tbuckley/cabot-search huggingface dataset:
NCCN Guidelines Insights: Breast Cancer, Version 1.2017
Authors: William J. Gradishar, Benjamin O. Anderson, Ron Balassanian, Sarah L. Blair, Harold J. Burstein, Amy Cyr, Anthony D. Elias, William B. Farrar, Andres Forero, Sharon Hermes Giordano, Matthew P. Goetz, Lori J. Goldstein, Steven J. Isakoff, Janice Lyons, P. Kelly Marcom, Ingrid A. Mayer, Beryl McCormick, Meena S. Moran, Ruth M. O'Regan, Sameer A. Patel, Lori J. Pierce, Elizabeth C. Reed, Kilian E. Salerno, Lee S. Schwartzberg, Amy Sitapati, Karen Lisa Smith, Mary Lou Smith, Hatem Soliman, George Somlo, Melinda Telli, John H. Ward, Dorothy A. Shead, Rashmi Kumar
Journal: Journal of the National Comprehensive Cancer Network (2017)

These NCCN Guidelines Insights highlight the important updates/changes to the surgical axillary staging, radiation therapy, and systemic therapy recommendations for hormone receptor-positive disease in the 1.2017 version of the NCCN Guidelines for Breast Cancer. This report summarizes these updates and discusses the rationale behind them. Updates on new drug approvals, not available at press time, can be found in the most recent version of these guidelines at NCCN.org.
Eric Lewis Blair
Authors: Stephen Blair
Journal: BMJ (2017)

Eric Lewis Blair held house officer posts in the Royal Victoria Infirmary in Newcastle upon Tyne. After national service in Germany, he worked for Sir Stanley Davidson in Edinburgh as medical registrar. In 1956 he was appointed lecturer in the department of physiology in Newcastle. He became senior lecturer in 1964, the same year in which he was awarded his MD in 1964. In 1968 he …
Abstract 76: Ablation of Parkin Attenuates Acute Cardiotoxicity of Doxorubicin Associated with Mitophagy
Authors: Chengqun Huang, Allen Andres, Jennifer Ramil, Roberta Gottlieb
Journal: Circulation Research (2012)

Parkin is an E3 ubiquitin ligase expressed in heart, skeletal muscle and brain. However, the function of Parkin in the heart is largely unknown. We previously showed in cardiomyocytes and the ischemic heart that Parkin translocates to mitochondria to selectively remove damaged mitochondria through autophagy. It has been shown that Doxorubicin (Dox) induces cardiotoxicity characterized by impaired mitochondrial respiration and energetic failure (PLoS One. 2010; 5:e12733). Here, we investigated the role of Parkin in acute Doxorubicin-induced cardiac dysfunction in mice. Acute cardiotoxicity was induced by IP injection of a single dose of 15 mg/kg Doxorubicin hydrochloride in 10-12 wk-old C57BL/6J (WT) mice and Parkin knock out (PKO) mice matched by age, sex and body weight. Analysis of histology, hemodynamics, and mitochondrial content was performed 7d after Dox. Dox induced significant loss of body weight but less in PKO mice (20% in WT vs 12% in PKO). Dox toxicity was more severe in male mice. Signs of discomfort (decreased mobility and hunched posture) were noted 4d after Dox in 90% of WT male mice vs. 20% of PKO males. Mortality at 7d was 30% in WT mice vs. 10% in PKO mice. Dox caused reduction in heart size to a greater extent (10-20%) in WT than in PKO mice. Significant deterioration of hemodynamics was seen in WT mice 7d after Dox; this was attenuated in PKO mice. Because Parkin mediates mitophagy, we examined autophagy and mitochondrial content 7d in Dox treated hearts. Dox resulted in extensive autophagy and decreased mitochondrial protein content in WT mice; this was attenuated in PKO mice. These results suggest that high-dose Dox triggers extensive Parkin-dependent mitophagy which may contribute to acute cardiac dysfunction. We suggest that therapy directed at the PINK1-Parkin mitophagy pathway may be beneficial in the setting of doxorubicin overdose.
Erratum: International uniform response criteria for multiple myeloma
Authors: B G M Durie, J-L Harousseau, J S Miguel, J Bladé, B Barlogie, K Anderson, M Gertz, M Dimopoulos, J Westin, P Sonneveld, H Ludwig, G Gahrton, M Beksac, J Crowley, A Belch, M Boccadaro, I Turesson, D Joshua, D Vesole, R Kyle, R Alexanian, G Tricot, M Attal, G Merlini, R Powles, P Richardson, K Shimizu, P Tosi, G Morgan
Journal: Leukemia (2006)

