tbuckley/cabot-search huggingface dataset:
Factors predicting a response to anti-androgen withdrawal maneuvers in prostate cancer patients failing combined androgen blockade
Authors: M. M. El Geneidy, G. Lewis, P. Dainer, M. K. Terris, J. Brown, T. Coleman
Journal: Journal of Clinical Oncology (2008)

16116 Background: Prostate cancer patients progressing on combined androgen blockade (CAB) will have a decline in serum PSA in 15–30% of cases when anti-androgens are withdrawn. We attempted to identify clinical disease characteristics that predicted a response to anti-androgen withdrawal. Methods: Sixty five patients on combined androgen blockade for primary metastatic tumor or relapse after definitive surgery or radiation therapy and in whom anti-androgens were withdrawn upon PSA progression after complete androgen blockade where retrospectively analyzed for differences in age at diagnosis, race, Gleason score, PSA at diagnosis, and stage at diagnosis, and initial response to therapy prior to anti-androgen withdrawal. Results: Forty three percent of patients experienced a transient decrease in serum PSA levels with anti-androgen withdrawal lasting an average of four months (range 2–35). By Chi-square analysis there were no differences in age at diagnosis (p=.77), race (p=.57), Gleason score (p=.57), PSA at diagnosis (p=.26), stage at diagnosis (p=.12), or response duration of initial therapy (p=.40) between responders and non-responders. Conclusions: None of the identified clinical factors consistently predicted a successful anti-androgen withdrawal response. Patients presenting with lower stage disease at diagnosis trended towards a higher likelihood of experiencing an anti-androgen withdrawal response. An analysis of clinical factors affecting anti-androgen withdrawal response duration is ongoing. No significant financial relationships to disclose.
Population Genomics Reveals Low Genetic Diversity and Adaptation to Hypoxia in Snub-Nosed Monkeys
Authors: Xuming Zhou, Xuehong Meng, Zhijin Liu, Jiang Chang, Boshi Wang, Mingzhou Li, Pablo Orozco-ter Wengel, Shilin Tian, Changlong Wen, Ziming Wang, Paul A Garber, Huijuan Pan, Xinping Ye, Zuofu Xiang, Michael W. Bruford, Scott V. Edwards, Yinchuan Cao, Shuancang Yu, Lianju Gao, Zhisheng Cao, Guangjian Liu, Baoping Ren, Fanglei Shi, Zalan Peterfi, Dayong Li, Baoguo Li, Zhi Jiang, Junsheng Li, Vadim N. Gladyshev, Ruiqiang Li, Ming Li
Journal: Molecular Biology and Evolution (2016)

Snub-nosed monkeys (genus Rhinopithecus) are a group of endangered colobines endemic to South Asia. Here, we re-sequenced the whole genomes of 38 snub-nosed monkeys representing four species within this genus. By conducting population genomic analyses, we observed a similar load of deleterious variation in snub-nosed monkeys living in both smaller and larger populations and found that genomic diversity was lower than that reported in other primates. Reconstruction of Rhinopithecus evolutionary history suggested that episodes of climatic variation over the past 2 million years, associated with glacial advances and retreats and population isolation, have shaped snub-nosed monkey demography and evolution. We further identified several hypoxia-related genes under selection in R. bieti (black snub-nosed monkey), a species that exploits habitats higher than any other nonhuman primate. These results provide the first detailed and comprehensive genomic insights into genetic diversity, demography, genetic burden, and adaptation in this radiation of endangered primates.
Efficacy and safety of lebrikizumab in patients with uncontrolled asthma (LAVOLTA I and LAVOLTA II): replicate, phase 3, randomised, double-blind, placebo-controlled trials
Authors: Nicola A Hanania, Phillip Korenblat, Kenneth R Chapman, Eric D Bateman, Petr Kopecky, Pierluigi Paggiaro, Akihito Yokoyama, Julie Olsson, Sarah Gray, Cecile T J Holweg, Mark Eisner, Charles Asare, Saloumeh K Fischer, Kun Peng, Wendy S Putnam, John G Matthews
Journal: The Lancet Respiratory Medicine (2016)
Primary plasma cell leukemia (PCL): Clinical and laboratory presentation and clinical outcome with total therapy (TT) protocols.
Authors: B. P. Nair, N. Petty, S. Waheed, A. Hoering, F. Van Rhee, E. J. Anaissie, R. Lorsbach, C. Bailey, B. Barlogie
Journal: Journal of Clinical Oncology (2010)

