tbuckley/cabot-search huggingface dataset:
Immune checkpoint inhibitor responses in KIT-mutated metastatic melanoma.
Authors: Meredith Ann McKean, Junna Oba, Junsheng Ma, Lauren Elaine Haydu, Roland L. Bassett, Scott Eric Woodman
Journal: Journal of Clinical Oncology (2018)

199 Background: KIT-mutated MM is a rare melanoma entity. Response rates of KIT-mutated MM to anti CTLA-4 and anti PD-1 have not previously been reported. Methods: A single-institution retrospective review identified patients (pts) with KIT-mutated MM treated with at least two doses of anti CTLA-4 or anti PD-1 between 2008-2017 with response determined by immune-related response criteria (irRC). Overall survival (OS) was from ICI start to death or last follow-up date, and progression-free-survival (PFS) was from ICI start to date of progression or death if pts deceased without disease progression. Results: Thirty-five pts treated with ipilimumab were identified. Median follow-up was 63.7 months. Median age at MM diagnosis was 65.4 years (range 26-81) and 54.3% were male. Subtypes were 51.4% mucosal, 22.9% acral-lentiginous, 22.9% cutaneous, and 2.9% unknown primary. KIT mutations were 57.1% exon 11, 25.7% exon 17, 11.4% exon 13, and 5.7% exon 2. Anatomical M stage at treatment initiation was 11.4% M1a, 34.3% M1b, and 54.3% M1c. Median OS was 11.8 months (8.4-35.6) and PFS was 3.0 months (2.8-5.8). Responses to ipilimumab were 8.6% complete response (CR), 11.4% partial response (PR), 28.6% stable disease (SD), and 51.4% progressive disease (PD) for a 48.6% clinical response rate (CRR). Twenty pts treated with anti PD-1 were identified. Median follow-up was 7.9 months. Median age at MM diagnosis was 66.7 years (range 42.6-86.8) and 70% were male. Subtypes were 40% mucosal, 30% cutaneous, 20% acral-lentiginous, and 10% unknown primary. KIT mutations were 45% exon 11, 35% exon 17, 10% exon 2, 5% exon 13 and and 5% exon 10. Anatomical M stage at treatment initiation was 10% M1a, 15% M1b, and 75% M1c. Median OS was 22.5 months (7.4-NA ) and PFS was 3.2 months (2.7-NA). Responses to anti PD-1 were 10.0% CR, 25.0% PR, 20.0% SD, and 45.0% PD for a 55.0% CRR. For both anti CTLA-4 and anti PD-1 treated cohorts, univariate analysis demonstrated no statistical significance between tumor response to ICI and clinical pt characteristics or KIT mutation exon. Conclusions: KIT-mutated MM demonstrated CRR of 48.6-55.0% to ICI. There was no correlation between pt characteristics or KIT exon mutation and response to therapy; however, analysis was limited by sample size.
A PET imaging agent for evaluating PARP-1 expression in ovarian cancer
Authors: Mehran Makvandi, Austin Pantel, Lauren Schwartz, Erin Schubert, Kuiying Xu, Chia-Ju Hsieh, Catherine Hou, Hyoung Kim, Chi-Chang Weng, Harrison Winters, Robert Doot, Michael D. Farwell, Daniel A. Pryma, Roger A. Greenberg, David A. Mankoff, Fiona Simpkins, Robert H. Mach, Lilie L. Lin
Journal: Journal of Clinical Investigation (2018)

BACKGROUND. Poly(ADP-ribose) polymerase (PARP) inhibitors are effective in a broad population of patients with ovarian cancer; however, resistance caused by low enzyme expression of the drug target PARP-1 remains to be clinically evaluated in this context. We hypothesize that PARP-1 expression is variable in ovarian cancer and can be quantified in primary and metastatic disease using a novel PET imaging agent.
Research training in the 21st century: the part time MSc
Authors: Patrick Maxwell
Journal: BMJ (2005)

T he government is committed to increasing consultant numbers to meet national service framework targets and comply with the European Working Time Directive. Consultant training has had to adapt and shorten. One consequence of this is that it is now unusual for trainees to undertake two or three years' full time research leading to an MD or PhD; until recently this was almost a requirement in many hospital specialties. Those opting for a competitive research career still need to make a commitment to research early on—but what about the majority of trainees, those who are not going to pursue a career in research. Would they benefit from research training?

