tbuckley/cabot-search huggingface dataset:
Time-dependent dose distribution changes in prostate brachytherapy with iodine seeds.
Authors: Charles Teyssier, Magali Quivrin, Julie Blanc, Aurelie Petitfils, Fabienne Bidault, Luc Cormier, Damien Chambade, Etienne Martin, Gilles Crehange
Journal: Journal of Clinical Oncology (2018)

115 Background: Prostate brachytherapy with iodine seeds has a lasting dose delivery due to a long half life of I 125 (i.e. 2 months). To assess changes in dose metrics over time in low-dose rate prostate brachytherapy with iodine seeds and its relationship with rectal distension. Methods: One hundred and twenty-one post-implant CT scans performed every 2 weeks over 2 months after the treatment procedure were analyzed for dosimetry. Each CT-scan was performed without and with rectal enema. The following rectal parameters were collected to evaluate the influence of rectal distension over time: rectal volume, cross-sectional surface area (CSA) and relative CSA calculated from the first CT-scan chosen as reference (CT ref ). Results: Mean V150% and V200% of the prostate volume increased significantly over time (p &lt; 0.0001) and were significantly higher on postimplant CT scan performed at day 45 (CT 45 ) (p = 0.024 and p = 0.003, respectively) and CT scan performed at day 60 (CT 60 ) (p = 0.0005 and p &lt; 0.0001, respectively) compared with CT ref . All dosimetric parameters for the rectum were significantly increased over time. No rectal parameters were significantly different after rectal enema and there was no difference in doses delivered to the prostate and the rectum after rectal emptying. Conclusions: Increased hot spots in the prostate and the rectum during the 2 months following the procedure with iodine seeds may be related to prostate shrinkage rather than rectal distension. We hypothesize that radioelements with shorter half-life (Pd 103 or Cs 131 ) or HDR may give less toxicity, as dose distribution is less time-dependent.
Association of Patient Volume With Online Ratings of California Urologists
Authors: Gregory P. Murphy, Mohannad A. Awad, Anas Tresh, Thomas W. Gaither, E. Charles Osterberg, Nima Baradaran, Benjamin N. Breyer
Journal: JAMA Surgery (2018)

Author(s): Murphy, Gregory P; Awad, Mohannad A; Tresh, Anas; Gaither, Thomas W; Osterberg, E Charles; Baradaran, Nima; Breyer, Benjamin N
What is clinical governance?
Authors: Carl Gray
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 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>
Please, Doc, Take It All This Time
Authors: Bernard E. Trappey
Journal: JAMA (2018)

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Platelets Regulate Pulmonary Inflammation and Tissue Destruction in Tuberculosis
Authors: Katharine A. Fox, Daniela E. Kirwan, Ashley M. Whittington, Nitya Krishnan, Brian D. Robertson, Robert H. Gilman, José W. López, Shivani Singh, Joanna C. Porter, Jon S. Friedland
Journal: American Journal of Respiratory and Critical Care Medicine (2018)

Rationale: Platelets may interact with the immune system in tuberculosis (TB) to regulate human inflammatory responses that lead to morbidity and spread of infection.Objectives: To identify a functional role of platelets in the innate inflammatory and matrix-degrading response in TB.Methods: Markers of platelet activation were examined in plasma from 50 patients with TB before treatment and 50 control subjects. Twenty-five patients were followed longitudinally. Platelet–monocyte interactions were studied in a coculture model infected with live, virulent Mycobacterium tuberculosis (M.tb) and dissected using qRT-PCR, Luminex multiplex arrays, matrix degradation assays, and colony counts. Immunohistochemistry detected CD41 (cluster of differentiation 41) expression in a pulmonary TB murine model, and secreted platelet factors were measured in BAL fluid from 15 patients with TB and matched control subjects.Measurements and Main Results: Five of six platelet-associated mediators were upregulated in plasma of patients with TB compared with control subjects, with concentrations returning to baseline by Day 60 of treatment. Gene expression of the monocyte collagenase MMP-1 (matrix metalloproteinase-1) was upregulated by platelets in M.tb infection. Platelets also enhanced M.tb-induced MMP-1 and -10 secretion, which drove type I collagen degradation. Platelets increased monocyte IL-1 and IL-10 and decreased IL-12 and MDC (monocyte-derived chemokine; also known as CCL-22) secretion, as consistent with an M2 monocyte phenotype. Monocyte killing of intracellular M.tb was decreased. In the lung, platelets were detected in a TB mouse model, and secreted platelet mediators were upregulated in human BAL fluid and correlated with MMP and IL-1β concentrations.Conclusions: Platelets drive a proinflammatory, tissue-degrading phenotype in TB.
Evidence Underpinning the Centers for Medicare &amp; Medicaid Services' Severe Sepsis and Septic Shock Management Bundle (SEP-1)
Authors: Dominique J. Pepper, Dharmvir Jaswal, Junfeng Sun, Judith Welsh, Charles Natanson, Peter Q. Eichacker
Journal: Annals of Internal Medicine (2018)

