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Isabella Zhang, Silvia C Formenti, Jonathan P S Knisely
The brain has long been considered an immunologically privileged site, and the role of immunotherapy in treating intracranial disease has only recently been revived-with preclinical evidence showing that the systemic immune system responds to immunotherapy for intracranial disease, and with clinical evidence demonstrating improved locoregional control and survival compared with historical outcomes when immune-directed therapies are combined with radiation. Pharmaceutical industry-supported multi-institutional drug efficacy studies routinely exclude patients with brain metastases, so current evidence for treatment of brain metastases using stereotactic radiosurgery combined with immunotherapy comes from single-institution studies...
March 15, 2018: Oncology (Williston Park, NY)
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)
Pauline Funchain, Ahmad A Tarhini
Rapidly advancing genomic sequencing technologies are changing all areas of cancer, from diagnosis to surveillance, and prognostication to treatment. The role of genomic testing in melanoma is expanding, and multiple genomically based tests are available, including somatic tumor sequencing for actionable genetic alterations and tumor mutational burden, prognostic gene expression profiling from tumor tissue, and germline genetic testing from blood. The available testing options have varying levels of supporting data, from robust to preliminary...
March 15, 2018: Oncology (Williston Park, NY)
Nadine Oppermann, Jürgen Weitz, Christoph Reißfelder, Sören Torge Mees
In Germany, medical students in their final year will work in hospitals or medical offices to gain clinical experience. The final year is designed to prepare medical students for their work as junior doctors. It is divided into three parts and includes internal medicine and general surgery as mandatory parts. Many students develop enthusiasm or lack of enthusiasm while working in specific disciplines and often apply for jobs based on their experience in their final year. Despite the importance of this educational phase, the 36 medical faculties have implemented several different curricula and there is significant heterogeneity...
March 16, 2018: Zentralblatt Für Chirurgie
Mariella G Filbin, Dominik Sturm
Gliomas are the most common primary central nervous system (CNS) neoplasms in children and adolescents and are thought to arise from their glial progenitors or stem cells. Although the exact cells of origin for most pediatric gliomas remain to be identified, our current understanding is that specific cell populations during CNS development are susceptible to particular oncogenic events during certain time windows and thus give rise to pediatric gliomas with distinct histological, molecular, and clinical features...
February 2018: Seminars in Neurology
Elizabeth R Gerstner, Kristian W Pajtler
Ependymoma can arise throughout the whole neuraxis. In children, tumors predominantly occur intracranially, whereas the spine is the most prevalent location in adults. Significant variance in the grade II versus grade III distinction of ependymomas has led to the acknowledgment that the clinical utility of histopathological classification is limited. Epigenomic profiling efforts have identified molecularly distinct groups of ependymomas that adequately reflect the biological, clinical, and histopathological heterogeneities across anatomical compartments, age groups, and grades...
February 2018: Seminars in Neurology
Zachary J Reitman, Frank Winkler, Andrew E H Elia
Glioblastoma (GBM) is the most common primary malignant tumor of the central nervous system. The current standard of care for GBM is maximal resection followed by postoperative radiation with concomitant and adjuvant temozolomide. Despite this multimodality treatment, the median survival for GBM remains marginally better than 1 year. In the past decade, genome-wide analyses have uncovered new molecular features of GBM that have refined its classification and provided new insights into the molecular basis for GBM pathogenesis...
February 2018: Seminars in Neurology
Julie J Miller, Wolfgang Wick
The majority of World Health Organization grade II and grade III gliomas harbor heterozygous mutations in the metabolic enzyme isocitrate dehydrogenase 1 (IDH1), and tumors with an IDH wild-type status show molecular features of a glioblastoma and simply may constitute a separate disease entity. This discovery has led to a profound shift in the way that gliomas are classified and, consequently, how treatment decisions are made. We will review the current understanding of IDH- mutant gliomagenesis and the preclinical models being used to investigate the underlying biology of these tumors and to explore new therapeutic options for these patients...
