tbuckley/cabot-search huggingface dataset:
Conservative Management of Adolescents With Abnormal Cytology and Histology
Authors: Anna-Barbara Moscicki
Journal: Journal of the National Comprehensive Cancer Network (2008)

Adolescents remain vulnerable to human papilloma virus (HPV) infection because of certain physiologic characteristics inherent in this age group and common sexual behaviors, including lack of condom use. The commonness of HPV in this age group also results in frequent abnormal cytology. Fortunately, most of the infections are transient, with frequent clearance of HPV and the lesion. Current strategies for adolescents with abnormal cytology include conservative management, avoiding invasive procedures. For cytologic atypical squamous cells of undetermined significance or squamous intraepithelial lesions (SIL), management can be obtaining cytology only at 1-year intervals for up to 2 years before referral for colposcopy is necessary. For biopsy-proven cervical intraepithelial neoplasia (CIN) I, management is similar with yearly cytology indefinitely or until high-grade–SIL or CIN II/III develops. CIN II in adherent adolescents can be managed with 6-month cytology and colposcopy.
5-Fluorouracil, mitomycin, and doxorubicin (FAM) in carcinoma of the biliary tract.
Authors: J H Harvey, F P Smith, P S Schein
Journal: Journal of Clinical Oncology (1984)

A phase II trial of the regimen 5-fluorouracil, doxorubicin, and mitomycin C (FAM) was conducted in 17 patients with advanced or recurrent biliary tract cancer. Among 14 patients with measurable disease, 31% achieved a partial response. An additional seven patients evidenced stabilization of disease for periods of three to 18+ months. One patient with advanced but unmeasurable tumor has survived 72 months after 12 cycles of treatment. There was no serious life-threatening toxicity, and with appropriate dosage adjustment, the drug was administered to patients with mild hepatic insufficiency. We recommend the initiation of a larger controlled trial and a potential application with radiotherapy for patients with less advanced disease.
Activation of peroxisome proliferator-activated receptor gamma is crucial for antitumoral effects of 6-iodolactone
Authors: Mario Nava-Villalba, Rosa E. Nuñez-Anita, Alexander Bontempo, Carmen Aceves
Journal: Molecular Cancer (2015)

Molecular iodine (I2) exhibits antiproliferative and apoptotic effects on in vivo and in vitro cancer models. These effects are thought to be mediated by an iodinated arachidonic acid derivative, 6-iodolactone (6IL), and one of the proposed mechanisms is that 6IL activates Peroxisome Proliferator-Activated Receptors type gamma (PPARG). These receptors have been implicated in the inhibition of carcinogenic processes, in addition to their classical role in maintaining lipid and glucose homeostasis. The aim of this study was to determine whether PPARG participates in the 6IL antiproliferative and apoptotic effects on the mammary cancer cell line MCF-7.The 6IL/PPARG complex was inhibited by the PPARG antagonist GW9662, in both an endogenous and overexpressed (adenoviral vector infection) context, and stable PPARG-knockdown MCF-7 cells (RNA interference, confirmed with hydrolysis probes and Western blot), were used to corroborate the PPARG participation. 6IL effects on proliferation (measured by Trypan Blue exclusion) and apoptosis (phosphatidylserine identification by flow cytometer) were evaluated in conditions of chemical inhibition (GW9662) and silencing (RNA interference). A wound-healing assay was conducted on wild-type and stable PPARG-knockdown MCF-7 cells to evaluate the antimigrational effect of 6IL. Caspase-8 activity was evaluated to determine if the extrinsic pathway is involved in the effects of 6IL and I2 treatment.Antiproliferative and pro-apoptotic 6IL effects require the activation of PPARG. In addition, wound-healing assays show that 6IL is able to inhibit MCF-7 cell migration and that PPARG plays a role in this phenomenon. Finally, the data exclude the participation of the extrinsic apoptotic pathway in 6IL- and I2-induced apoptosis.These results support the previously proposed mechanism, in which the I2 effects are mediated by 6IL, and they provide further support for the use of I2 as coadjuvant in breast cancer treatment.
Change in Plasma Protein Binding of Sn-38, an Active Metabolite of Irinotecan, in Cancer Patients with Severe Renal Failure (Srf)
Authors: K. Fujita, H. Okumura, Y. Masuo, Y. Sunakawa, K. Shimada, K. Kawara, Y. Akiyama, Y. Sasaki, Y. Kato
Journal: Annals of Oncology (2014)
LSC 2014 abstract - The role of the formyl peptide receptor in the development of pulmonary fibrosis
Authors: Andrew Fisher, Ben Millar, Lynne Murray, Donna Finch, Alan Carruthers, ohn Ferguson, Matt Sleeman, Donna Mann
Journal: European Respiratory Journal (2014)

