tbuckley/cabot-search huggingface dataset:
Gaps in Receipt of Clinically Indicated Genetic Counseling After Diagnosis of Breast Cancer
Authors: Steven J. Katz, Kevin C. Ward, Ann S. Hamilton, M. Chandler Mcleod, Lauren P. Wallner, Monica Morrow, Reshma Jagsi, Sarah T. Hawley, Allison W. Kurian
Journal: Journal of Clinical Oncology (2018)

Purpose Little is known about the extent to which genetic counseling is integrated into community practices for patients newly diagnosed with breast cancer. We examined the receipt of clinically indicated genetic counseling in these patients. Patients and Methods We surveyed 5,080 patients between the ages of 20 and 79 years, diagnosed from July 2013 to August 2015 with early-stage breast cancer and reported to the SEER registries of Georgia and Los Angeles County. Surveys were linked to SEER clinical data and genetic test results. The study sample (N = 1,711) comprised patients with indications for formal genetic risk evaluation. Results Overall, 47.4% did not get tested, 40.7% tested negative, 7.4% had a variant of uncertain significance only, and 4.5% had a pathogenic mutation. Three quarters (74.6%) received some form of genetic counseling (43.5%, formal counseling and 31.1%, physician-directed discussion). Virtually all tested patients (96.1%) reported some form of genetic discussion (62.2%, formal counseling and 33.9%, physician-directed discussion). However, only one half (50.6%) of those not tested received any discussion about genetics. Younger women were more likely to report some type of counseling, controlling for other factors: odds ratio, 4.5 (95% CI, 2.6 to 8.0); 1.9 (95% CI, 1.1 to 3.3); and 1.5 (95% CI, 1.0 to 2.3) for women younger than 50 years of age, 50 to 59 years of age, and 60 to 69 years of age versus those 70 years of age and older. Patients' assessments of the amount of information they received about whether to get tested were similarly high whether they were counseled by a genetics expert or by a physician only (80.8% v 79.4% stated information was just right, P = .59). Conclusion Less than one half (43.5%) of patients with clinical indications received formal genetic counseling. There is a large gap between mandates for timely pretest formal genetic counseling in higher-risk patients and the reality of practice today.
Developmental roots of episodic memory
Authors: Katherine Nelson
Journal: Behavioral and Brain Sciences (2018)

Abstract Two arguments imply that Mahr &amp; Csibra's (M&amp;C's) functional theory is insufficient as an explanation of episodic memory: (1) The developmental course supports a different social cultural division of episodic and semantic memory, and (2) the existence of long-term autobiographical memory is not explained in the functional theory but can be seen in a broader cultural framework.
Lead or be led
Authors: L James Livermore
Journal: BMJ (2010)

Lead or be led is a unique two day residential course for those who want to learn more about the structure and function of the NHS and to develop their leadership and management skills. The majority of the delegates on my course were specialist registrars, and there were a number of senior nurses, allied health professionals, and trainee managers.

I took this course during my first year of core surgical training.

The NHS chief executive and Lord Darzi in his Next Stage review have highlighted leadership at all levels as a key factor in precipitating change in the NHS, with a drive to increase the number of clinicians undertaking management roles. …
Electrophysiological Source Imaging: A Noninvasive Window to Brain Dynamics
Authors: Bin He, Abbas Sohrabpour, Emery Brown, Zhongming Liu
Journal: Annual Review of Biomedical Engineering (2018)

Brain activity and connectivity are distributed in the three-dimensional space and evolve in time. It is important to image brain dynamics with high spatial and temporal resolution. Electroencephalography (EEG) and magnetoencephalography (MEG) are noninvasive measurements associated with complex neural activations and interactions that encode brain functions. Electrophysiological source imaging estimates the underlying brain electrical sources from EEG and MEG measurements. It offers increasingly improved spatial resolution and intrinsically high temporal resolution for imaging large-scale brain activity and connectivity on a wide range of timescales. Integration of electrophysiological source imaging and functional magnetic resonance imaging could further enhance spatiotemporal resolution and specificity to an extent that is not attainable with either technique alone. We review methodological developments in electrophysiological source imaging over the past three decades and envision its future advancement into a powerful functional neuroimaging technology for basic and clinical neuroscience applications.
Abstract 19465: 3-D Super-Resolution Microscopy of Mitochondrial Internalization in Cardiac Cells
Authors: Douglas B Cowan, Rouan Yao, Jerusha K Thedsanamoorthy, Pedro J del Nido, James D McCully
Journal: Circulation (2016)

