tbuckley/cabot-search huggingface dataset:
Between-surgeon variation in 90-day mortality after radical cystectomy for bladder cancer.
Authors: Jan Krzysztof Rudzinski, Niels Jacobsen, Sunita Ghosh, Adrian S Fairey
Journal: Journal of Clinical Oncology (2018)

512 Background: Radical cystectomy for bladder cancer is a complex surgical oncology procedure. Given the high degree of skill required to perform radical cystectomy, it is plausible that outcomes may vary among surgeons. We determined whether between-surgeon variation, known as heterogeneity, exists for urologic surgeons practicing at a Canadian academic center. Methods: A retrospective analysis of data from the University of Alberta (UA) Radical Cystectomy Database was performed. Between September 1994 and August 2017, 1031 consecutive patients underwent curative-intent radical cystectomy for histologically proven urothelial carcinoma of the bladder (cTanyN1-3M0) by 1 of 11 urologic surgeons. The main outcome measure was 90-day mortality rate. Multivariable models were used to evaluate heterogeneity in 90-day mortality rate after adjustment for case mix. Statistical tests were two-sided (p≤0.05). Results: Data were evaluable for 1031 patients. There was between-surgeon variation in the 90-day mortality rate (unadjusted range, 0.9% to 13.1%). 3 surgeons had 90-day mortality rates ≤ 3% whereas 5 surgeons had 90-day mortality rates ≥ 5%. Conclusions: A patient’s likelihood of achieving an optimal perioperative outcome differs depending on which urologic surgeon performs his/her radical cystectomy. Research examining the mechanism (s) underlying surgical heterogeneity in perioperative outcome after radical cystectomy is needed.
Prehospital trauma life support course (PHTLS)
Authors: Jonathan Birks
Journal: BMJ (2007)

FURTHER INFORMATION 

The Royal College of Surgeons: www.rcseng.ac.uk; PHTLS@rcseng.ac.uk

Anyone with an interest in prehospital care, including doctors, nurses, and ambulance staff.

I completed the course in 2006, towards the end of my foundation year one rotation.

I took the course so that I could be a doctor for motorbike racing events, after I had also attained full registration.

It took me several weeks to read through the 400 page manual, …
Nico van Hasselt: the oldest practising GP in the Netherlands
Authors: Tony Sheldon
Journal: BMJ (2018)

Credit: Marc Driessen

When Nico van Hasselt died in Amsterdam, days before his 94th birthday, he was the Netherlands’ oldest practising general practitioner. To the end, he met the commitment he made while in a cell during the Nazi occupation of the Netherlands in the second world war: if he survived he would dedicate his life to helping others through medicine.

He did exactly that: he became a doctor, and despite the best intentions of some to persuade him to stop working, he refused. In doing so he won a legal battle which meant that GPs could no longer be asked to retire solely on the grounds of age. He was still seeing patients in the week before his death.

Van Hasselt had been set to follow his father into banking in the quiet eastern town of Deventer when war interrupted his education. He progressed from protesting against the sacking of his Jewish school headmaster to stealing a German soldier’s revolver. He was betrayed and sent to a concentration camp in Vught, from which he …
The classroom microbiome and asthma morbidity in children attending 3 inner-city schools
Authors: Peggy S. Lai, Raivo Kolde, Eric A. Franzosa, Jonathan M. Gaffin, Sachin N. Baxi, William J. Sheehan, Diane R. Gold, Dirk Gevers, Ramnik J. Xavier, Wanda Phipatanakul
Journal: Journal of Allergy and Clinical Immunology (2018)
Will joining one of the reservist organisations (such as the Territorial Army) as a junior doctor have any negative impact on my future career?
Authors: Ian Palmer
Journal: BMJ (2006)

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>
GMC publishes new guidance on continuing professional development
Authors: Helen Jaques
Journal: BMJ (2012)

The General Medical Council has published new guidance on continuing professional development (CPD) to help doctors stay up to date and prepare for revalidation. 

The guidance—developed after consultation with doctors, medical royal colleges, employers, patients, and the public earlier this year—describes how doctors should plan, carry out, and evaluate their CPD activities.

