaluate whether preoperative frailty [as determined by either short physical performance battery (SPPB) score ≤ 7/12 or 6-minute walk test (6-MWT) <200 >meters] is associated with poorer postoperative outcomes after LVAD implantation than non-frailty in adults with advanced heart failure.

Setting and Sample: This project …

Donor Age Effects On The Proliferative And Chondrogenic/Osteogenic Differentiation Performance Of Equine Bone Marrow- And Adipose Tissue Derived Mesenchymal Stem Cells In Culture, Jasmin Bagge

Theses and Dissertations--Veterinary Science

Orthopedic injuries are a major cause of lameness and morbidity in horses. Bone marrow (BM)- and adipose tissue (AT) derived mesenchymal stem cells (MSCs) have shown potential to facilitate the repair of orthopedic injuries and are being used increasingly in veterinary clinics. Presently, the use of MSCs as a therapy for equine patients is most commonly applied as autologous transplants, using BM- and AT-MSCs harvested from the patient shortly after the time of injury. Cell-based therapies are therefore delayed to enable primary cell numbers to be expanded in culture. Of concern, however, are human and rodent studies that have shown …

Latent Sensitization In A Mouse Model Of Ocular Neuropathic Pain, Jooyoung Cho, Nicholas Bell, Gregory Botzet, Paras Vora, Benjamin J. Fowler, Renee R. Donahue, Heather M. Bush, Bradley K. Taylor, Romulo J. C. Albuquerque

Ophthalmology and Visual Science Faculty Publications

Purpose: Chronic ocular pain is poorly understood and difficult to manage. We developed a murine model of corneal surface injury (CSI)–induced chronic ocular neuropathic pain. The study focuses on changes in corneal nerve morphology and associated short- and long-term pain-like behavior after CSI.

Methods: CSI was induced in mice by local application of an alkali solution (0.75 N NaOH). Corneal nerve architecture, morphology, density, and length were studied. Eye-wiping was evaluated before and after CSI in response to hypertonic saline (2 M NaCl). Naltrexone (NTX) or Naloxone-methiodide (NLX-me), opioid receptor antagonists, were given subcutaneously (s.c., 3 mg/kg) or …

Autologous Peripheral Nerve Grafts To The Brain For The Treatment Of Parkinson's Disease, Andrew Welleford

Theses and Dissertations--Neuroscience

Parkinson’s disease (PD) is a disorder of the nervous system that causes problems with movement (motor symptoms) as well as other problems such as mood disorders, cognitive changes, sleep disorders, constipation, pain, and other non-motor symptoms. The severity of PD symptoms worsens over time as the disease progresses, and while there are treatments for the motor and some non-motor symptoms there is no known cure for PD. Thus there is a high demand for therapies to slow the progressive neurodegeneration observed in PD. Two clinical trials at the University of Kentucky College of Medicine (NCT02369003, NCT01833364) are currently underway that …

Hdl In Endocrine Carcinomas: Biomarker, Drug Carrier, And Potential Therapeutic, Emily E. Morin, Xiang-An Li, Anna Schwendeman

Physiology Faculty Publications

High-density lipoprotein (HDL) have long been studied for their protective role against cardiovascular diseases, however recently relationship between HDL and cancer came into focus. Several epidemiological studies have shown an inverse correlation between HDL-cholesterol (HDL-C) and cancer risk, and some have even implied that HDL-C can be used as a predictive measure for survival prognosis in for specific sub-population of certain types of cancer. HDL itself is an endogenous nanoparticle capable of removing excess cholesterol from the periphery and returning it to the liver for excretion. One of the main receptors for HDL, scavenger receptor type B-I (SR-BI), is highly …

Are We Missing The Elephant In The Room? A Case For Thyroid Cancer Overdiagnosis As The Etiology For Its Increasing Incidence In India, Janeesh Sekkath Veedu, Aju Mathew

Internal Medicine Faculty Publications

No abstract provided.

