tbuckley/cabot-search huggingface dataset:
Inhaled steroids in patients admitted to hospital with pneumonia
Authors: Tejmahal Rehman, Vikas Somani, Conor McGeary, Rabinder Randhawa, Ajikumar Kavidasan, Milan Bhattacharya
Journal: European Respiratory Journal (2014)

Background 

It is well established that high dose inhaled steroids increase risk of pneumonia in COPD. As use of inhaled steroids rise, it poses a dilemma for practising physicians in patients with pneumonia. High mortality of patients with pneumonia at our hospital led to a retrospective audit, giving us an opportunity to look at steroid inhaler usage among them.

Methods 

Patients with pneumonia admitted to Milton Keynes Hospital from 01.07.12 to 30.06.13 were audited. Data for age, sex, length of stay, co-morbidity, medication and outcome were collected.

Results 

49 patients were admitted with 55 episodes of pneumonia. 29 were male and 20 female. Median age was 73 years (18-86 years) and mean LOS of 19.7 days. 26 patients did not use any inhalers. 21 were on inhaled steroids of which 18 (86%) were on fluticasone/salmeterol, 2 (10%) on budesonide/formeterol and 1(4%) was on beclomethasone/formeterol combination. All patients on inhalers either had COPD, bronchiectasis, asthma or lung fibrosis. Mean LOS for those on fluticasone/salmeterol was 26.8 days compared to mean LOS of 14.5 days for all others. Overall mortality was 18 out of 49 patients (37%). In those on fluticasone/salmeterol it was 9 out of 18 (50%) while 11 out of 31(35%) not on inhalers died.

Conclusion 

While limited by numbers, our audit did reveal a high prevalence of fluticasone/salmeterol usage among patients with pre-existing lung disease and pneumonia, with higher length of stay and mortality. Other large scale studies draw similar conclusion, warranting a review of inhaled steroid prescribing in patients who have had, or are susceptible to pneumonia.

1. Janson et al; BMJ 2013; 346:3306

2. Suissa et al; Thorax 2013; 68: 1029-1036.
Nonconventional MRI and microstructural cerebral changes in multiple sclerosis
Authors: Christian Enzinger, Frederik Barkhof, Olga Ciccarelli, Massimo Filippi, Ludwig Kappos, Maria A. Rocca, Stefan Ropele, Àlex Rovira, Torben Schneider, Nicola de Stefano, Hugo Vrenken, Claudia Wheeler-Kingshott, Jens Wuerfel, Franz Fazekas
Journal: Nature Reviews Neurology (2015)
Pharmacological inactivation of PI3Kδ in the tumor microenvironment enhances efficacy of other immunotherapeutic agents
Authors: Liang-Chuan S Wang, Holly Koblish, Michael Hansbury, Yue Zhang, Gengjie Yang, Timothy Burn, Paul Waeltz, Mark Rupar, Eddy Yue, Brent Douty, Thomas Maduskuie, Nikoo Falahatpisheh, Yun-Long Li, Andrew P Combs, Gregory Hollis, Reid Huber, Peggy Scherle
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts Pharmacological inhibition of the oncogenic PI3Kδ pathway has been shown to be efficacious in patients with hematopoietic malignancies. However, its therapeutic application in patients with solid tumors has not yet been tested. Recently, genetic inactivation of PI3Kδ in mice was
Quantitative fragment analysis of FLT3-ITD efficiently identifying poor prognostic group with high mutant allele burden or long ITD length
Authors: Y Kim, G D Lee, J Park, J-H Yoon, H-J Kim, W-S Min, M Kim
Journal: Blood Cancer Journal (2015)

