tbuckley/cabot-search huggingface dataset:
5-ALA-guided resection of glioblastoma: a single-centre, retrospective analysis of progression pattern and survival
Authors: Keerthi Senthil, Rory J Piper, William Sage, Rohit Sinha, Raj Jena, Stephen Price
Journal: Neuro-Oncology (2018)

The EORTC-NCIC trial in glioblastoma showed a median overall survival (OS) rate of 14.6 months following resection and chemoradiotherapy. This poor prognosis is attributed to early invasion and almost inevitable progression with failure to achieve local control. However, improvement in progression-free survival (PFS) has been shown in the use of 5-aminolevulinic acid (5-ALA), a fluorescent agent which accumulates in tumour cells. It has been adopted as an intraoperative tool to enhance the identification of the tumour-brain boundary, even beyond contrast enhancement on preoperative MRI, and thus aims to improve local control. However, it is not yet evident if 5-ALA alters pattern of progression. We therefore investigated the survival and progression patterns of glioblastoma after 5-ALA-guided resection. We retrospectively identified all glioblastoma patients who underwent 5-ALA-guided resection between 2009–2014 and received chemoradiotherapy. PFS and OS were analysed using Kaplan-Meier and log-rank tests. Progression pattern was classified as local (<30mm from the resection margin) or distal. We identified 157 patients. OS was significantly longer in those with complete versus incomplete resection (median survival of 16.9 vs. 13.9 months; p=0.013; n=153). PFS was not significantly different between the groups (11.5 vs 7.5 months; p=0.118). 85 patients had available follow-up MRI with evidence of progression. 55/85 (66%) had complete and 30/85 (34%) had incomplete resections. Of those that relapsed after complete resection only 3/55 (5%) patients had at least one distal lesion. In contrast, after incomplete resection, 3/30 (10%) had distal relapse. From our 5-ALA cohort, we have found comparable median OS rates to the EORTC-NCIC trial. We confirm a significant improvement in OS in complete than in incomplete resection. Despite using 5-ALA, and compared to other non-5-ALA studies, we have not been able to show better local control or any change to rate of distant progression.
Recent progress in Lynch syndrome and other familial colorectal cancer syndromes
Authors: Patrick M. Boland, Matthew B. Yurgelun, C. Richard Boland
Journal: CA A Cancer Journal for Clinicians (2018)

Abstract The current understanding of familial colorectal cancer was limited to descriptions of affected pedigrees until the early 1990s. A series of landscape‐altering discoveries revealed that there were distinct forms of familial cancer, and most were related to genes previously not known to be involved in human disease. This review largely focuses on advances in our understanding of Lynch syndrome because of the unique relationship of this disease to defective DNA mismatch repair and the clinical implications this has for diagnostics, prevention, and therapy. Recent advances have occurred in our understanding of the epidemiology of this disease, and the advent of broad genetic panels has altered the approach to germline and somatic diagnoses for all of the familial colorectal cancer syndromes. Important advances have been made toward a more complete mechanistic understanding of the pathogenesis of neoplasia in the setting of Lynch syndrome, and these advances have important implications for prevention. Finally, paradigm‐shifting approaches to treatment of Lynch‐syndrome and related tumors have occurred through the development of immune checkpoint therapies for hypermutated cancers. CA Cancer J Clin 2018;68:217–231 . © 2018 American Cancer Society .
Abundant production of exopolysaccharide by EAEC strains enhances the formation of bacterial biofilms in contaminated sprouts
Authors: Quintin Borgersen, David T. Bolick, Glynis L. Kolling, Matthew Aijuka, Fernando Ruiz-Perez, Richard L. Guerrant, James P. Nataro, Araceli E. Santiago
Journal: Gut Microbes (2018)

