Digital Commons Network^™

Efficacy And Safety Of Once-Weekly Insulin Regimes On Glycemic Control For Type 2 Diabetes: A Systematic Review And Network Meta-Analysis, Peng Wang, Yu Zhang, Wenhao Xu, Liyuan Peng, Ping Xu, Weelic Chong, Yang Hai, Lu Jia, Fang Fang

Student Papers, Posters & Projects

Background

Randomized controlled trials have found that once-weekly insulin resulted in greater glycemic control compared to once-daily insulin in patients with type 2 diabetes. However, no direct comparisons have been made between different types of once-weekly insulin thus far. This systematic review and network meta-analysis aimed to evaluate the effect of the two most advanced once-weekly insulin analogues, namely insulin icodec and insulin Fc, in patients with type 2 diabetes.

Methods

We conducted a thorough search in the databases PubMed, Embase, and the Cochrane Central Register of Controlled Trials. The search included articles published from the beginning to October 10, …

Postoperative Systemic Inflammatory Response Syndrome Predicts Increased Mortality In Patients After Elective Craniotomy, Liyuan Peng, Qi Gan, Yangchun Xiao, Jialing He, Xin Cheng, Peng Wang, Lvlin Chen, Tiangui Li, Yan He, Weelic Chong, Yang Hai, Chao You, Fang Fang, Yu Zhang

Department of Medical Oncology Faculty Papers

Introduction: Patients undergoing craniotomy are at high risk of perioperative morbidity and mortality due to excessive inflammatory responses. The purpose of the present study is to evaluate the prognostic utility of postoperative systemic inflammatory response syndrome (SIRS) in patients undergoing craniotomy.

Methods: We performed a retrospective cohort study of patients who underwent craniotomy between January 2011 and March 2021. SIRS was diagnosed based on two or more criteria (hypo-/hyperthermia, tachypnea, leukopenia/leukocytosis, tachycardia). We used univariate and multivariate analysis for the development of SIRS with postoperative 30-day mortality.

Results: Of 12,887 patients who underwent craniotomy, more than half of the patients …

"Once I Take That One Bite": The Consideration Of Harm Reduction As A Strategy To Support Dietary Change For Patients With Diabetes, Alexzandra Gentsch, Megan Reed, Amy Cunningham, Anna Marie Chang, Stephanie Kahn, Danielle Kovalsky, Amanda Doty, Geoffrey Mills, Judd Hollander, Kristin Rising

College of Population Health Faculty Papers

BACKGROUND: Despite well-established guidelines to treat diabetes, many people with diabetes struggle to manage their disease. For many, this struggle is related to challenges achieving nutrition-related lifestyle changes. We examined how people with diabetes describe barriers to maintaining a healthy diet and considered the benefits of using a harm reduction approach to assist patients to achieve nutrition-related goals.

METHODS: This is a secondary analysis of 89 interviews conducted with adults who had type 1 or type 2 diabetes. Interviews were analyzed using a content analysis approach. Themes regarding food or diet were initially captured in a "food" node. Data in …

Analyses Of Patients Who Self-Administered Diazepam Nasal Spray For Acute Treatment Of Seizure Clusters, Sunita Misra, Michael R Sperling, Vikram Rao, Jurriaan Peters, Patricia Penovich, James Wheless, R. Edward Hogan, Charles Davis, Enrique Carrazana, Adrian Rabinowicz

Department of Medicine Faculty Papers

For acute treatment of seizure clusters in patients with epilepsy, intranasal administration of acute seizure therapies has been shown to provide accessibility and ease of use to care partners as well as the potential for self-administration by patients. Diazepam nasal spray (Valtoco®) was approved by the US Food and Drug Administration for acute treatment of intermittent, stereotypic episodes of frequent seizure activity (ie, seizure clusters, acute repetitive seizures) in patients with epilepsy aged ≥6 years. Self-administration consistent with the prescribing information is feasible and was reported by a subgroup of patients (n = 27 of 163) in a long-term phase …

Outcomes Of The Nurosleeve And Occupational Ther E And Occupational Therapy On Upper Y On Upper Limb Function Of An Individual With Chronic Hemiparesis Following A Stroke: A Case Report, Nicole M. Gerhardt, Jeremy P. Armstrong, Mijail D. Serruya, Mj Mulcahey

Department of Occupational Therapy Faculty Papers

Background: Upper limb neuromuscular impairments can adversely impact function. This case report investigates the process and outcomes of occupational therapy (OT) for training in the use of the NuroSleeve, a novel research-grade exoskeletal powered orthosis, with a participant with chronic right hemiparesis following a stroke.

