tbuckley/cabot-search huggingface dataset:
Breast cancer liver metastases (BCLM): What may be the role of surgery combined with chemotherapy?
Authors: R. Adam, R. Salmon, D. Elias, M. Rivoire, D. Cherqui, D. Jaeck, J. Gigot, P. Le Treut, G. Mantion, J. Belghiti
Journal: Journal of Clinical Oncology (2007)

1039 Background: Despite recent treatment improvements, the prognosis of BCLM is still poor. Hepatic resection (HR) has been associated with better outcome in selected patients, but its place in multimodality treatment of BCLM remains controversial. This study aimed to examine the outcome of a large cohort of patients selected for HR of BCLM and to define prognostic factors of survival, in a way to better define the place of surgery. Methods: A standardized questionnaire reviewing the main diagnostic and treatment modalities of primary tumor, liver metastases, response to medical therapies, type of surgical procedures, postoperative outcome, and survival following surgery, was sent to all contributing centers. Results: 460 patients treated with liver resection for BCLM from 1980 to 2000, were collected from 31 hepatobiliary surgery centers. Mean age was 51.8 years. Primary tumor, mainly adenocarcinoma, was treated by resection combined with chemotherapy and/or radiotherapy in most cases. Diagnosis of BCLM was made after an average of 54 months from the treatment of the primary tumor. BCLM were unique in 56% and associated to limited extrahepatic disease in 18.5% of patients. After initial treatment by systemic therapy (70% of patients), HR achieved a R0 resection in 82% of patients and was combined to extrahepatic resection for distant metastases in 9% of patients. Postoperative mortality (= 2 months) was 0.2%. Median survival was 45.4 months after HR, with an overall survival of 41% and 22% at 5 and 10 years, respectively. Disease-free survival rates were 14% and 10%, respectively. Four predictive factors were independently associated to an unfavourable outcome: tumor progression on chemotherapy before surgery (p = 0.0006, RR = 2.9), disease-free interval &lt; 12 months after treatment of the primary tumor (p = 0.0003, RR = 2.1), extrahepatic metastases (p = 0.0002, RR = 1.9) and R2 liver resection (p &lt; 0.0001, RR = 3.0). Conclusions: Inclusion of HR in the multimodality treatment of BCLM is safe and associated with a hope of long term survival (22% at 10 years). Surgery should be discussed on a multidisciplinary basis, particularly when potentially radical, in patients well controlled by chemotherapy with a long disease-free interval, and in the absence of extrahepatic disease. No significant financial relationships to disclose.
Evaluation of Chronic Transfusion (Tx) Practices in Children with Sickle Cell Disease (SCD): A Survey of STOP II Investigators.
Authors: Ofelia Alvarez, Scott Miller, Brian Berman, Clark Brown, James Casella, Thomas Coates, Charles Daeschner, Beatrice Files, Janet Kwiatkowski, Margaret Lee, Winfred Wang, Gerald Woods
Journal: Blood (2004)
Correlates of patient referral to surgeons for treatment of breast cancer
Authors: S. J. Katz, T. P. Hofer, S. Hawley, P. M. Lantz, N. K. Janz, K. Schwartz, L. Liu, D. Deapen, M. Morrow
Journal: Journal of Clinical Oncology (2006)

