tbuckley/cabot-search huggingface dataset:
A national survey of radiation oncologists and urologists on active surveillance for low-risk prostate cancer.
Authors: Albert Kim, Robert Abouassaly, Simon P. Kim
Journal: Journal of Clinical Oncology (2018)

133 Background: Due to the growing concerns about over-diagnosis and overtreatment of localized prostate cancer (PCa), active surveillance (AS) has become an integral part of clinical practice guidelines. However, many men with low-risk PCa still receive primary therapy with surgery or radiation. Little is known about the barriers regarding the use of AS in clinical practice. To address this, we performed a national survey of radiation oncologists and urologists assessing the current attitudes and treatment for patients diagnosed with low-risk PCa. Methods: From January to July of 2017, 915 radiation oncologists and 940 urologists were surveyed about perceptions of AS for low-risk PCa. The survey queried respondents about their opinions and attitudes towards AS and treatment recommendations for a patient having low-risk PCa with clinical factors varying from patient age (55, 65 and 75 years old), PSA (4 and 8 ng per dl), and tumor volume for Gleason 3+3 disease (2, 4 and 6 cores). Pearson chi-square and multivariable logistic regression were used to identify respondent differences in treatment recommendations for low-risk PCa. Results: Overall, the response rate was 37.3% (n = 691) and similar for radiation oncologists and urologists (35.7% vs. 38.7%; p = 0.18). While both radiation oncologists and urologists viewed AS as effective for low-risk PCa (86.5% vs. 92.0%; p = 0.04), radiation oncologists were more likely to respond that AS increases patient anxiety (49.5% vs. 29.5%; p &lt; 0.001). Overall, recommendations varied markedly based on patient age, PSA, number of cores positive for Gleason 3+3 prostate cancer and respondent specialty. For a 55-year-old male patient with a PSA 8 and 6 cores of Gleason 6 PCa, recommendations of AS were low for both radiation oncologists and urologists (4.4 % vs. 5.2%; adjusted OR: 0.6; p = 0.28). For a 75-year-old patient with a PSA 4 and 2 cores of Gleason 6 PCa, radiation oncologists and urologists most often recommended AS (89.6% vs. 83.4%; adjusted OR: 0.5; p = 0.07). Conclusions: While both radiation oncologists and urologists consider AS effective in the clinical management of low-risk PCa, its use varies markedly by patient age, PCa volume, PSA and physician specialty.
A career in pre-hospital emergency medicine
Authors: Vera Nina Gotz
Journal: BMJ (2013)

The General Medical Council now recognises pre-hospital emergency medicine as a subspecialty. <b>Vera Nina Gotz</b> speaks to Robert Major, consultant in emergency and pre-hospital medicine, chair of the department of pre-hospital and retrieval medicine, and a network coordination consultant at Addenbrooke’s Hospital, Cambridge, about what a career in this new area of emergency medicine and anaesthetics entails
Troubled times ahead for IMGs
Authors: Umesh Prabhu
Journal: BMJ (2006)

The new immigration changes will have devastating effects on the 12 000 to 15 000 international medical graduates (IMGs) who are either already working in the NHS or who have passed the Professional and Linguistic Assessment Board's exam and are looking for jobs in the NHS.

To introduce such a rule without any discussions and without any consideration as to the effect that …
Contextual control of skin immunity and inflammation by <i>Corynebacterium</i>
Authors: Vanessa K. Ridaura, Nicolas Bouladoux, Jan Claesen, Y. Erin Chen, Allyson L. Byrd, Michael G. Constantinides, Eric D. Merrill, Samira Tamoutounour, Michael A. Fischbach, Yasmine Belkaid
Journal: The Journal of Experimental Medicine (2018)

How defined microbes influence the skin immune system remains poorly understood. Here we demonstrate that Corynebacteria, dominant members of the skin microbiota, promote a dramatic increase in the number and activation of a defined subset of γδ T cells. This effect is long-lasting, occurs independently of other microbes, and is, in part, mediated by interleukin (IL)-23. Under steady-state conditions, the impact of Corynebacterium is discrete and noninflammatory. However, when applied to the skin of a host fed a high-fat diet, Corynebacterium accolens alone promotes inflammation in an IL-23-dependent manner. Such effect is highly conserved among species of Corynebacterium and dependent on the expression of a dominant component of the cell envelope, mycolic acid. Our data uncover a mode of communication between the immune system and a dominant genus of the skin microbiota and reveal that the functional impact of canonical skin microbial determinants is contextually controlled by the inflammatory and metabolic state of the host.
Abstract P5-21-26: T-DM1 activity in metastatic HER2-positive breast cancer patients who have received prior trastuzumab and pertuzumab: NSABP B-005
Authors: SR Tiwari, T Sussman, K Kota, HC Moore, AJ Montero, GT Budd, S Puhalha, J Abraham
Journal: Cancer Research (2018)