Enteroaggregative E. coli (EAEC) is associated with food-borne outbreaks of diarrhea and growth faltering among children in developing countries. A Shiga toxin-producing EAEC strain of serotype O104:H4 strain caused one of the largest outbreaks of a food-borne infection in Europe in 2011. The outbreak was traced to contaminated fenugreek sprouts, yet the mechanisms whereby such persistent contamination of sprouts could have occurred are not clear. We found that under ambient conditions of temperature and in minimal media, pathogenic Shiga toxin-producing EAEC O104:H4 227-11 and non-Shiga toxin-producing 042 strains both produce high levels of exopolysaccharide structures (EPS) that are released to the external milieu. The exopolysaccharide was identified as colanic acid (CA). Unexpectedly, Shiga-toxin producing EAEC strain 227-11 produced 3-6-fold higher levels of CA than the 042 strain, suggesting differential regulation of the CA in the two strains. The presence of CA was accompanied by the formation of large biofilm structures on the surface of sprouts. The wcaF-wza chromosomal locus was required for the synthesis of CA in EAEC 042. Deletion in the glycosyltransferase wcaE gene abolished the production of CA in 042, and resulted in diminished adherence to sprouts when co-cultured at ambient temperature. In conclusion, this work suggests that copious production of CA may contribute to persistence of EAEC in the environment and suggests a potential explanation for the large Shiga toxin-producing EAEC outbreak in 2011.
GMC creates single set of guidelines for medical education
Authors: Abi Rimmer
Journal: BMJ (2015)

The General Medical Council has published a single set of standards for undergraduate and postgraduate medical education and training.

The standards replace Tomorrow’s Doctors , which is aimed at medical students, and The Trainee Doctor , aimed at postgraduate doctors in training, and come into effect in 2016 (www.gmc-uk.org/education/standards.asp …
NHS should develop staff into leaders and recruit “mavericks,” says King’s Fund
Authors: Matthew Limb
Journal: BMJ (2015)

NHS trust boards should plan effectively to develop staff as future leaders, including encouraging doctors to consider such roles and recruiting “mavericks,” a report by the think tank the King’s Fund recommends.

Its report on “talent management” highlights a “chronic absence” of members of black and other ethnic minority groups and women in senior and board leadership roles and says that more should also be done to improve diversity.1 In a blog for the fund the …
Junior doctors raise concern over “credentialing” during specialty training
Authors: Helen Jaques
Journal: BMJ (2013)

Junior doctors have raised concerns at the prospect of separate credentials being awarded for specific skills acquired during specialty training, arguing that such “credentialing” could erode working conditions and devalue training programmes.

In a training system that used credentialing, doctors would receive certification for their knowledge, skills, and competence in providing a particular service or performing a specific procedure.

Delegates at the BMA’s annual Junior Doctors Conference agreed that credentialing could damage training programmes, devalue the …
Minimally invasive surgery in the era of step-up approach for treatment of severe acute pancreatitis
Authors: Olga Morató, Ignasi Poves, Lucas Ilzarbe, Aleksandar Radosevic, Antonia Vázquez-Sánchez, Juan Sánchez-Parrilla, Fernando Burdío, Luís Grande
Journal: International Journal of Surgery (2018)
I would like to visit the United Kingdom as an observer in colorectal or endocrine surgery. How do I start the process?
Authors: Adam Poole
Journal: BMJ (2006)

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 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. <b>www.bmjcareers.com/advicezone</b>
Foundation training programme was oversubscribed for 2019
Authors: Abi Rimmer
Journal: BMJ (2019)

Almost 100 additional foundation training posts were created this year after the programme was oversubscribed by 425 places.

The Foundation Programme originally had 6974 places available. But Health Education England (HEE) said that 96 additional places were created after 425 applicants to the programme were placed on the reserve …
Diploma in aviation medicine (DAvMed)
Authors: Clare Hunter
Journal: BMJ (2005)

Contact for further information 

Anyone working in aviation medicine, including the aviation industry, aeromedical transport, and military aviation, or those who do Civil Aviation Authority (CAA) medicals.

I did it in 2004 during my military general duties time—in between preregistration house officer jobs and senior house officer jobs. (Most people do it later …
Safety and Efficacy of Pembrolizumab Monotherapy in Patients With Previously Treated Advanced Gastric and Gastroesophageal Junction Cancer
Authors: Charles S. Fuchs, Toshihiko Doi, Raymond W. Jang, Kei Muro, Taroh Satoh, Manuela Machado, Weijing Sun, Shadia I. Jalal, Manish A. Shah, Jean-Phillipe Metges, Marcelo Garrido, Talia Golan, Mario Mandala, Zev A. Wainberg, Daniel V. Catenacci, Atsushi Ohtsu, Kohei Shitara, Ravit Geva, Jonathan Bleeker, Andrew H. Ko, Geoffrey Ku, Philip Philip, Peter C. Enzinger, Yung-Jue Bang, Diane Levitan, Jiangdian Wang, Minori Rosales, Rita P. Dalal, Harry H. Yoon
Journal: JAMA Oncology (2018)