Ischemia and reperfusion of the heart negatively impacts the function of mitochondria, which results in energy deficits attributable to the impairment of oxidative phosphorylation through loss of high energy phosphate reserves, accumulation of calcium, and excessive reactive oxygen species generation. While these events are initiated during ischemia, they extend throughout reperfusion to compromise functional recovery and cell viability. To preserve cardiac viability and functional performance, we developed a unique approach to support the heart by injecting ischemic regions with exogenous mitochondria isolated from a remote, autologous, non-ischemic tissue at the onset of reperfusion. We discovered treated hearts have increased adenosine triphosphate (ATP) stores, reduced infarct sizes, and improved contractile function. Intriguingly, we observed some transplanted mitochondria were internalized by cardiomyocytes; however, little was known about their intracellular fate. Here, we used a baculovirus-expression system to target fluorescent proteins to specific organelles and cell structures in iPS-derived human cardiomyocytes and human cardiac fibroblasts. Cells were incubated with isolated mitochondria labeled with a different colored fluorophore for 0, 1, 2, 4, 8, and 24 hours. Following incubation, samples were prepared for 3-D super-resolution microscopy. Using structured illumination, we found internalized exogenous mitochondria fused with the endogenous mitochondrial network in both cell types. Although some internalized mitochondria were associated with early endosomes, there was little or no co-localization with late endosomes, lysosomes, the Golgi complex, or sarcoplasmic reticulum. Mitochondrial fusion was obvious by 4 hours and persisted for 24 hours. Measurements of ATP production and oxygen consumption in parallel experiments confirmed the addition of exogenous mitochondria functionally benefited treated cells. Further investigation of this biological phenomenon may guide the development of treatments directed at replacing or augmenting impaired mitochondria in the ischemic heart as well as in a wide range of mitochondrial diseases.
Pyotr Vasilyevich Nikolsky—The Man Behind the Sign
Authors: Aria Shakeri
Journal: JAMA Dermatology (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 Dermatology 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 Dermatology journal
Abstract P3-01-09: Re-evaluating the “10% rule” for sentinel lymph node biopsy with radioactive method in breast cancer; a single institutional retrospective study
Authors: H Miyamoto, T Aruga, M Onishi, R Goto, N Iwamoto, N Idera, K Horiguchi, Y Honda
Journal: Cancer Research (2018)

Abstract Background: When multiple radioactive sentinel lymph nodes (SLNs) are present during sentinel lymph node biopsy (SLNB), excision of those SLNs with &amp;gt;10% radioactive count per minute (high-CPM) of the most radioactive node (“10% rule”) has been proposed. Although this “10% rule” may avoid excessive removal of SLNs,the risk of false negative and remnant positive SLNs in the patients who have SLNs with &amp;lt;10% CPM (low-CPM) remain unclear. The purpose of this analysis is to determine the clinical validity of this “10% rule” for early breast cancer patients. Method: We reviewed the records of successful SLNBs using the radioisotope (RI) method performed between January 2001 and December 2016 in our institution. The radioactive count from each excised SLN was measured. Non-radioactive lymph nodes were excluded from this analysis. All SLNs were pathologically assessed by 2mm serial section with hematoxylin and eosin staining. Results: In the 3,043 patients with successful SLNB,the median number of radioactive SLNs removed was 2 (mean, 1.8; range, 1-10) and 599 patients (19.7%) had SLNs with low-CPM. The total number of radioactive SLNs was 5,472, and 875 (16.0%) out of 5,472 SLNs were low-CPM. Sixty-one (7.0%) out of these 875 SLNs with low CPM in 56 patients (1.8%) had metastatic disease by pathological assessment. The number of metastatic SLN with low-CPM was one in 51 patients and two in 5 patients. Nineteen patients (0.6%) had no metastatic lesion in SLNs with high-CPM. Discussion and Conclusions: If SLNB was performed by RI method alone with “10% rule”, false negative rate increased by 0.6% and underestimation increased up to 1.8%. Furthermore, 19.7% of the patients have the benefit of avoiding excessive removal of SLNs.Considering the risk and benefit, “10% rule” is a high validitymethod to capture metastatic SLNs even in the setting that ALND will not be performed. Citation Format: Miyamoto H, Aruga T, Onishi M, Goto R, Iwamoto N, Idera N, Horiguchi K, Honda Y. Re-evaluating the “10% rule” for sentinel lymph node biopsy with radioactive method in breast cancer; a single institutional retrospective study [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 P3-01-09.
Blood-brain barrier penetration of [14C]darolutamide compared with [14C]enzalutamide in rats using whole body autoradiography.
Authors: Christian Zurth, Steffen Sandmann, Dagmar Trummel, Dietrich Seidel, Hille Gieschen
Journal: Journal of Clinical Oncology (2018)

