tbuckley/cabot-search huggingface dataset:
Consultants reject calls to be “rostered like their juniors” for out of hours work
Authors: Helen Jaques
Journal: BMJ (2012)

Consultants have rejected suggestions that they all be “rostered like their juniors” at rates of pay consistent with the 2003 consultant contract so as to boost the number of senior doctors on hospital wards at evenings and weekends.

At the BMA’s annual consultants’ conference this week senior doctors acknowledged the importance of consultant based care in reducing hospital mortality outside normal hours but voted down a motion calling for all hospital consultants to be rostered to work shifts at evenings, nights, and weekends in a similar way to trainees. 

The motion was defeated largely on …
Abstract BS2-1: Ocogenic and microenvironmental signals driving early dissemination, dormancy and metastasis
Authors: JA Aguirre-Ghiso
Journal: Cancer Research (2018)

Abstract The mechanisms that produce early-disseminated cancer cells (eDCC) during early stages of breast cancer or that contribute to the development of metastasis from cancer of unknown primary (CUP) are poorly understood. Here we show that HER2+ cancer cells that are present during early stages of cancer before any overt tumors can be detected are highly efficient in systemically disseminating from primary sites. These eDCCs were HER2+/P-p38lo/P-ATF2lo/E-cadherinlo, and were found also in human DCIS samples. Further, eDCC precursors in early lesions activated a Wnt-dependent EMT-like program that was reversed by HER2 or Wnt signaling blockade or p38 activation. Intra-vital imaging of transgenic HER2-CFP mice revealed that eDCC precursors invade the local stroma, intravasate and circulate to target organs, a process that can be stimulated by blocking p38α/β signaling. This process was aided by CD206+/Tie2+ mammary tissue macrophages (MTMs) in a similar way as they regulate mammary branching morphogenesis. We found that macrophages are localized inside the epithelium of early cancer lesions but localize in the stroma of healthy tissue. MTM recruitment depends on upregulation of CCL2 in HER2+ mammary epithelial cells via activation of NFkB. Importantly, samples from patients with DCIS frequently contain intra-epithelial macrophages, correlating with E-Cadherin downregulation. MTMs produce Wnt-1 in response to CCL2 produced by HER2+ early lesion cells and Wnt1 cooperates with the intrinsic oncogene-driven EMT in early cancer cells. Importantly these MTMs contribute to eDCC spread. Surprisingly, although the vast majority of early HER2+ cancer cells are non-tumorigenic, they can spawn eDCCs that remain HER2+/TWIST1+ and dormant in lungs for long periods only to then initiate metastasis. Significantly, depletion of macrophages during early lesion development and before overt tumors appeared, drastically reduced early dissemination and even late metastasis onset. We reveal that during early stages of HER2-driven cancer when dissemination is not thought to occur, HER2 signaling aberrantly activates a side-branching morphogenesis-like program that through macrophage recruitment and cancer cell intrinsic induction of an EMT module causes early dissemination. Our findings reveal that residual cancer may comprise dormant eDCCs with metastasis initiating capacity. We propose our data may lead to changes in our understanding of metastasis onset and how it might be targeted effectively. Citation Format: Aguirre-Ghiso JA. Ocogenic and microenvironmental signals driving early dissemination, dormancy and metastasis [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr BS2-1.
Oral cavity squamous cell carcinoma and Waldeyer ring squamous cell carcinoma PDL-1 expression: A large, retrospective, single institution site series on head and neck squamous cell carcinoma, looking at the relationship with morphology, human papilloma virus and p16.
Authors: Chit Cheng Yeoh, Iolia Akaev, Sharon Glaysher, Mridula Chopra, Anzhela Krol, Siavash Rahimi
Journal: Journal of Clinical Oncology (2018)

