Medical Specialties Commons^™

Functional Characterization Of Age-Dependent P16 Epimutation Reveals Biological Drivers And Therapeutic Targets For Colorectal Cancer, Li Yang, Xiaomin Chen, Christy Lee, Jiejun Shi, Emily B Lawrence, Lanjing Zhang, Yumei Li, Nan Gao, Sung Yun Jung, Chad J Creighton, Jingyi Jessica Li, Ya Cui, Sumimasa Arimura, Yunping Lei, Wei Li, Lanlan Shen

Faculty, Staff and Students Publications

BACKGROUND: Methylation of the p16 promoter resulting in epigenetic gene silencing-known as p16 epimutation-is frequently found in human colorectal cancer and is also common in normal-appearing colonic mucosa of aging individuals. Thus, to improve clinical care of colorectal cancer (CRC) patients, we explored the role of age-related p16 epimutation in intestinal tumorigenesis.

METHODS: We established a mouse model that replicates two common genetic and epigenetic events observed in human CRCs: Apc mutation and p16 epimutation. We conducted long-term survival and histological analysis of tumor development and progression. Colonic epithelial cells and tumors were collected from mice and analyzed by RNA …

Using Cancer Proteomics Data To Identify Gene Candidates For Therapeutic Targeting, Diana Monsivais, Sydney E Parks, Darshan S Chandrashekar, Sooryanarayana Varambally, Chad J Creighton

Faculty, Staff and Students Publications

Gene-level associations obtained from mass-spectrometry-based cancer proteomics datasets represent a resource for identifying gene candidates for functional studies. When recently surveying proteomic correlates of tumor grade across multiple cancer types, we identified specific protein kinases having a functional impact on uterine endometrial cancer cells. This previously published study provides just one template for utilizing public molecular datasets to discover potential novel therapeutic targets and approaches for cancer patients. Proteomic profiling data combined with corresponding multi-omics data on human tumors and cell lines can be analyzed in various ways to prioritize genes of interest for interrogating biology. Across hundreds of cancer …

Srsf1 Haploinsufficiency Is Responsible For A Syndromic Developmental Disorder Associated With Intellectual Disability, Elke Bogaert, Aurore Garde, Thierry Gautier, Kathleen Rooney, Yannis Duffourd, Pontus Leblanc, Emma Van Reempts, Frederic Tran Mau-Them, Ingrid M Wentzensen, Kit Sing Au, Kate Richardson, Hope Northrup, Vincent Gatinois, David Geneviève, Raymond J Louie, Michael J Lyons, Lone Walentin Laulund, Charlotte Brasch-Andersen, Trine Maxel Juul, Fatima El It, Nathalie Marle, Patrick Callier, Raissa Relator, Sadegheh Haghshenas, Haley Mcconkey, Jennifer Kerkhof, Claudia Cesario, Antonio Novelli, Nicola Brunetti-Pierri, Michele Pinelli, Perrine Pennamen, Sophie Naudion, Marine Legendre, Cécile Courdier, Aurelien Trimouille, Martine Doco Fenzy, Lynn Pais, Alison Yeung, Kimberly Nugent, Elizabeth R Roeder, Tadahiro Mitani, Jennifer E Posey, Daniel Calame, Hagith Yonath, Jill A Rosenfeld, Luciana Musante, Flavio Faletra, Francesca Montanari, Giovanna Sartor, Alessandra Vancini, Marco Seri, Claude Besmond, Karine Poirier, Laurence Hubert, Dimitri Hemelsoet, Arnold Munnich, James R Lupski, Christophe Philippe, Christel Thauvin-Robinet, Laurence Faivre, Bekim Sadikovic, Jérôme Govin, Bart Dermaut, Antonio Vitobello