Correction to: Leukemia (2006) 20, 1467–1473. doi:10.1038/sj.leu.2404284 It has been identified by the authors that there was an error in the author list. The following author was omitted in error. M Cavo, Institute of Hematology and Medical Oncology 'Seràgnoli', University of Bologna, Italy. The corrected list is mentioned here.
Follow-up of Positive Fecal Test Results
Authors: Carolyn M. Rutter, John M. Inadomi
Journal: JAMA (2017)

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 Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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) 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
Diagnostic Accuracy of Spectralis SD OCT Automated Macular Layers Segmentation to Discriminate Normal from Early Glaucomatous Eyes
Authors: Marta Pazos, Agnieszka Anna Dyrda, Marc Biarnés, Alicia Gómez, Carlos Martín, Clara Mora, Gianluca Fatti, Alfonso Antón
Journal: Ophthalmology (2017)
Response assessment in medulloblastoma and leptomeningeal seeding tumors: recommendations from the Response Assessment in Pediatric Neuro-Oncology committee
Authors: Katherine E Warren, Gilbert Vezina, Tina Y Poussaint, Monika Warmuth-Metz, Marc C Chamberlain, Roger J Packer, Alba A Brandes, Moshe Reiss, Stewart Goldman, Michael J Fisher, Ian F Pollack, Michael D Prados, Patrick Y Wen, Susan M Chang, Christelle Dufour, David Zurakowski, Rolf D Kortmann, Mark W Kieran
Journal: Neuro-Oncology (2017)

Lack of standard response criteria in clinical trials for medulloblastoma and other seeding tumors complicates assessment of therapeutic efficacy and comparisons across studies. An international working group was established to develop consensus recommendations for response assessment. The aim is that these recommendations be prospectively evaluated in clinical trials, with the goal of achieving more reliable risk stratification and uniformity across clinical trials. Current practices and literature review were performed to identify major confounding issues and justify subsequently developed recommendations; in areas lacking scientific investigations, recommendations were based on experience of committee members and consensus was reached after discussion. Recommendations apply to both adult and pediatric patients with medulloblastoma and other seeding tumors. Response should be assessed using MR imaging (brain and spine), CSF cytology, and neurologic examination. Clinical imaging standards with minimum mandatory sequence acquisition that optimizes detection of leptomeningeal metastases are defined. We recommend central review prior to inclusion in treatment cohorts to ensure appropriate risk stratification and cohort inclusion. Consensus recommendations and response definitions for patients with medulloblastomas and other seeding tumors have been established; as with other Response Assessment in Neuro-Oncology recommendations, these need to now be prospectively validated in clinical trials.
Abstract 133: Impaired TNFα Signaling Deregulates Basal Nrf2-Antioxidant System in Myocardium
Authors: Gobinath Shanmugam, Sakthivel Ramasamy, Sandeep B Shelar, Madhusudhanan Narasimhan, Jennifer Hong, Nancy Atieno, Wayne E Bradley, Louis Dell`Italia, Victor M Darley-Usmar, John R Hoidal, Namakkal S Rajasekaran
Journal: Circulation Research (2015)

