tbuckley/cabot-search huggingface dataset:
Genomic alterations (GA) predicted to confer lack of benefit from trastuzumab in advanced esophagogastric cancers (EGC): Analysis of 527 <i>HER2</i>-amplified (<i>HER2</i>amp) cases.
Authors: Samuel Jacob Klempner, Joseph Chao, Mark Bailey, Seung Tae Kim, Jie He, Doron Lipson, Siraj Mahamed Ali, Vincent A. Miller, Jeffrey S. Ross, Jeeyun Lee, Alexa Betzig Schrock
Journal: Journal of Clinical Oncology (2018)

44 Background: The addition of trastuzumab to chemotherapy improves survival in first line treatment of advanced HER2 overexpressing EGC. However, the response rate is under 50% in this molecularly heterogeneous group of cancers. Genomic alterations (GA) associated with lack of benefit from trastuzumab are understudied. Methods: We prospectively analyzed clinical samples from patients with EGC using hybrid-capture based comprehensive genomic profiling (CGP). Pre-specified literature review was used to determine GA associated with de-novo trastuzumab resistance. Results: From 2,245 gastroesophageal junction (GEJ) adenocarcinomas and 1,883 gastric adenocarcinomas (GC) we identified 395 HER 2-amplified GEJ (18%) and 132 HER 2-amplified (HER2amp) GC (7.0%) cases. Median HER 2 copy number was 19 in GEJ and 16 in GC samples. PIK3CA GA and METamp were observed in ~9% and ~5% of both HER 2amp and non- HER2amp EGC cases; however, co-amplification of cell-cycle mediators CDK6 and CCCNE1 were each significantly enriched in HER 2amp cases (Table). MYCamp and deleterious SMAD4 GA were also significantly enriched in cases with Her2amp. CDKN2A GA were common regardless of HER 2amp, particularly in GEJ . In cases with &gt;100 estimated HER 2 copies, only PIK3CA GA were significantly less frequent than in those with 6-99 copies (2.3% vs. 9.8%, P =0.04). All HER 2amp cases were microsatellite stable. A clinically annotated HER 2amp cohort will be presented. Conclusions: GA predicted to decrease trastuzumab sensitivity exist in a significant portion of HER 2amp EGC, although not all are enriched relative to non- HER 2amp cases. CGP may provide additive information to traditional HER2 testing and identify patients less likely to benefit from therapy. Larger clinical datasets are needed to validate our observations. [Table: see text]
Correcting the Record on a Fracture Risk Assessment Tool
Authors: Laragh Gollogly, Susan Norris, Nathan Ford
Journal: New England Journal of Medicine (2018)

To the Editor: The World Health Organization (WHO) has requested corrections of the record with respect to the fracture risk assessment tool (FRAX) released by the University of Sheffield in 2007.1 The University of Sheffield Department of Genomic Medicine was a WHO Collaborating Center from 1991 through 2010. The FRAX tool is not a “WHO tool” and was not developed, endorsed, evaluated, or validated by the WHO. The WHO has received no income from sales of subscriptions to the FRAX tool, nor does it endorse any treatment recommendations associated with risk stratification resulting from the use of the tool. Numerous . . .
Building a practical curriculum in clinical ethics and responsible research for undergraduate medical students in Guatemala
Authors: Maria-Lorena Aguilera-Arevalo, Sergio Martinez, Francis Barchi
Journal: The Lancet Global Health (2018)

BackgroundDespite growing concerns over unprofessional conduct by physicians and medical trainees in the Guatemalan health system, little has been done to develop a practical curriculum in clinical ethics and responsible research for undergraduate medical students in Guatemala. As part of a training programme in ethics education supported by the US National Institutes of Health's Fogarty International Center, faculty at Universidad Francisco Marroquin (UFM) in Guatemala City aimed to incorporate active-learning ethics short-courses into an existing system of credit-bearing electives offered to students as part of their 6-year undergraduate medical education.MethodsTwo preliminary workshops led by Guatemalan faculty trainees with the assistance of US mentors from Rutgers University, Johns Hopkins University, and the University of Pennsylvania, were used to stimulate student interest in future ethics courses, illustrate the level of student demand, and provide an evidence base to guide the development of a formal curriculum.FindingsThe resulting ethics course includes six 2-h modules, each of which is a stand-alone unit with learning goals and objectives, assigned readings, a discussion case, and assessment. These structured case-based activities allow for flexibility in design and scheduling, do not compete with core requirements of the existing curriculum, and enable students to develop critical reasoning approaches to ethical situations they will encounter in medical practice. The courses enhance rather than challenge existing bioethics content that historically emphasised moral and religious doctrine but did little to develop practical skills. The course, which targets second and third year medical students, has thus far been offered twice, and two additional sessions are scheduled during the current academic year. To date, more than 80 students have participated in the workshops and courses. Evaluations are being used to refine pedagogical approaches and drive course content.InterpretationThe UFM ethics elective courses offer a model for transforming medical ethics education in undergraduate medical programmes throughout Guatemala and the region.FundingNone.
Healthcare workers split on final pensions offer as more unions announce ballot results
Authors: Helen Jaques
Journal: BMJ (2012)