The view of the Royal College of Physicians is that knowledge of research is a vital component of clinical training. We agree strongly with the college's statement that “research awareness training should be mandatory for all physicians.” But what …
OUTCOMES IN PATIENTS WITH SEVERE LEFT VENTRICULAR DYSFUNCTION AND ACUTE DECOMPENSATED HEART FAILURE UNDERGOING EMERGENT TRANS-CATHETER AORTIC VALVE REPLACEMENT
Authors: Swethika Sundaravel, Jesus Pino, Abdulah Alrifai, Mohamad Kabach, Edwin Grajeda, Pradeep Dayanand, Roberto Cubeddu, Eduardo Venegas, Lawrence Lovitz, Mark Rothenberg, George Daniel, Robert Chait, Eric Heller, Cristiano Faber, Marcos Nores
Journal: Journal of the American College of Cardiology (2018)
Screening for Ovarian Cancer in Asymptomatic Women
Authors: Karen H. Lu
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
Margaret McCartney: Hiding and seeking doctors’ conflicts of interest
Authors: Margaret McCartney
Journal: BMJ (2018)

Here’s a game: try to find a doctor’s conflicts of interest. Set a timer, and give yourself the freedom of the internet.

Yesterday I spent four hours trying to locate declarations made by members of a committee who wrote some guidelines three years ago. The declarations weren’t on the guideline; they were in the minutes of the committee’s meetings. But some members had attended only some meetings, and the minutes hadn’t been archived, so they were no longer publicly available—they had to be requested by email from the organisation and retrieved from its archives. I didn’t know that this was possible until I’d had a long series of emails with the organisation responsible.

Alternatively, try searching clinical commissioning groups’ gift registers. Many are hard …
Core skills in laparoscopic surgery
Authors: Alison Bradley, Michael D Gale
Journal: BMJ (2012)

Accomplishing the leap from camera person to laparoscopic surgeon is daunting for any surgical trainee. Laparoscopic skills have become a core skill set in many surgical specialties but are often only a small part of the basic surgical skills courses, which, with restricted working hours, limits the opportunities for trainees to develop these skills. Core skills in laparoscopic surgery is a two day course designed to bridge the gap between holding the camera and performing laparoscopic surgery. By the end of my course all participants had gained the skills to perform simulated diagnostic laparoscopy, laparoscopic appendicectomy, and laparoscopic cholecystectomy.

The course is designed for surgical trainees wishing to develop basic skills in laparoscopic surgery. I did the course as a year 1 core surgical trainee. Most of the participants on my course were core surgical trainees years 1 to 3, but more senior trainees wanting to refresh …
RCP is to highlight gap in performance between overseas doctors and UK graduates
Authors: Abi Rimmer
Journal: BMJ (2014)

The Royal College of Physicians is working to raise awareness of differential exam attainment between UK and international medical graduates, Jane Dacre, the college’s president, has announced.

Speaking at the conference of the British Association of Physicians of Indian Origin in Manchester on Sunday 30 November, Dacre thanked the association for tackling the issue of differential attainment. “I suppose it was an elephant in the room, and it’s been …
The expression of versican and its role in pancreatic neuroendocrine tumors.
Authors: Zhao Sun, Heli Gao, Junjie Gu, Yuejuan Cheng, Yuanjia Chen, Chunmei Bai
Journal: Journal of Clinical Oncology (2018)

