tbuckley/cabot-search huggingface dataset:
Evaluating changes in circulating tumor cell count in prostate cancer patients during androgen deprivation plus chemotherapy by using AxonDx enumeration device.
Authors: Reynolds Brobey, Robert J. Amato, Jeff Smith, Mehdi Dehghani, Kent Murphy, Yue Wang
Journal: Journal of Clinical Oncology (2018)

266 Background: Circulating tumor cell (CTC) counts have clinical utility as a prognostic marker in cancer. For prostate cancer (PCa), CTC counts ≥5 CTC/7.5 ml using the FDA-approved CellSearch system convey a negative prognosis with respect to overall survival, but the significance of changes in CTC count during treatment is not fully understood. To determine whether longitudinal CTC counts can be used as a prognostic and/or predictive marker of clinical outcome in PCa patients undergoing androgen deprivation therapy (ADT) plus chemotherapy, we used the AxonDx nCyte non-enrichment-based CTC detection and enumeration system to evaluate CTC counts at baseline, during, and after therapy in 18 patients for up to 11 months. Methods: Whole blood was drawn from PCa patients on clinical trials for ADT plus chemotherapy at PSA evaluation (±radiographic reevaluation) into vacutainers containing K3-EDTA and processed within 6 hr. PBMC containing nucleated cells harvested from 6 ml of whole blood were fixed, permeabilized and blocked with BSA buffer, and stained using a proprietary antibody cocktail containing DAPI, an anti-cytokeratin mixture, the pan-leukocyte marker CD45, and markers selective for granulocytes and lymphocytes. Stained cells were drawn onto 1.2 µm pore filters, washed, placed on counting slides, and analyzed. CTCs are identified as cytokeratin-positive, nucleus-positive and leukocyte marker-negative. Results: CTCs were obtained from 12 patients for 2-9 months at 2-7 time points; from 2 patients for 11 months at 5-7 time points, and from 4 patients for 1 month at 1 time point. We detected time-dependent changes in CTC counts following treatment that did not necessarily correlate with patient’s local prostate specific antigen (PSA) levels but were early indicators of subsequent increase in tumor burden. Conclusions: The AxonDx nCyte system can reliably detect CTCs from PCa patient samples that trend along with other signs of disease progression. CTCs can be used longitudinally for clinical monitoring of patients with PCa prior to signs of progression via tumor markers or scans during ADT plus chemotherapy, providing a reliable biomarker for PCa.
I have completed two years of medical school and recently did something very stupid. I have been cautioned for theft and was told this will be on my criminal record for two to three years. Am I still able to become a doctor and what barriers will I face? Whom do I need to inform? How much will this affect my career?
Authors: Brian Angus
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>
Trainees value consultant post location over all else, RCP says
Authors: Abi Rimmer
Journal: BMJ (2015)

Trainee physicians value the location of a job above all other factors when considering a consultant post, the Royal College of Physicians has found.

The college’s 2013-14 census surveyed consultant physicians in England, Wales, and Northern Ireland and received a 47% return rate.1 It found that respondents valued where they worked over all other factors and that most wanted to stay close to where they …
TAKOTSUBO CARDIOMYOPATHY SUPERIMPOSED TO HYPERTROPHIC CARDIOMYOPATHY PRESENTING AS CARDIOGENIC SHOCK: A DIAGNOSTIC CHALLENGE
Authors: Nicolas Isaza, Adriana Posada, Jhonattan Benavides, Mauricio E. Diaz, Daniel Isaza-Restrepo, Claudia Jaimes
Journal: Journal of the American College of Cardiology (2018)
Consultant numbers rising twice as fast as GP numbers
Authors: Abi Rimmer
Journal: BMJ (2015)

The number of full time equivalent (FTE) consultants rose by nearly 4% from 2013 to 2014, while that of GPs rose by just under 2%, show figures from the Health and Social Care Information Centre (HSCIC).

