Surgery Commons^™

Deletion Of The Mrna Stability Factor Elavl1 (Hur) In Pancreatic Cancer Cells Disrupts The Tumor Microenvironment Integrity, Grace A Mccarthy, Roberto Di Niro, Jennifer M Finan, Aditi Jain, Yifei Guo, Cory R Wyatt, Alexander R Guimaraes, Trent A Waugh, Dove Keith, Terry K Morgan, Rosalie C Sears, Jonathan R Brody

Department of Surgery Faculty Papers

Stromal cells promote extensive fibrosis in pancreatic ductal adenocarcinoma (PDAC), which is associated with poor prognosis and therapeutic resistance. We report here for the first time that loss of the RNA-binding protein human antigen R (HuR, ELAVL1) in PDAC cells leads to reprogramming of the tumor microenvironment. In multiple in vivo models, CRISPR deletion of ELAVL1 in PDAC cells resulted in a decrease of collagen deposition, accompanied by a decrease of stromal markers (i.e. podoplanin, αsmooth muscle actin, desmin). RNA-sequencing data showed that HuR plays a role in cell–cell communication. Accordingly, cytokine arrays identified that HuR regulates the secretion of …

Incidence And Risk Factors For Retinal Detachment And Retinal Tear After Cataract Surgery: Iris® Registry (Intelligent Research In Sight) Analysis, Michael J. Morano, M. Ali Khan, Qiang Zhang, Colleen P. Halfpenny, Douglas M. Wisner, James Sharpe, Alexander Li, Maurizio Tomaiuolo, Julia A A. Haller, Leslie Hyman, Allen C. Ho

Wills Eye Hospital Papers

Objective To report the incidence of and evaluate demographic, ocular comorbidities, and intraoperative factors for rhegmatogenous retinal detachment (RRD) and retinal tear (RT) after cataract surgery in the American Academy of Ophthalmology IRIS® Registry (Intelligent Research in Sight).

Design Retrospective cohort study.

Participants Patients aged ≥ 40 years who underwent cataract surgery between 2014 and 2017.

Methods Multivariable logistic regression was used to evaluate demographic, comorbidity, and intraoperative factors associated with RRD and RT after cataract surgery.

Main Outcome Measures Incidence and risk factors for RRD or RT within 1 year of cataract surgery.

Results Of the 3 177 195 …

Chewed Versus Swallowed Ticagrelor In P2y12 Inhibitor-Naïve Patients Undergoing Percutaneous Coronary Intervention, Thomas F. Wilson, Muddasir Ashraf, M. Fuad Jan, Tonga Nfor, Louie Kostopoulos, Joaquin Solis, Jayant Khitha, Ahmad Khraisat, Anthony C. Defranco, Tanvir Bajwa, Suhail Q. Allaqaband

Journal of Patient-Centered Research and Reviews

Purpose: Dual antiplatelet therapy is standard for patients undergoing percutaneous coronary intervention (PCI) with stents. Traditionally, patients swallow the loading dose of a P2Y12 inhibitor before or during PCI. Time to achieve adequate platelet inhibition after swallowing the loading dose varies significantly. Chewed tablets may allow more rapid inhibition of platelet aggregation. However, data for this strategy in patients with stable ischemic heart disease or non-ST-elevation acute coronary syndrome (NSTE-ACS) are less robust.

Methods: In this single-center prospective trial, 112 P2Y12-naïve patients with stable ischemic heart disease or NSTE-ACS on aspirin therapy and who received ticagrelor after coronary angiography but …

Quality Assurance In Extracorporeal Membrane Oxygenation Patients, Ruzica Mrkonjic

The VAD Journal

The selection of patients for extracorporeal membrane oxygenation (ECMO) support is a critical component of any perfusion program. Teams must evaluate when to start the support, how long to support the patient, and when is the ideal time to wean. The timing of ECMO support is debated. While some programs emphasize prompt timing, others suggest the conservative approach is better (>7 hours). Delaying ECMO support could increase complications; thus, more evidence has been attained for prompt support. Importantly, complications are common with ECMO support. Despite advances in ECMO support over the last ten years, bleeding remains a high risk. …