Abstract Background : The pivotal phase III EMILIA trial reported a progression free survival (PFS) rate of 9.6 months and an objective response rate of 43% with T-DM1 in patients with HER2-positive metastatic breast cancer previously treated with trastuzumab and a taxane. However, there is very limited data on the efficacy of T-DM1 in patients who have received prior pertuzumab either neoadjuvantly or as first line therapy in the metastatic setting. The primary goal of this study was to assess the clinical efficacy (tumor response rates and median duration on therapy) of T-DM1 in patients previously treated with pertuzumab and trastuzumab. Methods: After IRB approval, a cancer data registry and electronic pharmacy database were utilized to identify breast cancer patients receiving treatment with T-DM1 at Cleveland Clinic and University of Pittsburgh. Patients that received trastuzumab and pertuzumab, in either the neoadjuvant or metastatic setting, with baseline and follow up imaging available for review were identified. Patient charts were reviewed to collect accurate information about the treatment sequencing and outcomes. RECIST version 1.1 was utilized for tumor assessment and patients with measurable disease and non measurable disease were included in the study. Results: We identified a total of 23 patients with a median age of 55 years that met the inclusion criteria. 69% percent of patients received T-DM1 as first line or second line therapy and 31% received it as third line or later. All patients had at least 1 measurable lesion. Best overall response showed rates of complete response, partial response and stable disease of 17%, 26% and 22% respectively. 35% patients progressed on first assessment after start of treatment. The median duration on therapy was 5.3 months (range 3 weeks to 33 months) with 43% of patients receiving T-DM1 for greater than 6 months. Conclusion: Our results were comparable to those reported by EMILIA trial. T-DM1 has reasonable clinical efficacy in patients who have received prior treatment with pertuzumab and trastuzumab with an overall response rate of 43% and median duration on therapy of 5.3 months. Citation Format: Tiwari SR, Sussman T, Kota K, Moore HC, Montero AJ, Budd GT, Puhalha S, Abraham J. T-DM1 activity in metastatic HER2-positive breast cancer patients who have received prior trastuzumab and pertuzumab: NSABP B-005 [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 P5-21-26.
Fractal analysis improves the preoperative identification of atypical meningiomas
Authors: Marcin Czyz, Hesham Radwan, Jian Li, Chrisopher Filippi, Michael Schulder
Journal: Neuro-Oncology (2018)

There is no objective and readily accessible method for the preoperative determination of atypical characteristics of a meningioma grade. The aim of our study was to evaluate the feasibility of using fractal analysis as an adjunctive tool to conventional radiological techniques in identifying meningiomas with higher grade of malignancy. A group of 54 patients was enrolled into the study. 27 patients diagnosed with atypical (WHO Grade II) meningioma and a second age and sex matched group of 27 patients with benign (WHO Grade I) meningioma were analysed. Preoperative brain MR (T1W, post-gadolinium) were processed and analysed to determine the average (FDa) and maximum (FDm) fractal dimension of the contrast-enhancing region of the tumor. Box-count method and ImageJ 1.49 software were used. FDa and FDm as well as volume of the peritumoral oedema, incomplete peritumoral band, male sex and skull base localisation were included into the logistic regression model as possible predictors of malignancy. The cohort consisted of 34 women and 20 men, mean age of 62 ± 15 years. Fractal analysis showed good inter-observer reproducibility (Kappa >0.70). Both FDa and FDm were significantly higher in the atypical compared to the benign meningioma group (P < .0001). Multivariate logistic regression model reached statistical significance with P = .0001 and AUC = 0.87. The FDm, which was greater than 1.31 (odds ratio [OR], 12.30; P = .039), and non-skull base localisation (OR, .052; P = .015) were confirmed to be statistically significant predictors of the atypical phenotype. Fractal analysis of preoperative MR images appears to be a feasible adjunctive diagnostic tool in identifying meningiomas with potentially aggressive clinical behaviour.
Master Pass series—the perfect study aid?
Authors: Stephanie Young
Journal: BMJ (2005)

The MRCPsych examination induces anxiety and stress. It is common to regularly scrutinise shelves of many a bookstore in the hope of finding the “perfect” study aid. Fortunately, there have been improvements in the range and quality of these aids, and the Master Pass series is one example.