The figures show that, as at 30 September 2014, the total number of FTE staff working in the NHS in England was 1.2 …
CHARACTERISTICS AND DISTRIBUTION OF CALCIUM IN THE DISTAL LEFT MAIN BIFURCATION ASSESSED BY OPTICAL COHERENCE TOMOGRAPHY
Authors: Song-Yi Kim, Gary Mintz, Masaru Ishida, Mitsuaki Matsumura, Alec Goldberg, Allen Jeremias, Ziad Ali, Jane Cao, John Tang, Fernando Sosa, Jeffrey Moses, Elizabeth Haag, Richard Shlofmitz, Akiko Maehara
Journal: Journal of the American College of Cardiology (2018)
Love &amp; Other Vices
Authors: Marcia Willis
Journal: BMJ (2006)

Stryngs

Available from www.stryngs.com, SHCD03, 2006

Rating: ★★★★/5



This is the second long player from a band based in Cambridge and London. I had not come across them before. For those of you who don't want to read the whole of this review, I've given the album a rating so you can tell that I liked it.

Rating music is an odd thing to do. Writing about music is another strange activity, one prone to excess use of adjectives, misplaced metaphors, and fruitless efforts to pin down the indescribable. The 13 tracks …
<i>Notes from the Field</i>: Typhoid Fever Outbreak — Harare, Zimbabwe, October 2016–March 2017
Authors: William W. Davis, Prosper Chonzi, Kudzai P.E. Masunda, Lindsey M. Shields, Innocent Mukeredzi, Portia Manangazira, Emmaculate Govore, Rachael D. Aubert, Haley Martin, Elizabeth Gonese, John B. Ochieng, Bonaventure Juma, Hammad Ali, Kristi Allen, Beth A. Tippett Barr, Eric Mintz, Grace D. Appiah
Journal: MMWR Morbidity and Mortality Weekly Report (2018)
Association of Serum Retinol-Binding Protein 4 Concentration With Risk for and Prognosis of Amyotrophic Lateral Sclerosis
Authors: Angela Rosenbohm, Gabriele Nagel, Raphael S. Peter, Torben Brehme, Wolfgang Koenig, Luc Dupuis, Dietrich Rothenbacher, Albert C. Ludolph
Journal: JAMA Neurology (2018)