6032 Background: Characteristics of surgeons and their practice settings have been associated with cancer treatments and outcomes. Yet, there is little information about factors that are associated with referral pathways to surgeons and treatment settings. Methods: We merged and analyzed tumor registry and survey data from all women with DCIS and a 20% random sample of women with invasive breast cancer diagnosed in 2002 and reported to the Detroit and Los Angeles SEER registries (N = 1,844, response rate 77.4%,) and their surgeons (N = 365, response rate 80.0%). Results: About half of the patients (54.2%) reported that they were referred to their surgeon by another provider or health plan; 20.3% reported that they selected their surgeon; 21.9% reported that they both were referred and were involved in selecting their surgeon; and the remaining patients (4.9%) reported that they had a prior relationship with their surgeon primarily through previous surgery. Selecting their surgeon based on reputation was more frequently reported by white patients (36.5% vs 26.5%, p &lt; .001), and more highly educated patients (40.0% and 21.6%, respectively for highest and lowest education categories, p &lt; .001). Patients who selected their surgeon based on reputation were more likely to have received treatment from a high volume surgeon (adjusted odds ratio 2.3; 95% CI 1.7, 3.2) and more likely to have been treated in an American College of Surgeon approved cancer program or NCI-designated cancer center (adjusted odds ratio 1.8; 95% CI 1.1, 2.8; 3.0 95% CI 1.6, 5.3, respectively). Patients who were referred to their surgeon were less likely to be treated in an NCI-designated cancer center (adjusted OR 0.4; 95% CI 0.2, 0.8). Conclusions: Women with breast cancer who actively participate in the surgeon selection process are more likely to be treated by more experienced surgeons and in hospitals with approved cancer programs. Patients should be aware that provider or health plan-based referral may not connect them with the most experienced surgeon or comprehensive practice setting in their community. An active patient role in the surgeon selection process has important implications for both the type of treatment received and where care is delivered. No significant financial relationships to disclose.
Altered fractionated radiotherapy is cost-effective in the treatment of locally advanced head and neck cancer: An economic analysis of Radiation Therapy Oncology Group (RTOG) 90–03
Authors: A. A. Konski, M. Bhargavan, J. Owen, R. Paulus, J. Cooper, K. Fu, K. Ang, D. Watkins-Bruner
Journal: Journal of Clinical Oncology (2006)

6007 Background: RTOG 9003 compared altered fractionated radiotherapy (AIFX) to standard radiotherapy (SFX). Overall and disease-free survival was improved in the AIFX schedules but with increased toxicity. The specific aim of this study was to compare the cost-effectiveness of AIFX to SFX. Methods: Costs data included Medicare Part A and Part B costs from all providers—inpatient, outpatient, skilled nursing facility, home health, hospice, and physicians and other Part B providers were obtained from the Centers for Medicare &amp; Medicaid Services (CMS) for patients treated on RTOG 9003 from 1992–1996. Claims were restricted to those with a diagnosis of head and neck cancer. We calculated 56-month expected discounted costs for each arm of the trial in 1996 dollars, with Kaplan-Meier sampling average estimates of survival probabilities for each month and mean monthly costs. Costs were discounted back to the time of entry onto the trial, using an annual discount rate of 3% and indexed to 1996 dollars using the Consumer Price Index. The analysis was performed from a payer’s perspective. Incremental cost-effective ratios were calculated comparing AIFX schedules to SFX. Results: Of the 1,130 patients entered, 1,073 patients were analyzable for outcomes and Medicare cost data and clinical outcomes were available for 130 patients. The expected mean 56-month cost and incremental cost-effectiveness ratios (ICER) compared to SFX are presented in the table . Sensitivity analysis and 95% confidence ellipses will be presented. Conclusions: Although more toxic altered fractionated radiotherapy schedules were found to be cost-effective using a willingness to pay of $50,000/life year in patients &gt;65 years old. These results need to be confirmed in a cohort of younger patients. [Table: see text] No significant financial relationships to disclose.
Thrombotic and Hemorrhagic Complications after Surgery in Patients with Essential Thrombocythemia and Polycythemia Vera.
Authors: Marco Ruggeri, Francesco Rodeghiero, Alberto Tosetto, Giancarlo Castaman, Francesca Scognamiglio, Guido Finazzi, Federica Delaini, Caterina Micò, Alessandro M. Vannucchi, Elisabetta Antonioli, Valerio De Stefano, Tommaso Zà, Luigi Gugliotta, Alessia Tieghi, Maria Gabriella Mazzucconi, Cristina Santoro, Tiziano Barbui
Journal: Blood (2006)
Comment on Kazda et al. Evaluation of Efficacy and Safety of the Glucagon Receptor Antagonist LY2409021 in Patients With Type 2 Diabetes: 12- and 24-Week Phase 2 Studies. Diabetes Care 2016;39:1241–1249
Authors: Sweety Agrawal, Yashdeep Gupta
Journal: Diabetes Care (2016)