Introduction:  Mitochondrial damage-associated molecular patterns (mtDAMPs) are emerging as potential mediators in cancer & lung disease. Formyl peptides (FP) are a major source of mtDAMPs, aside from mitochondrial CpG-rich DNA, are bound by three main receptors in humans (FPR1-3) & eight in mice   Hypothesis:  Release of mtDAMPs & ligation of FPR1 may play an important role in driving a fibrogenic response in the lung after potent inflammatory injury   Methods:  FPR1 KO and C57bl/6 (WT) mice were treated intratracheally with bleomycin sulphate 0.007U/saline control with day 5 & day 21 timepoints. Expression of pro-inflammatory chemokines & cytokines was measured using Meso-scale discovery mouse cytokine assay on lung lobe homogenates. Lung collagen content was measured using a hydroxyproline assay. Expression of extra-cellular matrix molecules was assessed by ELISA, real-time PCR & immunohistochemistry. Immune cell phenotyping was performed using flow cytometry to identify inflammatory infiltrate   Results:  FPR1 KO mice exhibit a blunted pro-inflammatory chemokine & cytokine profile compared to WT mice at day 5. Collagen content & expression of α-smooth muscle actin & other extra-cellular matrix molecules were reduced at day 21 in FPR1 KO mice. Differences in macrophage activation were found between WT & KO injured mice after 21 days. Macrophages in WT mice exhibited an M2 phenotype, characterised by high levels of CD206/FIZZ-1 in contrast to FPR1 KO macrophages   Conclusion:  FPR1 KO mice are protected against fibrosis in response to bleomycin treatment indicating FPR interactions are important in driving fibrogenesis in the lung after an inflammatory injury.
Comparative effectiveness of pharmacological interventions for nonalcoholic steatohepatitis: A systematic review and network meta‐analysis
Authors: Siddharth Singh, Rohan Khera, Alina M. Allen, M. Hassan Murad, Rohit Loomba
Journal: Hepatology (2015)

We performed a Bayesian network meta‐analysis combining direct and indirect treatment comparisons to assess the comparative effectiveness of pharmacological agents for the treatment of nonalcoholic steatohepatitis (NASH). Through systematic literature review, we identified nine randomized, controlled trials (RCTs) including 964 patients with biopsy‐proven NASH, comparing vitamin E, thiazolidinediones (TZDs), pentoxifylline, or obeticholic acid to one another or placebo. The primary outcome was improvement in fibrosis stage; secondary outcomes were improvement in ballooning degeneration, lobular inflammation, and steatosis. We reported relative risks (RRs) and 95% confidence intervals (CIs) from direct meta‐analysis and 95% credible intervals (CrIs) from Bayesian network meta‐analysis, and used Grading of Recommendations Assessment, Development and Evaluation (GRADE) criteria to appraise quality of evidence. Moderate‐quality evidence supports the use of pentoxifylline (RR, 0.26; 95% CrI: 0.05‐1.00) and obeticholic acid (RR, 0.81; 95% CI: 0.70‐0.95) over placebo in improving fibrosis. High‐quality evidence supports the effect of vitamin E, TZDs, and obeticholic acid over placebo in improving ballooning degeneration. All four interventions seemed to have at least moderate‐quality evidence over placebo to improve steatosis. Moderate‐quality evidence supports that TZDs, pentoxifylline, and obeticholic acid decrease lobular inflammation. All the head‐to‐head comparisons were supported by very‐low‐quality evidence except for superiority of TZDs over vitamin E on improving steatosis and lobular inflammation, which had moderate‐quality evidence. Conclusions : Based on direct and network meta‐analysis, pentoxifylline and obeticholic acid improve fibrosis, and vitamin E, TZDs, and obeticholic acid improve ballooning degeneration in patients with NASH. Future comparative trials of combination therapies targeting distinct histological features are warranted. (H epatology 2015;62:1417–1432)
Cost-effectiveness of adult pneumococcal conjugate vaccination in the Netherlands
Authors: Marie-Josée J. Mangen, Mark H. Rozenbaum, Susanne M. Huijts, Cornelis H. van Werkhoven, Douwe F. Postma, Mark Atwood, Anna M.M. van Deursen, Arie van der Ende, Diederick E. Grobbee, Elisabeth A.M. Sanders, Reiko Sato, Theo J.M. Verheij, Conrad E. Vissink, Marc J.M. Bonten, G. Ardine de Wit
Journal: European Respiratory Journal (2015)