8116 Background: PCL, a rare manifestation of symptomatic multiple myeloma (MM), has a dismal prognosis. The definition of PCL is based on one of the following criteria: circulating plasma cells (PC) > 2,000/uL if the leukocyte count exceeds 10,000/uL or 20% PC with lower leukocyte levels. Methods: Patients with PCL were eligible for TT protocols with melphalan-based tandem transplants and included 7/231 in TT1, 12/668 in TT2 and 10/576 in TT3 and TT3-like protocols for an overall PCL incidence of 2.04%. Overall survival (OS), event-free survival (EFS), frequency of complete response (CR) and CR duration (CRD) in PCL are presented in the context of non-PCL cases to determine whether PCL is an independent adverse prognostic variable, after adjusting for other prognostic variables, and progress has been made in the management of PCL with transition from TT1 to TT2 to TT3 trials. Results: In comparison to the remainder, the 29 patients with PCL at baseline had highly significantly inferior OS (median, 1.8yr v 8.8yr; p<0.0001), EFS (median, 0.8yr v 5.2yr; p<0.0001) and CRD (median, 1.1yr v 6.8yr; p<0.0001), although CR rates were comparable at 43% in PCL vs 54% in non-PCL. Unlike in non-PCL cases, no significant improvement in survival outcomes were noted in PCL as we moved from TT1 to TT2 to TT3 regimens. According to Cox regression applied across protocols, PCL remained an independent highly significant adverse variable for OS (HR=2.51, p=0.002), EFS (HR=4.13, p<0.001) and CRD (HR=7.80, p<0.001), also when examined in the subset of patients with gene expression profiling (GEP) data. According to logistic regression, PCL was significantly linked to GEP high-risk, CA, high levels of LDH and B2M, low concentrations of albumin and hemoglobin; GEP-defined CD-1 and MF molecular subgroups were more frequent and HY less frequent in PCL. Conclusions: PCL, while equally sensitive to primary TT therapies in terms of CR rate, remains a rare MM subgroup with grave prognosis, requiring novel therapeutic interventions. No significant financial relationships to disclose.
Time-course evaluation of survival and treatment in FIRE-3 trial (AIO KRK0306).
Authors: Dominik Paul Modest, Ingrid Ricard, Sebastian Stintzing, Ludwig Fischer von Weikersthal, Alberto F. Sobrero, Thomas Decker, Alexander Kiani, Ursula Vehling-Kaiser, Salah-Eddin Al-Batran, Tobias Heintges, Christian A. Lerchenmuller, Christoph Kahl, Gernot Seipelt, Frank Kullmann, Martina Stauch, Werner Scheithauer, Markus H. Moehler, Swantje Held, Volker Heinemann
Journal: Journal of Clinical Oncology (2016)

