tbuckley/cabot-search huggingface dataset:
Multicenter performance evaluation of the MultiDrugQuant assay kit.
Authors: Peter Krajcsi, Katalin Tauber Jakab, Sandor Barath, Edit Gyimesi, Zsuzsanna Hevessy, Valeria Sziraki Kiss, Peter Szabo, Margit Tokes-Fuzesi, Eva Trucza, Janos Kappelmayer, Janos Marki-Zay
Journal: Journal of Clinical Oncology (2012)

e21140 Background: Multidrug resistance is the most frequent type of resistance to anticancer chemotherapy, which usually results from the overexpression of efflux transporters, such as the MDR1, MRP1 and BCRP. Unfortunatelly, neither the genetic polymorphisms nor the mRNA/protein expression levels correlate closely with the functional activity. On the other hand, although the functional methods separately gave promising results, standardization and reproducibility of these tests failed to conform with values required from routine diagnostic methods. MultiDrugQuant (MDQ) kit was developed as an improved functional assay system, which can measure the multidrug resistance activity of the three, clinically most relevant efflux transporters using flow cytometry in living tumor cells. The present study aimed to carry out the laboratory validation and to evaluate the performance of the MDQ-kit. Methods: Validation of the kit was carried out according to the standards of the Clinical Laboratory Standards Institute in three university centres. Mononuclear cells were separated using Ficoll gradient and tested at 2-5×10 6 /ml within 6 hours after specimen collection. Activities of the multidrug transporters were calculated from the difference between the mean fluorescent intensity of cells w/o the specific inhibitors, respectively. Inaccuracy and comparative measurements were carried out using cell lines with low and high activity of the transporters. Results on different flow cytometers were compared using CD45 CD19 or CD3 monoclonal antibodies for gating the population of interest. Results: The assay proved to be specific and robust at various concentrations of the fluorescent dyes (10-100 % of the original) or inhibitors (50-150 % of the original). Both intraassay and interassay reproducibilities were &lt;5 %. Multidrug resistance activity values determined on different flow cytometers were comparable and eligible. Conclusions: The MDQ assay provides quantitative results on the activity of the MDR1, MRP1 and BCRP in the target cells, which might be used to predict the resistance of these cells to particular cytotoxic agents. Recently, the MDQ-kit has been registered for in vitro diagnostic use in the EU.
CLO20-062: Comparative Efficacy of Elotozumab With Panobinostat and Ixazomib in Multiple Myeloma; A Meta-Analysis
Authors: Nishanth Thalambedu, Waqas Ullah, Ammar Ashfaq, Yasir Khan, Ammar Ashfaq, Qian Zhang, Mishal Shaukat
Journal: Journal of the National Comprehensive Cancer Network (2020)
A benchmark of algorithms for the analysis of pooled CRISPR screens
Authors: Sunil Bodapati, Timothy P. Daley, Xueqiu Lin, James Zou, Lei S. Qi
Journal: Genome biology (2020)

Abstract Genome-wide pooled CRISPR-Cas-mediated knockout, activation, and repression screens are powerful tools for functional genomic investigations. Despite their increasing importance, there is currently little guidance on how to design and analyze CRISPR-pooled screens. Here, we provide a review of the commonly used algorithms in the computational analysis of pooled CRISPR screens. We develop a comprehensive simulation framework to benchmark and compare the performance of these algorithms using both synthetic and real datasets. Our findings inform parameter choices of CRISPR screens and provide guidance to researchers on the design and analysis of pooled CRISPR screens.
PCSK9 INHIBITOR INITIATION AMONG VETERANS ACCORDING TO THE 2018 AHA/ACC BLOOD CHOLESTEROL GUIDELINES
Authors: Catherine G. Derington, Jordan King, Robert S. Rosenson, Bharat Poudel, Keri Monda, Ann Navar, Katherine Mues, James Cook, Vanessa Stevens, Jennifer S. Herrick, Paul Muntner, Lisandro Colantonio, Adam Phillip Bress
Journal: Journal of the American College of Cardiology (2020)
Intranasal midazolam for febrile seizures
Authors: Gideon Koren
Journal: BMJ (2000)

