Digital Commons Network^™

Epigenomic Programming In Early Fetal Brain Development, Luolan Li, Ting Wang, Et Al

2020-Current year OA Pubs

No abstract provided.

Role Of Micro-Rna For Pain After Surgery: Narrative Review Of Animal And Human Studies, Juan P Cata, Aysegul Gorur, Xiaoyi Yuan, Nathaniel K Berg, Anil K Sood, Holger K Eltzschig

Faculty, Staff and Student Publications

One of the most prevalent symptoms after major surgery is pain. When postoperative pain treatment is unsatisfactory, it can lead to poor surgical recovery, decreased quality of life, and increased health care costs. Current analgesics, single or in combination, have limited efficacy due to low potency, limited duration of action, toxicities, and risk of addiction. The lack of nonaddictive strong analgesics along with the over prescription of opioids has led to an opioid epidemic in the United States. Therefore, there is an urgent need for the development of newer analgesics. Microribonucleic acids (miRNAs) are small noncoding RNA molecules that modulate …

Surgical Endoepicardial Linear Ablation For Ventricular Tachycardia With Postinfarction Left Ventricular Aneurysm, Changcheng Liu, Zhaoping Su, Liangshan Wang, Bo Li, Jin Wang, Yang Yu, Chengxiong Gu

The Texas Heart Institute Journal

This retrospective study evaluated the feasibility of surgical endoepicardial linear ablation for ventricular tachycardia in patients with postinfarction left ventricular aneurysm. Sixty-four patients with multivessel coronary artery disease and left ventricular aneurysm but no mural thrombosis of the aneurysm or valve disease were treated at our institution from March 2012 through July 2015. All underwent off-pump coronary artery bypass grafting and left ventricular aneurysm repair by linear plication. Twenty-three patients (35.9%) had ventricular tachycardia and underwent surgical endoepicardial linear ablation on the beating heart guided by epicardial substrate mapping with the Carto 3 system. The remaining 41 patients (64.1%) composed …

The Wrinkling Of Time: Aging, Inflammation, Oxidative Stress, And The Circadian Clock In Neurodegeneration, Brian V Lananna, Erik S Musiek

2020-Current year OA Pubs

A substantial body of research now implicates the circadian clock in the regulation of an array of diverse biological processes including glial function, metabolism, peripheral immune responses, and redox homeostasis. Sleep abnormalities and other forms of circadian disruption are common symptoms of aging and neurodegeneration. Circadian clock disruption may also influence the aging processes and the pathogenesis of neurodegenerative diseases. The specific mechanisms governing the interaction between circadian systems, aging, and the immune system are still being uncovered. Here, we review the evidence supporting a bidirectional relationship between aging and the circadian system. Further, we explore the hypothesis that age-related …

Cardiac Involvement By Burkitt Lymphoma In A 49-Year-Old Man, Kainat Khalid, Nadeen Faza, Nasser M Lakkis, Rashed Tabbaa

The Texas Heart Institute Journal

Malignant metastases are among the most common cardiac masses. We report a rare case of cardiac involvement by Burkitt lymphoma in a 49-year-old man who presented with a 2-month history of dyspnea and palpitations. A transthoracic echocardiogram revealed 2 intracardiac masses in the right atrium (one of which partially encased the tricuspid valve), myocardial infiltration, and pericardial disease. Results of pleural fluid cytology and flow cytometry confirmed involvement by Burkitt lymphoma. Subsequent chemotherapy markedly reduced the intracardiac tumor burden and resolved the patient's presenting symptoms. Our case highlights the importance of cardiac imaging in diagnosing systemic illness, initiating early and …

Altered Mental Status And Hyponatremia After 20 Hours Of Amiodarone Therapy, Andrea Qi, John C Moscona, Justin Reed, Thierry H Le Jemtel

The Texas Heart Institute Journal

A 66-year-old woman with no relevant medical history presented at the emergency department with new-onset atrial fibrillation. We initiated intravenous amiodarone therapy. At 20 hours, the patient experienced severe neurologic symptoms, hyponatremia, and syndrome of inappropriate antidiuretic hormone. We discontinued amiodarone, infused saline solution, and restricted the patient's fluid intake. She recovered in 3 days. This case illustrates that amiodarone-induced syndrome of inappropriate antidiuretic hormone with hyponatremia can occur far earlier than expected during acute amiodarone therapy.