We would like to congratulate Kazda et al. (1) for reporting the first phase 2 study of the glucagon receptor antagonist LY2409021 as a novel therapy for type 2 diabetes. This study provides further proof of efficacy of glucagon antagonism as a treatment for type 2 diabetes with acceptable adverse effects at a dose of 30 mg. However, we would like the authors to clarify certain points in the phase 2a study, which would help readers …
Non-Myeloablative Allogeneic Hematopoietic Stem Cell Transplantation (allo-HSCT) for Patients with Severe Sickle Cell Disease (SCD)
Authors: Matthew M Hsieh, Courtney D Fitzhugh, R. Patrick Weitzel, Wynona Coles, M Beth Link, John F. Tisdale
Journal: Blood (2011)
Abstract IA03: Fibroblast heterogeneity in skin tumour stroma
Authors: Fiona M. Watt
Journal: Cancer Research (2016)

Abstract The fibroblasts of mouse skin connective tissue arise from two distinct lineages during embryonic development. One forms the upper dermis, including the dermal papilla, dermal sheath and arrector pili muscle, and is required for hair follicle formation. The other forms the lower dermis, including the reticular fibroblasts that synthesize the bulk of the fibrillar ECM, and the skin adipocyte layer. The lower dermal lineage is responsible for the first phase wound repair. We have been investigating the changes in the composition of adult mouse dermis when epidermal tumors arise through oncogenic beta-catenin activation. Our studies highlight the contribution of different fibroblast subpopulations to the stroma of skin tumors. Citation Format: Fiona M. Watt. Fibroblast heterogeneity in skin tumour stroma. [abstract]. In: Proceedings of the AACR Special Conference: Function of Tumor Microenvironment in Cancer Progression; 2016 Jan 7–10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2016;76(15 Suppl):Abstract nr IA03.
Does the Occurrence of Invasive Fungal Infection in Acute Leukemia Patients, Impact on the Chemotherapy Schedule and Event-Free Survival? a Case-Control Study
Authors: Caroline Even, Sylvie Bastuji-Garin, C.écile Pautas, Yosr Hicheri, Sebastien Maury, Mathieu Kuentz, Stephane Bretagne, Catherine Cordonnier
Journal: Blood (2008)
Taskforce to help integrate health and social care is scrapped
Authors: Matthew Limb
Journal: BMJ (2016)

Prime Minister Theresa May has come under fire for scrapping the Health and Social Care Implementation Taskforce which was set up by her predecessor, David Cameron.

Jon Ashworth, shadow health secretary, said that the decision showed that May had “no interest in the long term sustainability of our NHS and social care system.”

He told The BMJ , “Under the Tory government, the NHS has been engulfed in a funding and staffing crisis and the Care Quality Commission said last week that …
5T4-Targeted Therapy Ablates Cancer Stem Cells and Prevents Recurrence of Head and Neck Squamous Cell Carcinoma
Authors: Samuel A. Kerk, Kelsey A. Finkel, Alexander T. Pearson, Kristy A. Warner, Zhaocheng Zhang, Felipe Nör, Vivian P. Wagner, Pablo A. Vargas, Max S. Wicha, Elaine M. Hurt, Robert E. Hollingsworth, David A. Tice, Jacques E. Nör
Journal: Clinical Cancer Research (2016)