Antagonizing TNF-α and its signaling is proven to be a successful therapeutic strategy in various disease processes. Although blocking TNF-α signaling attenuated the disease activity, the overarching clinical contraindications remains to be a greater concern and reasons for the adverse effects are largely unknown. TNF-α induces ROS and as ROS is pivotal for activation of antioxidant transcription factor, Nrf2, we posit that any impairment in TNF-α signaling could affect Nrf2-dependent basal redox homeostasis. HL-1 cardiomyocytes, TNFR1/2 double knockout mice (DKO) that shows hampered TNF-α signaling were used as experimental models. Electron Paramagnetic Resonance Spectroscopy (EPR) measurements revealed that as low as 2 ng TNF-α/ml, ROS was induced significantly (p10ng/ml in HL-1 cells. TNF-α (2-5 ng /ml, for 2 h) evoked robust (p&lt;0.05, n=3) nuclear translocation of Nrf2 and increased nuclear binding (Trans AM DNA binding analysis) along with significant (p&lt;0.05) induction in trans-activation of Nrf2 targets. Additionally, this was associated with 2-fold increase (p&lt;0.05) in intracellular glutathione (GSH) that is associated with significant cell death only at higher (&gt;10 - 50 ng/ml) and later time points (12 h and 24 h). These results suggest that TNF-α mediated ROS induction activates Nrf2 dependent antioxidant system in cardiomyocytes. In vivo experiments with TNFR1/2 DKO demonstrates that the expression of Nrf2-regulated genes were significantly downregulated indicating a weakened antioxidant system. Also, the acute exercise stress (AES) induced Nrf2 trans-activation observed in WT mice was significantly blunted in TNFR1/2 DKO suggesting a need for TNF signaling in stress induced Nrf2 activation. These results support the concept that complete and/or sustained blockade of TNF signaling may result in compromised Nrf2-dependent antioxidant defense in the myocardium. This further necessitates that during chronic anti-TNF-α treatment, a finely tuned and maintenance of specific threshold of TNF-α signaling is essential to avoid oxidant stress based complications in cardiovascular system.
DOES FOOT PRONATION CAUSES VASCULAR CONSTRICTION?
Authors: Evi Wezenbeek, Tine Willems, Nele Mahieu, Ine Van Caekenberghe, Dirk De Clercq, Erik Witvrouw
Journal: British Journal of Sports Medicine (2017)

Background The most popular hypothesis of the etiology of Achilles tendinopathy suggests that excessive pronation causes conflicting rotational motions, leading to a vascular constriction of the Achilles tendon, described as the “whipping phenomenon” (Clement et al ., 1984). Although several studies identified pronation as a risk factor for the development of Achilles tendinopathy, the hypothesis that foot pronation causes vascular constriction of the tendon has not been investigated. Objective Therefore, the aim of this study was to investigate whether the amount of pronation during running influences the Achilles tendon blood flow. Design Cross-sectional study. Setting Runners Service Lab, Zwijndrecht, Belgium. Patients (or Participants) Twenty-five experienced runners (average running time 6.1±2.4 hours/week) aged 34.5±10.2 years participated in this study. Interventions (or Assessment of Risk Factors) 2D-lower limb kinematics during barefoot and shod running in both frontal and sagittal plane were assessed. Blood flow of the Achilles tendon was measured before and after barefoot and shod running, by use of the oxygen-to-see device. Main Outcome Measurements The increase of blood flow after running was registered as outcome variable. Mixed models analyses were executed with kinematic variables as fixed predictors. Results The results of this study confirm that the more pronation excursion during running, the lower the increase in blood flow after running in both insertion and midportion (p=0.085 and 0.037, respectively). In addition, this study revealed that a higher average pronation velocity indicates a lower increase in blood flow after running at insertion (p=0.044). Next, this study also showed that the dorsiflexion excursion or the foot strike pattern was not correlated with blood flow after running. Conclusions We can conclude that our findings indicate that foot pronation causes vascular constriction of the Achilles tendon, and therefore support this aspect of the whipping phenomenon.
P13.01 Transcriptome analysis of metastatic brain lesions of gastric carcinoma
Authors: C. Junjeong, S. Kim, S. Kang
Journal: Neuro-Oncology (2017)

Metastasis of gastric carcinoma to the brain is very rare and highly fatal. Little has been published regarding the transcriptome profile of metastatic brain lesions of gastric carcinoma. We performed a transcriptome analysis of bilateral metastatic brain tumors originated from the stomach. A 60-year old man was diagnosed as a gastric cancer and treated the disease with surgery and chemotherapy, but multiple brain metastatic lesions were identified in the right frontal area and left temporal area, with motor weakness and dysphasia. A palliative brain mass excision was performed in bilateral brain lesions and RNA sequencing of both lesions and primary lesion were performed. Comparison between primary and metastatic lesions as well as bilateral metastatic lesions were revealed series of genes that were differentially expressed between primary and metastatic lesions. IPA pathway analysis revealed upregulated markers such as metalloprotease (MMP1, MMP2 and MMP3) in bilateral metastatic lesions compared to the primary lesions. In addition, TGF-beta1 and TNF was predicted to be activated as an upstream regulator in bilateral metastatic lesions. There were findings that suggested the immune cell trafficking was differently present in metastatic lesions. Taken together, this study disclosed novel markers and altered transcriptomal structure in metastatic brain lesions of gastric carcinoma.
OS02.6 risk factors for hypersomnia and narcolepsy and response to therapy in survivors of childhood brain tumors
Authors: R. B. Khan, T. E. Merchant
Journal: Neuro-Oncology (2017)

