tbuckley/cabot-search huggingface dataset:
Multiparametric MRI-based intraprostatic tumor volume delineation in localized prostate cancer.
Authors: Joon Kyu Lee, Chang Liu, Mohamed A. Elshaikh, Ning Wen
Journal: Journal of Clinical Oncology (2018)

22 Background: Multiparametric MR imaging (mpMRI) has shown promising results in the diagnosis and localization of prostate cancer. Furthermore, mpMRI may play an important role in identifying a suitable target volume for intraprostatic radiotherapy boost. We sought to investigate the level of correlation between dominant tumor foci contoured on various mpMRI sequences. Methods: mpMRI data from 18 patients with MR-guided biopsy-proven prostate cancer were obtained from the SPIE-AAPM-NCI Prostate MR Classification Challenge. Each case consisted of T2-weighted, apparent diffusion coefficient (ADC), and k trans images computed from dynamic contrast-enhanced sequences. All image sets were rigidly co-registered, and the dominant tumor foci were identified and contoured for each MRI sequence. Hausdorff distance (HD), mean distance to agreement (MDA), and Dice and Jaccard coefficients were calculated between the contours for each pair of MRI sequences (i.e., T2 vs. ADC, T2 vs. k trans , and ADC vs. k trans ). The Pearson correlation coefficient (PCC) was also obtained for Dice and Jaccard between these image pairs. Results: The dominant tumor foci were located in the peripheral zone, transition zone, and anterior fibromuscular stroma in 5 (28%), 7 (39%), and 6 (33%) patients, respectively. Mean tumor volumes in the T2-weighted, ADC, and k trans sequences were 2.71 +/- 2.74 mL, 2.71 +/- 2.67 mL, and 2.21 +/- 1.86 mL, respectively. Mean HD and MDA were lowest (4.34 +/- 1.52 mm and 1.00 +/- 0.52 mm) and Dice and Jaccard coefficients highest (0.74 +/- 0.12 and 0.60 +/- 0.15) for T2 vs. ADC. The PCC for Dice was 0.15 between T2 vs. ADC and T2 vs. k trans , 0.37 between T2 vs. ADC and ADC vs. k trans , and 0.62 between T2 vs. k trans and ADC vs. k trans , and similar values were obtained for Jaccard (0.12, 0.32, and 0.67, respectively). Four patients were excluded in the PCC calculation as no vascular permeability was visible in the k trans maps. Conclusions: This analysis suggests that T2-weighted and ADC sequences have high correlation in identifying a suitable intraprostatic radiotherapy boost volume for localized prostate cancer. Furthermore, k trans maps may provide additional information for tumor volume delineation.
Reduce NHS reliance on migrants, HEE told
Authors: Abi Rimmer
Journal: BMJ (2016)

Health Education England (HEE) has been told by the government that it must produce a plan by September 2017 to reduce the NHS’s reliance on migrant workers.

Earlier this month Jeremy Hunt, health secretary for England, announced plans to increase medical school places by 25% in a bid to expand the number of home grown doctors and to replace doctors recruited from overseas.1

As part of HEE’s mandate from the government for April 2016 to March 2017, the Department of Health said that …
Deterioration of liver function after transarterial chemoembolization (TACE) in hepatocellular carcinoma (HCC): An exploratory analysis of OPTIMIS—An international observational study assessing the use of sorafenib after TACE.
Authors: Masatoshi Kudo, Jean-Luc Raoul, Han Chu Lee, Ann-Lii Cheng, Keiko Nakajima, Markus Peck-Radosavljevic
Journal: Journal of Clinical Oncology (2018)

