tbuckley/cabot-search huggingface dataset:
Hypertriglyceridaemia delays pancreatic regeneration after acute pancreatitis in mice and patients
Authors: Na Yang, Baiqiang Li, Yiyuan Pan, Jianfeng Tu, George Liu, Guotao Lu, Weiqin Li
Journal: Gut (2018)

We read with great interest the recent publication by Barlass et al in which morphine was demonstrated to aggravate the severity of acute pancreatitis (AP) and delay pancreatic regeneration. These results indicated the risk of morphine use in AP-associated pain treatment.1 Similar to their observation, we found another interesting phenomenon that hypertriglyceridaemia (HTG), a prevalent metabolic disorder, delayed pancreatic regeneration after AP in mice and patients. Moreover, the delayed regeneration process could be ameliorated by lipid-lowering therapy.

Two models of HTG (drug induced: poloxamer 407 (P407) and gene modified: glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1 (GPIHBP1) deficiency) were employed to explore the effect of HTG on AP repair. AP induced by caerulein infusion in both normal triglyceride (NTG) mice and HTG mice caused pancreatic acinar cell necrosis. The injured pancreas was reconstructed in 3 days and recovered its normal architecture in 7 days in the NTG mice (figure 1A–C). However, we observed reduced morphological recovery in the HTG mice, especially in the severe HTG mice that presented with prolonged necrosis until 7 days (figure 1A–C,  online supplementary figures 1–3). Furthermore, the key cellular responses involved in AP repair, including the fibroinflammatory response and acinar cell proliferation,2 were significantly delayed in the HTG mice (online supplementary figures 4–6). The above results …
I have been out of medicine for 13 years, busy having four children. How do I get back to work? So far my search has hit brick walls and much discouragement. I am 41 and feel I still have a lot to offer.
Authors: Rebecca Viney
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>
Progression free survival in patients with castrate resistant metastatic prostate cancer: Does sequence matter?
Authors: Adam McLain Kase, Cheryl Cook, Winston Tan
Journal: Journal of Clinical Oncology (2018)

356 Background: Approval of multiple therapeutic agents for castrate resistant prostate cancer (CPRPC) has improved survival and also quality of life. However, how to optimize sequencing is still an ongoing challenge for most clinicians. Methods: A retrospective chart review of patients treated with FDA approved regimens for castrate resistant prostate cancer from 2002 to 2017 at Mayo Clinical Florida was completed. Data on progression free survival of the various treatment sequences including abiraterone, docetaxel, and enzalutamide were reviewed. Results: One hundred patients were included in the study. Those on clinical trial were excluded. All patients were on LHRH agonist /antagonist and were continued while on the subsequent treatments. The first line therapy progression free survival (PFS) was 245 days with abiraterone acetate (AA), 307 days with enzalutamide (E) and docetaxel 285 days, respectively. The second line therapy PFS was 201 days with AA and 166 days with E. When AA was given after E PFS was 97 days and when E was given after AA the PFS was 68 days. E given after docetaxel resulted in a PFS of 390 days for one patient. Conclusions: In this chart review, enzalutamide had the longest PFS when used as the first line therapy and the PFS was improved when used as a second line after docetaxel. This retrospective review suggests therapy sequencing may be optimized to increase progressive free survival in patients with metastatic castrate resistant prostate cancer.
NEW PACEMAKER IMPLANTATION AFTER SURGICAL AORTIC VALVE REPLACEMENT IN THE PARTNER TRIALS: RATES, RISK FACTORS, AND CLINICAL OUTCOMES
Authors: Jose M. Dizon, Tamim Nazif, Angelo Biviano, Hasan Garan, Susheel K. Kodali, Craig R. Smith, Ashley Lowry, Eugene Blackstone, Vinod H. Thourani, Lars Svensson, Michael J. Mack, Martin B. Leon
Journal: Journal of the American College of Cardiology (2018)
East Australia is not the only way to go
Authors: Lee D Hudson
Journal: BMJ (2006)

