tbuckley/cabot-search huggingface dataset:
CARDIAC MIBG IMAGING MIGHT IDENTIFY PATIENTS WITH MILD TO MODERATE CHRONIC HEART FAILURE AND 30≤LVEF≤35% AT LOW RISK OF SUDDEN CARDIAC DEATH
Authors: Tsutomu Kawai, Takahisa Yamada, Takashi Morita, Yoshio Furukawa, Shunsuke Tamaki, Yusuke Iwasaki, Masato Kawasaki, Atsushi Kikuchi, Masahiro Seo, Iyo Ikeda, Eiji Fukuhara, Jun Nakamura, Makoto Abe, Kiyomi Kayama, Masatsugu Kawahira, Kazuya Tanabe, Masatake Fukunami
Journal: Journal of the American College of Cardiology (2018)
Data Analysis Strategies in Medical Imaging
Authors: Chintan Parmar, Joseph D. Barry, Ahmed Hosny, John Quackenbush, Hugo J.W.L. Aerts
Journal: Clinical Cancer Research (2018)

Abstract Radiographic imaging continues to be one of the most effective and clinically useful tools within oncology. Sophistication of artificial intelligence has allowed for detailed quantification of radiographic characteristics of tissues using predefined engineered algorithms or deep learning methods. Precedents in radiology as well as a wealth of research studies hint at the clinical relevance of these characteristics. However, critical challenges are associated with the analysis of medical imaging data. Although some of these challenges are specific to the imaging field, many others like reproducibility and batch effects are generic and have already been addressed in other quantitative fields such as genomics. Here, we identify these pitfalls and provide recommendations for analysis strategies of medical imaging data, including data normalization, development of robust models, and rigorous statistical analyses. Adhering to these recommendations will not only improve analysis quality but also enhance precision medicine by allowing better integration of imaging data with other biomedical data sources. Clin Cancer Res; 24(15); 3492–9. ©2018 AACR.
Initial whole blood-based gene expression profile assays in mCRPC pts.
Authors: Koji Tsumagari, Patrick Miller, Marcus Marie Moses, Elisa Ledet, A. Oliver Sartor
Journal: Journal of Clinical Oncology (2018)