Purpose: Locoregional recurrence is a frequent treatment outcome for patients with advanced head and neck squamous cell carcinoma (HNSCC). Emerging evidence suggests that tumor recurrence is mediated by a small subpopulation of uniquely tumorigenic cells, that is, cancer stem cells (CSC), that are resistant to conventional chemotherapy, endowed with self-renewal and multipotency.Experimental Design: Here, we evaluated the efficacy of MEDI0641, a novel antibody-drug conjugate targeted to 5T4 and carrying a DNA-damaging "payload" (pyrrolobenzodiazepine) in preclinical models of HNSCC.Results: Analysis of a tissue microarray containing 77 HNSCC with follow-up of up to 12 years revealed that patients with 5T4high tumors displayed lower overall survival than those with 5T4low tumors (P = 0.038). 5T4 is more highly expressed in head and neck CSC (ALDHhighCD44high) than in control cells (non-CSC). Treatment with MEDI0641 caused a significant reduction in the CSC fraction in HNSCC cells (UM-SCC-11B, UM-SCC-22B) in vitro Notably, a single intravenous dose of 1 mg/kg MEDI0641 caused long-lasting tumor regression in three patient-derived xenograft (PDX) models of HNSCC. MEDI0641 ablated CSC in the PDX-SCC-M0 model, reduced it by five-fold in the PDX-SCC-M1, and two-fold in the PDX-SCC-M11 model. Importantly, mice (n = 12) treated with neoadjuvant, single administration of MEDI0641 prior to surgical tumor removal showed no recurrence for more than 200 days, whereas the control group had 7 recurrences (in 12 mice; P = 0.0047).Conclusions: Collectively, these findings demonstrate that an anti-5T4 antibody-drug conjugate reduces the fraction of CSCs and prevents local recurrence and suggest a novel therapeutic approach for patients with HNSCC. Clin Cancer Res; 23(10); 2516-27. ©2016 AACR.
GW26-e0194 Apelin Ameliorates Myocardial Insulin Resistance and Improves Myocardial Injury in Diabetes
Authors: Hangxiang Zhang, Jiaojiao Chu, Tao Shen, Chongqing Yang, Xiuqing Huang, Shu Wang, Xiaoming Wang, Jian Li
Journal: Journal of the American College of Cardiology (2015)
Abstract A10: The hypoxic response in natural killer cells: Linking cytoxicity and tumor immune surveillance to angiogenesis
Authors: Ewelina Krzywinska, Chahrazade Kantari-Mimoun, Magali Castells, Dagmar Gotthardt, Yann Kerdiles, Ralph Klose, Joachim Fandrey, Veronika Sexl, Christian Stockmann
Journal: Cancer Research (2016)

