tbuckley/cabot-search huggingface dataset:
Cost-Effectiveness of N-Terminal Pro-B-Type Natriuretic-Guided Therapy in Elderly Heart Failure Patients
Authors: Sandra Sanders-van Wijk, Antoinette D.I. van Asselt, Hans Rickli, Werner Estlinbaum, Paul Erne, Peter Rickenbacher, Andre Vuillomenet, Martin Peter, Matthias E. Pfisterer, Hans-Peter Brunner-La Rocca
Journal: JACC Heart Failure (2013)
SCAI/ACC/HRS Institutional and Operator Requirements for Left Atrial Appendage Occlusion
Authors: Clifford J. Kavinsky, Fred M. Kusumoto, Anthony A. Bavry, Steven R. Bailey, Kenneth A. Ellenbogen, Paul L. Hess, Daniel L. Lustgarten, Issam D. Moussa, Christian Spies
Journal: Journal of the American College of Cardiology (2015)
cmFPA008, an anti-mouse CSF-1R antibody, combines with multiple immunotherapies to reduce tumor growth in nonclinical models
Authors: David Bellovin, Nebiyu Wondyfraw, Anita Levin, David G DeNardo, Emma Masteller, Thomas Brennan
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts The colony stimulating factor 1 receptor (CSF1R) signaling pathway drives the recruitment, differentiation, and survival of tumor-associated macrophages (TAMs) in the neoplastic microenvironment, promoting tumor progression and modulation of the immune response. As such, CSF1R
Cancer in Families: A Study of the Relatives of 200 Breast Cancer Probands.
Journal: Annals of Internal Medicine (1960)

The purpose of this book was to see whether cancer occurred more frequently in the relatives of persons who had cancer than in the relatives of persons who did not and, if so, whether the difference was greater in some relationships than in others. An introductory section reviews previous research on the subject and draws valuable lessons as to methodology from the conflicting and inconclusive publications of the past. Section 2 describes the authors' methods and shows to what lengths the authors went to secure comparable groups of probands with and without cancer. The findings are summarized in 47 pages of tables and text in section 3 and lead (page 64) to the conclusion (section 4) that, if a familial tendency to develop cancer did exist, it was not strong enough to be detected in this sample of 200 breast cancer patients. A critical comparison with a previous study by
Financial incentives for smoking cessation
Authors: D Shrikrishna
Journal: Thorax (2009)

Successful smoking cessation is fundamental to reducing the worldwide healthcare burden of chronic disease. This randomised controlled trial investigated the impact of financial incentives on smoking cessation among employees of a multinational company in the USA.

The study randomised 878 employees to receive information on available smoking cessation programmes (n = 442) or the same information with financial incentives (n = 436). These included …
Abstract 18977: Non-Syndromic Mitral Valve Prolapse From Gene Mutations to Modifiable Mechanisms
Authors: Russell Norris, Kimberly Sauls, Ronen Durst, David Peal, Katelynn Toomer, Maire Leyne, Michael E Talkowski, Harrison Brand, Maelle Perrocheau, Stacey N Lynch, Nabila Bouaia-Naji, Francesca N Delling, Lisa A Freed, Thierry Le Tourneau, Herve LeMarec, Xavier Estivill, Leticia Fernandez-Friera, Christian Dina, Jorge Solis, Daniel Trujillano, Kenneth D Irvine, Yaopan Mao, Stephan Ossowski, Any Wessels, Donald Menick, Harinath Kasiganesan, Ann-Marie Bromme, Katherine Williams, Jean-Jacques Schott, Albert A Hagege, Xavier Jeunemaitre, Roger R Markwald, David J Milan, Robert A Levine, Susan Slaugenhaupt
Journal: Circulation (2014)