370 Background: Although second generation androgen receptor (AR) targeting therapy, abiraterone (Abi) and enzalutamide (enza), improve therapeutic effect for patients of mCRPC, acquired resistance occurs. Biomarkers are clearly needed to predict the efficacy of AR targeting drugs for mCRPC patients and much work is occurring on this important issue. Circulating tumor cells are attractive biomaterials because of non-invasive collecting methods. In this study, we assessed whole blood RNA as a non-invasive methodology to access biomarkers of potential interest. Methods: We used whole blood (~5mL) preserved in PAXgene tubes from 10 patients (pts) with mCRPC with acquired resistance following Abi and 11 controls without prostate cancer. Total RNA was extracted followed by qRT-PCR for assessment of 10 transcripts including ARV7, HOXB13, GHLR2, KLK3, KLK2, FOXA1, SchLAP1, KIF2C, MIA, and NCAM1. All amplicons were normalized to β-actin. Results: ARV7 (2/10), GRHL2 (2/10), HOXB13 (4/10), KLK3 (7/10), and KLK2 (4/10) amplicons were detected only in the mCRPC prostate pts. FOXA1 (7/10) and SchLAP1 (3/10) amplicons were detected in mCRPC pts at higher concentrations in mCRPC pts as compared to controls ( p&lt; 0.001 and p = 0.02, respectively). In contrast, KIF2C (5/11), MIA (11/11), and NCAM1 (11/11) amplicons were present in pts but in lower concentrations in mCRPC as compared to controls (p = 0.03, p&lt; 0.001, and p&lt; 0.001, respectively). Conclusions: We identified 5 transcripts that can be detected from whole blood RNA assays only from PCa pts, additional transcripts were expressed at higher or lower concentrations as compared to controls. Although this is a small cohort, these findings highlight the potential role for whole blood RNA to assess mCRPC pts.
P075 Changes of metabolic biomarker levels upon anti-tnf therapy in rheumatoid arthritis
Authors: A Pusztai, E Végh, Á Horváth, S Szántó, G Szucs, A Hamar, A Domján, K Hodosi, I Seres, G Kerekes, Z Szekanecz
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Introduction</h3> Rheumatoid arthritis (RA) has been associated with cardiovascular disease and metabolic syndrome. Numerous pro-inflammatory cytokines (e.g. TNF-α, IL-1, IL-6) are released, which cytokines cause increased reactive oxygen species (ROS) production and thereby contribute to the increased lipid peroxidation and reduction of many antioxidants. These processes not only lead to the deterioration of joints and other tissues but may also contribute to comorbidities, such as atherosclerosis. <h3>Objectives</h3> The aim of this study was to assess the effects of anti-TNF therapy on different metabolic markers, such as PON1 (paraoxonase 1), arylesterase, chemerin and adiponectin. We also investigated whether these biomarkers correlated with various demographic, clinical and laboratory markers. <h3>Methods</h3> We treated 37 RA patients with either etanercept (ETN) or certolizumab pegol (CZP) in a 12 month follow-up study. Assessments were performed at baseline, and 3, 6 and 12 months after treatment initiation. Serum chemerin and adiponectin concentrations were measured by commercially available ELISA kits (R and D System, MN and USA). PON1 and arylesterase activities were measured by spectrophotometry. In addition, age, disease duration, disease activity (DAS28), CRP, anti-CCP, IgM rheumatoid factor and plasma lipid levels were also assessed. Arterial flow-mediated vasodilation (FMD), carotid intima-media thickness (cIMT) and arterial pulse-wave velocity (PWV) were assessed by ultrasound. <h3>Results</h3> Anti-TNF treatment resulted in a significant decrease in the levels of chemerin (p&lt;0.001) and adiponectin (p&lt;0.007) after 12 months. There were no significant changes in the levels of other metabolic biomarkers. We found the following correlations between the baseline values: the PON1 levels correlated with the age of patients (R=0.466, p=0.004). The adiponectin correlated with the disease activity (R=0.385, p=0.030), HDL-C (R=0.417, p=0.012) and the triglyceride levels (R=0.481, p=0.003). The total cholesterol correlated with the PWV (R=0.449, p=0.021) and the levels of the LDL-C (R=0.911, p&lt;0.001). The baseline triglyceride correlated with the IgM rheumatoid factor (R=0.343, p=0.021); and the levels of LDL-C correlated with the PWV values (R=0.444, p=0.023). <h3>Conclusions</h3> Metabolic factors, such as certain adipokines, PON1 and arylesterase may play a role in oxidative stress and atherosclerosis associated with RA. Anti-TNF treatment may affect adipokine levels. <h3>Acknowledgements</h3> The work is supported by the GINOP-2.3.2-15-2016- 00015/I-KOM TEAMING project. <h3>Disclosure of interest</h3> None declared
Basic hand surgery
Authors: Niroshan Sivathasan, Alun Yewlett
Journal: BMJ (2010)

The basic hand surgery course is a three day intensive programme that aims to equip the clinician with a fundamental understanding of the key facets of hand surgery. The convenor is Fortune Iwuagwu, a consultant hand and plastic surgeon at Broomfield Hospital, and the faculty tutors are all consultants.

This course is aimed primarily at junior surgical trainees (specialty training years 1-3) who deal with hand injuries, such as those in plastic surgery and orthopaedic surgery, but may also be useful for those in emergency medicine and general practice.

We did this course in …
EV20-mediated delivery of cytotoxic auristatin MMAF exhibits potent therapeutic efficacy in cutaneous melanoma
Authors: Emily Capone, Alessia Lamolinara, Daniela D'Agostino, Cosmo Rossi, Vincenzo De Laurenzi, Manuela Iezzi, Stefano Iacobelli, Gianluca Sala
Journal: Journal of Controlled Release (2018)

Cutaneous melanoma is one of the cancers with the fastest rising incidence and in its advanced metastatic form is a highly lethal disease. Despite the recent approval of several new drugs, the 5-year overall survival rate for advanced cutaneous melanoma is still below 20% and therefore, the development of novel treatments remains a primary need. Antibody-Drug Conjugates are an emerging novel class of anticancer agents, whose preclinical and clinical development has recently seen a remarkable increase in different tumors, including melanoma. Here, we have coupled the anti-HER-3 internalizing antibody EV20 to the cytotoxic drug monomethyl auristatin F (MMAF) to form a novel antibody-drug conjugate (EV20/MMAF). In a panel of human melanoma cell lines, this novel ADC shows a powerful, specific and target-dependent cell killing activity, independently of BRAF status. Efficacy studies demonstrated that a single administration of EV20/MMAF leads to a long-lasting tumor growth inhibition. Remarkably, the effect of this novel ADC was superior to the BRAF inhibitor vemurafenib in preventing kidney, liver and lung melanoma metastases. Overall, these results highlight EV20/MMAF as a novel ADC with promising therapeutic efficacy, warranting extensive pre-clinical evaluation in melanoma with high levels of HER-3 expression.
More than 80% of consultants have considered retiring early out of stress, survey finds
Authors: Abi Rimmer
Journal: BMJ (2015)

Over 80% of consultants have considered retiring early because of pressure at work, a survey has found.