<h3>Introduction</h3> There is an emerging epidemic of diabetes in China despite a relatively non-obese population. Genetics and lifestyle undoubtedly play a key role. We hypothesise that environmentally driven muscle mass acquisition at puberty may also be relevant. To test this hypothesis we examined the association of sex-steroids with muscle mass and of muscle mass with fasting glucose and insulin in a sample of Chinese adolescents. <h3>Methods</h3> In 40 adolescents (20 boys, 20 girls, age 12.9±0.1 years), from Hong Kong9s “Children of 1997” birth cohort, we assessed fasting glucose, insulin, sex-steroids and sex hormone binding globulin from a morning blood sample, and muscle and fat mass from a dual-energy x-ray absorptiometry scan. Lifestyle was obtained from a questionnaire. We used multivariable linear regression to assess adjusted associations. <h3>Results</h3> Free and bio-available testosterone were positively associated with muscle mass, as was physical activity. Muscle mass was associated with lower glucose (−0.04 mmol/l, 95% CI −0.08 to −0.01 per kg muscle mass) and lower insulin (−0.94 uU/ml, 95% CI −1.75 to −0.14); adjusted for sex and fat mass. <h3>Conclusions</h3> Environmentally driven muscle mass acquisition at puberty could potentially be an additional factor influencing diabetes, of which further investigation is warranted.
Efficacy and tolerability of Paclitaxel-Gemcitabine therapy for urothelial carcinoma in patients who have received prior platinum-based chemotherapy.
Authors: Ikko Tomisaki, Akinori Minato, Naohiro Fujimoto
Journal: Journal of Clinical Oncology (2018)

443 Background: Although platinum-based chemotherapy is the standard regimen as first line chemotherapy for urothelial carcinoma, the optimal second line regimen has not been yet established. The objective of this study was to evaluate the efficacy and safety of combination chemotherapy with paclitaxel (PTX) and gemcitabine (GEM) (PG therapy) for patients who have received prior platinum-based chemotherapy. Methods: We reviewed consecutive patients with locally advanced or metastatic urothelial carcinoma who received PG therapy after platinum-based chemotherapy. Doses and schedule of PG therapy were as follows; PTX, 200mg/m 2 on day 1, GEM, 1000/m 2 on days 1, 8, 15, repeated every 21 days. Imaging studies to assess the efficacy was repeated every 2 cycles of the therapy. Results: We identified 52 eligible patients. Of 52 patients, complete response (CR), partial response (PR), stable disease and progressive disease were observed in 2 (3.8%), 14 (26.9%), 18 (34.6%) and 18 (34.6%), respectively. With the median follow-up period of 9.8(IQR 5.5-16.3) months, the median progression free survival (PFS) after PG therapy was 4.7 months [95% confidence interval (CI), 3.6-5.8] and median overall survival (OS) after PG therapy was 11.6 months (95%CI:8.6-15.3). The sensitivity to PG therapy differed in disease sites, the response rate (CR+PR) of primary site, metastases in lymph nodes, lung, bone and liver was 8.3%, 48.7%, 29.4%, 0% and 33.3%, respectively. The response (CR or PR) to PG therapy [Hazard ratio (HR);0.42, 95% CI 0.18-0.95, p=0.04] and primary site (upper urinary tract) (HR;2.24, 95% CI 1.09-4.62, p=0.03) were associated with longer and shorter PFS, respectively. The response to PG therapy was also identified as a significant independent predictive factor for longer OS (HR;0.31, 95% CI 0.12-0.77, p=0.01). Myelosuppression was the most common adverse event. Only one patient discontinued the treatment due to an adverse event and there were no therapy-related deaths. Conclusions: PG therapy was safe and effective as second line regimen after platinum-based chemotherapy for urothelial carcinoma, especially in primary, lymph node and lung lesions.
Junior doctors to save hundreds of pounds after registration fees are made tax deductible
Authors: Helen Jaques
Journal: BMJ (2013)

Registration fees for bodies that monitor doctors’ training and make recommendations for certificates of completion of training will now be tax deductible, HM Revenue & Customs (HMRC) has announced.

Surgical trainees will now be able to claim back against taxable income the £185 a year they pay to the Joint Committee on Surgical Training. The committee …
I am a doctor from India. I came here after finishing my preregistration house officer posts and have passed the PLAB (Professional and Linguistic Assessments Board) tests. I want to work in genitourinary medicine; how do I progress and where should I apply?
Authors: Alexander McMillan
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>
Trump administration blames foreigners for US’s high drug costs
Authors: Owen Dyer
Journal: BMJ (2018)

A long awaited white paper from the Trump administration aimed at reducing high drug costs in the US puts much of the blame on foreign “free riding” and threatens action to deliberately drive up drug prices in other developed countries.