Method: The participant engaged in 24 OT sessions using the NuroSleeve over 10 weeks. Therapeutic interventions included neuromuscular reeducation, device management, and engagement in occupationbased activities with training to use the NuroSleeve. The Canadian Occupational Performance Measure (COPM), ABILHAND, Patient Reported Outcomes Measurement Information System Upper Extremity Short Form 7a (PROMIS UE SF), Action Research …

Iuphar-Review: The Integration Of Classic Psychedelics Into Current Substance Use Disorder Treatment Models, David Yaden, Andrea Berghella, Peter Hendricks, Mary Yaden, Michael Levine, Julia Rohde, Sandeep Nayak, Matthew Johnson, Albert Garcia-Romeu

SKMC Student Presentations and Publications

Substance use disorders (SUDs) have an enormous impact on public health. With classic psychedelic-assisted therapies showing initial promise in treating multiple SUDs, it is possible that these treatments will become legally available options for patients with SUDs in the future. This article highlights how classic psychedelic-assisted therapies might be integrated into current clinical practice. We first describe contemporary evidence-based treatments for SUDs and highlight how classic psychedelic-assisted therapies might fit within each treatment. We suggest that classic psychedelic-assisted therapies can be integrated into most mainstream evidence-based SUD treatments that are currently used in clinical settings, indicating broad compatibility of classic …

Acute Brachial Artery Occlusion Following Cisplatin-Based Chemotherapy: Case Report, Abenezer Melaku Tafese, Amanuel Yegnanew Adela, Assefa Getachew Kebede, Aklilu Sinte Tegegn, Elsabeth Tizazu Asare, Munir Awol

Student Papers, Posters & Projects

Thromboembolism is a significant cause of mortality and morbidity in cancer patients. While the link between cancer and venous thrombosis is well known, the recognition of arterial thrombosis as a serious complication of cancer and chemotherapeutic agents is a recent development. One of the chemotherapy agents frequently linked to acute vascular events is cisplatin. We discuss a rare case of cisplatin-related brachial arterial thrombosis in a 50-year-old man who was treated for cholangiocarcinoma with cisplatin and gemcitabine. Although rare, cisplatin-related arterial thrombosis demands careful monitoring, a high index of suspicion, and prompt management to prevent serious complications and mortality.

Suprachoroidal Space Injection Technique Expert Panel Guidance, Charles C. Wykoff, Robert L. Avery, Mark R. Barakat, David S. Boyer, David M. Brown, Alexander J. Brucker, Emmett T. Cunningham Jr., Jeffrey S. Heier, Nancy M. Holekamp, Peter K. Kaiser, Arshad M. Khanani, Judy E. Kim, Hakan Demirci, Carl D. Regillo, Glenn C. Yiu, Thomas A. Ciulla

Wills Eye Hospital Papers

Purpose:

To develop professional guidelines for best practices for suprachoroidal space (SCS) injection, an innovative technique for retinal therapeutic delivery, based on current published evidence and clinical experience.

Methods:

A panel of expert ophthalmologists reviewed current published evidence and clinical experience during a live working group meeting to define points of consensus and key clinical considerations to inform the development of guidelines for in-office SCS injection.

Results:

Core consensus guidelines for in-office SCS injection were reached and reported by the expert panel. Current clinical evidence and physician experience supported SCS injection as a safe and effective method for delivering retinal …

Examining Menstrual Health Experiences In Philadelphia, Pa: A Qualitative Investigation, Allison Casola, Oriana Pando, Lynette Medley, Brianna Kunes, Nya Mcglone, Olivia Rea

Department of Family & Community Medicine Faculty Papers

BACKGROUND: While menstruation is a physiologic process, it remains highly stigmatized. Despite the sheer number of menstruators, menstruation is a highly individualized experience, with wide variation in duration, symptoms, and management. This wide variability lends itself to large disparities in access to menstruation management products and subsequently the lived experience of menstruators.