Mutation of the fms-like tyrosine kinase 3-internal tandem duplication (FLT3-ITD), which is one of the most frequent genetic alterations, strongly contributes to an increased risk of treatment failure and to poor prognosis. In this study, we established quantitative fragment analysis of FLT3-ITD simultaneously measuring mutant allele burden and length, verified the analytical performance and evaluated the clinical significance in adult acute myeloid leukemia (AML) patients. FLT3-ITD was detected in 73 of 363 adult AML patients (20.1%) and high mutant allelic burden (⩾50%, n=13) and long ITD length (⩾70 base pairs, n=15) were significantly associated with inferior overall survival (OS; P=0.002 and 0.005, respectively) and event-free survival (EFS; P=0.004 and 0.007, respectively). FLT3-ITD poor prognostic group was identified as patients with high allele burden or long ITD length (n=24), which revealed significant adverse clinical outcome for both OS (P<0.001) and EFS (P<0.001). In cytogenetically normal AML, even FLT3-ITD low allele burden and short length was associated with poorer OS (P=0.037) and EFS (P=0.044) than wild type, whose influence was overcome when hematopoietic stem cell transplantation was performed. In minimal residual disease monitoring, FLT3-ITD negativity after consolidation therapy was a valuable predictor of better OS (P<0.001) and EFS (P<0.001). FLT3-ITD poor prognostic group with high mutant allele burden or long ITD length is efficiently identified by quantitative fragment analysis.
Estrogenic regulation of polyamine analogue cytotoxicity in human breast cancer cells
Authors: Yi Huang, Judith C. Keen, Allison Pledgie, Benjamin Frydman, Aldonia L. Valasinas, Venodhar K. Reddy, Laurence J. Marton, Robert A. Casero, Nancy E. Davidson
Journal: Cancer Research (2005)

Proc Amer Assoc Cancer Res, Volume 46, 2005

2332 

The polyamine metabolic pathway is an attractive target for therapeutic intervention with manipulation of cellular polyamine levels leading to decreased cell growth in cancer. Synthetic polyamine analogues can act as polyamine antimetabolites that deplete intracellular polyamines, or polyamine mimetics that displace natural polyamines from binding sites, but do not substitute in terms of growth promoting function. Our studies demonstrate that newly designed oligoamine analogues significantly inhibit the key polyamine biosynthesis enzyme, ornithine decarboxylase (ODC), induce the polyamine catabolism enzyme spermidine/spermine N 1-acetyltransferase (SSAT), and effectively inhibit in vitro and in vivo human breast cancer growth via induction of cell cycle arrest and apoptotic cell death. Oligoamines specifically suppress the protein and mRNA expression as well as the ligand-dependent transcriptional activity of the estrogen receptor α (ERα), a principal determinant of breast cell growth and differentiation, in several ER-positive human breast cancer cell lines including MCF-7 and T47D cells. The expressions of ERα-target genes including progesterone receptor (PR) and cyclinD1 are also down-regulated by oligoamines. However, neither ERβ nor other steroid hormonal receptors are affected by analogues. The constitutive expression of a CMV-driven exogenous ERα in ER-negative breast cancer MDA-MB-231 cells was not altered by oligoamines, suggesting that oligoamines specifically suppress transcription of ERα rather than degrade the protein. Simultaneous treatment with spermine reversed oligoamine-induced down-regulation of ERα expression and activity, implying that natural polyamines may play an important role of in maintaining normal ERα function. In ERα promoter deletion/mutation analysis, oligoamines inhibited the ERα promoter element containing the GC and CA rich boxes that have been shown to bind Sp1 transcription factors. Jun NH2-terminal Kinase specific inhibitor SP600125, which blocked oligoamine-induced activation of JNK/c-Jun pathway, inhibited ERα expression, and sensitized tumor cells to oligoamine-induced cell death, indicating that AP-1 transcription factor may positively regulate ERα to protect breast cancer cells against analogue cytotoxicity. Moreover, oligoamines significantly down-regulated the nuclear activity of NF-κB, and down-regulation of NF-κB by oligoamines was prevented by co-treatment of spermine or stably transfected exogenous ERα. These data suggest a possible novel regulation of estrogen signaling by polyamine analogues and interference with the estrogenic signaling pathway by analogues may contribute to polyamine analogue cytotoxicity in human breast cancer. [This work is supported by the grants P50CA88843, CA98454, CA51085, DAMD-17-03-1-0376, and W81XWH-04-1-0457]
Platelet activation indices in patients with Idiopathic Pulmonary Fibrosis
Authors: Paschalis Steiropoulos, Panagiotis Boglou, Paschalis Ntolios, Argyris Tzouvelekis, Maria Xanthoudaki, Maria Kouratzi, Andreas Koulelidis, Evangelia Nena, Marios E. Froudarakis, Demosthenes Bouros
Journal: European Respiratory Journal (2014)

