tbuckley/cabot-search huggingface dataset:
Enrolling Adolescents in Disease/Target-Appropriate Adult Oncology Clinical Trials of Investigational Agents
Authors: Meredith K. Chuk, Yeruk Mulugeta, Michelle Roth-Cline, Nitin Mehrotra, Gregory H. Reaman
Journal: Clinical Cancer Research (2016)

Abstract The enrollment of adolescents with cancer in clinical trials is much lower than that of younger pediatric patients. For adolescents with “adult-type” cancers, lack of access to relevant trials is cited as one of the reasons for this discrepancy. Adolescents are generally not eligible for enrollment in adult oncology trials, and initial pediatric trials for many drugs are conducted years later, often after the drug is approved. As a result, accrual of adolescents to these trials may be slow due to off-label use, prospectively collected safety and efficacy data are lacking at the time of initial approval, and, most importantly, these adolescents have delayed access to effective therapies. To facilitate earlier access to investigational and approved drugs for adolescent patients with cancer, and because drug exposure is most often similar in adolescents and adults, we recommend the inclusion of adolescents (ages 12–17) in disease- and target-appropriate adult oncology trials. This approach requires careful monitoring for any differential safety signals, appropriate pharmacokinetic evaluations, and ensuring that ethical requirements are met. Inclusion of adolescents in adult oncology trials will require the cooperation of investigators, cooperative groups, industry, institutional review boards, and regulatory agencies to overcome real and perceived barriers. Clin Cancer Res; 23(1); 9–12. ©2016 AACR.
Outcomes from hospitalised acute exacerbations of COPD: a bundle of optimism?
Authors: William D-C Man, Ruth Barker, Matthew Maddocks, Samantha S C Kon
Journal: Thorax (2016)

Exacerbations of COPD place enormous stress on acute healthcare systems—they are one of the most common causes of emergency hospital admission and frequently result in readmission. Acute healthcare provision in England and Wales has adapted to deliver ‘front-door’ efficiency, with the rise of acute physicians and an emphasis on seeing hospitalised patients quickly to improve safety and facilitate early discharge—an example of the popular healthcare improvement mantra that ‘every system is perfectly designed to get the results it gets’. From this perspective, the results of the most recent national secondary care COPD audit are highly satisfying, demonstrating reduced inpatient mortality and length of stay.1 However, there is substantial national variation in acute care1 and readmission rates remain worryingly high, with more than 60% of patients readmitted to hospital at least once in the year following discharge.2

Outcomes from acute exacerbations of COPD are dependent on several factors beyond quality of care. These include the severity of the acute event, whether physiological derangements respond and improve to treatment during the admission,3 the baseline severity of respiratory disease in the individual, the influence of comorbidities and extra-pulmonary manifestations such as sarcopenia and frailty,4–7 and the individual's self-management skills and resilience.8

This is illustrated in the work of …
The Effects of Mitochondrial Ferritin Expression in Normal and Sideroblastic Erythropoiesis.
Authors: Matteo G Della Porta, Vittorio Rosti, Anna Gallì, Erica Travaglino, Paolo Santambrogio, Carmela Marseglia, Valentina Matti, Luca Malcovati, Gaetano Bergamaschi, Sonia Levi, Rosangela Invernizzi, Mario Cazzola
Journal: Blood (2009)
GW26-e2353 The Immediate Effect of ATP and Nitroglycerin on Coronary Slow-flow Angina Pectoris
Authors: Zhiming Yang, Huiyu Yang, Yunfei Bian, Shuwen Gong, Fen Gao, Junnan Li, Jinlong Song, Fen Yan
Journal: Journal of the American College of Cardiology (2015)
GW26-e4380 Screening and Differences for Glycolytic Metabolism Related Genes Between Two Ventricles in Monocmtaline Induced Pulmonary Arterial Hypertension Rats
Authors: Meihong Qiu, Weihua Zhang, Rui Zhang, Hongda Zhang, Zhicheng Jing, Shouyan Zhang
Journal: Journal of the American College of Cardiology (2015)
Metabolic profiling of fatty liver in young and middle‐aged adults: Cross‐sectional and prospective analyses of the Young Finns Study
Authors: Jari E. Kaikkonen, Peter Würtz, Emmi Suomela, Miia Lehtovirta, Antti J. Kangas, Antti Jula, Vera Mikkilä, Jorma S.A. Viikari, Markus Juonala, Tapani Rönnemaa, Nina Hutri‐Kähönen, Mika Kähönen, Terho Lehtimäki, Pasi Soininen, Mika Ala‐Korpela, Olli T. Raitakari
Journal: Hepatology (2016)