Lysosomal Lipid Peroxidation Regulates Tumor Immunity, Monika Bhardwaj, Jennifer J Lee, Amanda M Versace, Sandra L Harper, Aaron R Goldman, Mary Ann S Crissey, Vaibhav Jain, Mahendra Pal Singh, Megane Vernon, Andrew E. Aplin, Seokwoo Lee, Masao Morita, Jeffrey D Winkler, Qin Liu, David W Speicher, Ravi K Amaravadi

Department of Surgery Faculty Papers

Lysosomal inhibition elicited by palmitoyl-protein thioesterase 1 (PPT1) inhibitors such as DC661 can produce cell death, but the mechanism for this is not completely understood. Programmed cell death pathways (autophagy, apoptosis, necroptosis, ferroptosis, and pyroptosis) were not required to achieve the cytotoxic effect of DC661. Inhibition of cathepsins, or iron or calcium chelation, did not rescue DC661-induced cytotoxicity. PPT1 inhibition induced lysosomal lipid peroxidation (LLP), which led to lysosomal membrane permeabilization and cell death that could be reversed by the antioxidant N-acetylcysteine (NAC) but not by other lipid peroxidation antioxidants. The lysosomal cysteine transporter MFSD12 was required for intralysosomal transport …

Microbubble Cavitation Restores Staphylococcus Aureus Antibiotic Susceptibility In Vitro And In A Septic Arthritis Model, Neil Zhao, Dylan Curry, Rachel E Evans, Selin Isguven, Theresa A. Freeman, John R. Eisenbrey, Flemming Forsberg, Jessica M Gilbertie, Sophie Boorman, Rachel Hilliard, Sana S. Dastgheyb, Priscilla Machado, Maria Stanczak, Marc I. Harwood, Antonia F Chen, Javad Parvizi, Irving Shapiro, Noreen J. Hickok, Thomas P Schaer

Department of Orthopaedic Surgery Faculty Papers

Treatment failure in joint infections is associated with fibrinous, antibiotic-resistant, floating and tissue-associated Staphylococcus aureus aggregates formed in synovial fluid (SynF). We explore whether antibiotic activity could be increased against Staphylococcus aureus aggregates using ultrasound-triggered microbubble destruction (UTMD), in vitro and in a porcine model of septic arthritis. In vitro, when bacterially laden SynF is diluted, akin to the dilution achieved clinically with lavage and local injection of antibiotics, amikacin and ultrasound application result in increased bacterial metabolism, aggregate permeabilization, and a 4-5 log decrease in colony forming units, independent of microbubble destruction. Without SynF dilution, amikacin + UTMD does …

The Role Of Klotho And Fgf23 In Cardiovascular Outcomes Of Diabetic Patients With Chronic Limb Threatening Ischemia: A Prospective Study, Federico Biscetti, Maria Margherita Rando, Andrea Leonardo Cecchini, Maria Anna Nicolazzi, Enrica Rossini, Flavia Angelini, Roberto Iezzi, Luis H. Eraso, Paul J. Dimuzio, Dario Pitocco, Antonio Gasbarrini, Massimo Massetti, Andrea Flex

Department of Surgery Faculty Papers

Cardiovascular complications after lower extremity revascularization (LER) are common in diabetic patients with peripheral arterial disease (PAD) and chronic limb threatening ischemia (CLTI). The Klotho-fibroblast growth factor 23 (FGF23) axis is associated with endothelial injury and cardiovascular risk. We aimed to analyze the relationship between Klotho and FGF23 serum levels and the incidence of major adverse cardiovascular events (MACE) and major adverse limb events (MALE) after LER in diabetic patients with PAD and CLTI. Baseline levels of Klotho and FGF23, and their association with subsequent incidence of MACE and MALE were analyzed in a prospective, non-randomized study in a population …

A Rare Metastatic Mesenteric Malignant Pecoma With Tsc2 Mutation Treated With Palliative Surgical Resection And Nab-Sirolimus: A Case Report, Luke Meredith, Timothy Chao, Avinoam Nevler, Atrayee Basu Mallick, Rajan Singla, Peter Mccue, Wilbur Bowne, Wei Jiang, Md, Phd

