tbuckley/cabot-search huggingface dataset:
Abstract P1-08-17: Pharmacy refill synchronization and oral endocrine therapy adherence
Authors: JM Neuner, N Fergestrom, AB Nattinger, PW Laud, L Pezzin
Journal: Cancer Research (2019)

Abstract Background: One-third to one-half of patients prescribed adjuvant endocrine therapy with tamoxifen or an aromatase inhibitor either discontinue early or skip a substantial number of pills. Research to improve this has been disappointing. We investigated whether poor pharmacy synchronization of medications is an unrecognized barrier to adherence. Methods: A cohort of women aged 66-90 years old with Stage 0-3 hormone receptor-positive breast cancer were identified from the Surveillance, Epidemiology and End Result (SEER)-Medicare claims-linked cancer registry. Women with Medicare pharmacy claims documenting at least one endocrine therapy prescription fill and at least one other medication fill were identified, and the 3-month synchronization of their medication fills was calculated as the quotient of the number of pharmacy visits and the number of filled medications subtracted from one. Logistic regression was used to assess the association between synchronization stratified by the number of medications and adherence to endocrine therapy (defined as medication possession ratio &amp;gt;80%) over the subsequent year. Results: The study cohort included 3,112 women treated with endocrine therapy for breast cancer (Table 1) . Over 31% were age 70 or younger, and 38.0% had stage 2 or 3 disease. During the three months after the first endocrine therapy prescription, the mean number of unique medications was 8.0 (S.D. 6.0) and the mean number of pharmacy visits was 8.6 S.D. 4.7) for a mean synchronization of 0.3 ( (S.D. 0.2) . In adjusted model, compared with the highest synchronization, those in the lowest synchronization quantile were less likely to be adherent (MPR &amp;gt;=80%) (Odds Ratio 0.71 (95% CI 0.57, 0.88)) as were those in the second-lowest (0.81 (0.65, 0.99). Neither age nor race/ethnicity were associated with adherence, and results were unchanged with inclusion of information about duration of fills (30 vs 90 days). Conclusions: Prescription fill synchronization is strongly associated with adherence to endocrine therapy. Research into interventions to improve adherence should include prescription synchronization and other health systems barriers. Citation Format: Neuner JM, Fergestrom N, Nattinger AB, Laud PW, Pezzin L. Pharmacy refill synchronization and oral endocrine therapy adherence [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P1-08-17.
Pomalidomide Alters Pancreatic Macrophage Populations to Generate an Immune-Responsive Environment at Precancerous and Cancerous Lesions
Authors: Ligia I. Bastea, Geou-Yarh Liou, Veethika Pandey, Alicia K. Fleming, Christina A. von Roemeling, Heike Doeppler, Zhimin Li, Yushi Qiu, Brandy Edenfield, John A. Copland, Han W. Tun, Peter Storz
Journal: Cancer Research (2019)

During development of pancreatic cancer, alternatively activated macrophages contribute to fibrogenesis, pancreatic intraepithelial neoplasia (PanIN) lesion growth, and generation of an immunosuppressive environment. Here, we show that the immunomodulatory agent pomalidomide depletes pancreatic lesion areas of alternatively activated macrophage populations. Pomalidomide treatment resulted in downregulation of interferon regulatory factor 4, a transcription factor for M2 macrophage polarization. Pomalidomide-induced absence of alternatively activated macrophages led to a decrease in fibrosis at PanIN lesions and in syngeneic tumors; this was due to generation of an inflammatory, immune-responsive environment with increased expression of IL1α and presence of activated (IFNγ-positive) CD4+ and CD8+ T-cell populations. Our results indicate that pomalidomide could be used to decrease fibrogenesis in pancreatic cancer and may be ideal as a combination treatment with chemotherapeutic drugs or other immunotherapies. SIGNIFICANCE: These findings reveal new insights into how macrophage populations within the pancreatic cancer microenvironment can be modulated, providing the means to turn the microenvironment from immunosuppressive to immune-responsive.
Childhood trauma: government rejects call for national strategy
Authors: Susan Mayor
Journal: BMJ (2019)

MPs have expressed their disappointment at the government’s failure to act on their recommendation for a national strategy to reverse the negative effects of adversity and trauma in childhood.