368 Background: TACE is commonly used for patients (pts) with unresectable HCC, and appropriate pt selection is important to obtain optimal outcomes. However, there is no globally accepted consensus on unsuitability and refractoriness to TACE. Retrospective studies suggest that continuing TACE after refractoriness or failure is harmful and may cause pts to become ineligible for further treatments because of liver function deterioration. This exploratory analysis of OPTIMIS evaluated the real-world incidence of liver function deterioration by baseline liver characteristics after first TACE. Methods: OPTIMIS enrolled 1670 pts with HCC for whom a decision to treat with TACE was made at the time of study entry. Liver function deterioration was defined as worsening of CTCAE grade compared with baseline for any of these parameters: aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin, albumin, and prothrombin international normalized ratio (INR). All analyses are descriptive. Results: A total of 977 pts received TACE. The incidence of liver deterioration was higher in pts with BCLC stage C vs stage B (52% vs 44%, respectively), in pts exceeding the up-to-7 criteria compared with those within (49% vs 43%, respectively), and in those deemed unsuitable for TACE at baseline versus those deemed eligible (53% vs 44%, respectively) (Table). Conclusions: Deterioration of liver function parameters was observed after TACE in pts with HCC in the real-world setting. Therefore, appropriate pt selection for TACE and preserving liver function are important to optimize the benefit of TACE and subsequent treatments. Clinical trial information: NCT01933945. [Table: see text]
Factors influencing risk‐based care of the childhood cancer survivor in the 21st century
Authors: Stephanie B. Dixon, Kari L. Bjornard, Nicole M. Alberts, Gregory T. Armstrong, Tara M. Brinkman, Wassim Chemaitilly, Matthew J. Ehrhardt, Israel Fernandez‐Pineda, Lisa M. Force, Todd M. Gibson, Daniel M. Green, Carrie R. Howell, Sue C. Kaste, Anne C. Kirchhoff, James L. Klosky, Kevin R. Krull, John T. Lucas, Daniel A. Mulrooney, Kirsten K. Ness, Carmen L. Wilson, Yutaka Yasui, Leslie L. Robison, Melissa M. Hudson
Journal: CA A Cancer Journal for Clinicians (2018)

Abstract The population of adult survivors of childhood cancer continues to grow as survival rates improve. Although it is well established that these survivors experience various complications and comorbidities related to their malignancy and treatment, this risk is modified by many factors that are not directly linked to their cancer history. Research evaluating the influence of patient‐specific demographic and genetic factors, premorbid and comorbid conditions, health behaviors, and aging has identified additional risk factors that influence cancer treatment‐related toxicity and possible targets for intervention in this population. Furthermore, although current long‐term follow‐up guidelines comprehensively address specific therapy‐related risks and provide screening recommendations, the risk profile of the population continues to evolve with ongoing modification of treatment strategies and the emergence of novel therapeutics. To address the multifactorial modifiers of cancer treatment‐related health risk and evolving treatment approaches, a patient‐centered and risk‐adapted approach to care that often requires a multidisciplinary team approach, including medical and behavioral providers, is necessary for this population. CA Cancer J Clin 2018;68:133‐152 . © 2018 American Cancer Society .
Cancer survivorship: a local and global issue in cancer control
Authors: Jennifer Jones, Doris Howell, Eva Grunfeld
Journal: The Lancet Global Health (2018)

Due to advances in detection and progressively more complex treatments, cancer-specific mortality for many prevalent cancers has decreased substantially in developed countries.1Allemani C Weir HK Carreira H et al.Global surveillance of cancer survival 1995–2009: analysis of individual data for 25 676 887 patients from 279 population-based registries in 67 countries (CONCORD-2).Lancet. 2015; 385: 977-1010Summary Full Text Full Text PDF PubMed Scopus (420) Google Scholar With advances in early detection and treatment, this trend is expected to extend to low-income and middle-income countries (LMICs) in the future. The post-treatment survivorship phase presents diverse and often unexpected challenges that are affected by clinical, individual, and socioeconomic factors. Post-treatment cancer survivors present with a range of persistent and late-onset side-effects such as lymphoedema, fatigue, pain, cognitive changes, cardiotoxicity, and psychosocial issues (eg, cancer recurrence, body image concerns, and anxiety).2Stein KD Syrjala KL Andrykowski MA Physical and psychological long-term and late effects of cancer.Cancer. 2008; 112: 2577-2592Crossref PubMed Scopus (420) Google Scholar, 3Ganz PA Survivorship: adult cancer survivors.Prim Care. 2009; 36: 721-741Summary Full Text Full Text PDF PubMed Scopus (157) Google Scholar Traditional delivery systems for cancer care have limited capacity to provide access to quality, long-term health care for the growing number of cancer survivors. Health care should include, as a minimum, surveillance for detection of new and recurrent cancer, interventions for consequences of cancer and its treatment, and coordination between specialists and primary care to ensure ongoing needs for preventive care are met.4McCabe MS Bhatia S Oeffinger KC et al.American Society of Clinical Oncology statement: achieving high-quality cancer survivorship care.J Clin Oncol. 2013; 31: 631-640Crossref PubMed Scopus (330) Google Scholar Integration of survivorship services into the standard of care needs an evidence base to inform best practices, optimal models for delivery of survivorship care, and investment in resources for care sectors such as primary care. The effect of and interplay between these factors are magnified in LMIC settings because access to health services, infrastructure, and resources are limited. These challenges are driving innovations in cancer care delivery, research, and education to direct individual, organisational, and systems-level change in developed countries such as Canada. These innovations can be adapted to LMICs through international collaboration and shared learning. Such global partnerships can enhance research and delivery of care for cancer survivors from diverse settings and address this challenge as a global public health care problem. We declare no competing interests.
UK doctors may face underemployment or even unemployment, BMA warns
Authors: Abi Rimmer
Journal: BMJ (2014)