Nonalcoholic fatty liver is associated with obesity‐related metabolic disturbances, but little is known about the metabolic perturbations preceding fatty liver disease. We performed comprehensive metabolic profiling to assess how circulating metabolites, such as lipoprotein lipids, fatty acids, amino acids, and glycolysis‐related metabolites, reflect the presence of and future risk for fatty liver in young adults. Sixty‐eight lipids and metabolites were quantified by nuclear magnetic resonance metabolomics in the population‐based Young Finns Study from serum collected in 2001 (n = 1,575), 2007 (n = 1,509), and 2011 (n = 2,002). Fatty liver was diagnosed by ultrasound in 2011 when participants were aged 34‐49 years (19% prevalence). Cross‐sectional associations as well as 4‐year and 10‐year risks for fatty liver were assessed by logistic regression. Metabolites across multiple pathways were strongly associated with the presence of fatty liver ( P &lt; 0.0007 for 60 measures in age‐adjusted and sex‐adjusted cross‐sectional analyses). The strongest direct associations were observed for extremely large very‐low‐density lipoprotein triglycerides (odds ratio [OR] = 4.86 per 1 standard deviation, 95% confidence interval 3.48‐6.78), other very‐low‐density lipoprotein measures, and branched‐chain amino acids (e.g., leucine OR = 2.94, 2.51‐3.44). Strong inverse associations were observed for high‐density lipoprotein measures, e.g., high‐density lipoprotein size (OR = 0.36, 0.30‐0.42) and several fatty acids including omega‐6 (OR = 0.37, 0.32‐0.42). The metabolic associations were attenuated but remained significant after adjusting for waist, physical activity, alcohol consumption, and smoking ( P &lt; 0.0007). Similar aberrations in the metabolic profile were observed already 10 years before fatty liver diagnosis. Conclusion : Circulating lipids, fatty acids, and amino acids reflect fatty liver independently of routine metabolic risk factors; these metabolic aberrations appear to precede the development of fatty liver in young adults. (H epatology 2017;65:491‐500).
Does ultrasociality really exist – and is it the best predictor of human economic behaviors?
Authors: Sarah S Stith, Jacob M Vigil
Journal: Behavioral and Brain Sciences (2016)

We agree that human economic structures can be informed by comparative analyses; however, we do not agree with several of Gowdy & Krall's specific assertions, which may hinder the generative potential of their model. We discuss these limitations from both biological and economic perspectives, and offer an alternative explanation for the expression of human economic behaviors based on individual optimization strategies.
Paediatric neurologist gets short suspension after support from colleagues and parents
Authors: Clare Dyer
Journal: BMJ (2016)

A consultant paediatric neurologist who was caught in a newspaper sting taking cocaine before going on call has been suspended from the medical register for four months.

The Mail on Sunday article in January 2015 included a videotape allegedly showing Colin Ferrie snorting cocaine and measuring out the “clubbers’ drug” gamma hydroxybutyrate (GHB) with a male escort.

Ferrie, an authority on childhood epilepsy with an international reputation, was prosecuted for possession of cocaine. He admitted the offence, was given a conditional discharge for 12 months at Leeds magistrates’ court, and lost his job at Leeds General Infirmary.