Norman Lamb, chair of the Science and Technology Committee, said, “It is extremely frustrating to see the government largely dismiss our recommendations, opting instead to list existing programmes and shifting responsibility onto …
Intravesical PAI-1 modifies the bladder tumor microenvironment and inhibits tumor invasion and angiogenesis
Authors: Shang-Chiung Chen, Dale Henry, Michael Wong
Journal: Cancer Research (2008)

1153  The depth of bladder tumor invasion into the underlying muscle wall is the strongest clinical prognostic factor in bladder cancer. Thus inhibiting this event will have a significant impact on patient outcome. Plasminogen activator inhibitor type-1 (PAI-1) is a member of the SERPIN (serine protease inhibitor) superfamily which potently inhibits urokinase-type plasminogen activator (uPA). This in turn limits the extent of extracellular matrix degradation and reduces activation of MMPs and growth factors. The literature reveals however that PAI-1 effects are concentration dependent. Thus we hypothesize that direct contact of PAI-1 to bladder tumors by intravesical application would be particularly efficacious. We exploit an orthotopic rat bladder tumor model to enable us to show for the first time that intravesical PAI-1 significantly and effectively impedes bladder tumor progression.  Intravesical implantation of AY-27 rat bladder transitional cell carcinoma cells (1x 106) into the acid-preconditioned bladder lumen of syngeneic female Fisher F344 rats results in a tumor take rate of 95% at 17 days. At 3 weeks post-implantation, rats received 1μM PAI-1 or BSA control, twice/week for 2 weeks via intravesical cannula. Bladders were harvested 3 days after the last treatment.  The treatment effects were immediately discernable on gross examination. Control group tumors grossly involved the underlying muscularis. These tumors were bulky, fleshy, and appeared red with a peritumoral rim of angiogenic vessels. In contrast, the PAI-1 treated tumors were smaller, pale, and flat. The average size of the control tumors was 762.03 mm3 compared to 362.80 mm3 in the PAI-1 group. Histological analysis confirmed that eight out of nine control treated tumors showed muscular invasion whereas most the tumors in the PAI-1 treatment group were superficially confined (Stage T1 or T2). The angiogenic index was significantly reduced in the PAI-1 group. PAI-1 treatment is accompanied with a decrease of uPA activity as determined by rat active uPA ELISA. This results in less matrix breakdown as shown by histologic stain and analysis. No rats from either groups developed distant metastases nor showed spleen, kidney, lung, liver, or heart toxicity.  To our knowledge, this is the first demonstration of the viability of intravesical treatment of bladder tumors using an matrix-modifying agent that inhibits both invasion and angiogenesis. Translation of these observations into a clinical trial is under development.
Soy isoflavones reduce asthma exacerbation in asthmatic patients with high PAI-1–producing genotypes
Authors: Seong H. Cho, Ara Jo, Thomas Casale, Su J. Jeong, Seung-Jae Hong, Joong K. Cho, Janet T. Holbrook, Rajesh Kumar, Lewis J. Smith
Journal: Journal of Allergy and Clinical Immunology (2019)
Oligoclonal Expansion of Cd8+ T Cells during Idiopathic Multicentric Castleman Disease Flares Suggests an Antigen Driven Process
Authors: Dustin Shilling, Jason E Stadanlick, Wenzhao Meng, Abhishek Rao, Vera P Krymskaya, Eline T. Luning Prak, Evgeniy B Eruslanov, David C Fajgenbaum
Journal: Blood (2018)
Medicinal chemistry efforts towards the identification and development of inhibitors of phosphatidylinositol 3-kinases (PI3Ks) and related protein kinases for cancer treatment
Authors: Frederic Stauffer, Carlos Garcia-Echeverria, Pascal Furet, Hans-Georg Capraro, Philipp Holzer, Michel Maira
Journal: Cancer Research (2007)

3953  Constitutive activation of the PI3K/Akt pathway seems to be a prerequisite for a wide spectrum of cancers, either by loss / mutations of PTEN, acquisition of activating mutations in the PI3K catalytic subunit, or amplification / overexpression of receptor tyrosine kinases upstream of PI3K. In this respect, PI3K/Akt pathway components such as members of the class I PI3Ks represent well validated molecules for the discovery and development of targeted anticancer drugs. Although they have sub-optimal pharmaceutical properties, PI3K inhibitors like the fungal metabolite wortmannin and the morpholino derivative LY294002 have shown that this class of lipid kinases is drug-able. This poster is disclosing our medicinal chemistry efforts to identify and optimize new pan class I PI3K inhibitors using the privilege kinase inhibitor scaffold imidazo[4,5-c]quinoline. From extensive structure activity relationship and in vivo studies, a clinical candidate has been selected from this chemotype. This PI3K inhibitor, which has suitable pharmacological properties for clinical development, shows an efficient control of the PI3K/Akt pathway in tumor cells by inhibiting the phosphorylation of Akt in cellular and in vivo settings.
Statistical Methodology in Studies of Prenatal Exposure to Mixtures of Endocrine-Disrupting Chemicals: A Review of Existing Approaches and New Alternatives
Authors: Nina Lazarevic, Adrian G. Barnett, Peter D. Sly, Luke D. Knibbs
Journal: Environmental Health Perspectives (2019)