254 Background: Pancreatic neuroendocrine tumor (pNET) is a group of rare and heterogeneous tumor. Prognostic biomarkers are essential to better predict patients’ prognosis and approve individualized chemotherapy. According to references, Versican(VCAN) expression plays an important role in the development of various tumors.Our previous study found VCAN had a tumor-specific expression in pNET tissues. Therefore, further study is performed to investigate the relationship between VCAN expression in pNET tissues and patients’ prognosis. Methods: Clinicopathological data of pNET patients who underwent surgery between 2005 and 2010 were collected, followed up and evaluated. VCAN expression was assessed by immunohistochemical (IHC) staining. The relationship between VCAN expression and clinicopathological characteristics of patients were analyzed by Chi square. The expression between VCAN expression and disease-free survival (DFS) of patients were analyzed by Kaplan-Meier. The relationship between patients’ DFS and relative clinicopathological characters were analyzed by Cox regression. Results: 174 pNET patients were enrolled in our research. Among them, 124 patients were VCAN positive and 50 were VCAN negative. VCAN expression was significantly associated with tumor stage. Better disease-free survival (DFS) was observed in patients with VCAN positive compared to those with VCAN negative (124.1±75.71m,99.35±12.14,respectively, p = 0.003).Multivariate analysis demonstrated that VCAN expression, Grade, tumor size were independent prognostic predictor for patients’ prognosis(p = 0.01,0.000,0.001,respectively). Subgroup analysis revealed that VCAN positive predicted a better DFS in patients with Grade 2, Tumor size &gt; 2cm, and Non-functional tumor(p = 0.04,0.002,0.01,respectively). Conclusions: pNET patients with VCAN positive had a longer DFS.
Abstract P3-03-05: Association between<i> BRCA1</i> and <i>BRCA2</i> mutations and survival in breast cancer patients according to molecular subtype
Authors: O Tredan, S De Talhouet, J Peron, A Friedlaender, A Vuilleumier, V Viassolo, A Ayme, PO Chappuis, A Buisson, V Bonadona, A Bodmer, SI Labidi-Galy
Journal: Cancer Research (2018)

Abstract Background: Germline mutations in BRCA1/BRCA2 genes increase the risk of breast and ovarian cancers. In ovarian cancer patients (pts) treated with platinum, BRCA1, and especially BRCA2, carriers have better survival than non-carriers. In breast cancer pts, BRCA1 carriers have higher response rate to neoadjuvant chemotherapy, however the benefit on survival remains unclear. Patients and Methods: A cohort study was conducted in France and Switzerland and consisted in 860 pts diagnosed with early breast cancer who underwent genetic screening for BRCA1/BRCA2 germline mutations and who received neo(adjuvant) chemotherapy. Disease-free survival (DFS) and Breast-cancer specific survival (BCSS) were analyzed according to BRCA1/BRCA2 mutations and breast cancer subtype (triple negative breast cancers (TNBC) vs non-TNBC). Results: One hundred and forty-three pts carried BRCA1 mutation; 88 had BRCA2 mutation; and 629 were non-carriers. Median age at diagnosis was 39 years; median follow-up was 4.8 years. Two hundred and fifty-three pts had TNBC (94 BRCA1, 14 BRCA2 and 145 non-carriers), and 607 had non-TNBC (49 BRCA1, 74 BRCA2 and 484 non-carriers). Among TNBC pts, BRCA2 mutations were associated with higher 5-years DFS (100% vs 71% for non-carriers and 80% for BRCA1 carriers; log-rank p=0.040), and BCSS (100% vs 78% for non-carriers and 92% for BRCA1 carriers; log-rank p=0.011). BRCA1 mutations were associated with higher 5-years DFS compared to non-carriers, but the association did not reach statistical significance (HR adjusted on nodal status=0.64; 95%CI 0.36-1.16, Wald test p=0.14). BRCA1 mutations were associated with an improved 5-years BCSS compared to non-carriers (HR adjusted on nodal status=0.38; 95%CI 0.16-0.87, Wald test p=0.022). In non-TNBC patients, BRCA1 or BRCA2 mutations were not associated with higher 5-years DFS (79% for BRCA1, 79% for BRCA2 carriers, and 80% for non-carriers; log-rank p=0.88) nor BCSS (94%, 92%, and 94% respectively; log-rank p=0.79). Conclusions: Among pts with TNBC, having BRCA germline mutation was associated with improved survival. In our cohort of TNBC pts, BRCA2 carriers did not present breast cancer relapse. Citation Format: Tredan O, De Talhouet S, Peron J, Friedlaender A, Vuilleumier A, Viassolo V, Ayme A, Chappuis PO, Buisson A, Bonadona V, Bodmer A, Labidi-Galy SI. Association between BRCA1 and BRCA2 mutations and survival in breast cancer patients according to molecular subtype [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 P3-03-05.
GMC has sped up CESR and CEGPR application process
Authors: Abi Rimmer
Journal: BMJ (2015)

The General Medical Council has cut the amount of time it takes to process applications for the certificate of eligibility for specialist registration (CESR) or the certificate of eligibility for GP registration (CEGPR). 

