tbuckley/cabot-search huggingface dataset:
Organ Dysfunction After Surgery in Patients Treated With Individualized or Standard Blood Pressure Management
Authors: Robert H. Thiele
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
Immune Infiltration in Invasive Lobular Breast Cancer
Authors: Christine Desmedt, Roberto Salgado, Marco Fornili, Giancarlo Pruneri, Gert Van den Eynden, Gabriele Zoppoli, Françoise Rothé, Laurence Buisseret, Soizic Garaud, Karen Willard-Gallo, David Brown, Yacine Bareche, Ghizlane Rouas, Christine Galant, François Bertucci, Sherene Loi, Giuseppe Viale, Angelo Di Leo, Andrew R Green, Ian O Ellis, Emad A Rakha, Denis Larsimont, Elia Biganzoli, Christos Sotiriou
Journal: JNCI Journal of the National Cancer Institute (2017)

Invasive lobular breast cancer (ILC) is the second most common histological subtype of breast cancer after invasive ductal cancer (IDC). Here, we aimed at evaluating the prevalence, levels, and composition of tumor-infiltrating lymphocytes (TILs) and their association with clinico-pathological and outcome variables in ILC, and to compare them with IDC. We considered two patient series with TIL data: a multicentric retrospective series (n = 614) and the BIG 02-98 study (n = 149 ILC and 807 IDC). We compared immune subsets identified by immuno-histochemistry in the ILC (n = 159) and IDC (n = 468) patients from the Nottingham series, as well as the CIBERSORT immune profiling of the ILC (n = 98) and IDC (n = 388) METABRIC and The Cancer Genome Atlas patients. All ILC/IDC comparisons were done in estrogen receptor (ER)–positive/human epidermal growth factor receptor 2 (HER2)–negative tumors. All statistical tests were two-sided. TIL levels were statistically significantly lower in ILC compared with IDC (fold-change = 0.79, 95% confidence interval = 0.70 to 0.88, P < .001). In ILC, high TIL levels were associated with young age, lymph node involvement, and high proliferative tumors. In the univariate analysis, high TIL levels were associated with worse prognosis in the retrospective and BIG 02-98 lobular series, although they did not reach statistical significance in the latter. The Nottingham series revealed that the levels of intratumoral but not total CD8+ were statistically significantly lower in ILC compared with IDC. Comparison of the CIBERSORT profiles highlighted statistically significant differences in terms of immune composition. This study shows differences between the immune infiltrates of ER-positive/HER2-negative ILC and IDC in terms of prevalence, levels, localization, composition, and clinical associations.
Drug Resistance in HER2-Positive Breast Cancer Brain Metastases: Blame the Barrier or the Brain?
Authors: Sheheryar Kabraji, Jing Ni, Nancy U. Lin, Shaozhen Xie, Eric P. Winer, Jean J. Zhao
Journal: Clinical Cancer Research (2018)

The brain is the most common site of first metastasis for patients with HER2-positive breast cancer treated with HER2-targeting drugs. However, the development of effective therapies for breast cancer brain metastases (BCBM) is limited by an incomplete understanding of the mechanisms governing drug sensitivity in the central nervous system. Pharmacodynamic data from patients and in vivo models suggest that inadequate drug penetration across the "blood-tumor" barrier is not the whole story. Using HER2-positive BCBMs as a case study, we highlight recent data from orthotopic brain metastasis models that implicate brain-specific drug resistance mechanisms in BCBMs and suggest a translational research paradigm to guide drug development for treatment of BCBMs. Clin Cancer Res; 24(8); 1795-804. ©2018 AACR.
Meningiomas: Brain invasion as a marker for classification
Authors: Giannis Sokratous, Charlotte Burford, Daniel Loh, Keyoumars Ashkan, Ranj Bhangoo, Francesco Vergani
Journal: Neuro-Oncology (2018)