Discovery Of A Selective Inhibitor Of Doublecortin Like Kinase 1, Fleur M Ferguson, Behnam Nabet, Srivatsan Raghavan, Yan Liu, Alan L Leggett, Miljan Kuljanin, Radha L Kalekar, Annan Yang, Shuning He, Jinhua Wang, Raymond W S Ng, Rita Sulahian, Lianbo Li, Emily J Poulin, Ling Huang, Jost Koren, Nora Dieguez-Martinez, Sergio Espinosa, Zhiyang Zeng, Cesear R Corona, James D Vasta, Ryoma Ohi, Taebo Sim, Nam Doo Kim, Wayne Harshbarger, Jose M Lizcano, Matthew B Robers, Senthil Muthaswamy, Charles Y Lin, A Thomas Look, Kevin M Haigis, Joseph D Mancias, Brian M Wolpin, Andrew J Aguirre, William C Hahn, Kenneth D Westover, Nathanael S Gray

Faculty, Staff and Students Publications

Doublecortin like kinase 1 (DCLK1) is an understudied kinase that is upregulated in a wide range of cancers, including pancreatic ductal adenocarcinoma (PDAC). However, little is known about its potential as a therapeutic target. We used chemoproteomic profiling and structure-based design to develop a selective, in vivo-compatible chemical probe of the DCLK1 kinase domain, DCLK1-IN-1. We demonstrate activity of DCLK1-IN-1 against clinically relevant patient-derived PDAC organoid models and use a combination of RNA-sequencing, proteomics and phosphoproteomics analysis to reveal that DCLK1 inhibition modulates proteins and pathways associated with cell motility in this context. DCLK1-IN-1 will serve as a versatile tool …

Our Duty Of Care In Pandemic Times, Perryn Ng

The Texas Heart Institute Journal

No abstract provided.

Incidental Cannulation Of Left Ventricular Thebesian Vein, Kalyan Chakravarthy Potu, Jay N Patel, Majd Ibrahim, Sujitha Sree Ketineni, Sudhir Mungee

The Texas Heart Institute Journal

No abstract provided.

Optimizing P2 Neochordal Length And Stability In Mitral Valve Repair With Use Of A Polypropylene Loop, Anil Ozen, Ertekin Utku Unal, Hamdi Mehmet Ozbek, Gorkem Yigit, Hakki Zafer Iscan

The Texas Heart Institute Journal

Determining the optimal length of artificial chordae tendineae and then effectively securing them is a major challenge in mitral valve repair. Our technique for measuring and stabilizing neochordae involves tying a polypropylene suture loop onto the annuloplasty ring. We used this method in 4 patients who had moderate-to-severe mitral regurgitation from degenerative posterior leaflet (P2) prolapse and flail chordae. Results of intraoperative saline tests and postoperative transesophageal echocardiography revealed only mild insufficiency. One month postoperatively, echocardiograms showed trivial regurgitation in all 4 patients. We think that this simple, precise method for adjusting and stabilizing artificial chordae will be advantageous in …

Emergency Potassium Normalization Treatment Including Sodium Zirconium Cyclosilicate: A Phase Ii, Randomized, Double-Blind, Placebo-Controlled Study (Energize), W Frank Peacock, Zubaid Rafique, Konstantin Vishnevskiy, Edward Michelson, Elena Vishneva, Tatiana Zvereva, Rajaa Nahra, Dao Li, Joseph Miller

Faculty, Staff and Students Publications

OBJECTIVES: Sodium zirconium cyclosilicate (SZC) is a novel, highly selective potassium binder currently approved in the United States and European Union for treatment of hyperkalemia. This pilot evaluation explored the efficacy of SZC with insulin and glucose as hyperkalemia treatment in the emergency department (ED).

