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Amar Patel, Lawrence Fong
Immunotherapies have emerged as a revolutionary modality for cancer treatment, and a variety of immune-based approaches are currently being investigated in the field of prostate cancer. Despite the 2010 approval of sipuleucel-T, subsequent progress in prostate cancer immunotherapy development has been limited by disappointing results with novel vaccination approaches and by prostate cancer's general resistance to immune checkpoint blockade. Nevertheless, there remains strong preclinical and clinical evidence to suggest that prostate cancer is a susceptible target for immune therapies...
March 15, 2018: Oncology (Williston Park, NY)
Michelle M Valdez, Maureen Liwanag, Charles Mount, Rechell Rodriguez, Elisea Avalos-Reyes, Andrew Smith, David Collette, Michael Starsiak, Richard Green
Introduction: Inefficiencies in the command approval process for publications and/or presentations negatively impact DoD Graduate Medical Education (GME) residency programs' ability to meet ACGME scholarly activity requirements. A preliminary review of the authored works approval process at Naval Medical Center San Diego (NMCSD) disclosed significant inefficiency, variation in process, and a low level of customer satisfaction. In order to facilitate and encourage scholarly activity at NMCSD, and meet ACGME requirements, the Executive Steering Council (ESC) chartered an interprofessional team to lead a Lean Six Sigma (LSS) Rapid Improvement Event (RIE) project...
March 14, 2018: Military Medicine
Gordon G Wisbach, Joshua Peters, Jenise Leon Guerrero, Nelson Mozzini, Helen Metzger
Introduction: The obesity epidemic in the USA includes active duty service members in the military and effects physical readiness. At the Naval Medical Center San Diego command, the Health & Wellness Department is charged with administering the Weight Management Programs (WMP) for sailors in the San Diego area to ensure military physical readiness requirements. The optimal allocation of personnel and resources to manage these programs is paramount for mission success. We analyzed the cost and effectiveness of the WMPs for the active duty population stationed at Naval Medical Center San Diego (NMCSD) with the intent of offering potential recommendations for program optimization...
March 14, 2018: Military Medicine
Sharon Reif, Rachel Sayko Adams, Grant A Ritter, Thomas V Williams, Mary Jo Larson
Introduction: Soldiers are at risk for acute and chronic pain due to the mental and physical challenges of military duties and ongoing training for force readiness. With the burden of pain on any individual attributable across pain sources, a broad perspective that goes beyond prior characterizations of pain is important. We aim to further the understanding of pain's effects among non-deployed active duty soldiers and the Military Health System (MHS), by describing prevalence of 10 painful conditions, reported pain levels, duration of pain and impact of pain on military duty limitations...
March 14, 2018: Military Medicine
Rachel A Hoopsick, D Lynn Homish, Paul T Bartone, Gregory G Homish
Background: Much research has focused on stress related to deployments; however, a substantial proportion of soldiers never deploy. In a study of 1.3 million veterans, suicide risk was higher among veterans who had never deployed. Thus, not being deployed may have an impact on soldiers' well-being; however, no measures exist to assess emotions regarding non-deployment. We aimed to develop and test an original measure of non-deployment emotions. Methods: We examined the Non-Deployment Emotions (NDE) questionnaire, a novel four-item measure of guilt, unit value, unit camaraderie, and unit connectedness in a sample of never-deployed male and female US Army Reserve/National Guard (USAR/NG) soldiers (N = 174)...
March 14, 2018: Military Medicine
Brian Shiner, Christine Leonard Westgate, Vanessa Simiola, Richard Thompson, Paula P Schnurr, Joan M Cook
Objective: Available studies on implementation of evidence-based psychotherapy (EBP) for patients attending Department of Veterans Affairs (VA) residential post-traumatic stress disorder (PTSD) programs rely on therapist self-report of EBP delivery. Patient-level data on receipt of EBP are needed both to corroborate therapist self-report and to understand patient factors that predict receipt of EBPs for PTSD. Materials and Methods: We identified 159 therapists from 38 VA residential PTSD programs who responded to a survey about EBP implementation during the 2015 fiscal year (FY15)...
March 14, 2018: Military Medicine
Christine A DeForest, Virginia Blackman, John E Alex, Lauren Reeves, Alejandra Mora, Crystal Perez, Joseph Maddry, Domenique Selby, Benjamin Walrath
Introduction: Military prehospital and en route care (ERC) directly impacts patient morbidity and mortality. Provider knowledge and skills are critical variables in the effectiveness of ERC. No Navy doctrine defines provider choice for patient transport or requires standardized provider training. Frequently, Search and Rescue Medical Technicians (SMTs) and Navy Nurses (ERC RNs) are tasked with this mission though physicians have also been used. Navy ERC provider training varies greatly by professional role...