TPS119 Background: The most frequent type of epithelial malignancy in oral cavity and Waldeyer's ring (WR) is squamous cell carcinoma (SCC). Patients with Head and Neck SCC (HNSCC) show reduced levels of CD3+, CD4+, and CD8+ T cells compare to healthy controls. SCCs with a higher number of intra-tumoural CD4+ and CD8+ lymphocytes are associated with better prognosis. Programmed death receptor ligand (PD-L1 ) is present on the surface of neoplastic cells in SCC. T cells harbour inhibitory receptors (the so-called immune checkpoints) such as PD-1. Activation of this immune checkpoints results in T cell deactivation. The PD-1/PDL-1 interaction provokes an immunosuppressive effect which allows the tumour to evade immune destruction. However, WR SCCs present some diversities comparing to oral cavity SCC: younger age, frequent neck LN metastasis, often cystic, distinct morphology: often undifferentiated and solid (nonkeratinizing basal cell morphology), better prognosis, often HPV+, often p16+, an increased number of CD56+ cytotoxic NK. Methods: We have a series of 90 cases of epithelial malignancy in oral cavity and Waldeyer's ring (WR)Squamous cell Carcinoma, registered for Ethics IRAS number for Translational study with Immunohistochemistry; Real-time quantitative reverse transcriptase-polymerase chain reaction (RT-PCR); Fluorescence in Situ Hybridisation (FISH); Next Generation Sequencing; Digital Imaging scanning and visualising microscopy. The Study will show the relationship of PDL-1 expression with morphology, Human Papilloma Virus (HPV) infection and p16 expression, answering if the oral cavity SCC and Waldeyer's Ring SCC express PD-L1 in the same way.
Abstract P6-12-03: Utilization of bioimpedance spectroscopy in the prevention of chronic breast cancer related lymphedema
Authors: D Kaufman, C Shah, F Vicini
Journal: Cancer Research (2018)

Abstract Background: With improved breast cancer outcomes, an increasing focus on sequelae of treatment as part of survivorship has emerged. Breast cancer related lymphedema (BCRL) represents one such sequelae. Increasing data and recent NCCN guidelines support the use of prospective BCRL surveillance to allow for early detection and intervention as a method to reduce chronic, irreversible BCRL. Therefore, this study was performed to evaluate the impact early detection and treatment of BCRL in breast cancer patients undergoing prospective surveillance with bioimpedance spectroscopy (BIS). Methods: From 8/2010 through 12/2016, 206 patients were evaluated with BIS as part of a prospective surveillance program.The protocol included pre-operative assessment with BIS as well as post-operative assessments with BIS at regular intervals. Patients with L-Dex readings increasing by more than 10 from baseline were considered to have subclinical BCRL and treated with a compression sleeve for 4 weeks. For the purpose of this analysis, high-risk was defined as receipt of ALND, regional nodal irradiation, or taxane chemotherapy. Chronic BCRL was defined as the need for complex decongestive physiotherapy. Results: A total of 206 patients were analyzed, with a mean age of 61 years old and a median follow up of 25.9 months. Overall, 17% of patients had least one high-risk feature, 8% had two factors, and 7% had all three factors. A total of 21 patients (9.8%) were diagnosed with subclinical BCRL. Increased rates of subclinical BCRL were seen in patients undergoing ALND (23% vs. 7%, p=0.01) with ALND and receipt of RNI associated with development of subclinical BCRL. At last follow-up, no patients had persistent, chronic BCRL following early, conservative intervention measures. Conclusions: The results of this study support prospective surveillance and early treatment utilizing BIS. Intervention triggered by subclinical BCRL detection with an elevated L-Dex score was associated with a very low rate of chronic BCRL. Citation Format: Kaufman D, Shah C, Vicini F. Utilization of bioimpedance spectroscopy in the prevention of chronic breast cancer related lymphedema [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P6-12-03.
ATRIAL ARRHYTHMIAS IN LEFT VENTRICULAR NONCOMPACTION: ASSOCIATION WITH CLINICAL AND ECHOCARDIOGRAPHIC CHARACTERISTICS
Authors: Melissa Lyle, Vaibhav Vaidya, Suraj Kapa, A. Nadipalli, Hector Michelena, Samuel Asirvatham, Heidi Connolly, Rowlens Melduni
Journal: Journal of the American College of Cardiology (2018)
THE EFFICACY AND SAFETY OF CANGRELOR FOR PATIENTS UNDERGOING SINGLE VESSEL VERSUS MULTI VESSEL PERCUTANEOUS CORONARY INTERVENTION: INSIGHTS FROM THE CHAMPION PHOENIX TRIAL
Authors: Christoph Olivier, Freddy Abnousi, Vandana Sundaram, Jaden Yang, Gregg Stone, Philippe Steg, C. Michael Gibson, Christian Hamm, Matthew Price, Efthymios Deliargyris, Jayne Prats, Harvey White, Robert Harrington, Deepak Bhatt, Kenneth Mahaffey, Celina Yong
Journal: Journal of the American College of Cardiology (2018)
How can I get a registrar job in critical care in Australia?
Authors: Miriam Martin
Journal: BMJ (2007)

