tbuckley/cabot-search huggingface dataset:
Association Between Aspirin Use and Risk of Hepatocellular Carcinoma
Authors: Tracey G. Simon, Yanan Ma, Jonas F. Ludvigsson, Dawn Q. Chong, Edward L. Giovannucci, Charles S. Fuchs, Jeffrey A. Meyerhardt, Kathleen E. Corey, Raymond T. Chung, Xuehong Zhang, Andrew T. Chan
Journal: JAMA Oncology (2018)

Prospective data on the risk of hepatocellular carcinoma (HCC) according to dose and duration of aspirin therapy are limited.To examine the potential benefits of aspirin use for primary HCC prevention at a range of doses and durations of use within 2 prospective, nationwide populations.Pooled analysis of 2 prospective US cohort studies: the Nurses' Health Study and the Health Professionals Follow-up Study. Data were accessed from November 1, 2017, through March 7, 2018. A total of 133 371 health care professionals who reported data on aspirin use, frequency, dosage, and duration of use biennially since 1980 in women and 1986 in men were included. Individuals with a cancer diagnosis at baseline (except nonmelanoma skin cancer) were excluded.Cox proportional hazards regression models were used to calculate multivariable adjusted hazard ratios (HRs) and 95% CIs for HCC.Of the 133 371 participants, 87 507 were women and 45 864 were men; in 1996, the median time of follow-up, the mean (SD) age was 62 (8) years for women and 64 (8) years for men. Over more than 26 years of follow-up encompassing 4 232 188 person-years, 108 incident HCC cases (65 women, 43 men) were documented. Compared with nonregular use, regular aspirin use (≥2 standard-dose [325-mg] tablets per week) was associated with reduced HCC risk (adjusted HR, 0.51; 95% CI, 0.34-0.77). This benefit appeared to be dose related: compared with nonuse, the multivariable-adjusted HR for HCC was 0.87 (95% CI, 0.51-1.48) for up to 1.5 standard-dose tablets per week, 0.51 (95% CI, 0.30-0.86) for more than 1.5 to 5 tablets per week, and 0.49 (95% CI, 0.28-0.96) for more than 5 tablets per week (P for trend = .006). Significantly lower HCC risk was observed with increasing duration (P for trend = .03); this decrease was apparent with use of 1.5 or more standard-dose aspirin tablets per week for 5 or more years (adjusted HR, 0.41; 95% CI, 0.21-0.77). In contrast, use of nonaspirin nonsteroidal anti-inflammatory drugs was not significantly associated with HCC risk (adjusted HR, 1.09; 95% CI, 0.78-1.51).This study suggests that regular, long-term aspirin use is associated with a dose-dependent reduction in HCC risk, which is apparent after 5 or more years of use. Similar associations were not found with nonaspirin NSAIDs. Further research appears to be needed to clarify whether aspirin use represents a feasible strategy for primary prevention against HCC.
Age-Related Changes in HAPLN1 Increase Lymphatic Permeability and Affect Routes of Melanoma Metastasis
Authors: Brett L. Ecker, Amanpreet Kaur, Stephen M. Douglass, Marie R. Webster, Filipe V. Almeida, Gloria E. Marino, Andrew J. Sinnamon, Madalyn G. Neuwirth, Gretchen M. Alicea, Abibatou Ndoye, Mitchell Fane, Xiaowei Xu, Myung Shin Sim, Gary B. Deutsch, Mark B. Faries, Giorgos C. Karakousis, Ashani T. Weeraratna
Journal: Cancer Discovery (2018)

