tbuckley/cabot-search huggingface dataset:
NF1+/− Hematopoietic Cells Accelerate Malignant Peripheral Nerve Sheath Tumor Development without Altering Chemotherapy Response
Authors: Rebecca D. Dodd, Chang-Lung Lee, Tess Overton, Wesley Huang, William C. Eward, Lixia Luo, Yan Ma, Davis R. Ingram, Keila E. Torres, Diana M. Cardona, Alexander J. Lazar, David G. Kirsch
Journal: Cancer Research (2017)

Haploinsufficiency in the tumor suppressor NF1 contributes to the pathobiology of neurofibromatosis type 1, but a related role has not been established in malignant peripheral nerve sheath tumors (MPNST) where NF1 mutations also occur. Patients with NF1-associated MPNST appear to have worse outcomes than patients with sporadic MPNST, but the mechanism underlying this correlation is not understood. To define the impact of stromal genetics on the biology of this malignancy, we developed unique mouse models that reflect the genetics of patient-associated MPNST. Specifically, we used adenovirus-Cre injections to generate MPNST in Nf1Flox/Flox; Ink4a/ArfFlox/Flox and Nf1Flox/-; Ink4a/ArfFlox/Flox paired littermate mice to model tumors from NF1-wild-type and NF1-associated patients, respectively. In these models, Nf1 haploinsufficiency in hematopoietic cells accelerated tumor onset and increased levels of tumor-infiltrating immune cells comprised of CD11b+ cells, monocytes, and mast cells. We observed that mast cells were also enriched in human NF1-associated MPNST. In a coclinical trial to examine how the tumor microenvironment influences the response to multiagent chemotherapy, we found that stromal Nf1 status had no effect. Taken together, our results clarify the role of the NF1-haploinsufficient tumor microenvironment in MPNST. Cancer Res; 77(16); 4486-97. ©2017 AACR.
Doctors have medical and social responsibilities in the Trump era
Authors: George A Gellert
Journal: BMJ (2017)

Merino and colleagues express concern about the Trump administration and call for the scientific and healthcare communities to commit to serving the public’s best interests.1

Mikhail Gorbachev recently wrote, “Politicians and military leaders sound increasingly belligerent, and defence doctrines more dangerous. Commentators and TV personalities are joining the bellicose chorus. It all looks as if the world is preparing for war.” He noted that the 80% reduction in the nuclear arsenals of superpowers in the 1980s was enabled by the awareness of leaders that “nuclear war cannot be won and must …
Abstract 248: Prolonged Adult Cardiac Arrest With Enhanced Cardiopulmonary Resuscitation and Sodium Nitroprusside: A Case Series
Authors: Jason C Schultz, Emily Caldwell, Mohammad Sarraf, Jim Kolbeck, Demetris Yannopoulos
Journal: Circulation (2013)