It also describes how doctors should use information from their CPD within their annual appraisals, which will form the …
Plasma biomarker dynamics following ramucirumab treatment and survival analysis after ramucirumab treatment failure in patients with advanced gastric cancer.
Authors: Yumiko Ota, Takeru Wakatsuki, Tetsuo Mashima, Daisuke Takahari, Keisho Chin, Takashi Ichimura, Mariko Ogura, TOMOHIRO MATSUSHIMA, Hiroki Osumi, Izuma Nakayama, Eiji Shinozaki, Mitsukuni Suenaga, Naomi Kawata, Yuki Horiike, Hiroyuki Seimiya, Naoya Fujita, Kensei Yamaguchi
Journal: Journal of Clinical Oncology (2018)

79 Background: Ramucirumab (RAM) showed significantly improved survivals of gastric cancer in the second line with paclitaxel or single use. It is known that RAM causes pharmacodynamic changes of plasma VEGF-A family levels during treatment. However, its clinical significance is still unclear. The aim of this study is to reveal the changes of plasma biomarker levels until disease progression, and to examine associations between plasma biomarker levels at disease progression and survival after RAM treatment failure. Methods: Plasma samples were collected at three points: base line, day 8, and disease progression. Nine kinds of plasma biomarker related to angiogenesis: VEGF-A, C, D, PlGF, sVEGFR-1, 2, Neuropilin-1 (NRP1), Angiopietin-1, and SDF-1α, were measured by means of ELISA. The dynamics of plasma biomarkers were compared using the ANOVA. Patients were dichotomized by optimal cut-off value in each biomarker. Survival after RAM treatment failure was estimated by Kaplan-Maier methods and compared by log-rank test. Results: Plasma samples were collected from 21 patients. Median age was 67 y.o and female was dominant (57%). Plasma VEGF-A and PlGF levels sharply increased at day 8 and these higher plasma levels were sustained until disease progression: the median VEGF-A and PlGF levels at baseline, day 8, and disease progression were 20.2, 350.2, and 596.7 pg/ml for VEGF-A (p&lt;0.001) and 10.5, 223.4, and 261.1 pg/ml for PlGF (p&lt;0.001), respectively. Conversely, plasma NRP1 levels consistently decreased during treatment course: the median NRP1 levels at baseline, day 8, and disease progression were 444.3, 309.2, and 230.9 mg/ml (p=0.001). The median survival after disease progression was 3.1 months (95%CI 2.5-3.7). Patients with higher VEGF-A and NRP1 levels showed shorter survival with 4.5 vs. 0.9 months (HR 3.15 95%CI 1.6-6.4 p&lt;0.001) for VEGF-A and 8.8 vs. 2.6 months (HR 2.92 95% CI 1.4-6.3 p=0.002) for NRP1. Conclusions: Our data suggest that not only a clue of mechanism of acquired resistance of RAM but necessity of new treatment strategy after RAM treatment failure. Further understanding of molecular correlates and clinical validation are warranted.
Cultural Sensitivity in Deployed US Medical Personnel—Reply
Authors: Peter A. Learn, Eric A. Elster
Journal: JAMA Surgery (2018)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Surgery HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Surgery journal
Radical prostatectomy in metastatic castration-resistant prostate cancer: Feasibility, safety, and quality of life outcomes.
Authors: Chad A. Reichard, Justin Gregg, Mary F. Achim, Ana Aparicio, Louis L. Pisters, John Francis Ward, John W. Davis, Brian Francis Chapin
Journal: Journal of Clinical Oncology (2018)

244 Background: Ongoing studies are evaluating the role of definitive treatment of the primary tumor in men with de novo metastatic prostate cancer. If proven beneficial, the optimal timing of the intervention will need to be considered. Little is known regarding the safety and quality of life outcomes of RP in metastatic castration resistant PCa (mCRPC). Methods: 14 pts undergoing RP on clinical trials and in the setting of mCRPC from 2008-2016 were analyzed. Intra-op and post-op complications were assigned Clavien-Dindo grade. Post-op expanded prostate cancer index composite (EPIC) urinary domains quality of life (QOL) outcomes were reviewed. Results: Patient characteristics were summarized (Table). 5 (36%) pts received platinum based chemo prior to RP. 4 pts had a decrease in PSA post RP (range: 0.2-57.3 ng/ml); 7 pts had an increase in PSA post RP (range: 0.1-24.5 ng/ml); and 3 pts’ PSA was unchanged. Positive surgical margin rate was 57%. 3 of 6 cN0 pts were pN1. 1 of 8 cN1 pts were pN0. 12/14 pts underwent extended lymphadenectomy with a median 3 (IQR 0-4) positive LNs out of 17 (IQR 11-25) LNs removed. Median op time was 239 min (IQR 186-304). Median EBL was 200cc (IQR 150-225). 8 pts had bilateral non-nerve sparing. Median pre-op and &lt;3month post-op EPIC urinary function QOL scores were 84 (IQR 70-95) and 78 (IQR 62-810) respectively. 30-day mortality was 0% and 12/14 pts were alive at 1 year post RP. There were no intra-op complications. There was one Clavien Grade III complication (pelvic abscess), with remaining 5 complications either Grade I or II. Conclusions: In this select cohort of pts with mCRPC, RP was feasible with limited complications. Differences in pre-op and post-op urinary QOL scores were not clinically significant. Given the retrospective nature of the review and the heterogeneity of this heavily pre-treated population, clinical benefit cannot be ascribed to the intervention. Thus, we caution against RP in mCRPC outside of well-designed clinical trials other than for palliation. [Table: see text]
CYP11A1 inhibition as a therapeutic approach for the treatment of castration resistant prostate cancer.
Authors: Riikka Oksala, Mari Karimaa, Outi Simola, Meri Ramela, Reetta Riikonen, Pirjo Vehmaan-Kreula, Petteri Rummakko, Gerd Wohlfahrt, Pekka Kallio, Mika VJ Mustonen
Journal: Journal of Clinical Oncology (2018)