Kimmel Cancer Center Faculty Papers

BACKGROUND: Malignant perivascular epithelioid cell tumors (PEComas) are exceedingly rare malignant mesenchymal neoplasms with characteristic morphological and immunohistochemical (IHC) patterns. However, some malignant PEComas are poorly differentiated with atypical histopathological features, making a definitive diagnosis difficult. PEComas are most commonly found in females and often show either TSC1 or TSC2 alterations, which result in the activation of the mTOR pathway, or TFE3 fusions. Given these molecular characteristics, mTOR inhibitors have recently been approved by the FDA in the treatment of malignant PEComas, particularly in those with TSC1/2 alterations. Therefore, molecular analyses may be helpful for both the diagnostic workup of …

Influence Of Trpm4 Rs8104571 Genotype On Intracranial Pressure And Outcomes In African Americans With Traumatic Brain Injury, Joseph D Krocker, Madeline E Cotton, Jacob B Schriner, Baron K Osborn, Michael M Talanker, Yao-Wei W Wang, Charles S Cox, Charles E Wade

Faculty, Staff and Student Publications

The TRPM4 gene codes for a membrane ion channel subunit related to inflammation in the central nervous system. Recent investigation has identified an association between TRPM4 single nucleotide polymorphisms (SNPs) rs8104571 and rs150391806 and increased intracranial (ICP) pressure following traumatic brain injury (TBI). We assessed the influence of these genotypes on clinical outcomes and ICP in TBI patients. We included 292 trauma patients with TBI. DNA extraction and real-time PCR were used for TRPM4 rs8104571 and rs150391806 allele discrimination. Five participants were determined to have the rs8104571 homozygous variant genotype, and 20 participants were identified as heterozygotes; 24 of these …

Prevention Of Surgical Site Infection: A Ten-Step Approach, Saad Tarabichi, Javad Parvizi

Rothman Institute Papers

Surgical site infection (SSI) is a common cause of morbidity and mortality in patients undergoing surgery. Similarly, periprosthetic joint infection (PJI), is a major cause of failure after total joint arthroplasty (TJA). As the annual volume of TJA procedures is projected to rise, so will the rate of subsequent SSI and PJI. Currently, prevention has been identified as the single most important strategy for combating SSI/PJI. Hence, the present article will serve as a summary of an evidence-based ten-step approach for SSI/PJI prevention that may help orthopedic surgeons with their infection prevention strategies.

Cold Atmospheric Pressure Plasma-Antibiotic Synergy In Pseudomonas Aeruginosa Biofilms Is Mediated Via Oxidative Stress Response, Jordanne-Amee Maybin, Thomas P. Thompson, Padrig B. Flynn, Timofey Skvortsov, Noreen J. Hickok, Theresa A. Freeman, Brendan F. Gilmore

Department of Orthopaedic Surgery Faculty Papers

Cold atmospheric-pressure plasma (CAP) has emerged as a potential alternative or adjuvant to conventional antibiotics for the treatment of bacterial infections, including those caused by antibiotic-resistant pathogens. The potential of sub-lethal CAP exposures to synergise conventional antimicrobials for the eradication of Pseudomonas aeruginosa biofilms is investigated in this study. The efficacy of antimicrobials following or in the absence of sub-lethal CAP pre-treatment in P. aeruginosa biofilms was assessed. CAP pre-treatment resulted in an increase in both planktonic and biofilm antimicrobial sensitivity for all three strains tested (PAO1, PA14, and PA10548), with both minimum inhibitory concentrations (MICs) and minimum biofilm eradication …

Dpp8 Selective Inhibitor Tominostat As A Novel And Broad-Spectrum Anticancer Agent Against Hematological Malignancies, Shohei Kikuchi, Akinori Wada, Yusuke Kamihara, Kosuke Okazaki, Paras Jawaid, Mati Ur Rehman, Eiji Kobayashi, Takeshi Susukida, Tomoki Minemura, Yoshimi Nabe

Department of Biological & Biomedical Sciences

DPP8/9 inhibition induces either pyroptotic or apoptotic cell death in hematological malignancies. We previously reported that treatment with the DPP8/9 inhibitor 1G244 resulted in apoptotic cell death in myeloma, and our current study further evaluates the mechanism of action of 1G244 in different blood cancer cell lines. Specifically, 1G244 inhibited DPP9 to induce GSDMD-mediated-pyroptosis at low concentrations and inhibited DPP8 to cause caspase-3-mediated-apoptosis at high concentrations. HCK expression is necessary to induce susceptibility to pyroptosis but does not participate in the induction of apoptosis. To further characterize this DPP8-dependent broad-spectrum apoptosis induction effect, we evaluated the potential antineoplastic role for …