The GMC said that, in 2014, 95% of CESR and CEGPR applications were processed within the three …
Abstract P3-08-09: Impact of gene-expression profiling in patients with early breast cancer when applied outside the guideline directed indication area
Authors: K Schreuder, A Kuijer, EJTh Rutgers, CH Smorenburg, T Van Dalen, S Siesling
Journal: Cancer Research (2018)

Abstract Purpose In Dutch guidelines gene expression profiles (GEP) are indicated in estrogen receptor positive early breast cancer patients in whom benefit of chemotherapy (CT) is controversial based on traditional prognostic factors alone. Aim of the current study is to assess the use and impact of GEP on administration of adjuvant CT in breast cancer patients who have according to national guidelines a clear indication to either use or withhold adjuvant chemotherapy (clinical high or low risk). Methods Clinical low- and high risk patients, according to Dutch breast cancer guidelines, diagnosed between 2011-2014 were selected from the Netherlands Cancer Registry (NCR). Influence of GEP use and GEP test result on CT administration was assessed with logistic regression. Results Overall, 26,425 patients were identified; 4.8% of patients with clinical low- risk (444/ 9,354), 7.5% of the patients with a clinical high-risk (1,281/ 17,071) received a GEP. GEP use was associated with a significantly increased odds of CT administration in clinical low-risk patients (OR=2.12 95%CI: 1.44-3.11). In clinical high-risk patients GEP use was associated with a decreased frequency of CT administration (OR=0.55, 95%CI: 0.48-0.63). Adherence to the GEP result was higher in clinical high-risk patients with a discordant GEP result as compared to clinical low-risk patients with a discordant GEP result: 71.7% vs. 52.2%, respectively. Conclusion GEP is frequently used outside the indicated area and significantly influenced the administration of adjuvant CT, although adherence to the test-result was limited. Citation Format: Schreuder K, Kuijer A, Rutgers EJTh, Smorenburg CH, Van Dalen T, Siesling S. Impact of gene-expression profiling in patients with early breast cancer when applied outside the guideline directed indication area [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 P3-08-09.
GMC pushes for automatic erasure when a doctor is convicted of a serious crime
Authors: Clare Dyer
Journal: BMJ (2018)

The General Medical Council is seeking power to strike off doctors from the UK medical register without holding a hearing if they are convicted of a serious criminal offence.

If such a power had existed when the trainee paediatrician Hadiza Bawa-Garba was convicted of gross negligence manslaughter,1 she would never have been able to present evidence of serious systemic failures to a medical practitioners’ tribunal. The tribunal took account of these in deciding not to strike her off but to suspend her for 12 months instead,2 a decision that was overturned by the High Court after the GMC appealed.3

In its response to a recent government consultation on reform to the system of professional regulation, the GMC asked for a change to its fitness to practise rules to create “a presumption of erasure from the register where a doctor …
This is a general question—is there much demand for experienced general practitioners in the English health system?
Authors: Anne Hastie
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.
Community Oncologists' Decision-Making for Treatment of Older Patients With Cancer
Authors: Supriya G. Mohile, Allison Magnuson, Chintan Pandya, Carla Velarde, Paul Duberstein, Arti Hurria, Kah Poh Loh, Megan Wells, Sandy Plumb, Nikesha Gilmore, Marie Flannery, Marsha Wittink, Ronald Epstein, Charles E. Heckler, Michelle Janelsins, Karen Mustian, Judith O. Hopkins, Jane Liu, Srihari Peri, William Dale
Journal: Journal of the National Comprehensive Cancer Network (2018)

