tbuckley/cabot-search huggingface dataset:
Abstract 15033: Utilization of Cardiac Resynchronization Therapy Among Eligible Patients Receiving an Implantable Cardioverter-Defibrillator: Insights From the NCDR ICD Registry
Authors: Lucas N Marzec, Pamela N Peterson, Haikun Bao, Jeptha P Curtis, Frederick A Masoudi, Paul D Varosy, Steven M Bradley
Journal: Circulation (2015)

Introduction: Although ICDs are used inconsistently among eligible patients, it is unknown if similar variation exists in the use of cardiac resynchronization therapy (CRT) devices. Methods: Within the National Cardiovascular Data Registry (NCDR) ICD Registry, we identified 72,115 patients with a class I or IIa indication for CRT according to 2008 guidelines who underwent ICD or CRTD implantation at 1521 hospitals between April 1, 2010 and June 30, 2014. A hierarchical model including hospital specific random-effects was used to identify patient, provider, and hospital factors associated with CRTD use. We then determined risk-standardized rates of CRTD use across hospitals for the overall population and by strength of guideline indication. We applied 2012 CRT guidelines in secondary analyses. Results: A total of 62,900 (87.2%) eligible patients by 2008 guidelines received CRTD, with 60,730 (84.2%) having a class I indication and 11,385 (15.8%) a class IIa indication for CRTD. Patient factors associated with higher use included increasing age (OR 1.07, 95% CI 1.04-1.1) and NYHA class IV symptoms (OR 1.13, 95% CI 1.02-1.25) while black race was associated with lower use of CRTD (OR 0.81, 95% CI 0.75-0.88). Non-electrophysiology providers were less likely to implant CRTD (OR 0.35, 95% CI 0.28-0.43). After accounting for patient, provider, and hospital factors, the median hospital risk standardized rate of CRTD use was 77.3% (range 24.3-100%) (Figure). The hospital median risk standardized rate of CRTD for class I indication was 79% (range 32.5-100%) and for class IIa was 83.9% (range 79.8-100%). Similar findings were seen with the application of 2012 CRTD guidelines. Conclusions: Among patients receiving device therapy who have guideline based indications for CRTD, the use of this therapy varies widely by hospital even after accounting for patient, provider, and hospital factors. Strategies to address this variation may improve patient outcomes through optimal use of CRTD.
Bicyclic Peptides as a New Modality for Imaging and Targeting of Proteins Overexpressed by Tumors
Authors: Matthias Eder, Silvia Pavan, Ulrike Bauder-Wüst, Katerine van Rietschoten, Ann-Christin Baranski, Helen Harrison, Spencer Campbell, Catherine L. Stace, Edward H. Walker, Liuhong Chen, Gavin Bennett, Gemma Mudd, Ursula Schierbaum, Karin Leotta, Uwe Haberkorn, Klaus Kopka, Daniel P. Teufel
Journal: Cancer Research (2019)

Abstract Molecular imaging of cancers using probes specific for tumor-associated target proteins offers a powerful solution for providing information regarding selection of targeted therapy, patient stratification, and response to therapy. Here we demonstrate the power of bicyclic peptides as targeting probes, exemplified with the tumor-overexpressed matrix metalloproteinase MT1-MMP as a target. A bicyclic peptide with subnanomolar affinity towards MT1-MMP was identified, and its radioconjugate showed selective tumor uptake in an HT1080 xenograft mouse model. Proteolytic stabilization of the peptide by chemical modification significantly enhanced the in vivo tumor signal [from 2.5%ID/g to 12%ID/g at 1 hour post injection (p.i.)]. Studies using mouse xenograft models with different cell lines show a robust correlation between tumor signals and in vivo MT1-MMP expression levels. Fatty acid modification of the bicyclic peptide extended its circulating half-life, resulting in increased tumor signals (36%ID/g at 6 hours p.i.). Comparative work with an equipotent radiolabeled MT1-MMP targeting antibody demonstrated starkly differential biodistribution and tumor accumulation properties, with the tumor signal slowly increasing to 6.2%ID/g within 48 hours. The rapid tumor penetration characteristics of bicyclic peptides, coupled with high potency and chemical versatility, thus offer high-contrast imaging probes for clinical diagnostics with compelling additional potential in targeted therapy. Significance: This work demonstrates the potential of bicyclic peptides as a platform for the development of high-contrast imaging probes for potential use in clinical cancer diagnostics and molecularly targeted therapeutics.
Abstract 12621: Efficacy and Tolerability of Long-Term Treatment With AMG 145 in Patients With Statin Intolerance
Authors: E A Stein, R Somaratne, M B Schou, F Civeira, D Sullivan, G F Watts, R Weiss, L A Simons, J B Kim, A Xue, R Scott, S M Wasserman, M J Tikkanen
Journal: Circulation (2013)