This article has been corrected. To see what has changed, please read the Letter to the Editor and the authors' response. The original version (PDF) is appended to this article as a Supplement.
Everolimus Plus Endocrine Therapy for Postmenopausal Women With Estrogen Receptor–Positive, Human Epidermal Growth Factor Receptor 2–Negative Advanced Breast Cancer
Authors: Melanie Royce, Thomas Bachelot, Cristian Villanueva, Mustafa Özgüroglu, Sergio J. Azevedo, Felipe Melo Cruz, Marc Debled, Roberto Hegg, Tatsuya Toyama, Carla Falkson, Joon Jeong, Vichien Srimuninnimit, William J. Gradishar, Christina Arce, Antonia Ridolfi, Chinjune Lin, Fatima Cardoso
Journal: JAMA Oncology (2018)

Cotargeting the mammalian target of rapamycin pathway and estrogen receptor may prevent or delay endocrine resistance in patients receiving first-line treatment for advanced breast cancer.To investigate the combination of everolimus plus endocrine therapy in first-line and second-line treatment settings for postmenopausal women with estrogen receptor-positive, human epidermal growth receptor 2-negative advanced breast cancer.In the multicenter, open-label, single-arm, phase 2 BOLERO-4 (Breast Cancer Trials of Oral Everolimus) clinical trial, 245 patients were screened for eligibility; 202 were enrolled between March 7, 2013, and December 17, 2014. A median follow-up of 29.5 months had been achieved by the data cutoff date (December 17, 2016).Patients received first-line treatment with everolimus, 10 mg/d, plus letrozole, 2.5 mg/d. Second-line treatment with everolimus, 10 mg/d, plus exemestane, 25 mg/d, was offered at the investigator's discretion upon initial disease progression.The primary end point was investigator-assessed progression-free survival in the first-line setting per Response Evaluation Criteria in Solid Tumors, version 1.0. Safety was assessed in patients who received at least 1 dose of study medication and at least 1 postbaseline safety assessment.A total of 202 women treated in the first-line setting had a median age of 64.0 years (interquartile range, 58.0-70.0 years) with metastatic (194 [96.0%]) or locally advanced (8 [4.0%]) breast cancer. Median progression-free survival was 22.0 months (95% CI, 18.1-25.1 months) with everolimus and letrozole. Median overall survival was not reached; 24-month estimated overall survival rate was 78.7% (95% CI, 72.1%-83.9%). Fifty patients started second-line treatment; median progression-free survival was 3.7 months (95% CI, 1.9-7.4 months). No new safety signals were observed. In the first-line setting, the most common all-grade adverse event was stomatitis (139 [68.8%]); the most common grade 3 to 4 adverse event was anemia (21 [10.4%]). In the second-line setting, the most common adverse events were stomatitis and decreased weight (10 [20.0%] each); the most common grade 3 to 4 adverse event was hypertension (5 [10.0%]). There were 50 (24.8%) deaths overall during the study; 40 were due to study indication (breast cancer).The results of this trial add to the existing body of evidence suggesting that everolimus plus endocrine therapy is a good first-line treatment option for postmenopausal women with estrogen receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer.clinicaltrials.gov Identifier: NCT01698918.
Sphingosine kinase (SphK) mediates transactivation of the epidermal growth factor receptor (EGFR) by estrogen in breast cancer cells
Authors: Olga A. Sukocheva, Carol Wadham, Andrew Holmes, Mathew A. Vadas, Pu Xia
Journal: Cancer Research (2006)

