Medical Specialties Commons^™

Comprehensive Review Of The Cardinal Ligament., Seif Eid, Joe Iwanaga, Rod J Oskouian, Marios Loukas, R Shane Tubbs

Articles, Abstracts, and Reports

The cardinal ligament is thought to be one of the important structures in providing support and stabilization for the pelvic organs e.g., the uterus. However, many discrepancies exist in the literature regarding terminology, anatomy, and histology. The cardinal ligament attaches the lateral side of the vagina and cervix to the lateral pelvic wall, which provides support to the vagina and cervix. Studies have shown variable findings in the collagen content and distribution in the cardinal ligaments of women with a prolapsed uterus. Uterine vessels and the branches of the inferior hypogastric plexus travel in the cardinal ligament, which is of …

The Deep Fascia Of The Forearm And The Ulnar Nerve: An Anatomical Study., Paul J Choi, Chidinma Nwaogbe, Joe Iwanaga, Georgi P Georgiev, Rod J Oskouian, R Shane Tubbs

Articles, Abstracts, and Reports

Introduction A reoperation for a cubital tunnel syndrome is not uncommon. Patients often complain of sensorimotor symptoms in the ulnar nerve distribution after their primary surgery. The documented etiologies for such a phenomenon include a "new" kinking of the distal ulnar nerve and a "new" compression of the ulnar nerve by the fascial septum in between or tendinous bands over the muscles of the forearm. The deep fascial plane along which the ulnar nerve travels in the forearm has had scant attention. We present an anatomical study to provide a better understanding of such etiologies to aid physicians in performing …

Review Of The Variations Of The Superficial Veins Of The Neck., Dominic Dalip, Joe Iwanaga, Marios Loukas, Rod J Oskouian, R Shane Tubbs

Articles, Abstracts, and Reports

The venous drainage of the neck can be characterized into superficial or deep. Superficial drainage refers to the venous drainage of the subcutaneous tissues, which are drained by the anterior and external jugular veins (EJVs). The brain, face, and neck structures are mainly drained by the internal jugular vein (IJV). The superficial veins are found deep to the platysma muscle while the deep veins are found encased in the carotid sheath. The junction of the retromandibular vein and the posterior auricular vein usually form the EJV, which continues along to drain into the subclavian vein. The anterior jugular vein is …

Ophthalmic Artery Aneurysm In A Cadaver: Case Report., Dominic Dalip, Joe Iwanaga, Marios Loukas, Rod J Oskouian, R Shane Tubbs

Articles, Abstracts, and Reports

The ophthalmic artery arises from the supraclinoid segment of the internal carotid artery (ICA) and enters the orbit through the optic canal. It perfuses the orbit and the orbit apparatus. Ophthalmic artery aneurysms (OAA) account for 0.5% to 11% of all intracerebral aneurysms. Patients are usually asymptomatic but, in some cases, patients can present with ophthalmoplegia and total blindness if these aneurysms rupture. Aneurysms are usually diagnosed using computed tomography (CT) angiography but can also be seen on magnetic resonance imaging (MRI) and four-vessel digital subtraction angiography. Treatment of OAA entails either surgical or endovascular approaches with the mortality rate …

An Unusual Back Muscle Identified Bilaterally: Case Report., Juan J Altafulla, Mayank Patel, R Shane Tubbs, Joe Iwanaga, Zachary Litvack

Articles, Abstracts, and Reports

Most muscular structures in the human body are named based on their function, origin/insertion, or shape. During routine dissection of the back, an unusual muscle was found deep to the rhomboid muscles. The details of this case and a review of the extant literature are provided.

Pelvic Kidney: A Review Of The Literature., Seif Eid, Joe Iwanaga, Marios Loukas, Rod J Oskouian, R Shane Tubbs

Articles, Abstracts, and Reports

Kidney development is a complex process that begins during the sixth to eighth weeks of life. Failure of ascent of the kidney will cause the kidney to remain in the pelvis i.e., pelvic kidney. Here, we review this entity in detail and illustrate such embryological derailment. In most cases, a pelvic kidney is an incidental finding and is usually asymptomatic. Anatomic variations of the renal vasculature have been reported in cases of pelvic kidneys and these are highlighted in this review. Clinicians who treat patients for renal or pelvic disease or interpret images of the pelvis should be well informed …

An Unusual Variation Of The Accessory Nerve., Yusuf Alimi, Joe Iwanaga, Marios Loukas, Rod J Oskouian, R Shane Tubbs

Articles, Abstracts, and Reports

The accessory nerve is an important nerve in the head and neck regions. Some variants of this nerve's anatomy have been reported. Herein, we present an unusual report and review the extant medical literature regarding other more commonly found derailments of this nerve's anatomy.

