tbuckley/cabot-search huggingface dataset:
Abstract 19503: Durability of Antiplatelet Effect of a Novel Extended-release Formulation of Acetylsalicylic acid, Durlaza in Patients With Diabetes
Authors: Paul A Gurbel, Kevin Blide P. P Bliden, Jeff Patrick Patrick, Katayoon Saadin Saadin, Udaya Tantry
Journal: Circulation (2015)

Background: High platelet turnover (HPT) is implicated in incomplete platelet inhibition and high platelet reactivity (HPR) during immediate release aspirin therapy in type II diabetes patients (T2DM). Durlaza is a new, extended-release orally administered aspirin formulation developed to provide 24-hour antithrombotic effects with once-daily dosing. Methods: In this open-label, single-center study, T2DM patients (n=40) and a history of cardiovascular disease (CVD) or multiple CVD risk factors were treated with daily 162.5 mg Durlaza for 14±4 days and adverse events were collected. Antiplatelet effects were determined by conventional aggregation (LTA), Multiplate analyzer, thrombelastography with PlateletMapping, PlateletWorks ,VerifyNow Assay, and serum thromboxane B2 (TxB2) at 1, 12, 16, and 24 hrs after the last dose. HPT was defined as immature platelet fraction of ≥3.0% or MPV≥11.0 fl. Patients exhibiting HPT and/or HPR (based on previously published cutpoints in ≥2 assays) were treated with Durlaza at 325mg for 14± 4 days and platelet function testing was repeated. Results: Prevalence of HPT and HPR was 47% and 27%, respectively. There was no loss of antiplatelet effect at 12, 16 and 24 h versus 1 h by all assays (Table 1). All patients responded to 162.5mg Durlaza as measured by arachidonic acid-induced aggregation with LTA and platelet reactivity levels were low at all timepoints (Table). Serum TxB2 was lower at 12 h (p&lt;0.03) as compared to 1 h after 162.5mg and was lower at all times with the 325 mg vs. the 162.5 mg Durlaza (p &lt; 0.05). HPT did not affect the PD profile of Durlaza (Pts with HPT vs. no HPT, p=NS for all). Patients had no serious adverse events and low treatment related AE rate (&lt;5%). Conclusion: In this first comprehensive assessment, a new, extended-release 162.5 Durlaza provided sustained antiplatelet effects over 24 h in T2DM patients with a favorable safety profile. Doubling the dose further lowered serum TxB2 in pts with HPT and/or HPR.
Safety Data from a First-in-Human Phase 1 Trial of NKG2D Chimeric Antigen Receptor-T Cells in AML/MDS and Multiple Myeloma
Authors: Sarah Nikiforow, Lillian Werner, Joana Murad, Matthew Jacobs, Lauren Johnston, Sarah Patches, Randie White, Heather Daley, Helene Negre, Jake Reder, Charles Sentman, Terri Wade, Adam Schmucker, Frédéric François Lehmann, Sarah Snykers, Rachel Allen, Heidi Dipietro, Kristen Cummings, Ilene Galinsky, Nikhil C. Munshi, Robert L. Schlossman, Richard M. Stone, Donna S. Neuberg, Robert J. Soiffer, Glenn Dranoff, Jerome Ritz, Susanne H.C. Baumeister
Journal: Blood (2016)
Plerixafor plus G-CSF (P+G) compared with G-CSF alone (G) for hematopoietic progenitor cell (HPC) mobilization in AL amyloidosis (AL).
Authors: Binod Dhakal, Christopher Sun Strouse, Carlos Arce-Lara, Anita D'souza, Jean Esselman, Daniel Eastwood, Marcelo C. Pasquini, Wael Saber, William R Drobyski, Parameswaran Hari, Mehdi Hamadani
Journal: Journal of Clinical Oncology (2014)