February 2018: Seminars in Neurology
Martha Nowosielski, Patrick Y Wen
The identification of more effective therapies for brain tumors has been limited in part by the lack of reliable criteria for determining response and progression. Since its introduction in 1990, the MacDonald criteria have been used in neuro-oncology clinical trials to determine response, but they fail to address issues such as pseudoprogression, pseudoresponse, and nonenhancing tumor progression that have arisen with more recent therapies. The Response Assessment in Neuro-Oncology (RANO) working group, a multidisciplinary international group consisting of neuro-oncologists, medical oncologists, neuroradiologists, neurosurgeons, radiation oncologists, and neuropsychologists, was formed to improve response assessment and clinical trial endpoints in neuro-oncology...
February 2018: Seminars in Neurology
Daniel Cahill, Sevin Turcan
Malignant glioma is a common type of brain tumor that remains largely incurable. Although a definitive cell of origin of gliomas remains elusive, numerous population studies, sequencing efforts, and genetically engineered mouse models have contributed to our understanding of the early events that may lead to gliomagenesis. Herein we summarize our current knowledge on the population epidemiology of gliomas, heritable genetic risk factors, the somatic events that contribute to tumor evolution, and mouse models that have shed light on the glioma cell of origin...
February 2018: Seminars in Neurology
Katharine D Wenstrom, Mary E D'Alton, Daniel F O'Keefe
OBJECTIVE:  To conduct a survey of the members of the Society for Maternal-Fetal Medicine (SMFM) to determine the practice patterns of maternal-fetal medicine (MFM) subspecialists in the United States and to estimate the likelihood that our work force is sufficient to support the proposed MFM staffing requirements for level III and IV maternity centers. STUDY DESIGN:  All regular SMFM members in the United States were invited to answer a 26 question survey by email...
March 16, 2018: American Journal of Perinatology
Justin M Curley, Coleen Crouch, Joshua E Wilk
Introduction: Medical readiness for deployment is arguably the most important component of personnel readiness in the U.S. Army. Administrative documents called profiles provide individualized medical recommendations to the commander regarding how to best provide for a soldier's health and welfare, and contribute to an aggregated enumeration of a unit's overall readiness to deploy. Profiles that convey behavioral health (BH) limitations thus reflect what can be called the "behavioral health readiness" of the force...
March 14, 2018: Military Medicine
Po-Han Chen, Jen-Tsan Chi, Michael Boyce
In metazoans, thousands of intracellular proteins are modified with O-linked β-N-acetylglucosamine (O-GlcNAc) in response to a wide range of stimuli and stresses. In particular, a complex and evolutionarily conserved interplay between O-GlcNAcylation and oxidative stress has emerged in recent years. Here, we review the current literature on the connections between O-GlcNAc and oxidative stress, with a particular emphasis on major signaling pathways, such as KEAP1/NRF2, FOXO, NFκB, p53 and cell metabolism...
March 14, 2018: Glycobiology
Michael J Ingargiola, Felipe Molina Burbano, Amy Yao, Saba Motakef, Paymon Sanati-Mehrizy, Nikki M Burish, Lisa R David, Peter J Taub
Background: The recently increased minimum aesthetic surgery requirements set by the Plastic Surgery Residency Review Committee of the ACGME highlight the importance of aesthetic surgery training for plastic surgery residents. Participation in resident aesthetic surgery clinics has become an important tool to achieve this goal. Yet, there is little literature on the current structure of these clinics. Objectives: The authors sought to evaluate current practices of aesthetic resident-run clinics in the United States...
March 14, 2018: Aesthetic Surgery Journal
Carla T Murray, Matthew Schmit
Introduction: We estimate the effect on health care spending of an option to change TRICARE. Under the option, which is based on a proposal made by the Military Compensation and Retirement Modernization Commission (MCRMC), most beneficiaries could choose from a range of commercial health networks instead of the current TRICARE plans. Military treatment facilities would become network providers under the commercial plans. Materials and Methods: We used data from the Department of Defense (DoD) to estimate the cost of providing the current health care benefit to working-age retirees and their dependents and survivors, and active duty family members...