OBJECTIVES: The research team sought to understand lived menstrual experiences, symptoms, management tactics, and commonly used and desired resources among 20 cisgendered women aged 18-45 years in Philadelphia.

DESIGN: This project was a qualitative research study.

METHODS: We used a collaborative, community-based participatory research approach with No More …

A Proposal For The Use Of A Fixed Low-Energy Selective Laser Trabeculoplasty For Open Angle Glaucoma, Zachary Sacks, L. Jay Katz, Gus Gazzard, Sarah H. Van Tassel, Eytan Z. Blumenthal, Fabian S. Lerner, Augusto Azuara-Blanco, Gregory John Roy Spooner, Yoram Solberg, Thomas Samuelson, Michael Belkin

Wills Eye Hospital Papers

Selective laser trabeculoplasty (SLT) has been in routine clinical use for over 20 years with millions of patients successfully treated and a low rate of clinically significant complications. The procedure requires the clinician to manually position the laser beam on the trabecular meshwork using a gonioscopy lens and to titrate the SLT laser energy based on the amount of pigmentation in the angle, as well as the observation of small bubbles produced by the laser effect. We propose that SLT energy titration is unnecessary either to achieve intraocular pressure (IOP) reduction or to minimize potential side effects. Ample evidence to …

The Bulletin: Sidney Kimmel Medical College At Thomas Jefferson University, Volume 102, Issue 1, Winter 2024

The Bulletin (formerly the Jefferson Medical College Alumni Bulletin)

This issue includes:

• 6 - Dean’s Column
• 8 - Bicentennial Celebrations
• 10 - ICYMI (In Case You Missed It)
• 12 - Cancer Moonshot Award
• 14 - SKMC Student Blends the Medical Field With the Sports Field: Azra Dees
• 16 - Leading Medicine’s Next Generation Into a New Century: Welcoming Said Ibrahim, MD, MBA, MPH
• 22 - Healthcare Quality and Patient Safety
• 26 - My First Mentee: Robert M. Stein, MD
• 28 - A Message From the SKMC Alumni Board President
• 30 - Alumni Weekend Recap
• 36 - A Message From a Class Agent
• 38 - Meet Cute, SKMC Graduates Find …

Integrating The Patient’S Voice Into The Research Agenda For Treatment Of Chemosensory Disorders, Claire Murphy, Pamela Dalton, Katie Boateng, Stephanie Hunter, Pamela Silberman, Jenifer Trachtman, Suz Schrandt, Bita Naimi, Emily Garvey, Paule Joseph, Conner Frank, Abigail Albertazzi, Gurston Nyquist, Nancy Rawson

Department of Otolaryngology - Head and Neck Surgery Faculty Papers

World-wide some 658 million people were infected with coronavirus disease 2019 (COVID-19) and millions suffer from chemosensory impairment associated with long COVID. Current treatments for taste and smell disorders are limited. Involving patients has the potential to catalyze the dynamic exchange and development of new ideas and approaches to facilitate biomedical research and therapeutics. We assessed patients' perceptions of the efficacy of treatments for chemosensory impairment using an online questionnaire completed by 5,815 people in the US Logistic regression determined variables predictive of reported treatment efficacy for patients aged 18 to 24, 25 to 39, 40 to 60, and 60+ …

Evaluation Of Potential Biomarkers For Lenvatinib Plus Pembrolizumab Among Patients With Advanced Endometrial Cancer: Results From Study 111/Keynote-146, Vicky Makker, Matthew H. Taylor, Carol Aghajanian, Allen L. Cohn, Marcia S. Brose, Christopher Di Simone, Zhu Alexander Cao, Leah Suttner, Andrey Loboda, Razvan Cristescu, Petar Jelinic, Robert Orlowski, Lea Dutta, Junji Matsui, Corina E. Dutcus, Yukinori Minoshima, Mark J. Messing

Department of Medical Oncology Faculty Papers

Background Lenvatinib plus pembrolizumab demonstrated clinically meaningful benefit in patients with previously treated advanced endometrial carcinoma in Study 111/KEYNOTE-146 (NCT02501096). In these exploratory analyses from this study, we evaluated the associations between clinical outcomes and gene expression signature scores and descriptively summarized response in biomarker subpopulations defined by tumor mutational burden (TMB) and DNA variants for individual genes of interest.