3528 Background: To investigate overall survival (OS) differences in FIRE-3 in context of exposure to treatments (i.e. first-, second-, third-line) in time course. Methods: We compared OS in FIRE-3 between the two treatment arms (FOLFIRI plus cetuximab vs FOLFIRI plus bevacizumab) by use of a Cox regression model and tested the model assumption of a constant hazard ratio at a significance level of 0.05. Results: The time-course hazard ratios of OS are summarized in TABLE 1. Pronounced differences in OS were observed between 24 and 30 months (73 of 297 (24.6%, arm A) and 74 of 295 patients (25.1%, arm B) received systemic therapy) and between 30 and 36 months (56 of 297 patients (18.9%, arm A) and in 48 of 295 patients (16.3%, arm B) received systemic therapy). Beyond two years after start of treatment, median time on treatment within six-month intervals was less than 2 months. Testing the assumption of a constant hazard ratio (Cox model) between the two trial arms did not prove a significant level of violation (P = 0.12). Conclusions: The differences in OS observed in FIRE-3 are pronounced within time intervals between 24 and 30 months as well as 30 and 36 months after randomization into the study, although no significant violation of a constant hazard ratio assumption is evident. A small number of patients received rather short courses of anti-tumor therapy in the respective 6-months intervals beyond two years. The difference in OS that manifest in time-frames between 24 and 30 months as well as between 30 and 36 months suggests that underlying effects on OS in FIRE-3 may include multiple factors and cannot be explained by the number of patients on active treatment alone. Clinical trial information: NCT00433927. Time interval (months) 0-6 > 6-12 > 12-18 > 18-24 > 24-30 > 30-36 > 36 KRAS exon 2 wild-type population No at risk (OS) in Arm (A/B) 297/295 272/273 229/230 177/176 125/127 95/77 69/55 time-wise hazard ratio of OS (95% CI) 1.23(0.65-2.32) 0.89(0.54-1.49) 0.77(0.48-1.21) 1.01(0.64-1.61) 0.48(0.27-0.85) 0.51(0.22-1.17) 0.78(0.47-1.28)
Assessing the potential of mathematical modelling in designing drug-releasing orthopaedic implants
Authors: David King, Sean McGinty
Journal: Journal of Controlled Release (2016)

Orthopaedic implants have been the subject of intense research in recent years, with academics, clinicians and industrialists seeking to broaden our understanding of their function and potential consequences within the human body. Current research is focussed on ways to improve the integration of an orthopaedic device within the body, whether it be to encourage better osseointegration, combat possible infection or stem the foreign body response. A key emerging strategy is the controlled delivery of therapeutics from the device, which may take the form of, for example, antibiotics, analgesics, anti-inflammatories or growth factors. However, the optimal device design that gives rise to the desired controlled release has yet to be defined. There are many examples in the literature of experimental approaches which attempt to tackle this issue. However, the necessity of having to conduct multiple experiments to test different scenarios is a major drawback of this approach. So enter stage left: mathematical modelling. Using a mathematical modelling approach can provide much more than experiments in isolation. For instance, a mathematical model can help identify key drug release mechanisms and uncover the rate limiting processes; allow for the estimation of values of the parameters controlling the system; quantify the effect of the interaction with the biological environment; and aid with the design of optimisation strategies for controlled drug release. In this paper we review current experimental approaches and some relevant mathematical models and suggest the future direction of such approaches in this field.
Long-Term Expansion and Self Renewal Is Contained in the CD34+, but Not the CD34- Subfraction of Nucleophosmin Mutated Acute Myeloid Leukemia Cells.
Authors: Carolien Woolthuis, Lina Han, Djoke van Gosliga, Philip Kluin, Edo Vellenga, Jan J. Schuringa, Geert Huls
Journal: Blood (2008)
Inflammation Triggers Zeb1-Dependent Escape from Tumor Latency
Authors: Jasmine M. De Cock, Tsukasa Shibue, Anushka Dongre, Zuzana Keckesova, Ferenc Reinhardt, Robert A. Weinberg
Journal: Cancer Research (2016)