Faculty, Staff and Students Publications

SRSF1 (also known as ASF/SF2) is a non-small nuclear ribonucleoprotein (non-snRNP) that belongs to the arginine/serine (R/S) domain family. It recognizes and binds to mRNA, regulating both constitutive and alternative splicing. The complete loss of this proto-oncogene in mice is embryonically lethal. Through international data sharing, we identified 17 individuals (10 females and 7 males) with a neurodevelopmental disorder (NDD) with heterozygous germline SRSF1 variants, mostly de novo, including three frameshift variants, three nonsense variants, seven missense variants, and two microdeletions within region 17q22 encompassing SRSF1. Only in one family, the de novo origin could not be established. All individuals …

Glynac (Glycine And N-Acetylcysteine) Supplementation In Old Mice Improves Brain Glutathione Deficiency, Oxidative Stress, Glucose Uptake, Mitochondrial Dysfunction, Genomic Damage, Inflammation And Neurotrophic Factors To Reverse Age-Associated Cognitive Decline: Implications For Improving Brain Health In Aging, Premranjan Kumar, Ob W Osahon, Rajagopal V Sekhar

Faculty, Staff and Students Publications

Cognitive decline frequently occurs with increasing age, but mechanisms contributing to age-associated cognitive decline (ACD) are not well understood and solutions are lacking. Understanding and reversing mechanisms contributing to ACD are important because increased age is identified as the single most important risk factor for dementia. We reported earlier that ACD in older humans is associated with glutathione (GSH) deficiency, oxidative stress (OxS), mitochondrial dysfunction, glucose dysmetabolism and inflammation, and that supplementing GlyNAC (glycine and N-acetylcysteine) improved these defects. To test whether these defects occur in the brain in association with ACD, and could be improved/reversed with GlyNAC supplementation, we …

Dimeric P53 Mutant Elicits Unique Tumor-Suppressive Activities Through An Altered Metabolic Program, Jovanka Gencel-Augusto, Xiaoping Su, Yuan Qi, Elizabeth M Whitley, Vinod Pant, Shunbin Xiong, Vrutant Shah, Jerome Lin, Encarnacion Perez, Marta L Fiorotto, Iqbal Mahmud, Abhinav K Jain, Philip L Lorenzi, Nicholas E Navin, Ellen R Richie, Guillermina Lozano

Faculty, Staff and Student Publications

Cancer-related alterations of the p53 tetramerization domain (TD) abrogate wild-type (WT) p53 function. They result in a protein that preferentially forms monomers or dimers, which are also normal p53 states under basal cellular conditions. However, their physiologic relevance is not well understood. We have established in vivo models for monomeric and dimeric p53, which model Li-Fraumeni syndrome patients with germline p53 TD alterations. p53 monomers are inactive forms of the protein. Unexpectedly, p53 dimers conferred some tumor suppression that is not mediated by canonical WT p53 activities. p53 dimers upregulate the PPAR pathway. These activities are associated with lower prevalence …

Dual Myristic Acid And Trans-Activator Of Transcription Conjugation Of Pkc Beta Ii Peptide Inhibitor Augments Cellular Delivery To Counteract Myocardial Ischemia/Reperfusion Injury, James Ramsarran, Logan Clair, Taurai Augustin, Zinya Talukder, Emily Andrews, Tameka Dean, Qian Chen, Robert J. Barsotti, Lindon H. Young

Research Day

INTRODUCTION: Dual conjugation of PKC Beta II peptide inhibitor (PKCβII-) with myristic acid (myr) and trans-activator of transcription (Tat) (Myr-Tat-CC-SLNPEWNET [myr-Tat-PKCβII-]) has been shown to enhance intracellular delivery and attenuate myocardial ischemia/reperfusion (I/R) injury in an ex-vivo rat model. Previously, myr-Tat-PKCβII- demonstrated significant cardioprotective effects from 100nM to the 1pM concentration.

OBJECTIVES: The lowest concentration at which myr-Tat-PKCβII- is still cardioprotective has yet to be determined; this study investigates the 100fM concentration.