Methods Patients with histologically confirmed metastatic endometrial carcinoma received oral lenvatinib 20 mg once daily plus intravenous pembrolizumab 200 mg every 3 weeks for 35 cycles. Archived formalin-fixed paraffin-embedded tissue was obtained from all patients. T-cell–inflamed gene expression …

A Word From The Writing Team (January 2024), Pam Walter, Mfa, Liz Declan, Ma, Mfa

A Word From the Writing Team (Newsletter)

This issue includes:

• Virtual Writing Retreats Return in February
• The OPWPC Canvas Page Offers Helpful Tools
• Academic Commons Will Host a Presentation on Refugee Health in Philadelphia
• Publication Spotlight
• The OPWPC Helps with Scholarly Communication and Publication
• Scott Memorial Library Renovations Continue
• Wiley Open Access Fees Waived for Jefferson Authors

Two-Pore Channel-2 And Inositol Trisphosphate Receptors Coordinate Ca2+ Signals Between Lysosomes And The Endoplasmic Reticulum, Yu Yuan, Vikas Arige, Ryo Saito, Qianru Mu, Gabriela C. Brailoiu, Gustavo J.S. Pereira, Stephen R. Bolsover, Marco Keller, Franz Bracher, Christian Grimm, Eugen Brailoiu, Jonathan S. Marchant, David I. Yule, Sandip Patel

College of Pharmacy Faculty Papers

Lysosomes and the endoplasmic reticulum (ER) are Ca2+ stores mobilized by the second messengers NAADP and IP3, respectively. Here, we establish Ca2+ signals between the two sources as fundamental building blocks that couple local release to global changes in Ca2+. Cell-wide Ca2+ signals evoked by activation of endogenous NAADP-sensitive channels on lysosomes comprise both local and global components and exhibit a major dependence on ER Ca2+ despite their lysosomal origin. Knockout of ER IP3 receptor channels delays these signals, whereas expression of lysosomal TPC2 channels accelerates them. High-resolution Ca2+ imaging reveals elementary events upon TPC2 opening and signals coupled to …

Chronic Hepatitis B: A Summarized Anecdote Of Complexities In Natural History, Treatment, And Complications, Nicholas Noverati, Jay W. Jun, Vivan Yan, Dina Halegoua-De Marzio, Hie-Won Hann

Division of Gastroenterology and Hepatology Faculty Papers

Chronic hepatitis B is still a disease process that affects millions around the world. Serologies used to diagnose and follow the progression (or resolution) of the disease can be confusing for clinicians. Further, throughout years of treatment, there may be nuances in presentation that complicate management even further. In this short communication, we highlight six themes in response to treatment and outcomes, including complications. We have the unique perspective of following many patients over extended periods of time at our institution, which has brought these themes to life in order that they can be shared with other clinicians who may …

A Prioritized Patient-Centered Research Agenda To Reduce Disparities In Telehealth Uptake: Results From A National Consensus Conference, Kristin L. Rising, Mackenzie Kemp, Amy E. Leader, Anna Marie Chang, Andrew J. Monick, Amanda Guth, Tracy Esteves Camacho, Gregory Laynor, Brooke Worster

Department of Emergency Medicine Faculty Papers

Introduction: We hosted a national consensus conference with a diverse group of stakeholders to develop a patient-centered research agenda focused on reducing disparities in telehealth use.

Methods: Attendees were purposively invited to participate in a 2-day virtual conference. The group developed a prioritized research agenda focused on reducing disparities in telehealth uptake, with discussion informed by findings from a scoping review. All work was conducted in partnership with a Steering Committee of national experts in telehealth and patient-centered care (n = 5) and a community-based Telehealth Advisory Board with experience with telehealth use and barriers (n = 8).