Part 1 now features extended matching items (EMIs), a technique not necessarily as familiar to candidates as old style MCQs. EMIs in Reilly and Raju's book …
Hospitals should provide gyms and healthier food to staff, says NHS England chief
Authors: Abi Rimmer
Journal: BMJ (2014)

Hospitals should provide gyms and healthier food to help NHS staff lose weight, the chief executive of NHS England has said.

In an interview with the Sun newspaper Simon Stevens said that he planned to introduce incentives to help doctors and nurses lose weight. According to the newspaper 700 000 of the NHS’s 1.3 million staff are overweight.1

The plans proposed by …
X-Linked Hypophosphatemia and FGF23-Related Hypophosphatemic Diseases: Prospect for New Treatment
Authors: Yuka Kinoshita, Seiji Fukumoto
Journal: Endocrine Reviews (2018)

Phosphate plays essential roles in many biological processes, and the serum phosphate level is tightly controlled. Chronic hypophosphatemia causes impaired mineralization of the bone matrix and results in rickets and osteomalacia. Fibroblast growth factor 23 (FGF23) is a bone-derived hormone that regulates phosphate metabolism. FGF23 excess induces hypophosphatemia via impaired phosphate reabsorption in the renal proximal tubules and decreased phosphate absorption in the intestines. There are several types of genetic and acquired FGF23-related hypophosphatemic diseases. Among these diseases, X-linked hypophosphatemia (XLH), which is caused by inactivating mutations in the phosphate-regulating endopeptidase homolog, X-linked (PHEX) gene, is the most prevalent form of genetic FGF23-related hypophosphatemic rickets. Another clinically relevant form of FGF23-related hypophosphatemic disease is tumor-induced osteomalacia (TIO), a paraneoplastic syndrome associated with FGF23-producing tumors. A combination of active vitamin D and phosphate salts is the current medical therapy used to treat patients with XLH and inoperative TIO. However, this therapy has certain efficacy- and safety-associated limitations. Several measures to inhibit FGF23 activity have been considered as possible new treatments for FGF23-related hypophosphatemic diseases. In particular, a humanized monoclonal antibody for FGF23 (burosumab) is a promising treatment in patients with XLH and TIO. This review will focus on the phosphate metabolism and the pathogenesis and treatment of FGF23-related hypophosphatemic diseases.
I want to start work in the United Kingdom as a junior house officer after I've finished my education in 18 months' time. What extra efforts should I make in order to secure a job?
Authors: Roger Charlton
Journal: BMJ (2004)

<i>Got 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.</i>
Antitumor Properties of RAF709, a Highly Selective and Potent Inhibitor of RAF Kinase Dimers, in Tumors Driven by Mutant RAS or BRAF
Authors: Wenlin Shao, Yuji M. Mishina, Yun Feng, Giordano Caponigro, Vesselina G. Cooke, Stacy Rivera, Yingyun Wang, Fang Shen, Joshua M. Korn, Lesley A. Mathews Griner, Gisele Nishiguchi, Alice Rico, John Tellew, Jacob R. Haling, Robert Aversa, Valery Polyakov, Richard Zang, Mohammad Hekmat-Nejad, Payman Amiri, Mallika Singh, Nicholas Keen, Michael P. Dillon, Emma Lees, Savithri Ramurthy, William R. Sellers, Darrin D. Stuart
Journal: Cancer Research (2018)