Abstract Older patients with melanoma have lower rates of sentinel lymph node (LN) metastases yet paradoxically have inferior survival. Patient age correlated with an inability to retain Technetium radiotracer during sentinel LN biopsy in more than 1,000 patients, and high Technetium counts correlated to better survival. We hypothesized that loss of integrity in the lymphatic vasculature due to extracellular matrix (ECM) degradation might play a role. We have implicated HAPLN1 in age-dependent ECM degradation in the dermis. Here, we queried whether HAPLN1 could be altered in the lymphatic ECM. Lymphatic HAPLN1 expression was prognostic of long-term patient survival. Adding recombinant HAPLN1 to aged fibroblast ECMs in vitro reduced endothelial permeability via modulation of VE-cadherin junctions, whereas endothelial permeability was increased following HAPLN1 knockdown in young fibroblasts. In vivo, reconstitution of HAPLN1 in aged mice increased the number of LN metastases, but reduced visceral metastases. These data suggest that age-related changes in ECM can contribute to impaired lymphatics. Significance: Our studies reveal that changes in the stroma during aging may influence the way tumor cells traffic through the lymphatic vasculature. Aging may dictate the route of metastatic dissemination of tumor cells, and understanding these changes may help to reveal targetable moieties in the aging tumor microenvironment. See related commentary by Marie and Merlino, p. 19. This article is highlighted in the In This Issue feature, p. 1
Abstract 16962: Two-year Outcomes Following Mitral Valve Repair or Replacement for Severe Ischemic Mitral Regurgitation
Authors: Daniel Goldstein, Gorav Ailawadi, Alan Moskowitz, Louis P Perrault, Michael Parides, Annetine Gelijns, Judy Hung, Francois Dagenais, A. Marc Gillinov, Vinod Thourani, Michael Argenziano, James Gammie, Michael Mack, Philippe Demers, Pavan Atluri, Eric A Rose, Karen O'Sullivan, Deborah Williams, Emilia Bagiella, Robert Michler, Richard Weisel, Marissa Miller, Wendy C Taddei-Peters, Peter K Smith, Ellen Moquete, Patrick O'Gara, Jessica R Overbey, Irving Kron, Michael A Acker
Journal: Circulation (2015)

Background: The Cardiothoracic Surgical Trials Network recently reported no difference in left ventricular end systolic volume index (LVESVI) at one year post-surgery between patients randomized to mitral repair (n=126) or replacement (n=125) for severe ischemic mitral regurgitation (MR). However, repair patients experienced significantly more recurrent MR than replacement patients. We report the 2-year follow-up of trial participants. Methods: We followed 251 patients randomized to repair or replacement for 2 years. LVESVI was assessed using a Wilcoxon rank sum test in which deaths were assigned the lowest rank. Results: Among surviving patients, mean 2-year LVESVI was 52.6 ±28mL/m2 in the repair and 60.7±39mL/m2 in the replacement arm (mean decrease from baseline 9.0mL/m2 and 6.5mL/m2, respectively). Two-year mortality was 19.1% for repair and 23.2% for replacement (HR 0.79, 95% CI 0.46-1.35; p=0.39). There was no significant between-group difference in LVESVI after adjustment for death (Z=-1.32, p=0.19). The rate of moderate or severe MR recurrence at 24 months was higher in the repair than replacement arm (36.3% vs.1.3%; p&lt; .0001). In the repair arm, the 2-year LVESVI was 62.5 ± 25 in patients with recurrent MR vs. 47.0 ± 29 in those without MR (p=0.0042). Four repair patients and 1 replacement patient underwent MV reoperation. There was no significant difference in the composite of MACCE, functional status or quality of life at 2 years. Rates (pt-yr) of serious adverse events (1.5 vs.1.3, p=0.18) and overall readmissions (0.8 vs. 0.7, p=0.14) were not different between arms, but repair patients experienced a higher rate of serious heart failure (0.24 vs. 0.15, p=0.049) and more CV readmissions (0.48 vs. 0.33, p=0.02) than replacement patients. Conclusions: We observed no difference in LV reverse remodeling or survival between repair and replacement at two years. Replacement provided more durable correction of MR, as well as fewer HF events and CV readmissions.
Durable response to anti-PD-1 immunotherapy in epithelioid angiomyolipoma: a report on the successful treatment of a rare malignancy
Authors: Michael Lattanzi, Fang-Ming Deng, Luis A. Chiriboga, Alisa N. Femia, Shane A. Meehan, Gopa Iyer, Martin H. Voss, Yuliya Sundatova, William C. Huang, Arjun V. Balar
Journal: Journal for ImmunoTherapy of Cancer (2018)