Background: Idiopathic Pulmonary Fibrosis (IPF) is associated with a prothrombotic state.

Aim: To evaluate platelet activation, expressed as Mean Platelet Volume (MPV) and Platelet Distribution Width (PDW) in recently diagnosed IPF patients in comparison with an age- and BMI-matched control group, and to explore possible correlations between these levels and respiratory function in IPF patients.

Materials and methods: This study included 56 IPF patients (age 64.9±7.4 years, BMI 28.55±4.41 Kg/m2) and 79 controls (age 64.2±5.9 years, BMI 28.92±2.98 Kg/m2; p=0.546 and p=0.559 respectively).

Results: As expected, respiratory function was significantly impaired in IPF patients vs. controls in terms of FEV1 (67.15±23.13 vs. 102.62±15.89 %predicted, p<0.001), FVC (65.32±20.99 vs. 95.24±16.09 %predicted, p<0.001), FEV1/FVC (83.07±14.97 vs. 87.5±6.39; p=0.041) and PaO2 (67.13±10.32 vs. 81.51±15.15 mmHg; p<0.001). In IPF patients DLCO was 36.42±16.34 %predicted and TLC was 61.79±16.64 %predicted.

Platelet count was significant lower in IPF patients compared to controls (230,286±59,859 vs 255,608±75,010 cells/ml; p=0.038). On the contrary, MPV was higher in these patients vs. controls (10.35±1.23 vs 9.85±1.23 fl; p=0.024). Difference in PDW was not statistically significant (13.46±1.99 vs. 13.34±2.36 fl, p=0.766).

Correlation analysis revealed no association between MPV and FVC (r=-0.1497, p=0.275) nor between MPV and DLCO (r=0.035, p=0.798) and MPV and TLC (r=0.032, p=0.820).

Conclusions: Platelet activation, expressed as MPV, is higher in IPF patients and is accompanied by a lower platelet count. This finding could be used as an initial biomarker in IPF patients, but further analysis is required.
Area under the reactance curve: Reference ranges and bronchodilator response (BDR) in healthy children
Authors: Shannon J. Simpson, Claudia Calogero, Massimo Palumbo, Judy Park, Peter Franklin, Enrico Lombardi, Peter D. Sly, Graham L. Hall
Journal: European Respiratory Journal (2011)

Introduction:  Lung function in children with asthma is frequently normal during asymptomatic periods, especially when assessed using respiratory resistance and reactance (Xrs). Disease related change in Xrs may be amplified by calculating the area under the reactance curve (AX). Increased sensitivity using AX has been reported in identifying a positive BDR in asthmatic children. However, baseline reference ranges and BDR in healthy children are yet to be defined. Therefore, we developed reference ranges and defined BDR by AX in a large population of healthy children.   Methods:  Impedance spectra were obtained in 760 healthy children (335 male), aged 2-13 years and with height 90-160 cm using a commercial forced oscillation device (FOT) device (I2M, Chess Medical, Belgium). AX between 6 Hz and the resonant frequency was calculated in 647 children. Backward stepwise linear regressions identified anthropometric predictors of AX, and z-score equations were generated. Absolute and relative changes in AX post bronchodilator were calculated in 496 children.   Results:  AX was predicted by height (p -1  and 82%, respectively.   Conclusions:  We have provided healthy reference ranges for AX to aid in disease detection, and defined cut-off values for a positive BDR by AX.
Preclinical to clinical translation of anti-PD-1 blockade
Authors: Heather Hirsch, Elaine Pinheiro, Mark Ayers, Jared Lunceford, Michael Nebozhyn, Erin Murphy, Mingmei Cai, Yanhong Ma, Manjiri Sathe, Terri McClanahan
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts Pembrolizumab (MK-3475), a humanized monoclonal IgG4 antibody against programmed death receptor 1 (PD-1), is currently being studied in clinical trials across more than 30 types of cancers. Immunotherapy with anti–PD-1 monoclonal antibodies such as pembrolizumab shows robust,
Paper Partition Chromatography of Free Amino Acids and Peptides of Normal Human Gastric Juice&lt;xref ref-type="fn" rid="fn1"&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/xref&gt;
Authors: D. Rourke Gilligan, M. S., J. Rothwell Moor, M. S., Shields Warren, M. D.
Journal: JNCI Journal of the National Cancer Institute (1951)