Resistance to the RAF inhibitor vemurafenib arises commonly in melanomas driven by the activated BRAF oncogene. Here, we report antitumor properties of RAF709, a novel ATP-competitive kinase inhibitor with high potency and selectivity against RAF kinases. RAF709 exhibited a mode of RAF inhibition distinct from RAF monomer inhibitors such as vemurafenib, showing equal activity against both RAF monomers and dimers. As a result, RAF709 inhibited MAPK signaling activity in tumor models harboring either BRAFV600 alterations or mutant N- and KRAS-driven signaling, with minimal paradoxical activation of wild-type RAF. In cell lines and murine xenograft models, RAF709 demonstrated selective antitumor activity in tumor cells harboring BRAF or RAS mutations compared with cells with wild-type BRAF and RAS genes. RAF709 demonstrated a direct pharmacokinetic/pharmacodynamic relationship in in vivo tumor models harboring KRAS mutation. Furthermore, RAF709 elicited regression of primary human tumor-derived xenograft models with BRAF, NRAS, or KRAS mutations with excellent tolerability. Our results support further development of inhibitors like RAF709, which represents a next-generation RAF inhibitor with unique biochemical and cellular properties that enables antitumor activities in RAS-mutant tumors.Significance: In an effort to develop RAF inhibitors with the appropriate pharmacological properties to treat RAS mutant tumors, RAF709, a compound with potency, selectivity, and in vivo properties, was developed that will allow preclinical therapeutic hypothesis testing, but also provide an excellent probe to further unravel the complexities of RAF kinase signaling. Cancer Res; 78(6); 1537-48. ©2018 AACR.
Mice with targeted Kras<sup>G12D</sup> and loss of p53 in the liver: A robust model for studying immunologic interventions for treating cholangiocarcinoma
Authors: Booyeon Julia Han, Nathania Figueroa, Brian Belt, Michael O'Dell, Aram F. Hezel, David Linehan
Journal: Journal of Clinical Oncology (2018)

281 Background: Inflammation in the tumor microenvironment—chronically elevated cytokines, chemokines, and inflammatory cells—promotes tumorigenesis. Cholangiocarcinoma (CC) is the most common liver malignancy within the biliary tree with few treatment options and a poor 5-year survival. CC tumors are characterized with a dense tumor stroma and abundant inflammatory immune cell infiltrate, yet little is known about the immune dynamics underlying the disease. Here, we characterize immune signaling pathways in human CC and a spontaneous mouse model of the disease to identify potential targets susceptible to immune based therapies. Methods: Histology and immunohistochemistry (IHC) were performed on archived human specimens and tissue microarrays of 52 CC specimens constructed under an IRB approved protocol to identify the prognostic significance of cytokine and immune markers. Peripheral blood, bone marrow, and tissue from mice with targeted activation of Kras G12D and loss of p53 (Kras-p53 -/- ) in the liver that spontaneously developed CC tumors versus normal controls were collected and analyzed by histology, IHC, quantitative gene expression, and flow cytometry based studies. Results: High levels of inflammatory leukocytes in human CC were predominantly of monocytic and granulocytic origin including macrophages (TAM) and granulocytic-myeloid derived suppressor cells (G-MDSC) respectively. Malignant cells expressed high levels of CCL2 and TAM stained positive for its cognate receptor CCR2. In addition, CD8 + and CD4 + T cells expressing PD-1 were associated with PD-L1 + tumor cells. Kras-p53 -/- mice developed CC tumors histologically similar to human disease: tumors had high levels of cytokines and induced myelopoiesis leading to significantly more monocytes and granulocytes in the bone marrow, blood, and spleen compared to normal liver controls. Tumors also expressed higher levels of CCL2 and PD-L1 with more CCR2 + TAMs and PD-1 + T cells compared to controls. Conclusions: Human CC utilizes immune signaling pathways and Kras-p53 -/- mice recapitulate the immune dynamics of the disease representing a model to study immune based therapies for treating CC.
I have GMC conditions on registration and can't find a post—even practices that can't find anyone else make some excuse. Any suggestions?
Authors: Adam Sandell
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.
Abstract 11921: Risk Stratification for Ventricular Arrhythmia in Patients With Repaired Tetralogy of Fallot (TOF) via Image-Based Computational Simulations: A Pilot Study
Authors: Mark J Cartoski, Adityo Prakosa, Plamen Nikolov, Patrick M Boyle, Philip J Spevak, Natalia Trayanova
Journal: Circulation (2016)