Introduction: Sudden cardiac death remains the leading cause of death in the United States, and overall survival with good neurological function nationally is about 8%. Prolonged refractory cardiac arrest requires an efficient method to maintain viability to the vital organs until a reversible cause, if present, can be treated. Sodium Nitroprusside Enhanced CPR, or SNPeCPR, is a new form of CPR consisting of active compression-decompression (ACD), impendence threshold device (ITD), abdominal binding, and large doses of sodium nitroprusside. We present here a series of 6 patients in whom these methods were utilized in the setting of cardiac arrest in the cardiac catheterization laboratory. Methods: 6 patients who suffered cardiac arrest (5 VT/VF and 1 PEA) and were treated for an average time of 32±12 minutes before arrival to the cardiac catheterization laboratory. Utilizing a LUCAS® device in combination with an ITD allowed for prolonged periods of CPR during which time percutaneous coronary intervention was performed to re-establish coronary blood flow. Abdominal binding was performed, and finally, alternating boluses of 2 and 1 mg of sodium nitroprusside for a total of 4 doses were given as treatment for no reflow in the coronary vascular bed throughout the duration of CPR. The etiology of the cardiac arrest was ostial LAD occlusion (4 cases), left main occlusion (1) contrast induced anaphylactic reaction and PEA (1). Results: Six patients were successfully treated with SNPeCPR. The mean time of CPR was 58±17 minutes. Hemodynamic measurements during CPR approached pre-arrest physiologic levels (mean±STD SBP/DBP was 88±23/38±12) . 5/6 patients survived to hospital discharge. All survivors had normal neurological function at hospital discharge and 1-month clinic follow up Cerebral Performance Category score of 1. Average LVEF at hospital discharge was 48±18 % . 4/5 survivors were alive at one year follow up. Conclusions: Sodium nitroprusside, in combination with mechanical adjuncts to CPR, is a safe and effective method of prolonged resuscitation. Further prospective studies will be required to further assess the efficacy of SNPeCPR in cases of prolonged cardiac arrest.
Characterizing glioma microenvironment with ultra-high gradient diffusion MRI.
Authors: Ina Ly, Barbara Wichtmann, Susie Yi Huang, Aapo Nummenmaa, Ovidiu Andronesi, Qiuyun Fan, William T. Curry, Daniel P. Cahill, Alexandra J Golby, Tracy Batchelor, Jayashree Kalpathy-Cramer, Bruce R. Rosen, Elizabeth Robins Gerstner
Journal: Journal of Clinical Oncology (2017)

2050 Background: The infiltrating nature of gliomas, particularly into the peritumoral area, is a major barrier to improving clinical outcome as microscopic disease remains even after apparent gross total resection. Conventional T1 post-contrast and T2/FLAIR MRI do not capture full tumor extent. A better imaging biomarker is needed to improve differentiation between tumor, peritumoral area and normal brain. Methods: 4 pre-surgical patients with non-enhancing, FLAIR-hyperintense lesions suspicious for glioma underwent ultra-high gradient diffusion MRI on the Connectome MRI scanner, a unique scanner with maximum gradient strength of 300 mT/m enabling mapping of cellular microstructures on a micron-level scale. The FLAIR area was defined as the tumor region of interest (ROI). Radiographically normal appearing brain up to 1 cm around the FLAIR area was defined as the peritumoral ROI. Using a novel 3 compartment diffusion model (Linear Multiscale Model), the volume fraction of water (VFW) was calculated within restricted (intracellular), hindered (extracellular) and free (CSF) spaces. VFW in the tumor, peritumoral ROI, contralateral normal white matter (WM) and cortex were compared. Results: Within the tumor ROI, the median VFW in the restricted compartment was decreased vs. the peritumoral ROI (↓ 34%), WM (↓ 46%) and cortex (↓ 18%) while median VFW in the hindered compartment was increased vs. the peritumoral ROI (↑ 26%), WM (↑ 54%) and cortex (↑ 25%). Within the peritumoral ROI, median VFW in the hindered compartment was increased compared to WM (↑ 23%). 3 patients had available histopathology revealing isocitrate dehydrogenase-mutant gliomas. Conclusions: Using ultra-high gradient diffusion MRI and a novel diffusion model, we detected distinct diffusion patterns in the tumor and peritumoral area not seen on conventional MRI. Lower VFW in the restricted compartment within the tumor may reflect decreased intracellular water mobility due to enlarged nuclei. Higher VFW in the hindered compartment in the tumor and peritumoral area may reflect higher degree of tissue permeability and edema. MRI-pathology and larger cohort validation studies are underway to elucidate microenvironment changes in response to treatment.
Prise en charge endoscopique des ictères par obstruction hilaire métastatique
Authors: T Duboeuf, JP Barbieux, J Viguier, EH Metman, E Dorval
Journal: Endoscopy (2005)