345 Background: Darolutamide (ODM-201) (Daro) is an investigational oral and high-affinity androgen receptor antagonist. In preclinical studies, penetration of Daro through the blood–brain barrier (BBB) is negligible and in a retrospective safety analysis of the ARADES database for CNS-related adverse events (AEs), only 1 report of urinary incontinence was linked to Daro (Fizazi K, et al. 2015). Various clinical trials on enzalutamide (Enza) have reported CNS AEs (eg, seizure, falls, fatigue, pain). To understand the differences in CNS outcomes, we report an in vivo tissue distribution study with [ 14 C]-labelled Enza and Daro in a head-to-head study in rats by means of quantitative whole-body autoradiography (QWBA). Methods: Male rats were orally dosed with 10 mg/kg [ 14 C]Daro or [ 14 C]Enza in the same formulation, administration volume, and radioactive dose. The animals were sacrificed at each drug’s specific t max (time to reach the maximum concentration) in blood and brain and processed for QWBA. Results: At early time points [ 14 C]Daro- and [ 14 C]Enza-derived radioactivity was rapidly absorbed from the gastrointestinal tract and homogenously distributed throughout the body. By 8 h post dose, [ 14 C]Daro was significantly eliminated from almost all organs/tissues, whereas [ 14 C]Enza remained constant within the body. In contrast to [ 14 C]Daro, high and persistent radioactivity was observed in brain for [ 14 C]Enza. At t max , the brain/blood-ratio of [ 14 C]Enza was ~0.765, while [ 14 C]Daro was about 10-fold lower at ~0.074. Conclusions: Results show that post dose, there was a 10-fold lower BBB penetration of [ 14 C]Daro compared with [ 14 C]Enza. At 8 h, [ 14 C]Daro was rapidly eliminated and almost undetectable in all tissues, including brain, in contrast to [ 14 C]Enza that remained constant. These data suggest that Daro might have a lower risk of inducing CNS-related AEs than Enza. Further clinical studies are ongoing.
Antidepressant Use by Class: Association with Major Adverse Cardiac Events in Patients with Coronary Artery Disease
Authors: Sherry L. Grace, Jose R. Medina-Inojosa, Randal J. Thomas, Heather Krause, Kristin S. Vickers-Douglas, Brian A. Palmer, Francisco Lopez-Jimenez
Journal: Psychotherapy and Psychosomatics (2018)

To assess use of antidepressants by class in relation to cardiology practice recommendations, and the association of antidepressant use with the occurrence of major adverse cardiovascular events (MACE) including death.This is a historical cohort study of all patients who completed cardiac rehabilitation (CR) between 2002 and 2012 in a major CR center. Participants completed the Patient Health Questionnaire (PHQ-9) at the start and end of the program. A linkage system enabled ascertainment of antidepressant use and MACE through 2014.There were 1,694 CR participants, 1,266 (74.7%) of whom completed the PHQ-9 after the program. Depressive symptoms decreased significantly from pre- (4.98 ± 5.20) to postprogram (3.57 ± 4.43) (p < 0.001). Overall, 433 (34.2%) participants were on antidepressants, most often selective serotonin reuptake inhibitors (SSRI; n = 299; 23.6%). The proportion of days covered was approximately 70% for all 4 major antidepressant classes; discontinuation rates ranged from 37.3% for tricyclics to 53.2% for serotonin-norepinephrine reuptake inhibitors (SNRI). Antidepressant use was significantly associated with lower depressive symptoms after CR (before, 7.33 ± 5.94 vs. after, 4.69 ± 4.87; p < 0.001). After a median follow-up of 4.7 years, 264 (20.9%) participants had a MACE. After propensity matching based on pre-CR depressive symptoms among other variables, participants taking tricyclics had significantly more MACE than those not taking tricyclics (HR = 2.46; 95% CI 1.37-4.42), as well as those taking atypicals versus not (HR = 1.59; 95% CI 1.05-2.41) and those on SSRI (HR = 1.45; 95% CI 1.07-1.97). There was no increased risk with use of SNRI (HR = 0.89; 95% CI 0.43-1.82).The use of antidepressants was associated with lower depression, but the use of all antidepressants except SNRI was associated with more adverse events.
Predictors of improved biochemical progression free survival for salvage prostate bed radiotherapy after radical prostatectomy.
Authors: Emma Grace Wright, Amarnath Challapalli, Paul White, Rajendra Persad, Susan Masson, Hannah Kirk, Serena Hilman, Anthony Koupparis, Edward Rowe, Amit Bahl
Journal: Journal of Clinical Oncology (2018)