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Impact of Body Mass Index on Heart Failure by Race/Ethnicity From the Get With The Guidelines–Heart Failure (GWTG–HF) Registry
Authors: Tiffany M. Powell-Wiley, Julius Ngwa, Selomie Kebede, Di Lu, Phillip J. Schulte, Deepak L. Bhatt, Clyde Yancy, Gregg C. Fonarow, Michelle A. Albert
Journal: JACC Heart Failure (2018)
γ-Secretase Inhibition Lowers Plasma Triglyceride-Rich Lipoproteins by Stabilizing the LDL Receptor
Authors: KyeongJin Kim, Ira J. Goldberg, Mark J. Graham, Meenakshi Sundaram, Enrico Bertaggia, Samuel X. Lee, Li Qiang, Rebecca A. Haeusler, Daniel Metzger, Pierre Chambon, Zemin Yao, Henry N. Ginsberg, Utpal B. Pajvani
Journal: Cell Metabolism (2018)
Real-world study of enzalutamide and abiraterone acetate (with prednisone) tolerability (REAAcT): Results.
Authors: Neal D. Shore, Daniel R. Saltzstein, Paul R. Sieber, Bryan Mehlhaff, Lawrence Gervasi, Jennifer Phillips, Yu-Ning Wong, Huiling Pei, Tracy McGowan
Journal: Journal of Clinical Oncology (2018)

296 Background: Enzalutamide (E) and abiraterone acetate with prednisone (AAP) are approved for treatment (tx) of metastatic castration resistant prostate cancer (mCRPC). Concerns of differences in CNS manifestations and tolerability between E and AAP have been reported. REAAcT evaluated tolerability in patients (pts) newly starting E and AAP for mCRPC. Methods: This was a multicenter, Phase IV, non-randomized, prospective real-world study (NCT02663193). The tx (E or AAP) determined by the treating physician was prescribed per USPI. PROs (EORTC QLQ 30, FACIT-Fatigue, FACT-Cog) and tests of 4 cognitive domains (Cogstate) were assessed at baseline (BL) and after 2 months (M2) tx and analyzed for evaluable pts who completed BL and M2 assessments with no major protocol deviations. Descriptive statistics were provided. BL Cogstate scores were used to estimate the rate of cognitive impairment defined as ≥2SD from age-matched normative means of healthy males on ≥2 tests. Reliable change index (RCI) was calculated. Pts were noted to have clinically meaningful cognitive change with a performance decline of |RCI|≥2 on ≥2 tests. Results: Of 100 pts treated, 92 pts were evaluable (E = 46 and AAP = 46). Median age was 75 years. At BL, characteristics and median scores were similar between arms, with mild cognitive impairment in ~20% of pts. Drug discontinuations due to AEs were similar (1 vs. 2 pts), but more dose reductions due to AEs occurred on E vs. AAP (16% vs. 6%). Overall, more AEs were reported on E vs. AAP (52% vs. 36%), but Grade 3/4 AEs (4% E vs. 6% AAP) were similar. Unique neuropsychiatric AEs on E included amnesia, cognitive disorders, memory impairment, and confusional state; on AAP: cerebrovascular accident, presyncope, and spinal cord compression. Regarding fatigue, more AEs were noted on E than AAP (26% vs. 8%) and showed greater worsening in E than AAP (median change -4 vs. 0) by FACIT-Fatigue. This change within E group was statistically significant (mean, 95% CI -4 (-6.61, -1.39)). Four pts on E and 1 pt on AAP had clinically meaningful cognitive decline. Conclusions: While baseline values were similar between arms, after 2 months of tx, differences of fatigue and neurocognition were noted more often with E than AAP. Clinical trial information: NCT02663193.
Association of Progressive Multifocal Leukoencephalopathy Lesion Volume With JC Virus Polymerase Chain Reaction Results in Cerebrospinal Fluid of Natalizumab-Treated Patients With Multiple Sclerosis
Authors: Martijn T. Wijburg, Iris Kleerekooper, Birgit I. Lissenberg-Witte, Marlieke de Vos, Clemens Warnke, Bernard M. J. Uitdehaag, Frederik Barkhof, Joep Killestein, Mike P. Wattjes
Journal: JAMA Neurology (2018)

