tbuckley/cabot-search huggingface dataset:
Association of chronic baseline prostate inflammation with lower tumor grade in men with prostate cancer on repeat biopsy.
Authors: Daniel M. Moreira, J. Curtis Nickel, Gerald L. Andriole, Ramiro Castro, Stephen J. Freedland
Journal: Journal of Clinical Oncology (2016)

75 Background: We have previously shown that chronic baseline prostate inflammation in an otherwise benign biopsy was associated with lower risk of prostate cancer in repeat prostate biopsies and lower tumor volumes for those who are diagnosed with cancer. In the present study, we evaluated whether baseline acute or chronic prostate inflammation among men with initial negative biopsies for prostate cancer was associated with cancer grade at the 2-year repeat prostate biopsy. Methods: Retrospective analysis of 889 men 50-75 years-old with negative baseline prostate biopsy and positive 2-year repeat biopsy for prostate cancer in the REDUCE study. Acute and chronic prostate inflammation (coded as present or absent) and cancer grade were determined by central pathology. The association of inflammation in baseline biopsies with 2-year repeat biopsy cancer grade (low-grade: Gleason scores 2-6 vs. high-grade: Gleason scores 7-10) was evaluated with t test, chi-squared test and logistic regression controlling for age, race, body-mass index (BMI), digital rectal exam (DRE), prostate volume, baseline pre-study PSA and treatment (dutasteride or placebo). Results: Chronic, acute inflammation and both were detected in 533 (60%), 12 (1%) and 85 (10%) baseline biopsies, respectively. Presence of acute and chronic inflammations were significantly associated with each other (P &lt; 0.001). Patients with chronic inflammation had significantly larger prostates (P &lt; 0.001). Both types of inflammation were unrelated to race, BMI, PSA or DRE. At 2-year biopsy, a total of 621 (70%) tumors were low-grade and 268 (30%) tumors were high-grade. In both uni- and multivariable analyses, men with baseline chronic inflammation had significantly less high-grade tumors (univariable OR = 0.64, 95% CI = 0.47-0.87, P = 0.004; multivariable OR = 0.68, 95% CI = 0.50-0.93, P = 0.016) than those without baseline chronic inflammation. Baseline acute inflammation was not associated with tumor grade. Conclusions: Among men undergoing repeat prostate biopsy 2 years after a negative baseline biopsy who all had cancer on the follow-up biopsy, the presence baseline chronic inflammation was associated with lower prostate cancer grade.
Functional Interaction of the Ankylosing Spondylitis–Associated Endoplasmic Reticulum Aminopeptidase 2 With the HLA–B*27 Peptidome in Human Cells
Authors: Adrian Martín‐Esteban, Pablo Guasp, Eilon Barnea, Arie Admon, José A. López de Castro
Journal: Arthritis & Rheumatology (2016)

To determine the influence of endoplasmic reticulum aminopeptidase 2 (ERAP-2) expression on the HLA-B*27 peptidome in live cells.Using immunoaffinity chromatography and acid extraction, HLA-B*27:05-bound peptides were isolated from 2 ERAP-2-negative lymphoblastoid cell lines and 1 ERAP-2-positive lymphoblastoid cell line expressing functionally indistinguishable ERAP-1 variants. More than 2,000-4,000 B*27:05 ligands were identified from each cell line, and their relative abundance was established by quantitative tandem mass spectrometry and MaxQuant-based peptide analyses. Pairwise comparisons were used to determine the structural features of peptides whose relative abundance was dependent on the presence of ERAP-2. Synthetic peptide digestions were performed with recombinant ERAP-1 and ERAP-2. Peptide affinity was estimated with standard algorithms.The B*27:05 peptidome from ERAP-2-positive cells showed 3-4% fewer peptides with N-terminal basic residues than did the peptidome from ERAP-2-negative cells. Among the shared peptides, those most abundant in the presence of ERAP-2 included more nonamers, fewer decamers, and fewer N-terminal basic residues than the peptides predominant in ERAP-2-negative cells. These ERAP-2-dependent changes did not alter the global affinity of the B*27:05 peptidome.ERAP-2 significantly influences the B*27:05-bound peptidome by destroying some ligands and decreasing the abundance of many more ligands with N-terminal basic residues, while increasing the abundance of nonamers. The former effects are best explained by direct ERAP-2 trimming. The effects on peptide length might be attributed to ERAP-2-induced activation of ERAP-1 trimming. These data support the notion of a peptide-mediated mechanism as the basis for the association of ERAP-2 with ankylosing spondylitis. Analogous effects on other major histocompatibility complex class I peptidomes might explain the involvement of ERAP-2 in HLA-B27-negative spondyloarthritis.
TCTAP A-149 Long-Term Evaluation of Safety and Efficacy of Biodegradable Polymer Coated Sirolimus-Eluting Indolimus Coronary Stent System
Authors: Rajasekhar Durgaprasad, Vamsidhar Akkulagari, Vanajakshamma Velam, Latheef Kasala, Sreedhar Naik Kanavat, Sowjenya Gopal
Journal: Journal of the American College of Cardiology (2016)
Screening and identification of mimotopes of the major shrimp allergen tropomyosin using one-bead-one-compound peptide libraries
Authors: Nicki YH Leung, Christine YY Wai, Marco HK Ho, Ruiwu Liu, Kit S Lam, Jin Jun Wang, Shang An Shu, Ka Hou Chu, Patrick SC Leung
Journal: Cellular and Molecular Immunology (2015)
Pharmacology of dextromethorphan: Relevance to dextromethorphan/quinidine (Nuedexta®) clinical use
Authors: Charles P. Taylor, Stephen F. Traynelis, Joao Siffert, Laura E. Pope, Rae R. Matsumoto
Journal: Pharmacology & Therapeutics (2016)

