tbuckley/cabot-search huggingface dataset:
Plasma miR371 for the detection of viable germ cell tumor in testicular cancer patients with enlarging or post chemotherapy residual nodes.
Authors: Lucia Nappi, Marisa Thi, Bernhard J. Eigl, Kim N. Chi, Martin Gleave, Alan I. So, Daniel Khalaf, Peter C. Black, Craig R. Nichols, Christian K. Kollmannsberger
Journal: Journal of Clinical Oncology (2018)

569 Background: The pathological constitution of post-chemotherapy residual disease (PCRD) or enlarged nodes in clinical stage I (CSI) patients (pts) with germ cell tumor (GCT) is guesswork, especially when tumor markers (β-HCG, AFP, LDH) are negative. Currently, accurate assessment requires clinical follow-up with imaging to establish patterns of growth or pathological confirmation with RPLND. A blood-based approach reliably to identify patients with non teratoma viable GCT (NTVGCT) would be valuable. Methods: miR371 extracted from plasma of 44 pts with GCT was analyzed by RT-PCR and relative expression calculated by the 2-ΔΔCt method. Plasma from healthy male volunteers was used as negative control while miR-93-5p as internal positive control. The sensitivity and specificity of miR371 were calculated correlating miR371 overexpression to the presence of relapsed/residual NTVGCT. Results: Fifty eight samples (20 CSI, 20 metastatic, 18 PCRD) were analyzed. Ten CSI pts presented with suspicious enlarging nodes (≥ IIA) and miR371 was overexpressed in 5/6 pts with confirmed tumor relapse. Neither CSI pts with unconfirmed enlarging nodes (n = 4) or with no signs of relapse (n = 10) presented high miR371 levels. miR371 was overexpressed in all the pre-chemotherapy metastatic pts (n = 10) and negative after chemotherapy (n = 10), with 4 pts presenting PCRD. miR371 was negative in all the pts with PCRD and no residual NTVGCT was detected in those pts by either pathology (n = 10) or clinical follow-up (n = 8). Sensitivity and specificity were 93.3% and 100%, respectively. Conclusions: Elevated plasma levels of miR371 correlate with the presence of NTVGCT and may lead to biological rather than radiographic assessment of active GCT. Since chemotherapy is first line option for NTVGCT while is inactive in teratoma, miR371 status may be used to select pts for chemotherapy or surgery. These encouraging findings inform upcoming North American trials for further definition of miR371 operating characteristics in all stages, sites of origin, gender and age specific GCTs. [Table: see text]
Government considers statutory regulation of public health professionals
Authors: Helen Jaques
Journal: BMJ (2012)

The Department of Health for England is considering compulsory statutory regulation of public health professionals after the Future Forum raised concerns about the lack of regulation of public health specialists who are not medically trained.

Professionals with a healthcare background such as nurses and scientists are able to take up public health registrar, consultant, and director posts without having completed a medical degree. However, they are not subject to compulsory regulation, unlike medically or dentally qualified …
P054 Monocyte-related biomarkers of rheumatoid arthritis development in undifferentiated arthritis patients – a pilot study
Authors: W Kurowska, E Kuca-Warnawin, A Radzikowska, M Maslinska, B Kwiatkowska, W Maslinski
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Introduction</h3> The enhanced/disturbed activities of monocytes are important for perpetuation and for development of rheumatoid arthritis (RA). Therefore, consistent analysis of monocytes activities and regulation of molecular pathways operating within monocytes, especially at early stages of RA development, may help to predict the progression to the full-blown disease. <h3>Objectives</h3> In this study we aimed to investigate the profile of miRNAs expression in circulating monocytes and monocyte-related cytokines in peripheral blood of individuals at undifferentiated arthritis (UA) stage as potential new biomarkers for RA development. <h3>Methods</h3> Magnetically sorted monocytes from peripheral blood (PB) of 20 individuals with UA served for total RNA isolation. RNA samples were used for microRNA profiling performed on the miRCURY LNA array. Concentrations of CCL3/MIP-1a, M-CSF, CCL2/MCP-1, IL-6, TNFa, IL-15 and eotaxin in sera of UA patients were measured using commercial ELISA assays. Verification of diagnosis after 4 years of follow-up led to the identification of patients who developed full-blown RA (UA→RA patients) and patients who remained in UA phase (UA→UA patients). Comparisons between patients groups were performed using two tailed Mann Whitney U test. <h3>Results</h3> Following computational unsupervised analysis we identified 50 miRNAs in PB monocytes that have the largest variation of expression across all patients samples. From these 50 miRNAs, expression of three miRNAs: miR-642b-5p (p=0.0380), miR-483–3 p (p=0.009), miR-371b-5p (=0.0381) were up-regulated, and two miRNAs: miR-25–3 p (=0.0317) and miR-378d (p=0.0059) were down-regulated in monocytes from UA→RA <i>vs</i> UA→UA patients. This specific pattern of miRNAs expression in circulating monocytes paralleled elevated IL-15 (p=0.003) and M-CSF (p=0.03) concentrations in sera of UA patients who progressed to RA. <h3>Conclusions</h3> Our results indicate that altered activity of monocytes can be detected at early stages of RA development. We found new miRNA candidates (miR-642b-5p, miR-483–3 p, miR-371b-5p, miR-25–3 p and miR-378d) differentially expressed in PB monocytes, and elevated concentrations of circulating IL-15 and M-CSF involved in monocyte activity and differentiation, as potential biomarkers identifying UA patients who subsequently developed RA. <h3>Acknowledgements</h3> This work was sponsored by grant No: UMO-2011/03/B/NZ6/05035 from National Science Centre and Polish Ministry of Science and Higher Education (core grant S/17). <h3>Disclosure of interest</h3> None declared
High-throughput sequencing of nodal marginal zone lymphomas identifies recurrent BRAF mutations
Authors: V. Pillonel, D. Juskevicius, C. K. Y. Ng, A. Bodmer, A. Zettl, D. Jucker, S. Dirnhofer, A. Tzankov
Journal: Leukemia (2018)