Il existe peu de données spécifiques à la prise en charge endoscopique palliative des ictères par obstruction du hile hépatique d'origine métastatique. A partir d'une série hospitalière monocentrique, les objectifs de notre étude étaient d'évaluer l'impact de la mise en place d'une prothèse biliaire chez des malades présentant un ictère par obstruction hilaire métastatique.
Selective HDAC6 Inhibitor ACY-241, an Oral Tablet, Combined with Pomalidomide and Dexamethasone: Safety and Efficacy of Escalation and Expansion Cohorts in Patients with Relapsed or Relapsed-and-Refractory Multiple Myeloma (ACE-MM-200 Study)
Authors: Ruben Niesvizky, Paul G. Richardson, Andrew J. Yee, Ajay K Nooka, Marc S Raab, Kenneth H. Shain, Nashat Y. Gabrail, Jeffrey Matous, Amit B. Agarwal, James Hoffman, Sumit Madan, John M. Pagel, Jesus San Miguel, Philippe Moreau, Maria-Victoria Mateos, Thierry Facon, David Tamang, Simon S Jones, Robert J Markelewicz, Catherine Wheeler, Nikolaus S. Trede, Noopur Raje, Evangelos Terpos, William I. Bensinger
Journal: Blood (2016)
Clinical Outcomes in Patients with Diffuse Large B Cell Lymphoma with Partial Responses to First-Line R-CHOP Chemotherapy: Prognostic Value of Secondary IPI Scores and FDG-PET
Authors: Hyewon Lee, Yu Ri Kim, Soo-Jeong Kim, Yong Park, Hyeon-Seok Eom, Sung Yong Oh, Hyo Jung Kim, Hye Jin Kang, Won-Sik Lee, Joon Ho Moon, Young-Woong Won, Myung Hee Chang, Hye In Park, Jin Seok Kim
Journal: Blood (2016)
CNS Tumors in Neurofibromatosis
Authors: Jian Campian, David H. Gutmann
Journal: Journal of Clinical Oncology (2017)

Neurofibromatosis (NF) encompasses a group of distinct genetic disorders in which affected children and adults are prone to the development of benign and malignant tumors of the nervous system. The purpose of this review is to discuss the spectrum of CNS tumors arising in individuals with NF type 1 (NF1) and NF type 2 (NF2), their pathogenic etiologies, and the rational treatment options for people with these neoplasms. This article is a review of preclinical and clinical data focused on the treatment of the most common CNS tumors encountered in children and adults with NF1 and NF2. Although children with NF1 are at risk for developing low-grade gliomas of the optic pathway and brainstem, individuals with NF2 typically manifest low-grade tumors affecting the cranial nerves (vestibular schwannomas), meninges (meningiomas), and spinal cord (ependymomas). With the identification of the NF1 and NF2 genes, molecularly targeted therapies are beginning to emerge, as a result of a deeper understanding of the mechanisms underlying NF1 and NF2 protein function. As we enter into an era of precision oncology, a more comprehensive awareness of the factors that increase the risk of developing CNS cancers in affected individuals, coupled with a greater appreciation of the cellular and molecular determinants that maintain tumor growth, will undoubtedly yield more effective therapies for these cancer predisposition syndromes.
Evaluation of tumor immune infiltrate as a determinant of response to neo-adjuvant lapatinib and trastuzumab (LT) in HER2-positive (+) breast cancer (BC).
Authors: Carmine De Angelis, Chandandeep Nagi, Cliff Hoyt, Liu Linying, Kristin Roman, Chichung Wang, Yi Zheng, Tao Wang, Rena Mao, Susan G. Hilsenbeck, Carolina Gutierrez, Antonio C. Wolff, C. Kent Osborne, Mothaffar F. Rimawi, Rachel Schiff
Journal: Journal of Clinical Oncology (2016)