The Community-Acquired Pneumonia Immunization Trial in Adults (CAPiTA) demonstrated the efficacy of 13-valent pneumococcal conjugate vaccine (PCV13) in preventing vaccine-type community-acquired pneumonia and vaccine-type invasive pneumococcal disease in elderly subjects. We examined the cost-effectiveness of PCV13 vaccination in the Netherlands. Using a Markov-type model, incremental cost-effectiveness ratios (ICER) of PCV13 vaccination in different age- and risk-groups for pneumococcal disease were evaluated using a societal perspective. Estimates of quality-adjusted life-years (QALYs), costs, vaccine efficacy and epidemiological data were based on the CAPiTA study and other prospective studies. The base-case was PCV13 vaccination of adults aged 65–74 years compared to no vaccination, assuming no net indirect effects in base-case due to paediatric 10-valent pneumococcal conjugate vaccine use. Analyses for age- and risk-group specific vaccination strategies and for different levels of hypothetical herd effects from a paediatric PCV programme were also conducted. The ICER for base-case was €8650 per QALY (95% CI 5750–17 100). Vaccination of high-risk individuals aged 65–74 years was cost-saving and extension to medium-risk individuals aged 65–74 years yielded an ICER of €2900. Further extension to include medium- and high-risk individuals aged ≥18 years yielded an ICER of €3100. PCV13 vaccination is highly cost-effective in the Netherlands. The transferability of our results to other countries depends upon vaccination strategies already implemented in those countries.
Dopamine release from nigral transplants visualized in vivo in a Parkinson's patient
Authors: Paola Piccini, David J. Brooks, Anders Björklund, Roger N. Gunn, Paul M. Grasby, Ornella Rimoldi, Patrik Brundin, Peter Hagell, Stig Rehncrona, Håkan Widner, Olle Lindvall
Journal: Nature Neuroscience (1999)
Heart failure with normal ejection fraction is uncommon in acute myocardial infarction settings but associated with poor outcomes: a study of 91 360 patients admitted with index myocardial infarction between 1998 and 2010
Authors: Liyew Desta, Tomas Jernberg, Jonas Spaak, Claes Hofman‐Bang, Hans Persson
Journal: European Journal of Heart Failure (2015)
Pre-existing cough predicts coughing during endobronchial ultrasound (EBUS)
Authors: Richard Turner, James Murray, Alice Repossi, Sheena Barnett, Gillian Tomlinson, Manoj Menon, Graham Bothamley, Angshu Bhowmik
Journal: European Respiratory Journal (2014)