METHODS: Isolated rat hearts from anesthetized male SD rats (275g to 300g) underwent global I(30-min)/R(50-min). Cardiac function was recorded via a pressure transducer. Treatments were infused during the …

Assessment Of The Impact Of Race And Proxies Of Socioeconomic Status On The Prevalence And Health Outcome Of Peripartum Cardiomyopathy (Ppcm) Using The “All Of Us” Databank, Nicole Blatt, Brian J. Balin Phd, Ahmad B. Cader, C. Scott Little, Eleonora Savio-Galimberti

Research Day

Background: Peripartum Cardiomyopathy (PPCM) is a form of cardiomyopathy occurring during the last month of pregnancy or within months after giving birth in women with previously normal hearts. PPCM is an idiopathic systolic dysfunction that causes a reduced left ventricle ejection fraction. The estimated incidence of PPCM worldwide is 1 diagnosis out of 2,000 live births, and the causes of PPCM remain unknown. A retrospective cohort study conducted at the University of Pennsylvania Health System by Getz et al. showed that black race and socioeconomic proxies (like neighborhood disadvantage index (NDI)) were independently associated with sustained cardiac dysfunction (Getz et …

A Rare Case Of Scalp Swelling In Infancy: Delayed Subaponeurotic Fluid Collection, Shreya Dundumalla

Research Day

Delayed subaponeurotic fluid collection (DSFC) is a rare cause of scalp swelling in infants presenting weeks to months after birth. DSFC is described as a mobile and soft swelling which crosses suture lines in healthy infants with no recent history of trauma or fall. A literature search in the National Library of Medicine revealed fewer than 15 publications on the topic since 2007. The exact etiology and long term consequences of DSFC remain unclear although birth trauma has been implicated as the main mechanism. A healthy 2 month old male infant presented to the ED with a one-day history of …

Comparison Of The Inhibition Of An Oct3 Transporter Inhibitor, Nilotinib, On Doxorubicin’S Effects On Cardiac And Cancer Cell Lines, Zachary G. Tan, Juliet Melnik, Aakash Belsare, James Huang, Meagan Lyons, Kimberly Dowes, Gurpreet Kaur, Lindon H. Young, Robert J. Barsotti, Qian Chen

Research Day

Introduction

Doxorubicin (DOX)-induced cardiotoxicity remains a significant barrier limiting its clinical application due to a lack of effective resolution. Targeting how DOX enters cardiac and cancer cells is a promising new strategy. Research suggests that an OCT3 transporter significantly contributes to DOX entry into the heart tissue. By contrast, it expresses much lower on breast cancer cell lines. Moreover, Nilotinib (NIB) can suppress OCT3 transporter function by 80%. Therefore, exploring the impact of NIB on the DOX’s effects on cardiac and cancer cell lines by altering DOX intracellular accumulation is intriguing.

Objective

First, we would establish a dose-response curve of …

Prolonged Length Of Stay In Illeal Conduit Compared To Neobladder Diversion In Radical Cystectomy Patients For Bladder Cancer, Ryan J. Moriarty, Young Son, Brian Thomas, Ronald Clearie, Lance Earnshaw, Dayna Devincentz, Thomas Mueller

Research Day

Background:

Radical cystectomy and urinary diversion has become the standard treatment for invasive and complicated malignancies of the bladder, urethra, and ureters. [1] Robotic-assisted radical cystectomy (RARC), introduced in the last decade, has been associated with favorable perioperative outcomes when compared to open radical cystectomy. Yet little is known about how different urinary diversion types compare in regards to length of hospital stay, readmission rates, and perioperative course. This data analysis seeks to identify the statistically significant differences in postoperative course of ileal conduit versus neobladder among patients with staged bladder cancer.

Methods:

The American College of Surgeons National Surgical …

Treatment Of Bullous Pemphigoid With Dupilumab: A Case Report, Margaret C. Hurley, Jocelynn F. Dillon, Harold J. Milstein

Research Day

Introduction: Bullous Pemphigoid (BP) is an autoimmune blistering condition that results from formation of autoantibodies against basement membrane hemidesmosome proteins, specifically BP180 and BP230. Classic BP presents as pruritic, tense blisters on the trunk and extremities, most commonly in the elderly. BP’s pathophysiology involves IL4/IL5/IL13 and eosinophils. Dupilumab is an IgG monoclonal antibody targeted at the IL4-α receptor that works to attenuate the IL4/IL13 pathway involved in T2 differentiation. Dupilumab has clinical applications for T2 mediated disease and shows promise in the therapy of BP.