A Comprehensive Review Of The Fabella Bone., Dominic Dalip, Joe Iwanaga, Rod J Oskouian, R Shane Tubbs

Articles, Abstracts, and Reports

The fabella is a sesamoid bone that is embedded in the lateral head of the gastrocnemius muscle and often articulates directly with the lateral femoral condyle. It is present in 10-30% of the general population with a higher incidence in Asians. The fabella can lead to various pathologies such as fabella pain syndrome and common fibular nerve palsy. Conservative treatment involves physical therapy or injecting local anesthetics or steroids around this bone. However, if symptoms persist, then a fabellectomy can be performed. Physicians should be aware of the fabella bone and the multiple pathologies associated with it in order to …

Evaluation Of A Digital Diabetes Prevention Program Adapted For The Medicaid Population: Study Design And Methods For A Non-Randomized, Controlled Trial., Sue E Kim, Cynthia M Castro Sweet, Eliza Gibson, Erica N Madero, Barbara Rubino, Janina Morrison, Debra Rosen, Wendy Imberg, Michael R Cousineau

Articles, Abstracts, and Reports

Previous studies have shown that lifestyle modification can successfully prevent or delay development of type 2 diabetes. This trial aimed to test if an underserved, low-income population would engage in a digital diabetes prevention program and successfully achieve lifestyle changes to reduce their risk of type 2 diabetes. Participants were recruited from three health care facilities serving low-income populations. The inclusion criteria were: a recent blood test indicating prediabetes, body mass index (BMI) > 24 kg/m

Using A Randomized Controlled Trial To Test Whether Modifications To Contingency Management Improve Outcomes For Heavy Drinkers With Serious Mental Illness., Oladunni Oluwoye, Jordan Skalisky, Ekaterina Burduli, Naomi S Chaytor, Sterling Mcpherson, Sean M Murphy, Jalene Herron, Katherine Hirchak, Mason Burley, Richard K Ries, John M Roll, Michael G Mcdonell

Articles, Abstracts, and Reports

BACKGROUND: In contingency management (CM), individuals receive rewards for alcohol abstinence. CM is associated with reduced alcohol use in adults with co-occurring serious mental illnesses (SMI). Pre-treatment urine ethyl glucuronide (uEtG) levels equivalent to daily heavy drinking (uEtG >349ng/mL) are associated with poor response to CM. Modifications to CM are needed to improve outcomes for non-responders.

AIMS: To determine if pre-treatment heavy drinkers, defined by uEtG, with SMI achieve higher levels of alcohol abstinence when they receive an increased magnitude of reinforcement for abstinence (High-Magnitude CM) or reinforcers for reduced drinking, prior to receiving reinforcers for abstinence (Shaping CM), relative …

Secukinumab Improves Active Psoriatic Arthritis Symptoms And Inhibits Radiographic Progression: Primary Results From The Randomised, Double-Blind, Phase Iii Future 5 Study., Philip Mease, Désirée Van Der Heijde, Robert Landewé, Shephard Mpofu, Proton Rahman, Hasan Tahir, Atul Singhal, Elke Boettcher, Sandra Navarra, Karin Meiser, Aimee Readie, Luminita Pricop, Ken Abrams

Articles, Abstracts, and Reports

OBJECTIVES: To evaluate the effect of subcutaneous (s.c.) secukinumab, an interleukin-17A inhibitor, on clinical signs and symptoms and radiographic progression in patients with psoriatic arthritis (PsA).

METHODS: Adults (n=996) with active PsA were randomised 2:2:2:3 to s.c. secukinumab 300 mg or 150 mg with loading dose (LD), 150 mg without LD or placebo. All groups received secukinumab or placebo at baseline, weeks 1, 2 and 3 and then every 4 weeks from week 4. The primary endpoint was the proportion of patients achieving an American College of Rheumatology 20 (ACR20) response at week 16.

RESULTS: Significantly more patients achieved an …

Erratum To Inequivalence Of Non-Aggressiveness In Clinically Diagnosed Lung Cancers And Overdiagnosis In Lung Cancer Screening Trials., Jerome M Reich, Jong S Kim

Articles, Abstracts, and Reports

[This corrects the article DOI: 10.21037/jtd.2018.01.164.].

