tbuckley/cabot-search huggingface dataset:
PDCT-20. FEASIBILITY AND SAFETY OF SURGICAL BIOPSY FOR PATIENTS WITH DIPG: PRELIMINARY RESULTS FROM DIPG-BATS
Authors: Nalin Gupta, Liliana Goumnerova, Kanya Ayyanar, William Gump, Anne Bendel, Mahmoud Nagib, Daniel Bowers, Bradley Weprin, Amy-Lee Bredlau, Sridharan Gururangan, Herbert Fuchs, Kenneth Cohen, George Jallo, Kathleen Dorris, Michael Handler, Melanie Comito, Mark Dias, Jason R Fangusaro, Stewart Goldman, Tadanori Tomita, Tord Alden, Arthur DiPatri, Sharon Gardner, Matthias Karajannis, David Harter, Karen Gauvain, David Limbrick, Jeffrey Leonard, J Russ Geyer, Sarah Leary, Samuel Browd, Ziad Khatib, John Ragheb, Sanjiv Bhatia, Tobey MacDonald, Dolly Aguilera, Barun Brahma, Peter Manley, Susan Chi, Sabine Mueller, Anuradha Banerjee, Jeffrey Murray, Kellie Nazemi, Lissa Baird, Nathan Robison, Erin Kiehna, Mark Krieger, Eric Sandler, Philipp Aldana, Joanne Wang, Sandeep Sood, Donna Neuberg, Maneka Puligandla, Lianne Greenspan, Karen Wright, Michael Prados, Pratiti Bandopadhayay, Keith Ligon, Mark Kieran
Journal: Neuro-Oncology (2017)

The DIPG Biology and Treatment Study (DIPG-BATS) incorporated a surgical biopsy at presentation and stratified patients to receive FDA-approved agents chosen on the basis of specific biologic targets. Subjects were enrolled in the DIPG-BATS trial if the imaging appearance of the tumors had typical features of a DIPG. Surgical biopsies were performed after enrollment and prior to definitive treatment. Subjects were all treated with conventional fractionated external radiotherapy, and bevacizumab. Subjects were stratified to receive erlotinib or temozolomide, both agents, or neither agent. Whole-genome sequencing (WGS) and RNA-sequencing were performed on tumor samples but not used for treatment planning. Fifty-three patients were enrolled at 23 participating institutions, of which 50 underwent biopsy. The median age was 6.4 years, with a male to female ratio of 24::29. Surgical biopsies were performed using standard stereotactic techniques with a transcerebellar approach. There were no deaths attributed to the surgical procedure. Two patients experienced grade 3 toxicities during the procedure (one patient with apnea and one with hypertension). One patient experienced a neurologic deficit (left hemiparesis) that did not recover. Of the 50 patients biopsied, 46 provided sufficient tissue to perform the assays (92%, two-stage exact binomial 90% confidence interval 83-97%). Surgical biopsy of DIPGs is technically feasible, associated with acceptable risks, and can provide biologic data that informs treatment decision making.
Inflammatory osteolysis: a conspiracy against bone
Authors: Gabriel Mbalaviele, Deborah V. Novack, Georg Schett, Steven L. Teitelbaum
Journal: Journal of Clinical Investigation (2017)

There are many causes of inflammatory osteolysis, but regardless of etiology and cellular contexts, the osteoclast is the bone-degrading cell. Thus, the impact of inflammatory cytokines on osteoclast formation and function was among the most important discoveries advancing the treatment of focal osteolysis, leading to development of therapeutic agents that either directly block the bone-resorptive cell or do so indirectly via cytokine arrest. Despite these advances, a substantial number of patients with inflammatory arthritis remain resistant to current therapies, and even effective anti-inflammatory drugs frequently do not repair damaged bone. Thus, insights into events such as those impacted by inflammasomes, which signal through cytokine-dependent and -independent mechanisms, are needed to optimize treatment of inflammatory osteolysis.
Defining the paralympic athlete: normative values for scat major components in healthy paralympic athletes
Authors: William J Moreau, Taylor Walden, Dustin Nabhan
Journal: British Journal of Sports Medicine (2017)