Doctors in the UK are at risk of underemployment or even unemployment in the future, the BMA has warned.

The association has published a discussion paper on the medical workforce, looking at medical unemployment and underemployment.1 “There are a number of warning signs that the UK medical workforce could be heading towards a period of significant change and uncertainty which, if poorly managed, could result in preventable medical underemployment and possibly unemployment,” the paper said.

The BMA said that, to avoid preventable underemployment and unemployment, it was “imperative” that UK-wide workforce planning be carried out before any large scale workforce changes are implemented. It argued that one major change that could affect the number of doctors employed in the UK was the implementation of the recommendations of the Shape of Training review.2 If introduced, the review’s recommendations would remove “a lot of the competitive entry points and competition ratios to …
Biomimetic nanoparticles with enhanced affinity towards activated endothelium as versatile tools for theranostic drug delivery
Authors: Jonathan O. Martinez, Roberto Molinaro, Kelly A. Hartman, Christian Boada, Roman Sukhovershin, Enrica De Rosa, Dickson Kuri, Shanrong Zhang, Michael Evangelopoulos, Angela M. Carter, James A. Bibb, John P. Cooke, Ennio Tasciotti
Journal: Theranostics (2018)

Activation of the vascular endothelium is characterized by increased expression of vascular adhesion molecules and chemokines.This activation occurs early in the progression of several diseases and triggers the recruitment of leukocytes.Inspired by the tropism of leukocytes, we investigated leukocyte-based biomimetic nanoparticles (i.e., leukosomes) as a novel theranostic platform for inflammatory diseases.Methods: Leukosomes were assembled by combining phospholipids and membrane proteins from leukocytes.For imaging applications, phospholipids modified with rhodamine and gadolinium were used.Leukosomes incubated with antibodies blocking lymphocyte function-associated antigen 1 (LFA-1) and CD45 were administered to explore their roles in targeting inflammation.In addition, relaxometric assessment of NPs was evaluated.Results: Liposomes and leukosomes were both spherical in shape with sizes ranging from 140-170 nm.Both NPs successfully integrated 8 and 13 µg of rhodamine and gadolinium, respectively, and demonstrated less than 4% variation in physicochemical features.Leukosomes demonstrated a 16-fold increase in breast tumor accumulation relative to liposomes.Furthermore, quantification of leukosomes in tumor vessels demonstrated a 4.5-fold increase in vessel lumens and a 14-fold increase in vessel walls.Investigating the targeting mechanism of action revealed that blockage of LFA-1 on leukosomes resulted in a 95% decrease in tumor accumulation.Whereas blockage of CD45 yielded a 60% decrease in targeting and significant increases in liver and spleen accumulation.In addition, when administered in mice with atherosclerotic plaques, leukosomes exhibited a 4-fold increase in the targeting of inflammatory vascular lesions.Lastly, relaxometric assessment of NPs demonstrated that the incorporation of membrane proteins into leukosomes did not impact the r1 and r2 relaxivities of the NPs, demonstrating 6 and 30 mM -1 s -1 , respectively.Conclusion: Our study demonstrates the ability of leukosomes to target activated vasculature and exhibit superior accumulation in tumors and vascular lesions.The versatility of the phospholipid backbone within leukosomes permits the incorporation of various contrast agents.Furthermore, leukosomes can potentially be loaded with therapeutics possessing diverse physical properties and thus warrant further investigation toward the development of powerful theranostic agents.
Amyloid-Beta Solubility in the Treatment of Alzheimer’s Disease
Authors: M. Paul Murphy
Journal: New England Journal of Medicine (2018)