METHODS:This exploratory, phase II, multicenter, randomized, double‐blind, placebo‐controlled study (NCT03337477) enrolled adult ED patients with blood potassium ≥ 5.8 mmol/L. Patients were randomized 1:1 to receive SZC 10 g or placebo, up to three times during a 10‐hour period, with insulin and glucose. The primary efficacy outcome was the mean change in serum …

Pooled Crispr Screens With Imaging On Microraft Arrays Reveals Stress Granule-Regulatory Factors, Emily C Wheeler, Anthony Q Vu, Jaclyn M Einstein, Matthew Disalvo, Noorsher Ahmed, Eric L Van Nostrand, Alexander A Shishkin, Wenhao Jin, Nancy L Allbritton, Gene W Yeo

Faculty, Staff and Students Publications

Genetic screens using pooled CRISPR-based approaches are scalable and inexpensive, but restricted to standard readouts, including survival, proliferation and sortable markers. However, many biologically relevant cell states involve cellular and subcellular changes that are only accessible by microscopic visualization, and are currently impossible to screen with pooled methods. Here we combine pooled CRISPR-Cas9 screening with microraft array technology and high-content imaging to screen image-based phenotypes (CRaft-ID; CRISPR-based microRaft followed by guide RNA identification). By isolating microrafts that contain genetic clones harboring individual guide RNAs (gRNA), we identify RNA-binding proteins (RBPs) that influence the formation of stress granules, the punctate protein-RNA …

Simultaneous Examination Of Cellular Pathways Using Multiplex Hextuple Luciferase Assaying, Alejandro Sarrion-Perdigones, Lyra Chang, Yezabel Gonzalez, Tatiana Gallego-Flores, Damian W Young, Koen J T Venken

Faculty, Staff and Students Publications

Multiplex experimentation that can assay multiple cellular signaling pathways in the same cells requires orthogonal genetically encoded reporters that report over large dynamic ranges. Luciferases are cost-effective, versatile candidates whose output signals can be sensitively detected in a multiplex fashion. Commonly used dual luciferase reporter assays detect one luciferase that is coupled to a single cellular pathway, and a second that is coupled to a control pathway for normalization purposes. We expanded this approach to multiplex hextuple luciferase assaying that can report on five cellular signaling pathways and one control, each of which is encoded by a unique luciferase. Light …

Acute Maltodextrin Supplementation During Resistance Exercise, Dylan T Wilburn, Steven B Machek, Thomas D Cardaci, Paul S Hwang, Darryn S Willoughby

Faculty, Staff and Students Publications

Most of the research investigating the ergogenic enhancing mechanisms of carbohydrate have been conducted using aerobic based exercise. Therefore, the purpose of this study was to investigate the effects of pre-exercise maltodextrin ingestion on resistance exercise performance, serum insulin, epinephrine, glucose, and muscle glycogen concentrations. In a double blind, cross over, repeated measures design, participants completed four sets to failure at 70% of 1-RM with 45s rest on the angled leg press with or without pre-exercise maltodextrin (2g/kg) after a 3hr fast. Serum glucose, epinephrine, and insulin were assessed at baseline, 30 min post-ingestion, immediately after, and 1hr post-exercise with …

Tfeb Is A Master Regulator Of Tumor-Associated Macrophages In Breast Cancer, Yong Li, Johnie Hodge, Qing Liu, Junfeng Wang, Yuzhen Wang, Trent D Evans, Diego Altomare, Yongzhong Yao, E. Angela Murphy, Babak Razani, Daping Fan

2020-Current year OA Pubs

BACKGROUND: Tumor-associated macrophages (TAMs) play key roles in the development of many malignant solid tumors including breast cancer. They are educated in the tumor microenvironment (TME) to promote tumor growth, metastasis, and therapy resistance. However, the phenotype of TAMs is elusive and how to regulate them for therapeutic purpose remains unclear; therefore, TAM-targeting therapies have not yet achieved clinical success. The purposes of this study were to examine the role of transcription factor EB (TFEB) in regulating TAM gene expression and function and to determine if TFEB activation can halt breast tumor development.