Prenatal exposures to endocrine-disrupting chemicals (EDCs) during critical developmental windows have been implicated in the etiologies of a wide array of adverse perinatal and pediatric outcomes. Epidemiological studies have concentrated on the health effects of individual chemicals, despite the understanding that EDCs act together via common mechanisms, that pregnant women are exposed to multiple EDCs simultaneously, and that substantial toxicological evidence of adverse developmental effects has been documented. There is a move toward multipollutant models in environmental epidemiology; however, there is no current consensus on appropriate statistical methods.We aimed to review the statistical methods used in these studies, to identify additional applicable methods, and to determine the strengths and weaknesses of each method for addressing the salient statistical and epidemiological challenges.We searched Embase, MEDLINE, and Web of Science for epidemiological studies of endocrine-sensitive outcomes in the children of mothers exposed to EDC mixtures during pregnancy and identified alternative statistical methods from the wider literature.We identified 74 studies and analyzed the methods used to estimate mixture health effects, identify important mixture components, account for nonmonotonicity in exposure–response relationships, assess interactions, and identify windows of exposure susceptibility. We identified both frequentist and Bayesian methods that are robust to multicollinearity, performing shrinkage, variable selection, dimension reduction, statistical learning, or smoothing, including methods that were not used by the studies included in our review.Compelling motivation exists for analyzing EDCs as mixtures, yet many studies make simplifying assumptions about EDC additivity, relative potency, and linearity, or overlook the potential for bias due to asymmetries in chemical persistence. We discuss the potential impacts of these choices and suggest alternative methods to improve analyses of prenatal exposure to EDC mixtures. https://doi.org/10.1289/EHP2207.
Left Ventricular Unloading During Extracorporeal Membrane Oxygenation in Patients With Cardiogenic Shock
Authors: Juan J. Russo, Natasha Aleksova, Ian Pitcher, Etienne Couture, Simon Parlow, Mohammad Faraz, Sarah Visintini, Trevor Simard, Pietro Di Santo, Rebecca Mathew, Derek Y. So, Koji Takeda, A. Reshad Garan, Dimitrios Karmpaliotis, Hiroo Takayama, Ajay J. Kirtane, Benjamin Hibbert
Journal: Journal of the American College of Cardiology (2019)

Venoarterial extracorporeal membrane oxygenation (VA-ECMO) is a widely used form of mechanical circulatory support in patients with refractory cardiogenic shock. A common drawback of this modality is a resultant increase in left ventricular afterload. The purpose of this meta-analysis was to examine the efficacy and safety of left ventricular unloading strategies during VA-ECMO in adult patients with cardiogenic shock. The authors performed a systematic search of studies examining left ventricular unloading during VA-ECMO in Medline, EMBASE, and the Cochrane library. The primary outcome was all-cause mortality. Secondary outcomes included limb ischemia, bleeding, need for renal replacement therapy, multiorgan failure, stroke or transient ischemic attack, and hemolysis. Of 2,221 publications identified, 17 observational studies met the inclusion criteria. In total, outcomes in 3,997 patients were included with 1,696 (42%) receiving a concomitant left ventricular unloading strategy while on VA-ECMO (intra-aortic balloon pump 91.7%, percutaneous ventricular assist device 5.5%, pulmonary vein or transseptal left atrial cannulation 2.8%). There were 2,412 deaths (60%) in the total cohort. Mortality was lower in patients with (54%) versus without (65%) left ventricular unloading while on VA-ECMO (risk ratio: 0.79; 95% confidence interval: 0.72 to 0.87; p < 0.00001). Hemolysis was higher in patients who underwent VA-ECMO with left ventricular unloading. Otherwise, secondary outcomes were not demonstrably different in patients treated with VA-ECMO with versus without left ventricular unloading. In observational studies, left ventricular unloading was associated with decreased mortality in adult patients with cardiogenic shock treated with VA-ECMO. In the absence of prospective randomized data, left ventricular unloading may be considered for appropriately selected patients undergoing VA-ECMO support.
Predictive value or peanut SPT and sIgE in peanut allergic patients diagnosed of LTP-Syndrome
Authors: Francisca Gomez, Gador Bogas, Carmen Rondon, Esther Barrionuevo, Maria Francisca Palomares, Ana Prieto del Prado, Beatriz de Julián, Maria Jose Rodriguez, Miguel Gonzalez, Cristobalina Mayorga, M.J. Torres
Journal: Journal of Allergy and Clinical Immunology (2019)
Abstract 12112: Clinical Outcomes of Percutaneous Epicardial Ablation
Authors: Ammar M Killu, Mohammed Al-Hijji, Alan M Sugrue, Christopher J McLeod, David O Hodge, Thomas M Munger, Siva K Mulpuru, Douglas L Packer, Samuel J Asirvatham, Paul A Friedman
Journal: Circulation (2015)