Background: In the GAUSS Phase 2 12-week placebo-controlled trial in statin-intolerant patients, AMG 145, a monoclonal antibody to PCSK9, was well tolerated and achieved dose dependent LDL-C reductions of 41%-63%. Patients completing the trial were eligible for an open-label long-term extension (OLE). Methods: The extension trial (NCT01439880) re-randomized patients 2:1 to either AMG 145 420 mg every 4 weeks with standard of care (SOC) or SOC alone for one year. The primary objective was to compare the safety and tolerability of the two therapies. Secondary objectives included comparison of long-term effects on lipid parameters. Results: Of 157 patients in the GAUSS trial, 126 (80%) entered into the OLE; 80 received AMG 145/SOC and 46, SOC. The mean (standard error) baseline LDL-C by ultracentrifugation based on entry into the original trial was 194 (6) mg/dL for the AMG 145 group and 195 (8) mg/dL for the SOC group. During follow-up, 3 (4%) of AMG 145/SOC and 2 (4%) of SOC-treated patients discontinued t...
The VWRPY Domain Is Essential for RUNX1 Function in Hematopoietic Progenitor Cell Maturation and Megakaryocyte Differentiation
Authors: Halah Alkadi, David McKellar, Tao Zhen, Tatiana Karpova, Lisa J Garrett, Yongxing Gao, Anfal A Alsadhan, Erika Mijin Kwon, James J Greene, David A Ball, Linzhao Cheng, April D Sorrell, Paul P Liu
Journal: Blood (2018)
Qualitative analysis of Iowa rectal cancer patients’ decisions on where to receive surgery.
Authors: Mary E. Charlton, Ariana Shahnazi, Irena Gribovskaja-Rupp, Chi Lin, Lisa Hunter, Elizabeth A. Chrischilles, Charles F Lynch, Marcia M Ward
Journal: Journal of Clinical Oncology (2018)

835 Background: Current literature suggests surgeons and hospitals that perform large volumes of rectal cancer care achieve superior outcomes, but only about half of rectal cancer resections are performed by high-volume surgeons in comprehensive hospitals. Little is known about considerations of patients with rectal cancer when deciding where to receive surgery. Methods: A purposive sample of stage II/III rectal adenocarcinoma survivors diagnosed 2013-2015 were identified through the Iowa Cancer Registry and interviewed by telephone about factors influencing decisions on where to receive rectal cancer surgery. Interviews were recorded and transcribed, and a thematic analysis was conducted. Results: Thematic saturation was reached after interviewing 15 survivors. Mean age was 63; 60% were male, 53% resided in non-metropolitan areas and 60% received surgery at low-volume centers. Recommendation from a trusted source, usually a physician, appeared to be a main driver of where patients received surgery. Patients who chose high-volume centers were directed by a trusted source to seek care there, whereas patients who chose low-volume centers described valuing hospitals that were closer to home, knowing individuals at the hospital and receiving prior care there, and being familiar with others who received care from a specific surgeon. Most considered surgeon volume and experience to be important determinants of outcomes, but few actually assessed it. Most characterized surgeon experience based on subjective assessments including interpersonal skills, ability to explain procedures and perceived surgeon confidence. Several reported not trusting online sources for treatment information. Conclusions: Most rectal cancer patients in our sample relied on physician referrals to decide where to receive surgery. Further research is needed to determine rectal cancer patients’ preferences for obtaining information about surgeon/hospital volume and experience since our findings suggest they are neither discussing these factors with their surgeon nor researching them on their own. Once preferences are determined, targeted interventions facilitating more informed decision-making by patients can be developed.
Predniso(lo)ne Dosage and Chance of Remission in Patients With Autoimmune Hepatitis
Authors: Simon Pape, Tom J.G. Gevers, Michail Belias, Ilyas F. Mustafajev, Jan Maarten Vrolijk, Bart van Hoek, Gerd Bouma, Carin M.J. van Nieuwkerk, Johannes Hartl, Christoph Schramm, Ansgar W. Lohse, Richard Taubert, Elmar Jaeckel, Michael P. Manns, Maria Papp, Felix Stickel, Michael A. Heneghan, Joost P.H. Drenth
Journal: Clinical Gastroenterology and Hepatology (2019)
Intra-Tumor Heterogeneity in Acute Myeloid Leukemia (AML): Results from a Real Life Cohort
Authors: Marco Cerrano, Marie Passet, Florence Rabian, Ramy Rahmé, Etienne Lengline, Emmanuel Raffoux, Nathalie Dhedin, Aurelie Cabannes-Hamy, Ilhem Rahal, Marie Sebert, Wendy Cuccuini, Odile Maarek, Anna Raimbault, Stéphanie Mathis, Karine Celli-Lebras, Lionel Ades, Pierre Fenaux, Nicolas Boissel, Jean Soulier, Herve Dombret, Emmanuelle Clappier, Raphael Itzykson
Journal: Blood (2018)
Transitioning childhood cancer survivors to adult care: A survey of pediatric oncologists.
Authors: Lisa Brazzamano Kenney, Patrice Melvin, Laurie Fishman, Joanne O'Sullivan-Oliveira, Gregory S Sawicki, Sonja Ziniel, Lisa Diller, Susan M Fernandes
Journal: Journal of Clinical Oncology (2014)