Mitral valve prolapse (MVP) is a common disease affecting nearly 1 in 40 individuals. It is the leading surgical indication for mitral valve regurgitation. Despite a clear heritable component, the genetic etiology of non-syndromic MVP has remained elusive. Individuals from a large multigenerational family segregating non-syndromic MVP underwent capture sequencing of a previously linked interval on chromosome 11. We found a novel missense mutation in DCHS1, the human homologue of the Drosophila cell polarity gene dachsous (ds) that segregates with MVP in the family. The familial mutation reduced protein stability in zebrafish and cultured cells. Morpholino knockdown of zebrafish dachsous1b yielded a regurgitant atrioventricular canal defect that could be rescued by wild-type human DCHS1 but not by mRNA with the familial mutation. Adult haploinsufficient Dchs1 mice had anatomic and functional prolapse of thickened, elongated leaflets recapitulating the human MVP phenotype. Dchs1 haploinsufficiency was associated with developmental defects in valve shape, cell migration and patterning during fetal morphogenesis, suggesting cell polarity as a previously unrecognized facet of valve morphogenesis. Studies of downstream changes identified increased MAP kinase activities and α-SMA+ cells (myofibroblasts) in the valves preceding myxomatous degeneration; these suggest potential future directions for blunting disease progression. Additional genetic studies identified a second family with a DCHS1 mutation and a significantly increased burden of novel DCHS1 mutations in sporadic MVP cases Interdisciplinary studies strongly support DCHS1 as the first identified disease-causing gene for non-syndromic MVP and suggest potential mechanisms for modifying disease natural history.
RETRACTED: The Ubiquitin Ligase Mul1 Induces Mitophagy in Skeletal Muscle in Response to Muscle-Wasting Stimuli
Authors: Sudarsanareddy Lokireddy, Isuru W Wijesoma, Serena Teng, Sabeera Bonala, Peter D Gluckman, Craig McFarlane, Mridula Sharma, Ravi Kambadur
Journal: Cell Metabolism (2012)
Aryl hydrocarbon hydroxylase and psoriasis
Authors: M. Rawlins, S. Shuster
Journal: BMJ (1982)

The administration of zinc supplements in pharmacological doses without knowledge of tissue zinc status carries risks, as this impairs absorption and may precipitate deficiency of other trace elements, particularly iron4 and copper.5We therefore suggest that tissue zinc depletion should be established before zinc supplementation and that the trace element profile is monitored during such treatment.
Electrotransfer of IL-15/IL-15Rα complex for the treatment of established melanoma
Authors: Shawna Shirley, Cathryn Lundberg, Niculina Burcus, Richard Heller
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts Interleukin-15 (IL-15) mediates the function of some innate and adaptive immune cells, which makes it an attractive target as an anti-cancer agent. Gene electrotransfer (GET) has been used to safely deliver plasmid DNA (pDNA) to tissues in a number of pre-clinical and clinical
Botulinum Toxin Injection in Epicardial Fat Pads Can Prevent Recurrences of Atrial Fibrillation After Cardiac Surgery
Authors: Evgeny Pokushalov, Boris Kozlov, Alexander Romanov, Artem Strelnikov, Sevda Bayramova, David Sergeevichev, Alexander Bogachev-Prokophiev, Sergey Zheleznev, Vladimir Shipulin, Nariman Salakhutdinov, Vladimir V. Lomivorotov, Alexander Karaskov, Sunny S. Po, Jonathan S. Steinberg
Journal: Journal of the American College of Cardiology (2014)
AIDS retrovirus antibodies in hemophiliacs treated with factor VIII or factor IX concentrates, cryoprecipitate, or fresh frozen plasma: prevalence, seroconversion rate, and clinical correlations
Authors: MV Ragni, GE Tegtmeier, JA Levy, LS Kaminsky, JH Lewis, JA Spero, FA Bontempo, C Handwerk-Leber, WL Bayer, DH Zimmerman
Journal: Blood (1986)
Postoperative pressure sores after epidural anaesthesia
Authors: Franz J Wiedermann, Werner Lingnau, Petra Innerhofer
Journal: BMJ (2001)

EDITOR—Shah reported three cases of heel ulcers related to pressure after epidural analgesia.1 A Medline search on the occurrence of pressure sores after epidural anaesthesia shows that, together with the cases reported by Shah, so far only 10 cases of heel ulcers have been reported in the literature.2-5 There are also two reports on seven patients developing decubitus ulceration after epidural analgesia administered during labour, in whom prolonged sitting and disinfectant pooling under and irritating the perineal skin could have been contributing factors.