Introduction  Coughing hinders EBUS and aerosolises secretions. Predictors of cough in bronchoscopy and methods of quantifying it are poorly described.   Method  Successive patients wore an audio recorder and microphone immediately before, during and after EBUS. Each recording was analysed by one of three authors; half were re-analysed by the main author. Coughs were counted using audio editing software.   Results  A mean (±SE) of 5.61±1.11 coughs/min were counted during EBUS from 24 patients with cancer (n=13), sarcoid (n=7), tuberculosis (n=2) or reactive mediastinal lymphadenopathy (n=2). The mean disagreement between listeners was 17.8±6.1%. Cough counts were higher in the 12 patients reporting a pre-existing cough (Figure; p=0.05). Coughing during the median (range) 18 (10-100) minutes prior to EBUS was not associated with cough rates during the procedure. There was a trend towards increased cough in the 11 current smokers, as well as those with lung abnormalities on imaging and with cancer, but this was not statistically significant (p=0.30, 0.10 and 0.14, respectively). All received topical lidocaine. There was no evidence of cough suppression in the 17 and 15 patients given 50-100 mcg intravenous fentanyl or 1-4 mg midazolam, respectively.   Conclusion  Cough frequency in EBUS is highly variable and its measurement difficult although it is higher with pre-existing cough. The influence of medication and other variables remains unclear.
Hand-held tidal breathing nasal nitric oxide measurement as a targeted case-finding tool for primary ciliary dyskinesia
Authors: June K. Marthin, Kim G. Nielsen
Journal: European Respiratory Journal (2012)

BACKGROUND: Nasal Nitric Oxide (nNO) measurement is a sensitive supplementary tool in diagnosis of Primary Ciliary Dyskinesia (PCD). Tidal Breathing (TB) nNO requires minimal cooperation, has potential as more widespread targeted case-finding tool for PCD in all age groups, and discriminative capacity between PCD and non-PCD has been previously established using stationary nNO analyzer (Marthin JK and Nielsen KG. Eur Respir J 2011; 37: 559-565).  AIM: Assess validity of hand-held TBnNO in a selected population.  METHODS: TBnNO was measured in PCDs, cystic fibrosis (CF) patients and healthy subjects (HS) using both an electrochemical hand-held device, NIOX MINO® Nasal equipped with a nasal research application, and two chemiluminiscence stationary systems: NIOX® and ANALYZER CLD 88sp®. All systems allow passive nasal sampling at a flow rate of 5 ml/s during tidal breathing. 2 ml/s sampling is an additional option with NIOX MINO® Nasal. Data were analysed by ROCC and Bland-Altman plots.  RESULTS: TBnNO values were compared in 41 subjects between 0.3 and 57 years: 15 PCDs, 13 CF patients, and 13 HS. MINO discriminated significantly between PCD and HS (P  CONCLUSION: Hand-held TBnNO separated significantly between PCD and HS, and between PCD and CF, with cut off value and sensitivity/specificity comparable to those of stationary systems.
Impact of an oncology management program using level I pathways, a nurse call system, and advance care planning.
Authors: J. Russell Hoverman, Ira Klein, Deb Harrison, Jad Hayes, Greg C. Nelson, Jody S. Garey, Robyn K. Harrell, Maria Sipala, Scott Houldin, John Ciaglo, Cynthia Taniguchi, Melissa Jameson, Mitra Abdullahpour, Jessica McQueen, Diana K. Verrilli, Marcus A. Neubauer
Journal: Journal of Clinical Oncology (2013)

119 Background: The Innovent Oncology Program (IOP) addresses rising costs of cancer treatment but maintains the use of evidence-based medicine. McKesson Specialty Health and Texas Oncology (TXO) collaborated with Aetna, Inc to launch a pilot program to evaluate IOP’s impact on Level I Pathways (PW) compliance, implement Patient Support Services (PSS), measure the rate and costs of chemotherapy-related ER visits and hospital admissions (IP), and evaluate the feasibility of introducing Advance Care Planning (ACP). Methods: Prospective, nonrandomized evaluation of pts enrolled in IOP June 1, 2010-May 31, 2012. Data from the iKnowMed electronic health record, McKesson Specialty Health’s financial data warehouse, and Aetna’s claims data warehouse were analyzed. Results: 221 pts were included and stratified by disease and age. 76% of ordered regimens were ON-PW, improved from TXO’s baseline adherence of 63%. Of 221 pts, 81% enrolled in PSS. ACP was introduced to 85% and 14% of these participated in ACP discussions. In the breast, colorectal, and lung groups, 14% and 24% had an ER visit and IP (baseline) vs. 10% and 18% in the IOP. Average IP days decreased from 2.1 to 1.2, respectively (table). Total savings for all 3 groups was $506,481. Conclusions: Implementation of IOP positively impacted pt care with fewer ER visits, IP, and IP days, cancer-related utilization costs, and increased Pathway adherence. [Table: see text]
Occupational asthma due to formaldehyde resin dust with and without reaction to formaldehyde gas
Authors: C Lemière, A Desjardins, Y Cloutier, D Drolet, G Perrault, A Cartier, J L Malo
Journal: European Respiratory Journal (1995)