The Hospital Consultants and Specialists Association surveyed 817 consultants about stress at work. Of the 755 respondents who answered a question in the survey on early retirement, 81% said that work related stress had led them to consider retirement earlier than they had previously thought. In addition, 73% said that they had had sleepless nights thinking about work, 80% said that they …
99mTc MDP SPECT-CT–Based Modified Mirels Classification for Evaluation of Risk of Fracture in Skeletal Metastasis
Authors: Saima Riaz, Humayun Bashir, Imran Khalid Niazi, Sumera Butt, Faisal Qamar
Journal: Clinical Nuclear Medicine (2018)

Mirels' scoring system quantifies the risk of sustaining a pathologic fracture in osseous metastases of weight bearing long bones. Conventional Mirels' scoring is based on radiographs. Our pilot study proposes Tc MDP bone SPECT-CT based modified Mirels' scoring system and its comparison with conventional Mirels' scoring. Cortical lysis was noted in 8(24%) by SPECT-CT versus 2 (6.3%) on X-rays. Additional SPECT-CT parameters were; circumferential involvement [1/4 (31%), 1/2 (3%), 3/4 (37.5%), 4/4 (28%)] and extra-osseous soft tissue [3%]. Our pilot study suggests the potential role of SPECT-CT in predicting risk of fracture in osseous metastases.
Review: Synovial Cell Metabolism and Chronic Inflammation in Rheumatoid Arthritis
Authors: Jane Falconer, Anne N. Murphy, Stephen P. Young, Andrew R. Clark, Stefano Tiziani, Monica Guma, Christopher D. Buckley
Journal: Arthritis & Rheumatology (2018)

Metabolomic studies of body fluids show that immune-mediated inflammatory diseases such as rheumatoid arthritis (RA) are associated with metabolic disruption. This is likely to reflect the increased bioenergetic and biosynthetic demands of sustained inflammation and changes in nutrient and oxygen availability in damaged tissue. The synovial membrane lining layer is the principal site of inflammation in RA. Here, the resident cells are fibroblast-like synoviocytes (FLS) and synovial tissue macrophages, which are transformed toward overproduction of enzymes that degrade cartilage and bone and cytokines that promote immune cell infiltration. Recent studies have shown metabolic changes in both FLS and macrophages from RA patients, and these may be therapeutically targetable. However, because the origins and subset-specific functions of synoviocytes are poorly understood, and the signaling modules that control metabolic deviation in RA synovial cells are yet to be explored, significant additional research is needed to translate these findings to clinical application. Furthermore, in many inflamed tissues, different cell types can forge metabolic collaborations through solute carriers in their membranes to meet a high demand for energy or biomolecules. Such relationships are likely to exist in the synovium and have not been studied. Finally, it is not yet known whether metabolic change is a consequence of disease or whether primary changes to cellular metabolism might underlie or contribute to the pathogenesis of early-stage disease. In this review article, we collate what is known about metabolism in synovial tissue cells and highlight future directions of research in this area.
Supporting diversity in surgical careers: flexibility in theatre uniforms
Authors: Samina Ali, Virginia Bowbrick
Journal: BMJ (2014)

Some women may be deterred from pursuing surgical careers because theatre uniforms go against their religious dress codes. <b>Samina Ali</b> and <b>Virginia Bowbrick</b> look at how flexibility in theatre scrubs can support Muslim women who wear the hijab and abaya, and how greater awareness of the provisions available could help to support diversity in surgical careers
IMPLEMENTATION OF A SHARED DECISION SUPPORT INTERVENTION FOR PATIENTS CONSIDERING DESTINATION THERAPY LEFT VENTRICULAR ASSIST DEVICE: THE DECIDE-LVAD TRIAL
Authors: Daniel D. Matlock, Jocelyn Thompson, Megan A. Morris, Colleen Kelley McIlvennan, Gracie Finnigan-Fox, Russell E. Glasgow, Erin C. Leister, Carmen Lewis, Larry Allen
Journal: Journal of the American College of Cardiology (2018)
Clinical Outcomes in Adolescents and Adults After the Fontan Procedure
Authors: Mark Dennis, Diana Zannino, Karin du Plessis, Andrew Bullock, Patrick J.S. Disney, Dorothy J. Radford, Tim Hornung, Leeanne Grigg, Rachael Cordina, Yves d’Udekem, David S. Celermajer
Journal: Journal of the American College of Cardiology (2018)
Lumbar Osteophyte Avid on 68Ga–Prostate-Specific Membrane Antigen PET/CT
Authors: Mads Ryø Jochumsen, Michael Alle Madsen, Lise Gammelgaard, Kirsten Bouchelouche
Journal: Clinical Nuclear Medicine (2018)