The reported concentration of bupivacaine in the postoperative continuous epidural infusion varied from 0.1% to 0.25%, the infusion rate from 6 ml/h to 10 ml/h. Patient controlled epidural analgesia with a background infusion of 2 ml/h and a demand dose of 2 ml of 0.11% bupivacaine together with adrenaline (epinephrine), sufentanil, and clonidine was reported in three cases.3 In the report by Shah the infusion rate of 0.15% bupivacaine is missing. The most prominent finding is the occurrence of a motor block on the first day after the operation in two patients.

So far in our hospital we have no documented cases of postoperative pressure sores related to epidural anaesthesia. In 1999, 608 patients received patient controlled epidural analgesia, mostly after orthopaedic (41%), gynaecological (20%), urological (16%), and thoracic or abdominal surgery (13%). Of 252 patients undergoing orthopaedic surgery, 69% had combined spinal epidural anaesthesia and 31% general combined with epidural anaesthesia. Patient controlled epidural analgesia with 0.0625% bupivacaine, 2 μg/ml fentanyl, and 2 μg/ml adrenaline (epinephrine) is administered as a continuous infusion of 6-8 ml/h and a demand dose of 3-4 ml (lockout time 30 minutes). The goal is to obtain sufficient analgesia without motor and profound sensory block, and any motor block should be limited to the immediate postoperative period. Patients may …
A phase 2 study of a novel transforming growth factor-beta (TGF-β1) receptor I kinase inhibitor, LY2157299 monohydrate (LY), in patients with advanced hepatocellular carcinoma (HCC).
Authors: Sandrine J. Faivre, Armando Santoro, Robin Kate Kelley, Philippe Merle, Ed Gane, Jean-Yves Douillard, Dirk Waldschmidt, Mary Frances Mulcahy, Charlotte Costentin, Beatriz Minguez, Pasqua Papappicco, Ivelina Gueorguieva, Ann Cleverly, Durisala Desaiah, Michael M. Lahn, Sophie Ameryckx, Karim A. Benhadji, Eric Raymond, Gianluigi Giannelli
Journal: Journal of Clinical Oncology (2014)

LBA173 Background: TGF-β signaling is associated with HCC progression in moderate to poorly differentiated tumors overexpressing alpha-fetoprotein (AFP) levels. We report here the safety, antitumor activity, and overall survival (OS) in HCC patients with elevated AFP treated with LY. Methods: Patients with advanced HCC who progressed on sorafenib (SF) or are ineligible to receive SF, advanced Child-Pugh A/B7 HCC, AFP ≥1.5x ULN, ECOG PS ≤1, measurable disease (RECIST 1.1), and ≤1 prior systemic regimen were eligible. LY was administered as intermittent dosing of 14 days on/off (28 days=1 cycle). Patients were randomized to either 160 mg/day (Arm A) or 300 mg/day (Arm B) LY. Primary endpoints were time-to-progression (TTP) and biomarker changes (serum AFP, TGF-β and E-cadherin) for each dose. AFP responders were defined as &gt;20% decline from baseline. Secondary endpoints included toxicity (CTCAE, V 4.0) and pharmacokinetics (PK). Available data from interims are presented. Results: 109 patients were enrolled (Arm A=37; B=72). Baseline characteristics were (Arm A/B): median age 61/63 years; PS=0, 60%/53%; Child-Pugh A 97%/88%; etiology: hepatitis C 30%/38%, hepatitis B 27%/24%, alcohol 24%/25%. Overall, 78%/83% of patients had received prior SF; 57%/53% had AFP &gt;400 ng/mL. Median TTP was 12.0 weeks (90% CI: 6.6, 12.6) in the overall population (Arm A/B, 12.1/10.0 weeks). In SF-naive patients, TTP was 18.3 weeks (90% CI: 6.6-42.4). TTP was higher in the non-alcohol compared to alcohol-only etiology group (median 12.1 vs. 6.1 weeks). Median baseline serum TGF-β1 was 3.4 ng/mL (range: 1.4-3.7) and E-cadherin was 6.1 mg/mL (range: 1.9-17.3). AFP decline of &gt;20% occurred in 24% of patients. Based on the latest interim, median OS was 36 weeks. In AFP responders, median OS was 93.1 weeks vs 29.6 weeks in non AFP responders (Log Rank p=0.0006). Four patients discontinued treatment due to AEs. Most common grade 3/4 related AEs were: neutropenia (n=3), fatigue (n=2), and anemia (n=3). Preliminary PK analysis (n=51) demonstrated moderate interpatient exposure variability (42%). Conclusions: Based on the manageable toxicity profile, the evidence for biomarker responses, analysis of the aggregate PK/PD data, the 300 mg/day dose was chosen for future studies in HCC. Both TTP and overall survival in AFP responding patients is promising.
Targeting focal adhesion kinase reprograms the pancreatic tumor microenvironment and renders pancreas cancer responsive to checkpoint immunotherapy
Authors: Hong Jiang, Brett Knolhoff, Yu Zhu, John Herndon, Irina Shapiro, David Weaver, Jonathan Pachter, Andrea Wang-Gillam, David G DeNardo
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts Checkpoint immunotherapeutics are promising agents with potential to improve patient outcomes in several cancer types. Unfortunately, to date, single agent immunotherapy has achieved limited clinical benefit in patients with pancreatic ductal adenocarcinoma (PDAC). This may be due
Preexposure Prophylaxis for HIV Prevention
Authors: Eileen E. Reynolds, Howard Libman, Kenneth H. Mayer
Journal: Annals of Internal Medicine (2015)