The new policy document by the President’s Council of Economic Advisers makes minor tweaks to Medicare reimbursement but also suggests that much of the blame and the solution for high drug prices in the US must be shouldered by foreigners.1

“Limiting under-pricing of drugs in foreign countries” should be a key policy focus for the Trump administration, the document argues. “Meaningful reforms would address the root of the problem: foreign, developed nations, that can afford to pay for novel drugs, free-ride by setting drug prices at …
Androgen deprivation therapy and overall survival for Gleason 8 versus Gleason 9-10 prostate cancer.
Authors: David Dewei Yang, Brandon Arvin Virgil Mahal, Vinayak Muralidhar, Neil E. Martin, Peter F. Orio, Kent William Mouw, Martin T. King, Toni K. Choueiri, Quoc-Dien Trinh, Karen E. Hoffman, Daniel Eidelberg Spratt, Felix Y Feng, Paul L. Nguyen
Journal: Journal of Clinical Oncology (2018)

23 Background: While the addition of androgen deprivation therapy (ADT) to external beam radiotherapy is known to improve overall survival in Gleason 8-10 prostate cancer, it has been hypothesized that Gleason 9-10 disease, which is less differentiated than Gleason 8 disease, may be less sensitive to ADT. To investigate this idea, we examined the association between ADT and overall survival for Gleason 8 versus Gleason 9-10 prostate cancer. Methods: We identified 20,139 men in the National Cancer Database diagnosed with localized or locally advanced, Gleason 8-10 prostate cancer from 2004 through 2011 who received external beam radiotherapy. Patients with clinical evidence of nodal or metastatic disease were excluded. Cox proportional hazards regression was used to examine the association between ADT and overall survival. Results: Median follow-up was 4.0 years. 78.2% (9,509) of the 12,160 men with Gleason 8 disease and 86.6% (6,908) of the 7,979 men with Gleason 9-10 disease received ADT. On multivariable analysis, ADT was associated with a significant improvement in overall survival for Gleason 8 patients (adjusted hazard ratio 0.79, 95% confidence interval 0.71-0.88, P&lt; 0.001) but not Gleason 9-10 patients (adjusted hazard ratio 0.96, 95% confidence interval 0.83-1.10, P= 0.532), with a significant interaction ( P interaction = 0.020). When considering Gleason 9-10 patients separately as Gleason 9 and Gleason 10, a higher Gleason score correlated with an increased adjusted hazard ratio for the association between ADT and overall survival ( P interaction = 0.012). Conclusions: In contrast to the significant survival advantage of ADT for Gleason 8 disease, our results strongly suggest that Gleason 9-10 disease may be less sensitive to ADT and that a higher Gleason score predicts lesser sensitivity. Consideration should be given to treatment intensification for Gleason 9-10 patients through enrollment in clinical trials or potentially adding novel antiandrogens or docetaxel, which have shown efficacy in both castration-resistant and castration-sensitive settings.
HIV-positive Kaposi sarcoma and immune checkpoint blockade.
Authors: Natalie Galanina, Aaron Goodman, Philip R Cohen, Razelle Kurzrock
Journal: Journal of Clinical Oncology (2018)

63 Title: HIV-Positive Kaposi Sarcoma and Immune Checkpoint Blockade Background: Kaposi sarcoma (KS) is an incurable, virally mediated malignancy arising in HIV-positive patients. We report the first observations on the safety and efficacy of checkpoint blockade in these patients. Methods: We identified eight evaluable patients with HIV-related Kaposi sarcoma who received ≥1 dose of checkpoint blockade. Data on demographics, treatment efficacy, and the effects on immune function (HIV and HHV8 viral load, CD4 count) and toxicity were curated. Results: Median age was 45.5 years (range, 38-63); all men; median, one prior regimen; all were treated with nivolumab 3mg/kg IV days 1 and 14 of each 28-day cycle. PD-L1 expression was assessed retrospectively and was low in 3 out of 4 patients with available data. All patients were receiving anti-retroviral therapy. The majority (75%) had preserved CD4 count and undetectable HIV viral load (Table). The response rate (RR) was 62.5% (5 of 8 patients) with 1 complete remission and 4 partial remissions; the remaining 3 patients have stable disease. Median follow up to date is 3.5 months and no patients has discontinued therapy. No grade &gt;2 toxicities were noted. Most common side effects included fatigue, gastrointestinal discomfort, pruritis, and onycholysis. There was an overall increase in CD4 counts. Conclusions: Preliminary observations suggest that checkpoint blockade with nivolumab has low toxicity and high anti-tumor activity in KS. Additionally, patients experienced improvement in CD4 count. [Table: see text]
Why become a trainee representative?
Authors: Karl Scheeres, Matt Tovey, Emma Hogan, Howard Ryland
Journal: BMJ (2015)