Introduction: According to international headache society guidelines, narcolepsy is diagnosed when mean sleep onset latency on multiple sleep latency test (MSLT) is <8 minutes and two or more sleep onset REM sleep episodes are present. Hypersomnia has similar criteria except only one or less sleep onset REM episodes are present on MSLT. A negative overnight polysomnogram is also required the night before the MSLT. Daytime sleepiness is recognized in brain tumor survivors but few studies have reported results of overnight polysomnogram and MSLT, risk factors for development of hypersomnia and narcolepsy, or response to therapy. Our objectives for this study were to understand prevalence of hypersomnia and narcolepsy in childhood brain tumor patients, describe the risk factors for its development, and response to stimulant therapy. Materials and methods: After obtaining institutional review board approval, medical records were reviewed of 156 brain tumor survivors coded as having sleep disorder, hypersomnia or narcolepsy. Hypersomnia or narcolepsy was diagnosed according to the international headache society classification based on overnight polysomnogram and MSLT. Each affected survivor was matched by gender, and age and time from tumor diagnosis to 2–3 survivors without reported daytime sleepiness. Study variables included tumor location, radiation dose, number of surgeries, ventricular shunt, and body mass index. Response to pharmacologic therapy was assessed via parent report. Results: The 39 survivors with hypersomnia (n=13) and narcolepsy (n=26) were matched with 110 controls. A total of 2336 brain tumor patients were treated during the study period, translating to an estimated hypersomnia and narcolepsy prevalence of 1670/100,000. Median time from tumor diagnosis to hypersomnia/narcolepsy was 6.1 years (range 0.4 - 13.2), and 4.7 years (range -1.5 - 10.4) from radiation. Of the many variables studied, only midline tumor location (OR 5.3, CI 2.2 - 12.7, p = <0.001) and radiation dose of >30 Gray (p = <0.01) correlated with hypersomnia and narcolepsy, while posterior fossa tumor location was protective (OR 0.1, CI 0.03 - 0.35, p=<0.001). Most of 37 survivors treated with stimulants showed improvement in wakefulness and school performance (response rate CI 0.97 [0.86 - 0.99] and 0.83 [0.65 - 0.94]); two were treated with strategic naps. CONCLUSION: Hypersomnia and narcolepsy prevalence of 1670/100,000 among childhood brain tumor survivors is much higher than 20–50/100,000 reported in general population. Midline tumor location and >30 gray radiation to the brain strongly correlated with hypersomnia and narcolepsy, while posterior fossa tumor location may be protective. Stimulant therapy is beneficial and is generally well tolerated in this population.
P09.26 FET PET radiomics - diagnosis of pseudoprogression in glioblastoma patients based on textural features
Authors: P. Lohmann, C. Lerche, G. Stoffels, C. P. Filss, C. Stegmayr, B. Neumaier, N. J. Shah, K. Langen, N. Galldiks
Journal: Neuro-Oncology (2017)