Dextromethorphan (DM) has been used for more than 50years as an over-the-counter antitussive. Studies have revealed a complex pharmacology of DM with mechanisms beyond blockade of N-methyl-d-aspartate (NMDA) receptors and inhibition of glutamate excitotoxicity, likely contributing to its pharmacological activity and clinical potential. DM is rapidly metabolized to dextrorphan, which has hampered the exploration of DM therapy separate from its metabolites. Coadministration of DM with a low dose of quinidine inhibits DM metabolism, yields greater bioavailability and enables more specific testing of the therapeutic properties of DM apart from its metabolites. The development of the drug combination DM hydrobromide and quinidine sulfate (DM/Q), with subsequent approval by the US Food and Drug Administration for pseudobulbar affect, led to renewed interest in understanding DM pharmacology. This review summarizes the interactions of DM with brain receptors and transporters and also considers its metabolic and pharmacokinetic properties. To assess the potential clinical relevance of these interactions, we provide an analysis comparing DM activity from in vitro functional assays with the estimated free drug DM concentrations in the brain following oral DM/Q administration. The findings suggest that DM/Q likely inhibits serotonin and norepinephrine reuptake and also blocks NMDA receptors with rapid kinetics. Use of DM/Q may also antagonize nicotinic acetylcholine receptors, particularly those composed of α3β4 subunits, and cause agonist activity at sigma-1 receptors.
Drug Pricing Trends for Orally Administered Anticancer Medications Reimbursed by Commercial Health Plans, 2000-2014
Authors: Stacie B. Dusetzina
Journal: JAMA Oncology (2016)

Reimbursed by Commercial Health Plans, 2000-2014Prescription drug pricing and changes in prices for existing drugs have been under intense scrutiny recently. 1For anticancer medications, high drug prices have the potential to affect access and adherence to therapies and increase financial burden for patients. [2]3][4][5] Given the rapidly evolving drug pricing landscape, it is important to evaluate recent pricing for anticancer medications.This study's objectives were to estimate changes in reimbursements for orally administered anticancer drugs paid by commercial health plans from 2000 through 2014, focusing on reimbursements during the year of product launch and changes in reimbursements over time.Methods | TruvenHealth MarketScan outpatient prescription drug data from January 1, 2000, through December 31, 2014, were used to identify claims for dispensed orally administered anticancer medications approved in 2000 or after, 6 excluding any claims for which the total paid was $0 or less or greater than $250 000.To ensure comparable estimates over time, only fills for a single month of therapy were included for all products.There were 483 587 drug fills included in this analysis.Because this was a secondary analysis of deidentified health plan claims, this study received an institutional review board waiver from the University of North Carolina at Chapel Hill.Measures.Mean per-fill payments to the pharmacy for a single month of supply of each product were summarized by calendar year (monthly spending).These payments included contributions made by the health plan and patient but do not include rebates received from manufacturers.Analysis.First, mean monthly spending was summarized for products during the year of initial approval from January 1, 2000, through December 31, 2014.Second, for products available since 2011, changes in monthly spending were estimated and productspecific monthly spending was compared between the launch year and 2014.For all analyses, generalized estimating equations with log links and normal distributions were used, and means and 95% CIs are presented.All dollars were inflation adjusted to 2014 US dollars using the medical component of the Consumer Price Index.In sensitivity analyses, the top 5% of spending for each drug was excluded to evaluate the influence of outliers on estimates.There were no substantive differences between these results and the primary analysis.
Clinical significances of preoperative serum IL-6 and CRP level in operable gastric cancer
Authors: S. Lee, D. Kim, S. Oh, H. Kwon, J. Jang, S. Kim, M. Kim, K. Kim, J. Han, H. Kim
Journal: Journal of Clinical Oncology (2009)