Adaptation Of Microelectrode Array Technology For The Study Of Anesthesia-Induced Neurotoxicity In The Intact Piglet Brain, Emily D. Geyer, Prithvi A. Shetty, Christopher J. Suozzi, David Z. Allen, Pamela P. Benavidez, Joseph Liu, Charles N. Hollis, Greg A. Gerhardt, Jorge E. Quintero, Jason J. Burmeister, Emmett E. Whitaker

Neuroscience Faculty Publications

Every year, millions of children undergo anesthesia for a multitude of procedures. However, studies in both animals and humans have called into question the safety of anesthesia in children, implicating anesthetics as potentially toxic to the brain in development. To date, no studies have successfully elucidated the mechanism(s) by which anesthesia may be neurotoxic. Animal studies allow investigation of such mechanisms, and neonatal piglets represent an excellent model to study these effects due to their striking developmental similarities to the human brain.

This protocol adapts the use of enzyme-based microelectrode array (MEA) technology as a novel way to study the …

Renal Granulomatosis Post Intravesical Bacillus Calmette-Guerin Therapy For Non-Muscle-Invasive Bladder Cancer, Karen Tran-Harding, Rashmi T. Nair, Halemane S. Ganesh

Radiology Faculty Publications

Intravesical Bacillus Calmette–Guerin (BCG) immunotherapy is a proven, effective treatment for intermediate- and high-risk non-muscle-invasive bladder cancer. Minor side effects are common and expected but systemic effects can occur in < 5% of treated patients. We present a rare case of a 49-year-old male that presented with fever and chills after 3 weeks of intravesical BCG therapy post transurethral resection of bladder tumor. New renal lesions were present on contrast-enhanced computed tomography scan which was histologically proven to be necrotizing renal granulomatosis.

Evaluating The Effectiveness Of Norton Cancer Institute’S Prompt Care Clinics, Stephanie L. Fred

DNP Projects

Purpose: The purpose of this project was to evaluate outcomes of implementation of the Norton Cancer Institute (NCI) Prompt Care Clinics (PCCs), to include number of emergency room (ER) visits and number of inpatient admissions. A second purpose of the study was to identify presenting symptoms for patients seen in the NCI PCCs and compare the average charge per case for patients seen in the ER or NCI PCCs with the same diagnosis.

Methods: This study employed a pre-post implementation retrospective review of NCI patient electronic medical records (EPIC) to examine the effectiveness of the NCI PCCs on …

The Impact Of The Nurse Practitioner In Pre-Admission Testing: A Comparative Review, Laurel A. Robinson

DNP Projects

Abstract

PURPOSE: The purpose of this study was to compare the efficiency of pre-admission testing (PAT) surgical clinic pre and post implementation of the APRN for patient assessment. Cancellation and delay occurrences for scheduled surgeries will be compared during two time periods on patients on the surgical schedule at Norton Women and Children’s Hospital (NWC).

METHODS: This study was a single-center, pre and post implementation retrospective comparative study of the impact of the NP led PAT unit at Norton Women and Children’s Hospital (NWC) in terms of delay and cancellation rates for day-of-surgery. The sample consisted of 411 patients for …

Using Foot Pressure Analysis To Predict Reoccurrence Of Deformity For Children With Unilateral Clubfoot, Juanita Jean Wallace

Theses and Dissertations--Kinesiology and Health Promotion

Reoccurrence of deformity can affect upwards of 64% of children with clubfoot. The ability to use foot function as a measure of reoccurrence has not been previously assessed. The purpose of this investigation was to utilize foot pressure analysis to predict the probability of reoccurrence in children with unilateral clubfoot. Retrospective foot pressure data revealed predictive algorithms detecting the probability of experiencing any type of reoccurrence (overall reoccurrence) and for experiencing a tibialis anterior tendon transfer (TATT). The equation for overall reoccurrence reported sensitivity and specificity of 0.82 and 0.81 and the equation for TATT reported values of 0.81 and …

Sustained Sensitizing Effects Of Tumor Necrosis Factor Alpha On Sensory Nerves In Lung And Airways, Ruei-Lung Lin, Qihai Gu, Mehdi Khosravi, Lu-Yuan Lee

