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Articles 2791 - 2820 of 14909

Full-Text Articles in Medicine and Health Sciences

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 Jan 2024

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 …


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 Jan 2024

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+ …


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 Jan 2024

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 …


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 Jan 2024

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 …


A Konnyaku Jelly Model For Ultrasound-Guided Fascia Iliaca Compartment Block, Arthraj J. Vyas, Matthew C. Lo, Arthur Au, Md Jan 2024

A Konnyaku Jelly Model For Ultrasound-Guided Fascia Iliaca Compartment Block, Arthraj J. Vyas, Matthew C. Lo, Arthur Au, Md

Alpha Omega Alpha Research Symposium Posters

Purpose

Konnyaku Jelly:

•Previously used as effective ultrasound-guided IV access phantom

•Withstands multiple needle piercings without phantom deterioration

•<$3 per pack


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

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 …


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 Jan 2024

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 Jan 2024

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


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 Jan 2024

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.


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 Dec 2023

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 Dec 2023

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 Dec 2023

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 Dec 2023

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.


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 Dec 2023

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 …


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 Dec 2023

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 …


Late-Onset Stiff-Person Syndrome: Challenges In Diagnosis And Management, Marinos Dalakas, Jessica Yi Dec 2023

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 Dec 2023

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 Dec 2023

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 …


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 Dec 2023

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 Dec 2023

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 …


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 Dec 2023

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 (IRA) 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 Dec 2023

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 …


Cabozantinib Plus Atezolizumab In Previously Untreated Advanced Hepatocellular Carcinoma And Previously Treated Gastric Cancer And Gastroesophageal Junction Adenocarcinoma: Results From Two Expansion Cohorts Of A Multicentre, Open-Label, Phase 1b Trial (Cosmic-021)., Daneng Li, Yohann Loriot, Adam Burgoyne, James Cleary, Armando Santoro, Daniel Lin, Santiago Ponce Aix, Ignacio Garrido-Laguna, Ramu Sudhagoni, Xiang Guo, Svetlana Andrianova, Scott Paulson Dec 2023

Cabozantinib Plus Atezolizumab In Previously Untreated Advanced Hepatocellular Carcinoma And Previously Treated Gastric Cancer And Gastroesophageal Junction Adenocarcinoma: Results From Two Expansion Cohorts Of A Multicentre, Open-Label, Phase 1b Trial (Cosmic-021)., Daneng Li, Yohann Loriot, Adam Burgoyne, James Cleary, Armando Santoro, Daniel Lin, Santiago Ponce Aix, Ignacio Garrido-Laguna, Ramu Sudhagoni, Xiang Guo, Svetlana Andrianova, Scott Paulson

Kimmel Cancer Center Faculty Papers

BACKGROUND: Cabozantinib is approved for previously treated advanced hepatocellular carcinoma (aHCC) and has been investigated in gastric cancer (GC) and gastroesophageal junction adenocarcinoma (GEJ). Atezolizumab plus bevacizumab is approved for unresectable or metastatic HCC untreated with prior systemic therapy. We evaluated efficacy and safety of cabozantinib plus atezolizumab in aHCC previously untreated with systemic anticancer therapy or previously treated GC/GEJ.

METHODS: COSMIC-021 (ClinicalTrials.gov, NCT03170960) is an open-label, phase 1b study in solid tumours with a dose-escalation stage followed by tumour-specific expansion cohorts, including aHCC (cohort 14) and GC/GEJ (cohort 15). Eligible patients were aged ≥18 years with measurable locally advanced, …


Harm Reduction In Undergraduate And Graduate Medical Education: A Systematic Scoping Review, Kelsey R. Smith, Nina K. Shah, Abby L. Adamczyk, Lara C. Weinstein, Erin L. Kelly Dec 2023

Harm Reduction In Undergraduate And Graduate Medical Education: A Systematic Scoping Review, Kelsey R. Smith, Nina K. Shah, Abby L. Adamczyk, Lara C. Weinstein, Erin L. Kelly

Department of Family & Community Medicine Faculty Papers

BACKGROUND: Substance use increasingly contributes to early morbidity and mortality, which necessitates greater preparation of the healthcare workforce to mitigate its harm. The purpose of this systematic scoping review is to: 1) review published curricula on harm reduction for substance use implemented by undergraduate (UME) and graduate medical education (GME) in the United States and Canada, 2) develop a framework to describe a comprehensive approach to harm reduction medical education, and 3) propose additional content topics for future consideration.