The U.S. Public Health Service recently issued guidelines about the daily use of medication as preexposure prophylaxis (PrEP) to prevent HIV infection. The guidelines, based on randomized trials showing substantial reduction in HIV transmission among those receiving a daily combination of tenofovir and emtricitabine, suggest physicians offer PrEP to patients at high risk, including nonmonogamous men who have sex with men, serodiscordant couples (in both male–male and male–female relationships), heterosexual men and women in other risk groups (such as sex workers or those with recent sexually transmitted infection), and injection drug users. Here, 2 prominent HIV experts debate the use of PrEP in a 45-year-old man whose husband has HIV infection with an undetectable viral load on treatment. They discuss the patient's risk for HIV transmission from his husband and from other partners, the magnitude of the risk reduction he would gain with PrEP, and nonpharmacologic alternatives to reduce his likelihood of contracting HIV infection.
Abstract 14021: Angiographic and Hemodynamic Features of Symptomatic Vertebrobasilar Disease: Baseline Data from the VERiTAS Study
Authors: Sepideh Amin-Hanjani, Xinjian Du, Linda Rose-Finnell, Dilip Pandey, DeJuran Richardson, Hui Xie, Keith R Thulborn, Mitchell S Elkind, Gregory J Zipfel, David S Liebeskind, Frank L Silver, Jeffrey Kramer, Scott E Kasner, Louis R Caplan, Colin P Derdeyn, Philip B Gorelick, Fady T Charbel
Journal: Circulation (2014)