Knowledge about the metabolic states of patients with amyotrophic lateral sclerosis (ALS) may provide a therapeutic approach.To investigate the association between the onset and prognosis of ALS and serum retinol-binding protein 4 (RBP4) concentration as a biomarker for insulin resistance and vitamin A metabolism.Case-control design for risk factors of ALS; cohort design for prognostic factors within ALS cases. Between October 1, 2010, and June 30, 2014, a population-based case-control study with randomly selected controls was established based on the ALS Registry Swabia in southern Germany, with a target population of 8.4 million inhabitants. Response rates were 64.8% among the cases and 18.7% among the controls. The dates of analysis were April 2016 to May 2017.Serum samples were measured for RBP4. Information on covariates was assessed by an interview-based standardized questionnaire. Main outcomes and measures were adjusted odds ratios for risk of ALS associated with serum RBP4 concentration, as well as time to death associated with RBP4 concentration at baseline in ALS cases only. Conditional logistic regression was applied to calculate multivariable odds ratios for risk of ALS. Survival models were used in cases only to appraise their prognostic value.Data from 289 patients with ALS (mean [SD] age, 65.7 [10.5] years; 172 [59.5%] male) and 504 controls (mean [SD] age, 66.3 [9.8] years; 299 [59.3%] male) were included in the case-control study. Compared with controls, ALS cases were characterized by lower body mass index, less educational attainment, smoking, light occupational work intensity, and self-reported diabetes. The median serum RBP4 concentration was lower in ALS cases than in controls (54.0 vs 59.5 mg/L). In the multivariable model, increasing RBP4 concentration was associated with reduced odds for ALS (top vs bottom quartile odds ratio, 0.36; 95% CI, 0.22-0.59; P for trend <.001), which persisted after further adjustment for renal function and for leptin and adiponectin. Among 279 ALS cases during a median follow-up of 14.5 months, 104 died (mean [SD] age, 68.9 [10.3] years; 56 [53.9%] male). In this ALS cohort, an inverse association was found between serum RBP4 concentration as a continuous measure and survival.RBP4 was inversely related to risk for and prognosis of ALS, suggesting that vitamin A metabolism or impaired insulin signaling could be involved. Further research, including a prospective design and other biological markers, is necessary to clarify the role of insulin resistance in the pathogenesis of ALS.
DIFFERENCES IN CLINICAL PROFILE AND PROGNOSIS BETWEEN TAKOTSUBO SYNDROME AND THE REST OF MYOCARDIAL INFARCTION WITH NON-OBSTRUCTIVE CORONARY ARTERIES
Authors: Javier Lopez Pais, Barbara Izquierdo Coronel, Maria Jesus Espinosa Pascual, David Galan Gil, Juan Gorriz Magana, Rebeca Mata Caballero, Carlos Gustavo Martínez Peredo, Paula Awamleh, Joaquin Alonso Martin
Journal: Journal of the American College of Cardiology (2018)
POST-DISCHARGE BLEEDING AND SUBSEQUENT MAJOR CARDIOVASCULAR EVENTS IN CHINESE PATIENTS WITH ACUTE CORONARY SYNDROME WHO UNDERWENT PERCUTANEOUS CORONARY INTERVENTION: A NATIONAL WIDE MULTICENTRE PROSPECTIVE STUDY
Authors: Yundai Chen, Tong Yin, Shuyang Zhang, Hongbing Yan, Juying Qian, Jiyan Chen, Xi Su, Zhimin Du, Lefeng Wang, Qin Qin, Chuanyu Gao, Yang Zheng
Journal: Journal of the American College of Cardiology (2018)
Real-world systemic therapy utilization in Medicare patients with locally advanced or metastatic urothelial carcinoma.
Authors: Michaela Ann Dinan, Mihaela Georgieva, Rahul Shenolikar, Charles D. Scales
Journal: Journal of Clinical Oncology (2018)

415 Background: Several immunotherapies recently have been approved for the treatment of locally advanced or metastatic bladder cancer that is prevalent in older adults. Utilization patterns in Medicare patients have not been examined and can provide an important context for emerging therapies. Methods: We conducted a retrospective analysis of SEER-Medicare beneficiaries diagnosed with locally advanced (T3-T4, N1-N3, M0) or metastatic urothelial carcinoma (any T, any N, M1) of the bladder or upper urinary tract from 2008 to 2012 and further characterized patients undergoing initial chemotherapy (within 30 days of diagnosis). Individuals receiving neoadjuvant chemotherapy were excluded. Results: A total of 3569 patients met study criteria. Among these, 48% received chemotherapy within 2 years of diagnosis. Receipt of chemotherapy was associated with younger age (median 75 vs 80 years, P&lt; .001) and fewer comorbid conditions, including diabetes (12% vs 16%), renal disease (6% vs 11%), and congestive heart failure (4% vs 8%). A total of 977 patients received chemotherapy, of which 38% had distant metastatic disease and 65% had locally advanced tumors. Most patients had no (70%) or only a single (14%) comorbid medical condition. These patients most commonly received doublet chemotherapy (67%) followed by single-agent (17%) or triple-agent (10%) treatment. Gemcitabine was the most common individual agent received as part of initial chemotherapy (81%), followed by carboplatin (50%), cisplatin (38%), and docetaxel or paclitaxel (each 13%). The most common combination received was gemcitabine/carboplatin (42%) followed by gemcitabine/cisplatin (36%). Conclusions: Only half of Medicare patients with advanced urothelial carcinoma received systemic therapy. Most received a platinum doublet regimen. Gemcitabine in combination with platinum-containing chemotherapy was the preferred treatment. Ongoing assessment of the risks and benefits of emerging treatments for Medicare patients may be warranted with the introduction of targeted and/or immune therapies.
BMA sets further strike dates, as royal colleges condemn action
Authors: Abi Rimmer
Journal: BMJ (2016)

Junior doctors in England will stage four rounds of industrial action from September until December, the BMA has announced.