There is general agreement that Alzheimer's disease will become a crisis by the middle of the century. The Alzheimer's Association estimates that 5 million Americans currently have Alzheimer's disease and that their loved ones devote nearly 18 billion hours annually toward their care. If Alzheimer's disease remains unchecked, these numbers are projected to more than triple by 2050, and the economic burden will exceed $1 trillion per year. The quest to find an effective therapy has been urgent. For nearly two decades, since the first report of a successful amyloid-beta (Aβ) immunotherapy in mice,1 this goal has seemed tantalizingly close. . . .
Surface-enhanced Raman nanoparticles for tumor theranostics applications
Authors: Yangyang Li, Qiaolin Wei, Fei Ma, Xin Li, Fengyong Liu, Min Zhou
Journal: Acta Pharmaceutica Sinica B (2018)

Raman spectroscopy, amplified by surface-enhanced Raman scattering (SERS) nanoparticles, can provide an in vivo imaging modality due to its high molecular specificity, high sensitivity, and negligible autofluorescence. The basis, composition, and methodologies developed for SERS nanoparticles are herein described. The research hotspots that are the focus in this paper are tumor imaging-guided theranostics and biosensing. The next breakthrough may be the development of biocompatible SERS nanoparticles and spectroscopic devices for clinical applications.
Medical research lags behind in gender equality, say researchers
Authors: Matthew Limb
Journal: BMJ (2016)

Despite more women being employed in medicine, research still “lags behind” in gender equality, a survey has found.

The Royal College of Physicians surveyed around 2000 UK doctors and found that men and women were equally likely to be employed in a research role.1 However, if not formally employed in a research role, women were less likely than men to engage in research in addition to their regular clinical duties, with only 29% doing so compared with 43% of men.

It …
Involvement of Heparanase in the Pathogenesis of Mesothelioma: Basic Aspects and Clinical Applications
Authors: Uri Barash, Moshe Lapidot, Yaniv Zohar, Cynthia Loomis, Andre Moreira, Sari Feld, Chandra Goparaju, Haining Yang, Edward Hammond, Ganlin Zhang, Jin-Ping Li, Neta Ilan, Arnon Nagler, Harvey I Pass, Israel Vlodavsky
Journal: JNCI Journal of the National Cancer Institute (2018)

Mammalian cells express a single functional heparanase, an endoglycosidase that cleaves heparan sulfate and thereby promotes tumor metastasis, angiogenesis, and inflammation. Malignant mesothelioma is highly aggressive and has a poor prognosis because of the lack of markers for early diagnosis and resistance to conventional therapies. The purpose of this study was to elucidate the mode of action and biological significance of heparanase in mesothelioma and test the efficacy of heparanase inhibitors in the treatment of this malignancy. The involvement of heparanase in mesothelioma was investigated by applying mouse models of mesothelioma and testing the effect of heparanase gene silencing (n = 18 mice per experiment; two different models) and heparanase inhibitors (ie, PG545, defibrotide; n = 18 per experiment; six different models). Synchronous pleural effusion and plasma samples from patients with mesothelioma (n = 35), other malignancies (12 non–small cell lung cancer, two small cell lung carcinoma, four breast cancer, three gastrointestinal cancers, two lymphomas), and benign effusions (five patients) were collected and analyzed for heparanase content (enzyme-linked immunosorbent assay). Eighty-one mesothelioma biopsies were analyzed by H-Score for the prognostic impact of heparanase using immunohistochemistry. All statistical tests were two-sided. Mesothelioma tumor growth, measured by bioluminescence or tumor weight at termination, was markedly attenuated by heparanase gene silencing (P = .02) and by heparanase inhibitors (PG545 and defibrotide; P < .001 and P = .01, respectively). A marked increase in survival of the mesothelioma-bearing mice (P < .001) was recorded. Heparanase inhibitors were more potent in vivo than conventional chemotherapy. Clinically, heparanase levels in patients' pleural effusions could distinguish between malignant and benign effusions, and a heparanase H-score above 90 was associated with reduced patient survival (hazard ratio = 1.89, 95% confidence interval = 1.09 to 3.27, P = .03). Our results imply that heparanase is clinically relevant in mesothelioma development. Given these preclinical and clinical data, heparanase appears to be an important mediator of mesothelioma, and heparanase inhibitors are worthy of investigation as a new therapeutic modality in mesothelioma clinical trials.
Reshaping of the Dendritic Cell Chromatin Landscape and Interferon Pathways during HIV Infection
Authors: Jarrod S. Johnson, Sasha Y. Lucas, Lynn M. Amon, Stephanie Skelton, Rodolfo Nazitto, Sara Carbonetti, D. Noah Sather, Dan R. Littman, Alan Aderem
Journal: Cell Host & Microbe (2018)
Should I stay on a senior house officer rotation even though the consultant in charge of the final six months (and the specialty I'm most keen on) is retiring?
Authors: Anita Houghton
Journal: BMJ (2004)