A 75-year-old man with recently diagnosed high-risk prostate cancer was referred for primary staging with Ga-prostate-specific membrane antigen (PSMA) PET/CT. The scan revealed intense Ga-PSMA uptake in a lumbar osteophyte on the right side of level L2/L3, whereas several other spinal osteophytes showed no Ga-PSMA uptake. MRI findings in the L3 vertebra was consistent with a benign Modic type 1 lesion, but MRI showed no signs of malignancy in the osteophyte with high Ga-PMSA uptake. This case presents an osteophyte as an addition to the list of potential benign pitfalls to be aware of when interpreting Ga-PSMA PET/CT.
Robotic-Assisted vs Laparoscopic Radical Nephrectomy
Authors: Marc A. Lubin, Ashutosh Tewari, Ketan K. Badani
Journal: JAMA (2018)

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GMC's response
Authors: Amanda Watson
Journal: BMJ (2004)

EDITOR—The article in GMC News 1 presented the headline figures of a poll we conducted of 1535 doctors who had passed the PLAB test between January and April 2003. The full results of the survey, together with a copy of the questionnaire we asked the doctors to complete, can be found on the registration pages of our website at www.gmc-uk.org/register. We were particularly interested …
Identification of novel liquid biopsy biomarker for monitoring the immune set point in both solid tumor and hematological malignancy patients.
Authors: David John King, Ryan Adams, Leslie Nangle, Elisabeth Mertsching, Kathy Ogilvie, Andrea Cubitt, John Mendlein
Journal: Journal of Clinical Oncology (2018)

52 Background: We identified an extracellular pathway that plays a role in modulating T cell activity in vivo, which we call the Resokine Pathway. The pathway specifically involves a 60 amino acid domain of the tRNA Synthetase for Histidine, which is an essential gene in all cells, including tumor cells, vis-a-vis protein synthesis. Methods: Circulating Resokine levels were measured in 466 plasma samples from patients bearing a number of different tumor types, as well as healthy individuals, using an ECLIA format with sensitivity to 5pM. Serum Resokine levels were also measured in tumor-bearing mice. Results: Low, Circulating Resokine Levels in Cancer Patients are Negligible Compared to Healthy Individuals: Resokine levels in healthy volunteers (n = 148) ranged from 8pM - &gt; 2333pM with 18% of the individuals possessing a level below 30pM. In contrast, levels measured across patients with all tumor types tested ranged from 20pM to &gt; 2333pM (above the upper limit of quantification) with only 4% of the patients possessing low levels, defined as &lt; 30pM; (P &lt; 0.0001). Tumors in Mice Induce Higher Circulating Resokine Levels: Resokine levels in serum from normal C57Bl6 mice ranged from 70 to 250pM (n = 10). Significantly higher levels (450-3000pM) were found in the serum of B16F10 tumor-bearing mice with up to a 10-fold increase in the mean serum level compared to healthy mice (p &lt; 0.001). Resokine levels were correlated with tumor size. Conclusions: Resokine levels correlate with tumor size in mice, and are elevated in human cancer patients. This is consistent with the hypothesis that tumors secrete Resokine, to avoid detection by the immune system. Measurement of levels of the Resokine protein may offer a new liquid biopsy biomarker for tracking immune cell activity in cancer patients. It may also be a target for therapeutic intervention but the pathway may be challenging to inhibit given the presumably higher levels at the tumor and that there are many splice variants of HARS with potential activity (Lo et al. Science 2014, 345:328-32). Acknowledgements: We would like to thank Jedd Wolchok and Phil Wong of MSKCC, New York for access to patient samples.
Foundation programme is oversubscribed for second year running
Authors: Helen Jaques
Journal: BMJ (2011)

The number of eligible applicants for the foundation programme has outstripped the number of places available for the second year in a row, the UK Foundation Programme Office (UKFPO) has confirmed. 