e15591 Background: The interleukin (IL)-6 pathway is one of the mechanisms liking inflammation and angiogenesis to malignancy. As the C-reactive protein (CRP) is representative marker of inflammation, recently CRP has been reported to be associated with processing of disease in many cancers. This study aims to determine the preoperative serum levels of IL-6 and CRP in gastric carcinoma, and correlate them with disease status and prognosis. Methods: A total of 115 patients receiving gastrectomy entered this study. Serum level of IL-6 was measured by using Enzyme-Linked Immuno-Sorbent Assay (ELISA) and CRP was measured by using immunoturbidimetry. Histological findings were included depth of tumor invasion, lymph node (LN) metastasis, and TNM stage (AJCC Stage Groupings The staging systems; Primary tumor, regional LN, metastasis). Results: The more cancer invasion and stage are high, the more preoperative serum IL-6 levels are high. IL-6 level was correlated with depth of invasion (P=0.006) and TNM stage (P&lt;0.001). Preoperative CRP level also correlated with depth of invasion (P&lt;0.001), TNM stage (P=0.001), and presence of peritoneal seeding metastasis (positive 0.66 ± 0.69 mg/dL, negative 0.20 ± 0.29 mg/dL; P&lt;0.001). When we put cutoff value of IL-6 level (6.77 pg/dL) by ROC curve, although patients’ survival did not reach the median value, it shows significant difference in time to progression (TTP; P&lt;0.001) and overall survival (OS; P&lt;0.010). But, CRP did not show significance to patients’ TTP and OS. Conclusions: Preoperative serum IL-6 and CRP levels might be markers of tumor invasion and TNM stage. Preoperative high IL- 6 level was a poor prognostic factor of disease recurrence and overall survival in patients with gastric cancers. No significant financial relationships to disclose.
Abstract P069: Modifiable Risk Factors as Drivers of Pharmaceutical Expenditures Among US Adults with Atherosclerotic Heart Disease: 2012 Medical Expenditure Panel Survey
Authors: Joseph A Salami, Javier Valero-Elizondo, Oluseye Ogunmoroti, Erica S Spatz, Jamal S Rana, Salim S Virani, Ron Blankstein, Michael J Blaha, Adnan Younus, Alejandro Arrieta, Emir Veledar, Khuram Nasir
Journal: Circulation (2016)

Background: Atherosclerotic Cardiovascular disease (ASCVD) remains the leading cause of deaths and costs in the US. Despite advancements in therapies, no study has evaluated drivers of pharmaceutical expenditures among individuals with ASCVD. We aimed to assess the economic impact of modifiable risk factors (MRF) on overall pharmaceutical expenditures among ASCVD patients. Methods: We studied the 2012 Medical Expenditure Panel Survey (MEPS) data of adults aged ≥40 years with Body Mass Index ≥18.5Kg/m2 and ICD-9 diagnosis of ASCVD (410, 413, 414, 433, 434, 435, 436, 437, 440, 443, and 447). Using total pharmacy expenditure variable in MEPS as our primary outcome, marginal and actual expenditures associated with predictors were estimated using a two-part econometric model with probit and glm, family(gamma) link (log). Results: Based on the 2012 MEPS, an estimated 140.7 million people in US are aged ≥40 years. An estimated 15.4 million had ASCVD (69±15 years; 41% female). Overall, total pharmaceutical expenditure among those with ASCVD was $52.7 billion (95% CI: $44.2-62.0 billion), which accounted for 33.7% of total pharmaceutical expenditures. Individuals with ASCVD had $1,847 (95% CI: $1,655 - 2,038) incremental pharmaceutical expenditure vs. those without it (p&lt;0.001). The two-part econometric model showed that all MRF independently impacted incremental expenditure. By aggregates of MRF, 50% had 2-3; 39% had 4-6; and the rest (11%) had one or none. The estimated pharmaceutical expenditures was lower with favorable MRF status irrespective of comorbid conditions. In adjusted analyses, as compared to those with ≥4 MRF, those with 2-3 had $1,881 (95% CI: $1,242 -2,521) and those with 0-1 MRF had $2,669 (95% CI: $2,317 - 3,020) lower pharmaceutical costs, respectively. Conclusion: Our study results suggest attainment of favorable modifiable risk status as delineated in AHA 2020 Impact goals can have a beneficial impact on pharmaceutical costs, which accounts for significant proportion of overall healthcare expenditure.
Progressive Hilar and Mediastinal Lymphadenopathy in Systemic Lupus Erythematosus on Corticosteroid Therapy
Authors: Stuart S. Kassan, Morton L. Moss, Robert L. Reddick
Journal: New England Journal of Medicine (1976)

