Medical Specialties Commons^™

Therapies In Stiff-Person Syndrome: Advances And Future Prospects Based On Disease Pathophysiology, Marinos Dalakas

Department of Neurology Faculty Papers

Among the glutamic acid decarboxylase (GAD)-antibody-spectrum disorders, the most common phenotypic subset is the stiff-person syndrome (SPS), caused by impaired GABAergic inhibitory neurotransmission and autoimmunity characterized by very high titers of GAD antibodies and increased GAD-IgG intrathecal synthesis. If not properly treated or untreated because of delayed diagnosis, SPS progresses leading to disability; it is therefore fundamental to apply the best therapeutic schemes from the outset. This article is focused on the rationale of specific therapeutic strategies based on the SPS pathophysiology targeting both the impaired reciprocal GABAergic inhibition to symptomatically improve the main clinical manifestations of stiffness in the …

Publication Rates Of Abstracts Presented Across 6 Major Spine Specialty Conferences, Tariq Z. Issa, Yunsoo Lee, Mark J. Lambrechts, Christopher Reynolds, Ryan Cha, James Kim, Jose A. Canseco, Alex R. Vaccaro, Christopher K. Kepler, Gregory D. Schroeder, Alan S. Hilibrand

Rothman Institute Papers

Background: Although scientific researchers aim to present their projects at academic conferences as a step toward publication, not all projects mature to become a peer-reviewed manuscript. The publication rate of meetings can be utilized to assess the quality of presented research. Our objective was to evaluate the contemporary publication rate of abstracts presented at spine conferences.

Methods: We reviewed annual meeting programs of North American Spine Society (NASS), Scoliosis Research Society (SRS), International Meeting on Advanced Spine Techniques (IMAST), Spine Global Spine Congress (GSC), Lumbar Spine Research Society (LSRS), and Cervical Spine Research Society (CSRS) from 2017 to 2019. Abstracts …

Does Prehabilitation Before Surgery Affect Return To Sport In Baseball Pitchers With Partial Ulnar Collateral Ligament Tears?, Kourtney Snigar, Ryan W. Paul, Joshua M. Spada, Usman Zareef, Anya Hall, Brandon J. Erickson, Michael G. Ciccotti, Stephen J. Thomas

Rothman Institute Papers

BACKGROUND: Purposeful rehabilitation before surgery (prehabilitation) has been researched and implemented in the treatment of anterior cruciate ligament tears. However, it is unclear whether prehabilitation would affect outcomes for baseball pitchers with partial ulnar collateral ligament (UCL) tears.

PURPOSE/HYPOTHESIS: The purpose of this study was to determine whether baseball pitchers with partial UCL tears who completed ≥4 weeks of prehabilitation (prehab group) have different return to play (RTP) outcomes than pitchers with 0 to 3 weeks of preoperative physical therapy (no prehab group). We hypothesized that pitchers in the prehab group would have similar RTP rates compared with pitchers in …

In Season Heart Rate And Session Rate Of Perceived Exertion In Collegiate Softball Athletes, Erin R. Pletcher, Phd, Atc, Cscs

Department of Exercise Science Posters

Introduction

• Monitoring of workload is vital to minimize risk of overuse musculoskeletal injuries in athletes while optimizing performance
• Heart rate (HR) and session rate of perceived exertion (sRPE) have been shown to be reliable measures of training intensity in steady state and interval exercise
• Relationship between training load and injury in running-based team sports has been established
• Limited studies have investigated internal load in throwing-dominant athletes despite rigorous competition season

Stent Vs. Stent-Less Ileal Conduits After Radical Cystectomies: Is There Difference In Early Postoperative Outcomes?, Rishabh K. Simhal, Md, Daniel Givner, Bs, Kerith Wang, Ba, Yash B. Shah, Zachary Prebay, Md, Daniel P. Simon, Md, Costas D. Lallas, Md, Leonard G. Gomella, Md, Mihir M. Shah, Md

Department of Urology Faculty Posters

Placing ureteral stents at the ureteroileal anastomosis for radical cystectomy with ileal conduit (RCIC) diversion has long been common practice, which has recently been called into question. In this study, we aim to investigate the difference in 30-day outcomes between patients who did and did not receive ureteral stents after RCIC.