Effect Of Drain Duration And Output On Perioperative Outcomes And Readmissions After Lumbar Spine Surgery, Brian A. Karamian, Parth Kothari, Gregory R. Toci, Mark J. Lambrechts, Jose A. Canseco, Jennifer Mao, Raj Narayan, Sammy Alfonsi, Francis Sirch, Nadim Kheir, Nicholas Semenza, Barrett I. Woods, Jeffrey A. Rihn, Mark Kurd, Kris Radcliff, I David Kaye, Alan S. Hilibrand, Christopher K. Kepler, Alex R. Vaccaro, Gregory D. Schroeder

Rothman Institute Papers

Study design: Single-center retrospective cohort.

Purpose: To compare surgical outcomes of patients based on lumbar drain variables relating to output and duration.

Overview of literature: The use of drains following lumbar spine surgery, specifically with respect to hospital readmission, postoperative hematoma, postoperative anemia, and surgical site infections, has been controversial.

Methods: Patients aged ≥18 years who underwent lumbar fusion with a postoperative drain between 2017 and 2020 were included and grouped based on hospital readmission status, last 8-hour drain output (<40 mL cutoff), or drain duration (2 days cutoff). Total output of all drains, total output of the primary drain, drain duration in days, drain output per day, last 8-hour output, penultimate 8-hour output, and last 8-hour delta (last 8-hour output subtracted by penultimate 8-hour output) were collected. Continuous and categorical data were compared between groups. Multivariate logistic regression analysis and receiver operating characteristic (ROC) analysis were performed to determine whether drain variables can predict hospital readmission, postoperative blood transfusions, and postoperative anemia. Alpha was 0.05.

Results: Our cohort consisted of 1,166 patients with 111 (9.5%) hospital readmissions. Results of regression analysis did not identify …

Implementation Of An Activity Protocol In The Acute Care Setting: A Quality Improvement Project, Crystal M. Ryan

DNP Projects

Background: Physical activity following cardiothoracic surgery can help decrease post-operative complications, expedite functional recovery, improve overall well-being, shorten hospital length of stay (LOS), and reduce morbidity and mortality (Miwa et al., 2017). Of these patients, 58% developed complications after cardiac surgery; of these complications, 31% were pulmonary, 16% were of cardiac in nature, and 14% were neurological (Yayla, 2018).

Purpose: This quality improvement project aims to implement an evidence-based protocol for evaluating the correlation between physical activity in uncomplicated post-operative coronary artery bypass and length of stay.

Methods: The Plan-Do-Study-Act (PDSA) tool from the Institute for Healthcare Improvement (IHI) guided …

Serotonin Reuptake Inhibitor Increases Pseudarthrosis Rates In Anterior Cervical Discectomy And Fusions, Mark J. Lambrechts, Nicholas D. D'Antonio, Gregory R R. Toci, Brian A. Karamian, Josuhu Pezzulo, Dominic Farronato, Jose Canseco, Ian David Kaye, Barrett Woods, Jeffrey A. Rihn, Mark Kurd, Joseph K. Lee, Md, Alan S. Hilibrand, Christopher K. Kepler, Alexander R. Vaccaro, Gregory D. Schroeder

Rothman Institute Papers

STUDY DESIGN: Retrospective cohort.

PURPOSE: To determine (1) the effects of serotonin reuptake inhibitors in pseudarthrosis rates after anterior cervical decompression and fusion (ACDF) and (2) to identify patient-reported outcome measures in patients taking serotonin reuptake inhibitors.

OVERVIEW OF LITERATURE: Recent literature suggests that selective serotonin reuptake inhibitors (SSRIs) may inhibit fracture healing via downregulation of osteoblast differentiation. Spinal fusion supplementation with osteoblast-rich substances enhances spinal fusion, thus SSRIs may be detrimental.