At a Medical Practitioners Tribunal Service hearing in Manchester, he admitted that he was uncontactable while on …
Circulating Apolipoprotein E Concentration and Cardiovascular Disease Risk: Meta-analysis of Results from Three Studies
Authors: Reecha Sofat, Jackie A. Cooper, Meena Kumari, Juan P. Casas, Jacqueline P. Mitchell, Jayshree Acharya, Simon Thom, Alun D. Hughes, Steve E. Humphries, Aroon D. Hingorani
Journal: PLoS Medicine (2016)

Background The association of APOE genotype with circulating apolipoprotein E (ApoE) concentration and cardiovascular disease (CVD) risk is well established. However, the relationship of circulating ApoE concentration and CVD has received little attention. Methods and Findings To address this, we measured circulating ApoE concentration in 9,587 individuals (with 1,413 CVD events) from three studies with incident CVD events: two population-based studies, the English Longitudinal Study of Ageing (ELSA) and the men-only Northwick Park Heart Study II (NPHSII), and a nested sub-study of the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT). We examined the association of circulating ApoE with cardiovascular risk factors in the two population-based studies (ELSA and NPHSII) and the relationship between ApoE concentration and coronary heart disease and stroke in all three studies. Analyses were carried out within study, and, where appropriate, pooled effect estimates were derived using meta-analysis. In the population-based samples, circulating ApoE was associated with systolic blood pressure (correlation coefficient 0.08, p < 0.001, in both ELSA and NPHSII), total cholesterol (correlation coefficient 0.46 and 0.34 in ELSA and NPHSII, respectively; both p < 0.001), low-density lipoprotein cholesterol (correlation coefficient 0.30 and 0.14, respectively; both p < 0.001), high-density lipoprotein (correlation coefficient 0.16 and −0.14, respectively; both p < 0.001), and triglycerides (correlation coefficient 0.43 and 0.46, respectivly; both p < 0.001). In NPHSII, ApoE concentration was additionally associated with apolipoprotein B (correlation coefficient 0.13, p = 0.001) and lipoprotein(a) (correlation coefficient −0.11, p < 0.001). In the pooled analysis of ASCOT, ELSA, and NPHSII, there was no association of ApoE with CVD events; the odds ratio (OR) for CVD events per 1-standard-deviation higher ApoE concentration was 1.02 (95% CI 0.96, 1.09). After adjustment for cardiovascular risk factors, the OR for CVD per 1-standard-deviation higher ApoE concentration was 0.97 (95% CI 0.82, 1.15). Limitations of these analyses include a polyclonal method of ApoE measurement, rather than isoform-specific measurement, a moderate sample size (although larger than any other study to our knowledge and with a long lag between ApoE measures), and CVD events that may attenuate an effect. Conclusions In the largest study to date on this question, we found no evidence of an association of circulating ApoE concentration with CVD events. The established association of APOE genotype with CVD events may be explained by isoform-specific functions as well as other mechanisms, rather than circulating concentrations of ApoE.
A phase II trial of ZD6474 plus docetaxel in patients with previously treated NSCLC: Follow-up results
Authors: J. V. Heymach, B. E. Johnson, D. Prager, E. Csada, J. Roubec, M. Pesek, I. Spasova, J. Hou, S. Kennedy, R. S. Herbst
Journal: Journal of Clinical Oncology (2006)