We report the cases of three subjects who developed asthma after being exposed to formaldehyde dust or gas. For two subjects, specific bronchial provocation tests with formaldehyde gas did not cause significant bronchoconstriction, whereas exposure to formaldehyde resin dust did. One subject experienced asthmatic reaction after being exposed to formaldehyde resin dust and gas. These findings suggest that the physical and chemical properties of formaldehyde are relevant to its likelihood of causing asthma.
Molecular characterization of acute erythroid leukemia (M6-AML) using targeted next-generation sequencing
Authors: N Cervera, N Carbuccia, S Garnier, A Guille, J Adélaïde, A Murati, N Vey, M-J Mozziconacci, M Chaffanet, D Birnbaum, V Gelsi-Boyer
Journal: Leukemia (2015)
ClinLabGeneticist: a tool for clinical management of genetic variants from whole exome sequencing in clinical genetic laboratories
Authors: Jinlian Wang, Jun Liao, Jinglan Zhang, Wei-Yi Cheng, Jörg Hakenberg, Meng Ma, Bryn D. Webb, Rajasekar Ramasamudram-chakravarthi, Lisa Karger, Lakshmi Mehta, Ruth Kornreich, George A. Diaz, Shuyu Li, Lisa Edelmann, Rong Chen
Journal: Genome Medicine (2015)
A systematic review of randomized controlled trials (RCTs) of EGFR-targeted monoclonal antibody (MAb) therapy in advanced colorectal cancer (ACRC): Impact of <i>KRAS</i> status.
Authors: C. L. Vale, J. F. Tierney, A. M. Meade, D. Fisher, R. S. Kaplan, R. Adams, T. S. Maughan, M. Parmar
Journal: Journal of Clinical Oncology (2010)

e14001 Background: Recently reported RCTs of 1st and 2nd line treatment with anti-EGFR-targeted MAbs in patients with aCRC have shown conflicting results. Methods: We conducted a systematic review of RCTs to assess the effects of anti-EGFR MAbs , by KRAS status, in chemotherapy (CT) responsive aCRC patients. Progression-free survival (PFS) is the primary outcome; overall survival (OS) a secondary outcome. Data were extracted from trial reports for patients with wild type (WT) and mutant (MT) KRAS and all patients, where available. Results were pooled in a meta-analysis. Pre-planned analyses explored whether the effect varied by the treatment setting, CT type or the choice of MAb, as well as anti-EGFR MAbs in the presence or absence of bevacizumab. Results: We identified12 eligible RCTs. Two are unreported and three have not reported by KRAS status. Therefore complete data are available for 7 trials; 5 of CT ± anti-EGFR MAb (4,851 patients) and 2 that added bevacizumab to both arms (1,385 patients). There is a significant benefit of anti-EGFR MAbs on PFS (HR = 0.81, 95% CI 0.74–0.89, p < 0.00001) for patients with WT KRAS, although there is some evidence of differences between trial results (heterogeneity p = 0.05, I2 = 58%). There was also some evidence of a difference in the effect with oxaliplatin or irinotecan (interaction p-0.044) and by choice of fluoropyrimidine (interaction p = 0.001). There is also a significant benefit on OS (HR = 0.88, 95% CI 0.80 – 0.97. p = 0.008) but with a suggestion that this benefit may be limited to trials using infusional 5FU (interaction p = 0.027). There was no clear evidence of a benefit of anti-EGFR MAbs, either for PFS (HR = 1.10, 95% CI 0.99–1.22, p = 0.09) or OS (HR = 1.06, 95% CI 0.95–1.18, p = 0.28) for patients with MT KRAS. Inclusion of trials using bevacizumab diluted the effect and introduced greater heterogeneity in the results for WT but not MT KRAS patients. Conclusions: Cetuximab and panitumumab improve PFS and OS for patients with aCRC expressing WT KRAS. This benefit appears to vary with the choice of partner CT. Data from unreported trials will be sought to further clarify the effects of anti-EGFR-targeted MAbs in aCRC. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Merck Serono Merck Serono Merck Serono Merck Serono
Abstract 3050: Assessment of Genetic Risk for Thoracic Aortic Aneurysm Among Hypertensive Patients
Authors: Kimihiko Kato, Mitsutoshi Oguri, Tetsuro Yoshida, Takeshi Hibino, Kazuhiro Yajima, Tetsuo Fujimaki, Kiyoshi Yoko, Hitoshi Matsuo, Shunichiro Warita, Tomonori Segawa, Sachiro Watanabe, Norifumi Metoki, Hidemi Yoshida, Kei Satoh, Yoshinori Nozawa, Sahoko Ichihara, Yoshiji Yamada
Journal: Circulation (2007)