Introduction: Atherosclerotic vertebrobasilar disease (VBD) is a significant etiology of posterior circulation stroke. In addition to thromboembolism, regional hypoperfusion is considered an important potential contributor to stroke risk. To examine the role of hemodynamic compromise in VBD, a prospective observational multi-center study, Vertebrobasilar Flow Evaluation and Risk of Transient Ischemic Attack and Stroke (VERiTAS), has recently been conducted. Here we report baseline features and vessel flow measurements from the study cohort. Methods: Baseline demographic and clinical data was collected in patients with recent vertebrobasilar TIA or stroke and ≥50% atherosclerotic stenosis or occlusion in vertebral and/or basilar arteries. Large vessel flow in the vertebrobasilar territory was assessed using quantitative MRA (QMRA). Results: The cohort (n=75, 56% male) had a mean age of 65.5 (range 40 to 90) years; two thirds presented with ischemic stroke. Hypertension (93%) and hyperlipidemia (79%) were the most prevalent vascular risk factors. Vertebral and basilar artery flows correlated negatively with degree of stenosis in the affected vessel, and positively to the minimal diameter at the site of stenosis (p&lt;0.01). A threshold effect was evident, with affected vessel flows dropping significantly in patients with ≥70% stenosis or occlusion (p&lt;0.05). Tandem disease involving the basilar and either or both the vertebrals had the greatest impact on immediate downstream flow in the basilar artery (38 ml/min vs. 74 ml/min, p&lt;0.01). Assessment of distal flow status, incorporating collateral flow, however correlated neither with multifocality of disease nor severity of the maximal stenosis. Conclusions: Flow in stenotic posterior circulation vessels correlate with residual diameter and stenosis and drop significantly in the setting of tandem disease. However, distal flow status, incorporating collateral capacity, is not well predicted by the severity or location of the disease. Final clinical outcome results from the ongoing VERiTAS study will further clarify the relevance of anatomic stenosis and hemodynamic assessment to predicting stroke risk in patients with vertebrobasilar disease.
Pharmacokinetic differences between subcutaneous and intramuscular administration of lanreotide: Results from a phase I study.
Authors: Amandine Manon, Edward M. Wolin, Christophe Chassaing, Andrew L. Lewis, Laurent Bertocchi, Joel Richard, Alexandria T. Phan
Journal: Journal of Clinical Oncology (2015)

e15186 Background: Recent data have shown that 38% of intended gluteal intramuscular (IM) injections with long-acting release octreotide were mistakenly given subcutaneously (SC); in carcinoid syndrome patients,this significantly increased the rate of flushing (P= 0.005; Boyd 2013, Pancreas). Lanreotide depot is indicated in the US for the treatment of acromegaly (60, 90, and 120 mg Q4W) and recently became the first FDA-approved somatostatin analog for the treatment of gastroenteropancreatic neuroendocrine tumors (120 mg Q4W) as a deep SC injection. Since lanreotide’s efficacy and pharmacokinetics (PK) have been demonstrated, including rapid initial release and long half-life of 23-30 days (d), we report PK parameters of SC vs IM routes of administration (ROA) for lanreotide depot in healthy volunteers. Methods: In a randomized, parallel, double-blind, phase I clinical study, healthy volunteers 18-45 years old received 1 mg lanreotide (IV bolus) followed by lanreotide 60 mg 0.246 mg/mg deep SC or IM.Serial blood samples were collected before and over the 8 hours after IV administration and ≥ 3 months after lanreotide depot administration to assess PK. Results: Of 42 volunteers (mean [SD] age 25±6 years, weight 66±10 kg), 11 received the same lanreotide dose (60 mg 0.246 mg/mg) as SC (n = 5) or IM (n = 6), 30 received other doses/concentrations, and 1 was excluded. Between 14 and 112 d, comparable mean concentration-time profiles of lanreotide were observed for both ROAs. After SC and IM injections, the mean Cmax (5.8±4 vs 6.8±3 μg/L) and mean T1/2 (33±14 vs 23±9 d) were deemed comparable, as were median Tmax (8 vs 16 hours) and median residence time (last) in serum (28 vs 20 d). Slightlylower AUClast (1651±54 vs 2007±172 h•μg/L) and AUCinf (1843±134 vs 2100±193 h•μg/L) were observed with SC vs IM injections. Conclusions: Lanreotide depot 60 mg 0.246 mg/mg SC and IM injection had similar PK profiles in this small cohort. The SC ROA was chosen for further development because slightly more lanreotide was available in the late-release phase after SC injection, providing a better long-term release profile. SC injection also provides ease-of-use for healthcare practitioners and patients.
Impact on overall survival (OS) with chemohormonal therapy versus hormonal therapy for hormone-sensitive newly metastatic prostate cancer (mPrCa): An ECOG-led phase III randomized trial.
Authors: Christopher Sweeney, Yu-Hui Chen, Michael Anthony Carducci, Glenn Liu, David Frasier Jarrard, Mario A. Eisenberger, Yu-Ning Wong, Noah M. Hahn, Manish Kohli, Nicholas J. Vogelzang, Matthew M. Cooney, Robert Dreicer, Joel Picus, Daniel H. Shevrin, Maha Hussain, Jorge A. Garcia, Robert S. DiPaola
Journal: Journal of Clinical Oncology (2014)