2934  Breast cancer presents as estrogen receptor alpha (ERα) positive or negative. ERα- tumors have a poor prognosis, are resistant to hormonal therapies, and frequently show overexpression, amplification, and/or hyperactivation of growth factor receptors, such as the erbB family. Using cell line models that mimic this elevated growth factor signaling by EGFR and erbB-2 in MCF-7 breast cancer cells, we have previously shown that hyperactivation of downstream p42/44 MAPK results in the reversible loss of ERα expression, and that in addition to the direct effect of MAPK on ERα, indirect activation of NFkB by MAPK also plays a role. In this study, we set out to determine if the inihibition of MAPK activity in established ERα- breast cancer cell lines could restore ERα expression and further, if this re-expressed ERα could now restore anti-estrogen response. MAPK inhibition via treatment with U0126 in 3 ERα- breast cancer cell lines, the EGFR overexpressing SUM 229s, the EGFR/c-erbB-2 dual overexperssing SUM 190s, and the RhoC overexpressing SUM 149s resulted in the sustained re-expression of ERα protein in all 3 cell lines. To ascertain that this re-expressed ERα could now restore anti-estrogen sensitivity, growth assays analyzing the effects of 4-hydroxy-tamoxifen (4HT) and the pure antiestrogen ICI 182,780 (faslodex) at 10-7 M alone, 5 μM U0126 alone, or the combination of 4HT or ICI and U0126 on cell proliferation were performed by WST-1 assay. ERα- SUM 229 and 149 cells were resistant to both 4HT and ICI. While having no growth inhibitory effects on its own, 5 μM U016 restored the growth inhibitory effects of both 4HT and ICI in ERα- SUM 229 cells, but not in SUM 149 cells. To determine if these in vitro cell line results would extrapolate to a real breast tumor situation, ERα- tumor specimens were obtained from the Tissue Procurement Core. Tumors were minced and divided evenly into a baseline sample and into tissue culture dishes containing medium alone, or supplemented with 10 μM U0126 or vehicle control DMSO. The minced tumor specimens in medium plus or minus U0126 were incubated at 37oC/5%CO2 for 20 hours. RNA was prepared from all treatment groups and analyzed for ERα mRNA level by qRT-PCR. Of the 12 tumors received to date, 6 displayed increased ERα mRNA levels after treatment with U0126. Collectively, these data are supportive of our hypothesis that there exists a population of ERα- tumors where upregulated growth factor signaling is directly involved in the generation of the ERα- phenotype by repressing ERα expression. Importanly, these data suggest that this reversible downregulation may be targeted clinically such that this repression can be reversed by inhibiting signaling through MAPK, resulting in re-expression of ERα and perhaps restoration of tamoxifen sensitivity.
Broad‐Spectrum Neutralization of Pore‐Forming Toxins with Human Erythrocyte Membrane‐Coated Nanosponges
Authors: Yijie Chen, Mengchun Chen, Yue Zhang, Joo Hee Lee, Tamara Escajadillo, Hua Gong, Ronnie H. Fang, Weiwei Gao, Victor Nizet, Liangfang Zhang
Journal: Advanced Healthcare Materials (2018)

Abstract Neutralization of bacterial toxins has become a compelling approach to treating bacterial infections as it may pose less selective pressure for the development of bacterial resistance. Currently, the majority of toxin neutralization platforms act by targeting the molecular structure of the toxin, which requires toxin identification and customized design for different diseases. Therefore, their development has been challenged by the enormous number and complexity of bacterial toxins. Herein, biomimetic toxin nanosponges are formulated by coating membranes of human red blood cells (hRBCs) onto polymeric nanoparticles, which act as a toxin decoy to absorb and neutralize a broad‐spectrum of hemolytic toxins regardless of their molecular structure. When tested with model pore‐forming toxins, including melittin, α‐hemolysin of methicillin‐resistant Staphylococcus aureus , listeriolysin O of Listeria monocytogenes , and streptolysin O of Group A Streptococcus , the hRBC nanosponges are able to completely inhibit toxin‐induced hemolysis in a concentration‐dependent manner. In addition, the nanosponge‐detained toxins show no cytotoxicity when tested on human umbilical vein endothelial cells and no lethality when injected into mice, which together indicate effective toxin neutralization. Overall, these results demonstrate the broad applicability and high effectiveness of the hRBC nanosponges as a novel antivirulence platform against hemolytic toxins from various strains of bacteria.
Abstract 14705: Quality of Life Improvement in Coronary Artery Disease by Adenosine Magnetic Resonance Driven Management in Comparison to Conventional Approach
Authors: Peter Bernhardt, Carsten Hackenbroch, Jürgen Steinacker, Dominik Buckert
Journal: Circulation (2017)