Introduction: Percutaneous epicardial access (EAc) is increasingly performed as part of VT/PVC ablation, especially in those that have failed prior ablation. We aimed to delineate the outcomes of EAc. Methods: We retrospectively analyzed individuals undergoing EAc for arrhythmia ablation between June 2004 and July 2014. Acute procedural success was defined as elimination/non-inducibility of the clinical arrhythmia after ablation; clinical success was defined as absence of symptoms/arrhythmia. Results: Of 175 patients, 126 (72%) were male with a mean age of 52.8±15.7 years. Eighty-three (47.4%) patients had NICM, 25 (14.3%) had ICM and 34 (19.4%) had normal hearts. Baseline EF was 44±16%. Patients had failed an average of 1.7±1.2 antiarrhythmic drugs; 139 patients (79%) had failed prior endocardial (endo) ablation (average 1.3±1.1). Six (3.4%) had prior EAc and 18 (10.3%) prior cardiac surgery. The indication for ablation was VT or PVC in 113 (64.6%) and 60 (34.3%) patients, respectively. Successful access was obtained in 168 (98%) patients. Anterior access, inferior access, or both, was utilized in 89 (52.7%), 77 (45.6%) and 2 (1.2%) patients, respectively. There were an average of 2.7±2.2 VT/PVCs identified, and 1.6±1.1 ablated. Endo, epicardial (epi) or combined ablation was performed in 58 (33.1%), 14 (8%), and 100 (57.1%) patients, respectively; 3 did not undergo ablation. Procedural success was obtained in 158 of 173 (91.3%) patients for whom data was available. At 12 months, clinical success was maintained in 62% with no difference between endo, epi or combined ablation (figure). Cardiac tamponade requiring repeat EAc occurred in 12 (6.9%) patients. There were no procedural related deaths. Conclusion: Epicardial access is feasible in almost all patients with no prior cardiac surgery, and permits acute procedural success in 91.3% of patients, most of whom had failed previous ablation. Furthermore, complications are relatively infrequent in this complex cohort.
Annals Graphic Medicine - Team Doctor
Authors: Shruti Sudhakar
Journal: Annals of Internal Medicine (2019)

Web Exclusives5 February 2019Annals Graphic Medicine - Team DoctorFREEShruti Sudhakar, MDShruti Sudhakar, MDUniversity of Maryland Medical Center, Baltimore, Maryland (S.S.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/G18-0013 SectionsAboutVisual AbstractPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Download figure Download PowerPoint Download figure Download PowerPoint Download figure Download PowerPoint Download figure Download PowerPoint Comments0 CommentsSign In to Submit A Comment Author, Article, and Disclosure InformationAffiliations: University of Maryland Medical Center, Baltimore, Maryland (S.S.)Disclosures: The author has disclosed no conflicts of interest. The form can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=G18-0013.Corresponding Author: Shruti Sudhakar, MD, is an anesthesiology resident at the University of Maryland (e-mail, [email protected]umaryland.edu). PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoAnnals Graphic Medicine - What It Is Like Gazi M. Rashid Reimagining the Cape: Exploring New Metaphors for Emerging Medical Professionals Michael J. Green Annals Graphic Medicine - The Tale of a Wannabe Superhero Michelle Sayad Reimagining the Cape: Exploring New Metaphors for Emerging Medical Professionals Michael J. Green Annals Graphic Medicine - The Med Student Mollie Kotzen Metrics Cited byReimagining the Cape: Exploring New Metaphors for Emerging Medical ProfessionalsMichael J. Green, MD, MS 5 February 2019Volume 170, Issue 3Page: W63-W67KeywordsAnesthesiologyConflicts of interestDisclosureHealth care ePublished: 5 February 2019 Issue Published: 5 February 2019 Copyright & PermissionsCopyright © 2019 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Up-regulation of glycolipid transfer protein by bicyclol causes spontaneous restriction of hepatitis C virus replication
Authors: Meng-Hao Huang, Hu Li, Rong Xue, Jianrui Li, Lihua Wang, Junjun Cheng, Zhouyi Wu, Wenjing Li, Jinhua Chen, Xiaoqin Lv, Qiang Li, Pei Lan, Limin Zhao, Yongfeng Yang, Zonggen Peng, Jiandong Jiang
Journal: Acta Pharmaceutica Sinica B (2019)