Papers p 83 

Despite their benign nature and prognosis, uncomplicated febrile seizures are extremely stressful for both families and medical staff. Most parents believe that these seizures are harmful, and during the first episode half of all parents fear that their child is dying.1 For decades children were given long term anticonvulsant drugs to prevent the recurrence of febrile seizures. Although some of these are effective, their serious adverse effects have led to an unacceptable ratio of benefits to risks.2 3

There is, however, a broad consensus that febrile seizures should be treated promptly. Traditionally, benzodiazepines, barbiturates, or other anticonvulsants have been given intravenously, but rectally administered diazepam is now used as an efficacious alternative.

The intranasal administration of therapeutic agents is undoubtedly the centre of tremendous interest in the field of therapeutics. That there is extensive and prompt absorption of molecules through the nasal mucosa into a rich vascular bed has long been recognised by cocaine users.

In …
ABBREVIATED DAPT FOLLOWED BY P2Y12 MONOTHERAPY AS COMPARED TO STANDARD DAPT POST-PCI: A SYSTEMATIC REVIEW AND META-ANALYSIS
Authors: Rajkumar P. Doshi, Ashish Kumar, Devina Adalja, Jay Shah, Perwaiz M. Meraj, Rajiv Jauhar
Journal: Journal of the American College of Cardiology (2020)
Analysis of the pathological response to primary chemotherapy in patients with locally advanced breast cancer (LABC) grouped according to ER, PR and HER2 status
Authors: L. A. Fernandez-Morales, E. Dalmau, S. Martinez, A. Arcusa, C. Pericay, J. M. Lain, J. Font, L. Tortajada, E. Saigi, M. A. Segui-Palmer
Journal: Journal of Clinical Oncology (2006)

626 Background: The determination of ER and PR has a considerable importance when evaluating the prognosis and the response to treatment in breast cancer (BC). Assessment of HER2 status is also a standard for the management of BC. Hormone receptors (HR), HER2, and increasingly, genomic profiles distinguish at least four major classes of BC: HER2+; HER2-HR+, which can be divided into two classes, favorable and unfavorable; and basal-like that express neither HER2 nor HR. In the clinical practice is possible to divided BC according to ER, PR and HER2: ER-PR-HER2+, ER-PR-HER2-, ER+PR+HER2-, ER+RP+HER2+; and less frequently ER+PR-HER2-, ER+PR-HER2+, ER-PR+HER2+ and ER-PR+HER2-. In the neoadjuvant setting the pathological complete response (pCR) to primary chemotherapy (PC) is associated to negativity for ER and PR receptors, and in patients (pts) with HER2 + BC, the addition of trastuzumab to PC increasing the rate of pCR. The aims of this study were to determine the pCR of PC with anthracyclines (A) and taxanes (T) in pts with LABC grouped according to ER, PR and HER2 status. Methods: Pts with LABC treated with PC including A and T were grouped according to ER, PR and HER2 status, and the pCR rate were analyzed using the chi-squared test and correlations with a p value of ≤0,05 were considered statistically significant. Results: A total of 103 pts were treated. There were 14.6% of ER-PR-HER2+ BC, 23.3% ER-PR-HER2-, 35.0%ER+PR+HER2-, 8.7% ER+PR+HER2+, 11.7% ER+PR-HER2-, 2.9% ER+PR-HER2+, 1.9% ER-PR+HER2+, and 1.9% ER-PR+HER2-. For the analysis of pCR only 100 pts were included. There were18 pts who achieved a pCR. Of these pts, 9/18 (50.0%) were RE-RP-HER2-, 5/18 (27.8%) ER-PR-HER2+, 3/18 (16.7%) ER+PR+HER2+, and 1/18 (5.6%) ER+PR+HER2- (p≤0.01). The table 1 show the pCR rate for each subgroup of BC. Conclusions: In patients with LABC to group BC according to ER, PR and HER2 status can help to predict pCR to PC. [Table: see text] No significant financial relationships to disclose.
LEFT VENTRICULAR FREE WALL RUPTURE CONTAINED BY POST-OPERATIVE INTRAPERICARDIAL ADHESIONS FROM PREVIOUS CORONARY ARTERY BYPASS SURGERY
Authors: Shruti Hegde, Argyro Papafilippaki, Abraham Cherukara, Vybhav Jetty, Michael Johnstone, Shaw Natan
Journal: Journal of the American College of Cardiology (2020)
Comparison of toxicity experienced by elderly (E) and younger (Y) patients in breast cancer (BC) clinical trials.
Authors: Caroline Joy Mariano, Mia Ivy Francl, Howard John Lim, Janice Pope, Linda Wong, Caroline A. Lohrisch
Journal: Journal of Clinical Oncology (2013)