10088 Background: Pediatric oncologists are responsible for facilitating the transition of childhood cancer survivors to risk based adult focused care. This study describes transition practices, perceived barriers to transfer to adult care, and identifies areas for potential intervention. Methods: An electronic survey of U.S. members of the Children’s Oncology Group; 492/1449 responded (34%) and 347/492 (71%) met eligibility (pediatric oncologist caring for outpatients > age 11 years). Results: Of the 347 respondents, 50% are male, median years in practice 10 (range 5-22), 82% are at an academic institution, 37% a free standing children’s hospital, and 5% are board certified in adult medicine. Almost all continue to care for patients up to age 21 years (96%), 42% report continuing to take care of adult patients over age 25 years, 16% over age 30 years, and only 8% over 40 years. While 66% of oncologists report providing transition education to their patients, the majority report also having other staff provide this education (89%). Compared to the 147 (42%) who care for adult patients older than 25 years, those who do not were more likely to endorse specific criteria for transfer including survivors’ age (p=0. 006), pregnancy (p=0.014), marriage (p=0.010), college graduation (p=0.006), and substance use (p=0.036). Most oncologists identified barriers to transfer to adult care including patients’ attachment to provider (91%), parents’ attachment to provider (90%), lack of knowledgeable adult providers (86%), cognitive delay (81%), and unstable social situation (80%). However, oncologists who continue to care for patients older than 25 years are more likely to perceive parents’ attachment to provider (p=0.037) and patients’ unstable social situation as barriers to transfer (p=0.044). Conclusions: Most pediatric oncologists report transferring adult childhood cancer survivors to adult care and providing transition education to their patients. Those who continue to care for survivors as adults are more likely to perceive psychosocial needs as barriers to transfer. Transition practices that address developmental and psychosocial challenges might facilitate successful transfer of childhood cancer survivors to adult care.
Durable remissions with obinutuzumab-based chemoimmunotherapy: long-term follow-up of the phase 1b GALTON trial in CLL
Authors: Jennifer R. Brown, Susan O’Brien, C. Daniel Kingsley, Herbert Eradat, John M. Pagel, Jamie Hirata, Tammy McIver, Rodica Morariu-Zamfir, Thomas J. Kipps
Journal: Blood (2018)
Fig (Ficus carica) leaf extract prevents diethylstilbestrol (DES)-induced DNA strand breaks in single-cell gel electrophoresis (SCGE)/COMET assay
Authors: Alrena Lightbourn, Alicia Tucker, Tunji Fadiora, Larry Russell, Ronald Thomas
Journal: Cancer Research (2008)