<h3>Importance</h3> The JC virus (JCV) was named after the first patient to be described with progressive multifocal leukoencephalopathy (PML), John Cunningham. Detection of JC virus DNA in cerebrospinal fluid (CSF) by polymerase chain reaction (PCR), and of specific lesions by brain magnetic resonance imaging (MRI), are both considered essential for the diagnosis of natalizumab-associated PML (NTZ-PML) in patients with multiple sclerosis. However, strict pharmacovigilance by MRI can result in detection of patients with small lesions and undetectable JCV DNA in CSF. <h3>Objective</h3> To investigate the association of PML lesion characteristics on MRI with both qualitative and quantitative JCV PCR results in CSF of patients with NTZ-PML. <h3>Design, Setting and Participants</h3> This was a retrospective, cross-sectional study conducted from January 2007 to December 2014 in patients considered to have NTZ-PML based on a set of predefined criteria. Follow-up was at least 6 months. Data of patients from the Dutch-Belgian NTZ-PML cohort and patients treated at multiple medical centers in Belgium and the Netherlands and selected for research purposes were included as a convenience sample. <h3>Main Outcomes and Measures</h3> Brain MRI scans were analyzed for PML lesion volume, location, dissemination, and signs of inflammation. Associations of the qualitative and quantitative CSF JCV PCR results with PML MRI characteristics were calculated. <h3>Results</h3> Of the 73 patients screened, 56 were included (37 were women). At inclusion, 9 patients (16.1%) had undetectable JCV DNA in CSF. Patients with a positive PCR had larger total PML lesion volumes than those with undetectable JCV DNA (median volume, 22.9 mL; interquartile range, 9.2-60.4 mL vs median volume, 6.7 mL; interquartile range, 4.9-14.7 mL;<i>P</i> = .008), and logistic regression showed that a lower PML lesion volume significantly increased the probability for undetectable JCV DNA. There was a positive correlation between PML lesion volume and JCV copy numbers (Spearman ρ, 0.32;<i>P</i> = .03). Progressive multifocal leukoencephalopathy lesion volume was higher in patients with PML symptoms and in patients with more widespread lesion dissemination. No association was found between PCR results and PML lesion dissemination, signs of inflammation, or PML symptoms. <h3>Conclusions and Relevance</h3> Smaller NTZ-PML lesions are associated with a higher likelihood of undetectable JCV DNA in CSF. This may preclude a formal diagnosis of PML and can complicate patient treatment in patients with small MRI lesions highly suggestive of PML detected early through pharmacovigilance.
How do I pursue a career in paediatric cardiology, and what are the prospects in the United Kingdom?
Authors: Shakeel Ahmed Qureshi
Journal: BMJ (2005)

Have a career or related problem that needs answering? Can9t find the right person to point you in the right direction? Log on to the Advice Zone (www.bmjcareers.com/advicezone) for reliable medical careers advice. You can post a question or see if one of our 300 advisers has already answered a similar question. Here is a selection of questions and answers posted on the site.
Key Implications of Data Sharing in Pediatric Genomics
Authors: Vasiliki Rahimzadeh, Christoph Schickhardt, Bartha M. Knoppers, Karine Sénécal, Danya F. Vears, Conrad V. Fernandez, Stefan Pfister, Sharon Plon, Sharon Terry, Janet Williams, Marc S. Williams, Martina Cornel, Jan M. Friedman
Journal: JAMA Pediatrics (2018)

Accurate clinical interpretation of children's whole-genome and whole-exome sequences relies on comparing the patient's linked genomic and phenotypic data with variant reference databases of both healthy and affected patients. The robustness of such comparisons, in turn, is made possible by sharing pediatric genomic and associated clinical data. Despite this, sparse ethical-legal policy attention has been paid to making such sharing routine in practice. The interdisciplinary Paediatric Task Team of the Global Alliance for Genomics and Health considered in detail the current ethical, legal, and social implications of sharing genomic and associated clinical data involving children. An initial set of points to consider was presented at a meeting of the Paediatric Task Team at the 4th Plenary of the Global Alliance for Genomics and Health. The Key Implications for Data Sharing (KIDS) framework for pediatric genomics was developed based on feedback from this group and was supplemented by findings from a critical appraisal of the data-sharing literature. The final points to consider that comprise the KIDS framework are categorized into the following 4 primary themes: children's involvement, parental consent, balancing benefits and risks, and data protection and release requirements.
The efficacy of direct anti-HCV drugs improves early post-liver transplant survival and induces significant changes in waiting list composition
Authors: Gonzalo Crespo, Núria Trota, Maria-Carlota Londoño, Ezequiel Mauro, Carme Baliellas, Lluís Castells, Jose Castellote, Jaume Tort, Xavier Forns, Miquel Navasa
Journal: Journal of Hepatology (2018)
Adolescents and young adults: a neglected population group for tuberculosis surveillance
Authors: Alberto L. García-Basteiro, H. Simon Schaaf, Roland Diel, Giovanni Battista Migliori
Journal: European Respiratory Journal (2018)