Case Description: We report a case of an 83-year-old Asian male who presented in the …

Maternal Psychiatric Functioning And Maternal-Infant Attachment Among Mothers Of Infants In The Neonatal Intensive Care Unit (Nicu), Elizabeth Greco, Alexa Bonacquisti

Research Day

Introduction: A growing body of research suggests that an infant’s admission to a neonatal intensive care unit (NICU) may adversely impact maternal psychiatric functioning, affecting quality of life, well-being, and patient outcomes. Additionally, there is accumulating evidence that stressful reproductive events related to a NICU admission) may even exacerbate pre-existing maternal psychiatric symptoms. The purpose of the current study was to examine the relationships between maternal mental health symptoms, including anxiety and stress, and maternal-infant attachment among mothers of infants in the NICU. By examining the psychiatric functioning measures both at the time of initial NICU admission and again 2-4 …

Cardioprotective Effects Of Naltrindole In Rat Myocardial Ischemia/Reperfusion Injury Are Concentration-Dependent, Logan Clair, Tanoh Boakye, James Ramsarran, Zinya Talukder, Nikola Maricic, Ukoha Kalu, Juliet Melnik, Tameka Dean, Qian Chen, Robert J. Barsotti, Lindon H. Young

Research Day

Myocardial infarction remains a major cause of mortality and morbidity globally and infarct size is a major determinant of prognosis. Early and successful restoration of myocardial reperfusion is effective to reduce final infarct size and improve clinical outcomes. However, reperfusion induces further damage to the myocardium, hence the need for adjunctive therapy. Cardioprotective therapies to limit myocardial hypercontracture that occurs during prolonged ischemia and is associated with ischemia-reperfusion (I/R) injury are an important clinical goal. Previously, naltrindole (NTI, 5µM), when given prior to ischemia, exerted cardioprotective effects in ex-vivo, rat myocardial I/R, in part, by attenuating ischemic hypercontracture that occurred …

Assessment Of Attitudes And Knowledge Of Osteopathic Manipulative Medicine Amongst Neurosurgeons, Devin Kolmetzky, Dillon B. Gooder, Evan Polly, Sarah Glisan, Zein Al-Atrache, Clint Badger, Steven Yocom, Alan Turtz, Donald Allison

Research Day

Introduction: Osteopathic Manipulative Medicine (OMM) is highly researched and integrated into many medical and surgical subspecialties. Though OMM has been shown to have benefits in treating non-specific cervical and lower back pain and managing post-operative pain, it has rarely been integrated or studied in the neurosurgical community.

Method: Using SurveyMonkey, a survey was dispersed to physicians of the American Association of Neurological Surgeons (AANS). Information collected included the provider’s type of practice, degree type (MD vs. DO), familiarity with the tenets of OMM, frequency of referral/use of OMM, comfort level with OMM as a non-surgical pre-op option, a post-op pain …

Association Between Race And Early Antibiotic Use In Newborns Admitted To The Neonatal Intensive Care Unit, Rodney Morrison Jr, Alvaro Zevallos Barboza, Diana Montoya-Williams, Dustin Daniel Flannery

Research Day

Introduction: Given the risk of early-onset sepsis, providers frequently prescribe empirical antibiotics to newborns admitted to the neonatal intensive care unit (NICU). Early and prolonged use of antibiotics in uninfected newborns is associated with many adverse effects and potentially life-threatening complications, particularly among those with very low birth weight (VLBW; <1500g). Studies of neonatal antibiotic utilization often adjust for race, acknowledged as a social construct, but there is a paucity of data on whether there is an independent association between race and antibiotic use in this population. We hypothesized that Black newborns have higher antibiotic use after adjusting for confounding factors compared to other races.