Physiology Faculty Publications

Tumor necrosis factor alpha (TNFα) plays a significant role in the pathogenesis of airway inflammatory diseases. Inhalation of aerosolized TNFα induced airway hyperresponsiveness accompanied by airway inflammation in healthy human subjects, but the underlying mechanism is not fully understood. We recently reported a series of studies aimed to investigate if TNFα elevates the sensitivity of vagal bronchopulmonary sensory nerves in a mouse model; these studies are summarized in this mini-review. Our results showed that intratracheal instillation of TNFα induced pronounced airway inflammation 24 hours later, as illustrated by infiltration of eosinophils and neutrophils and the release of inflammatory mediators and …

Laparoscopic Harvest Of The Rectus Abdominis For Perineal Reconstruction, Nneamaka Agochukwu, Alisha Bonaroti, Sandra Beck, James Liau

Surgery Faculty Publications

The rectus abdominis is a workhorse flap for perineal reconstruction, in particular after abdominoperineal resection (APR). Laparoscopic and robotic techniques for abdominoperineal surgery are becoming more common. The open harvest of the rectus abdominis negates the advantages of these minimally invasive approaches. (Sentence relating to advantages of laparoscopic rectus deleted here.) We present our early experience with laparoscopic harvest of the rectus muscle for perineal reconstruction. Three laparoscopic unilateral rectus abdominis muscle harvests were performed for perineal reconstruction following minimally invasive colorectal and urological procedures. The 2 patients who underwent APR also had planned external perineal skin reconstruction with local …

Mtor Kinase Inhibition Effectively Decreases Progression Of A Subset Of Neuroendocrine Tumors That Progress On Rapalog Therapy And Delays Cardiac Impairment, Melissa A. Orr-Asman, Zhengtao Chu, Min Jiang, Mariah Worley, Kathleen Lesance, Sheryl E. Koch, Vinicius S. Carreira, Hanan M. Dahche, David R. Plas, Kakajan Komurov, Xiaoyang Qi, Carol A. Mercer, Lowell B. Anthony, Jack Rubinstein, Hala E. Thomas

Internal Medicine Faculty Publications

Inhibition of mTOR signaling using the rapalog everolimus is an FDA-approved targeted therapy for patients with lung and gastroenteropancreatic neuroendocrine tumors (NET). However, patients eventually progress on treatment, highlighting the need for additional therapies. We focused on pancreatic NETs (pNET) and reasoned that treatment of these tumors upon progression on rapalog therapy, with an mTOR kinase inhibitor (mTORKi), such as CC-223, could overcome a number of resistance mechanisms in tumors and delay cardiac carcinoid disease. We performed preclinical studies using human pNET cells in vitro and injected them subcutaneously or orthotopically to determine tumor progression and cardiac function in mice …

Understanding The Patient Experience With Carcinoid Syndrome: Exit Interviews From A Randomized, Placebo-Controlled Study Of Telotristat Ethyl, Lowell B. Anthony, Claire Ervin, Pablo Lapuerta, Matthew H. Kulke, Pamela Kunz, Emily Bergsland, Dieter Hörsch, David C. Metz, Janice Pasieka, Nick Pavlakis, Marianne Pavel, Martyn Caplin, Kjell Öberg, John Ramage, Emily Evans, Qi Melissa Yang, Shanna Jackson, Karie Arnold, Linda Law, Dana B. Dibenedetti

Markey Cancer Center Faculty Publications

Purpose: Telotristat ethyl, an oral tryptophan hydroxylase inhibitor, is intended to treat carcinoid syndrome by reducing serotonin production. Telotristat ethyl was evaluated in TELESTAR, a Phase III study for patients who had carcinoid syndrome with at least 4 bowel movements (BMs) per day and who were receiving somatostatin analogue therapy. This interview substudy was conducted to provide insight into the patient experience in TELESTAR and to help understand whether reductions in BM frequency (the primary end point) and other symptoms were clinically meaningful.