340 Background: Castration-resistant prostate cancer (CRPC) is a major cause of cancer mortality worldwide. The mechanisms behind the development of resistance are complex and not fully understood; altered androgen synthesis, androgen receptor (AR) overexpression or gene amplification, and mutations have been indentified. However, tumor growth may still be responsive to therapies that can further suppress de novo intratumoral steroid synthesis upstream of CYP17A1. ODM-208 is an oral, non-steroidal and selective inhibitor of CYP11A1 enzyme that suppresses the synthesis of all steroid hormones and their precursors. Methods: The inhibition of CYP11A1 was measured in vitro by the formation of radiolabelled isocapronic acid in a human adrenal cortex cell line (H295R), and further analysing pregnenolone (Preg) and testosterone (T) formation by ELISA. The tumor growth inhibition of ODM-208 alone or in combination with prednisone (Pred) was studied in VCaP CRPC xenograft where also concentrations of main steroid hormones progesterone (P), corticosterone (CORT) and T in tumors and adrenals were analysed. In addition, plasma ACTH and LH levels were measured at the end of the xenograft study. In dogs an ACTH stimulation test was done. Toxicity studies were conducted in rats and dogs. Results: ODM-208 potently inhibits CYP11A1 and synthesis of Preg and T with nM concentrations in vitro. In the VCaP CRPC xenograft ODM-208 alone and in combination with Pred significantly inhibited tumor growth. Concentrations of T, P and CORT were significantly decreased in the adrenals, indicating strong CYP11A1 inhibition. Also, significantly decreased steroid levels in tumors was observedhe Pred combination increased plasma ACTH levels less than ODM-208 alone, whereas no difference was seen in the LH. In dogs ACTH-stimulated cortisol production was significantly inhibited after single oral dose of ODM-208. In toxicological studies ODM-208 showed expected reversible findings in target tissues, mainly related to the pharmacology. Conclusions: ODM-208 shows promising antitumor activity in preclinical CRPC models with favorable toxicological profile. Thus, ODM-208 might have potential for treating the patients with CRPC.
New 6-factor prognostic model for patients (pts) with advanced urothelial carcinoma (UC) receiving post-platinum atezolizumab.
Authors: Gregory Russell Pond, Guenter Niegisch, Jonathan E. Rosenberg, Robert Dreicer, Thomas Powles, Andrea Necchi, Xiao X. Wei, Petros Grivas, Arjun Vasant Balar, Matt D. Galsky, Sandy Srinivas, Toni K. Choueiri, Joaquim Bellmunt, Dean F. Bajorin, Guru Sonpavde
Journal: Journal of Clinical Oncology (2018)