Objective Describe normative baseline SCAT 2 and 3 (SCAT) performance in elite Paralympic athletes. Design Retrospective cohort. Setting United States Olympic Committee Sports Medicine Clinics. Participants Sixty-nine SCAT baseline evaluations were performed on a population of 60 elite athletes Paralympic (17 women and 43 men, mean age 30.1±7.3 years) representing 5 Summer and Winter Olympic sports as part of multimodal concussion programing. Intervention No intervention was applied. The SCAT evaluations were administered as a component of a baseline testing on healthy athletes. Main outcome measurements Baseline SCAT performance on major components is described. T-tests were used to compare differences in baseline performance by sex. Results During baseline evaluations, elite Paralympic athletes reported a mean (95%CI) of 2.2 (1.1–3.3) symptoms with an average symptom severity score of 4.7 (2.8–6.6). Mean scores on SCAT components in this population were; orientation 4.9 (4.8–5.0), immediate memory 14.3 (13.9–14.8), concentration 4.0 (3.7–4.2), tandem gait 15.4 (12.3–18.6), delayed recall 3.7 (3.4–4.0), balance 4.4 (1.9–7.06), SAC total 26.6 (25.8–27.4). This group reported a history of 2.6 (1.4–3.8) previous concussions. There were no significant differences between males and females in components of the SCAT. Conclusions Population specific normative values for baseline SCAT performance in a population of elite Paralympic athletes are presented in this cohort study. Clinical relevance Paralympic athletes are an understudied population. Clinicians are encouraged to reference population specific normative values when interpreting SCAT performance. For athletes with impairments, individual baselines may be preferred to the wide distribution of functional capacity. Acknowledgements None. Competing interests None.
Systolic Blood Pressure and Outcomes in Patients Hospitalized With Acute Heart Failure—Reply
Authors: Mihai Gheorghiade, Gregg C. Fonarow
Journal: JAMA (2007)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
TRTH-19. PRECLINICAL ANALYSIS OF SODIUM VALPROATE FOR THE TREATMENT OF DIPG BY CONVECTION ENHANCED DELIVERY
Authors: Clare Killick-Cole, Ali Bienemann, Daniel Asby, William Singleton, Marcella Wyatt, Lisa Boulter, Neil Barua, Steven Gill
Journal: Neuro-Oncology (2017)

There is a significant need to develop new treatment strategies to improve the prognosis of DIPG patients. We have previously shown that the HDAC inhibitor, sodium valproate (VPA), reduces the viability of DIPG cells in vitro. Whilst, VPA does cross the blood brain barrier, only 15% of serum concentrations reach the brain, therefore systemic delivery of VPA is unlikely to have significant anti-glioma effects without first incurring dose-limiting systemic toxicities. Convection enhanced delivery (CED) affords the direct administration of drugs to the tumour site, circumventing problems associated with central nervous system penetration of systemically administered drugs. Live/Dead assays were used to assess the effect of VPA on DIPG cell viability after 72 hours and sequential 6 hour drug exposures. In vitro neurotoxicity was determined by exposing normal hippocampal cells to VPA for 6 hours. To determine the feasibility of direct delivery to the brain, VPA was administered by CED to the brain of juvenile wistar rats. Toxicity was assessed by clinical and neuropathological examination of infused brain 21 days after treatment. In addition clearance and stability was analysed by LC-MS/MS. Results to date, demonstrate that VPA reduces cell viability in all DIPG cell lines tested. No significant differences were seen in cellular morphology and network of normal hippocampal derived glio-neuronal cultures in vitro. This was further substantiated by in vivo analysis of toxicity following acute VPA infusion by CED, showing minimal effect on neuronal and glial markers in normal brain. Mass spectrometric analysis determined VPA to be stable in artificial CSF and the half-life in rat brain to be two hours. This data suggests that VPA can feasibly be administered by CED to rat and supports further investigation into the in vivo efficacy of VPA and translation to the clinic.
Impact monitoring and king-devick ocular testing provide a relatively simple process for objectively identifying and managing concussion in sports participants
Authors: Adrian Cohen, Doug King, Alan J Pearce
Journal: British Journal of Sports Medicine (2017)