Methods: Participating sites were asked to invite (before randomization) all eligible patients to telephone interviews scheduled at …

Mri Of Suspected Appendicitis During Pregnancy: Interradiologist Agreement, Indeterminate Interpretation And The Meaning Of Non-Visualization Of The Appendix, Richard Tsai, Constantine Raptis, Kathryn J. Fowler, Joseph W. Owen, Vincent M. Mellnick

Radiology Faculty Publications

Objective: To determine the degree of interradiologist agreement between the MRI features of appendicitis during pregnancy, the outcomes associated with an indeterminate interpretation and the negative predictive value of non-visualization of the appendix.

Methods: Our study was approved by the institutional review board at the Washington University in St. Louis, Missouri (WUStL) and was HIPAA (Health Insurance Portability and Accountability Act of 1996)-compliant. The informed consent requirement was waived. Cases of suspected appendicitis during pregnancy evaluated using MRI were retrospectively identified using search queries. Scans were re-reviewed by two radiologists (7 and 9 years experience, respectively) to evaluate the interradiologist …

Cascaded Multi-View Canonical Correlation (Camcco) For Early Diagnosis Of Alzheimer's Disease Via Fusion Of Clinical, Imaging And Omic Features, Asha Singanamalli, Haibo Wang, Anant Madabhushi, Michael Weiner, Paul Aisen, Ronald Petersen, Clifford Jack, William Jagust, John Trojanowki, Arthur Toga, Laurel Beckett, Robert Green, Andrew Saykin, John Morris, Leslie Shaw, Jeffrey Kaye, Joseph Quinn, Lisa Silbert, Betty Lind, Raina Carter, Sara Dolen, Lon Schneider, Sonia Pawluczyk, Mauricio Beccera, Liberty Teodoro, Bryan Spann, James Brewer, Helen Vanderswag, Adam Fleisher, Judith Heidebrink, Charles Smith, Greg A. Jicha, Peter A. Hardy, Partha Sinha, Elizabeth Oates, Gary Conrad

Neurology Faculty Publications

The introduction of mild cognitive impairment (MCI) as a diagnostic category adds to the challenges of diagnosing Alzheimer's Disease (AD). No single marker has been proven to accurately categorize patients into their respective diagnostic groups. Thus, previous studies have attempted to develop fused predictors of AD and MCI. These studies have two main limitations. Most do not simultaneously consider all diagnostic categories and provide suboptimal fused representations using the same set of modalities for prediction of all classes. In this work, we present a combined framework, cascaded multiview canonical correlation (CaMCCo), for fusion and cascaded classification that incorporates all diagnostic …

An Objective Assessment Of The Variability In Number Of Drops Per Bottle Of Glaucoma Medication, Daniel B. Moore, Judy Beck, Richard J. Kryscio

Ophthalmology and Visual Science Faculty Publications

Background: The purpose of this study is to evaluate the number of eyedrops available per bottle of a variety of commonly prescribed glaucoma medications.

Methods: Six bottles of each glaucoma medication were tested: three each in the vertical and horizontal orientations. Bottles were housed in a customized force gauge apparatus designed to mimic ballpoint fingertip contact with a bottle. At a standard rate, all drops were expressed from each bottle and counted with an automated drop counter. Simultaneously, bottle volume was measured and drop size and number were also estimated. The main outcome measures were: total number of drops, volume …

Ultrasound Monitoring Of Extant Adnexal Masses In The Era Of Type 1 And Type 2 Ovarian Cancers: Lessons Learned From Ovarian Cancer Screening Trials, Eleanor L. Ormsby, Edward J. Pavlik, John P. Mcgahan

Obstetrics and Gynecology Faculty Publications

Women that are positive for an ovarian abnormality in a clinical setting can have either a malignancy or a benign tumor with probability favoring the benign alternative. Accelerating the abnormality to surgery will result in a high number of unnecessary procedures that will place cost burdens on the individual and the health delivery system. Surveillance using serial ultrasonography is a reasonable alternative that can be used to discover if changes in the ovarian abnormality will occur that favor either a malignant or benign interpretation. Several ovarian cancer screening trials have had extensive experiences with changes in subclinical ovarian abnormalities in …