Trevo Stent-Retriever Mechanical Thrombectomy For Acute Ischemic Stroke Secondary To Large Vessel Occlusion Registry., Osama O Zaidat, Alicia C Castonguay, Raul G Nogueira, Diogo C Haussen, Joey D English, Sudhakar R Satti, Jennifer Chen, Hamed Farid, Candace Borders, Erol Veznedaroglu, Mandy J Binning, Ajit Puri, Nirav A Vora, Ron F Budzik, Guilherme Dabus, Italo Linfante, Vallabh Janardhan, Amer Alshekhlee, Michael G Abraham, Randall Edgell, Muhammad Asif Taqi, Ramy El Khoury, Maxim Mokin, Aniel Q Majjhoo, Mouhammed R Kabbani, Michael T Froehler, Ira Finch, Sameer A Ansari, Roberta Novakovic, Thanh N Nguyen

Articles, Abstracts, and Reports

BACKGROUND: Recent randomized clinical trials (RCTs) demonstrated the efficacy of mechanical thrombectomy using stent-retrievers in patients with acute ischemic stroke (AIS) with large vessel occlusions; however, it remains unclear if these results translate to a real-world setting. The TREVO Stent-Retriever Acute Stroke (TRACK) multicenter Registry aimed to evaluate the use of the Trevo device in everyday clinical practice.

METHODS: Twenty-three centers enrolled consecutive AIS patients treated from March 2013 through August 2015 with the Trevo device. The primary outcome was defined as achieving a Thrombolysis in Cerebral Infarction (TICI) score of ≥2b. Secondary outcomes included 90-day modified Rankin Scale (mRS), …

Serious Mental Illness In Heavy Drinkers Is Associated With Poor Treatment Outcomes In Outpatients With Co-Occurring Disorders., Oladunni Oluwoye, Emily Leickly, Jordan Skalisky, Sterling Mcpherson, Katherine Hirchak, Debra Srebnik, John M Roll, Richard K Ries, Michael G Mcdonell

Articles, Abstracts, and Reports

The objective of this study was to determine whether the interaction between type of serious mental illness (SMI) and pre-treatment drinking severity, assessed by ethyl glucuronide (EtG), predicts EtG-positive urine samples submitted during treatment in outpatients with co-occurring alcohol dependence and SMI. Seventy-nine participants were randomized to treatment-as-usual or treatment-as-usual and contingency management (CM) targeting alcohol abstinence. Generalized estimating equations were used to assess the interaction of pre-treatment drinking (heavy drinking or light drinking) and SMI diagnosis (major depression, bipolar, or schizophrenia-spectrum disorders) across a 12-week treatment period. In the overall sample, the interaction of drinking severity and SMI diagnosis …

Targeting Twist1 Through Loss Of Function Inhibits Tumorigenicity Of Human Glioblastoma., Andrei M Mikheev, Svetlana A Mikheeva, Liza J Severs, Cory C Funk, Lei Huang, José L Mcfaline-Figueroa, Jeanette Schwensen, Cole Trapnell, Nathan D Price, Stephen Wong, Robert C Rostomily

Articles, Abstracts, and Reports

TWIST1 (TW) is a bHLH transcription factor (TF) and master regulator of the epithelial-to-mesenchymal transition (EMT). In vitro, TW promotes mesenchymal change, invasion, and self-renewal in glioblastoma (GBM) cells. However, the potential therapeutic relevance of TW has not been established through loss-of-function studies in human GBM cell xenograft models. The effects of TW loss of function (gene editing and knockdown) on inhibition of tumorigenicity of U87MG and GBM4 glioma stem cells were tested in orthotopic xenograft models and conditional knockdown in established flank xenograft tumors. RNAseq and the analysis of tumors investigated putative TW-associated mechanisms. Multiple bioinformatic tools revealed significant …

Secukinumab Versus Adalimumab For Psoriatic Arthritis: Comparative Effectiveness Up To 48 Weeks Using A Matching-Adjusted Indirect Comparison., Peter Nash, Iain B Mcinnes, Philip Mease, Howard Thom, Matthias Hunger, Andreas Karabis, Kunal Gandhi, Shephard Mpofu, Steffen M Jugl

Articles, Abstracts, and Reports

INTRODUCTION: Secukinumab and adalimumab are approved for adults with active psoriatic arthritis (PsA). In the absence of direct randomized controlled trial (RCT) data, matching-adjusted indirect comparison can estimate the comparative effectiveness in anti-tumor necrosis factor (TNF)-naïve populations.