Design/Methods: Retrospective cohort study including newborns admitted to a NICU from 2012-2021 included in the Premier Health database, which captures inpatient encounters from academic and community hospitals across the US. Early antibiotic initiation was defined as any parenteral antibiotic administered within the first 3 days after birth. Prolonged antibiotic duration …

Hypokalemic Periodic Paralysis Secondary To Thyrotoxicosis, Anugraha Kutty, Alexandra Hart, Danielle Palaferro, Pavel Itersky

Research Day

Background:

Hypokalemic Periodic Paralysis (HPP) is a rare neuromuscular disorder characterized by acute, transient muscle weakness and paralysis secondary to hypokalemia and can be complicated by cardiac arrhythmias. Thyrotoxic Periodic Paralysis (TPP) is an acquired type of HPP seen in the setting of thyrotoxicosis. Most TPP patients present with subtle signs and symptoms of thyrotoxicosis prior to an acute muscle paralysis event. Therefore, recognizing TPP in the emergency setting is critical in preventing life-threatening cardiac, respiratory, renal, or other systemic complications induced by a hypokalemic state.

Case Report:

An 18-year-old Hispanic male presented to the emergency department, with no past …

Pretreatment With Naltrindole Generates Dose Dependent Effects On Reduction Of Infarct Size During Myocardial Ischemia Reperfusion In An In-Vivo Model, Annam Humayun, Sunit Singh, Arianna Gray, Devani Johnson, Tameka Dean, Qian Chen, Robert J. Barsotti, Lindon H. Young, Wangde Dai, Robert Kloner

Research Day

Over one million individuals experience a myocardial infarction (MI) every year. Currently, no therapeutic is available to salvage necrotic cardiac tissue following an MI. The use of a prophylactic agent to reduce infarct size in patients at high risk for an MI would attenuate the development of heart failure. Interventional cardiologists state that a 25% reduction in infarct size is clinically meaningful to reduce heart failure. Previously, a 5 min pretreatment with high dose (HD) naltrindole (NTI) (7.5 mg/kg x 5 min = 37.5 mg/kg, n=3) resulted in a robust 74% (15±6%) reduction in infarct size compared to control in …

A Case Of Double-Positive Anti-Gbm And Mpo-Anca Vasculitis With No Pulmonary Involvement, Deonnie W. Huang, Patrick May, Thanh Nguyen

Research Day

Introduction

Anti-glomerular basement membrane (anti-GBM) disease is a small vessel vasculitis caused by autoantibodies directed at the glomerular and alveolar basement membranes. Anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitis is pauci-immune with no immune deposits. Both vasculitides can lead to precipitation of rapidly progressive glomerulonephritis and diffuse alveolar hemorrhage. We report a case of a 58 year-old male who presented with acute renal failure with double positive anti-GBM and myeloperoxidase-anti neutrophil cytoplasmic antibodies (MPO-ANCA) but no pulmonary involvement.

Case Presentation

Patient is a 58-year-old male with a past medical history of nicotine dependence who presented to the hospital with abnormal blood work. …

Vision Loss: A Rare Complication Of Intravenous T-Pa In The Treatment Of Acute Ischemic Stroke, Shreya Dundumalla, Brian Smith

Research Day

An 86-year-old African American female presented to a community hospital with intractable left shoulder pain and was admitted for the correction of electrolyte abnormalities. Three days into her hospital course, she developed altered mental status, dysarthria, and facial droop. A CT scan showed no evidence of acute intracranial hemorrhage. After neurologic evaluation and informed consent was given by the patient’s daughter, the decision was made to administer intravenous t-PA for the treatment of acute ischemic stroke. Two hours after tPA administration, a CT scan showed no evidence of hemorrhagic conversion. Four hours later, the patient began to complain of redness, …

The Effects Of Mitoquinone Pretreatment On Doxorubicin-Induced Acute Cardiac Dysfunction, Kimberly Dawes, Juliet Melnik, Meagan Lyons, Jonathan Amora, Lindon H. Young, Robert J. Barsotti, Qian Chen

Research Day

Introduction:

Doxorubicin (DOX) is a widely used anti-cancer drug notorious for its irreversible cardiac toxicity. Currently, Dexrazoxane is the only FDA-approved treatment for this toxicity. However, Dexrazoxane still bears some serious adverse events, and developing new strategies to mitigate DOX-induced heart damage is critical. Our lab has shown that pretreatment of the H9c2 myoblast cells with mitoquinone (MitoQ), a mitochondrial-targeted antioxidant, and significantly improved cells’ resiliency to DOX. This study aimed to determine if MitoQ pretreatment can preserve cardiac function against DOX-induced damage in isolated rat hearts.

Objectives:

The effects of DOX and MitoQ on cardiac function were evaluated in …

Perfect Storm? Covid-19, Area Deprivation, And Their Association With Pediatric Trauma, Devon Pace, Paulo Castro, Julia Gong, Brandon George, Russell Mcintire, Charles Paidas, Loren Berman, Rosemary Frasso, Colin Plover

Research Day

Introduction: Social determinants of health (SDOH) affect pediatric injury patterns as vulnerable populations are likely to experience more frequent or severe injuries. This study evaluates the association of COVID-19 and area deprivation with pediatric traumatic injuries.

Methods: We retrospectively evaluated institutional level I pediatric trauma encounters from 1/2018-8/2022. Patients were assessed relative to the U.S. pandemic declaration date (3/11/2020): pre-COVID (<3/11/2020), early post-COVID (3/11/2020-3/11/2021), and late post-COVID (>3/11/2021). The Area Deprivation Index (ADI) measured SDH-related risk at a census block tract group level. Associations between ADI and COVID-19 and injury mechanism and outcomes (intensive care unit [ICU]/ventilator duration, hospital length of stay, and mortality) were assessed …

Association Of Operative Approach With Postoperative Outcomes In Neonates Undergoing Surgical Repair Of Esophageal Atresia And Tracheoesophageal Fistula, Devon Pace, Paulo Castro, Shale J. Mack, David H. Rothstein, Courtney Devin, Emily Sagalow, Allison F. Linden, Matthew Boelig, Loren Berman

Research Day

Introduction: Minimally invasive surgery (MIS) is gaining traction as a first-line approach to repair congenital anomalies. This study aims to evaluate outcomes for neonates undergoing open versus MIS repairs for esophageal atresia/tracheoesophageal fistula (EA/TEF).

Methods: Neonates undergoing EA/TEF repair from 2013-2020 were identified using the National Surgical Quality Improvement Program-Pediatric database. Proportions of operative approach (open vs. MIS) over time were analyzed. A propensity score-matched analysis using preoperative characteristics was performed and outcomes were compared including composite morbidity and reintervention rates (overall, major [thoracoscopy, thoracotomy], and minor [chest/feeding tube placement, endoscopy]) between operative approaches. Pearson’s chi-square or Fisher’s exact test …

Maternal Attitudes, Adjustment, Health Behaviors, And Social Support Among Mothers Of Infants In The Neonatal Intensive Care Unit, Ryanne N. Schaad, Alexa Bonacquisti, Elizabeth Greco, Chloe Hriso

Research Day

Introduction: A growing body of research suggests that an infants’ admission to a neonatal intensive care unit (NICU) is associated with adverse maternal mental health outcomes. Maternal attitudes, adjustment to motherhood, social support, and health behaviors may be important modifiable factors that could improve quality of life and well-being among NICU mothers. The current study examined the relationships among maternal attitudes, adjustment to motherhood, health behaviors, social support, and psychological functioning in NICU mothers.