METHODS: Microarrays were used to analyze the …

Phase 2 Study Of Cemiplimab In Patients With Metastatic Cutaneous Squamous Cell Carcinoma: Primary Analysis Of Fixed-Dosing, Long-Term Outcome Of Weight-Based Dosing, Danny Rischin, Leonel Hernandez-Aya, Et Al

2020-Current year OA Pubs

BACKGROUND: Cemiplimab, a high-affinity, potent human immunoglobulin G4 monoclonal antibody to programmed cell death-1 demonstrated antitumor activity in a Phase 1 advanced cutaneous squamous cell carcinoma (CSCC) expansion cohort (NCT02383212) and the pivotal Phase 2 study (NCT02760498). Here we report the primary analysis of fixed dose cemiplimab 350 mg intravenously every 3 weeks (Q3W) (Group 3) and provide a longer-term update after the primary analysis of weight-based cemiplimab 3 mg/kg intravenously every 2 weeks (Q2W) (Group 1) among metastatic CSCC (mCSCC) patients in the pivotal study (NCT02760498).

METHODS: The primary objective for each group was objective response rate (ORR) per …

Natural History Of Geographic Atrophy Secondary To Age-Related Macular Degeneration: Results From The Prospective Proxima A And B Clinical Trials, Nancy Holekamp, Charles C Wykoff, Steffen Schmitz-Valckenberg, Jordi Monés, Eric H Souied, Hugh Lin, Melvin D Rabena, Ronald A Cantrell, Erin C Henry, Fan Tang, Balakumar Swaminathan, Jillian Martin, Daniela Ferrara, Giovanni Staurenghi

2020-Current year OA Pubs

PURPOSE: To better characterize visual function decline and geographic atrophy (GA) progression secondary to age-related macular degeneration (AMD).

DESIGN: Proxima A (NCT02479386)/Proxima B (NCT02399072) were global, prospective, noninterventional, observational clinical trials.

PARTICIPANTS: Eligible patients were aged ≥50 years. Patients in Proxima A had bilateral GA without choroidal neovascularization (CNV) in either eye (N = 295). Patients in Proxima B had GA without CNV in the study eye and CNV±GA in the fellow eye (fellow eye CNV cohort, n = 168) or GA without CNV in the study eye, no CNV/GA in the fellow eye (fellow eye intermediate AMD cohort, n …

Effects Of Ruxolitinib Cream On Pruritus And Quality Of Life In Atopic Dermatitis: Results From A Phase 2, Randomized, Dose-Ranging, Vehicle- And Active-Controlled Study, Brian S Kim, Kang Sun, Kim Papp, May Venturanza, Adnan Nasir, Michael E. Kuligowski

2020-Current year OA Pubs

BACKGROUND: Atopic dermatitis (AD), a chronic, highly pruritic skin disorder, impairs quality of life (QoL). Janus kinase inhibitors suppress inflammatory and pruritus-associated cytokine signaling in AD.

OBJECTIVE: To report the effects of ruxolitinib (RUX) cream on itch and QoL in AD.

METHODS: A total of 307 adult patients with an Investigator's Global Assessment (score of 2 or 3) and 3% to 20% affected body surface area were randomly assigned for 8 weeks to receive double-blind treatment with RUX (1.5% twice daily, 1.5% once daily, 0.5% once daily, or 0.15% once daily), vehicle twice daily, or triamcinolone cream (0.1% twice daily …

Dupilumab Treatment Results In Early And Sustained Improvements In Itch In Adolescents And Adults With Moderate To Severe Atopic Dermatitis: Analysis Of The Randomized Phase 3 Studies Solo 1 And Solo 2, Ad Adol, And Chronos, Jonathan I. Silverberg, Gil Yosipovitch, Eric L. Simpson, Brian S. Kim, Jashin J. Wu, Laurent Eckert, Isabelle Guillemin, Zhen Chen, Marius Ardeleanu, Ashish Bansal, Mandeep Kaur, Ana B. Rossi, Neil M. H. Graham, Naimish Patel, Abhijit Gadkari

2020-Current year OA Pubs

BACKGROUND: Pruritus (itch) is a cardinal symptom in atopic dermatitis (AD).