<h3>Background</h3> Malignant angiomyolipoma is an uncommon tumor of the class of perivasciular epithelioid cell neoplasms (PEComas). These tumors are characteristically driven by deleterious mutations in the tumor suppressors <i>TSC1</i> and <i>TSC2</i>, whose gene products typically act to inhibit mTOR. There are several cases of malignant angiomyolipoma which exhibit transient responses to mTOR inhibitors, forming the basis of current practice guidelines in malignant PEComa. However the tumors ultimately acquire resistance, and there is no well-established second-line option. Despite the increasing prevalence of immunotherapy across a wide range of solid tumors, little is known about the immune infiltrate and PD-L1 expression of angiomyolipoma. Furthermore, there is no reported case on the treatment of malignant angiomyolipoma with an immune checkpoint inhibitor. <h3>Case presentation</h3> A 38&nbsp;year-old man presented with gross hematuria and was diagnosed with renal epithelioid angiomyolipoma. Despite surgical resection, the tumor recurred and metastasized. Targeted genomic sequencing revealed a deleterious mutation in <i>TSC2</i>, and the patient was treated with the mTOR inihbitor everolimus. The patient went on to have a partial response but ultimately progressed. He was then treated with the anti-PD-1 immune checkpoint inhibitor nivolumab, and achieved a durable near-complete response which is ongoing after two years of treatment. Immunohistochemical staining of tumor tissue revealed strong PD-L1 expression and a brisk T-cell infiltrate. <h3>Conclusions</h3> We report on the first durable systemic treatment of malignant epithelioid angiomyolipoima with the use of PD-1 antibody nivolumab. Given the absence of prospective clinical trials in this exceedingly rare disease, particularly in the second-line setting, immune checkpoint inhibitors like nivolumab should be considered.
Reviewer Acknowledgment 2007
Authors: Harmon J. Eyre, Ted Gansler
Journal: CA A Cancer Journal for Clinicians (2007)

The editors of CA depend on the wisdom and advice of many experts in deciding which topics to pursue, which manuscripts to publish, and what modifications to make to ensure medical and scientific accuracy and suitability for our readers. We thank our Associate Editors, who have performed these services for us in the past year. We are also greatly indebted to the following individuals for reviewing at least one and, in some cases, many manuscripts for the journal from October 1, 2006, to July 30, 2007. Norbert Avril, MD Dileep Bal, MD Keith Bellizzi, PhD, MPH George Bock, MD Amy Chen, MD Nessa Coyle, PhD Rebecca Crane-Okada, PhD Jonathan Epstein, MD Thomas Flaig, MD Juri Gelovani, MD, PhD Jeffrey Gershenwald, MD Thomas Glynn, PhD Michael Graham, MD, PhD Marcia Grant, RN, DNSc, FAAN Marie Helweg-Larsen, PhD Robert Hiatt, MD, PhD Melissa Hudson, MD Carol Huff, MD Mohit Kasibhatla, MD William Lydiatt, MD Mary McCabe, RN, MA Marjorie McCullough, ScD Ann Mertens, PhD Mark Messina, PhD James Montie, MD Ruth O'Regan, MD Judith Paice, PhD, RN, FAAN Russell Portenoy, MD Carrie Rinker-Schaeffer, PhD Mack Ruffin, MD, MPH William Stetler-Stevenson, PhD Jamie Studts, PhD Theodoros Teknos, MD Guido Tricot, MD, PhD Elizabeth Ward, PhD
Linear accelerator stereotactic radiosurgery and radiotherapy for multiple brain metastases: outcomes from a tertiary centre
Authors: Dr Mark O’Beirn, Dr Paul Sanghera, Mr Peter Nightingale, Dr Sara Meade, Dr Andrew Hartley, Dr Vijay Sawlani, Prof Garth Cruickshank, Dr Helen Benghiat
Journal: Neuro-Oncology (2018)