38 Predictors of improved biochemical progression free survival for salvage prostate bed radiotherapy after radical prostatectomy Background: About a third of patients undergoing radical prostatectomy (RP) develop biochemical recurrence, the rate of which increases to ~50% in high risk patients, with adverse features such as positive margins &amp; seminal vesicle invasion. Postop salvage radiotherapy (SRT) to the prostate bed improves biochemical progression free survival (bPFS). We sought to evaluate the benefit of SRT and predictors of bPFS. Methods: Patients who received SRT from Jan11 to Dec15 were retrospectively analysed. All patients had prostate bed radiotherapy (66Gy/33#/6.5wks). Hormone therapy (HT), when used was for a short duration of 3-6 months. PSA relapse after SRT was defined as serum PSA rising above the posttreatment nadir to a level of ≥0.2 ng/mL or by the initiation of HT after completion of SRT. The bPFS was calculated as the time from start of SRT till date of undetectable PSA, analysed by Kaplan-Meier estimates and log-rank test. Results: Overall, 111 patients were analysed. Median follow-up was 46 (range; 6-80) months. 46% (51/111) patients received HT. The median pre-SRT PSA was 0.4 ng/mL (range, 0.07 to 4.9). The bPFS rate was 60.4% overall, 65%for those with a pre-SRT PSA (ng/mL) level of ≤0.5 (n = 74), 53.6% for those with a PSA of &gt; 0.5 to ≤1.5 (n = 28), 44.4% for those with a PSA of &gt; 1.5 (n = 9); (p = 0.33). There was no significant difference in bPFS rates for pre-SRT PSA of ≤0.2 compared to PSA ≤0.5. Significantly improved bPFS rates were seen with an interval of &gt; 6m from detectable PSA to start of SRT (69% vs. 46.5%: p = 0.026), and a trend towards better bPFS rates when the time interval was &gt; 24m from RP to first detectable PSA (73% vs. 53%: p = 0.08). However, bPFS was similar in the proportion of patients (46%) who had HT compared to those (54%) who did not have HT. Conclusions: We have shown that there was no significant difference in bPFS rates between early (detectable PSA at 0.2) and deferred SRT and our data supports the practice of deferred SRT prior to PSA going above 0.5. Short course of HT was not shown to improve bPFS. The ongoing RADICALS and RAVE trials will further clarify these aspects.
Blocking IFNAR1 inhibits multiple myeloma–driven Treg expansion and immunosuppression
Authors: Yawara Kawano, Oksana Zavidij, Jihye Park, Michele Moschetta, Katsutoshi Kokubun, Tarek H. Mouhieddine, Salomon Manier, Yuji Mishima, Naoka Murakami, Mark Bustoros, Romanos Sklavenitis Pistofidis, Mairead Reidy, Yu J. Shen, Mahshid Rahmat, Pavlo Lukyanchykov, Esilida Sula Karreci, Shokichi Tsukamoto, Jiantao Shi, Satoshi Takagi, Daisy Huynh, Antonio Sacco, Yu-Tzu Tai, Marta Chesi, P. Leif Bergsagel, Aldo M. Roccaro, Jamil Azzi, Irene M. Ghobrial
Journal: Journal of Clinical Investigation (2018)