Abstract Hypoxia-inducible transcription factors (HIFs) are central mediators of cellular adaptation to low oxygen and play a pivotal role in inflammatory responses. Natural Killer (NK) cells, unifying characteristics of innate and adaptive immunity, are cytotoxic innate lymphoid cells with a unique ability to instantly recognize and kill “aberrant” cancer cells while sparing “normal” cells. Owing to these tumoricidal features, NK cells are able to restrict primary tumor growth and limit metastatic spread. By genetic targeting HIFs in NK cells HIFs, we define a crucial role of HIF-1 in NK cell function and cancer immune surveillance. We show that NK cells preferentially infiltrate into hypoxic zones of solid primary tumors and that HIF-1-deficiency in NK cells slows impairs primary tumor growth as well as distant metastasis. This is due to reduced susceptibility of HIF-1-deficient NK cells to tumor cell-derived inhibitory stimuli, resulting in improved recognition and killing of tumor cells. Furthermore, we define the hypoxic response in NK cells as a critical mediator of tumor angiogenesis. Paradoxically, HIF-1-deficiency in NK cells results in decreased expression of various angiostatic factors within the tumor microenvironment, resulting in unproductive tumor angiogenesis, characterized by immature, non-functional vessel and severe tumor hypoxia. This suggests that the hypoxic response in NK cells slows down overall tumor angiogenesis in order to allow for vessel formation in a more coordinated fashion. In summary, we define HIF-1 as a critical mediator of NK cell effector function and cancer immune surveillance. Secondly, we show that HIF-1 in NK cells acts as a negative regulator of tumor angiogenesis that ensures the fine-tuning of the angiogenic response. These results indicate that exploiting the hypoxic response in NK cells may represent a novel therapeutic avenue. Citation Format: Ewelina Krzywinska, Chahrazade Kantari-Mimoun, Magali Castells, Dagmar Gotthardt, Yann Kerdiles, Ralph Klose, Joachim Fandrey, Veronika Sexl, Christian Stockmann. The hypoxic response in natural killer cells: Linking cytoxicity and tumor immune surveillance to angiogenesis. [abstract]. In: Proceedings of the AACR Special Conference: Function of Tumor Microenvironment in Cancer Progression; 2016 Jan 7–10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2016;76(15 Suppl):Abstract nr A10.
HLA Mismatched MSC Suppress T Lymphocyte Allo responses in Vitro and Do Not Induce Immunological Memory in Recipients of MSC Infusion
Authors: Mikael Sundin, A. John Barrett, Olle Ringdén, Mehmet Uzunel, Helena Lönnies, Åsa-Lena Dackland, Birger Christensson, Katarina Le Blanc
Journal: Blood (2008)
Interaction of Age and Comorbidities and Their Impacts on Hematopoietic Cell Transplantation (HCT) Outcomes
Authors: Fabiana Ostronoff, Barry Storer, Rainer Storb, Smita Bhatia, Richard T. Maziarz, Michael A. Pulsipher, Michael T. Maris, H. Joachim Deeg, Paul J. Martin, Frederick R. Appelbaum, David G. Maloney, Brenda M. Sandmaier, Mohamed L. Sorror
Journal: Blood (2011)
Anti-cancer chemosensitization in vitro and in vivo by a novel potent poly(ADP-ribose) polymerase (PARP1) inhibitor, TBI-361.
Authors: NJ Curtin, SB Barton, MA Batey, CR Calabrese, AH Calvert, BW Durkacz, RJ Griffin, BT Golding, S Kyle, Newell, HD Thomas, L Wang, R Almassy, T Boritzki, S Canan-Koch, Z Hostomsky, K Maegley, S Webber
Journal: Clinical Cancer Research (2001)
Ramucirumab combined with FOLFOX as front-line therapy for advanced esophageal, gastroesophageal junction, or gastric adenocarcinoma: a randomized, double-blind, multicenter Phase II trial
Authors: H.H. Yoon, J.C. Bendell, F.S. Braiteh, I. Firdaus, P.A. Philip, A.L. Cohn, N. Lewis, D.M. Anderson, E. Arrowsmith, J.D. Schwartz, L. Gao, Y. Hsu, Y. Xu, D. Ferry, S.R. Alberts, Z.A. Wainberg
Journal: Annals of Oncology (2016)
Prevalence and Clinical Implications of IDH2 R140 and R172 Mutations in Older Adults with AML: A Report From SWOG,
Authors: Phoenix A. Ho, Megan Othus, Fabiana Ostronoff, Stephen H. Petersdorf, Jeanne E. Anderson, John E. Godwin, Cheryl L Willman, Jerald P. Radich, Frederick R. Appelbaum, Derek L. Stirewalt, Soheil Meshinchi
Journal: Blood (2011)
Protein-RNA Networks Regulated by Normal and ALS-Associated Mutant HNRNPA2B1 in the Nervous System
Authors: Fernando J. Martinez, Gabriel A. Pratt, Eric L. Van Nostrand, Ranjan Batra, Stephanie C. Huelga, Katannya Kapeli, Peter Freese, Seung J. Chun, Karen Ling, Chelsea Gelboin-Burkhart, Layla Fijany, Harrison C. Wang, Julia K. Nussbacher, Sara M. Broski, Hong Joo Kim, Rea Lardelli, Balaji Sundararaman, John P. Donohue, Ashkan Javaherian, Jens Lykke-Andersen, Steven Finkbeiner, C. Frank Bennett, Manuel Ares, Christopher B. Burge, J. Paul Taylor, Frank Rigo, Gene W. Yeo
Journal: Neuron (2016)
Heritability of Choroidal Thickness in the Amish
Authors: Rebecca J. Sardell, Muneeswar G. Nittala, Larry D. Adams, Reneé A. Laux, Jessica N. Cooke Bailey, Denise Fuzzell, Sarada Fuzzell, Lori Reinhart-Mercer, Laura J. Caywood, Violet Horst, Tine Mackay, Debbie Dana, SriniVas R. Sadda, William K. Scott, Dwight Stambolian, Jonathan L. Haines, Margaret A. Pericak-Vance
Journal: Ophthalmology (2016)