METHODS: Individual patient data from the FUTURE 2 RCT (secukinumab vs. placebo; N = 299) were adjusted to match baseline characteristics of the ADEPT RCT (adalimumab vs. placebo; N = 313). Logistic regression determined adjustment weights for age, body weight, sex, race, methotrexate use, psoriasis affecting ≥ 3% of body surface area, Psoriasis Area and Severity Index score, Health Assessment Questionnaire Disability Index …

Telesurgery: Past, Present, And Future., Paul J Choi, Rod J Oskouian, R Shane Tubbs

Articles, Abstracts, and Reports

Telesurgery uses wireless networking and robotic technology to allow surgeons to operate on patients who are distantly located. This technology not only benefits today's shortage of surgeons, but it also eliminates geographical barriers that prevent timely and high-quality surgical intervention, financial burden, complications, and often risky long-distance travel. The system also provides improved surgical accuracy and ensures the safety of surgeons. In this paper, we describe the current trend of telesurgery's innovative developments and its future.

Extreme Lateral Interbody Fusion Complicated By Fungal Osteomyelitis: Case Report And Quick Review Of The Literature., Ronen Blecher, Emre Yilmaz, Marc Moisi, Rod J Oskouian, Jens Chapman

Articles, Abstracts, and Reports

The authors describe a 67-year-old man with a prior history of alcohol abuse who presented with a complaint of worsening low back pain. Four months prior to his presentation, the patient had undergone extreme lateral interbody fusion (XLIF) of his lumbar 3-4 segment for the treatment of his chronic low back and legs pain. Imaging revealed a loosening of his interbody fusion implant on top of his prior lumbar spine instrumentation. In surgery, the removal of his loose implant was followed by decompression, the stabilization of the collapsed segment, and the implant of antibiotic-impregnated polymethyl-methacrylate (PMMA) spacer and beads. At …

Substance-Induced Anxiety Disorder After One Dose Of 3,4-Methylenedioxymethamphetamine: A Case Report., Kaeley Kaplan, Fiona Kurtz, Kelly Serafini

Articles, Abstracts, and Reports

BACKGROUND: In this report, we describe a case of a patient with substance-induced anxiety disorder occurring after a single dose of 3,4-methylenedioxymethamphetamine. Furthermore, we describe the use and efficacy of the Primary Care Behavioral Health model, a collaborative approach to integrative primary mental health care, in evaluating and treating this rare mental health disorder.

CASE PRESENTATION: Three days following ingestion of one dose of 3,4-methylenedioxymethamphetamine, a 35-year-old Hispanic man with no significant prior mental health history and no history of prior 3,4-methylenedioxymethamphetamine use presented to our hospital with severe, acute anxiety and panic symptoms. He was initially treated with a …

Variant Distal Ulnar Nerve Loop: A Previously Undescribed Anatomical Finding., Mayank Patel, Joe Iwanaga, Rod J Oskouian, R Shane Tubbs

Articles, Abstracts, and Reports

A previously undescribed variant ulnar nerve loop was discovered during the routine anatomic forearm and hand dissection of an adult female. The major finding was that of a large loop traveling around the distal tendon of the flexor carpi ulnaris. The variation presented here appears to be unique. The exact function of such derailed anatomy is not clear but, if found during surgery, might confound normal dissection methods or, when present, could result in varied clinical presentations regarding the sensory or motor examination of the hand.

Tumor Cure By Radiation Therapy And Checkpoint Inhibitors Depends On Pre-Existing Immunity., Marka R Crittenden, Lauren Zebertavage, Gwen Kramer, Shelly Bambina, David Friedman, Victoria Troesch, Tiffany Blair, Jason R Baird, Alejandro F Alice, Michael J Gough

Articles, Abstracts, and Reports

Radiation therapy is a source of tumor antigen release that has the potential to serve as an endogenous tumor vaccination event. In preclinical models radiation therapy synergizes with checkpoint inhibitors to cure tumors via CD8 T cell responses. To evaluate the immune response initiated by radiation therapy, we used a range of approaches to block the pre-existing immune response artifact initiated by tumor implantation. We demonstrate that blocking immune responses at tumor implantation blocks development of a tumor-resident antigen specific T cell population and prevents tumor cure by radiation therapy combined with checkpoint immunotherapy. These data demonstrate that this treatment …

Gastric Hibernoma: A Novel Location And Presentation Of A Rare Tumor., Shane P Smith, Andrew F Feczko, Matias Mihura, Jey-Hsin Chen, Alexander S Farivar