2258  Diethylstilbestrol (DES) is a complete carcinogen, known to induce and promote the development of malignant tumors in human breast epithelial cells and rodent models. DES is actively biotransformed by cytochrome P450 drug-metabolizing enzymes to its primary metabolically active intermediate, DES-4,4’-quinone (DES-Q). The interaction of DES-Q with DNA causes DNA adducts and strand breaks. Although the nutritional benefits of figs (ficus carica) have been appreciated for many centuries, little is known about its physiologically active components that may prevent disease. Fig trees are among the oldest plants on earth and are known to have polyphenolic compounds and high fiber content, which are implicated in chemopreventive properties of other natural products. However, the role of ficus carica in preventing cancer has not been elucidated. We therefore hypothesized that fig leaf extract would inhibit (or attenuate) DES-induced DNA single strand breakage in MCF10A human breast epithelial cells. To test this hypothesis, MCF10A cells were dosed with various concentrations of DES (1, 10, 100 µM), various volumes of fig leaf extract (5, 10, 15 µL), and concomitant doses of DES (100 µM)/fig leaf extract (5, 10, 15 µL). The cells were analyzed for DNA strand breakage using the single cell gel electrophoresis (SCGE)/COMET assay with mean olive tail moment as an indicator of DNA damage. DES induced DNA strand breaks at all treatment levels compared to dimethylsulfoxide (DMSO) and non-treatment controls. DES at concentrations of 1, 10, and 100 µM produced mean olive tail moments of 1.2082, 1.2702, and 1.1275, respectively, which were statistically significantly (p
Is laparoscopic resection in select T4 colorectal lesions comparable to open resection for achieving adequate margins?
Authors: Ahmad Elnahas, Fady Saleh, Allan Okrainec, Timothy D. Jackson, Fayez A. Quereshy
Journal: Journal of Clinical Oncology (2014)

e14527 Background: Laparoscopic resection has been considered a relative contraindication for T4 colonic and rectal lesions due to concern over inadequate margins. The objective of this study is to compare planned laparoscopic and open resections of T4 lesions with respect to the positive margin rate. Methods: Data was obtained from the American College of Surgeons National Surgical Quality Improvement Program participant use file to perform a retrospective cohort analysis. The study population consisted of patients that underwent a colorectal resection for a primary T4 lesion during 2011 and 2012. Patients were excluded if they had evidence of metastatic disease. A multiple logistic regression analysis was performed to determine the adjusted odds ratio (OR) of positive margins based on surgical approach (i.e. laparoscopic vs. open). Results: The sub-selected population consisted of 304 and 478 patients in the laparoscopic and open group, respectively. There were no statistical differences between the two groups with respect to demographic and clinical variables including age, sex, body mass index, number of emergency cases, and patients with coagulopathy. However, a significantly higher proportion of patients received neoadjuvant therapy in the open group (p <0.01). The laparoscopic group had 66 (22.68%) cases with positive margins and the open group had 126 (27.9%). Among patients with a planned laparoscopic approach, 77 (25%) required conversion to an open procedure with 19 (25%) cases resulting in positive margins. No statistical difference was found between planned laparoscopic and open resections with respect to positive margin status (OR 0.76, p = 0.13, 95% CI [0.54-1.08]). In addition, no significant clinical predictors for positive margin status were identified. Conclusions: Using this large national surgical database, select patients with T4 lesions that underwent planned laparoscopic colorectal resections did not have a significantly higher positive margin rate compared to patients with open operations. Experienced laparoscopic surgeons are able to selectively perform adequate resections for T4 colorectal lesions.
Association of the prognostic role of CXCR4/CXCL12 polymorphism with treatment outcomes after bevacizumab-based chemotherapy in metastatic colorectal cancer.
Authors: Satoshi Matsusaka, Fotios Loupakis, Wu Zhang, Dongyun Yang, Yan Ning, Sebastian Stintzing, Yu Sunakawa, Shinichi Yamauchi, Stefan Stremitzer, Ana Sebio, Rita Elie El-Khoueiry, Giulia Pasquini, Federica Marmorino, Marta Schirripa, Naoko Inoshita, Yuichi Ishikawa, Masashi Ueno, Nobuyuki Mizunuma, Heinz-Josef Lenz
Journal: Journal of Clinical Oncology (2014)