9542 Background: E patients (pts), age 65 and older, form a large percent of BC pts, but are under-represented in trials, due to actual/perceived frail health, or actual/perceived greater potential toxicity from therapy (rx). With ethics approval, we examined whether E pts had more toxicity than Y pts (&lt; 65 years) in clinical trials. Methods: All BC phase II and III drug trials open from 1999 to 2012 at British Columbia Cancer Agency Vancouver Center were reviewed, excluding trials with only premenopausal pts. Adverse events (AE) were captured from case report forms and charts. The primary endpoint was meaningful toxicity (MTOX), defined as any grade 3 or 4 AE; any AE with dose delay or reduction; or premature discontinuation of rx. Frequencies of MTOX were compared using chi-square tests, means were compared with T-tests. Results: Among 46 trials enrolling 799 pts, rx types were chemotherapy ([CT], 18% of pts), hormone ([HT] 40%), skeletal ([ST] 14%), targeted ([T] 14%]) and CT + T (14%). Pts were 19% E (age range 65-84) and 81% Y (age range 25-64). E pts were more likely to enroll in HT and ST trials; Y pts were evenly distributed among all rx types. Toxicity data (Table) was available for 778 pts (97%). Conclusions: In non CT trials, E and Y pts had similar frequency and number of MTOX. Few E (5%) enrolled in CT trials, but with no more MTOX than Y pts. Discontinuation of rx was equal in E and Y, considering all rx types. Appropriate selection of E pts by eligibility criteria, self selection, and/or clinician assessment allows safe participation of E pts in BC trials. Fear of increased MTOX should not exclude fit E pts from trial participation. [Table: see text]
Is there any prognostic importance of pretreatment serum M30 and serum M65 levels on progression-free survival of patients with metastatic renal cell carcinoma treated with first-line sunitinib?
Authors: Mert Basaran, Ibrahim Yildiz, Fatma Sen, Leyla Kilic, Serkan Keskin, Emin Darendeliler, Sevil E. Bavbek
Journal: Journal of Clinical Oncology (2013)