8606 Background: Cytokine-based HPC mobilization in AL is frequently complicated by fluid overload, weight (wt.) gain, arrhythmia, collection failure and peri-mobilization mortality. Methods: We analyzed HPC mobilization outcomes of 49 consecutive AL pts. at our institution between 2004-2013 with G alone (10μg/kg/d) (n=25) vs. an institutional protocol to limit G exposure using plerixafor (P+G) (P at 0.24mg/kg SC starting 3 day of G 10μg/kg) (n=24). CD34+ HPC yield on day 1 of collection, total CD34+ yield, apheresis days and perimobilization morbidity were analyzed. Mobilization failure was defined as failure to collect ≥2×106cells/kg body weight. Results: Baseline characteristics of two groups are shown in Table. P+G strategy yielded higher total CD34+ cells/kg (12.8 ×106 vs. 6.3 ×106; p<0.001), CD34+ cells/kg collected on day 1(10.8 ×106 vs. 4.9 ×106, p=0.004) compared with G alone cohort. More P+G pts. collected ≥5 ×106 CD34+HPCs/kg (22 vs.16, p=0.02) and ≥10 ×106 CD34+ HPCs/kg (13 vs. 5,p=0.01). Four pts. (16%) had mobilization failure with G alone, none with P+G. G exposure was less and peri-mobilization weight gain lower with P+G strategy (median weight gain 1 lbs. vs. 7 lbs., p=0.009). Numbers of apheresis sessions (median 1 vs. 1,p=0.52), the hospital days during mobilization (1.1 vs. 1.6,p=0.52), transfusion, antibiotic needs and arrythmia were similar between groups. Conclusions: This first report of upfront P+G mobilization in AL provides key feasibility data. Robust HPC mobilization in AL pts. with no unexpected adverse events was achieved with P+G.Superior HPC numbers, no mobilization failure and less weight gain are advantages compared to G alone. Variables G G+P P value Age yr. (median, range) 56.6(30.1-75) 56.9(44.1-71.1) 0.34 Male sex, N (%) 11(44%) 12(50%) 0.67 Prior lines of therapy (median, range) 0(0-4) 1(0-3) <0.001 KPS (median, range) 90(60-100) 90(60-100) 0.05 BM plasma cell (%) Dx 0.1(0-0.4) 0.1(0-0.8) 0.19 ≥PR with therapy 3(12%) 10(42%) <0.001 3+ organs involved, N (%) 14(56) 7(29.2) 0.20
Highly active antiretroviral therapy
Authors: Rita Murri
Journal: BMJ (2005)

Exhaustion of treatment options is a challenge that can be delayed 

A n HIV infected person can possibly live a normal lifespan today, provided she or he takes highly active antiretroviral therapy and takes it perfectly. As pointed out by Sabin et al in this issue,1 even though new drugs are available each year, a noteworthy proportion of people are at risk of exhausting their treatment options. This proportion is only an imperfect surrogate of the presence of mutations giving rise to resistance to antiretrovirals. For an increasing number of patients, identifying a new regimen that could lower the HIV viraemia, increase the CD4 cell count, and prevent clinical progression is somewhat complicated. Looking at reasons why a current regimen is no longer working may help to make the available options clearer.

Suboptimal adherence to treatment is the most common and crucial reason for failing an antiretroviral regimen. Taking treatment at the correct …
FOXO1 Is Involved in the Regulation of B-Cell Precursor Acute Lymphoblastic Leukemia Survival and Serves As a Novel Target for Directed Therapy
Authors: Salih Demir, Fan Wang, Franziska Gehringer, Clarissa Weitzer, Klaus-Michael Debatin, Thomas Wirth, Lüder Hinrich Meyer, Alexey Ushmorov
Journal: Blood (2016)
Toll-like receptors in COPD
Authors: Philip M. Hansbro, Tatt Jhong Haw, Malcolm R. Starkey, Kensuke Miyake
Journal: European Respiratory Journal (2017)

Chronic obstructive pulmonary disease (COPD) is a major cause of illness and death globally; treatments that effectively halt progression or reverse the disease, or reduce the occurrence and/or severity of exacerbations, are urgently required [1]. The lack of effective treatments results largely from the incomplete understanding of the mechanisms of pathogenesis of COPD. The pathogenesis of this disease is driven by chronic inhalation of noxious particles, often cigarette smoke, that persistently stimulates innate and inflammatory responses [2]. Over time, these responses cause repeated cycles of wound and repair that result in airway remodelling with mucus hypersecretion, collagen deposition, and fibrosis and emphysema. These combine to obstruct the airways and reduce lung function, which is characteristic of the disease. TLR4 and NODs could be potential therapeutic targets in chronic obstructive pulmonary disease <http://ow.ly/qaqt30b7YAy>
French comment on article Premedication with simethicone and N-acetylcysteine in improving visibility during upper endoscopy: a double-blind randomized trial1 Prémédication par siméticone et N-acetylcystéine pour améliorer la visualisation lors de gastroscopie : une étude randomisée en double aveugle
Journal: Endoscopy (2017)