e22008 Background: The chemokine stromal cell-derived factor-1 (SDF-1)/CXCL12 represents the single natural ligand for the chemokine receptor CXCR4. The CXCL12/CXCR4 axis promotes angiogenesis and the migration of tumor cells into the metastatic sites in many cancers. CXCR4 expression on tumor cells is upregulated by hypoxia and angiogenic factors, such as vascular endothelial growth factor (VEGF). Therefore, we analyzed the association between CXCR4/CXCL12 polymorphisms and prognosis in metastatic colorectal cancer (mCRC) patients underwent bevacizumab-based chemotherapy. Methods: This study included 144 Japanese pts for evaluation set and 424 Italian pts for validation set, with mCRC treated with Bevacizumab-based chemotherapy as first line. A total of 424 Italian patients (pts) (male/female; 252/172, median age 62 years; median follow-up time; 2.8 years), and 144 Japanese pts with (male/female; 81/63, median age 61 years, median follow-up 4.2 years) were enrolled in a pharmacogenomics translational study. Genomic DNA was extracted from the pts’ blood or tissue. One functionally significant CXCR4 single nucleotide polymorphisms (SNP) (rs2228014) and two CXCL12 SNPs (rs1801157, rs3740085) were analyzed by PCR-based direct sequencing. All candidate SNPs were analyzed for association with progression-free survival (PFS) and overall survival (OS). Results: In univariate analysis, rs2228014 (CXCR4) showed a significant difference in PFS [(G/G 15.5 months, any A allele 12.9 months, HR (95% CI) 1.68 (1.03-2.73), p=0.038)]. In multivariate analysis adjusted for baseline characteristics (Liver metastasis, Lung metastasis) and rs2228014 were significant in PFS [HR (95% CI) 1.77 (1.08-2.89), p =0.023]. In the validation set, pts with GG genotype had significantly longer PFS compared to those with any A allele (10.5 vs 9.6 months, HR (95% CI) 1.40 (1.02-1.93), p =0.035) in univariate analysis. Overall, these polymorphisms were not associated with survival. Conclusions: This study shows for the first time that the CXCR4 polymorphism, rs2228014, may serve as a predictive marker in patients with mCRC treated with bevacizumab-based chemotherapy.
Nasopharengeal carcinoma in children and adolescents: Clinical and therapeutical characteristics and long-term outcome.
Authors: Rejin Kebudi, Rasim Meral, Omer Gorgun, Fatma Betul Cakir, Sukran Celikarslan, Fulya Yaman Agaoglu, O. Bulent Zulfikar, Emin Darendeliler, Inci Ayan, Musa Altun
Journal: Journal of Clinical Oncology (2014)

e21012 Background: The aim of this study was to evaluate the demographic, clinical and therapeutic characteristics and long-term outcome in childhood and adolescent nasopharyngeal carcinoma (NPC) retrospectively in a single center. Methods: From November 1989 to January 2014, the files of 85 patients younger than 18 years of age with NPC, treated in Istanbul University Oncology Institute, were evaluated. All patients received three courses of neoadjuvant chemotherapy (1989-1994; cisplatinum-based regimens; 1995-2008; bleomycin, epirubicin and cisplatinum- BEP; since 2008- ;EP) followed by radiotherapy given both to the primary tumor and to the metastatic cervical lymph nodes. Results: Sixty-four boys and 21 girls with a median age of 14 yrs (6-18) presented mostly with a lump in the neck, headache, and ear and nose problems. The median duration of symptoms was 4 months (1-24 mo.). The median follow-up time was 118 months (1mo.-24 years). Eighty-eight % (n=75) of NPC were WHO type III tumors. Most patients had advanced stage tumors (III=40, IVA=17, IVB=23) with 2 distant metastatic sites (IVC=2) according to AJCC staging system. BEP and EP were followed with radiotherapy 60Gy to the primary tumor and involved lymph nodes, and 50-54Gy to the cervical nodal region. The 10-year overall (OS) and event-free survival (EFS) rates were 79.5% and 78.7%, respectively. There was no significant difference in 10 yr-OS and EFS in BEP or EP (no bleomycin) receivers. Eight patients died due to relapsed/progressive disease. Secondary malignancy developed in two patients; one developed osteosarcoma in the radiation field (at 42. months posttreatment), the other had PNET. Late effects included hypothyroidism, neck fibrosis, xerostomia, bony hypoplasia, skin problems and hearing loss. Conclusions: Children and adolescents with advanced NPC had a relatively good rate of long-term survival. Neoadjuvant therapy and radiotherapy leads to high locoregional control and survival in advanced stage NPC; EP seems to be as effective as BEP, suggesting that bleomycin may be omitted. Survivors should be followed for long-term morbidities.
NHS to set up new alcohol and tobacco services for patients admitted to hospital
Authors: Gareth Iacobucci
Journal: BMJ (2019)

The NHS will establish new dedicated alcohol and tobacco treatment services to help vulnerable problem drinkers and smokers admitted to hospitals in England.

New alcohol care teams will be set up in up to 50 NHS hospitals to provide on the spot support to patients and their families dealing with alcohol misuse. The teams will be rolled out in areas with the highest number of alcohol related admissions, working with local community services to provide support such as counselling and medically assisted help.

And 600 000 smokers admitted to hospitals in areas of the country with the greatest …