Results: Sixty …

Epilepsy Networks And Their Surgical Relevance, Kevin Hines, Chengyuan Wu

Department of Neurosurgery Faculty Papers

Surgical epilepsy is a rapidly evolved field. As the understanding and concepts of epilepsy shift towards a network disorder, surgical outcomes may shed light on numerous components of these systems. This review documents the evolution of the understanding of epilepsy networks and examines the data generated by resective, ablative, neuromodulation, and invasive monitoring surgeries in epilepsy patients. As these network tools are better integrated into epilepsy practice, they may eventually inform surgical decisions and improve clinical outcomes.

Structural Basis For Dna Proofreading, Gina Buchel, Ashok Nayak, Karl Herbine, Azadeh Sarfallah, Viktoriia Sokolova, Angelica Zamudio-Ochoa, Dmitry Temiakov

Department of Biochemistry and Molecular Biology Faculty Papers

DNA polymerase (DNAP) can correct errors in DNA during replication by proofreading, a process critical for cell viability. However, the mechanism by which an erroneously incorporated base translocates from the polymerase to the exonuclease site and the corrected DNA terminus returns has remained elusive. Here, we present an ensemble of nine high-resolution structures representing human mitochondrial DNA polymerase Gamma, Polγ, captured during consecutive proofreading steps. The structures reveal key events, including mismatched base recognition, its dissociation from the polymerase site, forward translocation of DNAP, alterations in DNA trajectory, repositioning and refolding of elements for primer separation, DNAP backtracking, and displacement …

A Novel Multimodal Postoperative Pain Protocol For 1- To 2-Level Open Lumbar Fusions: A Retrospective Cohort Study, Michael Markowitz, Barrett I. Woods, Gregory D. Schroeder, Christopher K Kepler, David Kaye, Mark Kurd, Joshua Armstrong, Alex R. Vaccaro, Kris Radcliff

Rothman Institute Papers

BACKGROUND: There has been increased interest in exploring methods to reduce postoperative pain without opioid medications. In 2015, a multimodal analgesia protocol was used involving the perioperative use of celecoxib, gabapentin, intravenous acetaminophen, lidocaine, and liposomal bupivacaine. Overall, the goal was to reduce the utilization of scheduled opioids in favor of nonopioid pain management.

METHODS: The results of a consecutive series of 1- to 2-level open primary lumbar fusions were compared to a cohort of patients after the implementation the perioperative multimodal pain management protocol. Primary endpoints included patient-reported pain scores and secondary endpoints included length of stay.

RESULTS: There …

Effect Of Flecainide And Ibutilide Alone And In Combination To Terminate And Prevent Recurrence Of Atrial Fibrillation, Alexander Burashnikov, José M. Di Diego, Bence Patocskai, Debra S. Echt, Luiz Belardinelli, Charles Antzelevitch

Division of Cardiology Faculty Papers

BACKGROUND: There is a need for improved approaches to rhythm control therapy of atrial fibrillation (AF).

METHODS: The effectiveness of flecainide (1.5 µmol/L) and ibutilide (20 nmol/L), alone and in combination, to cardiovert and prevent AF recurrence was studied in canine-isolated coronary-perfused right atrioventricular preparations. We also examined the safety of the combination of flecainide (1.5 µmol/L) and ibutilide (50 nmol/L) using canine left ventricular wedge preparations.

RESULTS: Sustained AF (>1 hour) was inducible in 100%, 60%, 20%, and 0% of atria in the presence of acetylcholine alone, acetylcholine+ibutilide, acetylcholine+flecainide, and acetylcholine+ibutilide+flecainide, respectively. When used alone, flecainide and ibutilide …

Late-Onset Stiff-Person Syndrome: Challenges In Diagnosis And Management, Marinos Dalakas, Jessica Yi

Department of Neurology Faculty Papers

BACKGROUND: Stiff person syndrome (SPS) is a rare slowly progressive autoimmune neuronal hyperexcitability disease with very-high GAD-65 antibody titers that most commonly presents above the age of 20, with muscle stiffness, painful muscle spasms, slow gait, and falls leading to disability. In other autoimmune disorders, late-onset disease has different symptom-spectrum and outcomes, but there is no information regarding late-onset SPS (LOSPS).