On attache de plus en plus d’importance à la qualité des examens endoscopiques et en particulier en coloscopie. Qu’en est-il de la gastroscopie? Dans la majorité des pays, seule l’observation d’un jeûne de 6 heures est requise avant une gastroscopie. Au Japon, la plupart des patients reçoivent du siméticone (effet antimousse) et de la pronase (effet mucolytique) avant une endoscopie digestive haute dont le but est d’améliorer la visualisation de la muqueuse. La pronase n’étant pas disponible dans la majorité des pays, elle peut être remplacée par la N-Acétylcystéine. Dans cette étude portugaise, prospective, monocentrique, contrôlée, randomisée en double aveugle, 300 patients recevaient 15 à 30 minutes avant leur gastroscopie réalisée vigile sans sédation: groupe A (n = 99) placebo — 100 ml d’eau) ; groupe B (n = 101) — 100 ml d’eau + 100 mg de siméticone et groupe C (n = 100) — 100 ml d’eau + 100 mg de siméticone + 600 mg de N-Acétylcystéine. Le score endoscopique de visibilité était défini comme suit: excellent, adéquate ou inadéquate. L’objectif principal de cette étude était atteint, car la prise de siméticone (groupe B) ou la prise de siméticone et de N-Acetylcysteine amélioraient le score de visualisation de la muqueuse comparée à l’eau seule (groupe C). Voici respectivement les résultats en détail de 3 segments du tube digestif haut: œsophage (91,1 % B et 86,7 % C versus 71,4 % A), estomac (76,2 % B et 74,5 % C versus 38,8 % A). Dans le duodénum, la différence n’était pas significative 85,1 % B et 81,6 % C versus 73,5 % A (p = 0.11). Par contre, il n’y avait pas de différence significative entre le groupe B et C et donc l’ajout de N Acétylcystéine, n’apportait rien sur la qualité de la visibilité intestinale. Un seul effet secondaire non sévère est à déplorer dans cette étude (0, 3 %) : un patient a présenté des vomissements pendant l’endoscopie, mais ceux-ci ne pourraient être attribués au siméticone ou à la N-Acétylcystéine, car il est survenu dans le groupe A (eau seule). Cette étude démontre que la prise de siméticone avec un verre d’eau avant une gastroscopie améliore la visualisation de la muqueuse du tractus digestif haut et en particulier l’œsophage et l’estomac. Par contre, le nombre de lésions visualisées était plus nombreux dans le groupe des patients avec prémédication, mais la différence n’était pas significative. En conclusion, cette étude démontre un clair bénéfice de la prise de siméticone sur la visualisation de la muqueuse oeso-gastrique. Il existe une place pour une étude plus large et multicentrique pour étudier si cette prémédication permet de détecter plus de lésions et en particulier les lésions prénéoplasiques dans l’estomac.
Prescribing preferences (PPrefs) of US-based medical oncologists (MOs) for 1st salvage therapy (Tx) after response to 1st-line crizotinib (CRZ) in patients with anaplastic lymphoma kinase (ALK) positive non-small cell lung cancer (NSCLC).
Authors: Mark A. Socinski, Arden Buettner, Maria L. Lankford, Doug B. Neely, Brynn Tiscione, Joanne P. Willey, Mark R. Green
Journal: Journal of Clinical Oncology (2015)

e19137 Background: Crizotinib is standard 1st line Tx for ALK-positive NSCLC. 2nd line Tx after progression on CRZ is less well defined. Shaw, et al (N Engl J Med 2013; 368:2385-2394) showed that ALK-positive NSCLC patients have higher response rates and improved PFS with pemetrexed (PEM) relative to docetaxel in the 2nd line setting. Prior to the FDA approval of ceritinib (CER) on April 29, 2014, no salvage Tx specifically targeting ALK was available. Methods: Prescribing preferences (PPrefs) of 364 U.S.-based medical oncologists (MOs) were studied using a validated, proprietary, live, case-based market research tool (Challenging Cases). Data were acquired using blinded, audience-response iPad technology and acquisition events took place in April, May, August and November 2014. A core case was constructed and PPrefs for three different patterns of treatment failure were assessed. Core case: 57-year-old man has a new diagnosis of stage IV adenocarcinoma of the lung. Pathology showed ALK positive NSCLC. You began the patient on daily CRZ. He had a clear RECIST PR after 8 weeks. He tolerated the Tx well and he has been on Tx continuously for 8 months. Results: See table. PPrefs for CER increased in each scenario post FDA approval. A single site of failure, managed definitively with local Tx, triggers a move away from CRZ less than half the time. PPrefs for CER increased most as the number of sites of progression increased. Conclusions: These data indicate that patterns of failure strongly influence prescribing preferences after 1st line Tx with CRZ for patients with ALK positive NSCLC. PPrefs by pre- and post-FDA approval of CER by pattern of failure.* N = 360 N = 364 N = 360 Pattern of Failure Single brain met (resected) Brain met (resected) and liver met Brain, bone, lung, intrathoracic, and adrenal mets FDA Approval Pre Post Pre Post Pre Post Continue CRZ 78% 58% 14% 7% NO NO Radiate liver site and continue CRZ NO NO 36% 24% NO NO PEM-based CT 7% 10% 12% 12% 37% 28% Other CT 1% 4% 6% 2% 11% 4% CER 10% 26% 30% 51% 44% 61% Other-including other ALK inhibitors 3% 3% 2% 4% 7% 5% NO - not offered; *May not equal 100% due to rounding
Kinome in renal cell carcinoma: Mutation analysis of 518 kinases and expression of 400 tumors
Authors: B. T. Teh
Journal: Journal of Clinical Oncology (2007)