The news came as the Academy of Medical Royal Colleges said that the planned action was not proportionate to junior doctors’ concerns and would cause “real problems” for patients.

The BMA said that junior doctors would stage a series of actions comprising full withdrawal of labour between the hours of 8 am and 5 pm for five consecutive weekdays: during 12-16 September; 5-7 October and 10-11 October; 14-18 November, and 5-9 December. The BMA originally announced just one week of strikes, …
Does antiplatelet therapy really reduce the risk of hepatocellular carcinoma in hepatitis B patients with antiviral drugs?
Authors: Gin‐Ho Lo
Journal: Hepatology (2018)

Potential conflict of interest: Nothing to report. TO THE EDITOR: I read with interest the article by Lee et al. regarding the use of antiplatelet therapy to reduce the risk of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B who receive antiviral treatment.1 The authors demonstrated that the use of aspirin or clopidogrel could significantly reduce the occurrence of HCC in chronic hepatitis B patients who were taking antiviral drugs with a viral load <2000 IU/mL. Although this finding is an interesting one, several points need further clarification. First, the duration of antiviral use in both groups before enrollment was not disclosed. The proportion of patients using antivirals such as lamivudine in both groups of this study was not revealed. A previous study and the current study have both shown that the incidence of hepatic decompensation or HCC may not be reduced by the development of viral breakthrough.1 Second, patients in the antiplatelet group had a lower incidence of positive hepatitis B e antigen (HBeAg) and older age than patients in the non‐antiplatelet group, and it has been well established that positive HBeAg and older age are important risk factors for HCC development during antiviral therapy.3 Third, Child‐Pugh class C patients were not excluded from the study. This seems unreasonable given that Child‐Pugh class C patients were 0% in both groups and Child‐Pugh class C became a risk factor in Cox proportional hazards regression analysis. Finally, the 5‐year cumulative incidence of HCC was 5.2% in the non‐antiplatelet group. Though not a head‐to‐head comparison, this figure is higher than the 5‐year cumulative HCC incidence of 2.7%‐3.7% in Japanese patients with hepatitis B virus who are taking antivirals.4 In addition, all types of malignancy have a severe impact on lifespan. Malignancies other than HCC developed in 2.6% and 4.8% of patients in the non‐antiplatelet and antiplatelet groups, respectively. If pooled together, the 5‐year cumulative incidence of all malignancies would be 7.8% in the non‐antiplatelet group and 6.4% in the antiplatelet group; it is unknown whether a statistical difference still exists. Thus, the beneficial effect of reducing HCC or all malignancies through the use of antiviral and antiplatelet therapy in HBV patients is dubious, and further study is necessary.
Abstract 17417: ABCC6 Deficiency Promotes Atherosclerosis
Authors: Christopher Brampton, Li-Hsieh Chen, Ailea Apana, Georges Leftheriotis, Ludovic Martin, Sara McCurdy, William A Boisvert, Olivier Le Saux
Journal: Circulation (2015)