Adipose Tissue Metabolic Changes In Chronic Kidney Disease, Eurico Serrano, Prashamsa Shenoy, Maria Paula Martinez Cantarin

Division of Nephrology Faculty Papers

Adipose tissue is a complex organ whose functions go beyond being an energy reservoir to sustain proper body energy homeostasis. Functioning as an endocrine organ, the adipose tissue has an active role in the body's metabolic balance regulation through several secreted factors generally termed as adipokines. Thus, adipose tissue dysregulation in chronic kidney disease (CKD) can have a deep impact in the pathophysiology of diseases associated with metabolic dysregulation including metabolic syndrome, insulin resistance (IR), atherosclerosis, and even cachexia. CKD is a progressive disorder linked to increased morbidity and mortality. Despite being characterized by renal function loss, CKD is accompanied …

Telehealth-Based Music Therapy Versus Cognitive Behavioral Therapy For Anxiety In Cancer Survivors: Rationale And Protocol For A Comparative Effectiveness Trial, Kevin T Liou, Kelly M Mcconnell, M Beatriz Currier, Raymond E Baser, Jodi Macleod, Desiree Walker, Camila Casaw, Greta Wong, Lauren Piulson, Karen Popkin, Anamaria Lopez, Katherine Panageas, Joke Bradt, Jun J Mao

Department of Medical Oncology Faculty Papers

Background: Cancer survivors represent one of the fastest growing populations in the United States. Unfortunately, nearly 1 in 3 survivors experience anxiety symptoms as a long-term consequence of cancer and its treatment. Characterized by restlessness, muscle tension, and worry, anxiety worsens the quality of life; impairs daily functioning; and is associated with poor sleep, depressed mood, and fatigue. Although pharmacological treatment options are available, polypharmacy has become a growing concern for cancer survivors. Music therapy (MT) and cognitive behavioral therapy (CBT) are evidence-based, nonpharmacological treatments that have demonstrated effectiveness in treating anxiety symptoms in cancer populations and can be adapted …

Extracellular Targets To Reduce Excessive Scarring In Response To Tissue Injury, Jolanta Fertala, Mark L. Wang, Michael Rivlin, Pedro K. Beredjiklian, Joseph Abboud, William V. Arnold, Andrzej Fertala

Department of Orthopaedic Surgery Faculty Papers

Excessive scar formation is a hallmark of localized and systemic fibrotic disorders. Despite extensive studies to define valid anti-fibrotic targets and develop effective therapeutics, progressive fibrosis remains a significant medical problem. Regardless of the injury type or location of wounded tissue, excessive production and accumulation of collagen-rich extracellular matrix is the common denominator of all fibrotic disorders. A long-standing dogma was that anti-fibrotic approaches should focus on overall intracellular processes that drive fibrotic scarring. Because of the poor outcomes of these approaches, scientific efforts now focus on regulating the extracellular components of fibrotic tissues. Crucial extracellular players include cellular receptors …

A Novel Method For Measuring The Burden Of Breast Cancer In Neighborhoods, Russell K. Mcintire, Hee-Soon Juon, Scott W. Keith, Nicole L. Simone, Dexter Waters, Eleanor Lewis, Charnita Zeigler-Johnson

College of Population Health Faculty Papers

Community-based breast cancer prevention efforts often focus on women who live in the same neighborhoods, as they tend to have similar demographic characteristics, health behaviors, and environmental exposures; yet little research describes methods of selecting neighborhoods of focus for community-based cancer prevention interventions. Studies frequently use demographics from census data, or single breast cancer outcomes (e.g., mortality, morbidity) in order to choose neighborhoods of focus for breast cancer interventions, which may not be optimal. This study presents a novel method for measuring the burden of breast cancer among neighborhoods that could be used for selecting neighborhoods of focus. In this …