Methods: One hundred twenty-seven women were recruited from NICUs at three hospitals in the Philadelphia area and completed self-report measures while in the NICU. Descriptive analyses …

A Multimodal Smartphone Application Intervention To Achieve Target Weight Goals In Overweight Adult Diabetics, Michael Thomas Schwuchow

Evidence-Based Practice Project Reports

Obesity is the leading risk factor for developing type 2 diabetes mellitus (American Diabetes Association, 2022). Diabetes mellitus (DM) and obesity put individuals at higher risk for developing heart disease, stroke, and hypertension, therefore, it is essential to properly manage both conditions. The purpose of this project is to determine if the implementation of an evidence-based weight loss intervention, MyFitnessPal© will result in reduction in body mass index (BMI) and lower hemoglobin A1c (HbA1c) levels in overweight adults with DM. A comprehensive literature search of six databases, hand searching, and citation chasing yielded 13 pieces of moderate to high quality …

Bibliometric Analysis Of Academic Journal Recommendations And Requirements For Surgical And Anesthesiologic Adverse Events Reporting, Tamir N. Sholklapper, Jorge Ballon, Aref S. Sayegh, Anibal La Riva, Laura C. Perez, Sherry Huang, Michael Eppler, Gregg Nelson, Giovanni Marchegiani, Robert Hinchliffe, Luca Gordini, Marc Furrer, Michael J. Brenner, Salome Dell-Kuster, Chandra Shekhar Biyani, Nader Francis, Haytham M.A. Kaafarani, Matthias Siepe, Des Winter, Julie A. Sosa, Francesco Bandello, Robert Siemens, Jochen Walz, Alberto Briganti, Christian Gratzke, Andre L. Abreu, Mihir M. Desai, Rene Sotelo, Riaz Agha, Keith D. Lillemoe, Steven Wexner, Gary S. Collins, Inderbir Gill, Giovanni E. Cacciamani

Einstein Health Papers

BACKGROUND: Standards for reporting surgical adverse events (AEs) vary widely within the scientific literature. Failure to adequately capture AEs hinders efforts to measure the safety of healthcare delivery and improve the quality of care. The aim of the present study is to assess the prevalence and typology of perioperative AE reporting guidelines among surgery and anesthesiology journals.

MATERIALS AND METHODS: In November 2021, three independent reviewers queried journal lists from the SCImago Journal & Country Rank (SJR) portal (www.scimagojr.com), a bibliometric indicator database for surgery and anesthesiology academic journals. Journal characteristics were summarized using SCImago, a bibliometric indicator database extracted …

Colonizing And Virulence Factors In Enterotoxigenic Escherichia Coli From Peru, Fulton P Rivera, Anicia Medina, Maribel Riveros, Theresa J Ochoa, Maria J Pons, Joaquim Ruiz

Faculty, Staff and Student Publications

Enterotoxigenic Escherichia coli (ETEC) ranks among the most relevant diarrheagenic pathogens. Efforts to design vaccines to fight ETEC have been focused on colonizing factors (CFs) and atypical virulence factors (AVF). An effective vaccine must account for differences in the regional prevalence of these CFs and AVFs to be truly effective in a given area. In the present study, the presence of 16 CFs and 9 AVFs, as well as the heat-stable (ST) variants (STh or STp), was established by polymerase chain reaction in 205 Peruvian ETEC isolates (120 from diarrhea cases and 85 from healthy controls). Ninety-nine (48.3%) isolates were …

Microparticle-Delivered Cxcl9 Prolongs Braf Inhibitor Efficacy In Melanoma, Gabriele Romano, Francesca Paradiso, Peng Li, Pooja Shukla, Lindsay N Barger, Olivia El Naggar, John P Miller, Roger J Liang, Timothy L Helms, Alexander J Lazar, Jennifer A Wargo, Francesca Taraballi, James C Costello, Lawrence N Kwong

Faculty, Staff and Student Publications

Patients with BRAF-mutant melanoma show substantial responses to combined BRAF and MEK inhibition, but most relapse within 2 years. A major reservoir for drug resistance is minimal residual disease (MRD), comprised of drug-tolerant tumor cells laying in a dormant state. Towards exploiting potential therapeutic vulnerabilities of MRD, we established a genetically engineered mouse model of BrafV600E-driven melanoma MRD wherein genetic BrafV600E extinction leads to strong but incomplete tumor regression. Transcriptional time-course analysis after BrafV600E extinction revealed that after an initial surge of immune activation, tumors later became immunologically "cold" after MRD establishment. Computational analysis identified candidate T-cell recruiting chemokines as …