Despite significant advances in the treatment of multiple myeloma (MM), most patients succumb to disease progression. One of the major immunosuppressive mechanisms that is believed to play a role in myeloma progression is the expansion of regulatory T cells (Tregs). In this study, we demonstrate that myeloma cells drive Treg expansion and activation by secreting type 1 interferon (IFN). Blocking IFN α and β receptor 1 (IFNAR1) on Tregs significantly decreases both myeloma-associated Treg immunosuppressive function and myeloma progression. Using syngeneic transplantable murine myeloma models and bone marrow (BM) aspirates of MM patients, we found that Tregs were expanded and activated in the BM microenvironment at early stages of myeloma development. Selective depletion of Tregs led to a complete remission and prolonged survival in mice injected with myeloma cells. Further analysis of the interaction between myeloma cells and Tregs using gene sequencing and enrichment analysis uncovered a feedback loop, wherein myeloma-cell-secreted type 1 IFN induced proliferation and expansion of Tregs. By using IFNAR1-blocking antibody treatment and IFNAR1-knockout Tregs, we demonstrated a significant decrease in myeloma-associated Treg proliferation, which was associated with longer survival of myeloma-injected mice. Our results thus suggest that blocking type 1 IFN signaling represents a potential strategy to target immunosuppressive Treg function in MM.
PRIMARY CARDIAC TUMOR PRESENTING WITH CARDIAC TAMPONADE: ACUTE EMERGENCY BY PERCUTANEOUS CORONARY INTERVENTION
Authors: Alexandra Shilova, Ekaterina Konstantinova, Viktoria Shemenkova, Dmitry Shchekochikhin, Anna Udovichenko, Michail Gilarov, Alexey Svet
Journal: Journal of the American College of Cardiology (2018)
Readily prepared biodegradable nanoparticles to formulate poorly water soluble drugs improving their pharmacological properties: The example of trabectedin
Authors: Umberto Capasso Palmiero, Lavinia Morosi, Ezia Bello, Marianna Ponzo, Roberta Frapolli, Cristina Matteo, Mariella Ferrari, Massimo Zucchetti, Lucia Minoli, Marcella De Maglie, Pierpaolo Romanelli, Massimo Morbidelli, Maurizio D'Incalci, Davide Moscatelli
Journal: Journal of Controlled Release (2018)
A clinical insight into therapeutic sequence in advanced melanoma.
Authors: Jesus Vera Aguilera, Jonas Paludo, Marcella Tschautscher, Cecilia Yu, Narjust Duma, Svetomir Markovic
Journal: Journal of Clinical Oncology (2018)

186 Background: The optimal sequence strategy of BRAF/MEK inhibitors, anti-PD- 1/PDL-1 and anti-CTLA-4 in metastatic BRAF-mutated melanoma patients (pts) is unknown and no treatment guidelines exist. Therefore, we report a single-institution experience of different treatment approaches using targeted therapy (TT) and immunotherapy and its impact on outcomes. Methods: BRAF-mutated metastatic melanoma pts treated with TT and immunotherapy from 2012 to2017 were analyzed. Six groups were identified based on treatment strategy. All time-to-event analyses were calculated using the Kaplan-Meier method and Wilcoxon test. Results: Forty-four pts were identified. The median age at diagnosis was 49 years (range 21-73), 54% pts were females and 43% developed brain metastases during disease course. The most common approach strategy was immunotherapy followed by TT, the median duration of treatment was 11 and 19 weeks, respectively. Time-to-next therapy (TTNT) following 1 st line treatment was similar in pts treated with TT (median 23 weeks [95% CI: 15-31]) or immunotherapy (median 26 weeks [95% CI: 10-33], p = 0.94). A trend towards better overall survival (OS) was seen in pts who received immunotherapy followed by TT (p = 0.09); patients who received salvage chemotherapy (carboplatin/paclitaxel) had significantly longer OS (median 7 years [95% CI: 3.2-7.08]) ( p = 0.03). Conclusions: No differences in TTNT were seen with immunotherapy, TT or combined (triple therapy) when used as 1 st or 2 nd line. The significant longer OS benefit with 1 st line immunotherapy was only seen in patients who received chemotherapy later in their treatment course. [Table: see text]
<i>Editor’s Choice</i>Paving the way to general practice
Authors: Tom Moberly
Journal: BMJ (2016)

Currently, there is only one way into a career as a doctor in general practice. This is to pass the membership examination of the Royal College of General Practitioners (the MRCGP exam).

Kamal Sidhu believes that it is time not only to update the exam but also to think about whether we should …
CORRELATION OF EKG BASED SITE OF ORIGIN OF VENTRICULAR ARRHYTHMIAS WITH SITE OF INFLAMMATION ON FDG-PET SCAN IN PATIENTS WITH ARRHYTHMOGENIC INFLAMMATORY CARDIOMYOPATHY
Authors: Bharath Yarlagadda, Madhav Lavu, Tawseef Dar, Venkat Lakshmi Kishan Vuddanda, Ali Jazayeri, Mohit Turagam, Valay Parikh, Seth Sheldon, Rhea Pimentel, Martin Emert, Loren Berenbom, Raghuveer Dendi, Madhu Reddy, Kalyanam Shivkumar, Roderick Tung, Luigi Di Biase, Andrea Natale, Dhanunjaya R. Lakkireddy
Journal: Journal of the American College of Cardiology (2018)
Doctors are professional group most likely to claim on car insurance
Authors: Abi Rimmer
Journal: BMJ (2014)

Doctors are the professional group most likely to make claims on car insurance, analysis by the comparison website GoCompare.com has found. In a list of the top 10 professions of drivers who made at least one claim in 2013, GPs came first and hospital consultants second, and all but one of the top 10 professions were health related.

GoCompare.com found that, of the 3366 GPs who used the …