OBJECTIVE: Highlight delayed diagnosis and poor tolerance or incomplete response to therapies of patients with LOSPS and outline how best to increase disease awareness early at onset.

DESIGN A RETROSPECTIVE CHART REVIEWMETHODS: We reviewed GAD-positive SPS patients with symptom …

The 2023 Orthopedic Research Society's International Consensus Meeting On Musculoskeletal Infection: Summary From The In Vitro Section, Noreen J. Hickok, Bingyun Li, Ebru Oral, Sebastian A.J. Zaat, David A. Armbruster, Gerald J. Atkins, Antonia F. Chen, Débora C. Coraça-Huber, Tianhong Dai, Edward M. Greenfield, Rajendra Kasinath, Matthew Libera, Cláudia N.H. Marques, T. Fintan Moriarty, K. Scott Phillips, Kapil Raghuraman, Dacheng Ren, Lia Rimondini, Kordo Saeed, Thomas P. Schaer, Edward M. Schwarz, Christopher Spiegel, Paul Stoodley, Vi Khanh Truong, Shao-Ting Jerry Tsang, Britt Wildemann, Anja R. Zelmer, Annelies S. Zinkernagel

Department of Orthopaedic Surgery Faculty Papers

Antimicrobial strategies for musculoskeletal infections are typically first developed with in vitro models. The In Vitro Section of the 2023 Orthopedic Research Society Musculoskeletal Infection international consensus meeting (ICM) probed our state of knowledge of in vitro systems with respect to bacteria and biofilm phenotype, standards, in vitro activity, and the ability to predict in vivo efficacy. A subset of ICM delegates performed systematic reviews on 15 questions and made recommendations and assessment of the level of evidence that were then voted on by 72 ICM delegates. Here, we report recommendations and rationale from the reviews and the results of …

Hormone Replacement Therapy Is Associated With Disease Activity Improvement Among Post-Menopausal Women With Inflammatory Bowel Disease, Morgan Freeman, Lauren Lally, Levi Teigen, Elliot Graziano, Raina Shivashankar, Eugenia Shmidt

Division of Gastroenterology and Hepatology Faculty Papers

(1) Background: There are limited data available to guide clinical decision-making regarding the effects of hormone replacement therapy (HRT) in post-menopausal women with inflammatory bowel disease (IBD). In this study, we sought to characterize a population of post-menopausal women with IBD and to determine the effects of HRT on their disease activity. (2) Methods: A multicenter, retrospective, case–control cohort study of post-menopausal women with IBD was conducted. The physician global assessment (PGA) score was used to quantify disease activity. To control for the effects of menopause, IBD patients who had not undergone HRT were used as controls. (3) Results: There …

Autocrine Igf-Ii-Associated Cancers: From A Rare Paraneoplastic Event To A Hallmark In Malignancy, Pierluigi Scalia, Ignazio R. Marino, Salvatore Asero, Giuseppe Pandini, Adda Grimberg, Wafik S. El-Deiry, Stephen J. Williams

Department of Surgery Faculty Papers

The paraneoplastic syndrome referred in the literature as non-islet-cell tumor hypoglycemia (NICTH) and extra-pancreatic tumor hypoglycemia (EPTH) was first reported almost a century ago, and the role of cancer-secreted IGF-II in causing this blood glucose-lowering condition has been widely established. The landscape emerging in the last few decades, based on molecular and cellular findings, supports a broader role for IGF-II in cancer biology beyond its involvement in the paraneoplastic syndrome. In particular, a few key findings are constantly observed during tumorigenesis, (a) a relative and absolute increase in fetal insulin receptor isoform (IR^A) content, with (b) an increase …

Variables Affecting The Extraction Of Antioxidants In Cold And Hot Brew Coffee: A Review, Brian Yust, Frank Wilkinson, Niny Rao