Introduction: The differentiation of pseudoprogression (PsP) from tumor progression (TP) in glioblastoma patients is difficult on the basis of standard MRI alone. Textural feature analysis as part of the concept of radiomics offers a quantitative method to describe tumor heterogeneity and gains increasing interest in the field of neuro-oncology. In our study, we investigated the potential of textural features of O-(2-[18F]fluoroethyl)-L-tyrosine (FET) PET to discriminate between PsP and TP in glioblastoma patients. Materials and Methods: Twenty-three newly diagnosed glioblastoma patients with MRI findings suspicious for TP within 12 weeks after completion of chemoradiation with temozolomide underwent an additional dynamic FET PET scan. Volumes-of-interest were defined on summed images from 20-40 min post-injection (p.i.) by a 3-dimensional auto-contouring process using a tumor-to-brain ratio (TBR) of 1.6 or more. For each lesion, TBRs and the time-activity curves (TACs) of the FET uptake were determined. The TACs were used to evaluate the dynamic FET PET parameters time-to-peak (TTP), slope (slope of linear regression line 20-50 min p.i.) and intercept (intercept of linear regression line with y-axis). Additionally, 39 textural parameters were calculated using the software LifeX (lifexsoft.org). The diagnostic accuracy of TBRs, TTP, slope, intercept, and textural parameters to discriminate between PsP and TP was evaluated using ROC analyses. In order to further increase the diagnostic accuracy, parameters were combined using linear logistic regression for classification of PsP and TP. Results: Fourteen patients had a clinico-radiological diagnosis of TP and nine patients had PsP. The FET PET parameters TBRmean, TBRmax, TTP and intercept yielded a diagnostic accuracy to discriminate between PsP and TP of 79%, 79%, 58%, 63%, respectively. The dynamic FET PET parameter slope yielded the highest diagnostic accuracy of 83% to discriminate between PsP and TP. Two textural features showed a comparable accuracy of 79%. The diagnostic accuracy could not be increased by combination of parameters. Conclusions: Textural features yielded a comparable diagnostic accuracy for diagnosis of pseudoprogression in glioblastoma patients in comparison with static and dynamic FET PET parameters. Textural features might yield additional valuable information for this highly relevant clinical problem and should be further evaluated in larger cohort prospective studies.
Association of tumor infiltrating lymphocytes (TILs) with pathologic response in baseline and post-brief exposure HER2+ breast cancer biopsies from BrUOG-211B.
Authors: Stefanie Avril, Vinay Varadan, Kristy Miskimen, Jahnavi Gollamudi, Maysa M. Abu-Khalaf, George Somlo, William M. Sikov, Lyndsay Harris, Shaveta Vinayak
Journal: Journal of Clinical Oncology (2015)

619 Background: Increased TILs are prognostic and predictive of therapy response in HER2+ breast cancer (BC). BrUOG-211B, a phase II neoadjuvant trial included early stage HER2+ BC pts treated with single-agent trastuzumab (T) or nab-paclitaxel (N) followed by 6 cycles of T, N and carboplatin combination. This correlative study evaluated TILs in both baseline and post-brief exposure biopsies in association with pathologic response. Methods: Stromal (sTILs) and intratumoral (iTILs) TILs were evaluated on H&E sections at baseline (n = 46) and post-brief exposure (n = 43) and scored by deciles (mean of multiple core biopsies) according to the TILs Working Group guidelines. Pathologic response was assessed by residual cancer burden (RCB) index and grouped as responders (R = pCR/RCB 0 & RCB I) or non-responders (NR = RCB II & III). Results: Of 60 eligible pts 49 were available for analysis (49% R). Median iTILs were 10% [range 10-40%] and 20% [10-70%], median sTILs were 30% [10-100%] and 35% [20-100%] at baseline and post-brief exposure respectively. sTILs and iTILs were highly correlated (r = 0.8). Higher iTILs (p = 0.02) and sTILs (p < 0.01) were significantly associated with ER-neg status. Median sTILs were significantly higher in R vs NR at both baseline (35% vs 25%; p = 0.02) and post-brief exposure (50% vs 25%; p < 0.01). iTILs were not significantly associated with response. Overall, each 10% increase in baseline (OR 1.4; p = 0.03) and post-brief exposure sTILs (OR 1.5; p = 0.01) was associated with higher response, independent of ER-status. Lymphocyte predominant BC ( ≥ 50% sTILs) was seen in 22% and not significantly associated with response (70% vs 47% R; p = 0.2). There was no significant change in iTILs or sTILs after brief-exposure to T, and a non-significant trend for increase after N. Conclusions: Levels of sTILs do not change significantly in HER2+ BC following brief-exposure to single-agent T or N based on morphologic assessment; however, both baseline and post-brief exposure sTILs significantly predict for pathologic response. Further analyses are needed to determine potential changes in lymphocytic subpopulations.