Brain invasion in meningiomas is considered a significant prognostic factor, as suggested by the most recent WHO classification on brain tumours. In the present study, we review the impact of brain invasion on the grading, treatment protocols and prognosis of meningiomas in a general neuro-oncology practice. Retrospective analysis of data from 2008 until 2016 using the electronic record system used in our institution. We collected data on the overall number of patients with grade I, II and unclassified grade, gender, year of operation, presence of brain invasion or not, Simpson grading and treatment following surgery. 512 patients with meningiomas grade I, II and unclassified grading were identified. Brain invasion was reported in 10.9%, no invasion in 88.5% and probable invasion was reported in 3.51% of all patients. Of the latter group 23.5% were reported as grade I, 41.2% as grade II and 35.3% as unclassified meningiomas with probable brain invasion. For the patients with probable brain invasion: 100% of patients with grade I meningioma had resection Simpson grade II; 42.8% of patients with grade II meningioma had resection Simpson grade IV and 57.1% resection grade II; 50% of patients in the unclassified group had resection Simpson grade II and 50% had resection grade IV. Following surgery, all patients were followed up with image surveillance. Recurrence was observed in two patients in the unclassified group and in one patient in the meningioma grade II group. Brain invasion in meningiomas is common (1 in 11 in our series): this will increase the number of meningiomas classified as grade II according to the new WHO classification, with likely implications on follow up and treatment. In a small number of cases, uncertainty on the presence of brain invasion made it difficult to accurately grade the meningioma.
The Economic Value of CTL019 Therapy for Pediatric Patients with Relapsed and Refractory Acute Lymphoblastic Leukemia in the United Kingdom
Authors: Julia Snider, Michelle Brauer, Yanni Hao, Pinar Karaca-Mandic, Mahlet Gizaw Tebeka, Jie Zhang, Katharine Batt
Journal: Blood (2017)
My work in epidemiology does not include any clinical practice, but clinical registration was a necessary qualification for the post and I use my clinical knowledge daily. What is my position with regard to appraisal?
Authors: Brian Keighley
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>
Long-term efficacy of reduced-intensity versus myeloablative conditioning before allogeneic haemopoietic cell transplantation in patients with acute myeloid leukaemia in first complete remission: retrospective follow-up of an open-label, randomised phase 3 trial
Authors: Frederick Fasslrinner, Johannes Schetelig, Andreas Burchert, Michael Kramer, Rudolf Trenschel, Ute Hegenbart, Michael Stadler, Kerstin Schäfer-Eckart, Michael Bätzel, Hans Eich, Martin Stuschke, Rita Engenhart-Cabillic, Mechthild Krause, Peter Dreger, Andreas Neubauer, Gerhard Ehninger, Dietrich Beelen, Wolfgang E Berdel, Timo Siepmann, Matthias Stelljes, Martin Bornhäuser
Journal: The Lancet Haematology (2018)
BMA says it is willing to continue consultant contract negotiations
Authors: Abi Rimmer
Journal: BMJ (2015)

The BMA has said that it would be willing to resume negotiations with the government on the contract for consultants.

Negotiations on the contract for consultants in England and Northern Ireland were referred to the Review Body on Doctors’ and Dentists’ Remuneration (DDRB) in October 2014 after talks between the BMA and NHS Employers stalled.1

Speaking to BMJ Careers, Paul Flynn, chairman of the BMA’s Consultants Committee, said that the BMA was willing to continue negotiations …
Association of Rideshare-Based Transportation Services and Missed Primary Care Appointments
Authors: Krisda H. Chaiyachati, Rebecca A. Hubbard, Alyssa Yeager, Brian Mugo, Stephanie Lopez, Elizabeth Asch, Catherine Shi, Judy A. Shea, Roy Rosin, David Grande
Journal: JAMA Internal Medicine (2018)

<h3>Importance</h3> Transportation barriers contribute to missed primary care appointments for patients with Medicaid. Rideshare services have been proposed as alternatives to nonemergency medical transportation programs because of convenience and lower costs. <h3>Objective</h3> To evaluate the association between rideshare-based medical transportation and missed primary care appointments among Medicaid patients. <h3>Design, Setting, and Participants</h3> In a prospective clinical trial, 786 Medicaid beneficiaries who resided in West Philadelphia and were established primary care patients at 1 of 2 academic internal medicine practices located within the same building were included. Participants were allocated to being offered complimentary ride-sharing services (intervention arm) or usual care (control arm) based on the prescheduled day of their primary care appointment reminder. Those scheduled on even-numbered weekdays were in the intervention arm and on odd-numbered weekdays, the control arm. The primary study outcome was the rate of missed appointments, estimated using an intent-to-treat approach. All individuals receiving a phone call reminder were included in the study sample, regardless of whether they answered their phone. The study was conducted between October 24, 2016, and April 20, 2017. <h3>Interventions</h3> A model of providing rideshare-based transportation was designed. As part of usual care, patients assigned to both arms received automated appointment phone call reminders. As part of the study protocol, patients assigned to both arms received up to 3 additional appointment reminder phone calls from research staff 2 days before their scheduled appointment. During these calls, patients in the intervention arm were offered a complimentary ridesharing service. Research staff prescheduled rides for those interested in the service. After their appointment, patients phoned research staff to initiate a return trip home. <h3>Main Outcomes and Measures</h3> Missed appointment rate (no shows and same-day cancellations) in the intervention compared with control arm. <h3>Results</h3> Of the 786 patients allocated to the intervention or control arm, 566 (72.0%) were women; mean (SD) age was 46.0. (12.5) years. Within the intervention arm, 57 among 288 (19.8%) participants who answered the phone call used ridesharing. The missed appointment rate was 36.5% (144 of 394) for the intervention arm and 36.7% (144 of 392) for the control arm (<i>P</i> = .96). <h3>Conclusions and Relevance</h3> The uptake of ridesharing was low and did not decrease missed primary care appointments. Future studies trying to reduce missed appointments should explore alternative delivery models or targeting populations with stronger transportation needs. <h3>Trial Registration</h3> clinicaltrials.gov Identifier:NCT02955433
The effect of surfactant on the physical properties of coconut oil nanoemulsions
Authors: Sirikarn Pengon, Nawinda Chinatangkul, Chutima Limmatvapirat, Sontaya Limmatvapirat
Journal: Asian Journal of Pharmaceutical Sciences (2018)