Paper Partition Chromatography of Free Amino Acids and Peptides of Normal Human Gastric Juice D. Rourke Gilligan, M. S., D. Rourke Gilligan, M. S. Laboratories of Pathology of the New England Deaconess Hospital and the Harvard Cancer Commission, Boston, Mass. Search for other works by this author on: Oxford Academic PubMed Google Scholar J. Rothwell Moor, M. S., J. Rothwell Moor, M. S. Laboratories of Pathology of the New England Deaconess Hospital and the Harvard Cancer Commission, Boston, Mass. Search for other works by this author on: Oxford Academic PubMed Google Scholar Shields Warren, M. D. Shields Warren, M. D. Laboratories of Pathology of the New England Deaconess Hospital and the Harvard Cancer Commission, Boston, Mass. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 12, Issue 3, December 1951, Pages 657–676, https://doi.org/10.1093/jnci/12.3.657 Published: 01 December 1951 Article history Received: 01 August 1951 Published: 01 December 1951
2015 Presidential Address: 75 Years of Battling Diabetes−Our Global Challenge
Authors: Samuel Dagogo-Jack
Journal: Diabetes Care (2015)

This address was delivered by Samuel Dagogo-Jack, MD, President, Medicine &amp; Science, of the American Diabetes Association (ADA), at the Association’s 75th Scientific Sessions in Boston, MA, on 7 June 2015. Dr. Dagogo-Jack is a professor of medicine and the director of the Division of Endocrinology, Diabetes and Metabolism and the director of the Clinical Research Center at The University of Tennessee Health Science Center, Memphis, TN, where he holds the A.C. Mullins Endowed Chair in Translational Research. He has been an ADA volunteer since 1991 and has served on several national committees and chaired the Association’s Research Grant Review Committee. At the local level, he has served on community leadership boards in St. Louis, MO, and Tennessee. A physician-scientist, Dr. Dagogo-Jack’s current research focuses on the interaction of genetic and environmental factors in the prediction and prevention of prediabetes, diabetes, and diabetes complications. He is the principal investigator of the Pathobiology of Prediabetes in a Biracial Cohort (POP-ABC) study and also directs The University of Tennessee site for the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) and the Diabetes Prevention Program (DPP)/DPP Outcomes Study (DPPOS). Dr. Dagogo-Jack earned his medical and research doctorate degrees from the University of Ibadan College of Medicine in Nigeria, holds a master’s of science from the University of Newcastle upon Tyne in England, and completed his postdoctoral fellowship training in metabolism at the Washington University School of Medicine in St. Louis in Missouri. A board-certified endocrinologist, Dr. Dagogo-Jack has been elected to the Association of American Physicians and is the 2015 recipient of the Banting Medal for Leadership from the ADA. The ADA and Diabetes Care thank Dr. Dagogo-Jack for his outstanding leadership and service to the Association.
Delay in time to worsening of symptoms (TWS) of advanced non-small cell lung cancer (NSCLC) using gemcitabine (gem) maintenance therapy
Authors: P. Peterson, M. Zwitter, M. Krzakowski, M. Wenczl, V. Tzekova, R. Ramlau, T. Ciuleanu, A. Liepa, C. Zielinski, T. Brodowicz
Journal: Journal of Clinical Oncology (2006)