OBJECTIVE: To evaluate the timing and effect of dupilumab on itch.

METHODS: Analysis of data from 1505 patients with moderate to severe AD included in 4 randomized controlled studies, treated for up to 52 weeks. Adults received dupilumab 300 mg every 2 weeks or placebo monotherapy (SOLO 1: NCT02277743; SOLO 2: NCT02277769), with concomitant topical corticosteroids (CHRONOS: NCT02260986); adolescents (≥12 to <18 y) were treated with dupilumab monotherapy every 2 weeks (200 mg for baseline weight of <60 kg; 300 mg for baseline weight of ≥60 kg) or placebo (AD ADOL: NCT03054428).

RESULTS: Dupilumab showed significant rapid improvements from baseline in daily Peak Pruritus Numerical Rating Scale scores versus placebo, by day 2 in adults and day 5 in adolescents. …

Maternal Viral Load Monitoring: Coverage And Clinical Action At 4 Kenyan Hospitals., Matthew Sandbulte, Melinda Brown, Catherine Wexler, May Maloba, Brad Gautney, Kathy Goggin, Elizabeth Muchoki, Shadrack Babu, Nicodemus Maosa, Sarah Finocchario-Kessler

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Kenya's guidelines for prevention of mother-to-child transmission of HIV (PMTCT) recommend routine viral load (VL) monitoring for pregnant and breastfeeding women.

METHOD: We assessed PMTCT VL monitoring and clinical action occurring between last menstrual period (LMP) and 6 months postpartum at 4 Kenyan government hospitals. Pregnant women enrolled in the HIV Infant Tracking System from May 2016-March 2018 were included. We computed proportions who received VL testing within recommended timeframes and who received clinical action after unsuppressed VL result.

RESULTS: Of 424 participants, any VL testing was documented for 305 (72%) women and repeat VL testing was documented for …

Multi-Dose Oral Ondansetron For Pediatric Gastroenteritis: Study Protocol For The Multi-Dose Oral Ondansetron For Pediatric Acute Gastroenteritis (Dose-Age) Pragmatic Randomized Controlled Trial, Stephen B Freedman, Sarah Williamson-Urquhart, Anna Heath, Petros Pechlivanoglou, Gareth Hopkin, Serge Gouin, Amy C Plint, Andrew Dixon, Darcy Beer, Gary Joubert, Christopher Mccabe, Yaron Finkelstein, Terry P Klassen

Paediatrics Publications

BACKGROUND: There are limited treatment options that clinicians can provide to children presenting to emergency departments with vomiting secondary to acute gastroenteritis. Based on evidence of effectiveness and safety, clinicians now routinely administer ondansetron in the emergency department to promote oral rehydration therapy success. However, clinicians are also increasingly providing multiple doses of ondansetron for home use, creating unquantified cost and health system resource use implications without any evidence to support this expanding practice.

METHODS/DESIGN: DOSE-AGE is a randomized, placebo-controlled, double-blinded, six-center, pragmatic clinical trial being conducted in six Canadian pediatric emergency departments (EDs). In September 2019 the study began …

Decomposing Loss Aversion From Gaze Allocation And Pupil Dilation, Feng Sheng, Arjun Ramakrishnan, Darsol Seok, Wenjia Joyce Zhao, Samuel Thelaus, Puti Cen, Michael Louis Platt

Faculty, Staff and Student Publications

Loss-averse decisions, in which one avoids losses at the expense of gains, are highly prevalent. However, the underlying mechanisms remain controversial. The prevailing account highlights a valuation bias that overweighs losses relative to gains, but an alternative view stresses a response bias to avoid choices involving potential losses. Here we couple a computational process model with eye-tracking and pupillometry to develop a physiologically grounded framework for the decision process leading to accepting or rejecting gambles with equal odds of winning and losing money. Overall, loss-averse decisions were accompanied by preferential gaze toward losses and increased pupil dilation for accepting gambles. …