608 Background: Dual HER2 blockade with LT without chemotherapy resulted in a substantial pathologic complete response (pCR) rate in HER2+ BC patients (pts) (TBCRC006). High levels of tumor infiltrating lymphocytes (TILs) at diagnosis have shown to be associated with greater benefit to T and chemotherapy in early-stage HER2+ BC pts. However the predictive value of TILs, TILs’ subsets, and other immune cells in pts receiving anti-HER2 treatment alone without chemotherapy is still unknown. Methods: Pre-treatment biopsies from pts enrolled in the TBCRC006 trial were used to investigate tumor immune infiltrate at diagnosis. Hematoxylin and eosin (H&E)-stained slides were evaluated as currently recommended (Ann Oncol 26: 259, 2015) for the % of stromal TILs; a threshold of 60% was used to define lymphocyte-predominant BC (LPBC). Single formalin-fixed paraffin-embedded slides from 10 cases were co-stained for CD4, CD8, CD20, CD68, FoxP3, cytokeratin, and DAPI by multiplexed immunofluorescence (m-IF) using PerkinElmer Opal system. Multispectral imaging and digital analysis to visualize and quantify specific immune infiltrates are being performed using PerkinElmerVectra system. Results: TILs evaluation was available for 59 of the 64 pts who were evaluable for pathologic response. Twelve of 59 pts (20%) exhibited a LBPC. The pCR rate was numerically higher in LBPC compared to non-LPBC (50% vs. 19%, P = 0.057). Multispectral imaging successfully captured and quantified multiple immune cell types in all the so far m-IF-stained samples. The density of stromal TILs (calculated as the total number of cells positive for the above immune markers/mm2) significantly correlated with % of stromal TILs evaluated on the H&E-stained slides (r = 0.76, P = 0.01). Conclusions: LBPC was associated with numerically higher pCR rate than non-LPBC in patients with HER2+ BC treated with anti-HER2 agents without chemotherapy. However, P-value did not reach statistical significance. Characterizing TILs with m-IF is feasible and may help correlate various TIL subpopulations with response to treatment. Complete results for the entire cohort will be presented at the meeting.
Disease model discovery from 3,328 gene knockouts by The International Mouse Phenotyping Consortium
Authors: Terrence F Meehan, Nathalie Conte, David B West, Julius O Jacobsen, Jeremy Mason, Jonathan Warren, Chao-Kung Chen, Ilinca Tudose, Mike Relac, Peter Matthews, Natasha Karp, Luis Santos, Tanja Fiegel, Natalie Ring, Henrik Westerberg, Simon Greenaway, Duncan Sneddon, Hugh Morgan, Gemma F Codner, Michelle E Stewart, James Brown, Neil Horner, Melissa Haendel, Nicole Washington, Christopher J Mungall, Corey L Reynolds, Juan Gallegos, Valerie Gailus-Durner, Tania Sorg, Guillaume Pavlovic, Lynette R Bower, Mark Moore, Iva Morse, Xiang Gao, Glauco P Tocchini-Valentini, Yuichi Obata, Soo Young Cho, Je Kyung Seong, John Seavitt, Arthur L Beaudet, Mary E Dickinson, Yann Herault, Wolfgang Wurst, Martin Hrabe de Angelis, K C Kent Lloyd, Ann M Flenniken, Lauryl M J Nutter, Susan Newbigging, Colin McKerlie, Monica J Justice, Stephen A Murray, Karen L Svenson, Robert E Braun, Jacqueline K White, Allan Bradley, Paul Flicek, Sara Wells, William C Skarnes, David J Adams, Helen Parkinson, Ann-Marie Mallon, Steve D M Brown, Damian Smedley
Journal: Nature Genetics (2017)
Endocrine treatment-related symptoms and outcomes in breast cancer: A systematic review and meta-analysis.
Authors: Shusen Wang, Qiufan Zheng, Wen Xia, Fei Xu, Ge Qin, Qianyi Lu, Ruoxi Hong, Tao Qin, Xin An, Cong Xue, Jia Jia Huang, Roujun Peng, Zhongyu Yuan, Yanxia Shi
Journal: Journal of Clinical Oncology (2016)