e15569 Background: Effective cancer biomarkers for early detection, prognosis, or prediction of therapy response are urgently need in metastatic renal cell cancer (RCC). Soluble cytokeratin 18 fragments (M30, M65) are released from human cancer cells during epitelial cell death. Specific enzyme-linked immunosorbent assays (ELISA) using related antibodies distinguish between apoptotic (M30) or apoptotic and necrotic (M65) tumor cell death in serum samples. The aim of this study was to determine the prognostic value of plasma M30 and M65 levels in predicting survival rates of patients with metastatic RCC treated with first-line sunitinib. Methods: Thirty-nine patients with metastatic RCC and 39 healthy controls were included in this study. The patients’ samples were collected prior to the first cycle of sunitinib therapy and serum M30 and M65 levels were measured by ELISA. Results: The median ages of the patients and controls were 60 and 58 years, respectively. No difference was detected in the median serum M30 level between the patients and controls (53.7 vs. 49.1 U/l, P = 0.31). The median serum M65 level was significantly higher in patients than in controls (334.0 vs. 179.1 U/l, P&lt;0.001). Receiver operating characteristic (ROC) analysis revealed that the best cut-off value for serum M65 level for predicting progression-free survival (PFS) was 313.6 U/l. The median PFS of patients whose M65 levels were lower than or equal to 313.6 U/l was better than that of patients whose M65 levels were greater than 313.6 U/l (P = 0.03) in univariate analysis. But serum M65 levels in patient group were not found to be an important prognostic factor for PFS in the multivariate analysis. Conclusions: Serum M65 levels were significantly elevated in patients with metastatic RCC compared to healthy individuals. Future prospective studies with large sample sizes are needed to address the possible impact of M30 and M65 levels on the treatment responses of patients and whether these markers may be prognostic factors for PFS or OS in patients with RCC.
LIPOPROTEIN(A) AND CORONARY ARTERY CALCIUM SCORE FOR PREDICTING ATHEROSCLEROTIC CARDIOVASCULAR DISEASE RISK
Authors: Nestor Vasquez, Anurag Mehta, Colby Ayers, Jaideep Patel, Ananya Hooda, Amit Khera, Michael Blaha, Roger S. Blumenthal, Michael Tsai, Laurence S. Sperling, Michael D. Shapiro, Salim S. Virani, Parag Joshi
Journal: Journal of the American College of Cardiology (2020)
PTH-103 Outcomes following the introduction of anti-tnf drug and antibody testing to a biologics clinic for patients with inflammatory bowel disease
Authors: A Boal, SI Squires, GD Naismith
Journal: Gut (2017)

Introduction  The Royal Alexandra and Vale of Leven Hospitals have a comprehensive and structured yearly biologicals meeting to carry out case reviews on all patients receiving anti-TNF treatment. This report aims to describe outcomes following the introduction of drug level and antibody testing (TDM) to our assessment criteria.  Method  In July 2015, drug level and antibody testing was introduced as part of the case review process for all patients actively treated with either Infliximab (IFx) or Adalimumab (ADA). Bloods obtained were processed at the Exeter Clinical Laboratory using ELISA assay kits. Drug levels were sub-categorised; greater than or equal to 3 µg/mL [Group 1-therapeutic] greater than 0.8 µg/mL but less than 3 µg/mL [Group 2- subtherapeutic] or less than 0.8 µg/mL [Group 3- undetectable]. This information was used in addition to clinical assessment which included colonoscopy, faecal calprotectin, serum biomarkers and radiological imaging where applicable. Treatment decisions were then made based on the available information and an algorithm was adapted to guide treatment changes  Results  44 patients had TDM levels obtained (32 ADA and 12 IFx).  In group 1; 31/44 (70%) had therapeutic drug levels. Despite therapeutic drug levels, 6/31 patients (19%) had ongoing disease activity and switched biological agent.  In group 2; 3/44 (7%) had subtherapeutic levels with ongoing disease activity and had switch of biologic agent.  In group 3; 10/44 (23%) had undetectable levels and 9/10 (90%) had developed antibodies. 5/10 (50%) had endoscopic remission and were withdrawn from treatment and maintained on thiopurines. All 5 maintain remission to date at 18 months post withdrawal. 5/10 (50%) had ongoing disease activity and had a switch of biologic agent.  In total 13/44 (30%) had treatment changes based on TDM.  Conclusion  The addition of TDM contributed to clinical decision making in 30% of this cohort. TDM facilitated early identification of 11% of this cohort suitable for treatment withdrawal who sustained remission at 18 months. These data may support other units establishing a business plan for introduction of TDM.  Disclosure of Interest  None Declared
Review of practice patterns of primary granulocyte-colony stimulating factor prophylaxis and impact on febrile neutropenia rate and chemotherapy delivery in patients with early breast cancer treated with modern adjuvant chemotherapy.
Authors: Mihaela Mates, Wilma Hopman, Abdullah Khalaf Altwairgi
Journal: Journal of Clinical Oncology (2012)