The emergence of metastatic disease in cancer patients many years or decades after initial successful treatment of primary tumors is well documented but poorly understood at the molecular level. Recent studies have begun exploring the cell-intrinsic programs, causing disseminated tumor cells to enter latency and the cellular signals in the surrounding nonpermissive tissue microenvironment that maintain the latent state. However, relatively little is known about the mechanisms that enable disseminated tumor cells to escape cancer dormancy or tumor latency. We describe here an in vivo model of solitary metastatic latency in the lung parenchyma. The induction of a localized inflammation in the lungs, initiated by lipopolysaccharide treatment, triggers the awakening of these cells, which develop into macroscopic metastases. The escape from latency is dependent on the expression of Zeb1, a key regulator of the epithelial-to-mesenchymal transition (EMT). Furthermore, activation of the EMT program on its own, as orchestrated by Zeb1, is sufficient to incite metastatic outgrowth by causing carcinoma cells to enter stably into a metastasis-initiating cell state. Cancer Res; 76(23); 6778-84. ©2016 AACR.
Phase II study with docetaxel (D), cisplatin (C), and continuous capecitabine (CAP) combination (TCX) in advanced gastric cancer: Preliminary data.
Authors: C. Pericay, F. Losa, A. Pisa, J. Alfaro, L. Cirera, A. Salud, E. Falco, E. Dotor, P. Vicente, E. Casado, J. C. Oliva, E. Saigí
Journal: Journal of Clinical Oncology (2011)

e14611 Background: Activity in first line in advanced gastric carcinoma with D, C and CAP has been describe. But there is no much information about continuous treatment with capecitabine in this setting. We performed this study in order to obtain data in this patients. Methods: Patients (pts) were enrolled if they had the main subsequent criteria: histologically confirmed diagnosis of advanced gastric cancer (AGC) (local advanced or metastatic disease); normal renal and hepatic function; no myocardial infarction or angina pectoris; no uncontrolled severe diseases or active infections. Treatment schedule: D at fixed dose of 75 mg/m2 on day 1, C at fixed dose of 60 mg/m2 on day 1, CAP at fixed dose of 1,300 mg/m2 in two daily administration from day 1 to day 21, every 3 weeks. Colony stimulating factors were used as a primary profilaxis. Dose-limiting toxicity (DLT): Grade (G) 3 non-haematological or G4 haematological. Study design: Open phase II trial. Primary endpoint was response rate (RR). Secondary endpoints were time to progression (TTP), overall survival (OS), toxicity and quality of life. Results: 45 pts were enrolled. We present preliminary results of 41pts. Median age of 61 years (range 32-80). Median number of cycles per pt was 5 (range 1-6). Total cycles administered: 172. Main G1-2 toxicities were: diarrhea 22%, neurotoxicity 18%. Cumulative G3-4 toxicities were: neutropenia 6.9%, neutropenia febril 3.4%, mucositis 2%, asthenia 9%. Median received-dose intensity (DI) of D: 72.5 mg/m2 (96.7% of recommended-DI), C 51 mg/m2 (84.3%), CAP 1083.0 mg/m2/day (83.37%) per patient. Efficacy: 36 pts were assessable for response:18 (50%) had partial response, 10 (27.8%) had stable disease and 8 (22.2%) had progression. At moment of the last analysis 16 (39%) were exitus. Mean OS was 17.8 months (CI 95% 14.4-21.2). Conclusions: The combination TCX is tolerable without G3-4 toxicity and preliminary data show very high activity. On behalf ACROSS group.
Childhood obesity in relation to poor asthma control and exacerbation: a meta-analysis
Authors: Fariba Ahmadizar, Susanne J.H. Vijverberg, Hubertus G.M. Arets, Anthonius de Boer, Jason E. Lang, Meyer Kattan, Colin N.A. Palmer, Somnath Mukhopadhyay, Steve Turner, Anke H. Maitland-van der Zee
Journal: European Respiratory Journal (2016)