Introduction: Patients with repaired TOF have increased arrhythmia risk due to myocardial fibrosis, scar and right ventricular dilation. Current risk stratification lacks consistent predictive value and clinical practicality. We surmised that personalized models developed from cardiac late gadolinium enhancement MRI (LGE-MRI) could correctly assess risk of arrhythmia in patients with repaired TOF using our previously-validated Virtual Arrhythmia Risk Prediction (VARP) protocol. Methods: As a proof-of-concept retrospective study, we developed personalized 3D computational models of TOF hearts from LGE-MRI scans. Three patients with clinically disparate arrhythmia status were included: patient 1 (P1) had clinical episodes of sustained ventricular tachycardia (VT) and inducibility in electrophysiologic study (EPS); patient 2 (P2) had negative EPS despite documented runs of non-sustained VT; patient 3 (P3) had no clinical evidence of VT. Then, for each heart, we applied our VARP protocol to generate a computational model, including personalized representations of scar and fibrosis. We then assessed the inducibility of reentrant arrhythmia from 26 pacing sites. Results: For all three cases, VARP outcomes correlated with clinical observations. In the P1 model sustained VT was induced with rapid ventricular pacing, while only non-sustained VT was induced in the P2 model (Fig 1). No arrhythmia was induced in the P3 model. Reentrant wavefronts in P1 and P2 occurred near the right ventricular outflow tract (RVOT) or ventricular septal defect patch, common sites of reentry observed in EPS in patients with TOF (Fig 1). Conclusion: Application of the VARP approach in repaired TOF patients is feasible and has the potential to correctly identify patients with a high risk of developing arrhythmia. With additional validation this non-invasive technique could serve as an effective tool for longitudinal risk assessment and help guide clinical decision making.
EFFECT OF RANOLAZINE ON SYMPTOMS AND QUALITY OF LIFE IN PATIENTS WITH ANGINA IN THE ABSENCE OF OBSTRUCTIVE CORONARY ARTERY DISEASE: A RETROSPECTIVE COHORT STUDY
Authors: Vedant Pargaonkar, Jennifer Tremmel, Ingela Schnittger, Abha Khandelwal
Journal: Journal of the American College of Cardiology (2018)
Succeeding as a Hospital Doctor—The Experts Share Their Secrets (3rd ed.)
Authors: Jonathan Dewhurst
Journal: BMJ (2007)

The title of this book is somewhat misleading. I was expecting it to patronise me with tips and advice on where I've been going wrong. What I found was an informative book that took it as given that readers can find their way around hospitals and are prepared for busy on calls. It's written by experienced doctors, from an array of hospital specialties, as well as experts in finance, human resources, and medicolegal matters. Subjects covered are diverse, ranging from research to setting up private practice. The …
Diagnostic Performance of Fully Automated Pixel-Wise Quantitative Myocardial Perfusion Imaging by Cardiovascular Magnetic Resonance
Authors: Li-Yueh Hsu, Matthew Jacobs, Mitchel Benovoy, Allison D. Ta, Hannah M. Conn, Susanne Winkler, Anders M. Greve, Marcus Y. Chen, Sujata M. Shanbhag, W. Patricia Bandettini, Andrew E. Arai
Journal: JACC. Cardiovascular imaging (2018)

The authors developed a fully automated framework to quantify myocardial blood flow (MBF) from contrast-enhanced cardiac magnetic resonance (CMR) perfusion imaging and evaluated its diagnostic performance in patients. Fully quantitative CMR perfusion pixel maps were previously validated with microsphere MBF measurements and showed potential in clinical applications, but the methods required laborious manual processes and were excessively time-consuming. CMR perfusion imaging was performed on 80 patients with known or suspected coronary artery disease (CAD) and 17 healthy volunteers. Significant CAD was defined by quantitative coronary angiography (QCA) as ≥70% stenosis. Nonsignificant CAD was defined by: 1) QCA as <70% stenosis; or 2) coronary computed tomography angiography as <30% stenosis and a calcium score of 0 in all vessels. Automatically generated MBF maps were compared with manual quantification on healthy volunteers. Diagnostic performance of the automated MBF pixel maps was analyzed on patients using absolute MBF, myocardial perfusion reserve (MPR), and relative measurements of MBF and MPR. The correlation between automated and manual quantification was excellent (r = 0.96). Stress MBF and MPR in the ischemic zone were lower than those in the remote myocardium in patients with significant CAD (both p < 0.001). Stress MBF and MPR in the remote zone of the patients were lower than those in the normal volunteers (both p < 0.001). All quantitative metrics had good area under the curve (0.864 to 0.926), sensitivity (82.9% to 91.4%), and specificity (75.6% to 91.1%) on per-patient analysis. On a per-vessel analysis of the quantitative metrics, area under the curve (0.837 to 0.864), sensitivity (75.0% to 82.7%), and specificity (71.8% to 80.9%) were good. Fully quantitative CMR MBF pixel maps can be generated automatically, and the results agree well with manual quantification. These methods can discriminate regional perfusion variations and have high diagnostic performance for detecting significant CAD. (Technical Development of Cardiovascular Magnetic Resonance Imaging; NCT00027170)