Midwives, physiotherapists, and NHS managers have all voted to accept the government’s final proposals for changes to the NHS pension scheme, but healthcare workers who are members of the union Unite have taken part in a second day of industrial action over the issue. 

More than three quarters (78%) of members of the union Managers in Partnership voted to accept the government’s proposals versus 22% to reject, on a turnout of 22%.

Members of the Royal College of Midwives and the Chartered Society of Physiotherapy have also accepted the government’s final offer by, respectively, 72% to 28% (20% turnout) and 68% to 32% (36% turnout).

NHS staff who …
New HSP90 selective inhibitors as therapeutic agents for prostate and bladder cancer.
Authors: Weiya Liu, Derek Jensen, Eugene Lee, Jessie Gills, Jeffrey M. Holzbeierlein
Journal: Journal of Clinical Oncology (2018)

285 Background: Hsp90 is a molecular chaperone responsible for folding many of the proteins directly associated with cancer progression and consequently, inhibition of the Hsp90 protein folding machinery results in a combinatorial attack on numerous oncogenic pathways. Hsp90 family consist of four isoforms; Hsp90α, Hsp90β, Grp94 and Trap-1. The development of Hsp90 isoform-selective inhibitors represent an alternative approach towards the treatment of cancer that may limit some of the detriments. We demonstrate novel Hsp90 inhibitors, on prostate and bladder cancer cells, which shows both potent antiproliferative effects and specific selectivity for Hsp90β. Methods: PC3MM2, LNCap-LN3, C4-2b, LAPC4 (prostate cancer) and T24, UC3 (bladder cancer) cancer cells were utilized. Cell Titer-Glo luminescent anti-proliferative assay was used to determine the IC50 numbers after 72h treatment. Trypan Blue Cytotoxicity assay was performed for 24h treatment with increasing concentrations of KUNB inhibitors. Effects of KUNB inhibitors on Hsp90’s client protein degradation were investigated by Western Blot. Results: KUNB31 manifested an IC50 of 3.00 µM against UC3 bladder cancer cells, UC3 cells were then evaluated via western blot analyses of known Hsp90α- and Hsp90β-dependent client proteins following treatment with KUNB31 for 24 hours. The data showed that, KUNB31 would not induce the heat shock response like 17AAG, and did cause Hsp90β related protein degradation (CXCR4). Moreover, Hsp27, PKM2, Her2, Hsf-1and Akt all showed degradation to different extent. KUNB105 exhibited potent anti-proliferative in both prostate and bladder cancer cells. IC50 number was determined as 1.24 µM for PC3MM2, 1.18 µM for LNCap-LN3, 1.03 µM for C4-2b, 2.56 µM for LAPC4, 0.20 µM for T24, and 0.30 µM for UC3 cancer cells. Conclusions: KUNB novel Hsp90β selective inhibitors, exhibit potent anti-proliferative and cytotoxic activity along with client protein degradation, without induction of HSR in prostate and bladder cancer cell lines. KUNB compound’s selective inhibition on Hsp90β isomers supports the development of Hsp90-selective inhibitors as a method to overcome the detriments associated with pan-inhibition in cancer treatment.
National Clinical Assessment Service to join NHS Litigation Authority
Authors: Caroline White
Journal: BMJ (2012)

The National Clinical Assessment Service (NCAS), which works with NHS organisations to resolve concerns about doctors’ performance, is to join the NHS Litigation Authority, the Department of Health has announced.

The service will become an operating division of the authority from April next year, when its agreed one year hosting by the National Institute for Health and Clinical Excellence comes to an end.