The aim of this study was to develop the water compatible form of coconut oil through nano-emulsification. The effect of different types and amounts of surfactants on the physical characteristics of nanoemulsions containing coconut oil was investigated. Coconut oil nanoemulsions containing varied amounts of surfactants including polyethylene glycol octyl phenyl ether (PGO), polyoxyethylene sorbitan monostearate (POS), polyethylene glycol hydrogenated castor oil (PHC), sodium lauryl sulfate (SLS) and poloxamer 407 (PLX) were formulated and comparatively evaluated for their physical properties. The results showed that the coconut oil nanoemulsions using PGO, POS and PHC as surfactants exhibited low percent creaming index indicating excellent stability, while those containing SLS and PLX demonstrated the higher percent creaming index suggesting lesser physical stability. The droplet sizes of nanoemulsions consisting of 5% (w/w) PGO, POS and PHC were 22.843, 4.458 and 0.162 µm, respectively. Thus, coconut oil nanoemulsions with the smallest size could be obtained when PHC was applied. Furthermore, the droplet size of nanoemulsions decreased from 33 µm to less than 200 nm with an increase in the amount of PHC from 1% to 10% (w/w). Additionally, the properties of coconut oil based nanoemulsions containing PHC were not changed through temperature cycling test. From these results, it was suggested that the fabrication of stable coconut oil nanoemulsions with small particle size could be easily achieved by using 5% (w/w) PHC as a surfactant. The knowledge gained from the study might provide the basic guideline for the fabrication of stable nanoemulsions for food, cosmetic and pharmaceutical fields in the future.
The perineural invasion paradox: Is perineural invasion an independent prognostic indicator of biochemical recurrence risk in patients with pT2N0 prostate cancer?
Authors: Ryan Kraus, Nathan Cheng, Lingyun Ji, Richard Lester Stephen Jennelle, Susan G. Groshen, Leslie Ballas
Journal: Journal of Clinical Oncology (2018)

6 Background: Perineural invasion is a histologic feature present in approximately 19% of patients with prostate cancer. The prognostic significance of perineural invasion is controversial with recent studies yielding contradictory results. This study aims to assess whether perineural invasion on surgical pathology of patients with pT2N0 disease is an independent prognostic indicator of the risk of biochemical recurrence. Methods: We identified 201 patients with non-metastatic pT2N0 prostate cancer at our institution between 1/1/2008-12/31/2014. We reviewed the electronic medical record of these patients and identified whether the patient had biochemical recurrence (defined as PSA &gt; 0.2 after surgery). A multivariable analysis was then performed using clinical and histological data for each patient to assess the association between perineural invasion and biochemical recurrence. Results: Of the 201 patients identified, 68.1% (137/201) had perineural invasion and 14% (28/201) had biochemical recurrence. Perineural invasion was associated with pT2c disease (p &lt; 0.001), an increased number of positive cores on biopsy (p &lt; 0.001), and a higher surgical Gleason score (p &lt; 0.001). 19% of patients with perineural invasion had disease recurrence compared to 3.1% without perineural invasion (p = 0.001, Hazard ratio of 6.2). After performing a multivariable analysis and accounting for pathologic tumor staging and Gleason score, perineural invasion had a trend towards a significant association with recurrence (p = 0.085, Hazard ratio of 3.2). Conclusions: Perineural invasion may be an indicator of unfavorable histology such as a high Gleason score or more widespread disease rather than an independent prognostic indicator of the risk of biochemical recurrence.
Lifestyle factors and risk of sporadic colorectal cancer by microsatellite instability status: a systematic review and meta-analyses
Authors: P.R. Carr, E. Alwers, S. Bienert, J. Weberpals, M. Kloor, H. Brenner, M. Hoffmeister
Journal: Annals of Oncology (2018)