LBA2 Background: Docetaxel (D) improves OS of men with mPrCa who have progressed on androgen deprivation therapy (ADT). We aimed to assess the benefit of upfront chemohormonal therapy for metastatic PrCa. Methods: 1:1 randomization to ADT alone or ADT + D dosed 75mg/m2 every 3 weeks for 6 cycles within 4 month (mos) of starting ADT. Stratification factors: high volume (HV) vs. low volume (LV) disease (HV: visceral metastases and/or 4 or more bone metastases); anti-androgen use beyond 30 days; Age ≥70 vs. &lt; 70 years; ECOG PS 0-1 vs. 2; Prior adjuvant ADT &gt; 12 vs. ≤ 12 mos; FDA approved drug for delaying skeletal related events. Key eligibility criteria: suitable organ and neurological function for D; adjuvant ADT ≤ 24 mos and no progression within 12 mos of adjuvant ADT. OS was the primary endpoint and the study was powered to assess for a 33.3% improvement in median OS (80% power and 1-sided alpha=2.5%). Projected median OS for ADT alone: HV-33 mos; LV-67 mos. Results: 790 men were accrued from 7/28/06 to 11/21/2012: ADT N=393; ADT + D: N=397; balanced for demographic, stratification and disease factors. Median age: 63 years (range: 36 to 91); 98% ECOG PS 0 or 1; 89% Caucasian; 24% prior radiotherapy, 24% prior prostatectomy; HV 64% on ADT and 67% on ADT + D. Data released after 4th interim analysis in Sept 2013 when O’Brien Fleming upper boundary was crossed with 53.1% information. This report reflects 1/16/2014 data with median follow-up of 29 mos with 137 deaths on ADT alone vs. 104 deaths on ADT+D. ADT+D: Grade (G) 3/4 Neutropenic fever: 4%/2%; G3 neuropathy: 1% sensory, 1% motor; 1 death due to treatment (no deaths due to treatment on ADT). Efficacy data is in the table below. After disease progression, 123 pts on ADT alone and 45 pts on ADT + D received docetaxel. Conclusions: ADT + D improves OS over ADT alone in men with HV mPrCa. Longer follow-up is needed for men with LV mPrCa. Clinical trial information: NCT00309985. [Table: see text]
TV: Doctors from Hell
Authors: K. Abbasi
Journal: BMJ (1999)

The Cook Report , ITV, 9 00 pm Tuesday 24 August

“Would you let any of them treat you?” challenges Roger Cook, after reeling off a list of “doctors from hell,” and quickly provides the answer: “Tonight we go undercover to examine the scandal of the doctors you'd never want to treat you or your family.”

Cook is an avenging angel of gargantuan proportions, and crooks and swindlers of every hue are his target. Why, then, should miscreant doctors be spared? Lulled into a soft admission or compromising position, Cook's quarry seldom know what to do when confronted by his robust inquisition and a microphone thrust in their direction. Fight or flight? Silence is the usual answer, but the verbal battering from Cook leaves little doubt as to the culpability of the accused.

His huge frame undoubtedly helps—usually deterring a direct assault, although Cook has taken blows in the past. Little matter, it all makes for great television, and Cook knows he can push his trial by camera to the limit. The other advantage of …
Serum immunoregulatory proteins as predictors of overall survival of metastatic melanoma patients treated with ipilimumab
Authors: Yoshinobu Koguchi, Helena Hoen, Shelly Bambina, Michael Rynning, Richard Fuerstenberg, Zipei Feng, Bernard Fox, Carlo Bifulco, Brendan D Curti, Walter Urba, Christina Milburn, Alan J Korman, Keith S Bahjat
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts Treatment with ipilimumab improves overall survival (OS) in patients with metastatic melanoma. Because ipilimumab targets T lymphocytes and not the tumor itself, efficacy may be uniquely sensitive to immunomodulatory factors present at the time of treatment. We analyzed serum