Nodal marginal zone lymphoma (NMZL) is a rare small B-cell lymphoma lacking disease-defining phenotype and precise diagnostic markers. To better understand the mutational landscape of NMZL, particularly in comparison to other nodal small B-cell lymphomas, we performed whole-exome sequencing, targeted high-throughput sequencing, and array-comparative genomic hybridization on a retrospective series. Our study identified for the first time recurrent, diagnostically useful, and potentially therapeutically relevant BRAF mutations in NMZL. Sets of somatic mutations that could help to discriminate NMZL from other closely related small B-cell lymphomas were uncovered and tested on unclassifiable small B-cell lymphoma cases, in which clinical, morphological, and phenotypical features were equivocal. Application of targeted gene panel sequencing gave at many occasions valuable clues for more specific classification.
Revalidation must be simplified and made fairer, GPs say
Authors: Matthew Limb
Journal: BMJ (2016)

GP representatives have rejected a call for revalidation to be suspended, but they have demanded that the process be simplified.

Delegates at a special BMA conference of local medical committees (LMCs) backed a demand for a simpler system and fewer appraisals after warnings that GPs were being robbed of time for direct patient care by bureaucratic processes.

Views were sharply divided on the value of revalidation and appraisals at the BMA meeting in London on 30 January. Stephanie De Giorgio, of Kent LMC, said that revalidation should be suspended immediately, “potentially with a view to scrapping it.”

“It has no evidence base to show it …
Tumor fraction in circulating free DNA as a biomarker of disease dynamics in metastatic prostate cancer.
Authors: Atish Dipankar Choudhury, Lillian Werner, Gavin Ha, Samuel Freeman, Justin Rhoades, Sarah Reed, Greg Gydush, Denisse Rotem, Christopher Lo, Mary-Ellen Taplin, Lauren Christine Harshman, Zhenwei Zhang, Edward P O'Connor, Jesse Boehm, Gad Getz, Matthew Meyerson, J. Christopher Love, William C. Hahn, Viktor Adalsteinsson
Journal: Journal of Clinical Oncology (2018)