413 Background: Prognostic factors for overall survival (OS) have been identified in pts receiving post-platinum chemotherapy for advanced UC, but it is unknown whether these factors and/or others optimally predict OS for pts treated with PD1/PD-L1 inhibitor therapy. Methods: Pt level data from two UC salvage trials evaluating atezolizumab were used: IMvigor210 (n = 310) for training and PCD4989g (n = 95) for validation. Univariable and multivariable Cox regression analyses were performed to evaluate the association of the prognostic factors recognized in the chemotherapy setting (ECOG performance status [ECOG-PS], liver metastasis (LM), anemia, treatment-free interval, albumin), neutrophil-lymphocyte ratio (NLR), eosinophil count, platelet count (PLT), site of primary/metastases, stage at diagnosis, smoking, LDH, prior therapies and immune cell PD-L1 status by IHC with OS. Clinical factors were dichotomous and lab values normalized by logarithmic transformation as needed. Stepwise selection was employed to propose an optimal model using the training dataset; pts were then categorized by number of risk factors. Concordance, discrimination (c-statistic) and calibration were assessed in the validation dataset using bootstrap analyses. Results: The factors included in the optimal prognostic model for OS were: ECOG-PS 1 vs. 0 (HR 1.64 [95% CI: 1.20, 2.24], p = 0.002), LM (1.45 [1.08, 1.94], p = 0.014), PLT (1.73 [1.14, 2.61], p = 0.010), NLR (1.84 [1.45, 2.34], p &lt; 0.001), LDH (1.54 [1.19, 1.99], p = &lt; 0.001) and anemia (HR = 1.60 [1.17, 2.21] p = 0.004). The c-statistic was 0.690 (95% CI = 0.649-0.715) and 0.759 (0.694-0.795) in the training and validation datasets, respectively. 1-year OS of pts in the training and the validation cohorts were similar. PD-L1 score was statistically significant when adjusted for the optimal model, but did not improve clinical interpretability (c-statistic = 0.698). Conclusions: A new validated 6-factor prognostic model for OS including ECOG-PS, LM, PLT, NLR, LDH and anemia is proposed in the setting of post-platinum atezolizumab for advanced UC. Applicability of the model to other PD1/PD-L1 inhibitors and PD-L1 IHC assays warrant investigation.
Government offers concessions on QOF but will impose other 2013-14 GP contract changes
Authors: Helen Jaques
Journal: BMJ (2013)

The government has agreed to ameliorate some of its proposed changes to the Quality and Outcomes Framework (QOF) for the GP contract in England for 2013-14.

But it will still press ahead in April with plans to phase out the minimum practice income guarantee, introduce four new local enhanced services, remove the organisational domain of QOF, and increase thresholds for all QOF indicators.

Last autumn the Department of Health announced its proposals for the new general medical services (GMS) contract for England and its intention to impose the changes irrespective of agreement with the profession.12 In response to a consultation on the proposals the government confirmed its intention to go ahead with …
Reply to Dorrington <i>et al.</i> and to Swenson: “Hypercapnic Pulmonary Vasoconstriction Contributes to Regional Perfusion Distribution: Relevance to Asthma” and “Hypercapnic Pulmonary Vasoconstriction as a Mechanism for Regional Perfusion Redistribution in Asthma”
Authors: Vanessa J. Kelly, Tilo Winkler, R. Scott Harris
Journal: American Journal of Respiratory and Critical Care Medicine (2017)
LETTER OF THE MONTH Careers advice for doctors
Authors: Anne L Appleton
Journal: BMJ (2007)

We welcome your rapid responses, whether in direct response to an article in Career Focus or as a way of sharing your own ideas. As long as it isn9t libellous or offensive, we9ll post it on our website. We print a selection of rapid reponses here and the writer of the best each month wins an <i>Oxford Handbook</i> of their choice. Letter of the month prize is donated by OUP.
Dual-stimuli-responsive albumin-polyplex nanoassembly for spatially controlled gene release in metastatic breast cancer
Authors: Santhosh Kalash Rajendrakumar, Kondareddy Cherukula, Hyeong Ju Park, Saji Uthaman, Yong Yeon Jeong, Byeong-Il Lee, In-Kyu Park
Journal: Journal of Controlled Release (2018)
Flexible Devices: Ultrastretchable Kirigami Bioprobes (Adv. Healthcare Mater. 3/2018)
Authors: Yusuke Morikawa, Shota Yamagiwa, Hirohito Sawahata, Rika Numano, Kowa Koida, Makoto Ishida, Takeshi Kawano
Journal: Advanced Healthcare Materials (2018)

The most remarkable features of Kirigami are that unstretchable materials can gain stretchability and that its strain force is very small compared to other elastomer-based stretchable materials. These features are suitable for applications related to deformable soft biological samples. In article number 1701100, Takeshi Kawano and co-workers propose the ultrastretchable bioprobe device using a 'Kirigami' design and demonstrate the recordings of biological signals in mouse brain and heart.
Adenosine-to-Inosine Editing of MicroRNA-487b Alters Target Gene Selection After Ischemia and Promotes Neovascularization
Authors: Reginald V.C.T. van der Kwast, Eva van Ingen, Laura Parma, Hendrika A.B. Peters, Paul H.A. Quax, A. Yaël Nossent
Journal: Circulation Research (2017)