Introduction: Aneurysms and dissections at the thoracic aorta (TAA) are the leading causes of mortality and morbidity in the United States and Japan. Although hypertension is a major risk for TAA, several studies have indicated that genetic factors also influence the structural formation of TAA. The purpose of the present study was to identify gene polymorphisms associated with TAA among hypertensive patients for assessment of the genetic risk for this condition. Methods: This case-control study comprised 1351 hypertensive individuals, including 88 subjects with TAA and 1263 without any cardiovascular complications. The genotypes for 142 polymorphisms of 121 candidate genes were determined by a method that combines the polymerase chain reaction and sequence-specific oligonucleotide probes with suspension array technology. Results: Evaluation of genotype distributions by the chi-square test and subsequent multivariable logistic regression analysis with adjustment for age, sex, body mass index, and prevalence of smoking, diabetes mellitus, hypercholesterolemia, and metabolic syndrome revealed that the T→G (3′ UTR) polymorphism of the thrombospondin 2 gene ( THBS2 ; odds ratio, 4.7) is significantly (P &lt; 0.05) associated with TAA in hypertensive subjects, with the variant G allele representing a risk factor for this condition. Furthermore, the -110A→C polymorphism of heat-shock 70-kD protein 8 gene ( HSPA8 ; odd ratio, 0.3), the C→T (Pro198Leu) polymorphism of the glutathione peroxidase gene ( GPX1 ; odds ratio, 0.3), the -6G→A polymorphism of angiotensin 1 gene ( AGT ; odds ratio, 0.3), and the -850C→T polymorphism of tumor necrosis factor gene ( TNF ; odds ratio, 0.5) were significantly associated with this condition, with the variant allele of each polymorphism being protective against this condition. A stepwise forward selection procedure revealed that polymorphisms of THBS2 , HSPA8 , GPX1 , AGT , and TNF significantly affected the prevalence of TAA. Conclusions: Genetic variant of THBS2 may be a risk factor for TAA in hypertensive patients, whereas variants of HSPA8 , GPX1 , AGT , and TNF may be protective against this condition. Determination of genotypes for these polymorphisms may prove informative for assessment of the genetic risk for TAA.
Abstract 13406: Quantification of the Energy Loss in the Left Ventricle Using Color Doppler-Based Vector Flow Mapping in a Dog Model of Aortic Regurgitation
Authors: Hikaru Koriyama, Kasumi Masuda, Daisuke Sakurai, Toshihiko Asanuma, Keiichi Itatani, Kagami Miyaji, Satoshi Nakatani
Journal: Circulation (2013)

Background: Intracardiac blood flow patterns are potentially important to efficient cardiac pumping. Vector Flow Mapping (VFM®, Hitachi-Aloka Medical) is a novel software based on continuity equati...