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https://www.readbyqxmd.com/read/29207939/tocilizumab-for-the-management-of-immune-mediated-adverse-events-secondary-to-pd-1-blockade
#1
Chipman Rg Stroud, Aparna Hegde, Cynthia Cherry, Abdul R Naqash, Nitika Sharma, Srikala Addepalli, Sulochana Cherukuri, Teresa Parent, Jessica Hardin, Paul Walker
Background Immune checkpoint inhibitors are poised to revolutionize the management of a growing number of malignancies. Unfortunately, the management of steroid-refractory immune mediated adverse events is based on a paucity of randomized data and limited to single center experiences. Our initial experience with the IL-6 receptor antagonist tocilizumab showed clinical improvement in a wide variety of irAEs. As a result, we adopted the use of tocilizumab for the management of steroid refractory irAEs. Methods The character and clinical course of irAEs were abstracted from the medical record and analyzed...
January 1, 2017: Journal of Oncology Pharmacy Practice
https://www.readbyqxmd.com/read/29189290/period-dependent-associations-between-hypotension-during-and-for-4-days-after-noncardiac-surgery-and-a-composite-of-myocardial-infarction-and-death-a-substudy-of-the-poise-2-trial
#2
Daniel I Sessler, Christian S Meyhoff, Nicole M Zimmerman, Guangmei Mao, Kate Leslie, Skarlet M Vásquez, Packianathaswamy Balaji, Jesús Alvarez-Garcia, Alexandre B Cavalcanti, Joel L Parlow, Prashant V Rahate, Manfred D Seeberger, Bruno Gossetti, S A Walker, Rajendra K Premchand, Rikke M Dahl, Emmanuelle Duceppe, Reitze Rodseth, Fernando Botto, P J Devereaux
BACKGROUND: The relative contributions of intraoperative and postoperative hypotension to perioperative morbidity remain unclear. We determined the association between hypotension and a composite of 30-day myocardial infarction and death over three periods: 1) intraoperative; 2) remaining day of surgery; and 3) during the initial four postoperative days. METHODS: This was a substudy of POISE-2, a 10,010-patient factorial-randomized trial of aspirin and clonidine for prevention of myocardial infarction...
November 21, 2017: Anesthesiology
https://www.readbyqxmd.com/read/29136283/population-pk-analyses-of-ubrogepant-mk-1602-a-cgrp-receptor-antagonist-enriching-in-clinic-plasma-pk-sampling-with-outpatient-dried-blood-spot-sampling
#3
Chi-Chung Li, Marissa Dockendorf, Ken Kowalski, Bei Yang, Yang Xu, Iris Xie, Huub Jan Kleijn, Rolien Bosch, Christopher Jones, Bob Thornton, Eugene E Marcantonio, Tiffini Voss, Kevin P Bateman, Prajakti A Kothare
Merck & Co., Inc. (Kenilworth, New Jersey) has recently published an integrated strategy for implementation of dried blood spots (DBS) in late-stage trials for population pharmacokinetic (PK) modeling. We applied this strategy for another late-stage clinical program: ubrogepant (MK-1602), a novel oral calcitonin gene-related peptide receptor antagonist for acute treatment of migraine. At the time of implementation, ubrogepant was entering phase 2 development. DBS was implemented to acquire PK information proximal to an acute migraine event to enable exposure-response modeling...
November 14, 2017: Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/29133290/cd137-4-1bb-costimulation-modifies-dna-methylation-in-cd8-t-cell-relevant-genes
#4
M Angela Aznar, Sara Labiano, Angel Diaz-Lagares, Carmen Molina, Saray Garasa, Arantza Azpilicueta, Inaki Etxeberria, Alfonso R Sanchez-Paulete, Alan J Korman, Manel Esteller, Juan Sandoval, Ignacio Melero
CD137 (4-1BB) costimulation imprints long-term changes that instruct the ultimate behavior of T cells that have previously experienced CD137 ligation. Epigenetic changes could provide a suitable mechanism for these long-term consequences. Genome-wide DNA-methylation arrays were carried out on human peripheral blood CD8+ T lymphocytes stimulated with agonist monoclonal antibody to CD137, including urelumab, which is in phase I/II clinical trials for cancer immunotherapy. Several genes showed consistent methylation patterns in response to CD137 costimulation, which were confirmed by pyrosequencing in a series of healthy donors...