e19541 Background: Febrile neutropenia (FN) is a major complication of chemotherapy and is associated with substantial morbidity and mortality. Primary prophylaxis with granulocyte colony-stimulating factors (PP-G-CSF) is recommended for regimens with FN risk above 20%. We undertook a review of practice patterns of PP-G-CSF and impact on febrile neutropenia rate and chemotherapy delivery in patients with early breast cancer (EBC) treated with modern adjuvant chemotherapy (ACT) at the Cancer Centre of Southeastern Ontario. Methods: Women with EBC receiving at least one cycle of modern ACT (taxane containing regimens with or without anthracyclines) between January 2009 and December 2011 were included in our review. We collected demographic, disease-related, treatment-related, and outcome variables for each patient. Results: 239 women were treated with modern ACT during the specified period and were included in our analysis. Median age was 55 (32-80); 197 (82%) were &lt;65 years and 148 (62%) were postmenopausal. 212 (89%) patients were treated with an anthracycline-taxane (A-T) regimen and 27 (11%) with a taxane (T) regimen. 145 patients (61%) received PP-G-CSF: 47 (32%) with filgrastim (F) and 98 (68%) with pegfilgrastim (PF). Of all patients 50 (21%) developed at least one FN episode. PP-G-CSF led to lower FN rate (15% vs 31%; p=0.002), reduced dose delay (17% vs 27%; p=0.060) and dose reduction (19% vs 25%; p=0.28) of planned ACT. In women receiving PP-G-CSF higher rate of FN was associated with age ≥ 65 years (27% vs 12% if &lt; 65 years; OR 2.8, p=0.053); T regimen (30% vs 12% for A-T; OR 3.1, p=0.041) and F use (28% [n=13] vs 8% [n=8] with PF; OR 4.3, p=0.003). Conclusions: In this single-centre retrospective cohort study patients with EBC treated with modern ACT had a high rate of FN (31%) without PP-G-CSF. More than half (61%) of the patients received PP-G-CSF which led to fewer FN episodes and increased delivery of planned ACT; however, the risk of FN remained high at 15%. Factors linked to higher rate of FN despite PP-G-CSF were older age, taxane-based chemotherapy and use of filgrastim.
TRENDS IN TRANSCATHETER AND SURGICAL AORTIC VALVE REPLACEMENT AMONG MEDICARE BENEFICIARIES IN THE UNITED STATES, 2012-2017
Authors: Aakriti Gupta, Yun Wang, Susheel K. Kodali, Isaac George, Torsten Vahl, Makoto Mori, Ajay Kirtane, Martin Leon, Harlan M. Krumholz
Journal: Journal of the American College of Cardiology (2020)
The prognostic role of XRCC1, ERCC1, ERCC2, and TP53 single nucleotide polymorphisms (SNPs) in resected non-small cell lung cancer (NSCLC).
Authors: Caglayan Geredeli, Mehmet Artac, Selman Yildirim, Isa Dede, Ali Inal, Tunc Guler, Melih Cem Boruban, Ayse Gul Zamani, Hakan Bozcuk, Ahmet Demirkazik
Journal: Journal of Clinical Oncology (2013)