IntroductionThe association of lifestyle factors with molecular pathological subtypes of colorectal cancer (CRC), such as microsatellite instability (MSI), could provide further knowledge about the colorectal carcinogenic process. The aim of this review was to evaluate possible associations between lifestyle factors and risk of sporadic CRC by MSI status.MethodsPubMed and Web of Science were searched for studies investigating the association between alcohol, body mass index, dietary fiber, hormone replacement therapy (HRT), non-steroidal anti-inflammatory drugs, physical activity, red meat, smoking, or statin use, with MSI-high (MSI-H) and microsatellite stable (MSS) CRC. Meta-analyses were carried out to calculate summary relative risks (sRR).ResultsOverall, 31 studies reporting on the association between lifestyle factors and CRC according to MSI status were included in this review. Ever smoking was associated with MSI-H (sRR = 1.62; 95% CI: 1.40–1.88) and MSS/MSI-low CRC (sRR = 1.10; 95% CI: 1.01–1.20), but the association was significantly stronger for MSI-H CRC. The use of HRT was associated with a 20% decrease (sRR = 0.80; 95% CI: 0.73–0.89) in the risk of MSS CRC, but was not associated with MSI-H CRC. An increase in body mass index per 5 kg/m2 was equally associated with MSS and MSI-H CRC (sRR = 1.22, in both cases), but was statistically significant for MSS CRC only (95% CI: 1.11–1.34 and 0.94–1.58, respectively). Limited evidence for associations between other lifestyle factors and CRC by MSI status exists.ConclusionsLifestyle factors, such as HRT and smoking are differentially associated with the risk of MSI-H and MSS CRC. Further research on associations of lifestyle factors and CRC subtypes is necessary to provide a better understanding of the CRC disease pathway.
Abstract BS3-2: Breast cancer intra-tumor heterogeneity and its clinical implications
Authors: CM Perou Perou
Journal: Cancer Research (2018)

Abstract Breast cancer is a known heterogeneous disease with significant inter-tumor differences being manifested on many levels including histology, response to therapy, and patient survival outcomes. Importantly, even within an individual tumor, significant heterogeneity may exist. This intra-tumor heterogeneity (ITH) poses a challenge to understanding the biology of breast cancer, and an open question is what impact does ITH have on the clinical decision making process? Over the past ten years, a rich body of genetic, genomic, and proteomic data has been accumulated concerning the ITH of breast cancers. Much of these data is coming from Massively Parallel Sequencing, and it is yielding a wealth of quantitative data concerning DNA- and RNA-based ITH. This variation can be in the form of somatic mutations, DNA copy number changes, and gene expression differences due to epigenetic differences (i.e. cell state changes) and or microenvironmental influences. Notable recent examples of DNA-based ITH include PIK3CA mutation heterogeneity across different metastatic sites within the same patient with some lesions responding to PI3K inhibitors while others did not. Another key example of ITH are ESR1 mutations that arise within the setting of aromatase inhibitor treatment, where it is sometimes seen that within an individual, multiple different mutations in ESR1 can occur and that confer estrogen independence. Lastly, significant epigenetic ITH can also occur, with a prime example being epithelial tumor cell plasticity, which is often manifested as “state changes”. Examples of this include chemotherapy induced changes that may select for epithelial cells with more mesenchymal features (often referred to as EMT), and which is also typically linked to a more treatment resistant state. Another important concept that is emerging is that it might be better to target the clonal (or trunk) alterations, as opposed to targeting the subclonal variation. The latter, by definition, is not present within all tumor cells, and thus even if that therapy is effective, it will not target all tumor cells. Conversely, if clonal variants (i.e. those present within the founding clone) are targeted, the treatment may be more effective and cause regression and/or complete response. These multiple examples of ITH are biologically important, but the question still remains, what are the clinical implications? These ITH topics will be presented and discussed within the context of how these findings might affect treatment options and decision making. Citation Format: Perou Perou CM. Breast cancer intra-tumor heterogeneity and its clinical implications [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 BS3-2.
GPs in Scotland agree three year contract freeze
Authors: Abi Rimmer
Journal: BMJ (2014)

GPs in Scotland will not have their contracts negotiated again for three years, the BMA has announced.

Last year the BMA’s General Practitioners Committee for Scotland agreed changes with the Scottish government to the GP contract for 2014-15.1 But the BMA announced on Wednesday that it had agreed a deal with the Scottish government meaning that the contract …
Characteristics Associated With Preferences for Parent-Centered Decision Making in Neonatal Intensive Care
Authors: Elliott Mark Weiss, Dawei Xie, Noah Cook, Katherine Coughlin, Steven Joffe
Journal: JAMA Pediatrics (2018)

Little is known about how characteristics of particular clinical decisions influence decision-making preferences by patients or their surrogates. A better understanding of the factors underlying preferences is essential to improve the quality of shared decision making.