Background: This study's objectives were to describe community oncologists' beliefs about and confidence with geriatric care and to determine whether geriatric-relevant information influences cancer treatment decisions. Methods: Community oncologists were recruited to participate in 2 multisite geriatric oncology trials. Participants shared their beliefs about and confidence in caring for older adults. They were also asked to make a first-line chemotherapy recommendation (combination vs single-agent vs no chemotherapy) for a hypothetical vignette of an older patient with advanced pancreatic cancer. Each oncologist received one randomly chosen vignette that varied on 3 variables: age (72/84 years), impaired function (yes/no), and cognitive impairment (yes/no). Other patient characteristics were held constant. Logistic regression models were used to identify associations between oncologist/vignette-patient characteristics and treatment decisions. Results: Oncologist response rate was 61% (n=305/498). Most oncologists agreed that “the care of older adults with cancer needs to be improved” (89%) and that “geriatrics training is essential” (72%). However, <25% were “very confident” in recognizing dementia or conducting a fall risk or functional assessment, and only 23% reported using the geriatric assessment in clinic. Each randomly varied patient characteristic was independently associated with the decision to treat: younger age (adjusted odds ratio [aOR], 5.01; 95% CI, 2.73–9.20), normal cognition (aOR, 5.42; 95% CI, 3.01–9.76), and being functionally intact (aOR, 3.85; 95% CI, 2.12–7.00). Accounting for all vignettes across all scenarios, 161 oncologists (52%) said they would offer chemotherapy. All variables were independently associated with prescribing single-agent over combination chemotherapy (older age: aOR, 3.22; 95% CI 1.43–7.25, impaired cognition: aOR, 3.13; 95% CI, 1.36–7.20, impaired function: aOR, 2.48; 95% CI, 1.12–5.72). Oncologists' characteristics were not associated with decisions about providing chemotherapy. Conclusion: Geriatric-relevant information, when available, strongly influences community oncologists' treatment decisions.
Pulmonary Arterial Hypertension-Related Morbidity Is Prognostic for Mortality
Authors: Vallerie V. McLaughlin, Marius M. Hoeper, Richard N. Channick, Kelly M. Chin, Marion Delcroix, Sean Gaine, Hossein-Ardeschir Ghofrani, Pavel Jansa, Irene M. Lang, Sanjay Mehta, Tomás Pulido, B.K.S. Sastry, Gérald Simonneau, Olivier Sitbon, Rogério Souza, Adam Torbicki, Victor F. Tapson, Loïc Perchenet, Ralph Preiss, Pierre Verweij, Lewis J. Rubin, Nazzareno Galiè
Journal: Journal of the American College of Cardiology (2018)

Registry data suggest that disease progression in pulmonary arterial hypertension (PAH) is indicative of poor prognosis. However, the prognostic relevance of PAH-related morbidity has not been formally evaluated in randomized controlled trials. The purpose of these analyses was to assess the impact of morbidity events on the risk of subsequent mortality using the landmark method and data from the SERAPHIN and GRIPHON studies. For each study, the risk of all-cause death up to the end of the study was assessed from the landmark time point (months 3, 6, and 12) according to whether a patient had experienced a primary endpoint morbidity event before the landmark. Each analysis was conducted using data from all patients who were available for survival follow-up at the landmark. In the SERAPHIN study, on the basis of the 3-month landmark time point, patients who experienced a morbidity event before month 3 had an increased risk of death compared with patients who did not (hazard ratio [HR]: 3.39; 95% confidence interval [CI]: 1.94 to 5.92). In the GRIPHON study, on the basis of the 3-month landmark time point, there was also an increased risk with a HR of 4.48; (95% CI: 2.98 to 6.73). Analyses based on 6-month and 12-month landmarks also showed increased risk in patients who experienced morbidity events, albeit with a reduced HR. These results demonstrate the prognostic relevance of PAH-related morbidity as defined in the SERAPHIN and GRIPHON studies, highlighting the importance of preventing disease progression in patients with PAH and supporting the clinical relevance of SERAPHIN and GRIPHON morbidity events. (Study of Macitentan [ACT-064992] on Morbidity and Mortality in Patients With Symptomatic Pulmonary Arterial Hypertension [SERAPHIN]; NCT00660179; Selexipag [ACT-293987] in Pulmonary Arterial Hypertension [GRIPHON]; NCT01106014)