March 14, 2018: Military Medicine
Gregory D Bowden, Kirkwood M Land, Roberta M O'Connor, Heather M Fritz
The apicomplexan parasite Sarcocystis neurona is the primary etiologic agent of equine protozoal myeloencephalitis (EPM), a serious neurologic disease of horses. Many horses in the U.S. are at risk of developing EPM; approximately 50% of all horses in the U.S. have been exposed to S. neurona and treatments for EPM are 60-70% effective. Advancement of treatment requires new technology to identify new drugs for EPM. To address this critical need, we developed, validated, and implemented a high-throughput screen to test 725 FDA-approved compounds from the NIH clinical collections library for anti-S...
February 16, 2018: International Journal for Parasitology, Drugs and Drug Resistance
Silvia Salerno, Aída Nelly García-Argáez, Elisabetta Barresi, Sabrina Taliani, Francesca Simorini, Concettina La Motta, Giorgio Amendola, Stefano Tomassi, Sandro Cosconati, Ettore Novellino, Federico Da Settimo, Anna Maria Marini, Lisa Dalla Via
Inhibition of angiogenesis via blocking vascular endothelial growth factor receptor (VEGFR) signaling pathway emerged as an established approach in anticancer therapy. So far, many monoclonal antibodies and ATP-competitive small molecule inhibitors have been clinically validated and approved. In this study, structure-activity relationships (SAR) within the 2-phenylamino-substituted benzothiopyrano[4,3-d]pyrimidine class of kinase inhibitors were further refined by the synthesis and biological evaluation of new compounds 1-21 featuring different substitution patterns on the pendant phenyl moiety, combined with H, OCH3 , or Cl at 8-position...
March 7, 2018: European Journal of Medicinal Chemistry
Sophie Outh-Gauer, Marie Alt, Christophe Le Tourneau, Jérémy Augustin, Chloé Broudin, Cassandre Gasne, Thomas Denize, Haitham Mirghani, Elizabeth Fabre, Madeleine Ménard, Florian Scotte, Eric Tartour, Cécile Badoual
Cancer occurrence can be understood as the result of dysfunctions in immune tumoral microenvironment. Here we review the recent understandings of those microenvironment changes, regarding their causes and prognostic significance in head and neck (HN) carcinoma. We will focus on HN squamous cell cancer (SCC) and nasopharyngeal carcinomas (NPC). Their overall poor prognosis may be improved with immunotherapy in a subset of patients, as supported by current clinical trials. However, finding reliable markers of therapeutic response is crucial for patient selection, due to potential severe adverse reactions and high costs...
March 1, 2018: Cancer Treatment Reviews
Ruiting Lin, Siyuan Xia, Changliang Shan, Dong Chen, Yijie Liu, Xue Gao, Mei Wang, Hee-Bum Kang, Yaozhu Pan, Shuangping Liu, Young Rock Chung, Omar Abdel-Wahab, Taha Merghoub, Michael Rossi, Ragini R Kudchadkar, David H Lawson, Fadlo R Khuri, Sagar Lonial, Jing Chen
Dietary supplements such as vitamins and minerals are widely used in the hope of improving health but may have unidentified risks and side effects. In particular, a pathogenic link between dietary supplements and specific oncogenes remains unknown. Here we report that chondroitin-4-sulfate (CHSA), a natural glycosaminoglycan approved as a dietary supplement used for osteoarthritis, selectively promotes the tumor growth potential of BRAF V600E-expressing human melanoma cells in patient- and cell line-derived xenograft mice and confers resistance to BRAF inhibitors...
March 15, 2018: Molecular Cell
Lynn Jakobs
BACKGROUND: Medullary thyroid cancer (MTC) is a rare cancer that has historically been managed by endocrinologists. In 2011, the first of several multi- targeted tyrosine kinase inhibitors was approved as treatment for MTC. These drugs have changed the management of MTC to teams that include oncologists and oncology nurses. OBJECTIVES: This article illustrates MTC diagnostics, surveillance, management of adverse drug reactions, and disease progression through a case study...
April 1, 2018: Clinical Journal of Oncology Nursing
Karen Kinsley, Wendy Pritchett
Recent approaches in treating pancreatic adenocarcinoma, an aggressive disease with limited survival, include the use of liposomal irinotecan as an option when first-line therapy has failed. Liposomal irinotecan has been approved in combination with 5-fluorouracil and leucovorin for patients with metastatic pancreatic cancer. Liposomal irinotecan is a newer therapy requiring oncology nurses to obtain knowledge and skills for proper administrating, monitoring of hypersensitivity reactions during infusion, managing side effects, and providing patient education...
April 1, 2018: Clinical Journal of Oncology Nursing
Gennaro Ilardi, Daniela Russo, Silvia Varricchio, Giovanni Salzano, Giovanni Dell'Aversana Orabona, Virginia Napolitano, Rosa Maria Di Crescenzo, Alessandra Borzillo, Francesco Martino, Francesco Merolla, Massimo Mascolo, Stefania Staibano
Human Papilloma Virus (HPV) can play a causative role in the development of sinonasal tract malignancies. In fact, HPV may be the most significant causative agent implicated in sinonasal tumorigenesis and is implicated in as many as 21% of sinonasal carcinomas. To date, there are no definitive, reliable and cost-effective, diagnostic tests approved by the FDA for the unequivocal determination of HPV status in head and neck cancers. We followed an exhaustive algorithm to correctly test HPV infection, including a sequential approach with p16INK4a IHC, viral DNA genotyping and in situ hybridization for E6/E7 mRNA...