Therapeutic options are needed for patients with advanced gastric cancer whose disease has progressed after 2 or more lines of therapy.To evaluate the safety and efficacy of pembrolizumab in a cohort of patients with previously treated gastric or gastroesophageal junction cancer.In the phase 2, global, open-label, single-arm, multicohort KEYNOTE-059 study, 259 patients in 16 countries were enrolled in a cohort between March 2, 2015, and May 26, 2016. Median (range) follow-up was 5.8 (0.5-21.6) months.Patients received pembrolizumab, 200 mg, intravenously every 3 weeks until disease progression, investigator or patient decision to withdraw, or unacceptable toxic effects.Primary end points were objective response rate and safety. Objective response rate was assessed by central radiologic review per Response Evaluation Criteria in Solid Tumors, version 1.1, in all patients and those with programmed cell death 1 ligand 1 (PD-L1)-positive tumors. Expression of PD-L1 was assessed by immunohistochemistry. Secondary end points included response duration.Of 259 patients enrolled, most were male (198 [76.4%]) and white (200 [77.2%]); median (range) age was 62 (24-89) years. Objective response rate was 11.6% (95% CI, 8.0%-16.1%; 30 of 259 patients), with complete response in 2.3% (95% CI, 0.9%-5.0%; 6 of 259 patients). Median (range) response duration was 8.4 (1.6+ to 17.3+) months (+ indicates that patients had no progressive disease at their last assessment). Objective response rate and median (range) response duration were 15.5% (95% CI, 10.1%-22.4%; 23 of 148 patients) and 16.3 (1.6+ to 17.3+) months and 6.4% (95% CI, 2.6%-12.8%; 7 of 109 patients) and 6.9 (2.4 to 7.0+) months in patients with PD-L1-positive and PD-L1-negative tumors, respectively. Forty-six patients (17.8%) experienced 1 or more grade 3 to 5 treatment-related adverse events. Two patients (0.8%) discontinued because of treatment-related adverse events, and 2 deaths were considered related to treatment.Pembrolizumab monotherapy demonstrated promising activity and manageable safety in patients with advanced gastric or gastroesophageal junction cancer who had previously received at least 2 lines of treatment. Durable responses were observed in patients with PD-L1-positive and PD-L1-negative tumors. Further study of pembrolizumab for this group of patients is warranted.clinicaltrials.gov Identifier: NCT02335411.
Publisher Correction: Elastomeric sensor surfaces for high-throughput single-cell force cytometry
Authors: Ivan Pushkarsky, Peter Tseng, Dylan Black, Bryan France, Lyndon Warfe, Cynthia J. Koziol-White, William F. Jester, Ryan K. Trinh, Jonathan Lin, Philip O. Scumpia, Sherie L. Morrison, Reynold A. Panettieri, Robert Damoiseaux, Dino Di Carlo
Journal: Nature Biomedical Engineering (2018)
Postgraduate certificate in education (PGCE) as applied to medicine
Authors: Richard Hunt
Journal: BMJ (2005)

Anyone interested in teaching, including doctors, nurses, physiotherapists, and other professionals allied to medicine. It's designed for people who work full time.

2004, between my basic surgical rotation and applying for higher surgical training (specialist registrar) posts. It can take between one and three years to complete as a distance learning course.