March 14, 2018: Military Medicine
Jiannan Dai, Lei Xing, Haibo Jia, Yinchun Zhu, Shaotao Zhang, Sining Hu, Lin Lin, Lijia Ma, Huimin Liu, Maoen Xu, Xuefeng Ren, Huai Yu, Lulu Li, Yanan Zou, Shaosong Zhang, Gary S Mintz, Jingbo Hou, Bo Yu
Aims: Plaque erosion is a significant substrate of acute coronary thrombosis. This study sought to determine in vivo predictors of plaque erosion in patients with ST-segment elevation myocardial infarction (STEMI). Methods and results: A prospective series of 822 STEMI patients underwent pre-intervention optical coherence tomography. Using established diagnostic criteria, 209 had plaque erosion (25.4%) and 564 had plaque rupture (68.6%). Plaque erosion was more frequent in women <50 years when compared with those ≥50 years of age (P = 0...
March 13, 2018: European Heart Journal
Dan Rusinaru, Yohann Bohbot, Anne Ringle, Sylvestre Maréchaux, Momar Diouf, Christophe Tribouilloy
Aims: In patients with severe aortic stenosis (AS) and preserved left ventricular ejection fraction (LVEF), low flow (LF) is currently defined using Doppler-echocardiography by a stroke volume index (SVi)<35 mL/m2. However, the relationship between LF and outcome remains unclear as data on normal reference values defining LF are scarce, and previous studies did not explore the risk associated with other SVi cut-points. We analysed the relationship between LF and mortality in severe AS to establish prognostic LF values associated with mortality risk...
March 13, 2018: European Heart Journal
Huanhuan Hu, Naoko Sasaki, Takayuki Ogasawara, Satsue Nagahama, Shamima Akter, Keisuke Kuwahara, Takeshi Kochi, Masafumi Eguchi, Ikuko Kashino, Taizo Murakami, Makiko Shimizu, Akihiko Uehara, Makoto Yamamoto, Tohru Nakagawa, Toru Honda, Shuichiro Yamamoto, Ai Hori, Chihiro Nishiura, Hiroko Okazaki, Teppei Imai, Akiko Nishihara, Toshiaki Miyamoto, Kentaro Tomita, Isamu Kabe, Tetsuya Mizoue, Naoki Kunugita, Seitaro Dohi
Introduction: We aimed to determine the prospective association of smoking status, smoking intensity, and smoking cessation with the risk of hearing loss in a large Japanese cohort. Methods: The cohort study included 50195 employees, who were aged 20-64 years and free of hearing loss at baseline. Participants were followed up for a maximum of 8 years. Pure-tone audiometric testing was performed annually to identify hearing loss at 1 and 4 kHz. Cox proportional hazards regression models were used to investigate the association between smoking and hearing loss...
March 14, 2018: Nicotine & Tobacco Research: Official Journal of the Society for Research on Nicotine and Tobacco
Brooke N Wolford, Cristen J Willer, Ida Surakka
The combination of Electronic Health Records (EHRs) with genetic data has ushered in the next wave of complex disease genetics. Population-based biobanks and other large cohorts provide sufficient sample sizes to identify novel genetic associations across the hundreds to thousands of phenotypes gleaned from EHRs. In this review we summarize the current state of these EHR-linked biobanks, explore ongoing methods development in the field, and highlight recent discoveries of genetic associations. We enumerate the many existing biobanks with EHRs linked to genetic data, many of which are available to researchers via application and contain sample sizes > 50,000...
March 14, 2018: Human Molecular Genetics
Nathan H Johnson, Carol Vidal, Flavius R W Lilly
Background: Current prevalence estimates are 15% for depression and 20% for anxiety disorders among college students. These disorders are known to negatively impact academic achievement and persistence. It is important to understand the effects of parental military service on the mental health of children across development. The purpose of this study is to examine the influence of being raised in a military household on current and historical depression and anxiety disorders among college students...
March 14, 2018: Military Medicine
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