7140 Background: Palliation of disease-related symptoms is an important clinical benefit. For advanced disease, this may be relief or delay of worsening of symptoms. Since benefit evaluation in clinical trials is usually focused on radiological assessments, development is needed to establish symptom improvement as an efficacy endpoint. Methods: To determine if gem maintenance therapy delayed the worsening of symptoms, retrospective analyses were performed using symptom data reported by patients (pts) with advanced NSCLC from a randomized trial of gem plus cisplatin followed by gem maintenance therapy plus best supportive care (GBSC) or best supportive care (BSC) (Krzakowski, ASCO 2004). Pts rated 6 symptoms using the Lung Cancer Symptom Scale (LCSS) at baseline and every cycle. Symptom worsening was retrospectively defined as a 15-mm increase in the severity score for any symptom (based on 100-mm scales) from randomization (start of maintenance therapy). Analyses were repeated for 10- and 20-mm increases. Data were analyzed using Kaplan-Meier (KM) plots and Cox regression, with censoring at the last LCSS for pts with no worsening. Results: At randomization, 73% were stage IV and 48% had Karnofsky performance status &gt;80. Of the 206 pts randomized, 171 were included in the symptom analyses. Although not significant, the KM plot for TWS based on the 15-mm definition (defn) showed a separation between arms in favor of GBSC beginning ∼2.5 months after randomization (p = 0.24, HR = 0.79). TWS results for the 20-mm defn were significant in favor of GBSC (p = 0.013, HR = 0.59). When the same analysis was applied to individual symptoms, all symptoms showed the same numerical trend (HR&lt;0.77) in favor of GBSC, with significant TWS advantage for GBSC (HR&lt;0.56) for appetite loss and fatigue (15- and 20-mm defn) and for pain (20-mm defn). Additional analyses suggested a strong correlation between TWS and time to progressive disease. Conclusions: In addition to prolonging time to disease progression, gem maintenance therapy delays pt-reported worsening of symptoms. Correlation of TWS with time to progression suggests that delayed TWS may be a clinical benefit of delayed onset of progressive disease. [Table: see text]
Comment on Erondu et al. Diabetic Ketoacidosis and Related Events in the Canagliflozin Type 2 Diabetes Clinical Program. Diabetes Care 2015;38:1680–1686
Authors: Ketan Dhatariya
Journal: Diabetes Care (2015)

I read with interest the article by Erondu et al. (1) on the Janssen Research & Development, LLC, experience of diabetic ketoacidosis (DKA) in a canagliflozin series of studies. They reported the characteristics of 12 cases of DKA in their cohort of 17,596 patients in their studies. However, there remain some potentially troubling issues. In their report, they described 4 out of the 12 patients as having DKA, but they did not report the patients’ pH, bicarbonate, anion gap, or ketone measurements (and in one of the …
Distinct localization and function of1,4,5IP3 receptor subtypes and the1,3,4,5IP4 receptor GAP1IP4BP in highly purified human platelet membranes
Authors: Samer S. El-Daher, Yatin Patel, Ashia Siddiqua, Sheila Hassock, Scott Edmunds, Benjamin Maddison, Geeta Patel, David Goulding, Florea Lupu, Richard J. H. Wojcikiewicz, Kalwant S. Authi
Journal: Blood (2000)
Guest Editorial by Ernest L. Wynder and Marvin A. Schneiderman
Authors: Philippe Shubik, D. B. Clayson
Journal: JNCI Journal of the National Cancer Institute (1974)