Objective This study presents data using multimodal assessment via impact sensors and oculomotor function to quantify neurophysiological changes in the acute period following concussion. Design Cohort study. Participants Data on impact magnitude and frequency were collected with a wireless head impact sensor (XPatch1) worn by senior amateur rugby players participating in a domestic season. King-Devick Tests2 were performed pre-season and after significant impact scores (PLA&gt;100 g, PRA&gt;10,000 rads/sec/sec).). Participants underwent a one hour baseline assessment of balance, cognition and transcranial magnetic stimulation testing. Following concussive episodes or significant head impacts (as measured by impact sensors), players were re-tested to elicit any differences and to assist in providing objective criteria for the return to play process. Interventions Any impact that resulted in a witnessed concussion or that was suspected on the basis of significant impact scores required post-match testing utilising the King-Devick test to help determine appropriate return to play readiness. Outcome measures Impact number, peak linear and peak rotational acceleration, risk weighted exposure. Time and errors completing the King-Devick test. Main result 20 concussions were detected in all, of which only 3 were witnessed (2 players unconscious on the field, one with balance disturbance resulting in removal from play). Conclusions A combination of regular impact monitoring and King-Devick Ocular testing provides a relatively simple process for objectively identifying and managing concussion in sports participants. Competing interests AJP is supported, in part, by a research grant by the Australian Football League
Concussed elite athletes have better tandem gait performance
Authors: Dustin Nabhan, Taylor Walden, William J Moreau
Journal: British Journal of Sports Medicine (2017)

Objective Describe tandem gait score performance in concussed elite athletes as compared to asymptomatic baselines. Design Within subjects, repeated measures. Setting United States Olympic Committee Sports Medicine Clinics Participants Six hundred forty-one elite athletes (291 women and 350 men, mean age 24.9±5.2 years) representing 23 Olympic sports participated in this study. Intervention The SCAT3 was administered during a preseason baseline and repeated as clinically indicated during initial evaluations and serially as part of a multimodal concussion management program. Outcome measures SCAT3 performance measures of concussed elite athletes were compared to baseline SCAT3 performance. Results Tandem gait performance was significantly better in concussed elite athletes than on athletes tested for healthy asymptomatic baselines (9.6 vs. 11.7, P&lt;0.001), despite concussed athletes reporting significantly higher total number of symptoms (6.4 vs. 2.1, P&lt;0.001) and symptom severity scores (13.1 vs. 3.4, P&lt;0.001) during concussion recovery. Conclusions There is a paradoxical relationship between concussion status and tandem gait performance in elite athletes, with concussed athletes performing better on average than athletes evaluated for a baseline SCAT3 evaluation. Clinical Relevance Tandem gait performance is not impaired in athletes with symptoms of concussion. Intrinsic motivation to return to play may result in enhanced tandem gait performance in concussed athletes. Competing interests None.
The impacts of different embolization techniques on splenic artery embolization for blunt splenic injury: a systematic review and meta-analysis
Authors: Jing-Jing Rong, Dan Liu, Ming Liang, Qing-Hua Wang, Jing-Yang Sun, Quan-Yu Zhang, Cheng-Fei Peng, Feng-Qi Xuan, Li-Jun Zhao, Xiao-Xiang Tian, Ya-Ling Han
Journal: Military Medical Research (2017)