To evaluate the heritability of choroidal thickness and its relationship to age-related macular degeneration (AMD).Cohort study.Six hundred eighty-nine individuals from Amish families with early or intermediate AMD.Ocular coherence tomography was used to quantify choroidal thickness, and fundus photography was used to classify eyes into categories using a modified Clinical Age-Related Maculopathy Staging (CARMS) system. Repeatability and heritability of choroidal thickness and its phenotypic and genetic correlations with the AMD phenotype (CARMS category) were estimated using a generalized linear mixed model (GLMM) approach that accounted for relatedness, repeated measures (left and right eyes), and the effects of age, gender, and refraction.Heritability of choroidal thickness and its phenotypic and genetic correlation with the AMD phenotype (CARMS category).Phenotypic correlation between choroidal thickness and CARMS category was moderate (Spearman's rank correlation, rs = -0.24; n = 1313 eyes) and significant (GLMM posterior mean, -4.27; 95% credible interval [CI], -7.88 to -0.79; P = 0.02) after controlling for relatedness, age, gender, and refraction. Eyes with advanced AMD had thinner choroids than eyes without AMD (posterior mean, -73.8; 95% CI, -94.7 to -54.6; P < 0.001; n = 1178 eyes). Choroidal thickness was highly repeatable within individuals (repeatability, 0.78; 95% CI, 0.68 to 0.89) and moderately heritable (heritability, 0.40; 95% CI, 0.14 to 0.51), but did not show significant genetic correlation with CARMS category, although the effect size was moderate (genetic correlation, -0.18; 95% CI, -0.49 to 0.16). Choroidal thickness also varied with age, gender, and refraction. The CARMS category showed moderate heritability (heritability, 0.49; 95% CI, 0.26 to 0.72).We quantify the heritability of choroidal thickness for the first time, highlighting a heritable, quantitative trait that is measurable in all individuals regardless of AMD affection status, and moderately phenotypically correlated with AMD severity. Choroidal thickness therefore may capture variation not captured by the CARMS system. However, because the genetic correlation between choroidal thickness and AMD severity was not significant in our data set, genes associated with the 2 traits may not overlap substantially. Future studies should therefore test for genetic variation associated with choroidal thickness to determine the overlap in genetic basis with AMD.
GW26-e4813 Impact of Anatomically-guided Ganglionated Plexus Ablation on Electrical Firing from Isolated Pulmonary Veins
Authors: Ruhong Jiang, Qiang Liu, Xia Sheng, Ya-xun Sun, Lu Yu, Pei Zhang, Zu-wen Zhang, Yang Ye, Shi-quan Chen, Guo-sheng Fu, Chenyang Jiang
Journal: Journal of the American College of Cardiology (2015)
Abdominal pain in a 24 year old woman
Authors: Joseph Dalby Sinnott, David C Howlett
Journal: BMJ (2016)

A 24 year old woman was admitted to the surgical assessment unit with a tender, distended abdomen. She mentioned increasingly frequent bloody diarrhoea for the past week. Clinically she was dehydrated and pyrexial (38.6°C). She was also tachycardic (124 bpm) and had a raised white cell count (14×109/L). A supine abdominal radiograph was obtained (fig 1 …