LYMPH-node enlargement occurs in approximately half of all patients with systemic lupus erythematosus.1 Although the histologic characteristics were described by Short2 in 1907, until 1943, lymphadenopathy in the disease received only brief mention, for early workers regarded much of the lymph-node enlargement in this disease as secondary to tuberculosis.3 , 4 In the more recent literature, lymph-node enlargement has been a relatively common finding mostly affecting cervical, axillary or inguinal regions. Bilateral hilar lymphadenopathy, however, alone or in association with generalized lymphadenopathy, is rarely encountered in the disease. In the following case of steroid-resistant enlargement of hilar and mediastinal lymph nodes in . . .
Case 15-1971
Authors: Louis M. Sherwood, Benjamin Castleman
Journal: New England Journal of Medicine (1971)

Presentation of CaseA 54-year-old man was referred to the hospital because of hypercalcemia.For 20 years his intake of alcohol had been heavy, but he was able to continue his work as a carpenter. Ten years before admission he was disabled by a "stroke," about which no further details could be obtained. At approximately that time he was informed that he had a duodenal ulcer; thereafter he consumed small amounts of Maalox and 2 quarts of milk daily. Six months before entry he began to experience exertional dyspnea on climbing stairs. One month before admission anorexia, polydipsia, polyuria and . . .
TCTAP A-091 Different Plaque Re-Distribution Between Non-Slip Element Balloon and Conventional Balloon in De Novo Coronary Artery Lesions: 3D-IVUS Study
Authors: Yuki Saka, Kazuyuki Maeda, Katsuhisa Waseda, Hiroaki Takashima, Akiyoshi Kurita, Hirohiko Ando, Shinichiro Sakurai, Akihiro Suzuki, Tetsuya Amano
Journal: Journal of the American College of Cardiology (2016)
The Patient You Least Want to See
Authors: Jonathan H. Chen
Journal: JAMA (2016)

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Hunt offers to meet BMA chair to try to avert all-out strike by junior doctors
Authors: Gareth Iacobucci
Journal: BMJ (2016)

England’s health secretary, Jeremy Hunt, has offered to meet with the BMA’s chairman of council, Mark Porter, in a last ditch attempt to avert this week’s plan for an all-out strike by junior doctors.

In a letter to Porter sent on Saturday 23 April,1 Hunt said that he would be willing to meet to discuss “a range of issues that can improve the terms and conditions for junior doctors” if the BMA agreed to call off the full withdrawal of labour by junior doctors on Tuesday 26 and Wednesday 27 April.

But Porter said that talks could take place only if the health secretary removed his threat to impose the new contract on junior doctors.

Against this backdrop, the heads of 13 medical royal colleges wrote to the prime minister, David Cameron, on Monday 25 …
Relation of Counterregulatory Responses to Hypoglycemia in Type I Diabetics
Authors: Kenneth Polonsky, Richard Bergenstal, Guillermo Pons, Michael Schneider, Jonathan Jaspan, Arthur Rubenstein
Journal: New England Journal of Medicine (1982)