Stereotactic radiosurgery (SRS) and radiotherapy (SRT) are considered standard of care for patients with 1–3 brain metastases with favourable prognosis. The role of SRS/SRT for multiple metastases remains debated. This project evaluated SRS/SRT outcomes when treating 4 or more brain metastases up to a maximum volume of 20cc. METHODS: Treatment episodes for patients with 4 or more brain metastases were identified from a single centre prospective database from August 2013 to October 2017. All patients were WHO PS 0–1 and treated using Cyberknife. Target volumes were neuroradiology approved with no additional margin beyond the enhancing volume. A retrospective review of electronic records and imaging was undertaken. Overall survival (OS) and distant brain recurrence free survival were calculated using Kaplan-Meier method from the date of treatment, censoring at last clinic visit or MRI respectively. RESULTS: 69 episodes (61 SRS, 7 SRT) were identified with a total of 458 metastases. Primary sites were melanoma (31.9%), lung (29%), breast (27.5%), renal (5.8%), other (5.7%). Median number of targets per episode was 5 (range 4–36). Median SRS dose was 21Gy (range 15-24Gy). Median SRT dose was 24Gy in 3 fractions (range 17.7/3#-27/3#). Median OS was 9.4 months (95% CI 6.5–12.4 months). In patients <65 years median OS was 12.1 months versus 5.9 months for >65 years (p<0.001). Follow up imaging was available for 59 patients and 36 developed new metastases. Median time to distant brain failure was 9.1 months in patients <65 years versus 3 months for patients >65 years(p=0.001). Median OS was 14 months for breast cancer versus 8.4 months for other primary sites (p=0.094). Number of metastases was not predictive of OS or occurrence of distant brain metastases. DISCUSSION: Data supports the ongoing use of volume rather than number of metastases alongside established prognostic factors including age when selecting patients for SRS/SRT.
A <i>Candida auris</i> Outbreak and Its Control in an Intensive Care Setting
Authors: David W. Eyre, Anna E. Sheppard, Hilary Madder, Ian Moir, Ruth Moroney, T. Phuong Quan, David Griffiths, Sophie George, Lisa Butcher, Marcus Morgan, Robert Newnham, Mary Sunderland, Tiphanie Clarke, Dona Foster, Peter Hoffman, Andrew M. Borman, Elizabeth M. Johnson, Ginny Moore, Colin S. Brown, A. Sarah Walker, Tim E.A. Peto, Derrick W. Crook, Katie J.M. Jeffery
Journal: New England Journal of Medicine (2018)

Candida auris is an emerging and multidrug-resistant pathogen. Here we report the epidemiology of a hospital outbreak of C. auris colonization and infection.After identification of a cluster of C. auris infections in the neurosciences intensive care unit (ICU) of the Oxford University Hospitals, United Kingdom, we instituted an intensive patient and environmental screening program and package of interventions. Multivariable logistic regression was used to identify predictors of C. auris colonization and infection. Isolates from patients and from the environment were analyzed by whole-genome sequencing.A total of 70 patients were identified as being colonized or infected with C. auris between February 2, 2015, and August 31, 2017; of these patients, 66 (94%) had been admitted to the neurosciences ICU before diagnosis. Invasive C. auris infections developed in 7 patients. When length of stay in the neurosciences ICU and patient vital signs and laboratory results were controlled for, the predictors of C. auris colonization or infection included the use of reusable skin-surface axillary temperature probes (multivariable odds ratio, 6.80; 95% confidence interval [CI], 2.96 to 15.63; P<0.001) and systemic fluconazole exposure (multivariable odds ratio, 10.34; 95% CI, 1.64 to 65.18; P=0.01). C. auris was rarely detected in the general environment. However, it was detected in isolates from reusable equipment, including multiple axillary skin-surface temperature probes. Despite a bundle of infection-control interventions, the incidence of new cases was reduced only after removal of the temperature probes. All outbreak sequences formed a single genetic cluster within the C. auris South African clade. The sequenced isolates from reusable equipment were genetically related to isolates from the patients.The transmission of C. auris in this hospital outbreak was found to be linked to reusable axillary temperature probes, indicating that this emerging pathogen can persist in the environment and be transmitted in health care settings. (Funded by the National Institute for Health Research Health Protection Research Unit in Healthcare Associated Infections and Antimicrobial Resistance at Oxford University and others.).
Effect of Ciliary Neurotrophic Factor on Retinal Neurodegeneration in Patients with Macular Telangiectasia Type 2
Authors: Emily Y. Chew, Traci E. Clemons, Glenn J. Jaffe, Charles A. Johnson, Sina Farsiu, Eleonora M. Lad, Robyn Guymer, Philip Rosenfeld, Jean-Pierre Hubschman, Ian Constable, Henry Wiley, Lawrence J. Singerman, Mark Gillies, Grant Comer, Barbara Blodi, Dean Eliott, Jiong Yan, Alan Bird, Martin Friedlander
Journal: Ophthalmology (2018)
An Input-Specific Orphan Receptor GPR158-HSPG Interaction Organizes Hippocampal Mossy Fiber-CA3 Synapses
Authors: Giuseppe Condomitti, Keimpe D. Wierda, Anna Schroeder, Sara E. Rubio, Kristel M. Vennekens, Cesare Orlandi, Kirill A. Martemyanov, Natalia V. Gounko, Jeffrey N. Savas, Joris de Wit
Journal: Neuron (2018)
SHARED DECISION MAKING, THE BRIDGE BETWEEN PATERNALISM AND AUTONOMY.
Authors: Julian Cahill, Georgios Zilidis, Paul Grundy
Journal: Neuro-Oncology (2018)