Introduction:  Cardiac magnetic resonance imaging (CMR) currently plays a marginal role in the daily practice work-up of coronary artery disease (CAD). However, it provides high accuracy regarding inducible myocardial ischemia and necrosis. A CMR driven management of CAD patients may thus contribute to quality of life improvement.   Hypothesis:  This prospective and randomized trial aimed to prove improvement of quality of life assessed by the Seattle Angina Questionnaire (SAQ) using a CMR driven therapy approach in comparison to a conventional approach.   Methods:  Patients presenting with typical angina, positive prior stress test other than CMR, and intermediate CAD probability were included into the study. All patients had an indication for coronary x-ray angiography (CXA) and received optimal medical therapy according to current guidelines. Patients were randomized in a CMR or CXA group. All CMR subjects underwent adenosine (140μg/kg/min for 3 minutes) CMR at 3 Tesla (0.075 mmol Gd-DOTA/kg). Patients in the CMR group only underwent CXA, if myocardial ischemia was detected. All patients in the CXA arm underwent CXA procedure. PCI was performed in case of significant stenosis (>75% in LAD, CX, or RCA or >50% in LM).   Results:  CXA and CMR group did not differ significantly in the primary endpoint (p=0.16). Baseline SAQ was not different for all SAQ subscales. At one year SAQ subscales 1 (0.8 ±0.04 vs. 0,71 ± 0.06, p=0.007), 4 (0.82 ± 0.04 vs. 0.77 ± 0.04, p=0.046), and 5 (0.74 ± 0.05 vs. 0.65 ± 0.06, p=0.015) were significantly better in the CMR group. After two and three years of follow-up SAQ subscales did not differ between CXA and CMR group.   Conclusions:  Event free survival in CMR driven CAD management does not differ to conventional management. During the first year angina stability, treatment satisfaction, and disease perception is better in the CMR group. However, after one year, there is no significant difference. Hence, CMR driven management is safe and improves quality of life compared to conventional CAD management.
THE IMPACT OF PERCUTANEOUS CORONARY INTERVENTION USING THE NOVEL DYNAMIC CORONARY ROADMAP SYSTEM
Authors: Takayuki Yabe, Toshiya Muramatsu, Reiko Tsukahara, Masatsugu Nakano, Yukako Takimura, Hideyuki Takimura, Mami Kawano, Tasuku Hada
Journal: Journal of the American College of Cardiology (2018)
Editorial: Ensuring the Future of Rheumatology: A Multi‐Dimensional Challenge and Call to Action
Authors: William F. Harvey, Afton L. Hassett, Sharad Lakhanpal
Journal: Arthritis & Rheumatology (2018)

Arthritis Care & Research (2) project a startling picture of the future of the rheumatology workforce in the US.The 2015 Rheumatology Workforce study describes how, based on a variety of contributing factors, there will be inadequate numbers of practicing rheumatologists and rheumatology health professionals to care for patients with rheumatic and musculoskeletal diseases in the coming years.It further describes how limitations in our training pipeline may exacerbate this situation.These two important articles serve as a call to action to understand and address the wide range of factors that contribute to these issues.This will require important strategic initiatives by professional societies, government, practice groups, and training programs in order to assure a healthy and vibrant rheumatology workforce.Indeed, the new strategic plan for the American College of Rheumatology (ACR) represents an important starting point for this process.In this editorial, we will summarize some key workforce study findings presented in the articles by Bolster et al (1) and Battafarano et al (2) and highlight some of the key strategies to consider as we rise to meet these challenges.
The chief operating officer of NHS Evidence
Authors: Kieran Walsh
Journal: BMJ (2009)

At school I was interested in studying medicine, but was advised not to apply because I hadn’t taken O level physics. I didn’t have a physics O level because, in my class, the boys studied physics and the girls biology! I didn’t lose my desire to study medicine, though, and eventually went to medical school after taking a first degree in physiology.