METHODS: PubMed, Scopus, ERIC: Education Resources Information Center (Ovid), and MedEdPORTAL were searched. Studies included any English language curricula about harm …


27-Hydroxycholesterol And Dna Damage Repair: Implication In Prostate Cancer, Gloria Cecilia Galvan, Nadine Friedrich, Sanjay Das, James Daniels, Sara Pollan, Shweta Dambal, Ryusuke Suzuki, Sergio Sanders, Sungyong You, Hisashi Tanaka, Yeon-Joo Lee, Wei Yuan, Johann De Bono, Irina Vasilevskaya, Karen Knudsen, Michael Freeman, Stephen Freedland Dec 2023

27-Hydroxycholesterol And Dna Damage Repair: Implication In Prostate Cancer, Gloria Cecilia Galvan, Nadine Friedrich, Sanjay Das, James Daniels, Sara Pollan, Shweta Dambal, Ryusuke Suzuki, Sergio Sanders, Sungyong You, Hisashi Tanaka, Yeon-Joo Lee, Wei Yuan, Johann De Bono, Irina Vasilevskaya, Karen Knudsen, Michael Freeman, Stephen Freedland

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

INTRODUCTION: We previously reported that cholesterol homeostasis in prostate cancer (PC) is regulated by 27-hydroxycholesterol (27HC) and that CYP27A1, the enzyme that converts cholesterol to 27HC, is frequently lost in PCs. We observed that restoring the CYP27A1/27HC axis inhibited PC growth. In this study, we investigated the mechanism of 27HC-mediated anti-PC effects.

METHODS: We employed in vitro models and human transcriptomics data to investigate 27HC mechanism of action in PC. LNCaP (AR+) and DU145 (AR-) cells were treated with 27HC or vehicle. Transcriptome profiling was performed using the Affymetrix GeneChip™ microarray system. Differential expression was determined, and gene set enrichment …


Olanzapine Pharmacokinetics: A Clinical Review Of Current Insights And Remaining Questions, Priyanka Kolli, Grace Kelley, Marianela Rosales, Justin Faden, Ryan Serdenes Dec 2023

Olanzapine Pharmacokinetics: A Clinical Review Of Current Insights And Remaining Questions, Priyanka Kolli, Grace Kelley, Marianela Rosales, Justin Faden, Ryan Serdenes

Department of Psychiatry and Human Behavior Faculty Papers

Olanzapine is one of the most widely used antipsychotics since its initial approval by the US Food and Drug Administration in 1996 and has undergone extensive pharmacokinetic study. Despite being utilized in clinical psychiatry for decades, there remain questions regarding the variety of available formulations, the utility of therapeutic drug monitoring, altered kinetic properties in special populations/medical illnesses, the use of high-dose olanzapine, and drug interactions, among many others. We performed a narrative literature review of olanzapine pharmacokinetics in June 2023 using the US National Library of Medicine's PubMed.gov resource (https://www.ncbi.nlm.nih.gov/pubmed) and Google Scholar. Herein, we review clinically relevant aspects …


Immunosequencing Applications In Cutaneous T-Cell Lymphoma, Jenna Mandel, Laura Gleason, Daniel Joffe, Safiyyah Bhatti, Neda Nikbakht Dec 2023

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 …


The Effect Of Postoperative Naloxone In Certain Otolaryngologic Surgeries, Natalie M. Perlov, Sohan S. Shah, Joann Bluj, Zachary D. Urdang, Rebecca C. Chiffer Dec 2023

The Effect Of Postoperative Naloxone In Certain Otolaryngologic Surgeries, Natalie M. Perlov, Sohan S. Shah, Joann Bluj, Zachary D. Urdang, Rebecca C. Chiffer

Department of Otolaryngology - Head and Neck Surgery Faculty Papers

OBJECTIVE: To evaluate the association of postoperative naloxone with the development of new substance use disorder (SUD), overdose, and death within 6 months of otolaryngologic surgery.

STUDY DESIGN: Retrospective cohort database study on TriNetX.