7016 Background: ZD6474, a once-daily oral agent, targets key signaling pathways in cancer by inhibiting VEGF, EGF and RET receptor tyrosine kinases. ZD6474 in combination with docetaxel (Doc) was assessed in patients (pts) with refractory non-small-cell lung cancer (NSCLC). Methods: Pts eligible for this randomized, double-blind study had locally advanced or metastatic (stage IIIB/IV) NSCLC after failure of 1st-line platinum-based chemotherapy. The primary objective was to determine whether once-daily oral ZD6474 (100 or 300 mg) + Doc (75 mg/m 2 i.v. infusion every 21 days) prolonged progression-free survival (PFS) vs Doc alone (80% power to detect 50% prolongation at P&lt;0.2). Overall survival was a secondary objective. Results: A total of 127 pts (73 male/54 female; median age 59 yrs, range 29–82) received ZD6474 100 mg + Doc (n=42), ZD6474 300 mg + Doc (n=44) or Doc (n=41). The study met its primary objective of PFS prolongation with the addition of ZD6474: median PFS was 19 wks for ZD6474 100 mg + Doc (HR=0.64; P=0.074); 17 wks for ZD6474 300 mg + Doc (HR=0.83; P=0.461); and 12 wks for Doc. A total of 64 pts (50%) presented with histology other than adenocarcinoma, including 37 with squamous, and 13 pts (10%) entered with CNS metastases. Exploratory subgroup analyses suggest advantages in PFS for ZD6474 + Doc vs Doc both for adenocarcinoma and for other lung cancer histologies. Common adverse events (AEs) included diarrhea, rash and asymptomatic QTc prolongation, all responded to standard management or dose interruption/reduction. Four pts with squamous experienced hemoptysis (ZD6474 100 mg + Doc, n=2 CTC grade 1/2; Doc, n=2 CTC grade 3/4). No fatal episodes of hemoptysis or any CNS hemorrhage AEs were reported in pts receiving ZD6474. Overall survival data were immature at the time of PFS analysis, and a mature survival analysis will be conducted at ∼75% of deaths (anticipated April 2006, and will be presented at the meeting). As of December 2005, 40/127 (31%) pts were alive, 5 of whom continue to receive ZD6474. The minimum follow-up of pts still alive was 17 months. Conclusions: ZD6474 + Doc prolonged PFS vs Doc alone, and these promising data have led to the initiation of Phase III evaluation of ZD6474 + Doc in 2nd-line NSCLC. [Table: see text]
The effect of surgical resection on serum proteomic profiles in non-small cell lung cancer (NSCLC)
Authors: A. Alzetani, D. G. Ward, S. Rathinam, J. Starczynski, P. B. Rajesh, A. Martin, N. D. James, P. J. Johnson
Journal: Journal of Clinical Oncology (2007)

21143 Background: Surface-enhanced laser desorption/ionisation time-of-flight mass spectrometry (SELDI) was used to detect characteristic serum proteomic profiles that discriminate between Non-small Cell Lung Cancer (NSCLC) and non-cancer controls. The changes in these profiles in response to curative resection were examined to determine if they returned to “normal” as would conventional tumor markers. Methods: Serum samples were collected from 70 patients and 75 controls. Further samples were obtained from 25 of these patients following resection with curative intent. SELDI analyses using CM10 &amp; IMAC ProteinChip arrays were undertaken. The Wilcoxon rank test was used to detect differentially expressed peaks. Results: A preliminary analysis using CM10 on 39 patients, 38 controls, and 17 follow-ups showed 19 differentially expressed peaks (p&lt;0.01) but no evidence of return to normal after treatment. The IMAC chip analysis, on all samples, revealed 40 discriminatory peaks (p&lt;0.01). These data were used to classify patients with a specificity and sensitivity of more than 75%. Some of these cancer associated peaks returned to normal at follow-up. We have identified 10 of the discriminatory proteins. Conclusions: SELDI profiling has detected differentially expressed proteins in the serum of lung cancer patients. Successful treatment resulted in some, but not all, of the discriminatory peaks returning to non-cancer levels. It could be hypothesized there is a tumour specific profile which changes with treatment and a host specific profile that represents the patient's response to the presence of the disease or its inducing factors. No significant financial relationships to disclose.
Effect Of Genotype On Pulmonary Hypertension In Patients With Thalassemia
Authors: Nattiya Teawtrakul, Phuangpaka Ungprasert, Burabha Pussadhamma, Patcharawadee Prayalaw, Supan Fucharoen, Arunee Jetsrisuparb, Saranya Pongudom, Chittima Sirijerachai, Kanchana Chansung, Chinadol Wanitpongpun, Suporn Chuncharunee
Journal: Blood (2013)
Macrophage Infiltration of Skin Lesions Correlates to Prognosis of Gvhd; A Clue to Refractory Gvhd
Authors: Satoshi Nishiwaki, Seitaro Terakura, Tatsunori Goto, Aika Seto, Keisuke Watanabe, Nobuhiko Imahashi, Shokichi Tsukamoto, Makoto Shimba, Yukiyasu Ozawa, Koichi Miyamura, Masafumi Ito
Journal: Blood (2008)
Outcomes for Patients Who Fail High Dose Chemoradiotherapy and Autologous Stem Cell Rescue for Relapsed and Primary Refractory Hodgkin Lymphoma.
Authors: Alison Moskowitz, Joachim Yahalom, Tarun Kewalramani, Manfred Tejerina, Andrew D. Zelenetz, Craig H. Moskowitz
Journal: Blood (2007)
THE COST EFFECTIVENESS OF EXERCISE-BASED CARDIAC REHABILITATION: A SYSTEMATIC REVIEW
Authors: K Edwards, N Jones, J Newton, C Foster, A Judge, K Jackson, NK Arden, R Pinedo-Villanueva
Journal: British Journal of Sports Medicine (2016)