Got a career or related problem that needs answering? Can't 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.
A randomized phase II trial of pazopanib (PAZ) versus temsirolimus (TEM) in patients (pts) with advanced clear-cell renal cell carcinoma (aCCRCC) of intermediate and poor-risk (the TemPa trial).
Authors: Nizar M. Tannir, Jeremy Aaron Ross, Catherine E Devine, Anuradha Chandramohan, Xuemei Wang, Zita Dubauskas Lim, Jennifer Wang, Paul Gettys Corn, Amado J. Zurita
Journal: Journal of Clinical Oncology (2018)

583 Background: TEM has level 1 evidence in aRCC with poor-risk disease. No trial compared a VEGFR-TKI with TEM as first-line (1L) therapy in this disease state. Methods: We randomly assigned (1:1) treatment-naïve pts with aCCRCC and &gt; = 3 risk factors (as per Hudes et al., NEJM 2007) to receive PAZ 800 mg po qd or TEM 25 mg iv qw. Pts were offered to receive the alternative agent at disease progression (PD). The primary endpoint was progression-free survival (PFS), and the secondary endpoints were overall survival (OS), objective response rate (ORR) and safety. A blinded radiologist assessed the radiographic response using RECIST v1.1. A sample size of 90 pts was based on an assumption of improved median PFS from 3.8 mo with TEM to 6.1 mo with PAZ. Pts were stratified by prior nephrectomy (Nx). The Kaplan-Meier method was used for PFS and OS analysis, and the Fisher’s exact test was used for comparison of ORR between PAZ and TEM. Results: The study was closed to new patient enrollment when the results of the CheckMate 214 and CABOSUN studies were presented at ESMO 2017. A total of 69 pts were eligible and evaluable (median age 61, 52 males [75%], 44 [64%] had poor-risk by IMDC criteria). Thirty pts [43%] had prior Nx. Thirty-five pts received PAZ (intermediate-risk 13, poor-risk 22) and 34 pts received TEM (intermediate-risk 12, poor-risk 22). Of the 69 pts, 67 had PD or died. The median PFS was 5.2 mo (95% CI: 3.6 –7.4) for PAZ and 2.6 mo (95% CI: 1.9 –4.2) for TEM (p = 0.16). In 1 pt, no date of death was available. Of the remaining 68 pts, 58 (85.3%) have died. The median OS was 12.0 mo (95% CI: 8.3–20.1) for PAZ and 7.4 mo (95% CI: 5.3–17.4) for TEM (p = 0.61). Sixty-eight pts were evaluable for response: 9/35 pts (26%) who received PAZ and 2/33 pts (6%) who received TEM had partial response (p = 0.046). Adverse events (AEs) were consistent with the known safety profiles of PAZ and TEM. Only 2 pts in each arm discontinued treatment due to AEs. Conclusions: PAZ extended PFS and OS and yielded a significantly higher ORR than TEM as 1L therapy in pts with aCCRCC and intermediate/poor-risk disease. Clinical trial information: NCT01392183.