Guest Editorial by Ernest L. Wynder and Marvin A. Schneiderman Philippe Shubik, D.M., D. Phil., Philippe Shubik, D.M., D. Phil. Eppley Institute for Research in Cancer, Omaha, Nebraska 68105 Search for other works by this author on: Oxford Academic PubMed Google Scholar D. B. Clayson, Ph.D. D. B. Clayson, Ph.D. Department of Experimental Pathology and Cancer Research School of Medicine, Leeds LS2 9NL, England Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 53, Issue 2, August 1974, Pages 595–596, https://doi.org/10.1093/jnci/53.2.595 Published: 01 August 1974
A Clinical Trial Comparing Primary Stenting of the Infarct-Related Artery With Optimal Primary Angioplasty for Acute Myocardial Infarction
Authors: David Antoniucci, Giovanni M Santoro, Leonardo Bolognese, Renato Valenti, Maurizio Trapani, Pier Filippo Fazzini
Journal: Journal of the American College of Cardiology (1998)
P-179 Gemcitabine plus nab-Paclitaxel in metastatic or locally inoperable pancreatic cancer – a single center experience
Authors: U. Vogl, L. Vormittag, T. Winkler, A. Kafka, M. Henry, W. Schima, A. Klaus, J. Zacherl, L. Öhler
Journal: Annals of Oncology (2015)
A detailed characterization of peripheral blood lymphocytes in patients with myeloproliferative disease treated with pegylated-interferon alpha
Authors: Magdalena Kovacsovics-Bankowski, Christy Warby, Olga Effimova, Todd W Kelley, Soo Kim, Sabina Swierczek, Josef Prchal
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts Pegylated-Interferon alpha (Peginfa) treatment of patients with polycythemia vera or essential thrombocythemia has resulted in long-term clinical response, decrease JAK2 V617F allelic burden and restoration of polyclonal hematopoiesis. Characterizing the peripheral blood
Abstract 4501: Development of novel Lithocholic acid carboxamides with antiproliferative and pro-apoptotic effects on human cancer cells
Authors: Srinivasa R. Ramisetti, Deepkamal Karelia, Melanie Neagley, Shantu Amin, Arun K. Sharma
Journal: Cancer Research (2015)

Abstract Bile acids, the products of cholesterol catabolism, are synthesized in the liver and subsequently excreted into the bile canaliculus and the digestive tract as N-acyl conjugates of glycine or taurine. Among all bile acids, Lithocholic acid (LCA) and Ursodeoxycholic acid (UDCA) conjugates have been reported to inhibit the growth of various human cancer cells both in vitro and in vivo. Most importantly LCA has been shown to inhibit growth of different cancer cell lines including prostate and neuroblastoma cells, while sparing normal cells. In addition, a report has shown LCA-amphiphiles to be effective anti-tumor agents in a colon cancer xenograft model. In contrast, there are reports indicating that LCA may promote dimethyl hydrazine (DMH) induced colon carcinogenesis and may also act as a carcinogen itself. This indicates that in spite of having anti-cancer properties, LCA may pose a risk of developing colon cancer. We hypothesized that LCA structure can be optimized to eliminate the carcinogenesis promoting properties, while enhancing its potency to create effective therapeutics against colon, prostate, and other cancers. Therefore, we designed and synthesized a series of novel cyclic and acyclic LCA-carboxamides by blocking the acid functionality of LCA. The cytotoxicity of the novel analogs was evaluated against colon (HT29) and prostate (DU145) cancer cells. Three analogs ASR-320, ASR-322 and ASR-339 inhibited the viability of these cells with an EC50 value of 5-10 μM, while LCA had no effect on cell viability at highest dose used (50 μM). The results suggests that the new analogs are at least 10 times more potent than the parent compound, LCA. One of the agents, induced apoptosis in both prostate (DU145) and colon (HT29) cancer cell lines, as indicated by Caspase 3 activation and PARP degradation. Currently, we are further optimizing the structure based on the initial leads and investigating efficacy and mechanistic studies in prostate and colon cancer models. Detailed results of these investigations will be presented. Citation Format: Srinivasa R. Ramisetti, Deepkamal Karelia, Melanie Neagley, Shantu Amin, Arun K. Sharma. Development of novel Lithocholic acid carboxamides with antiproliferative and pro-apoptotic effects on human cancer cells. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4501. doi:10.1158/1538-7445.AM2015-4501