Aims Economic evaluations provide a useful comparative approach for considering costs and consequences on patient outcomes, thus providing a foundation for effective policy and decision making.1 2 This descriptive review aims to better understand how economic evaluations of cardiac rehabilitation (CR) services are conducted to inform future research addressing the impact of a physical exercise component on cost-effectiveness. Methods Electronic databases were searched for economic evaluations of exercise-based CR programs published in English between 2000 and 2014. The methodological quality of included economic evaluations was reviewed using criteria taken from the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) statement.3 Results Fifteen economic studies met the eligibility criteria but exhibited wide variability in study perspective, time horizon, setting, comparators and included costs, with significant heterogeneity for exercise dose between interventions. Ten evaluations were based on randomised controlled trials (RCTs) with time horizons between 6–24 months, but which largely produced weak or inconclusive results. Excluding two modelling studies, only three studies utilised longer time horizons (3.5–5 years), and findings suggest exercise-based CR leads to lowered costs, reduced rehospitalisation's and longer cumulative lifetime in the long-term. Conclusions Variability in CR program delivery and exercise dose along with weak consistency between study perspective and included costs makes it difficult to compare cost and health outcomes between studies and accumulate evidence in support of a particular exercise regime. The dominance of RCTs with their extensive patient selectivity process and exclusion of comorbid patients questions whether cost-effectiveness findings would translate to a real-world setting. The use of longer time horizons would be more compatible with a chronic condition and allow the long-term effects of exercise-based CR to be evaluated.
Safety and efficacy of nivolumab and standard chemotherapy drug combination in patients with advanced non-small-cell lung cancer: a four arms phase Ib study
Authors: S. Kanda, K. Goto, H. Shiraishi, E. Kubo, A. Tanaka, H. Utsumi, K. Sunami, S. Kitazono, H. Mizugaki, H. Horinouchi, Y. Fujiwara, H. Nokihara, N. Yamamoto, H. Hozumi, T. Tamura
Journal: Annals of Oncology (2016)