e18521 Background: Identification of biomarkers that can be used for the prognostic evaluation of NSCLC patients is important. The aim of this study was to evaluate the potential prognostic value of XRCC1, ERCC1, ERCC2 and, TP53 SNPs in completely resected NSCLC patients. Methods: In total 130 patients, who had been surgically treated for NSCLC between 2000 and 2012, were included in this study. Analysis of SNPs from peripheral blood cells was performed by polymerase chain reaction. XRCC1 Arg399Gln, ERCC1 Asn118Asn, ERCC2 Lys751Gln and, TP53 Arg72Pro polymorphisms were evaluated in conjunction with clinical and pathological parameters and survival. Kaplan-Meier method and Cox regression analysis were used. Results: In the univariate analysis for disease free survival (DFS) post operative stage (HR,0.50; 95%CI, 0.26-0.96; P=0.03), ERCC2 genotype (HR, 2.47; 95%CI, 1.28-4.78; P=0.007) and PET-CT staging (HR, 0.27;95%CI, 0.14-0.52; P&lt;0.001) were significant parameters. Adjuvant chemotherapy, age and the other SNPs were not significant. In the multivariate analysis post operative stage (HR, 0.40;95%CI, 0.20-0.81; P=0.01), ERCC2 genotype (HR, 2.66;95%CI, 1.35-5.27; P=0.005), PET-CT staging (HR, 0.24;95%CI, 0.12-0.47; P&lt;0.001) retained their significance. The median DFS was 56.5 months (95%CI, 24.6-88.4 months) for the ERCC2 mutant (TT) and heterozygote (GT) genotypes, and 28.3 months (95%CI, 20.8-35.8 months) for the ERCC2 normal (GG) genotype (P=0.005). Conclusions: In addition to stage and PET-CT staging, ERCC2 genotype independently predicted DFS in resected NSCLC patients. Future prospective studies are needed for the further evaluation of potential prognostic SNPs in resected NSCLC.
Longitudinal study reveals HIV-1–infected CD4+ T cell dynamics during long-term antiretroviral therapy
Authors: Annukka A.R. Antar, Katharine M. Jenike, Sunyoung Jang, Danielle N. Rigau, Daniel B. Reeves, Rebecca Hoh, Melissa R. Krone, Jeanne C. Keruly, Richard D. Moore, Joshua T. Schiffer, Bareng A.S. Nonyane, Frederick M. Hecht, Steven G. Deeks, Janet D. Siliciano, Ya-Chi Ho, Robert F. Siliciano
Journal: Journal of Clinical Investigation (2020)

Proliferation of CD4+ T cells harboring HIV-1 proviruses is a major contributor to viral persistence in people on antiretroviral therapy (ART). To determine whether differential rates of clonal proliferation or HIV-1–specific cytotoxic T lymphocyte (CTL) pressure shape the provirus landscape, we performed an intact proviral DNA assay (IPDA) and obtained 661 near–full-length provirus sequences from 8 individuals with suppressed viral loads on ART at time points 7 years apart. We observed slow decay of intact proviruses but no changes in the proportions of various types of defective proviruses. The proportion of intact proviruses in expanded clones was similar to that of defective proviruses in clones. Intact proviruses observed in clones did not have more escaped CTL epitopes than intact proviruses observed as singlets. Concordantly, total proviruses at later time points or observed in clones were not enriched in escaped or unrecognized epitopes. Three individuals with natural control of HIV-1 infection (controllers) on ART, included because controllers have strong HIV-1–specific CTL responses, had a smaller proportion of intact proviruses but a distribution of defective provirus types and escaped or unrecognized epitopes similar to that of the other individuals. This work suggests that CTL selection does not significantly check clonal proliferation of infected cells or greatly alter the provirus landscape in people on ART.
NON-INVASIVE MOLECULAR IMAGING OF INFLAMMATION IN TISSUE-ENGINEERED VASCULAR GRAFTS USING 18F-FDG PET/CT
Authors: Rosamaria Tricarico, Ting-Heng Chou, Susan Natalie Eisert, James Reinhardt, Kejal Shah, Yuichi Matsuzaki, Jason Zakko, Toshiharu Shinoka, Christopher K. Breuer, Mitchel R. Stacy
Journal: Journal of the American College of Cardiology (2020)
THE MECHANISM OF BALLOON UNCROSSABILITY ASSESSED BY INTRAVASCULAR ULTRASOUND
Authors: Hanan Salem, Gary Mintz, Mitsuaki Matsumura, Mingyou Zhang, Khady Fall, Ziad Ali, Ajay Kirtane, Tamim Nazif, Manish Parikh, Michael Collins, Jeffrey Moses, Dimitri Karmpaliotis, Akiko Maehara
Journal: Journal of the American College of Cardiology (2020)