To estimate the association between obesity and poor asthma control or risk of exacerbations in asthmatic children and adolescents, and to assess whether these associations are different by sex. A meta-analysis was performed on unpublished data from three North-European paediatric asthma cohorts (BREATHE, PACMAN (Pharmacogenetics of Asthma medication in Children: Medication with Anti-inflammatory effects) and PAGES (Pediatric Asthma Gene Environment Study)) and 11 previously published studies (cross-sectional and longitudinal studies). Outcomes were poor asthma control (based on asthma symptoms) and exacerbations rates (asthma-related visits to the emergency department, asthma-related hospitalisations or use of oral corticosteroids). Overall pooled estimates of the odds ratios were obtained using fixed- or random-effects models. In a meta-analysis of 46 070 asthmatic children and adolescents, obese children (body mass index ≥95th percentile) compared with non-obese peers had a small but significant increased risk of asthma exacerbations (OR 1.17, 95% CI 1.03–1.34; I 2 : 54.7%). However, there was no statistically significant association between obesity and poor asthma control (n=4973, OR 1.23, 95% CI 0.99–1.53; I 2 : 0.0%). After stratification for sex, the differences in odds ratios for girls and boys were similar, yet no longer statistically significant. In asthmatic children, obesity is associated with a minor increased risk of asthma exacerbations but not with poor asthma control. Sex does not appear to modify this risk.
Expression Of Histological markers and PET-CT Maximal Standardized Uptake for Follicular Lymphoma
Authors: Caroline Delette, Christine Robin, Jean-Fortuné Ikoli, Lazhar Saidi, Anne Parcelier, Bruno Royer, Gandhi Damaj, Lavinia Merlusca, Amandine Charbonnier, Eric Guiheneuf, Henri Sevestre, Jean Pierre Marolleau
Journal: Blood (2013)
Msi2 Directly Regulates The TGF-β Signaling Pathway and Myeloid Lineage Bias In Hematopoietic Stem Cells
Authors: Sun-Mi Park, Raquel P Deering, Yuheng Lu, Tivnan Patrick, Varun Shenoy, Steve Lianoglou, Fatima Al-Shahrour, Christina Leslie, Benjamin L. Ebert, Christopher Lengner, George Q Daley, Michael G Kharas
Journal: Blood (2013)
Albumin-bounded Paclitaxel (nab-Paclitaxel) in metastatic breast cancer: new insights from a real life multicenter Italian experience
Authors: R. Palumbo, M.E. Cazzaniga, E. Simoncini, C. Tondini, E. Piazza, A. Ferzi, D. Grasso, M. Danova, E. Tarenzi, A. Bernardo
Journal: Annals of Oncology (2015)
<i>Annals</i> Graphic Medicine - Judgment Call
Authors: Sharon Rosenzweig
Journal: Annals of Internal Medicine (2016)

Web Exclusives6 September 2016Annals Graphic Medicine - Judgment CallFREESharon Rosenzweig, BFA, MFASharon Rosenzweig, BFA, MFASearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/G16-0010 SectionsAboutVisual AbstractPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Download figure Download PowerPoint Download figure Download PowerPoint Download figure Download PowerPoint Download figure Download PowerPoint Download figure Download PowerPoint Comments0 CommentsSign In to Submit A Comment Author, Article, and Disclosure InformationAffiliations: Disclosures: The author has disclosed no conflicts of interest. Form can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=G16-0010.Author Information: Sharon Rosenzweig is an investigative cartoonist (thecomictorah.com); e-mail, [email protected]com.Author Contributions: Conception and design: S. Rosenzweig.Analysis and interpretation of the data: S. Rosenzweig.Drafting of the article: S. Rosenzweig.Critical revision for important intellectual content: S. Rosenzweig.Final approval of the article: S. Rosenzweig.Administrative, technical, or logistic support: S. Rosenzweig.Collection and assembly of data: S. Rosenzweig.Written and illustrated by Sharon Rosenzweig, BFA, MFA. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 6 September 2016Volume 165, Issue 5Page: W6-W11KeywordsConflicts of interestDisclosureHealth care ePublished: 6 September 2016 Issue Published: 6 September 2016 Copyright & PermissionsCopyright © 2016 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Growing gaps in paediatric rotas threaten children’s healthcare, says royal college
Authors: Ingrid Torjesen
Journal: BMJ (2016)

Paediatricians are calling for an urgent increase in training numbers and for consultant service redesign because UK paediatric services have been struggling with growing gaps in staff rotas.