195 Background: Quantification of circulating free DNA (cfDNA) has been proposed both as a prognostic biomarker and as a biomarker of response and resistance to therapy. However, dynamics of cfDNA derived from both tumor and non-cancerous tissues through dense longitudinal monitoring over the course of treatment with multiple therapeutic modalities have not been well described. Methods: CfDNA isolated from banked and prospectively collected plasma samples from pts with metastatic castration-resistant prostate cancer (mCRPC) was subject to ultra-low pass (~0.1x coverage) whole genome sequencing (ULP-WGS). The fraction of cfDNA derived from tumor rather than non-cancerous tissues (i.e. the tumor fraction, or TFx) in each sample was estimated using a novel computational tool called ichorCNA, and was correlated with clinical features and response to therapy. Results: 663 plasma samples from 140 pts were included (median 3 samples/pt; range 1-20). TFx was correlated with the number of bone metastases (median TFx = 0.014 with no bone mets, 0.047 with 1-3, 0.190 for 4+), and with the presence of distant visceral mets (p &lt; 0.0001). In multi-variate analysis, TFx was positively correlated with Alk Phos (p = 0.0227) and negatively correlated with Hgb (p &lt; 0.001), but was not correlated with PSA (p = 0.75). All new treatment starts leading to &gt; = 30% PSA decline at &gt; = 6 weeks were associated with a decline in TFx from baseline when baseline TFx was &gt; 7% (median TFx change -92.2%, range -70.3% to -100%); however, TFx in patients being subsequently maintained on secondary hormonal therapy without radiographic progression was quite dynamic. The total yield of cfDNA derived from both tumor and non-cancerous tissues tracked closely with TFx, and did not markedly change with initiation of therapies expected to lead to generalized tissue damage, such as chemotherapy and radiation, over the time scales examined. Conclusions: Decline in TFx is a promising biomarker for initial response to therapy, but subsequent temporary rises in TFx do not necessarily indicate the cessation of clinical benefit from secondary hormonal therapies. Analysis of cfDNA may allow a window into short-term tumor dynamics not easily assayed through other methods.
Development of a radiomic signature for prediction of pathological complete response following neoadjuvant chemoradiotherapy in esophageal cancer.
Authors: Anupam Rishi, India Eaford, Geoffrey Zhang, Alexander Viera, Kujtim Latifi, Jessica M. Frakes, Jose Mario Pimiento, Jacques-Pierre Fontaine, Sarah E. Hoffe
Journal: Journal of Clinical Oncology (2018)

106 Background: Pivotal to personalized therapy is accurate pre-treatment patient selection based on predictive biomarkers. We developed a radiomic signature model to predict pathological complete response (pCR) following neoadjuvant chemo-radiotherapy (NACRT) in esophageal cancers. Methods: We retrospectively identified 68 patients with esophageal cancer, treated with NACRT followed by esophagectomy, with baseline 18F-fluorodeoxyglucose Positron Emission Tomography (PET) and computed tomography (CT) scans performed at our institution. In-house data-characterization algorithm was used to extract 3D radiomics features from the segmented primary disease. Prediction models were constructed and internally validated (2/3 rd training, 1/3 rd validation) using machine learning software. Cox regression hazard used to assess association with relapse free survival (RFS). Results: pCR was observed in 34 (50%) patients. A total of 126 features were extracted individually from PET and CT scans. On univariate analysis, 16 PET and 14 CT features were found to independently predict pCR. Three separate predictive models were built for CT, PET and combined CT+PET. Individually, both CT and PET had a good predictive power with AUC 0.74 and 0.730, respectively. Combined CT+PET radiomic features resulted in a significant improvement of predicting power, with AUC 0.856. Good discrimination (82.6%) was observed in validation dataset. Final model was: 13.439-34.632(CT-eccentricity)-2.469(CT-LRLGE)+10.626(CT-Gnorm_HIE)-2.094(CT-SD_Lac2)-19.337(CT-FD_SD)-0.344(PET-Contrast), where eccentricity is shape feature, LRLGE a gray level run length feature, Gnorm_HIE gray-level size zone feature, SD_Lac2 a fractal dimension feature. Stratifying patients with low vs. high radiomic signature score predicted RFS: median RFS 80.1 vs. 40.1 months; and 2-year RFS 77.4% vs. 52.6% [Hazard Ratio: 2.24, 95% CI 1.01-5.58], respectively. Conclusions: The developed radiomics signature models were highly predictive of pCR following NACRT. Further validation in larger data sets is needed to determine whether the model can predict clinical outcomes.
The sexually transmitted infection foundation (STIF) course
Authors: Fiona Ross
Journal: BMJ (2006)

General practitioners (GPs), GP registrars, practice nurses, trainees in obstetrics and gynaecology, general medical and infectious disease doctors—anyone who might need to assess a patient's risk for sexually acquired infections.

I did it in my third year on a general medical rotation.

I was considering a career in genitourinary medicine and felt it would be a good introduction to the topic.