The Risk Of Malignant Degeneration Of Müllerian Derivatives In Pmds: A Review Of The Literature, Federica Gagliardi, Augusto Lauro, Livia De Anna, Domenico Tripodi, Anna Esposito, Flavio Forte, Daniele Pironi, Eleonora Lori, Patrizia Alba Gentile, Ignazio R. Marino, Ernesto T. Figueroa, Vito D'Andrea

Department of Urology Faculty Papers

Persistent Müllerian Duct Syndrome (PMDS) is a rare autosomal recessive disorder of sex development characterized by the presence of fallopian tubes, uterus and upper one-third of the vagina in individuals with XY genotype and normal male phenotype. The main complications of PMDS are infertility and the rare risk of malignant degeneration of both testicular and Müllerian derivatives. We report the case of a 49-year-old man who, during repair of an incisional hernia, was incidentally found to have a uterine-like structure posterior to the bladder. In the past at the age of 18 months, he had undergone bilateral orchidopexies for bilateral …

Persistently Elevated Hbv Viral-Host Junction Dna In Urine As A Biomarker For Hepatocellular Carcinoma Minimum Residual Disease And Recurrence: A Pilot Study, Selena Y Lin, Dina Halegoua-De Marzio, Peter Block, Yu-Lan Kao, Jesse M. Civan, Fwu-Shan Shieh, Wei Song, Hie-Won Hann, Ying-Hsiu Su

Department of Medicine Faculty Papers

Hepatitis B virus (HBV)-host junction sequences (HBV-JSs) has been detected in the urine of patients with HBV infection. This study evaluated HBV-JSs as a marker of minimum residual disease (MRD) and tumor recurrence after treatment in HBV-hepatocellular carcinoma (HCC) patients. Archived serial urine DNA from two HBV–HCC with recurrence as confirmed by MRI and four HBV-related cirrhosis (LC) patients were used. Urinary HBV-JSs were identified by an HBV-targeted NGS assay. Quantitative junction-specific PCR assays were developed to investigate dynamic changes of the most abundant urinary HBV-JS. Abundant urinary HBV-JSs were identified in two cases of tumor recurrence. In case 1, …

Trametinib-Induced Epidermal Thinning Accelerates A Mouse Model Of Junctional Epidermolysis Bullosa, Grace Tartaglia, Pyung Hung Park, Michael H. Alexander, Alexander Nyström, Joel Rosenbloom, Andrew P. South

Department of Dermatology and Cutaneous Biology Faculty Papers

Junctional epidermolysis bullosa (JEB) patients experience skin and epithelial fragility due to a pathological deficiency in genes associated with epidermal adhesion. Disease severity ranges from post-natal lethality to localized skin involvement with persistent blistering followed by granulation tissue formation and atrophic scarring. We evaluated the potential of utilizing Trametinib, an MEK inhibitor previously shown to target fibrosis, with and without the documented EB-anti-fibrotic Losartan for reducing disease severity in a mouse model of JEB; Lamc2jeb mice. We found that Trametinib treatment accelerated disease onset and decreased epidermal thickness, which was in large part ameliorated by Losartan treatment. Interestingly, a range …

A Rare Case Of Autopsy Proven Achromobacter Xylosoxidans Endocarditis Involving Tricuspid Valve: A Case Report, Chaitra Janga, Mackenzie Kramer, Ifrah Naeem, Lucy Checchio, Md, Zahra Qamar

Abington Jefferson Health Papers

Infective endocarditis refers to infection of one or more valves of the heart, with Achromobacter xylosoxidans (A. xylosoxidans) being a rare cause. So far, 24 cases of A. xylosoxidans endocarditis were reported, with only one case describing tricuspid valvular involvement. Despite the rarity of A. xylosoxidans endocarditis, it is important for clinicians to be aware of atypical presentation and the high mortality associated with it. We present an autopsy-proven case of tricuspid valve endocarditis in the setting of A. xylosoxidans bacteremia in a 43-year-old female.