A technique for the absolute measurement of regional lung volume using transmission scintigraphy is described. A gamma camera placed behind the patient detects radiation passing through the chest from a uniform source containing <sup>99m</sup>Tc placed in front. The regional distribution of counts transmitted through the chest is recorded on a data handling unit linked to the camera. The regional distribution of anteroposterior chest thickness is also measured. From these two distributions it is possible, using a digital computer, to calculate the regional variation of lung volume. Total lung volumes measured in this way correlate very well with spirometer measurements. This technique overcomes the errors of regional lung volume measurement using <sup>133</sup>Xe gas where chest thickness variation, blood background, and nonuniform labeling of gas in poorly ventilating areas give false values. The technique is useful for measuring distributions of lung volume at different levels of respiration.
REAL-WORLD OPPORTUNITY OF EMPAGLIFLOZIN IN CARDIOVASCULAR RISK FACTOR MODIFICATION: AN NCDR® “RESEARCH-TO-PRACTICE” PROJECT FROM THE DIABETES COLLABORATIVE REGISTRY (DCR)
Authors: Suzanne Arnold, Leo Seman, Fengming Tang, Darren McGuire, Sanjeev Mehta, Abhinav Goyal, Laurence Sperling, Mikhail Kosiborod
Journal: Journal of the American College of Cardiology (2018)
General practices risk termination of contracts over industrial action
Authors: Helen Jaques
Journal: BMJ (2012)

General practices that take part in the BMA’s day of industrial action on 21 June to protest against changes to the NHS pension scheme risk termination of their general medical services (GMS) or personal medical services (PMS) contract, the association has warned. 

Taking lawful industrial action is a breach of contract, so a primary care organisation could attempt to terminate a GMS or PMS/17c contract if a practice takes part in the day of action later this month, the BMA has said.

It said that the risk of a contract being terminated on these grounds is “very low” …
Government bullying over GP contract is akin to culture at Mid Staffs, warns BMA
Authors: Helen Jaques
Journal: BMJ (2013)

The government’s focus on targets and its imposition of contract changes reflect the same “bullying” culture that led to the failings identified at Mid Staffordshire NHS Foundation Trust, the BMA says.

The BMA’s General Practitioners Committee said that the Department of Health’s attitude in forcing through changes to the general medical services (GMS) contract for 2013-14 is akin to the culture at the Mid Staffordshire trust. 

Around 500 patients died needlessly at the trust’s Stafford Hospital between 2005 and 2008 as a result of poor …
Prediction of outcome in bone metastatic, castration-resistant prostate-cancer-patients under enzalutamide by combining biomarkers.
Authors: Katrin Schlack, Andres Jan Schrader, Laura-Maria Krabbe, Karoline Kannen, Axel Semjonow, Martin Boegemann
Journal: Journal of Clinical Oncology (2018)

334 Background: Under early Enzalutamide (Enza) treatment of bone mCRPC (bmCRPC), prostate-specific antigen (PSA) might be misleading, since a PSA-flare may occur. Bouncing of alkaline phosphatase (APB) was shown as a promising surrogate for survival outcome. Low lactate dehydrogenase (LDH) usually predicts better outcome. The purpose of this study was to evaluate the prognostic ability of APB, LDH, PSA and information of the pooled markers after initiation of Enza. Methods: 89 bmCRPC-patients were analyzed. PSA, LDH and AP were monitored at 2, 4, 8, 12 and 20 weeks. APB was defined as an increase of AP after initiation of Enza with a subsequent, significant decline below baseline during the first 8 weeks of therapy. APB vs. no Bounce as well as LDH and PSA increase vs. decline were analyzed using Kaplan-Meier analyses (KMA) and uni- and multivariate (UV/MV) cox-regression models. Results: In KMA declining PSA and LDH as well as APB were associated with longer median PFS with 7 (95% confidence interval: 4.2-9.8) vs. 3 months (2.3-3.7) for PSA, 6 (4.1-8) vs. 2 (1.2-2.8) for LDH and 8 (0-16.3) vs. 3 (1.9-4.1) for APB. Analysis of OS showed similar results with 17 (11.7-22.3) vs. 12 months (7.0-17.1) for PSA, 17 (13.2-20.8) vs. 7 (5,8-8.2) for LDH and 19 (7.9-30.1) vs. 12 (7.7-16.3) for APB. In UV APB (Hazard Ratio (HR): 0.52 (0.3-1.0); p = 0.02), PSA-decline ≥50% (HR: 0.49 (0.3-0.7); p &lt; 0.01) and LDH-normalization (LDHnorm) (HR: 0.39 (0.2-0.6); p &lt; 0.01) were significantly associated with longer PFS. Considering OS LDHnorm was a significant prognosticator for longer survival (HR: 0.39 (0.2-0.6); p &lt; 0.01). In MV only LDHnorm showed a trend towards better OS (HR: 0.49 (0.2.-1.1); p = 0.09). Combining those markers and separating a group with APB, LDHnorm and PSA-decline and a group with PSA-decline alone KMA showed better PFS (11 (0.2-21.8) vs. 4 (0-8.6)) and OS (20 (17.7-22.3) vs. 8 (0.3-15.7)) in favor of the group with 3 beneficial markers. In UV the presence of all 3 markers was significantly associated with longer PFS (HR: 0.23 (0.1-0.7); p &lt; 0.01) and OS (HR: 0.26 (0.1-0.8); p = 0.02). Conclusions: APB and LDHnorm may add to identifying bmCRPC-patients with favorable prognosis during early Enza-therapy.
Abstract P1-16-01: Tumor subtype concordance between breast and bone biopsies in bone only metastasis patients
Authors: AM Parkes, KK Clifton, A Al Awadhi, OC Oke, CL Warneke, JK Litton, GN Hortobagyi
Journal: Cancer Research (2018)