BMJ Careers understands that several options were considered but that the NHS Litigation Authority was deemed the most appropriate location for the service, which had previously …
I will be starting medical school this year at the age of 34, and I am worried that my age will affect my future career prospects. Should I be worried?
Authors: Emma Baker
Journal: BMJ (2004)

<i>Got 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 (www.bmjcareers.com/advicezone) 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.</i>
Estimated 24-Hour Urinary Sodium and Potassium Excretion in US Adults
Authors: Mary E. Cogswell, Catherine M. Loria, Ana L. Terry, Lixia Zhao, Chia-Yih Wang, Te-Ching Chen, Jacqueline D. Wright, Christine M. Pfeiffer, Robert Merritt, Claudia S. Moy, Lawrence J. Appel
Journal: JAMA (2018)

In 2010, the Institute of Medicine (now the National Academy of Medicine) recommended collecting 24-hour urine to estimate US sodium intake because previous studies indicated 90% of sodium consumed was excreted in urine.
End-of-Life Care Options and Decision Making for Older Patients With Malignant Brain Tumors—Reply
Authors: Laura L. Dover, Caleb R. Dulaney, Gabrielle Rocque
Journal: JAMA Oncology (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 Oncology 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 Oncology journal
Are there any particular SHO jobs that I should be considering before embarking on paediatrics?
Authors: Elitham Turya
Journal: BMJ (2004)

<i>Got 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 (www.bmjcareers.com/advicezone) 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.</i>
I am trying to find an organisation that I can go to the tsunami areas with as a volunteer. I am willing to do anything from working with children to cleaning up. I feel an overwhelming need to help.
Authors: Mark Wilson
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 (www.bmjcareers.com/advicezone) 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.
Calling all doctorpreneurs
Authors: Fiona Godlee
Journal: BMJ (2018)

How much do you love or hate the tools and systems you work with every day?If you hate them, do you have the energy or skills to invent new ones?A growing number of "doctorpreneurs" are finding that they do, and, as Anne Gulland reports (doi:10.1136/bmj.k685),the NHS is supporting innovations that offer better quality of care at less cost.
A phase II study of chemotherapy and immune checkpoint blockade with pembrolizumab in the perioperative and maintenance treatment of locoregional gastric or GE junction adenocarcinoma.
Authors: Paul Eliezer Oberstein, Beth Schrope, Tamas Gonda, Amrita Sethi, Arnold Han, Gary K. Schwartz, Manish A. Shah
Journal: Journal of Clinical Oncology (2018)

TPS197 Background: Gastric cancer is a prevalent worldwide disease for which surgical resection alone is insufficient to cure the majority of localized patients. Peri-operative chemotherapy is a standard of care approach that has demonstrated modest improved survival rates. Immune checkpoint therapy has proven efficacy in a subset of patients with refractory disease but it’s role in earlier stage disease and in combination with chemotherapy is not defined. By combining chemotherapy with immune checkpoint blockade utilizing pembrolizumab we hypothesize that we will obtain improved tumor response and prolonged disease control compared to chemotherapy alone. Tissue specimens will be obtained at baseline and at the time of surgery for novel correlative studies including single cell T cell receptor characterization and expression profiling. Methods: This Phase 2, multicenter study investigates the efficacy and safety of oxaliplatin/FU based chemotherapy plus pembrolizumab in the perioperative treatment of locally advanced, resectable gastric or GE junction adenocarcinoma. A total of 40 eligible patients with T2-4 and/or N1, M0 tumors on imaging or EUS will be treated with capecitabine, oxaliplatin and epirubicin (epirubicin can be omitted at investigator discretion) plus fixed dose pembrolizumab at 200mg for 3 cycles prior to surgery plus one additional dose of pembrolizumab alone before surgery. Following completion of post-operative chemotherapy with pembrolizumab, patients continue pembrolizumab for 1 year of maintenance therapy (17 cycles). The primary endpoint is disease free survival at 24 months (DFS 24) with an estimated 80% power to detect a clinically significant 24 month DFS rate of 65%. A key secondary endpoint is pathCR at surgery, additional endpoints include response rate (RECIST 1.1), 12 month DFS, and overall survival. Safety, including surgical outcomes, will be assessed. Multiple correlative analyses utilizing baseline and post-treatment tissue, PD-L1 staining, and serum samples will also be performed. Enrollment opened in March 2017. Clinical trial information: NCT02918162.
Utility of a Clinical Prediction Rule to Exclude Pulmonary Embolism Among Low-Risk Emergency Department Patients
Authors: Jeffrey A. Kline
Journal: JAMA (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 HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Abstract P5-12-04: The impact of bariatric surgery on mammographic breast density
Authors: A Hosseini, AL Khoury, J Carter, JM Wong, MD Alvarado, C Ewing, LJ Esserman, RA Mukhtar
Journal: Cancer Research (2018)