Educational Case: Ovarian Neoplasms: A Series Of Educational Cases To Review Malignancies Of Epithelial, Stromal, And Germ Cell Origin, Jordyn B. Tumas, Joanna Chan

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

No abstract provided.

That’S Not Your Implant!, Janet Han, Do, Elizabeth Paterek, Md, Faaem

Department of Emergency Medicine Posters

History of Present Illness

CHIEF COMPLAINT: Left breast pain/swelling

53-year-old female with PMHx of bilateral breast implants, IV drug use, and hypertension presents to the emergency department with swelling and pain to the left breast over the last 5 months after an assault with trauma to the area. She was seen at a previous hospital for these symptoms 3 months ago and reports fluid was drained from the left breast at that time. She reports subjective fevers and chills but denies other symptoms at this time including drainage or discharge from the breast/ nipple, chest pain, or shortness of breath. …

Lived Experience-Centred Word Clouds May Improve Research Uncertainty Gathering In Priority Setting Partnerships, Oliver D. Mowforth, Lance Burn, Danyal Z. Khan, Xiaoyu Yang, Sybil R.L. Stacpoole, Toto Gronlund, Lindsay Tetreault, Sukhvinder Kalsi-Ryan, Michelle L. Starkey, Iwan Sadler, Ellen Sarewitz, Delphine Houlton, Julia Carter, Paige Howard, Vafa Rahimi-Movaghar, James D. Guest, Bizhan Aarabi, Brian K. Kwon, Shekar N. Kurpad, James Harrop, Jefferson R. Wilson, Robert Grossman, Emma K. Smith, Angus Mcnair, Michael G. Fehlings, Mark R.N. Kotter, Benjamin M. Davies

Department of Neurosurgery Faculty Papers

INTRODUCTION: AO Spine RECODE-DCM was a multi-stakeholder priority setting partnership (PSP) to define the top ten research priorities for degenerative cervical myelopathy (DCM). Priorities were generated and iteratively refined using a series of surveys administered to surgeons, other healthcare professionals (oHCP) and people with DCM (PwDCM). The aim of this work was to utilise word clouds to enable the perspectives of people with the condition to be heard earlier in the PSP process than is traditionally the case. The objective was to evaluate the added value of word clouds in the process of defining research uncertainties in National Institute for …

Association Of Radiotherapy Duration With Clinical Outcomes In Patients With Esophageal Cancer Treated In Nrg Oncology Trials: A Secondary Analysis Of Nrg Oncology Randomized Clinical Trials, Christopher L. Hallemeier, Jennifer Moughan, Michael G. Haddock, Arnold M. Herskovic, Bruce D. Minsky, Mohan Suntharalingam, Kenneth L. Zeitzer, Madhur K. Garg, Bruce D. Greenwald, Ritsuko U. Komaki, Lindsay L. Puckett, Hyun Kim, Shane Lloyd, David A. Bush, Harold E. Kim, Thomas E. Lad, Joshua E. Meyer, Gordon S. Okawara, Adam Raben, Tracey E. Schefter, Jerry L. Barker, Carla I. Falkson, Gregory M.M. Videtic, Rojymon Jacob, Kathryn A. Winter, Christopher H. Crane

Einstein Health Papers

IMPORTANCE: For many types of epithelial malignant neoplasms that are treated with definitive radiotherapy (RT), treatment prolongation and interruptions have an adverse effect on outcomes.

OBJECTIVE: To analyze the association between RT duration and outcomes in patients with esophageal cancer who were treated with definitive chemoradiotherapy (CRT).