Abstract Background: Bone is the most common site of metastasis in metastatic breast cancer patients. Notably, bone biopsy is considered technically challenging with concerns regarding yield and reproducibility of immunohistochemistry technique. Our goal was to assess tumor subtype concordance between breast and bone biopsies done in patients with bone only metastases. Methods: We identified patients followed at MD Anderson Cancer Center for at least 6 months from 01/01/1997 to 12/31/2015 with bone as first site of metastasis. Breast and bone biopsy immunohistochemistry was used to categorize tumor subtype with hormone receptor positive (HR+) defined as ER or PR &amp;gt;1%. The following four tumor subtypes were identified: luminal A-like (HR+, HER2-), luminal B-like (HR+, HER2+), triple negative (HR-, HER2-), and HER positive (HR-, HER2+). Results: We identified 805 bone only metastasis patients with positive bone biopsies, 395 (49%) of which had hormone receptor and HER2 characterization available. Of these 395 patients, 293 (74%) were luminal A-like, 44 (11%) were luminal B-like, 51 (13%) were triple negative, and 7 (2%) were HER2 positive. Of these patients, we identified 281 patients with tumor subtype data available for both primary breast biopsy and bone metastasis biopsy, of which 237 (84%) were concordant, while 44 (16%) were discordant (Table 1). Table 1. Concordance between breast and bone biopsies based on initial breast biopsy tumor subtypeBreast Biopsy Tumor Subtype (n = 281)Concordance with Bone Biopsy Tumor SubtypeDiscordant Bone Biopsy Tumor SubtypeLuminal A-like, HR+ HER2- (225/80%)Concordant: 199 (88%), Discordant: 26 (12%)10 Luminal B-like, 16 Triple negativeLuminal B-like, HR+ HER2+ (33/12%)Concordant: 19 (58%), Discordant: 14 (42%)11 Luminal A-like, 2 Triple negative, 1 HER2 positiveTriple negative, HR- HER2- (20/7%)Concordant: 16 (80%), Discordant: 4 (20%)3 Luminal A-like, 1 Luminal B-likeHER2 positive, HR- HER2+ (3/1%)Concordant: 3 (100%), Discordant: 0 (0%)NA Conclusions: When available, bone biopsy tumor subtype had significant concordance with breast biopsy tumor subtype in this large study of bone only metastasis patients. Discordant tumor subtype results were more common in patients with luminal B-like tumor subtype on initial breast biopsy. Citation Format: Parkes AM, Clifton KK, Al Awadhi A, Oke OC, Warneke CL, Litton JK, Hortobagyi GN. Tumor subtype concordance between breast and bone biopsies in bone only metastasis patients [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P1-16-01.
FROM BENCH TO IMPROVED PRE-HOSPITAL DIAGNOSIS OF VERY EARLY AMI: CARDIAC MYOSIN-BINDING PROTEIN C
Authors: Thomas Edward Kaier, Carsten Stengaard, Jack Marjot, Jacob Sorensen, Stavroula Stavropoulou-Tatla, Christian Terkelsen, Luke Williams, Kristian Thygesen, Hans Botker, Michael Marber
Journal: Journal of the American College of Cardiology (2018)