March 16, 2018: International Journal of Molecular Sciences
Clémence Granier, Alain Gey, Charles Dariane, Arnaud Mejean, Marc-Olivier Timsit, Charlotte Blanc, Virginie Verkarre, Camélia Radulescu, Elisabeth Fabre, Yann Vano, Stéphane Oudard, Cécile Badoual, Éric Tartour
T cells harboring multiple co-inhibitory molecules lose their anti-tumoral functionality. PD-1 is a clinically approved target in cancer therapy, but its expression alone does not mean dysfunctionality. The expression of Tim-3 on numerous cell types (T cell, Treg, dendritic cell, myeloid cells) favors tumor escape to immune cells. Within many tumors, PD-1/Tim-3 coexpressing CD8-T cells lose their ability to secrete cytokines (IFNγ, IL-2, TNFα) and their intratumoral infiltration correlates with a bad prognosis...
March 2018: Médecine Sciences: M/S
Bryan Markinson, Mahmoud Ghannoum, Tate Winter, Anthony Rycerz, Fernando Rock, Aditya K Gupta
Onychomycosis is a fungal infection of the nail primarily caused by the dermatophytes Trichophyton rubrum and Trichophyton mentagrophytes. The topical-based treatment of onychomycosis remains a challenge because of the difficulty associated with penetrating the dense, protective structure of the keratinized nail plate. Tavaborole is a novel small-molecule antifungal agent recently approved in the United States for the topical treatment of toenail onychomycosis. The low molecular weight, slight water solubility, and boron chemistry of tavaborole maximize nail penetration after topical application, allowing for effective targeting of the infection in the nail bed...
January 2018: Journal of the American Podiatric Medical Association
Oscar H L Bing
Ammonia plays a central role in the life and death of all living organisms and has been studied for over one hundred years. Ammonia is necessary for growth and development but it is toxic in excess and, as a result, differing methods of ammonia neutralization have evolved. Following physiological and pathological stress to the heart, tissue ammonia levels rise. Local ammonia neutralization may be inadequate and excess ammonia may exert its toxic effects. Phenylbutyrate (PBA), which is FDA approved for the treatment of elevated blood ammonia in urea cycle disorders, provides an accessory pathway for ammonia clearance...
March 16, 2018: American Journal of Physiology. Heart and Circulatory Physiology
Kristin Bjørnland, Maren Hinna, Gunnar Aksnes, Kjetil Juul Stensrud, Kjetil Ertresvåg, Anniken Bjørnstad-Østensen, Truls Sanengen, Pål-Dag Line, Ingegerd Aagenæs, Lars Aabakken, Ragnhild Emblem, Runar Almaas
OBJECTIVES: The importance of case load for treatment of extrahepatic biliary atresia (BA) is debated. The aim of this study was to register results of BA treatment in a small volume centre. METHODS: Retrospective chart review study of patients with BA treated from 2000 to 2017. The institutional review board approved the study. RESULTS: Forty-five babies were identified of which 42 (93%) are alive. Forty-one patients had a Kasai portoenterostomy (PE), two had a hepaticojejunostomy and two had a primary liver transplantation...
March 16, 2018: Scandinavian Journal of Gastroenterology
Young-A Heo, Emma D Deeks
A fixed-dose combination of the hepatitis C virus (HCV) NS5B polymerase inhibitor sofosbuvir, the HCV NS5A inhibitor velpatasvir and the HCV NS3/4A protease inhibitor voxilaprevir (sofosbuvir/velpatasvir/voxilaprevir; Vosevi® ) is approved in the EU for the treatment of chronic HCV genotype 1, 2, 3, 4, 5 or 6 infection in adults. In the phase III POLARIS trials, in patients who had HCV genotype 1-6 infection with or without compensated cirrhosis, overall rates of sustained virological response at 12 weeks post-treatment (SVR12 ) with sofosbuvir/velpatasvir/voxilaprevir were high after 8 weeks of treatment in direct-acting antiviral (DAA)-naïve patients and 12 weeks of treatment in DAA-experienced patients...
March 15, 2018: Drugs
Massimo Galia, Francesco Agnello, Gianvincenzo Sparacia, Domenica Matranga, Domenico Albano, Massimo Midiri, Roberto Lagalla
PURPOSE: To retrospectively analyze the evolution of indeterminate hepatocellular nodules in cirrhotic patients on serial Gd-EOB-DPTA-enhanced MRI, and to identify predictors of HCC development. MATERIALS AND METHODS: This IRB approved study included 33 cirrhotic patients with 69 indeterminate hepatocellular nodules (mean diameter 1.1 cm) at baseline Gd-EOB-DPTA-enhanced MRI and a Gd-EOB-DPTA-enhanced-MRI follow-up of at least 2 years. Two radiologists evaluated size and signal intensity of each nodule at baseline and follow-up...
March 15, 2018: La Radiologia Medica
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