We compared counterregulatory metabolic and hormonal responses in 8 normal controls with responses in 16 Type I (insulin-dependent) diabetics, 7 of whom had had repeated attacks of severe hypoglycemia, in an effort to determine whether these responses are related to the occurrence of hypoglycemia in the latter group. In response to insulin-induced hypoglycemia, peak values for glucose production (5.7±0.5 vs. 2.5±0.3mg per kilogram of body weight per minute) (P<0.0001), glucagon (195±26 vs. 93±18 pg per milliliter) (P<0.0001), and growth hormone (63±8 vs. 37±5 ng per milliliter) (P<0.006) were significantly higher in the controls than in the diabetics. However, peak values for glucose production, glucagon, epinephrine, norepinephrine, cortisol, and growth hormone were similar in the diabetics with and without clinical hypoglycemia. Thus, with the present dose and method of insulin administration we were unable to predict the presence of severe hypoglycemic reactions in a group of Type I diabetics. Although deficient counterregulatory hormonal responses are important in the pathogenesis of hypoglycemic reactions, we conclude that other factors in the daily lives of such patients also play a major part in determining whether reactions will occur. (N Engl J Med. 1982; 307:1106–12.)
Adenosine Is A Common Factor Regulating Erythrocyte 2,3-Bisphosphate Induction In Normal Individuals At High Altitude and In Patients With Sickle Cell Disease
Authors: Yujin Zhang, Hong Liu, Kaiqi Sun, Anren Song, Harry Karmouty-Quintana, Ning-Yuan Chen, Almut Grenz, Rodney E. Kellems, Modupe Idowu, Harinder S. Juneja, Robert Roach, Holger Eltzschig, Michael R. Blackburn, Yang Xia
Journal: Blood (2013)
A Monovalent Chimpanzee Adenovirus Ebola Vaccine Boosted with MVA
Authors: Katie Ewer, Tommy Rampling, Navin Venkatraman, Georgina Bowyer, Danny Wright, Teresa Lambe, Egeruan B. Imoukhuede, Ruth Payne, Sarah Katharina Fehling, Thomas Strecker, Nadine Biedenkopf, Verena Krähling, Claire M. Tully, Nick J. Edwards, Emma M. Bentley, Dhanraj Samuel, Geneviève Labbé, Jing Jin, Malick Gibani, Alice Minhinnick, Morven Wilkie, Ian Poulton, Natalie Lella, Rachel Roberts, Felicity Hartnell, Carly Bliss, Kailan Sierra-Davidson, Jonathan Powlson, Eleanor Berrie, Richard Tedder, Francois Roman, Iris De Ryck, Alfredo Nicosia, Nancy J. Sullivan, Daphne A. Stanley, Olivier T. Mbaya, Julie E. Ledgerwood, Richard M. Schwartz, Loredana Siani, Stefano Colloca, Antonella Folgori, Stefania Di Marco, Riccardo Cortese, Edward Wright, Stephan Becker, Barney S. Graham, Richard A. Koup, Myron M. Levine, Ariane Volkmann, Paul Chaplin, Andrew J. Pollard, Simon J. Draper, W. Ripley Ballou, Alison Lawrie, Sarah C. Gilbert, Adrian V.S. Hill
Journal: New England Journal of Medicine (2015)

The West African outbreak of Ebola virus disease that peaked in 2014 has caused more than 11,000 deaths. The development of an effective Ebola vaccine is a priority for control of a future outbreak.
Finding a new role for NEMO: A key player in preventing hepatocyte apoptosis and liver tumorigenesis by inhibiting RIPK1
Authors: I‐Fang Hsin, Erica Montano, Ekihiro Seki
Journal: Hepatology (2016)

Hsin, I‐Fang M.D.1; Montano, Erica M.S.1; Seki, Ekihiro M.D., Ph.D.1 Author Information
Abstract 53: Tenascin-C Expression in Cardiovascular Lesion of Kawasaki disease.
Authors: Yuki Yokouchi, Toshiaki Oharaseki, Yasunori Enomoto, Shiro Naoe, Kyoko Imanaka-Yoshida, Kei Takahashi
Journal: Circulation (2015)

Background: Tenascin-C (TN-C) is an extracellular matrix that is closely associated with tissue remodeling and inflammation. It is expressed under pathological condition such as myocarditis, myocardial infarction, atherosclerosis and aneurysm. However, examination of TN-C expression in Kawasaki disease (KD) has not been yet performed. Materials and methods: The tissue samples of myocardium and coronary arteries were obtained from 25 autopsy cases of KD(age: 3 months to 20 years old, sex: 18 males and 7 females, duration of the illness: 6 days to 17 years). Histological findings of the myocardium and coronary artery were analyzed and correlated with TN-C expression by immunohistochemistry. Results: 1) Myocardium: Myocarditis was observed in 8 KD patients who died within 33 days after the onset. On the other hand, chronic persistent myocarditis and post-inflammatory myocardial fibrosis were not seen in the patients who died after 33th day of the disease. Myocardial infarction was observed in 9 patients who died in the convalescent and remote phases of KD. Expression of TN-C in the myocardium corresponded to the area with inflammatory cell infiltration and granulation tissue. The degree of expression correlated with the severity of the inflammation. 2) Coronary artery: Intense TN-C expression was observed at the site of active inflammation of coronary arteries in acute stage. Regarding convalescent period (27 to 57 days after the onset) when the inflammation began to disappear, the TN-C expression still remained in the intima and media but weakened in the adventitia and surrounding connective tissue. In remote phase, TN-C expression was limited to the neovascular vessels in the thickened intima and recanalized vessels. Conclusion: The results of this histological study demonstrate that TN-C may be a useful biomarker for indicating in KD cardiovascular lesions.