5013 Background: Protein kinases are frequently mutated in human cancer and inhibitors of mutant protein kinases have proven to be effective anticancer drugs. In addition, expression levels of these protein kinases have also been associated with drug efficacy allowing prediction of drug response. Renal Cell Carcinoma (RCC) constitutes approximately 3% of all cancer incidence and deaths. Methods: We screened the coding sequences of 518 protein kinases (approximately 1.3 mb of DNA per sample) for somatic mutations in 69 kindey tumors of different subtypes. We also studied the expression of these kinases in 400 kidney tumors of different subtypes and prognosis by gene expression profiling using the Affymetrix HG-U133 Plus 2.0 GeneChip platform. The bioinformatic analysis is focused on the 518 protein kinases. Results: We identified 22 mutations (16 missense, 3 silent, 1 nonsense, 1 frameshift and 1 in-frame) in 16 samples. In expression profiling, we detected differential expression of protein kinases between different subtypes and between good- and poor- prognosis subgroups. Conclusions: This is the most comprehensive kinome profile in RCC known to date. The mutant protein kinases may play a role in the tumorigenesis of a subset of kidney cancer. These, together with over-expressed protein kinases, may serve as potential therapeutic targets and bio-markers for diagnosis, prognosis and drug response prediction. Other gene families may also be involved in RCC. No significant financial relationships to disclose.
Regional- and Age-Related Differences in Pain in Children with Sickle Cell Anemia: Results from the Multinational DOVE Study
Authors: Julie Kanter, Lori E Heath, Chunmei Zhou, Tsiri Agbenyega, Raffaella Colombatti, Carlton Dampier, Hoda M Hassab, Deepa Manwani, Nancy Robitaille, Patricia B Brown, Joseph A. Jakubowski, Suqin Yao, Jack Knorr, Carolyn C Hoppe
Journal: Blood (2016)
New York state hospitals serving the poor: Does the proportion of Medicaid patients affect lung cancer surgical short-term outcomes?
Authors: Cardinale B. Smith, Natalia Egorova, Jason Parker Gonsky, Benjamin Philip Levy, Sofya Pintova, Rebeca Franco, Nina A. Bickell
Journal: Journal of Clinical Oncology (2015)

e17660 Background: Historically, hospitals serving the poor provide worse quality care. Under the Affordable Care Act, Disproportionate Share Hospitals (DSH) will receive reduced reimbursement which can increase financial strain and affect care delivery. We assessed the relationship between short term outcomes following lung cancer surgery of patients treated at hospitals with increasing proportions of Medicaid, sites that will likely experience future economic stress. Methods: Using 2008-2013 NYS hospital discharge data linked to vital records, we identified the index hospitalization for patients with a lung cancer diagnosis undergoing surgery (open vs VATS limited resection, lobectomy or pneumonectomy). The proportion of Medicaid patients per hospital including adult non-OB hospitalizations was divided into quintiles. We used bi- and multi-variate regression analyses to assess 30-day mortality, post-operative complications (respiratory, cardiovascular, thromboembolic & neurologic) and length of stay (LOS). We used mixed models to account for clustering within hospitals. Results: Of the 10,078 lung cancer patients treated at 138 hospitals, 16% had Medicaid. Proportion of Medicaid patients at the hospitals ranged from 1-84%, median = 26%. Mean 30-day mortality was 2.4% (range: 1.8-2.7%) with no risk adjusted hospital differences (p = 0.42). There were no differences by hospital Medicaid quintile in respiratory, cardiac, thromboembolic or neurologic complications (p = 0.67; 0.75; 0.23; 0.28, respectively). However, patients treated at hospitals in the highest Medicaid quintile had a longer LOS (9.1d vs 7.2d; p < 0.001), controlling for type of surgery, comorbidities and demographics. Conclusions: The quality of care at NYS hospitals serving larger proportions of Medicaid patients is similar to hospitals with few Medicaid patients as measured by 30d mortality and major post-surgical complications. However, lung cancer patients treated at high quintile Medicaid hospitals have longer LOS. NYS has generous Medicaid hospital reimbursements but as DSH payments decline under the ACA, it will be important to monitor the quality of care received.
Abstract A22: The effects of Lipocalin-2 in the early stages of colorectal cancer metastasis
Authors: Daniel Hughes, Celestia Davis, Yu Zhang, John Bonaparte, Maria Pena
Journal: Cancer Research (2016)