Ten Important Considerations For Ovarian Cancer Screening, Edward J. Pavlik

Obstetrics and Gynecology Faculty Publications

The unique intricacies of ovarian cancer screening and perspectives of different screening methods are presented as ten considerations that are examined. Included in these considerations are: (1) Deciding on the number of individuals to be screened; (2) Anticipating screening group reductions due to death; (3) Deciding on the duration and frequency of screening; (4) Deciding on an appropriate follow-up period after screening; (5) Deciding on time to surgery when malignancy is suspected; (6) Deciding on how screen-detected ovarian cancers are treated and by whom; (7) Deciding on how to treat the data of enrolled participants; (8) Deciding on the most …

Ovarian Cancer Incidence Corrected For Oophorectomy, Lauren A. Baldwin, Quan Chen, Thomas C. Tucker, Connie G. White, Robert N. Ore, Bin Huang

Obstetrics and Gynecology Faculty Publications

Current reported incidence rates for ovarian cancer may significantly underestimate the true rate because of the inclusion of women in the calculations who are not at risk for ovarian cancer due to prior benign salpingo-oophorectomy (SO). We have considered prior SO to more realistically estimate risk for ovarian cancer. Kentucky Health Claims Data, International Classification of Disease 9 (ICD-9) codes, Current Procedure Terminology (CPT) codes, and Kentucky Behavioral Risk Factor Surveillance System (BRFSS) Data were used to identify women who have undergone SO in Kentucky, and these women were removed from the at-risk pool in order to re-assess incidence rates …

Symptoms Relevant To Surveillance For Ovarian Cancer, Robert M. Ore, Lauren Baldwin, Dylan Woolum, Erika Elliott, Christiaan Wijers, Chieh-Yu Chen, Rachel W. Miller, Christopher P. Desimone, Frederick R. Ueland, Richard J. Kryscio, John R. Van Nagell, Edward J. Pavlik

Obstetrics and Gynecology Faculty Publications

To examine how frequently and confidently healthy women report symptoms during surveillance for ovarian cancer. A symptoms questionnaire was administered to 24,526 women over multiple visits accounting for 70,734 reports. A query of reported confidence was included as a confidence score (CS). Chi square, McNemars test, ANOVA and multivariate analyses were performed. 17,623 women completed the symptoms questionnaire more than one time and > 9500 women completed it more than one four times for > 43,000 serially completed questionnaires. Reporting ovarian cancer symptoms was ~245 higher than ovarian cancer incidence. The positive predictive value (0.073%) for identifying ovarian cancer based on symptoms …

Venoarterial Extracorporeal Membrane Oxygenation For Cardiogenic Shock: A Retrospective Analysis Based On The Etiology Of Shock, Andrew Burchett, Thomas Tribble, Richard Charnigo, Susan Smyth, Maya Guglin

The VAD Journal

Abstract:

Background: We performed a retrospective analysis to evaluate the efficacy of VA-ECMO support in cardiogenic shock based on various etiologies.

Methods: We retrospectively analyzed 99 patients supported with VA-ECMO from January 1, 2012 to January 1, 2015. Outcomes included survival to discontinuation of VA-ECMO support and survival to hospital discharge. The etiologies of cardiogenic shock included cardiac arrest (CPR), acute myocardial infarction (AMI), decompensated congestive heart failure (CHF), pulmonary embolism (PE), right ventricular failure (RVF) not secondary to an acute pulmonary embolism, and post-cardiotomy syndrome (PCS). The PCS group was used as a reference group; odds ratios were estimated …

Complications From Surgeries Related To Ovarian Cancer Screening, Lauren A. Baldwin, Edward J. Pavlik, Emma Ueland, Hannah E. Brown, Kelsey M. Ladd, Bin Huang, Christopher P. Desimone, John R. Van Nagell, Frederick R. Ueland, Rachel W. Miller

Obstetrics and Gynecology Faculty Publications

The aim of this study was to evaluate complications of surgical intervention for participants in the Kentucky Ovarian Cancer Screening Program and compare results to those of the Prostate, Lung, Colorectal and Ovarian Cancer Screening trial. A retrospective database review included 657 patients who underwent surgery for a positive screen in the Kentucky Ovarian Cancer Screening Program from 1988–2014. Data were abstracted from operative reports, discharge summaries, and office notes for 406 patients. Another 142 patients with incomplete records were interviewed by phone. Complete information was available for 548 patients. Complications were graded using the Clavien–Dindo (C–D) Classification of Surgical …