DESIGN, SETTING, AND PARTICIPANTS: This study was an unplanned, post hoc secondary analysis of 3 prospective, multi-institutional phase 3 randomized clinical trials (Radiation Therapy Oncology Group [RTOG] 8501, RTOG 9405, and RTOG 0436) of the National Cancer Institute-sponsored NRG Oncology (formerly the National Surgical Adjuvant Breast and Bowel Project, RTOG, and Gynecologic Oncology …

Improved Tumor Control Following Radiosensitization With Ultrasound-Sensitive Oxygen Microbubbles And Tumor Mitochondrial Respiration Inhibitors In A Preclinical Model Of Head And Neck Cancer, Quezia Lacerda, Hebah Falatah, Ji-Bin Liu, Corinne Wessner, Brian Oeffinger, Ankit K. Rochani, Dennis B. Leeper, Flemming Forsberg, Joseph M. Curry, Gagan Kaushal, Scott W Keith, Patrick O'Kane, Margaret A Wheatley, John R. Eisenbrey

Department of Radiology Faculty Papers

Tumor hypoxia (oxygen deficiency) is a major contributor to radiotherapy resistance. Ultrasound-sensitive microbubbles containing oxygen have been explored as a mechanism for overcoming tumor hypoxia locally prior to radiotherapy. Previously, our group demonstrated the ability to encapsulate and deliver a pharmacological inhibitor of tumor mitochondrial respiration (lonidamine (LND)), which resulted in ultrasound-sensitive microbubbles loaded with O2 and LND providing prolonged oxygenation relative to oxygenated microbubbles alone. This follow-up study aimed to evaluate the therapeutic response to radiation following the administration of oxygen microbubbles combined with tumor mitochondrial respiration inhibitors in a head and neck squamous cell carcinoma (HNSCC) tumor model. …

Nivolumab Plus Ipilimumab Versus Extreme Regimen As First-Line Treatment For Recurrent/Metastatic Squamous Cell Carcinoma Of The Head And Neck: The Final Results Of Checkmate 651., Robert I. Haddad, Kevin Harrington, Makoto Tahara, Robert L. Ferris, Maura Gillison, Jerome Fayette, Amaury Daste, Piotr Koralewski, Bogdan Zurawski, Miren Taberna, Nabil F. Saba, Milena Mak, Andrzej Kawecki, Gustavo Girotto, Miguel Angel Alvarez Avitia, Caroline Even, Joaquin Gabriel Reinoso Toledo, Alexander Guminski, Urs Müller-Richter, Naomi Kiyota, Mustimbo Roberts, Tariq Aziz Khan, Karen Miller-Moslin, Li Wei, Athanassios Argiris

Department of Medical Oncology Faculty Papers

Purpose: CheckMate 651 (ClinicalTrials.gov identifier: NCT02741570) evaluated first-line nivolumab plus ipilimumab versus EXTREME (cetuximab plus cisplatin/carboplatin plus fluorouracil ≤ six cycles, then cetuximab maintenance) in recurrent/metastatic squamous cell carcinoma of the head and neck (R/M SCCHN).

Methods: Patients without prior systemic therapy for R/M SCCHN were randomly assigned 1:1 to nivolumab plus ipilimumab or EXTREME. Primary end points were overall survival (OS) in the all randomly assigned and programmed death-ligand 1 combined positive score (CPS) ≥ 20 populations. Secondary end points included OS in the programmed death-ligand 1 CPS ≥ 1 population, and progression-free survival, objective response rate, and …

Chronicles Of Hbv And The Road To Hbv Cure, Rukaiya Bashir Hamidu, Richard R. Hann, Hie-Won Hann

Division of Gastroenterology and Hepatology Faculty Papers

Chronic hepatitis B remains a major public health concern and a leading cause of morbidity and mortality worldwide, specifically through its causative role in chronic liver disease and hepatocellular carcinoma. Worldwide, it affects up to 292 million people. In this paper, we review the historic discovery of the hepatitis B virus and chronicle the significant advances in our understanding of the virus and its interactions with the human host to cause disease. We also overview advancements in therapies for hepatitis B virus and the current absence of curative therapies and highlight on-going therapeutic efforts in search of curative therapies to …

The Role Of Interleukin-15 In The Development And Treatment Of Hematological Malignancies, Paola Sindaco, Hritisha Pandey, Colleen Isabelle, Nitin Chakravarti, Jonathan Edward Brammer, Pierluigi Porcu, Anjali Mishra

Kimmel Cancer Center Faculty Papers

Cytokines are a vital component of the immune system that controls the activation and growth of blood cells. However, chronic overexpression of cytokines can trigger cellular events leading to malignant transformation. The cytokine interleukin-15 (IL-15) is of particular interest, which has been shown to contribute to the development and progression of various hematological malignancies. This review will provide an overview of the impact of the immunopathogenic function of IL-15 by studying its role in cell survival, proliferation, inflammation, and treatment resistance. We will also review therapeutic approaches for inhibiting IL-15 in blood cancers.