Abstract Colorectal cancer (CRC) is the second leading cause of cancer deaths in the United States. When diagnosed at an early, localized stage, the five year survival rate is approximately 90%; however, when patients are diagnosed at the metastatic stage, this drops to 12%. Metastasis, the spread of cancer cells from the primary tumor to a distant organ, is the primary cause of death in cancer patients. In CRC, metastasis is typically found in the liver, asymptomatic, and often detected at the final stage when therapeutic options are few. The genetic and cellular mechanisms driving the early stages of metastasis are still poorly understood. Recent studies have shown that prior to the arrival of cancer cells at the secondary organ, molecular signals from the tumor direct the recruitment of bone marrow derived cells to create a pre-metastatic niche where cancer cells can attach and develop into a metastatic lesion. Identifying and understanding these molecules can lead to the development of methods for early diagnosis or targets for intervention. Using an orthotopic model of CRC liver metastasis, we performed microarray analyses of the liver microenvironment in tumor bearing mice before and after the arrival of metastatic cells. We found that Lipocalin-2 (LCN2, 24p3, NGAL) was highly expressed in the liver and in circulation of mice bearing highly metastatic cells. LCN2 is a 25 kD secreted glycoprotein that binds small lipophilic molecules. Its expression is upregulated in a number of primary tumors of epithelial origin, but its role in metastasis remains unclear. It has contrasting roles in metastasis in breast cancer models and has been associated with poor prognosis in CRC patients; however its role in the tumor microenvironment has not been studied. Our studies thus far show that overexpression of Lcn2 in mouse colon cancer cells either had little impact on tumor growth and invasiveness, or it enhanced invasion in the presence of macrophages; however, it resulted in an overall reduction of circulating iron levels in sera from tumor bearing mice. In-vitro, iron also seems to have an effect in conjunction with Lcn2 on the invasiveness of the tumor cells. The results from this study will allow us to better describe the role of LCN2 in tumor and stromal cells in the early stages of liver metastasis. Citation Format: Daniel Hughes, Celestia Davis, Yu Zhang, John Bonaparte, Maria Pena. The effects of Lipocalin-2 in the early stages of colorectal cancer metastasis. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Metastasis; 2015 Nov 30-Dec 3; Austin, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(7 Suppl):Abstract nr A22.
Prevalence of Arthritis and Arthritis-Attributable Activity Limitation by Urban-Rural County Classification — United States, 2015
Authors: Michael A. Boring, Jennifer M. Hootman, Yong Liu, Kristina A. Theis, Louise B. Murphy, Kamil E. Barbour, Charles G. Helmick, Terry J. Brady, Janet B. Croft
Journal: MMWR Morbidity and Mortality Weekly Report (2017)

Rural populations in the United States have well documented health disparities, including higher prevalences of chronic health conditions (1,2). Doctor-diagnosed arthritis is one of the most prevalent health conditions (22.7%) in the United States, affecting approximately 54.4 million adults (3). The impact of arthritis is considerable: an estimated 23.7 million adults have arthritis-attributable activity limitation (AAAL). The age-standardized prevalence of AAAL increased nearly 20% from 2002 to 2015 (3). Arthritis prevalence varies widely by state (range = 19%-36%) and county (range = 16%-39%) (4). Despite what is known about arthritis prevalence at the national, state, and county levels and the substantial impact of arthritis, little is known about the prevalence of arthritis and AAAL across urban-rural areas overall and among selected subgroups. To estimate the prevalence of arthritis and AAAL by urban-rural categories CDC analyzed data from the 2015 Behavioral Risk Factor Surveillance System (BRFSS). The unadjusted prevalence of arthritis in the most rural areas was 31.8% (95% confidence intervals [CI] = 31.0%-32.5%) and in the most urban, was 20.5% (95% CI = 20.1%-21.0%). The unadjusted AAAL prevalence among adults with arthritis was 55.3% in the most rural areas and 49.7% in the most urban. Approximately 1 in 3 adults in the most rural areas have arthritis and over half of these adults have AAAL. Wider use of evidence-based interventions including physical activity and self-management education in rural areas might help reduce the impact of arthritis and AAAL.