It's a two day course consisting of lectures and workshops. A precourse …
Management of Patients With Febrile Neutropenia
Authors: Colin Bergstrom, Srikanth Nagalla, Arjun Gupta
Journal: JAMA Internal Medicine (2018)

This Teachable Moment uses the case of a woman in her 30s undergoing chemotherapy for stage 2A breast cancer who was hospitalized for febrile neutropenia to illustrate the need to avoid overtreatment for low-risk patients with this common oncological complication.
<i>Vital Signs</i>: Trends in Emergency Department Visits for Suspected Opioid Overdoses — United States, July 2016–September 2017
Authors: Alana M. Vivolo-Kantor, Puja Seth, R. Matthew Gladden, Christine L. Mattson, Grant T. Baldwin, Aaron Kite-Powell, Michael A. Coletta
Journal: MMWR Morbidity and Mortality Weekly Report (2018)

From 2015 to 2016, opioid overdose deaths increased 27.7%, indicating a worsening of the opioid overdose epidemic and highlighting the importance of rapid data collection, analysis, and dissemination.Emergency department (ED) syndromic and hospital billing data on opioid-involved overdoses during July 2016-September 2017 were examined. Temporal trends in opioid overdoses from 52 jurisdictions in 45 states were analyzed at the regional level and by demographic characteristics. To assess trends based on urban development, data from 16 states were analyzed by state and urbanization level.From July 2016 through September 2017, a total of 142,557 ED visits (15.7 per 10,000 visits) from 52 jurisdictions in 45 states were suspected opioid-involved overdoses. This rate increased on average by 5.6% per quarter. Rates increased across demographic groups and all five U.S. regions, with largest increases in the Southwest, Midwest, and West (approximately 7%-11% per quarter). In 16 states, 119,198 ED visits (26.7 per 10,000 visits) were suspected opioid-involved overdoses. Ten states (Delaware, Illinois, Indiana, Maine, Missouri, Nevada, North Carolina, Ohio, Pennsylvania, and Wisconsin) experienced significant quarterly rate increases from third quarter 2016 to third quarter 2017, and in one state (Kentucky), rates decreased significantly. The highest rate increases occurred in large central metropolitan areas.With continued increases in opioid overdoses, availability of timely data are important to inform actions taken by EDs and public health practitioners. Increases in opioid overdoses varied by region and urbanization level, indicating a need for localized responses. Educating ED physicians and staff members about appropriate services for immediate care and treatment and implementing a post-overdose protocol that includes naloxone provision and linking persons into treatment could assist EDs with preventing overdose.
Fall in suspensions of GPs could be due to disorder during reforms
Authors: Helen Jaques
Journal: BMJ (2012)

The number of GPs who were suspended from work fell in the first half of 2011-12 for the first time in England since 2005, possibly as a result of less vigilant monitoring of performance in primary care during implementation of the government’s changes to the NHS, the National Clinical Assessment Service has said.

A total of 24 new suspensions were initiated between April and September 2011, down from 42 in the same period in 2010 and 43 from April to September …
ECHOCARDIOGRAPHY DERIVED PREDICTORS OF LONG-TERM OUTCOMES AFTER TAVR
Authors: Zaher Fanari, Mohammad Al-Akchar, Hadi Mahmaljy, Jennifer Nichelson, Kurt Heil, John Gill, Shalish Nandish, Nilesh Goswami, Gregory Mishkel, Jeffrey Goldstein
Journal: Journal of the American College of Cardiology (2018)
Cardiovascular Imaging With 18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography in Patients With Fibroinflammatory Disorders
Authors: Marat Fudim, Matthew P Thorpe, Leslie L Chang, E William St Clair, Lynne M Hurwitz Koweek, Andrew Wang
Journal: JACC. Cardiovascular imaging (2018)

Fibroinflammatory disorders are rare disorders characterized by chronic inflammation in combination with fibrosis that affect multiple organs. Among the fibroinflammatory disorders, 2 present with specific cardiovascular involvement, the immunoglobulin G4–related disease, which presents with
Welsh GPs to receive 1% pay rise
Authors: Abi Rimmer
Journal: BMJ (2017)

The 2017-18 Welsh GP contract will deliver a 1% pay increase, the Welsh government has said.

In a speech to the annual conference of the Welsh local medical committees in Newport on Saturday 4 March, Vaughan Gething, Welsh cabinet secretary for health, wellbeing, and sport, announced changes to the GP contract for 2017-18.1

The Welsh government said that as a result of contract changes agreed between itself, the BMA’s Welsh General Practitioner’s Committee (GPC Wales), and NHS Wales, investment in …
A phase I/II study of sitravatinib (MGCD-516) plus nivolumab in patients (pts) with metastatic clear-cell renal cell carcinoma (ccRCC) that progressed on prior VEGF-targeted therapy.
Authors: Pavlos Msaouel, Peter F. Thall, Ying Yuan, Isan Chen, Nizar M. Tannir
Journal: Journal of Clinical Oncology (2018)