I've always been involved in teaching undergraduates, junior doctors, and nursing staff but I did not know if I was doing it effectively. …
P002 How do glycans affect immune cells in rheumatoid arthritis?
Authors: A Molhoek, L Hafkenscheid, R Toes, S van Vliet, Y van Kooyk
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Introduction</h3> Anti-Citrullinated Protein Antibodies (ACPAs) are specific for Rheumatoid Arthritis (RA) and have been implicated in disease pathogenesis. The fragment antigen-binding domain (Fab) of ACPA was recently shown to be extensively glycosylated.<sup>1</sup> It is known that glycans play a key role in controlling innate and adaptive immunity,<sup>2</sup> however to date there is limited understanding on the mode of action of glycans in RA. We hypothesise that the glycans on ACPA interact with glycan binding receptors and thus modulate immune responses in RA. Therefore, our aim is to elucidate the glycan effect of ACPA and other glycans on immune cells of RA patients to increase our understanding of RA pathogenesis. <h3>Methods</h3> A whole blood flow assay was used to study glycan interactions with leukocytes. Leukocytes were isolated from blood and cells were incubated for 2 hours at 4°C with 15 µg/ml highly glycosylated ACPA and immunomodulatory glycoconjugates, such as sialic acid, Lewis-x, Lewis-y, mannose and as a negative control GlcNac. Glycan binding and identification of immune cell subsets was assessed with flow cytometry using a whole blood flow antibody panel. <h3>Results</h3> This study examined the glycan-binding capacity of leukocytes in healthy donors via the whole blood flow assay. B cells appear to be superior in their interaction capacity with a variety of glycans, including the Fab glycan on APCA. This is an important finding because B cells play a key role in the pathogenesis of RA, through their antigen presenting capacity as well as their production of ACPA. In future studies RA patients material will be used to assess the glycan binding capacity to immune cell and to elucidate their role in the pathogenesis of RA. <h3>Conclusions</h3> This study examined the glycan-binding capacity of leukocytes in healthy donors via the whole blood flow assay. B cells appear to be superior in their interaction capacity with a variety of glycans, including the Fab glycan on APCA. This is an important finding because B cells play a key role in the pathogenesis of RA, through their antigen presenting capacity as well as their production of ACPA. In future studies RA patients material will be used to assess the glycan binding capacity to immune cell and to elucidate their role in the pathogenesis of RA. <h3>References</h3> . Rombouts Y. Extensive glycosylation of ACPA-IgG variable domains modulates binding to citrullinated antigens in rheumatoid arthritis. Annals of the rheumatic diseases2016;75(3):578–85. . Johnson L. The regulatory power of glycans and their binding partners in immunity. <i>Trend in Immunology</i>2013;34(6):290–298. <h3>Disclosure of interest</h3> None declared
Application of the ASCO Value Framework and ESMO Magnitude of Clinical Benefit Scale to assess the value of abiraterone acetate (AA) and enzalutamide (E) in advanced prostate cancer: clinical value and cost considerations.
Authors: Sarah Wong, Louis Everest, Di Maria Jiang, Ronak Saluja, Kelvin K. Chan, Srikala S. Sridhar
Journal: Journal of Clinical Oncology (2018)

276 Background: AA and E improve overall survival (OS) in metastatic castration resistant prostate cancer (mCRPC). AA also improves OS in metastatic castration sensitive disease (mCSPC). However, concerns exist over the cost implications of earlier treatment versus the clinical benefit gained. We aimed to quantify and compare the clinical value of AA and E and their drug costs in both the mCRPC and mCSPC settings. Methods: We identified 6 randomized Phase 3 trials of AA and E in mCRPC and mCSPC. Net clinical benefit was quantified by the ASCO Value Framework version 2 (range &lt; 180) and ESMO MCBS version 1.1 (range 1-5)—both consider benefits in overall survival, progression free survival, and quality of life, against increase in drug toxicity. A higher score indicates greater value. Incremental cancer drug costs were also calculated, using average wholesale price from the REDBOOK and the trials’ reported duration of treatment. Results: (Table). Conclusions: AA and E administered in early mCSPC do not provide consistent increases in net clinical benefit compared to mCRPC, but they incur exponential cost considerations. Alternatives such as chemotherapy, which may provide similar net clinical benefit at less incremental costs, still warrant major consideration for clinicians and patients. Until more information is available to define the optimal sequencing of AA, E and other available treatment modalities, current cost implications may hinder moving these agents to earlier treatment settings.[Table: see text]
Serendipitous Diagnosis of Achalasia Cardia on a Radionuclide Study
Authors: Shrikant Solav, Sanjay Agarwal
Journal: Clinical Nuclear Medicine (2010)

Achalasia cardia is a motility disorder, involving the distal esophagus, resulting in elevated lower esophageal sphincter pressure, increased intraesophageal pressure, incomplete relaxation of lower esophageal sphincter in response to deglutition and loss of esophageal peristalsis. It usually presents between third and fifth decades of life with the most common symptom of dysphagia. We present a case of middle-aged lady who complained of intermittent vomiting after meal and excessive postprandial sense of fullness in abdomen. It was suspected to be related to delayed gastric emptying. Therefore, a gastric emptying time study was requested. The solid bolus of radioactive meal was held up in the lower end of esophagus, thereby suggesting achalasia. Barium meal examination confirmed the diagnosis.
Abstract P2-05-15: Oncotype DX Breast Recurrence Score®: Real-life utilization among node positive patients in Ontario
Authors: R Richardson, A Macchiusi, A Bhasin, C Takizawa
Journal: Cancer Research (2018)