e12001 Background: Endocrine therapy is associated with definite improvements in disease-free survival in hormone receptor-positive breast cancer, but also with many adverse events. We conducted a systematic review and meta-analysis to examine whether newly occurring treatment-related adverse events, including vasomotor symptoms and musculoskeletal symptoms, were associated with outcomes. Methods: EMBASE, Web of Science, PubMed, and the Cochrane library were searched to identify studies that compared treatment efficacy between patients in whom adverse events did and did not occur during hormone therapy. Hazard ratios (HRs) and associated 95% confidence intervals (CIs) for disease-free survival (DFS) and overall survival (OS) were estimated and pooled using random-effects models. All statistical tests were two-sided. Results: Of 6413 citations identified, nine studies incorporating 30022 patients were included in the meta-analysis. The presence of newly occurring endocrine symptoms was associated with improved DFS in patients compared to patients without newly occurring symptoms (HR = 0.77; 95% CI = 0.68 to 0.87). Results were consistent across different subgroups: symptom collection via patient response (HR = 0.78, 95% CI = 0.68–0.89), symptom collection via a prespecified checklist (HR = 0.72, 95% CI = 0.54–0.96), vasomotor symptoms (HR = 0.76, 95% CI = 0.66–0.87), musculoskeletal symptoms (HR = 0.75, 95% CI = 0.60–0.94), aromatase inhibitor (HR = 0.69, 95% CI 0.57–0.85), and tamoxifen (HR = 0.74, 95% CI = 0.60–0.93). However, no significant difference in OS was observed between the two groups (HR = 0.83; 95% CI = 0.56–1.24). Conclusions: Endocrine treatment-emergent adverse events were correlated with superior survival outcomes and may therefore be helpful in predicting treatment efficacy of hormone therapy in patients with breast cancer.
Cardiac Testing After Emergency Department Evaluation for Chest Pain
Authors: Benjamin C. Sun, Rita F. Redberg
Journal: JAMA Internal Medicine (2017)

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Volumetric variation pre and postoperative in low-grade gliomas (LGG) assessed by mean tumor diameter (MTD).
Authors: Natalia Moreno Perez Fraile, Vanessa Montes Santos, Marcella Coelho Mesquita, Rossana Mendonza LÃ Â³pez, Fabiana Campos Cordeiro Hirata, Aline Sgnolf Ayres, Olavo Feher
Journal: Journal of Clinical Oncology (2016)