TPS708 Background: Sitravatinib is a potent oral tyrosine kinase inhibitor that targets multiple receptor tyrosine kinase pathways including the vascular endothelial growth factor (VEGF), c-MET, and the Tyro3, Axl, and MER family. These pathways can allow tumor cells to escape immune surveillance despite immune checkpoint therapy. We therefore hypothesized that combining sitravatinib with the anti-PD1 antibody nivolumab will enhance antitumor immune responses in pts with ccRCC. The present study is designed to determine the optimal dose for this combination using efficacy and toxicity as co-primary outcomes. Methods: This phase I/II trial uses the sequentially adaptive late-onset EffTox design (Jin et al. J Am Stat Assoc 2014), which accounts for potential late-onset toxicities induced by immunotherapy, and allows dose-finding based on both the efficacy and toxicity of each successive dose. Eligible pts have metastatic ccRCC that progressed on prior VEGF-targeted therapy. Each pt receives initially a pre-specified daily oral dose, among 4 dose levels (60mg, 80 mg, 120 mg, 150 mg), of sitravatinib monotherapy for 2 weeks to allow the drug to reach a pharmacokinetic steady state. Nivolumab is then added at the dose of 240 mg intravenously every 2 weeks. A maximum of 60 pts will be treated in up to 20 cohorts of 3 pts each. Tumor biopsies and peripheral blood are collected to assess changes in tumor microenvironment and immune markers at 4 different time points: 1) at baseline, up to 14 days prior to initiation of sitravatinib, 2) following 2 weeks of sitravatinib monotherapy, 3) after 2 infusions of nivolumab in combination with sitravatinib, and 4) at disease progression. The primary endpoint is optimal dose of sitravatinib based on toxicity (by week 12) and disease control rate (at week 6). Secondary endpoints include objective response rate, progression-free survival, and overall survival. At deadline for abstract submission, 4 pts have been treated on this study. Clinical trial information: NCT03015740.
Modified XELIRI (capecitabine plus irinotecan) versus FOLFIRI (leucovorin, fluorouracil, and irinotecan), both either with or without bevacizumab, as second-line therapy for metastatic colorectal cancer (AXEPT): a multicentre, open-label, randomised, non-inferiority, phase 3 trial
Authors: Rui-Hua Xu, Kei Muro, Satoshi Morita, Satoru Iwasa, Sae Won Han, Wei Wang, Masahito Kotaka, Masato Nakamura, Joong Bae Ahn, Yan-Hong Deng, Takeshi Kato, Sang-Hee Cho, Yi Ba, Hiroshi Matsuoka, Keun-Wook Lee, Tao Zhang, Yasuhide Yamada, Junichi Sakamoto, Young Suk Park, Tae Won Kim
Journal: The Lancet Oncology (2018)
Adenocarcinoma Prostate With Neuroendocrine Differentiation
Authors: Girish Kumar Parida, Sarthak Tripathy, Shreya Datta Gupta, Abhinav Singhal, Rakesh Kumar, Chandrasekhar Bal, Shamim Ahmed Shamim
Journal: Clinical Nuclear Medicine (2018)

Ga-PSMA PET/CT is the upcoming imaging modality for staging, restaging and response assessment of prostate cancer. However, due to neuroendocrine differentiation in some of patients with prostate cancer, they express somatostatin receptors instead of prostate specific membrane antigen. This can be exploited and other modalities like Ga-DOTANOC PET/CT and F-FDG PET/CT should be used in such cases for guiding management. We hereby discuss a similar case of 67-year-old man of adenocarcinoma prostate with neuroendocrine differentiation, which shows the potential pitfall of Ga-PSMA PET/CT imaging and benefit of Ga-DOTANOC PET/CT and F-FDG PET/CT in such cases.
ANTITHROMBOTIC MANAGEMENT PATTERNS AND LONG-TERM OUTCOMES OF PATIENTS WITH ACUTE CORONARY SYNDROME UNDERGOING PERCUTANEOUS CORONARY INTERVENTION IN ASIA: AN EPICOR ASIA (LONG-TERM FOLLOW-UP OF ANTITHROMBOTIC MANAGEMENT PATTERNS IN ACUTE CORONARY SYNDROME PATIENTS IN ASIA) ANALYSIS
Authors: Shuning Zhang, Wei Wang, Jitendra Sawhney, Rungroj Krittayaphong, Hyo-Soo Kim, Vo Thanh Nhan, Stephen Lee, Tiong Kiam Ong, Chee Tang Chin, Stuart Pocock, Yong Huo, Juying Qian, Jun Bo Ge
Journal: Journal of the American College of Cardiology (2018)