Myeloma Cells Shift Osteoblastogenesis To Adipogenesis By Inhibiting The Ubiquitin Ligase Murf1 In Mesenchymal Stem Cells, Zhiqiang Liu, Huan Liu, Jin He, Pei Lin, Qiang Tong, Jing Yang

Faculty, Staff and Students Publications

The suppression of bone formation is a hallmark of multiple myeloma. Myeloma cells inhibit osteoblastogenesis from mesenchymal stem cells (MSCs), which can also differentiate into adipocytes. We investigated myeloma-MSC interactions and the effects of such interactions on the differentiation of MSCs into adipocytes or osteoblasts using single-cell RNA sequencing, in vitro co-culture, and subcutaneous injection of MSCs and myeloma cells into mice. Our results revealed that the α4 subunit of integrin on myeloma cells stimulated vascular cell adhesion molecule 1 (VCAM1) on MSCs, leading to the activation of protein kinase C β1 (PKCβ1) signaling and repression of the muscle ring-finger …

Study Protocol: Improving Cognition In People With Progressive Multiple Sclerosis: A Multi-Arm, Randomized, Blinded, Sham-Controlled Trial Of Cognitive Rehabilitation And Aerobic Exercise (Cogex), Anthony Feinstein, Amber Salter, Et Al

Open Access Publications

BACKGROUND: Cognitive dysfunction affects up to 70% of people with progressive MS (PMS). It can exert a deleterious effect on activities of daily living, employment and relationships. Preliminary evidence suggests that performance can improve with cognitive rehabilitation (CR) and aerobic exercise (EX), but existing data are predominantly from people with relapsing-remitting MS without cognitive impairment. There is therefore a need to investigate whether this is also the case in people with progressive forms of the disease who have objectively identified cognitive impairment. It is hypothesized that CR and EX are effective treatments for people with PMS who have cognitive impairment, …

Adiponectin Inhibits Cardiac Arrest/Cardiopulmonary Resuscitation‑Induced Apoptosis In Brain By Increasing Autophagy Involved In Adipor1‑Ampk Signaling., Yarong He, Bofu Liu, Peng Yao, Yuming Shao, Yanwei Cheng, Jie Zhao, Jiang Wu, Zhi Wei Zhao, Wen Huang, Theodore A. Christopher, Bernard Lopez, Xin-Liang Ma, Yu Cao

Department of Emergency Medicine Faculty Papers

Emerging evidence suggests that both apoptosis and autophagy contribute to global cerebral ischemia-reperfusion (GCIR)-induced neuronal death, which results from cardiac arrest (CA). However, the mechanism of how GCIR may affect the balance between apoptosis and autophagy resulting from CA remains to be elucidated. Additionally, the role of adiponectin (APN) in reversing the apoptosis and autophagy induced by GCIR following cardiac arrest-cardiopulmonary resuscitation (CA-C PR) is unclear. Thus, the aim of the present study was to investigate how GCIR affect the apoptosis and autophagy in response to CA and to clarify whether APN may alter the apoptosis and autophagy of neuronal …

Vascular Risk Reduction In Obesity Through Reduced Granulocyte Burden And Improved Angiogenic Monocyte Content Following Bariatric Surgery., David A Hess, Justin Z Trac, Stephen A Glazer, Daniella C Terenzi, Adrian Quan, Hwee Teoh, Mohammed Al-Omran, Deepak L Bhatt, C David Mazer, Ori D Rotstein, Subodh Verma

Physiology and Pharmacology Publications

Bariatric surgery, in addition to the benefit of sustained weight loss, can also reduce cardiometabolic risk and mortality. Lifelong vessel maintenance is integral to the prevention of cardiovascular disease. Using aldehyde dehydrogenase activity, an intracellular detoxifying enzyme present at high levels within pro-vascular progenitor cells, we observed an association between chronic obesity and "regenerative cell exhaustion" (RCE), a pathology whereby chronic assault on circulating regenerative cell types can result in adverse inflammation and diminished vessel repair. We also describe that, at 3 months following bariatric surgery, systemic inflammatory burden was reduced and pro-angiogenic macrophage precursor content was improved in subjects …