Longitudinal Measurement And Hierarchical Classification Framework For The Prediction Of Alzheimer's Disease, Meiyan Huang, Wei Yang, Qianjin Feng, Wufan Chen, Michael Weiner, Paul Aisen, Ronald Petersen, Clifford R. Jack Jr., William Jagust, John Trojanowki, Arthur W. Toga, Laurel Beckett, Robert C. Green, Andrew Saykin, John Morris, Leslie M. Shaw, Jeffrey Kaye, Joseph Quinn, Lisa Silbert, Betty Lind, Raina Carter, Sara Dolen, Lon S. Schneider, Sonia Pawluczyk, Mauricio Beccera, Liberty Teodoro, Bryan Spann, James Brewer, Helen Vanderswag, Adam Fleisher, Charles D. Smith, Greg A. Jicha, Peter A. Hardy, Partha Sinha, Elizabeth Oates, Gary Conrad

Neurology Faculty Publications

Accurate prediction of Alzheimer’s disease (AD) is important for the early diagnosis and treatment of this condition. Mild cognitive impairment (MCI) is an early stage of AD. Therefore, patients with MCI who are at high risk of fully developing AD should be identified to accurately predict AD. However, the relationship between brain images and AD is difficult to construct because of the complex characteristics of neuroimaging data. To address this problem, we present a longitudinal measurement of MCI brain images and a hierarchical classification method for AD prediction. Longitudinal images obtained from individuals with MCI were investigated to acquire important …

The Utility Of Remote Hemodynamic Monitoring Devices In Patients With A Ventricular Assist Device, Bennet George, Amanda Hart, Sarah Branam, Maya Guglin

The VAD Journal

Remote intracardiac hemodynamic monitoring is a growing area of interest to help aid in the management of patients with chronic congestive heart failure. The utility of remote hemodynamic monitoring has not previously been investigated with a ventricular assist device population. We present two cases of patients with ventricular assist devices in which we employed remote hemodynamic monitoring data to aid in patient management.

Human Igg1 Antibodies Suppress Angiogenesis In A Target-Independent Manner, Sasha Bogdanovich, Younghee Kim, Takeshi Mizutani, Reo Yasuma, Laura Tudisco, Valeria Cicatiello, Ana Bastos-Carvalho, Nagaraj Kerur, Yoshio Hirano, Judit Z. Baffi, Valeria Tarallo, Shengjian Li, Tetsuhiro Yasuma, Parthasarathy Arpitha, Benjamin James Fowler, Charles B. Wright, Ivana Apicella, Adelaide Greco, Arturo Brunetti, Menotti Ruvo, Annamaria Sandomenico, Miho Nozaki, Ryo Ijima, Hiroki Kaneko, Yuichiro Ogura, Hiroko Terasaki, Balamurali K. Ambati, Jeanette H. W. Leusen, Wallace Y. Langdon, Michael R. Clark, Bradley D. Gelfand, Jayakrishna Ambati

Ophthalmology and Visual Science Faculty Publications

Aberrant angiogenesis is implicated in diseases affecting nearly 10% of the world’s population. The most widely used anti-angiogenic drug is bevacizumab, a humanized IgG1 monoclonal antibody that targets human VEGFA. Although bevacizumab does not recognize mouse Vegfa, it inhibits angiogenesis in mice. Here we show bevacizumab suppressed angiogenesis in three mouse models not via Vegfa blockade but rather Fc-mediated signaling through FcγRI (CD64) and c-Cbl, impairing macrophage migration. Other approved humanized or human IgG1 antibodies without mouse targets (adalimumab, alemtuzumab, ofatumumab, omalizumab, palivizumab and tocilizumab), mouse IgG2a, and overexpression of human IgG1-Fc or mouse IgG2a-Fc, also inhibited angiogenesis in wild-type …