METHODS: Patients with 1-year postoperative dynamic cervical spine radiographs following ACDF were grouped into serotonin reuptake inhibitor prescriptions (SSRI, serotonin-norepinephrine reuptake inhibitor [SNRI], or tricyclic antidepressant [TCA]) and …

Challenges In Closing The Gap Between Evidence And Practice: International Survey Of Institutional Surgical Stabilization Of Rib Fractures Guidelines, Jeff Choi, Avanti Badrinathan, Ryan Shine, Cecilia Benz, Alyssa Toia, Sarahann Whitbeck, Mark Kryskow, Thomas White, Jordan Kirsch

School of Medicine Publications

Background: Surgical stabilization of rib fractures (SSRF) has gained increasing interest over the past decade, yet few candidates who could benefit from SSRF undergo operative management. We conducted an international survey of institutional SSRF guidelines comparing congruence between practice and contemporary evidence. We hypothesized that few guidelines reflect comprehensive evidence to facilitate standardized patient selection, operation, and post-operative management.

Methods: A request for institutional rib fracture guidelines was distributed from the Chest Wall Injury Society. SSRF-specific guideline contents were extracted using a priori-designed extraction sheets and compared against 28 SSRF evidence-based recommendations outlined by a panel of 14 international experts. …

A Metabolic, Mechanical, Multi-Organ Masterpiece: Dural Device Support Bridge To En-Bloc Heart-Liver Transplantation In Propionic Acidemia, Rebecca Juhl, Brian Birnbaum, Aliessa P. Barnes, William Gibson, Bhargava Mullapudi, Beth Lang, Megan Faseler, Daniel E. Heble, Victoria Urban, Ryan T. Fischer, Jennifer L. Gannon, David Sutcliffe

Posters

Introduction: Propionic Acidemia (PA) is a disorder related to abnormal protein and lipid metabolism resulting in progressive neurological injury and dilated cardiomyopathy (DCM). Interventions for PA and secondary disease manifestations can require multi-organ transplantation. Herein we report the case of a child with PA and end-stage DCM requiring left ventricular assist device (LVAD) support with eventual heart-liver transplant. Case Report: A 17 year old male diagnosed in childhood with PA developed chronically progressive DCM culminating in end stage heart failure with acute decompensations. In a recurrent admission, he progressed to require dual inotropic support and systemic anticoagulation for new LV …

Iv Dexamethasone To Assist With Post Operative Pain And Nausea, Tasha Coumbs

Articles, Abstracts, and Reports

No abstract provided.

Enoxaparin May Be Associated With Lower Rates Of Mortality Than Unfractionated Heparin In Neurocritical And Surgical Patients, Sophie Samuel, Catherine To, Yaobin Ling, Kai Zhang, Xiaoqian Jiang, Elmer V Bernstam

Faculty, Staff and Student Publications

Unfractionated heparin (UFH) and low molecular weight heparin (LMWH) are often administered to prevent venous thromboembolism (VTE) in critically ill patients. However, the preferred prophylactic agent (UFH or LMWH) is not known. We compared the all-cause mortality rate in patients receiving UFH to LMWH for VTE prophylaxis. We conducted a retrospective propensity score adjusted analysis of patients admitted to neuro-critical, surgical, or medical intensive care units. Patients were included if they were screened with venous duplex ultrasonography or computed tomography angiography for detection of VTE. The primary outcome was all-cause mortality. Secondary outcomes included the prevalence of VTE, deep vein …

Berberine Disrupts Staphylococcal Proton Motive Force To Cause Potent Anti-Staphylococcal Effects, Neil Zhao, Selin Isguven, Rachel Evans, Thomas P Schaer, Noreen J. Hickok

Department of Orthopaedic Surgery Faculty Papers

The presence of antibiotic resistance has increased the urgency for more effective treatments of bacterial infections. Biofilm formation has complicated this issue as biofilm bacteria become tolerant to antibiotics due to environmental factors such as nutrient deprivation and adhesion. In septic arthritis, a disease with an 11% mortality rate, bacteria in synovial fluid organize into floating, protein-rich, bacterial aggregates (mm-cm) that display depressed metabolism and antibiotic tolerance. In this study, Staphylococcus aureus (S. aureus), which is the most common pathogen in septic arthritis, was tested against different inhibitors that modulate bacterial surface protein availability and that should decrease bacterial aggregation. …