Does Sars-Cov-2 Infection Cause Chronic Neurological Complications?, Erin R Hascup, Kevin N Hascup

Articles

The current pandemic caused by severe acute respiratory syndrome coronavirus (SARS-CoV)-2 has created an unparalleled health crisis. Besides the acute respiratory infection, CoVs are neuroinvasive causing additional inflammation and neurodegeneration. This is likely also true of SARS-CoV-2 given reports of neurological manifestations in coronavirus disease 2019 (COVID-19) positive patients. Older adults > 65 years of age constitute a high-risk group prone to severe infection and death. Despite the higher mortality rate, a majority of cases are expected to recover and survive from this viral outbreak. But, the long-term consequences of SARS-CoV-2 neuroinfection are unknown. We discuss these potential chronic changes to …

Site-Specific Siderocalin Binding To Ferric And Ferric-Free Enterobactin As Revealed By Mass Spectrometry, Chunyang Guo, Lindsey K Steinberg, Ming Cheng, Jong Hee Song, Jeffrey P Henderson, Michael L Gross

Open Access Publications

Both host and pathogen competitively manipulate coordination environments during bacterial infections. Human cells release the innate immune protein siderocalin (Scn, also known as lipocalin-2/Lcn2, neutrophil gelatinase-associated lipocalin/NGAL) that can inhibit bacterial growth by sequestering iron in a ferric complex with enterobactin (Ent), the ubiquitous

A Randomized Controlled Phase Iii Study Of Vb-111 Combined With Bevacizumab Vs Bevacizumab Monotherapy In Patients With Recurrent Glioblastoma (Globe), Timothy F Cloughesy, Andrew Brenner, John F De Groot, Nicholas A Butowski, Leor Zach, Jian L Campian, Benjamin M Ellingson, Laurence S Freedman, Yael C Cohen, Noa Lowenton-Spier, Tamar Rachmilewitz Minei, Shifra Fain Shmueli, Globe Study Investigators, Patrick Y Wen

2020-Current year OA Pubs

BACKGROUND: Ofranergene obadenovec (VB-111) is an anticancer viral therapy that demonstrated in a phase II study a survival benefit for patients with recurrent glioblastoma (rGBM) who were primed with VB-111 monotherapy that was continued after progression with concomitant bevacizumab.

METHODS: This pivotal phase III randomized, controlled trial compared the efficacy and safety of upfront combination of VB-111 and bevacizumab versus bevacizumab monotherapy. Patients were randomized 1:1 to receive VB-111 1013 viral particles every 8 weeks in combination with bevacizumab 10 mg/kg every 2 weeks (combination arm) or bevacizumab monotherapy (control arm). The primary endpoint was overall survival (OS), and secondary …

A Dose-Finding Phase 2 Study Of Single Agent Isatuximab (Anti-Cd38 Mab) In Relapsed/Refractory Multiple Myeloma, Joseph Mikhael, Ravi Vij, Et Al

Open Access Publications

A Phase 2 dose-finding study evaluated isatuximab, an anti-CD38 monoclonal antibody, in relapsed/refractory multiple myeloma (RRMM; NCT01084252). Patients with ≥3 prior lines or refractory to both immunomodulatory drugs and proteasome inhibitors (dual refractory) were randomized to isatuximab 3 mg/kg every 2 weeks (Q2W), 10 mg/kg Q2W(2 cycles)/Q4W, or 10 mg/kg Q2W. A fourth arm evaluated 20 mg/kg QW(1 cycle)/Q2W. Patients (N = 97) had a median (range) age of 62 years (38-85), 5 (2-14) prior therapy lines, and 85% were double refractory. The overall response rate (ORR) was 4.3, 20.0, 29.2, and 24.0% with isatuximab 3 mg/kg Q2W, 10 mg/kg …