Introduction: Vascular calcification is associated with aging and common conditions such as hypercholesterolemia and certain genetic disorders. A molecular pathway inhibiting ectopic calcification is initiated by ABCC6, a membrane transporter primarily expressed in liver. ABCC6 facilitates the cellular efflux of ATP from hepatocytes, which is rapidly converted into pyrophosphate (PPi) in the liver vasculature. ABCC6 is responsible for the majority of the PPi release from the liver, and ~60% of plasma PPi in both in humans and mice. As PPi is a major inhibitor of calcification, mutations in ABCC6 underlie the currently incurable calcification disorder pseudoxanthoma elasticum (PXE), some cases of generalized arterial calcification of infancy (GACI). Hypothesis: Multiple lines of evidence have suggested a pathological synergy between ABCC6 and hyperlipidemia. Methods: We examined crosses between Abcc6-/- and Ldlr-/- mice and serum samples from human PXE patients. Three mouse genotypes were generated Ldlr-/-, Ldlr-/-xAbcc6-/- and Ldlr-/- xAbcc6+/-. Results: When subjected to a high fat diet, mice with reduced or no Abcc6 expression displayed a 2-fold increase of atherosclerotic plaque area (p=0.0001). Interestingly, atherosclerotic plaque was also found in Abcc6-deficient mice fed a normal diet but not in control Ldlr-/- animals. Aortic calcification was not significantly affected by Abcc6 expression except in Ldlr-/-xAbcc6-/- mice fed regular chow (p=0.0001). We observed an increased proliferation of smooth muscle cells of but no increase in monocyte-macrophage infiltration in the plaque of Ldlr-/-xAbcc6-/- mice. Importantly, we determined that the cholesterol efflux from isolated macrophages towards HDL (mediated by ABCG1) was significantly decreased (-28%, p=0.006) in Ldlr-/-xAbcc6-/- mice while the efflux towards ApoA1 (mediated by ABCA1) was unchanged. The analysis of high-density lipoprotein (HDL) and low-density lipoprotein (LDL) fractions in these mice showed altered profiles similar to those found with human PXE plasma samples. Conclusions: Our results indicated that, in addition to being an important inhibitor of vascular calcification, ABCC6 inhibits atherogenesis by modulating reverse cholesterol transport.
Pregnancy in women with congenital heart disease
Authors: Matthew Cauldwell, Francois Dos Santos, Philip J Steer, Lorna Swan, Michael Gatzoulis, Mark R Johnson
Journal: BMJ (2018)

Thank you for your interest in spreading the word about The BMJ.NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address. Username * Your Email * Send To * You are going to email the following Pregnancy in women with congenital heart disease Your Personal Message CAPTCHA This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Circadian clock component REV-ERBα controls homeostatic regulation of pulmonary inflammation
Authors: Marie Pariollaud, Julie E. Gibbs, Thomas W. Hopwood, Sheila Brown, Nicola Begley, Ryan Vonslow, Toryn Poolman, Baoqiang Guo, Ben Saer, D. Heulyn Jones, James P. Tellam, Stefano Bresciani, Nicholas C.O. Tomkinson, Justyna Wojno-Picon, Anthony W.J. Cooper, Dion A. Daniels, Ryan P. Trump, Daniel Grant, William Zuercher, Timothy M. Willson, Andrew S. MacDonald, Brian Bolognese, Patricia L. Podolin, Yolanda Sanchez, Andrew S.I. Loudon, David W. Ray
Journal: Journal of Clinical Investigation (2018)

Recent studies reveal that airway epithelial cells are critical pulmonary circadian pacemaker cells, mediating rhythmic inflammatory responses. Using mouse models, we now identify the rhythmic circadian repressor REV-ERBα as essential to the mechanism coupling the pulmonary clock to innate immunity, involving both myeloid and bronchial epithelial cells in temporal gating and determining amplitude of response to inhaled endotoxin. Dual mutation of REV-ERBα and its paralog REV-ERBβ in bronchial epithelia further augmented inflammatory responses and chemokine activation, but also initiated a basal inflammatory state, revealing a critical homeostatic role for REV-ERB proteins in the suppression of the endogenous proinflammatory mechanism in unchallenged cells. However, REV-ERBα plays the dominant role, as deletion of REV-ERBβ alone had no impact on inflammatory responses. In turn, inflammatory challenges cause striking changes in stability and degradation of REV-ERBα protein, driven by SUMOylation and ubiquitination. We developed a novel selective oxazole-based inverse agonist of REV-ERB, which protects REV-ERBα protein from degradation, and used this to reveal how proinflammatory cytokines trigger rapid degradation of REV-ERBα in the elaboration of an inflammatory response. Thus, dynamic changes in stability of REV-ERBα protein couple the core clock to innate immunity.
Digital Circulating Tumor Cell Analyses for Prostate Cancer Precision Oncology
Authors: Ellen Heitzer, Michael R. Speicher
Journal: Cancer Discovery (2018)