Articles, Abstracts, and Reports

We present a case of gastric hibernoma, an unusual tumor with a location novel to the literature. A 39-year-old female presented with one year of upper gastrointestinal bleeding and dysphagia. Gastroenterology performed an esophagogastroduodenoscopy with ultrasound and identified a 6 cm mass within the muscularis propria of the antrum. Computed tomography demonstrated a 9.7 × 7.8 × 4.8 cm

Extracellular Vesicle Rnas Reflect Placenta Dysfunction And Are A Biomarker Source For Preterm Labour., Shannon Fallen, David Baxter, Xiaogang Wu, Taek-Kyun Kim, Oksana Shynlova, Min Young Lee, Kelsey Scherler, Stephen Lye, Leroy Hood, Kai Wang

Articles, Abstracts, and Reports

Preterm birth (PTB) can lead to lifelong complications and challenges. Identifying and monitoring molecular signals in easily accessible biological samples that can diagnose or predict the risk of preterm labour (PTL) in pregnant women will reduce or prevent PTBs. A number of studies identified putative biomarkers for PTL including protein, miRNA and hormones from various body fluids. However, biomarkers identified from these studies usually lack consistency and reproducibility. Extracellular vesicles (EVs) in circulation have gained significant interest in recent years as these vesicles may be involved in cell-cell communication. We have used an improved small RNA library construction protocol and …

Alt-803, An Il-15 Superagonist, In Combination With Nivolumab In Patients With Metastatic Non-Small Cell Lung Cancer: A Non-Randomised, Open-Label, Phase 1b Trial., John M Wrangle, Vamsidhar Velcheti, Manish R Patel, Elizabeth Garrett-Mayer, Elizabeth G Hill, James G Ravenel, Jeffrey S Miller, Mohammad Farhad, Kate Anderton, Kathryn Lindsey, Michele Taffaro-Neskey, Carol Sherman, Samantha Suriano, Marzena Swiderska-Syn, Amy Sion, Joni Harris, Andie R Edwards, Julie A Rytlewski, Catherine M Sanders, Erik C Yusko, Mark D Robinson, Carsten Krieg, William L Redmond, Jack O Egan, Peter R Rhode, Emily K Jeng, Amy D Rock, Hing C Wong, Mark P Rubinstein

Articles, Abstracts, and Reports

BACKGROUND: Immunotherapy with PD-1 or PD-L1 blockade fails to induce a response in about 80% of patients with unselected non-small cell lung cancer (NSCLC), and many of those who do initially respond then develop resistance to treatment. Agonists that target the shared interleukin-2 (IL-2) and IL-15Rβγ pathway have induced complete and durable responses in some cancers, but no studies have been done to assess the safety or efficacy of these agonists in combination with anti-PD-1 immunotherapy. We aimed to define the safety, tolerability, and activity of this drug combination in patients with NSCLC.

METHODS: In this non-randomised, open-label, phase 1b …

Population-Specific Genetic Modification Of Huntington's Disease In Venezuela., Michael J Chao, Kyung-Hee Kim, Jun Wan Shin, Diane Lucente, Vanessa C Wheeler, Hong Li, Jared C Roach, Leroy Hood, Nancy S Wexler, Laura B Jardim, Peter Holmans, Lesley Jones, Michael Orth, Seung Kwak, Marcy E Macdonald, James F Gusella, Jong-Min Lee

Articles, Abstracts, and Reports

Modifiers of Mendelian disorders can provide insights into disease mechanisms and guide therapeutic strategies. A recent genome-wide association (GWA) study discovered genetic modifiers of Huntington's disease (HD) onset in Europeans. Here, we performed whole genome sequencing and GWA analysis of a Venezuelan HD cluster whose families were crucial for the original mapping of the HD gene defect. The Venezuelan HD subjects develop motor symptoms earlier than their European counterparts, implying the potential for population-specific modifiers. The main Venezuelan HD family inherits HTT haplotype hap.03, which differs subtly at the sequence level from European HD hap.03, suggesting a different ancestral origin …

A Randomized, Placebo-Controlled Trial Of Cenicriviroc For Treatment Of Nonalcoholic Steatohepatitis With Fibrosis., Scott L Friedman, Vlad Ratziu, Stephen A Harrison, Manal F Abdelmalek, Guruprasad P Aithal, Juan Caballeria, Sven Francque, Geoffrey Farrell, Kris V Kowdley, Antonio Craxi, Krzysztof Simon, Laurent Fischer, Liza Melchor-Khan, Jeffrey Vest, Brian L Wiens, Pamela Vig, Star Seyedkazemi, Zachary Goodman, Vincent Wai-Sun Wong, Rohit Loomba, Frank Tacke, Arun Sanyal, Eric Lefebvre