Shared Decision Making (SDM) has been shown to be an effective tool in allowing patients to determine the treatment options best suited to their individual needs and is becoming the new standard of care in modern healthcare. It is invaluable in situations where reasonable options exist for a patient’s management, such as Neuro-Oncology. A clinical decision grid was developed for three conditions, low and high grade gliomas and metastases. Three options were given to patients: best medical management or biopsy or resection (+/- adjuvant treatment) for gliomas and stereotactic radiosurgery or resection for metastases. The suitability, advantages and disadvantages were explained for each option and patients encouraged to choose the option that they felt suited them best. We analysed health care professional’s attitude towards SDM before and after training using the Advanced Quality Alliance (AQuA) questionnaire. We assessed patient’s response to consultations before and after the implementation of SDM using CollaboRATE questionnaire in the first cycle of a Plan Do Study Act (PDSA) process. Five members of staff were trained in SDM and in response to the 19 point questionnaire (AQuA) there was an overall 28% improvement from 65% to 93% (in their attitude to SDM following training). The breakdown will be presented. 3 decision grids were used in 44 patients by 2 neurosurgeons and CollaboRATE scores remained high and did not change after full implementation with mean scores of 26/27 (range 15–27). SSDM is a useful process that allows patients to make informed decisions regarding their treatment options. Although a significant improvement was seen amongst staff following the introduction of SDM, no difference was seen in the patient response analysis. This may relate to the department already using this methodology prior to its full implementation and the lack of sensitivity of the collaboRATE test.
Abstract 20089: Efficacy and Safety of Extended Dual Antiplatelet Therapy in Stable Post-myocardial Infarction 1-year Survivors
Authors: Sungmin Lim, Kiyuk Chang, Youngkeun Ahn, Eun Ho Choo, Ik Jun Choi, Byung-Hee Hwang, Suk Min Seo, Yoon-Seok Koh, Hun-Jun Park, Pum-Joon Kim, Dong-Bin Kim, Sung-Ho Her, Jong Min Lee, Chul Soo Park, Hee-Yeol Kim, Ki-Dong Yoo, Doo Soo Jeon, Wook Sung Chung, Doo Sun Sim, Young Joon Hong, Ju Han Kim, Myung Ho Jeong, Ki-Bae Seung
Journal: Circulation (2017)

Background: In patient with acute myocardial infarction (AMI), continuation of dual-antiplatelet therapy (DPAT) for longer than 12 months after percutaneous coronary intervention (PCI) may be consi...
Abstract 18572: Limitations of Endocardial Unipolar Voltage Mapping in Predicting the Epicardial Substrate
Authors: Yalçin Gökoglan, Mahmut F Günes, Luigi Di Biase, Carola Gianni, Sanghamitra Mohanty, Chintan Trivedi, Rong Bai, Amin Al-Ahmad, J D Burkhardt, Joseph G Gallinghouse, Rodney Horton, Patrick M Hranitzky, Javier E Sanchez, Andrea Natale
Journal: Circulation (2015)