METHODS: Adult patients who underwent tonsil surgery (noncancerous), thyroid/parathyroid, septorhinoplasty, otology/neurotology, sinus/anterior skull base, and head and neck cancer surgeries between January 2003 and April 2023. Patients were excluded if they had an instance of SUD or overdose recorded in their charts prior to surgery, or had undergone another surgery within that 6-month time frame. We hypothesized that patients prescribed naloxone postoperatively would have decreased odds …


The Concise Guide To Pharmacology 2023/24: Catalytic Receptors, Stephen P.H. Alexander, Doriano Fabbro, Eamonn Kelly, Alistair A. Mathie, John A. Peters, Emma L. Veale, Jane F. Armstrong, Elena Faccenda, Simon D. Harding, Jamie A. Davies, Annie Beuve, Peter Brouckaert, Clare Bryant, John C. Burnett, Richard W. Farndale, Andreas Friebe, John Garthwaite, Adrian J. Hobbs, Gavin E. Jarvis, Doris Koesling, Michaela Kuhn, David Macewan, Tom P. Monie, Lincoln R. Potter, Michael Russwurm, Harald H.H.W. Schmidt, Johannes-Peter Stasch, Scott A. Waldman Dec 2023

The Concise Guide To Pharmacology 2023/24: Catalytic Receptors, Stephen P.H. Alexander, Doriano Fabbro, Eamonn Kelly, Alistair A. Mathie, John A. Peters, Emma L. Veale, Jane F. Armstrong, Elena Faccenda, Simon D. Harding, Jamie A. Davies, Annie Beuve, Peter Brouckaert, Clare Bryant, John C. Burnett, Richard W. Farndale, Andreas Friebe, John Garthwaite, Adrian J. Hobbs, Gavin E. Jarvis, Doris Koesling, Michaela Kuhn, David Macewan, Tom P. Monie, Lincoln R. Potter, Michael Russwurm, Harald H.H.W. Schmidt, Johannes-Peter Stasch, Scott A. Waldman

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

The Concise Guide to PHARMACOLOGY 2023/24 is the sixth in this series of biennial publications. The Concise Guide provides concise overviews, mostly in tabular format, of the key properties of approximately 1800 drug targets, and nearly 6000 interactions with about 3900 ligands. There is an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands (https://www.guidetopharmacology.org/), which provides more detailed views of target and ligand properties. Although the Concise Guide constitutes almost 500 pages, the material presented is substantially reduced compared to information and links presented on the website. It …


Prt543, A Protein Arginine Methyltransferase 5 Inhibitor, In Patients With Advanced Adenoid Cystic Carcinoma: An Open-Label, Phase I Dose-Expansion Study, Renata Ferrarotto, Paul Swiecicki, Dan Zandberg, Robert Baiocchi, Robert Wesolowski, Cristina Rodriguez, Meredith Mckean, Hyunseok Kang, Varun Monga, Rajneesh Nath, Neil Palmisiano, Naveen Babbar, William Sun, Glenn Hanna Dec 2023

Prt543, A Protein Arginine Methyltransferase 5 Inhibitor, In Patients With Advanced Adenoid Cystic Carcinoma: An Open-Label, Phase I Dose-Expansion Study, Renata Ferrarotto, Paul Swiecicki, Dan Zandberg, Robert Baiocchi, Robert Wesolowski, Cristina Rodriguez, Meredith Mckean, Hyunseok Kang, Varun Monga, Rajneesh Nath, Neil Palmisiano, Naveen Babbar, William Sun, Glenn Hanna

Department of Medical Oncology Faculty Papers

OBJECTIVES: Currently, no systemic treatments are approved for patients with recurrent and/or metastatic (R/M) adenoid cystic carcinoma (ACC). PRT543, a protein arginine methyltransferase 5 inhibitor that downregulates NOTCH1 and MYB signalling in tumours, is a potential candidate for R/M ACC treatment. We report the safety, tolerability and preliminary efficacy of PRT543 in a dose-expansion cohort of patients with R/M ACC.

MATERIALS AND METHODS: This phase I multicentre, open-label, sequential-cohort, dose-escalation and dose-expansion study (NCT03886831) enrolled patients with advanced solid tumours and select haematologic malignancies. Dose-escalation study design and results were reported previously. In the dose expansion, patients with R/M ACC …