Articles, Abstracts, and Reports

The aim of this study was to evaluate cenicriviroc (CVC), a dual antagonist of CC chemokine receptor types 2 and 5, for treatment of nonalcoholic steatohepatitis (NASH) with liver fibrosis (LF). A randomized, double-blind, multinational phase 2b study enrolled subjects with NASH, a nonalcoholic fatty liver disease activity score (NAS) ≥4, and LF (stages 1-3, NASH Clinical Research Network) at 81 clinical sites. Subjects (N = 289) were randomly assigned CVC 150 mg or placebo. Primary outcome was ≥2-point improvement in NAS and no worsening of fibrosis at year 1. Key secondary outcomes were: resolution of steatohepatitis (SH) and no …

A Randomized Trial Of Obeticholic Acid Monotherapy In Patients With Primary Biliary Cholangitis., Kris V Kowdley, Velimir Luketic, Roger Chapman, Gideon M Hirschfield, Raoul Poupon, Christoph Schramm, Catherine Vincent, Christian Rust, Albert Parés, Andrew Mason, Hanns-Ulrich Marschall, David Shapiro, Luciano Adorini, Cathi Sciacca, Tessa Beecher-Jones, Olaf Böhm, Richard Pencek, David Jones

Articles, Abstracts, and Reports

Obeticholic acid (OCA), a potent farnesoid X receptor agonist, was studied as monotherapy in an international, randomized, double-blind, placebo-controlled phase 2 study in patients with primary biliary cholangitis who were then followed for up to 6 years. The goals of the study were to assess the benefit of OCA in the absence of ursodeoxycholic acid, which is relevant for patients who are intolerant of ursodeoxycholic acid and at higher risk of disease progression. Patients were randomized and dosed with placebo (n = 23), OCA 10 mg (n = 20), or OCA 50 mg (n = 16) given as monotherapy once …

Recognizing Our Experts:, Karsten Wiechert, Jens R Chapman, Jeffrey C Wang

Articles, Abstracts, and Reports

No abstract provided.

Digitizing Omics Profiles By Divergence From A Baseline., Wikum Dinalankara, Qian Ke, Yiran Xu, Lanlan Ji, Nicole Pagane, Anching Lien, Tejasvi Matam, Elana J Fertig, Nathan D Price, Laurent Younes, Luigi Marchionni, Donald Geman

Articles, Abstracts, and Reports

Data collected from omics technologies have revealed pervasive heterogeneity and stochasticity of molecular states within and between phenotypes. A prominent example of such heterogeneity occurs between genome-wide mRNA, microRNA, and methylation profiles from one individual tumor to another, even within a cancer subtype. However, current methods in bioinformatics, such as detecting differentially expressed genes or CpG sites, are population-based and therefore do not effectively model intersample diversity. Here we introduce a unified theory to quantify sample-level heterogeneity that is applicable to a single omics profile. Specifically, we simplify an omics profile to a digital representation based on the omics profiles …

Potent Immune Modulation By Medi6383, An Engineered Human Ox40 Ligand Igg4p Fc Fusion Protein., Michael D Oberst, Catherine Augé, Chad Morris, Stacy Kentner, Kathy Mulgrew, Kelly Mcglinchey, James Hair, Shino Hanabuchi, Qun Du, Melissa Damschroder, Hui Feng, Steven Eck, Nicholas Buss, Lolke De Haan, Andrew J Pierce, Haesun Park, Andrew Sylwester, Michael K Axthelm, Louis Picker, Nicholas P Morris, Andrew D Weinberg, Scott A Hammond

Articles, Abstracts, and Reports

Ligation of OX40 (CD134, TNFRSF4) on activated T cells by its natural ligand (OX40L, CD252, TNFSF4) enhances cellular survival, proliferation, and effector functions such as cytokine release and cellular cytotoxicity. We engineered a recombinant human OX40L IgG4P Fc fusion protein termed MEDI6383 that assembles into a hexameric structure and exerts potent agonist activity following engagement of OX40. MEDI6383 displayed solution-phase agonist activity that was enhanced when the fusion protein was clustered by Fc gamma receptors (FcγRs) on the surface of adjacent cells. The resulting costimulation of OX40 on T cells induced NFκB promoter activity in OX40-expressing T cells and induced …