Abstract Background: Bariatric surgery decreases breast cancer risk, but its impact on mammographic findings is not well understood. Obesity and breast density both increase breast cancer risk, but paradoxically are inversely related. We investigated how mammographic density changes after bariatric surgery, and whether or not that change is related to amount of weight loss. Methods: We reviewed records for 349 prospectively collected patients who underwent bariatric surgery between 2013-2015, and identified 45 women with pre- and post-operative screening mammograms within 1.5 years of surgery. We recorded body mass index (BMI), Breast Imaging-Reporting and Data System density, and calculated excess BMI loss. Data were analyzed in Stata 14.2. Results: Average age was 54 years, mean pre-operative BMI was 44 (range 36-72), and mean percentage excess BMI lost was 73% at 1.3 years. One third had a change in mammographic breast density, which increased 93% of the time (p&amp;lt;0.001). Amount of weight loss was not associated with density change; in fact, weight loss was lower in those with a density change than in those without a density change (68% versus 75% excess BMI lost). Conclusions: The majority of women with a mammographic change had an increase in breast density, despite bariatric surgery being associated with reduced breast cancer risk. Interestingly, the amount of weight loss was not associated with change in breast density. These findings suggest the metabolic effects of bariatric surgery have an effect on breast cancer risk independent of BMI reduction. Future work will include studying mammographic changes associated with non-surgical weight loss. Citation Format: Hosseini A, Khoury AL, Carter J, Wong JM, Alvarado MD, Ewing C, Esserman LJ, Mukhtar RA. The impact of bariatric surgery on mammographic breast density [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 P5-12-04.
Tumour related epilepsy: an integrated management approach
Authors: Laura Mullens, Katia Cikurel, Jillian Maccoll, Victoria Hurwitz, Liz Ford, Jess La, Keyoumars Ashkan
Journal: Neuro-Oncology (2018)

In patients with brain tumours, seizures are common. 90% of patients with gangliogliomas and DNET tumours and 80% of patients with diffused low-grade gliomas could experience seizures at some point during their disease. Whereas, 50% of patients with high-grade glioma could develop seizures. This leads to a large neurology workload which is managed at Kings College Hospital (KCH) by an integrated service of a Neurologist and Clinical Nurse Specialists. To examine the practice provided to patients with tumour related epilepsy by the integrated service at KCH and assess how our service benefits patients, avoids GP/A&amp;E visits and reduces hospital admissions. Four-month data collection grouped and presented into categories. 86 patients had contact with the integrated neuro-oncology team regarding neurology needs from 1 November 2016 to 28 February 2017: 51% required review in clinic only15% required a clinic review with email/telephone input34% were supported via email/telephone input alone21% required more than one visit31% had a diagnosis of a low-grade glioma, 22% of a high-grade glioma, 22% of a meningioma 14% attended A&amp;E/admitted to hospital despite our advice Of those patients supported by email/telephone alone: 78% were contacted by telephone, 22% via email63% reported seizure activity, 37% had medication queries 29% attended A&amp;E/admitted to hospital despite our advice71% avoided hospital/GP appointments and/or attending A&amp;E Tumour related epilepsy data provided from a large neuro-oncology service at KCH is worthy of being shared. It can highlight the importance of an integrated neuro-oncology service which is accessible to patients through various means: email, telephone, clinics. A personalized service adjusted to the needs of patients. Moreover by utilising the expertise of the Neurologist we have shown that an integrated service may reduce the use of hard-pressed NHS resources in primary care settings and within hospitals.
Medical academics fight threat to jobs linked to success in obtaining funding
Authors: Matthew Limb
Journal: BMJ (2015)

Medical academics have called for help to fight the “growing threat” of redundancies at universities that is ostensibly linked to performance reviews and success in obtaining research funding.

Joannis Vamvakopoulos, a clinical lecturer at the University of Birmingham, said it was an “injustice” that academics were being laid off because they were allegedly “not hitting targets in terms of attracting funding.” He said, “Academic redundancies are not a new thing . . . but they’ve gathered pace in recent years due partly to funding cuts.” Vamvakopoulos, a member of the BMA’s medical academic staff committee (MASC), spoke at the conference …
Evidence is poor that financial incentives in primary care improve patients’ wellbeing
Authors: Susan Mayor
Journal: BMJ (2011)

Research evidence fails to show that providing financial incentives to primary care services improves patients’ wellbeing, concludes a Cochrane review published this week. The report warns policy makers to think carefully about the design of such programmes if they are to achieve real improvements for patients.

Anthony Scott, a professorial research fellow, and colleagues at the University of Melbourne’s Institute of Applied Economic and Social Research searched the literature for studies that assessed the effects of financial incentive schemes on the quality of care given by primary care practitioners. They looked for the degree to which changes in doctors’ behaviour improved patients’ wellbeing.

Despite hundreds of financial incentive schemes being introduced into primary care in the United States, Australia, the United Kingdom, and elsewhere they found only seven studies (from …