Kruppel-Like Factor 8 Regulates Triple Negative Breast Cancer Stem Cell-Like Activity, Giang Le Minh, Emily M Esquea, Tejsi T Dhameliya, Jessica Merzy, Mi-Hye Lee, Lauren E Ball, Mauricio J Reginato

Kimmel Cancer Center Faculty Papers

INTRODUCTION: Breast tumor development is regulated by a sub-population of breast cancer cells, termed cancer stem-like cells (CSC), which are capable of self-renewing and differentiating, and are involved in promoting breast cancer invasion, metastasis, drug resistance and relapse. CSCs are highly adaptable, capable of reprogramming their own metabolism and signaling activity in response to stimuli within the tumor microenvironment. Recently, the nutrient sensor O-GlcNAc transferase (OGT) and O-GlcNAcylation was shown to be enriched in CSC populations, where it promotes the stemness and tumorigenesis of breast cancer cells in vitro and in vivo. This enrichment was associated with upregulation of the …

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 …

Effect Of Phacoemulsification On Intraocular Pressure In Eyes With Functioning Tube Shunts, Wesam Shamseldin Shalaby, Sonali Patel, Sophia Lam, Allen Ganjei, Aakriti Garg Shukla, Natasha Kolomeyer, Daniel Lee, L. Jay Katz, Marlene Moster, Jonathan Myers, Reza Razeghinejad

Wills Eye Hospital Papers

Purpose: To evaluate the effect of phacoemulsification on intraocular pressure (IOP) in eyes with functioning tube shunts.

Methods: This was a retrospective chart review of primary open-angle glaucoma (POAG) patients with a functioning tube who underwent phacoemulsification and had ≥24 months of follow-up. The primary end point was defined as surgical failure (IOP > 21 mmHg) at month 24, progression to no light perception (NLP) vision, glaucoma reoperation, or implant removal. Surgical failure defined as IOP >18 and >15 mmHg, changes in visual acuity (VA), IOP, and number of medications were assessed.

Results: Twenty-seven eyes of 27 patients with moderate or …

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 …

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 …

Review Of Cardiovascular Risk Of Androgen Deprivation Therapy And The Influence Of Race In Men With Prostate Cancer, James Fradin, Felix J. Kim, Grace Lu-Yao, Eugene Storozynsky, William K. Kelly

Department of Medical Oncology Faculty Papers

Androgen deprivation therapy is the cornerstone of prostate cancer therapy. Recent studies have revealed an association between androgen deprivation therapy and cardiovascular adverse effects such as myocardial infarction and stroke. This review summarizes the available research on the cardiovascular risk of men using androgen deprivation therapy. We also discuss racial disparities surrounding both prostate cancer and cardiovascular disease, emphasizing the importance of biological/molecular and socioeconomic factors in assessing baseline risk in patients beginning androgen ablation. Based on the literature, we provide recommendations for monitoring patients who are at high risk for a cardiovascular adverse event while being treated on androgen …

Current Barriers To Eye Care, Annika Samuelson, Bs

inSIGHT

Barriers to care penetrate all aspects within our healthcare system and ophthalmology is no exception. The World Health Organization (WHO) estimates 2.2 billion people worldwide have vision impairment, half of which are due to preventable causes and/or remain untreated. In the United States, 6 million people are reported to have visual impairment and over one million people are blind.² The leading causes of blindness within the United States are macular degeneration, cataract, glaucoma, and diabetic retinopathy.³ Management of these diseases require access to early detection, therapeutic intervention, and follow up care at regular intervals; for example, nearly half …