e13523 Background: LGG grow progressively over time before transforming to high-grade gliomas. A mathematical model of evolution of gliomas, taking into account not only the proliferation but also migration of tumor cells, predicts a linear growth of MTD on MRI. This study aims to evaluate the impact of attempt surgical resection on MTD and its dynamics. Methods: Retrospective analysis of clinical and radiological findings of 175 consecutive patients (pts) diagnosed with LGG (WHO grade II) at the Instituto do Câncer do Estado de São Paulo (ICESP), from May 2008 to June 2013, followed up to June 2015. Thirty six patients underwent surgical attempt, and had a pre and postoperative MRI retrievable from our electronic archive. MTD is defined as cubic root of the products of the largest diameters in the anteroposterior and perpendicular axes (axial plane) in FLAIR sequences and the largest diameter in craniocaudal (coronal plane), using T2-weighted sequences. The primary end point was volumetric assessment of tumor resection based on MTD variation. Univariable analysis was performed using paired T-Student test, correlating: age, seizures, ECOG performance status (PS), hystologic subtype and localization to extent of MTD variation. Survival analysis was performed using Kaplan-Meier curves and log-rank test for comparison between survival curves. We used the software SPSS for Windows v.18 ©. The 5% significance level was adopted for statistical tests. Results: Themedian MTD variation was 30,09% of reduction of MTD value considering before and after surgery. With a median follow up of 28 months, univariate analysis did not identify any significant independent predictor for MTD variation or OS. MTD variation analyzed as a categorical variable using a cutoff of 50% did not impact on OS (p = 0.289). Conclusions: Despite our analysis limitations, results suggest that surgery impact on OS cannot be seen in medium or short term, assessed by MTD variation. However, assessment of MTD variations in LGG is feasible and reproducible and might be a valuable surrogate for true volumetric tumor measurement and warrants further studies.
Reconstruction of the mouse extrahepatic biliary tree using primary human extrahepatic cholangiocyte organoids
Authors: Fotios Sampaziotis, Alexander W Justin, Olivia C Tysoe, Stephen Sawiak, Edmund M Godfrey, Sara S Upponi, Richard L Gieseck, Miguel Cardoso de Brito, Natalie Lie Berntsen, María J Gómez-Vázquez, Daniel Ortmann, Loukia Yiangou, Alexander Ross, Johannes Bargehr, Alessandro Bertero, Mariëlle C F Zonneveld, Marianne T Pedersen, Matthias Pawlowski, Laura Valestrand, Pedro Madrigal, Nikitas Georgakopoulos, Negar Pirmadjid, Gregor M Skeldon, John Casey, Wenmiao Shu, Paulina M Materek, Kirsten E Snijders, Stephanie E Brown, Casey A Rimland, Ingrid Simonic, Susan E Davies, Kim B Jensen, Matthias Zilbauer, William T H Gelson, Graeme J Alexander, Sanjay Sinha, Nicholas R F Hannan, Thomas A Wynn, Tom H Karlsen, Espen Melum, Athina E Markaki, Kourosh Saeb-Parsy, Ludovic Vallier
Journal: Nature Medicine (2017)
Prevention of incisional hernia with prophylactic onlay and sublay mesh reinforcement versus primary suture only in midline laparotomies (PRIMA): 2-year follow-up of a multicentre, double-blind, randomised controlled trial
Authors: An P Jairam, Lucas Timmermans, Hasan H Eker, Robert E G J M Pierik, David van Klaveren, Ewout W Steyerberg, Reinier Timman, Arie C van der Ham, Imro Dawson, Jan A Charbon, Christoph Schuhmacher, André Mihaljevic, Jakob R Izbicki, Panagiotis Fikatas, Philip Knebel, René H Fortelny, Gert-Jan Kleinrensink, Johan F Lange, Hans J Jeekel, Jeroen Nieuwenhuizen, Wim C J Hop, Pim C W Burger, Hence J Verhagen, Pieter J Klitsie, Michiel van de Berg, Markus Golling
Journal: The Lancet (2017)
CONSORT Statement for Randomized Trials of Nonpharmacologic Treatments: A 2017 Update and a CONSORT Extension for Nonpharmacologic Trial Abstracts
Authors: Isabelle Boutron, Douglas G. Altman, David Moher, Kenneth F. Schulz, Philippe Ravaud
Journal: Annals of Internal Medicine (2017)

Incomplete and inadequate reporting is an avoidable waste that reduces the usefulness of research. The CONSORT (Consolidated Standards of Reporting Trials) Statement is an evidence-based reporting guideline that aims to improve research transparency and reduce waste. In 2008, the CONSORT Group developed an extension to the original statement that addressed methodological issues specific to trials of nonpharmacologic treatments (NPTs), such as surgery, rehabilitation, or psychotherapy. This article describes an update of that extension and presents an extension for reporting abstracts of NPT trials. To develop these materials, the authors reviewed pertinent literature published up to July 2016; surveyed authors of NPT trials; and conducted a consensus meeting with editors, trialists, and methodologists. Changes to the CONSORT Statement extension for NPT trials include wording modifications to improve readers' understanding and the addition of 3 new items. These items address whether and how adherence of participants to interventions is assessed or enhanced, description of attempts to limit bias if blinding is not possible, and specification of the delay between randomization and initiation of the intervention. The CONSORT extension for abstracts of NPT trials includes 2 new items that were not specified in the original CONSORT Statement for abstracts. The first addresses reporting of eligibility criteria for centers where the intervention is performed and for care providers. The second addresses reporting of important changes to the intervention versus what was planned. Both the updated CONSORT extension for NPT trials and the CONSORT extension for NPT trial abstracts should help authors, editors, and peer reviewers improve the transparency of NPT trial reports.