November 13, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/29117629/medical-and-dietary-interventions-for-preventing-recurrent-urinary-stones-in-children
#5
REVIEW
Adam Kern, Gwen Grimsby, Helen Mayo, Linda A Baker
BACKGROUND: Nephrolithiasis, or urinary stone disease, in children causes significant morbidity, and is increasing in prevalence in the North American population. Therefore, medical and dietary interventions (MDI) for recurrent urinary stones in children are poised to gain increasing importance in the clinical armamentarium. OBJECTIVES: To assess the effects of medical and dietary interventions (MDI) for the prevention of idiopathic urinary stones in children aged from one to 18 years...
November 9, 2017: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/29091379/dupilumab-for-moderate-to-severe-atopic-dermatitis
#6
R Vangipuram, S K Tyring
Atopic dermatitis (AD) is the most common chronic inflammatory disease affecting 2-10% of adults and up to 15-30% of children. Despite a rising prevalence, effective and safe therapeutics for patients with moderate-to-severe AD are limited due to toxicity and side effects. Dupilumab, an interleukin (IL)-4 and IL-13 antagonist that limits type 2 T helper (Th2) driven inflammatory activity, is a promising therapeutic option. In clinical trials, it has demonstrated efficacy by reducing clinical activity and symptoms, and showed improvement in the AD genomic phenotype, including a significant reduction in Th2 chemokines and reversal of key epidermal markers of AD...
November 2017: Skin Therapy Letter
https://www.readbyqxmd.com/read/29083112/immunity-to-crispr-cas9-and-cas12a-therapeutics
#7
REVIEW
Wei Leong Chew
Genome-editing therapeutics are poised to treat human diseases. As we enter clinical trials with the most promising CRISPR-Cas9 and CRISPR-Cas12a (Cpf1) modalities, the risks associated with administering these foreign biomolecules into human patients become increasingly salient. Preclinical discovery with CRISPR-Cas9 and CRISPR-Cas12a systems and foundational gene therapy studies indicate that the host immune system can mount undesired responses against the administered proteins and nucleic acids, the gene-edited cells, and the host itself...
October 30, 2017: Wiley Interdisciplinary Reviews. Systems Biology and Medicine
https://www.readbyqxmd.com/read/29050696/pharmacogenomics-in-acute-lymphoblastic-leukemia
#8
REVIEW
Shawn H R Lee, Jun J Yang
Pharmacogenomics is a fast-growing field of personalized medicine using a patient's genomic profile to determine drug disposition or response to drug therapy, in order to develop safer and more effective pharmacotherapy. Childhood acute lymphoblastic leukemia (ALL), being the most common malignancy in childhood, which is treated with uniform and standardized clinical trials, is remarkably poised for pharmacogenomic studies. In the last decade, unbiased genome-wide association studies have identified multiple germline risk factors that strongly modify host response to drug therapy...
September 2017: Best Practice & Research. Clinical Haematology
https://www.readbyqxmd.com/read/29026524/beyond-adhesion-%C3%A2-emerging-roles-for-integrins-in-control-of-the-tumor-microenvironment
#9
REVIEW
Whitney Longmate, C Michael DiPersio
While integrins were originally discovered as cell adhesion receptors, recent studies have reinforced the concept that integrins have central roles in cancer that extend far beyond controlling cell adhesion and migration. Indeed, as transmembrane cell surface receptors that occupy a critical position at the interface of cellular and extracellular interactions and are capable of both "inside-out" and "outside-in" signaling, integrins are uniquely poised to regulate the cell's ability to promote, sense, and react to changes in the tumor microenvironment...
2017: F1000Research
https://www.readbyqxmd.com/read/28926357/first-in-human-treatment-with-a-dendritic-cell-targeting-lentiviral-vector-expressing-ny-eso-1-lv305-induces-deep-durable-response-in-refractory-metastatic-synovial-sarcoma-patient
#10
Seth M Pollack, Hailing Lu, Sacha Gnjatic, Neeta Somaiah, Ryan B O'Malley, Robin L Jones, Frank J Hsu, Jan Ter Meulen
Effective induction of antitumor T cells is a pivotal goal of cancer immunotherapy. To this end, lentiviral vectors (LV) are uniquely poised to directly prime CD8 T-cell responses via transduction of dendritic cells in vivo and have shown promise as active cancer therapeutics in preclinical tumor models. However, until now, significant barriers related to production and regulation have prevented their widespread use in the clinic. We developed LV305, a dendritic cell-targeting, integration-deficient, replication incompetent LV from the ZVex platform, encoding the full-length cancer-testis antigen NY-ESO-1...