College of Life Sciences Faculty Papers

Coffee beans are a readily available, abundant source of antioxidants used worldwide. With the increasing interest in and consumption of coffee beverages globally, research into the production, preparation, and chemical profile of coffee has also increased in recent years. A wide range of variables such as roasting temperature, coffee grind size, brewing temperature, and brewing duration can have a significant impact on the extractable antioxidant content of coffee products. While there is no single standard method for measuring all of the antioxidants found in coffee, multiple methods which introduce the coffee product to a target molecule or reagent can be …

Safety And Efficacy Of Ixoberogene Soroparvovec In Neovascular Age-Related Macular Degeneration In The United States (Optic): A Prospective, Two-Year, Multicentre Phase 1 Study, Arshad M. Khanani, David S. Boyer, Charles C. Wykoff, Carl D. Regillo, Brandon G. Busbee, Dante Pieramici, Carl J. Danzig, Brian C. Joondeph, James C. Major, Adam Turpcu, Szilárd Kiss

Wills Eye Hospital Papers

Background

Gene therapy, successfully used in rare, monogenetic disorders, may prove to be a durable management approach for common, polygenetic conditions, including neovascular age-related macular degeneration (nAMD). Repeated injections, oftentimes monthly, and possibly for decades, of vascular endothelial growth factor antagonists (anti-VEGF), is the standard for nAMD. We hypothesised that an in-office, intravitreal administration of ixoberogene soroparvovec (ixo-vec, formerly ADVM-022), a single-dose gene therapy encoding for the proven anti-VEGF protein, aflibercept, would transform retinal cells to continually produce aflibercept to minimise treatment burden in nAMD.

Methods

In this two-year, open-label, prospective, multicentre phase 1 study, patients with nAMD responding to …

The Function Of Ask1 In Sepsis And Stress-Induced Disorders, John Kostyak, Steven Mckenzie, Ulhas Naik

Cardeza Foundation for Hematologic Research

Apoptosis signal-regulating kinase 1 (ASK1) is a serine-threonine kinase that is ubiquitously expressed in nucleated cells and is responsible for the activation of multiple mitogen-activated protein kinases (MAPK) to regulate cell stress. Activation of ASK1 via cellular stress leads to activation of downstream signaling components, activation of transcription factors, and proinflammatory cytokine production. ASK1 is also expressed in anucleate platelets and is a key player in platelet activation as it is important for signaling. Interestingly, the mechanism of ASK1 activation is cell type-dependent. In this review we will explore how ASK1 regulates a variety of cellular processes from innate immune …

Desmoglein-2 As A Cancer Modulator: Friend Or Foe?, Kay Myo Min, Charlie Ffrench, Barbara Mcclure, Michael Ortiz, Emma Dorward, Michael Samuel, Lisa Ebert, Mỹ Mahoney, Claudine Bonder

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

Desmoglein-2 (DSG2) is a calcium-binding single pass transmembrane glycoprotein and a member of the large cadherin family. Until recently, DSG2 was thought to only function as a cell adhesion protein embedded within desmosome junctions designed to enable cells to better tolerate mechanical stress. However, additional roles for DSG2 outside of desmosomes are continuing to emerge, particularly in cancer. Herein, we review the current literature on DSG2 in cancer and detail its impact on biological functions such as cell adhesion, proliferation, migration, invasion, intracellular signaling, extracellular vesicle release and vasculogenic mimicry. An increased understanding of the diverse repertoire of the biological …

Immunosequencing Applications In Cutaneous T-Cell Lymphoma, Jenna Mandel, Laura Gleason, Daniel Joffe, Safiyyah Bhatti, Neda Nikbakht

Department of Dermatology and Cutaneous Biology Faculty Papers

Immunosequencing has emerged as a newer clinical test for assessment of T-cell clonality in the blood and skin of cutaneous T-cell lymphoma (CTCL) patients. Utilization of immunosequencing, also known as high-throughput sequencing of the T-cell receptor (HTS-TCR), enables identification and quantification of the precise genetic signature of dominant T-cell clones. Although immunosequencing is more sensitive than commonly used methods such as polymerase chain reaction (PCR) paired with capillary electrophoresis or flow cytometry, it remains underutilized for CTCL management. Nonetheless, incorporation of HTS-TCR in clinical practice offers distinct advantages compared to other molecular analyses that may improve diagnostic evaluation, prognostication, and …