Tuberculosis (TB) remains a serious public health concern and it is considered the leading infectious cause of death globally. The World Health Organization (WHO) Global Tuberculosis Report of 2017 showed an estimated 10.4 million new TB cases for 2016, of which 6.7 million (64.4%) were males and 1.04 million (10%) were children 0–14 years of age [1]. Unfortunately, these figures represent estimates, an attempt to quantify the real number of TB cases, since the notifications provided from many national surveillance systems, including some of the high-burden TB countries, fail to capture many TB cases. This is either because TB cases are not diagnosed or not recorded and reported to the health authorities. In fact, the WHO estimates that only 61% of all TB cases are notified to national health authorities [1]. Other available global estimates using a different methodology, such as those by the Institute for Health Metrics and Evaluation (IHME), derived from the Global Burden of Disease project, present a similar diagnostic gap of at least one-third of the cases [2]. Trying to close this gap between real and diagnosed/reported cases (those who are likely to receive adequate treatment) with active case-finding strategies has been the target of many TB control efforts, with different levels of success [2]. The premise is clear: undiagnosed cases have much higher mortality and perpetuate the spread of the disease within communities [3, 4]. Improved surveillance systems are essential for understanding the true burden of TB in adolescents and young adults <http://ow.ly/94Pz30iaixA>
Relationship between desmoplastic pattern and lymphocytes infiltration in pancreatic cancer.
Authors: Takahiro Einama, Tadakazu Ao, Yoshiki Kajiwara, Takahiro Sueyama, Eiji Shinto, Makoto Nishikawa, Takuji Noro, Mayumi Hoshikawa, Suefumi Aosasa, Kazuo Hase, Yoshihisa Yaguchi, Shuichi Hiraki, Hironori Tsujimoto, Hideki Ueno, Junji Yamamoto
Journal: Journal of Clinical Oncology (2018)

317 Background: The proposed histologic desmoplastic reaction (DR) categorization and lymphocyte infiltration (LI) directly reflects tumor behavior in a modulating stromal environment and could provide valuable prognostic information for colorectal cancer patients, but the prognostic role of DR and LI has not been investigated in pancreatic cancer patients. Methods: A total of 87 pancreatic cancer patients who underwent potentially curative surgery for their tumors in our hospital (2008 to 2013) were included. DR was classified as mature, intermediate, or immature on the basis of the existence of keloid-like collagen and myxoid stroma-distinctive histologic products of extracellular matrix remodeling. LI was classified as Pattern I; circumferential lymphocytes zone without disruptions around tumor, Pattern II; lymphocytes zone with partial disruptions and thinning around tumor, Pattern III; focal lymphocytes foci around tumor at most invasive border without lymphocyte zone, and Pattern IV; no lymphocyte foci around tumor. Results: With regard to DR, 0, 23, and 64 patients were classified as mature, intermediate, and immature, respectively. Five-year overall survival rates (#%) were higher in immature group (p=0.0040) than those of intermediate group (#%). Multivariate analysis revealed that DR was an independent prognostic factor along with residual tumor (p=0.0300). With regard to LI, 0, 6, 70, and 11 patients were classified as Pattern I, Pattern II, Pattern III, and Pattern IV, respectively. There was no relationship between DR and LI. Conclusions: The DR categorization seemed to reflect tumor behavior and could provide valuable prognostic information for pancreatic cancer patients. We did not show any relationship between DR and LI in pancreatic cancer.
TRANSRADIAL ACCESS IS ASSOCIATED WITH LOWER RISK OF DIALYSIS AND ACUTE RENAL FAILURE THAN TRANSFEMORAL ACCESS IN PATIENTS UNDERGOING CARDIAC CATHETERIZATION OR PERCUTANEOUS CORONARY INTERVENTION
Authors: Yash Rameshbhai Patel, Pedro Moreno, Chirag Bavishi, Dhaval Kolte, J. Abbott, Herbert D. Aronow
Journal: Journal of the American College of Cardiology (2018)
THE PREDICTORS OF VERY LATE RESTENOSIS AFTER SECOND GENERATION DES IMPLANTATION
Authors: Takahiro Tokuda, Yoshiaki Ito, Hirano Keisuke, Masahiro Yamawaki, Motoharu Araki, Norihiro Kobayashi, Shinsuke Mori, Yasunari Sakamoto, Masakazu Tsutsumi
Journal: Journal of the American College of Cardiology (2018)
An adaptive function of mental time travel: Motivating farsighted decisions
Authors: Roland G. Benoit, Ruud M. W. J. Berkers, Philipp C. Paulus
Journal: Behavioral and Brain Sciences (2018)

Abstract The episodic memory system allows us to experience the emotions of past, counterfactual, and prospective events. We outline how this phenomenological experience can convey motivational incentives for farsighted decisions. In this way, we challenge important arguments for Mahr &amp; Csibra's (M&amp;C's) conclusion that future-oriented mental time travel is unlikely to be a central function of episodic memory.