“As predicted earlier this year,” there are more applicants to the foundation programme starting in August 2012 than places currently available, the organisation has said.

To remedy the situation, applicants who did not provide proof of their right to work in the United Kingdom by 7 October 2011 will now be withdrawn from the process.

All applications from people with the right to work and remain in the UK will be ranked according to the Foundation Programme …
Frequency and prognostic role of tumor infiltrating lymphocytes and MMR status in advanced non-colorectal GI malignancies.
Authors: Uqba Khan, Ameer Hamza, Renny Abraham, Muhammad S Khurram, Tarik H. Hadid, Paul Mazzara, Zyad Kafri
Journal: Journal of Clinical Oncology (2018)

89 Background: Tumor infiltrating lymphocytes (TILs) and mismatch repair gene mutation (MMR) status are emerging biomarkers in immunotherapy. MMR status and TILs have significant clinical implications with respect to treatment with checkpoint inhibitors. We designed a study to determine the frequency and prognostic utility of TILs and MMR in advanced unresectable non-colorectal GI (NCGI) cancers. Methods: This is a retrospective cohort study of patients who were diagnosed with metastatic or unresectable NCGI cancers between 2009 and 2015 at St. John Hospital and Medical Center. Immunohistochemistry panels were performed on representative tissue sections for MMR testing. TILs were assessed on the hematoxylin and eosin stained slide of the same tissue section. MMR was interpreted as deficient (d) or proficient and TILs were categorized as ≤5 or &gt; 5 per high power field. Descriptive statistics were generated using frequency distributions, medians and means. Kaplan-Meier analysis was performed to determine the impact of TILS and MMR on survival; differences by factor were assessed with the Log_Rank test. Results: We analyzed 132 patients; the mean age at diagnosis was 66.7 years, 62.1% were male. All samples had proficient MMR status. The percentage of patients with TILs ≤ 5 was 46.2. There was no statistically significant difference in median overall survival (OS) by TILs when stratified by stage of tumor. When stratified by type of tumor, median OS by TILs level was significantly different only for hepatocellular cancers (HCC) (≤ 5 TILs, 86 days vs. &gt; 5 TILs 312 days, p = 0.031), table 1. Conclusions: Our study suggests that MMR-d tumors are quite rare in advanced NCGI malignancies. TILs can be present in tumor microenvironment of NCGI malignancies. Though the number of patients in our study was small, there was a statistically significant difference in median OS of patients with HCC when stratified by TILs status.[Table: see text]
Scientific methods and research techniques (SMaRT) course
Authors: Peter Featherstone, Elisabeth Harvey
Journal: BMJ (2012)

If you have ever wondered what constitutes medical research and how you might establish a project, get ethical approval, organise data collection, analyse your results, or present your findings, the scientific methods and research techniques (SMaRT) course is for you.

An understanding of research is essential for all doctors in training. We were both interested in doing some research but wanted to see what it would really be like before taking the plunge. 

We did this course in November 2011, when we were both year 5 specialty registrars in anaesthesia. Although the SMaRT course has been designed for those who have passed the fellowship of the Royal College of Anaesthetists exam, it is suitable for trainees from all backgrounds. Our group of delegates included a foundation year 2 doctor as well as trainees of various grades from medicine, surgery, and psychiatry.

The course is delivered by the University of …
Competences for the foundation programme Part 1: Clinical decision making
Authors: Ed Neville
Journal: BMJ (2005)

After the foundation programme was launched in August 2005, Career Focus asked the curriculum developers to unpack the required competences. In the first part of our new series, <i>Ed Neville</i> explains how clinical decision making will be developed and assessed in the foundation years. Future issues will look at other foundation competences, such as time management, team working, patient safety, and evidence based practice
NHS is set to train 60% more consultants than needed by 2020
Authors: Ingrid Torjesen
Journal: BMJ (2012)

The NHS will have 60% more consultants by 2020 if it continues to recruit and train hospital doctors at the rate it is doing now, a report from the Centre for Workforce Intelligence has estimated.

This scenario would provide the NHS with more fully trained hospital doctors than the current projected demand indicates, leaving many jobless and the money spent on their training wasted. Alternatively if all eligible doctors were given consultant posts, consultants’ salaries would cost the NHS £6bn a year in 2020—£2.2bn more than they cost in 2010.

The report, published this week, sets out the …