Two main reasons really. Firstly, an interest in preventing disease, stimulated early in my medical training by seeing a large number of patients on the wards with potentially preventable cardiovascular disease; and secondly, an interest in the evidence base behind different treatment options. Early in my clinical experience, I was struck …
ETIOLOGIES AND TRENDS OF 90-DAY READMISSIONS AFTER SPONTANEOUS CORONARY ARTERY DISSECTION (SCAD): A NATIONAL POPULATION-BASED COHORT STUDY
Authors: Byomesh Tripathi, Fnu Hafeez Hassan, Michael Viray, Jasmin Martinez Castellanos, Emiliana Franco Ladron De Guevara, Saima Dean, Harshil Shah, Sanjog Kalra, Raphael Bonita, Aman Amanullah, Jon George, Gregg Pressman, Vincent Figueredo
Journal: Journal of the American College of Cardiology (2018)
Comparison of bimodality versus trimodality therapy for esophageal or gastroesophageal junction (GEJ) cancer: Experience from the Princess Margaret Cancer Centre.
Authors: Akina Natori, Hao-Wen Sim, Bryan Anthony Chan, Peiran Sun, Stephanie Moignard, Daniel Yokom, Charles Henry Lim, Di Maria Jiang, Lucy Xiaolu Ma, Eric Xueyu Chen, Geoffrey Liu, Jennifer J. Knox, Gail Elizabeth Darling, Johnathan Chi-Wai Yeung, Rebecca Wong, Sara Hafezi-Bakhtiari, James Conner, Patrik Rogalla, Raymond Woo-Jun Jang, Elena Elimova
Journal: Journal of Clinical Oncology (2018)

4066 Background: There are no phase 3 trials comparing definitive chemoradiation (bimodality) vs. perioperative chemoradiation (trimodality) for locoregional esophageal/GEJ cancer. Methods: A retrospective analysis (2011-2016) compared bimodality and trimodality therapy in patients (pts) with locoregional esophageal/GEJ cancer treated with curative intent. Overall survival (OS) and disease-free survival (DFS) were calculated from the date of diagnosis. Uni- and multivariable Cox proportional hazards regression adjusted for patient and disease factors. Results: Of 141 patients, 107 (76%) were male. Mean ages were 66.7 ± 12.4 years (bimodality; N = 57) and 58.6 ± 11.3 years (trimodality; N = 84). For bimodality pts, 49% had adenocarcinoma (adeno) and 51% had squamous cell carcinoma (SCC). For trimodality pts, 76% had adeno and 24% had SCC. Bimodality pts received a higher radiation dose compared to trimodality pts (59.4 ± 7.2 vs. 44.9 ± 5.8 Gy). We found that trimodality therapy significantly improved OS and DFS compared to bimodality therapy (4-year OS: 40% vs. 31%, HR 0.56, 95%CI 0.36-0.87, p = 0.008; 4-year DFS: 33% vs. 23%, HR 0.60, 95%CI 0.40-0.90, p = 0.01). This difference was confined to the subgroup with adeno histology (OS: HR 0.28, 95%CI 0.16-0.47, p < 0.001; DFS: HR 0.26, 95%CI 0.16-0.43, p < 0.001). In the SCC subgroup, OS and DFS were similar (OS: HR 1.30, 95%CI 0.48-2.64, p = 0.77; DFS: HR 0.91, 95%CI 0.43-1.94, p = 0.82). Using multivariable regression with AIC backward selection, the only retained prognostic factors were treatment modality (p < 0.001) and histology (p = 0.002). Conclusions: Our findings support preferential use of trimodality therapy for pts with adeno histology given superior OS and DFS, whereas bimodality and trimodality therapy appeared comparable in pts with SCC histology. Pending confirmation in a larger series with longer follow-up, these findings suggest differential treatment algorithms for locoregional esophageal and GEJ cancer based on tumor histology.
UTILIZATIONS OF EMERGENCY MEDICAL SERVICES BY PATIENTS WITH ST-SEGMENTS ELEVATION ACUTE MYOCARDIAL INFARCTION IN CHINA: FINDINGS FROM CHINA MYOCARDIAL INFARCTION (CAMI) REGISTRY
Authors: Jingang Yang, Haiyan Xu, Wei Li, Xiaojin Gao, YueJin Yang
Journal: Journal of the American College of Cardiology (2018)