Abstract Aims: The 21-gene Oncotype DX (ODX) Recurrence Score (RS) has been extensively validated to predict the risk of distant recurrence and the magnitude of response to hormone and chemotherapy in patients with ER+ N0 and N+ (up to 3 positive nodes) HER2- early stage breast cancer. Outcomes data from multiple large studies further confirm the assays clinical validity and utility. The test is currently reimbursed in Ontario for N0 but not for N1 patients. In 2016, a market access program has been initiated to address lack of data in current clinical practice in Ontario among N1 patients. It collects data assessing the real-life use of the test in Ontario and its impact on treatment decision. This analysis presents the interim analysis until end of May 2017. Methods : The program allows for prospective data collection in key breast cancer centers in Ontario. Through an online dedicated platform patient data are collected including classical pathological and clinical parameters (e.g. histology, tumor grade and size, ER, PR, and HER2 status), patients age, ODX Recurrence Score results and recommended treatment both before and after the test results have been reported. Results: A total of 7 qualified breast cancer centers or network of centers participated in the program and collected 90 cases so far. Study results demonstrated that ODX is used among a wide variety of patients profiles: 28% G1, 58% G2 and 14% of G3, 18% pre-, 12% peri- &amp; 69% are post-menopausal, 20% are aged 40-49, 24% are 50-59, 29% are 60-69 and 26% are 70 and older, 3% tumor are &amp;lt;1cm, 38% are 1-&amp;lt;2cm, 52% are 2-&amp;lt;5cm and 7% tumor size are &amp;gt;5cm. RS distribution is the following: &amp;lt;18 (67%), 18-30 (30%) and &amp;gt;30 (3%). In addition, pre-ODX 90% of patients had a treatment recommendation for chemo-hormonotherapy (CT-HT). Post-testing, the number of patients recommended CT-HT decreased to 36%, highlighting that the test reduces unnecessary use of CT. In fact, the ODX led to an overall 54% net reduction in chemotherapy. Conclusions: This real-life survey confirms that ODX provides critical information beyond clinical and pathological criteria. The assay changes treatment decisions among N+ patients in Ontario, sparing CT which could result in potential savings to the healthcare system. Citation Format: Richardson R, Macchiusi A, Bhasin A, Takizawa C. Oncotype DX Breast Recurrence Score®: Real-life utilization among node positive patients in Ontario [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 P2-05-15.
LncRNA PFL contributes to cardiac fibrosis by acting as a competing endogenous RNA of let-7d
Authors: Haihai Liang, Zhenwei Pan, Xiaoguang Zhao, Li Liu, Jian Sun, Xiaomin Su, Chaoqian Xu, Yuhong Zhou, Dandan Zhao, Bozhi Xu, Xuelian Li, Baofeng Yang, Yanjie Lu, Hongli Shan
Journal: Theranostics (2018)

Rationale: Cardiac fibrosis is associated with various cardiovascular diseases and can eventually lead to heart failure.Dysregulation of long non-coding RNAs (lncRNAs) has recently been recognized as one of the key mechanisms involved in cardiac diseases.However, the potential roles and underlying mechanisms of lncRNAs in cardiac fibrosis have not been explicitly delineated.Methods and Results: Using a combination of in vitro and in vivo studies, we identified a lncRNA NONMMUT022555, which is designated as a pro-fibrotic lncRNA (PFL), and revealed that PFL is up-regulated in the hearts of mice in response to myocardial infarction (MI) as well as in the fibrotic cardiac fibroblasts (CFs).We found that knockdown of PFL by adenoviruses carrying shRNA attenuated cardiac interstitial fibrosis and improved ejection fraction (EF) and fractional shortening (FS) in MI mice.Further study showed that forced expression of PFL promoted proliferation, fibroblast-myofibroblast transition and fibrogenesis in mice CFs by regulating let-7d, whereas silencing PFL mitigated TGF-β1-induced myofibroblast generation and fibrogenesis.More importantly, PFL acted as a competitive endogenous RNA (ceRNA) of let-7d, as forced expression of PFL reduced the expression and activity of let-7d.Moreover, let-7d levels were decreased in the MI mice and in fibrotic CFs.Inhibition of let-7d resulted in fibrogenesis in CFs, whereas forced expression of let-7d abated fibrogenesis through targeting platelet-activating factor receptor (Ptafr).Furthermore, overexpression of let-7d by adenoviruses carrying let-7d precursor impeded cardiac fibrosis and improved cardiac function in MI mice. Conclusion:Taken together, our study elucidated the role and mechanism of PFL in cardiac fibrosis, indicating the potential role of PFL inhibition as a novel therapy for cardiac fibrosis.