The human IgG4 monoclonal antibody nivolumab targets programmed cell death-1 (PD-1) and promotes antitumor response by blocking the interaction of PD-1 with its ligands. This single-center phase Ib study investigated the tolerability, safety, and pharmacokinetics of nivolumab combined with standard chemotherapy in patients with advanced non-small-cell lung cancer (NSCLC).Patients who had stage IIIB without indication for definitive radiotherapy, stage IV, or recurrent NSCLC were eligible. Regimens were nivolumab 10 mg/kg + gemcitabine/cisplatin (arm A), pemetrexed/cisplatin (arm B), paclitaxel/carboplatin/bevacizumab (arm C), or docetaxel (arm D). Regimens A, B, and D were repeated every 3 weeks for up to four cycles and regimen C was repeated for up to six cycles; nivolumab alone (arm A), with pemetrexed (arm B), bevacizumab (arm C), or docetaxel (arm D) was continued every 3 weeks as maintenance therapy until disease progression or unacceptable toxicity. Dose-limiting toxicity (DLT) was evaluated during the first treatment cycle.As of March 2014, six patients were enrolled in each arm. The combination of nivolumab 10 mg/kg and chemotherapy was well tolerated. DLT was observed in only one patient in arm A (alanine aminotransferase increased). Select adverse events (those with a potential immunologic cause) of any grade were observed in six, four, six, and five patients in arms A, B, C, and D, respectively. Three, three, six, and one patient achieved partial response while median progression-free survival was 6.28, 9.63 months, not reached, and 3.15 months in arms A, B, C, and D, respectively.Combination of nivolumab 10 mg/kg and chemotherapy showed an acceptable toxicity profile and encouraging antitumor activity in patients with advanced NSCLC.Japanese Pharmaceutical Information Center Clinical Trials Information (JapicCTI)-132071.
Identification of a FGFR3-TACC3 fusion in esophageal cancer
Authors: T. Mizukami, K. Sakai, S. Naruki, T. Taniyama, Y. Horie, N. Izawa, T. Tsuda, T. Fujino, N. Boku, H. Yasuda, T. Fukunaga, T.Eguchi Nakajima, K. Nishio
Journal: Annals of Oncology (2016)
Biomarkers for glioblastoma: MMP2 and NGAL.
Authors: Jennifer Shehan, Suprit Gupta, Satyanarayana Rachagani, Yan Zhang, Kavita Mallya, Priya Pai, Sukhwinder Kaur, Maneesh Jain, Alice Kueh, Matthew White, Michele Aizenberg, Rodney McComb, Lynette Smith, Surinder Batra, Nicole A. Shonka
Journal: Journal of Clinical Oncology (2016)

e13516 Background: Pseudoprogression and necrosis makemagnetic resonance imaging (MRI) interpretation challenging in glioblastoma (GBM). We hypothesized that matrix metalloproteinase-2 (MMP2) and neutrophil gelatinase-associated lipocalin (NGAL) would correlate with tumor burden in urine and serum of patients with GBM, allowing improved MRI interpretation and prediction of overall survival (OS). Methods: NGAL and MMP2 were analyzed by immunohistochemistry in GBM (N = 13) and non-tumor epileptic control (N = 10) tissues taken during surgery. Serum and urine samples were collected pre and postoperatively and at each MRI for GBM patients. Enzyme-linked immunosorbent assay was used to evaluate MMP2 and NGAL. MRI results, calculated tumor volumes (Olea Sphere 2.3), and survival were recorded. Results: NGAL expression was higher in GBM versus control tissues. Preoperative serum MMP2 was significantly higher in GBM versus controls (p = 0.0112) and was highest in patients who only underwent biopsy (p = 0.0038). Serum and urine NGAL and serum MMP2 increased non-significantly with tumor volume (p = 0.124, p = 0.2798 and p = 0.8215). Biomarkers did not differentiate pseudoprogression or necrosis from tumor growth. Serum NGAL decreased over time (p = 0.0040). Those on steroids or bevacizumab had higher MRI tumor volumes (p = 0.0005 and p = 0.012), and the use of bevacizumab correlated with higher urine NGAL (p = 0.049). Higher preoperative biomarkers non-significantly correlated with shorter survival. The correlation between preoperative urine NGAL and PFS with a cutoff of 6 ng/mL was nearly significant (p = 0.082). Conclusions: While MMP2 and NGAL show some initial trend for prognostic efficacy, undetermined factors may unduly influence these as biomarkers in GBM. Urine markers did not reliably recapitulate serum markers. Intra-patient biomarker changes did not elucidate equivocal MRI results. Serum NGAL levels significantly decreased over time, but NGAL may be influenced by steroids. Further studies with a larger sample size are warranted.