Rationale: Adenosine-to-inosine editing of microRNAs has the potential to cause a shift in target site selection. 2′-O-ribose-methylation of adenosine residues, however, has been shown to inhibit adenosine-to-inosine editing. Objective: To investigate whether angiomiR miR487b is subject to adenosine-to-inosine editing or 2′-O-ribose-methylation during neovascularization. Methods and Results: Complementary DNA was prepared from C57BL/6-mice subjected to hindlimb ischemia. Using Sanger sequencing and endonuclease digestion, we identified and validated adenosine-to-inosine editing of the miR487b seed sequence. In the gastrocnemius muscle, pri-miR487b editing increased from 6.7±0.4% before to 11.7±1.6% ( P =0.02) 1 day after ischemia. Edited pri-miR487b is processed into a novel microRNA, edited miR487b, which is also upregulated after ischemia. We confirmed editing of miR487b in multiple human primary vascular cell types. Short interfering RNA–mediated knockdown demonstrated that editing is adenosine deaminase acting on RNA 1 and 2 dependent. Using reverse-transcription at low dNTP concentrations followed by quantitative-PCR, we found that the same adenosine residue is methylated in mice and human primary cells. In the murine gastrocnemius, the estimated methylation fraction increased from 32.8±14% before to 53.6±12% 1 day after ischemia. Short interfering RNA knockdown confirmed that methylation is fibrillarin dependent. Although we could not confirm that methylation directly inhibits editing, we do show that adenosine deaminase acting on RNA 1 and 2 and fibrillarin negatively influence each other’s expression. Using multiple luciferase reporter gene assays, we could demonstrate that editing results in a complete switch of target site selection. In human primary cells, we confirmed the shift in miR487b targeting after editing, resulting in a edited miR487b targetome that is enriched for multiple proangiogenic pathways. Furthermore, overexpression of edited miR487b, but not wild-type miR487b, stimulates angiogenesis in both in vitro and ex vivo assays. Conclusions: MiR487b is edited in the seed sequence in mice and humans, resulting in a novel, proangiogenic microRNA with a unique targetome. The rate of miR487b editing, as well as 2′-O-ribose-methylation, is increased in murine muscle tissue during postischemic neovascularization. Our findings suggest miR487b editing plays an intricate role in postischemic neovascularization.
ECHOCARDIOGRAPHY UTILIZATION AS A PREDICTOR OF INHOSPITAL MORTALITY IN ACUTE MYOCARDIAL INFARCTION
Authors: Ali Hama Amin, Sirish Shrestha, Tracy Cook-Carney, Marton Tokodi, Grace Casaclang-Verzosa, Muhammad Ashraf, Jason Moreland, Mohamad Alkhouli, Bryan Raybuck, Partho P. Sengupta
Journal: Journal of the American College of Cardiology (2018)
Inherited germline mutations in men with prostate cancer.
Authors: Robert Reid, Marcie DiGiovanni, Ryan Bernhisel, Krystal Brown, Jennifer Saam, Johnathon Lancaster
Journal: Journal of Clinical Oncology (2018)

357 Background: Recent studies have demonstrated a high prevalence of pathogenic variants (PVs) in genes that confer hereditary cancer risk among men with metastatic prostate cancer (PC); however, PC does not currently receive attention as an indication for genetic testing. We assessed the clinical features of men with PC who received clinical testing as well as the distribution of PVs identified. Methods: Men with PC who underwent testing with a multi-gene hereditary cancer panel (Myriad Genetic Laboratories) from September 2013–September 2017 were included. Clinical information was obtained from provider-completed test request forms. Individuals with PC only were evaluated separately from those who had ≥1 additional malignancy. Personal/family history was evaluated relative to the 2013 NCCN guidelines for hereditary breast and ovarian cancer (HBOC) testing. Results: Overall, 1004 men with a personal history of PC were identified: 606 (60.4%) with only PC and 398 (39.6%) with PC and ≥1 additional malignancy. The most common additional malignancies were breast (136) and colorectal cancer (134). The median age of diagnosis in men with only PC was 59, which is younger than tested men who had an additional malignancy (63) and the SEER data (2009-2013) for all men with PC (66). HBOC testing criteria were met by 78.0% of men, including 68 (6.8%) who met based only on a personal/family history of PC and 330 (32.9%) who met in part due to a personal/family history of PC. PVs were identified in 12.9% of all men: 11.2% of men with PC only and 15.4% of men with PC and a second malignancy (Table). Conclusions: PC patients selected for genetic testing here were younger than men diagnosed with PC from the general population (SEER), and about a third had a diagnosis of an additional malignancy. They also have a high positive mutation rate across a broad spectrum of genes. [Table: see text]