Splenic artery embolization (SAE) has been an effective adjunct to the Non-operative management (NOM) for blunt splenic injury (BSI). However, the optimal embolization techniques are still inconclusive. To further understand the roles of different embolization locations and embolic materials in SAE, we conducted this system review and meta-analyses. Clinical studies related to SAE for adult patients were researched in electronic databases, included PubMed, Embase, ScienceDirect and Google Scholar Search (between October 1991 and March 2013), and relevant information was extracted. To eliminate the heterogeneity, a sensitivity analysis was conducted on two reduced study sets. Then, the pooled outcomes were compared and the quality assessments were performed using Newcastle-Ottawa Scale (NOS). The SAE success rate, incidences of life-threatening complications of different embolization techniques were compared by χ 2 test in 1st study set. Associations between different embolization techniques and clinical outcomes were evaluated by fixed-effects model in 2nd study set. Twenty-three studies were included in 1st study set. And then, 13 of them were excluded, because lack of the necessary details of SAE. The remaining 10 studies comprised 2nd study set, and quality assessments were performed using NOS. In 1st set, the primary success rate is 90.1% and the incidence of life-threatening complications is 20.4%, though the cases which required surgical intervention are very few (6.4%). For different embolization locations, there was no obvious association between primary success rate and embolization location in both 1st and 2nd study sets (P > 0.05). But in 2nd study set, it indicated that proximal embolization reduced severe complications and complications needed surgical management. As for the embolic materials, the success rate between coil and gelfoam is not significant. However, coil is associated with a lower risk of life-threatening complications, as well as less complications requiring surgical management. Different embolization techniques affect the clinical outcomes of SAE. The proximal embolization is the best option due to the less life-threatening complications. For commonly embolic material, coil is superior to gelfoam for fewer severe complications and less further surgery management.
Molecular diagnostics and lack of clinical allergy in helminth-endemic areas in Indonesia
Authors: Firdaus Hamid, Serge A. Versteeg, Aprilianto E. Wiria, Linda J. Wammes, Sitti Wahyuni, Taniawati Supali, Erliyani Sartono, Ronald van Ree, Maria Yazdanbakhsh
Journal: Journal of Allergy and Clinical Immunology (2017)
Dendritic Mesoporous Silica Nanoparticles for pH‐Stimuli‐Responsive Drug Delivery of TNF‐Alpha
Authors: Arne Kienzle, Sven Kurch, Janine Schlöder, Carsten Berges, Robert Ose, Jonathan Schupp, Andrea Tuettenberg, Henning Weiss, Jennifer Schultze, Svenja Winzen, Meike Schinnerer, Kaloian Koynov, Markus Mezger, Nikolas K. Haass, Wolfgang Tremel, Helmut Jonuleit
Journal: Advanced Healthcare Materials (2017)

Tumor necrosis factor-alpha (TNF-α) is a pleiotropic immune stimulatory cytokine and natural endotoxin that can induce necrosis and regression in solid tumors. However, systemic administration of TNF-α is not feasible due to its short half-life and acute toxicity, preventing its widespread use in cancer treatment. Dendritic mesoporous silica nanoparticles (DMSN) are used coated with a pH-responsive block copolymer gate system combining charged hyperbranched polyethylenimine and nonionic hydrophilic polyethylenglycol to encapsulate TNF-α and deliver it into various cancer cell lines and dendritic cells. Half-maximal effective concentration (EC50 ) for loaded TNF-α is reduced by more than two orders of magnitude. Particle stability and premature cargo release are assessed with enzyme-linked immunosorbent assay. TNF-α-loaded particles are stable for up to 5 d in medium. Tumor cells are grown in vitro as 3D fluorescent ubiquitination-based cell cycle indicator spheroids that mimic in vivo tumor architecture and microenvironment, allowing real-time cell cycle imaging. DMSN penetrate these spheroids, release TNF-α from its pores, preferentially affect cells in S/G2/M phase, and induce cell death in a time- and dose-dependent manner. In conclusion, DMSN encapsulation is demonstrated, which is a promising approach to enhance delivery and efficacy of antitumor drugs, while minimizing adverse side effects.
Seed-effect modeling improves the consistency of genome-wide loss-of-function screens and identifies synthetic lethal vulnerabilities in cancer cells
Authors: Alok Jaiswal, Gopal Peddinti, Yevhen Akimov, Krister Wennerberg, Sergey Kuznetsov, Jing Tang, Tero Aittokallio
Journal: Genome Medicine (2017)

Genome-wide loss-of-function profiling is widely used for systematic identification of genetic dependencies in cancer cells; however, the poor reproducibility of RNA interference (RNAi) screens has been a major concern due to frequent off-target effects. Currently, a detailed understanding of the key factors contributing to the sub-optimal consistency is still a lacking, especially on how to improve the reliability of future RNAi screens by controlling for factors that determine their off-target propensity.
Randomized Trial of Exercise on Quality of Life in Women With Ovarian Cancer: Women’s Activity and Lifestyle Study in Connecticut (WALC)
Authors: Yang Zhou, Brenda Cartmel, Linda Gottlieb, Elizabeth A Ercolano, Fangyong Li, Maura Harrigan, Ruth McCorkle, Jennifer A Ligibel, Vivian E von Gruenigen, Radhika Gogoi, Peter E Schwartz, Harvey A Risch, Melinda L Irwin
Journal: JNCI Journal of the National Cancer Institute (2017)