September 18, 2017: Journal of Immunotherapy
https://www.readbyqxmd.com/read/28902700/effectiveness-of-collaboration-between-emergency-department-and-intensive-care-unit-teams-on-mortality-rates-of-patients-presenting-with-critical-illness-a-systematic-review
#11
Kerchelle McDowald, Svetlana Direktor, Elizabeth A Hynes, Anna Sahadeo, Margaret E Rogers
BACKGROUND: The increasing volume of adult patients with critical illness entering emergency departments (EDs) burdens the resources of EDs worldwide. This subpopulation faces a high risk of mortality because they require specialized care which many EDs are not yet poised to deliver. An element crucial to delivering care and decreasing the mortality of critically ill patients in the ED is expert collaborative practice across disciplines. Several ED and intensive care unit (ICU) collaborative models exist including: emergency department intensive care units (EDICU) and medical emergency teams (MET)...
September 2017: JBI Database of Systematic Reviews and Implementation Reports
https://www.readbyqxmd.com/read/28891906/first-in-human-treatment-with-a-dendritic-cell-targeting-lentiviral-vector-expressing-ny-eso-1-lv305-induces-deep-durable-response-in-refractory-metastatic-synovial-sarcoma-patient
#12
Seth M Pollack, Hailing Lu, Sacha Gnjatic, Neeta Somaiah, Ryan B O'Malley, Robin L Jones, Frank J Hsu, Jan Ter Meulen
Effective induction of antitumor T cells is a pivotal goal of cancer immunotherapy. To this end, lentiviral vectors (LV) are uniquely poised to directly prime CD8 T-cell responses via transduction of dendritic cells in vivo and have shown promise as active cancer therapeutics in preclinical tumor models. However, until now, significant barriers related to production and regulation have prevented their widespread use in the clinic. We developed LV305, a dendritic cell-targeting, integration-deficient, replication incompetent LV from the ZVex platform, encoding the full-length cancer-testis antigen NY-ESO-1...
October 2017: Journal of Immunotherapy
https://www.readbyqxmd.com/read/28774338/-18-f-fdg-pet-ct-response-in-a-phase-1-2-trial-of-nab-paclitaxel-plus-gemcitabine-for-advanced-pancreatic-cancer
#13
Ronald L Korn, Daniel D Von Hoff, Mitesh J Borad, Markus F Renschler, Desmond McGovern, R Curtis Bay, Ramesh K Ramanathan
BACKGROUND: Positron emission tomography (PET) is poised to become a useful imaging modality in staging and evaluating therapeutic responses in patients with metastatic pancreatic cancer (mPC). This analysis from a phase 1/2 study examined the utility of early PET imaging in patients with mPC treated with nab-paclitaxel plus gemcitabine. METHODS: Tumors were measured by [(18)F]2-fluoro-2-deoxyglucose PET/computed tomography (CT) in patients who received nab-paclitaxel 100 (n = 13), 125 (n = 38), or 150 (n = 1) mg/m(2) plus gemcitabine 1000 mg/m(2) on days 1, 8, and 15 of a 28-day cycle...
August 3, 2017: Cancer Imaging: the Official Publication of the International Cancer Imaging Society
https://www.readbyqxmd.com/read/28675174/landmarks-in-the-treatment-of-muscle-invasive-bladder-cancer
#14
REVIEW
Niyati Lobo, Chloe Mount, Kawa Omar, Rajesh Nair, Ramesh Thurairaja, Muhammad Shamim Khan
Muscle-invasive bladder cancer is an aggressive disease associated with high morbidity and mortality. Radical cystectomy is the mainstay of treatment and has evolved since the first reported cystectomy in 1887 to include pelvic lymph node dissection and the creation of increasingly sophisticated urinary diversions, such as neobladders and pouches, which enable patients to maintain continence. Pioneering work in the 1970s established the therapeutic activity of cisplatin in patients with bladder cancer and resulted in the introduction of cisplatin-based neoadjuvant chemotherapy, which led to the first improvement in survival outcomes in decades...
September 2017: Nature Reviews. Urology
https://www.readbyqxmd.com/read/28622175/predictors-prognosis-and-management-of-new-clinically-important-atrial-fibrillation-after-noncardiac-surgery-a-prospective-cohort-study
#15
MULTICENTER STUDY
Pablo Alonso-Coello, Deborah Cook, Shou Chun Xu, Alben Sigamani, Otavio Berwanger, Soori Sivakumaran, Homer Yang, Denis Xavier, Luz Ximena Martinez, Pedro Ibarra, Purnima Rao-Melacini, Janice Pogue, Kelly Zarnke, Pilar Paniagua, Jack Ostrander, Salim Yusuf, P J Devereaux
BACKGROUND: Despite the frequency of new clinically important atrial fibrillation (AF) after noncardiac surgery and its increased association with the risk of stroke at 30 days, there are limited data informing their prediction, association with outcomes, and management. METHODS: We used the data from the PeriOperative ISchemic Evaluation trial to determine, in patients undergoing noncardiac surgery, the association of new clinically important AF with 30-day outcomes, and to assess management of these patients...