Bicyclol is a synthetic drug for hepatoprotection in clinic since 2004. Preliminary clinical observations suggest that bicyclol might be active against hepatitis C virus (HCV) with unknown mechanism. Here, we showed that bicyclol significantly inhibited HCV replication in vitro and in hepatitis C patients. Using bicyclol as a probe, we identified glycolipid transfer protein (GLTP) to be a novel restrictive factor for HCV replication. The GLTP preferentially bound host vesicle-associated membrane protein-associated protein-A (VAP-A) in competition with the HCV NS5A, causing an interruption of the complex formation between VAP-A and HCV NS5A. As the formation of VAP-A/NS5A complex is essential for viral RNA replication, up-regulation of GLTP by bicyclol reduced the level of VAP-A/NS5A complex and thus inhibited HCV replication. Bicyclol also exhibited an inhibition on HCV variants resistant to direct-acting antiviral agents (DAAs) with an efficacy identical to that on wild type HCV. In combination with bicyclol, DAAs inhibited HCV replication in a synergistic fashion. GLTP appears to be a newly discovered host restrictive factor for HCV replication, Up-regulation of GLTP causes spontaneous restriction of HCV replication.
Sin1/mTORC2 regulate B cell growth and metabolism by activating mTORC1 and Myc
Authors: Man Li, Adam S. Lazorchak, Xinxing Ouyang, Huihui Zhang, Hongzhi Liu, Omotooke A. Arojo, Lichong Yan, Jingsi Jin, Yuheng Han, Guojun Qu, Yuhong Fu, Xiaocao Xu, Xiaobo Liu, Wenqian Zhang, Zhengfeng Yang, Chuan Ruan, Qijun Wang, Dou Liu, Chuanxin Huang, Lu Lu, Shibo Jiang, Fubin Li, Bing Su
Journal: Cellular and Molecular Immunology (2019)
Outcomes and utilization of adjuvant chemotherapy (AT) for stage II colon cancer (CC-II) in elderly population.
Authors: Afsaneh Barzi, Xiayu Jiao, Joel W Hay, Sarmad Sadeghi
Journal: Journal of Clinical Oncology (2019)

701 Background: The use of AT in elderly patients (pts) with CC-II is controversial. We used Surveillance Epidemiology End Results (SEER) linkage with Medicare claims to explore the patterns of AT and survival in pts with CC-II diagnosed between 2004-2010. Methods: Colon cancer was identified using ICD-O-3 codes. TNM staging information was used to classify pts as stage II and its subgroups. We restricted our cohort to pts who had surgery within 4 months (mos) of the diagnosis using ICD-9 codes: 45.7x and 45.8x and excluded pts who died within 3 mos after the surgery as well as those who were enrolled on a health maintenance organization. We searched Medpar, outpatient facility, or carrier claims in the 4 mos after surgery to identify pts who received AT using ICD-9 diagnosis and procedure codes, HCPCS, and revenue center codes. Logistic regression was used to assess the relationship between demographics and clinical characteristics of pts in each group and receipt of AT. Kaplan-Meier method was used for survival analysis. We performed a flexible parametric survival analysis to estimate the 3-year overall survival benefit for AT while controlling for demographics and clinical characteristics. Results: A total of 15,310 pts were included in our study. Among those, 14% (n=2,168ss received AT of which 718 (33%) received oxaliplatin containing regimen. Pts and tumor characteristics are reported in the table. After adjusting for pts and tumor characteristics, probability of survival at 3 years was 72.9% for pts who received AT and 74.2% for those who did not, HR=1.06 (95% CI, 0.96-1.17), with P-value: 0.229. The AT use was declining over time. Conclusions: Although AT is used in healthier and higher risk elderly pts with colon cancer, it was not associated with significantly improved overall survival. [Table: see text]