Ovarian cancer survivors experience a wide range of treatment side effects that can negatively affect health-related quality of life (HRQOL). Physical activity has been shown to improve HRQOL and cancer-related fatigue (CRF) for other cancer survivors; however, no large randomized controlled trial (RCT) has been conducted for ovarian cancer. This study examined the impact of a six-month RCT of exercise vs attention control on change in HRQOL (Short Form Health Survey-36) and CRF (Functional Assessment of Cancer Therapy-Fatigue Scale) in ovarian cancer survivors. Women (n = 144) were randomly assigned to study arms between May 1, 2010, and March 20, 2014. All statistical tests were two-sided. A total of 74 women were randomly assigned to exercise and 70 to attention control. A total of 113 (78.5%) of the participants completed the six-month assessment. Adherence to the exercise intervention was excellent (166.0±66.1 minutes/week in the exercise arm). At six months, women in the exercise arm had improved physical HRQOL (SF-36 Physical Component Summary Score) compared with the control arm, 1.8 (SD = 1.1) vs –2.0 (SD = 1.2) , respectively (group difference = 3.7, SD = 1.2, 95% confidence interval [CI] = 0.7 to 6.8, P = .02). No group differences were seen for change in mental HRQOL. There was a statistically significant improvement in the fatigue score (Functional Assessment of Cancer Therapy–Fatigue) for exercisers (4.0, SD = 1.1, 95% CI = 1.8 to 6.2, P < .001) but not for controls (1.2, SD = 1.2, 95% CI = –1.1 to 3.5, P = .31), with a between-group difference of 2.8 (SD = 1.5, 95% CI = –0.2 to 5.7, P = .06). We found a six-month home-based, telephone-delivered exercise intervention of primarily brisk walking to be associated with improved physical HRQOL in women with ovarian cancer. Given that higher HRQOL and exercise have both been associated with overall survival in women diagnosed with ovarian cancer, oncologists and primary care providers should recommend and refer women diagnosed with ovarian cancer to clinic- or community-based exercise programs.
Weekly vinorelbine and paclitaxel in elderly patients with advanced non-small cell lung cancer: A Fred and Pamela Buffett Cancer Center Clinical Trials Network phase II study.
Authors: Mary Mereta Huerter, M. Anne Kessinger, Addison R. Tolentino, Mehmet Sitki Copur, Holly Despiegelaere, Sarah Radniecki, Beth M Kos, Alissa S. Marr, Karin Swenson, Susan Kruse, Apar Kishor Ganti
Journal: Journal of Clinical Oncology (2015)

e19016 Background: Platinum-based doublet chemotherapy is the standard of care for advanced NSCLC for which the median age at diagnosis is 70 years. Despite a demonstrated benefit, the majority of patients over 65 years do not receive chemotherapy due to toxicity concerns. Vinorelbine and paclitaxel have single agent response rates of 20% in advanced NSCLC and preclinical studies show synergism between the two. Our phase II study evaluates the safety and efficacy of this combination in patients over 70 with advanced NSCLC. Methods: Patients with metastatic NSCLC were administered one cycle that comprised of 6 weekly doses of vinorelbine (22.5 mg/m2) and paclitaxel (40 mg/m2). Patients with radiographic progression noted on imaging two weeks after completion of the first cycle came off study; others received a second cycle. Toxicity was assessed after 10 patients enrolled and again after a total of 19 patients. The study was powered to detect a disease control rate (complete response + partial response + stable disease) of 30% with stable or improved quality of life score (n = 29). Other outcomes measured were safety and efficacy, progression free and overall survival and quality of life. Kaplan-Meier method was used for statistical analysis. Results: Mean age of the 19 enrolled patients was 76.9 years (range: 71-82 years). Enrollment was closed after the second interim analysis as it met the toxicity threshold with 6/19 patients developing grade 4 non-hematologic toxicities. Of the 16 evaluable patients, 7 completed the study. Causes of discontinuation were disease progression (n = 5), death (n = 3), infection (n = 3) and infusion reaction to paclitaxel (n = 1). The partial response rate was 26% (n = 5); another 21% (n = 4) had stable disease, while 37% (n = 7) had progressive disease. The median progression free survival was 3.48 months (95% CI: 1.4, 5.5 months) and the median overall survival was 7.8 months (95% CI: 1.9, 13.6 months). Conclusions: Although the combination met its response end points, increased toxicity makes this combination unsuitable for older patients. Quality of life data are being analyzed and will be reported at the time of the meeting. Clinical trial information: NCT00602797.