July 2017: Anesthesia and Analgesia
https://www.readbyqxmd.com/read/28619757/cdk4-6-inhibitors-sensitize-rb-positive-sarcoma-cells-to-wee1-kinase-inhibition-through-reversible-cell-cycle-arrest
#16
Ashleigh M Francis, Angela Alexander, Yanna Liu, Smruthi Vijayaraghavan, Kwang Hui Low, Dong Yang, Tuyen Bui, Neeta Somaiah, Vinod Ravi, Khandan Keyomarsi, Kelly K Hunt
Research into the biology of soft tissue sarcomas has uncovered very few effective treatment strategies that improve upon the current standard of care which usually involves surgery, radiation, and chemotherapy. Many patients with large (>5 cm), high-grade sarcomas develop recurrence, and at that point have limited treatment options available. One challenge is the heterogeneity of genetic drivers of sarcomas, and many of these are not validated targets. Even when such genes are tractable targets, the rarity of each subtype of sarcoma makes advances in research slow...
September 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28608597/perineal-techniques-during-the-second-stage-of-labour-for-reducing-perineal-trauma
#17
REVIEW
Vigdis Aasheim, Anne Britt Vika Nilsen, Liv Merete Reinar, Mirjam Lukasse
BACKGROUND: Most vaginal births are associated with trauma to the genital tract. The morbidity associated with perineal trauma can be significant, especially when it comes to third- and fourth-degree tears. Different interventions including perineal massage, warm or cold compresses, and perineal management techniques have been used to prevent trauma. This is an update of a Cochrane review that was first published in 2011. OBJECTIVES: To assess the effect of perineal techniques during the second stage of labour on the incidence and morbidity associated with perineal trauma...
June 13, 2017: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/28515847/pacemaker-recycling-a-notion-whose-time-has-come
#18
REVIEW
Mason W Runge, Timir S Baman, Sheldon Davis, Kevin Weatherwax, Ed Goldman, Kim A Eagle, Thomas C Crawford
The purpose of this paper is to summarize the need, feasibility, safety, legality, and ethical perspectives of pacemaker reutilization in low- and middle-income countries (LMICs). It will also describe, in-depth, Project My Heart Your Heart (PMHYH) as a model for pacemaker reuse in LMICs. The primary source of the discussion points in this paper is a collection of 14 publications produced by the research team at the University of Michigan and its collaborative partners. The need for pacemaker reutilization in LMICs is evident...
April 26, 2017: World Journal of Cardiology
https://www.readbyqxmd.com/read/28480326/combining-oncolytic-virotherapy-with-p53-tumor-suppressor-gene-therapy
#19
REVIEW
Christian Bressy, Eric Hastie, Valery Z Grdzelishvili
Oncolytic virus (OV) therapy utilizes replication-competent viruses to kill cancer cells, leaving non-malignant cells unharmed. With the first U.S. Food and Drug Administration-approved OV, dozens of clinical trials ongoing, and an abundance of translational research in the field, OV therapy is poised to be one of the leading treatments for cancer. A number of recombinant OVs expressing a transgene for p53 (TP53) or another p53 family member (TP63 or TP73) were engineered with the goal of generating more potent OVs that function synergistically with host immunity and/or other therapies to reduce or eliminate tumor burden...
June 16, 2017: Molecular Therapy Oncolytics
https://www.readbyqxmd.com/read/28428885/the-why-what-and-how-of-the-new-fact-standards-for-immune-effector-cells
#20
EDITORIAL
Marcela V Maus, Sarah Nikiforow
Novel cellular therapies outside of traditional hematopoietic stem cell transplantation or hematopoietic progenitor cell (HPC) therapy are currently under evaluation in clinical trials across the United States and around the world. Several cellular products, e.g., CD19-directed Chimeric Antigen Receptor (CAR) T cells, are poised for FDA approval and thus increased use at a wider range of academic centers within the next year, with the likelihood of dissemination to standard oncology practice once safety is confirmed...
2017: Journal for Immunotherapy of Cancer
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