More than half of paediatric services in the UK were not staffed to recommended levels, shows the latest workforce survey, published on 16 August by the Royal College of Paediatrics and Child Health. Services were struggling to cope with rising numbers of vacant posts and had to rely on consultants to cover gaps in rotas because they could not get locum cover.1

The survey adds to mounting evidence of the growing crisis affecting the medical workforce. In June a report from the Royal College of Anaesthetists …
Added Sugars and Cardiovascular Disease Risk in Children: A Scientific Statement From the American Heart Association
Authors: Miriam B. Vos, Jill L. Kaar, Jean A. Welsh, Linda V. Van Horn, Daniel I. Feig, Cheryl A.M. Anderson, Mahesh J. Patel, Jessica Cruz Munos, Nancy F. Krebs, Stavra A. Xanthakos, Rachel K. Johnson
Journal: Circulation (2016)

Background: Poor lifestyle behaviors are leading causes of preventable diseases globally. Added sugars contribute to a diet that is energy dense but nutrient poor and increase risk of developing obesity, cardiovascular disease, hypertension, obesity-related cancers, and dental caries. Methods and Results: For this American Heart Association scientific statement, the writing group reviewed and graded the current scientific evidence for studies examining the cardiovascular health effects of added sugars on children. The available literature was subdivided into 5 broad subareas: effects on blood pressure, lipids, insulin resistance and diabetes mellitus, nonalcoholic fatty liver disease, and obesity. Conclusions: Associations between added sugars and increased cardiovascular disease risk factors among US children are present at levels far below current consumption levels. Strong evidence supports the association of added sugars with increased cardiovascular disease risk in children through increased energy intake, increased adiposity, and dyslipidemia. The committee found that it is reasonable to recommend that children consume ≤25 g (100 cal or ≈6 teaspoons) of added sugars per day and to avoid added sugars for children &lt;2 years of age. Although added sugars most likely can be safely consumed in low amounts as part of a healthy diet, few children achieve such levels, making this an important public health target.
Predictors and Prognostic Significance of Right Ventricular Ejection Fraction in Patients With Ischemic Cardiomyopathy
Authors: Marwa A. Sabe, Sharif A. Sabe, Kenya Kusunose, Scott D. Flamm, Brian P. Griffin, Deborah H. Kwon
Journal: Circulation (2016)

Decreased right ventricular (RV) ejection fraction (RVEF) portends poor prognosis in patients with ischemic cardiomyopathy, and previous studies have suggested an association between mitral regurgitation (MR) and RVEF. We sought to evaluate this association and whether mitral valve repair or replacement affects the relationship between RV function and mortality.We included 588 patients (mean age, 63±11 years; 75% male) with ischemic cardiomyopathy who underwent cardiac magnetic resonance imaging between 2002 and 2008. Baseline characteristics, left ventricular ejection fraction, MR severity, treatment modality, scar burden, and RVEF were assessed. Multivariable linear regression and Cox proportional hazards models were used to assess the association between MR and RVEF and between RVEF and mortality, respectively.After adjustment for age, sex, left ventricular ejection fraction, right bundle-branch block, and RV scar, MR severity was found to be associated independently with RVEF. There were a total of 240 deaths during a median follow-up time of 5.7 years. After multivariable adjustment, every 10% decrease in RVEF was associated with a 17% increased risk of death (P=0.008). Although decreasing RVEF was associated with a poor prognosis in the nonrepair group (hazard ratio, 1.28; 95% confidence interval, 1.12-1.47; P<0.001), it was not associated with death in the mitral valve repair or replacement group (P for interaction=0.046).MR severity was found to be an independent predictor of RVEF, as were right bundle-branch block, left ventricular ejection fraction, and the presence of RV scar. Decreasing RVEF is associated with increased mortality in patients with ischemic cardiomyopathy; however, this association may be mitigated in patients who undergo mitral valve repair or replacement.