Introduction: Bipolar voltage mapping detects areas of scar and guides ablation of VT. The role of endocardial unipolar voltage mapping is not well defined. We examined the endo-epicardial substrate in a mixed cohort of patients with structural heard disease (SHD) to determine whether an endocardial unipolar low voltage area predicts the presence and location of an epicardial scar. Results: Data from 24 consecutive patients with SHD (11 ICM, 6 NICM, 3 HCM, 2 ARVC, 1 myocarditis, 1 Brugada) with a detailed (mean points per map 200) combined endocardial-epicardial substrate mapping were retrospectively reviewed. Maps were obtained using a 3D mapping system (CARTO 3) and normal thresholds used were ≤1.5 mV for bipolar voltage, and ≤5.5 (RV) or ≤8.3 mV (LV) for unipolar voltage. Mapping was performed in the LV in 17 patients, in the RV in 6 patients, in both in 1 patient. An endocardial unipolar low voltage area was found in 21/25 maps. In 12/21 maps there was no corresponding epicardial scar, while in 3/4 cases an epicardial scar was detected despite a negative unipolar map (PPV=43%, NPV=25%, P=NS; Fig. 1). In the 9 cases with both positive endocardial unipolar and epicardial bipolar maps, the epicardial scar was found in the corresponding ventricular region of the endocardial low-voltage area, although unipolar area had a tendency to overestimate the area of the scar (115 vs 95 cm 2 ). Conclusion: In this series of patients with SHD, analysis of unipolar voltage maps could not reliably predict the epicardial arrhythmogenic substrate. There is a modest correlation between areas of endocardial unipolar low voltage and epicardial scars (57% of patients with an abnormal unipolar map had a normal epicardial substrate). Moreover, an epicardial substrate cannot be safely excluded based on a normal unipolar endocardial map. Fig. 1 Abnormal bipolar epicardial map (left) with corresponding normal unipolar endocardial map (right) in a patient with ARVC. Pink dots represent area of defragmentation.
Globo H expression is lower in breast cancer stem cells and its biosynthesis involves fucosyl transferases 1 and 2
Authors: WenWei Chang, Chien Hsin Lee, Peishan Lee, Juway Lin, Chien-Wei Hsu, John Yu, Chi-Huey Wong, Jyh-Cherng Yu, Alice L. Yu
Journal: Cancer Research (2008)

2026  Breast cancer stem cells (BCSCs) has been identified as CD24-CD44+ cells and shown to display engraftment capabilities with phenotypic diversity. Globo H is a tumor associated glycolipid in many epithelial cancers including breast cancer, but its expression on BCSCs remains unknown. By flow cytometric analysis, we found that 16 of 27 (59.3%) human breast cancer specimens expressed Globo H. Non-BCSCs from all 16 tumors were positive for Globo H but BCSCs from only 4 of 26 (15.3%) expressed Globo H. The precursor of Globo H, SSEA3, was detected in 11 of 14 (78.6%) breast cancer specimens tested, including 7/7 of Globo H positive tumors and 4/7 of Globo H negative tumors. Subpopulation analysis revealed that SSEA3 was detected in non-BCSCs from all 11 SSEA3 expressing tumors, but in BCSCs from only 7/14 (50%) tumors tested. Within BCSCs subpopulation, SSEA3 expression was noted in 2 of the 7 Globo H negative tumors and 5 of 7 Globo H positive tumors. The latter included one tumor which expressed Globo H in BCSCs and 4 of 6 tumors which did not. Using siRNA strategy in human breast cancer cell lines, we demonstrated for the first time that both fucosyltransferase (FUT) 1 and 2, the enzymes responsible for alpha-1, 2 linkage of fucose, were involved in the biosynthesis of Globo H. Furthermore, we found that FUT2 expression was significantly lower in BCSCs than non-BCSCs harvested from a xenografted primary human breast cancer in NOD/SCID mouse while FUT1 was slightly lower in BCSCs. In conclusion, the Globo H expression is lower or absent on BCSCs than non-BCSCs. Although the overall frequency of the expression of its precursor, SSEA3, is higher than Globo H, SSEA3 is also less frequently detected in BCSCs than in non-BCSCs. Thus, the lower expression of Globo H in BCSCs may be attributed in part to the less frequent expression of SSEA3, in part to lower expression levels of FUT2/FUT1, which is responsible for the biosynthesis of Globo H.