Impact Of Clonal Plasma Cells In Autografts On Outcomes In High-Risk Multiple Myeloma Patients, Oren Pasvolsky, Denái R Milton, Mikael Rauf, Sassine Ghanem, Adeel Masood, Ali H Mohamedi, Mark R Tanner, Qaiser Bashir, Samer Srour, Neeraj Saini, Paul Lin, Jeremy Ramdial, Yago Nieto, Guilin Tang, Hans C Lee, Krina K Patel, Partow Kebriaei, Sheeba K Thomas, Donna M Weber, Robert Z Orlowski, Katy Rezvani, Richard Champlin, Elizabeth J Shpall, Pei Lin, Muzaffar H Qazilbash

Faculty, Staff and Student Publications

Most patients with multiple myeloma (MM) undergoing autologous hematopoietic stem cell transplantation (autoHCT) eventually relapse, perhaps due to the presence of clonal plasma cells (CPC) in the autograft. We conducted a retrospective analysis to evaluate the impact of CPC in the autograft on the outcomes of high-risk chromosomal abnormalities (HRMM) patients undergoing autoHCT between 2008 and 2018. Patients were divided into CPC+ or CPC- in the autograft by next-generation flow cytometry (NGF). There were 75 CPC + autografts (18%) and 341 CPC- (82%). The CPC + group was less likely to achieve MRD-negative complete remission post-transplant (11% vs. 42%; p < 0.001). Median progression free survival (PFS) and overall survival (OS) were (12.8 vs. 32.1 months) and (36.4 vs. 81.2 months) in the CPC + and CPC- groups, respectively (both p < 0.001). Also in the subset of patients with MRD-negative ≥VGPR prior to autoHCT, those with CPC + autografts had inferior PFS (HR 4.21, p = 0.006) and OS (HR 7.04, p = 0.002) compared to CPC-. In multivariable analysis, the degree of CPC positivity in the autograft was independently predictive of worse PFS (HR 1.50, p = 0.001) and OS (HR 1.37, p = 0.001). In conclusion, both the presence and degree of CPC in the autograft were highly predictive of inferior PFS and OS.

Clinical Outcomes Of Immunotherapy Continued Beyond Radiographic Disease Progression In Older Adult Patients With Advanced Non-Small Cell Lung Cancer, Eric K Singhi, Frank Mott, Michelle Worst, Cheuk Hong Leung, J Jack Lee, Brett Carter, Carolyn J Presley, John V Heymach, Mehmet Altan

Faculty, Staff and Student Publications

Immunotherapy is an effective and generally well-tolerated treatment strategy for older adult patients (aged ≥70 years) with advanced non-small cell lung cancer (NSCLC). Unfortunately, most patients who receive immunotherapy eventually exhibit disease progression during treatment. The present study reports on a subset of older adult patients with advanced NSCLC who could effectively continue immunotherapy beyond radiographic disease progression due to perceived clinical benefit. Local consolidative radiotherapy may be used in select older adult patients to prolong the duration of immunotherapy they receive, with a particular consideration of their preexisting co-morbidities, performance status and tolerance of potential toxicities associated with combined …

The Effect Of Implementing Behavioral Counseling For Elevated Ldl Levels, Blake L. Hansen

Evidence-Based Practice Project Reports

Hyperlipidemia is a key risk factor in cardiovascular mortality, and is prevalent in approximately 38% of American adults (CDC, 2022b). Cholesterol levels are intensified by unhealthy lifestyle choices, which means a change in lifestyle behaviors could prevent cardiovascular related deaths (WHO, 2022). The PICOT question for this project was: In adults aged 20 years or older in the primary care setting who have elevated low-density lipoprotein (LDL) levels (P), does the implementation of behavioral counseling on lifestyle modifications (I) compared to current practice (C) decrease LDL levels (O) over a 10- to 12- week period (T)? Fourteen participants from a …