Abstract Summary: In this issue of Cancer Discovery, Miyamoto and colleagues adapted their microfluidic CTC-iChip isolation platform with a digital RNA-PCR readout for eight prostate-specific transcripts and two assays for the androgen receptor mRNA splice variant ARV7 and the TMPRSS2–ERG translocation transcript. In patients with metastatic castrate-resistant prostate cancer at initiating abiraterone therapy in a first-line setting, the resulting RNA-based digital circulating tumor cell signatures identified patients with a shorter overall survival, and in patients with clinically localized disease, the signatures identified those with seminal vesicle invasion and pelvic lymph node involvement. Cancer Discov; 8(3); 269–71. ©2018 AACR. See related article by Miyamoto et al., p. 288.
Infections associated with mesh repairs of abdominal wall hernias: Are antimicrobial biomaterials the longed-for solution?
Authors: O. Guillaume, R. Pérez-Tanoira, R. Fortelny, H. Redl, T.F. Moriarty, R.G. Richards, D. Eglin, A. Petter Puchner
Journal: Biomaterials (2018)
OPTIMAL POSITIONING OF MEDTRONIC CORE VALVE BEFORE DEPLOYMENT DECREASES PARAVALVULAR REGURGITATION POST TRANSCATHETER AORTIC VALVE REPLACEMENT (TAVR)
Authors: Razvan Tudor Dadu, Jiaqiong Xu, Colin Barker, Mahesh Ramchandani, Hasan Rehman, Ross Reul, Michael Reardon, Neal Kleiman
Journal: Journal of the American College of Cardiology (2018)
Suicide Rates, Psychiatric Hospital Bed Numbers, and Unemployment Rates From 1999 to 2015: A Population-Based Study in Hong Kong
Authors: Edwin Ho Ming Lee, Christy Lai Ming Hui, Pik Ying Chan, Wing Chung Chang, Sherry Kit Wa Chan, Eric Yu Hai Chen
Journal: American Journal of Psychiatry (2018)

Use and Health (N596,100), more than a third of medical marijuana users used recreational marijuana in the past year (1).In a study from Washington state, medical (N5131) and recreational (N5525) marijuana users had similar mean drug use scores on the Addiction Severity Index (medical50.14 [SD50.09],compared with recreational50.13[SD50.11]),and similar percentages of users reported depression (64% compared with 62%), violent behavior (14% compared with 15%), and hallucinations (8% compared with 9%), although recent medical problems were more common in the medical marijuana group than in the recreational marijuana group (76% compared with 51%) (2).In a second study, adults with a history of medical marijuana use were similar to nonmedical marijuana users except that medical marijuana users were more likely to have used cocaine (3).The extent to which medical cannabinoids can effectively reduce chronic pain deserves further study.At present, empirical support remains modest.In a meta-analysis of eight placebo-controlled studies of cannabinoids for pain, five studies failed to separate from placebo, and the overall effect on pain improvement across the eight studies fell just below statistical significance (odds ratio51.41,95% CI50.99-2.00)(4).By contrast, there is stronger evidence supporting the effectiveness of several nonpharmacological therapies, such as exercise, multidisciplinary rehabilitation, and acupuncture, for low back pain (5), the leading source of worldwide disability.We further urge caution against overinterpreting results from ecological studies, which temporally tie medical marijuana legislation to declining opioid mortality, because they do not include information on whether individuals who use marijuana alter their risk of developing opioid use disorder.Much remains to be learned about the complex relationships between cannabis and opioid use and how these interactions vary by patient characteristics and cannabinoid formulation.In the absence of prospective clinical evidence demonstrating protective effects, however, there is currently little medical justification for authorizing medical cannabis to lower nonmedical opioid use.