tbuckley/cabot-search huggingface dataset:
Hidden Curricula, Ethics, and Professionalism: Optimizing Clinical Learning Environments in Becoming and Being a Physician: A Position Paper of the American College of Physicians
Authors: Lisa Soleymani Lehmann, Lois Snyder Sulmasy, Sanjay Desai
Journal: Annals of Internal Medicine (2018)

Much of what is formally taught in medicine is about the knowledge, skills, and behaviors required of a physician, including how to express compassion and respect for patients at the bedside. What is learned, however, includes not only admirable qualities but also behaviors and qualities that are inconsistent with ethics and professionalism. Positive role models may reinforce the character and values the profession seeks to cultivate; negative ones directly contradict classroom lessons and expectations of patients, society, and medical educators. These positive and negative lessons, which are embedded in organizational structure and culture, are the hidden curricula conveyed in medical schools, residency programs, hospitals, and clinics. This position paper from the American College of Physicians focuses on ethics, professionalism, and the hidden curriculum. It provides strategies for revealing what is hidden to foster the development of reflective and resilient lifelong learners who embody professionalism and clinicians who are, and are perceived as, positive role models. Making the hidden visible and the implicit explicit helps to create a culture reflecting medicine's core values.
Transcriptional Profiling of Synovial Macrophages Using Minimally Invasive Ultrasound‐Guided Synovial Biopsies in Rheumatoid Arthritis
Authors: Arthur M. Mandelin, Philip J. Homan, Alexander M. Shaffer, Carla M. Cuda, Salina T. Dominguez, Emily Bacalao, Mary Carns, Monique Hinchcliff, Jungwha Lee, Kathleen Aren, Anjali Thakrar, Anna B. Montgomery, S. Louis Bridges, Joan M. Bathon, John P. Atkinson, David A. Fox, Eric L. Matteson, Christopher D. Buckley, Costantino Pitzalis, Deborah Parks, Laura B. Hughes, Laura Geraldino‐Pardilla, Robert Ike, Kristine Phillips, Kerry Wright, Andrew Filer, Stephen Kelly, Eric M. Ruderman, Vince Morgan, Hiam Abdala‐Valencia, Alexander V. Misharin, G. Scott Budinger, Elizabeth T. Bartom, Richard M. Pope, Harris Perlman, Deborah R. Winter
Journal: Arthritis & Rheumatology (2018)

Objective Currently, there are no reliable biomarkers for predicting therapeutic response in patients with rheumatoid arthritis ( RA ). The synovium may unlock critical information for determining efficacy, since a reduction in the numbers of sublining synovial macrophages remains the most reproducible biomarker. Thus, a clinically actionable method for the collection of synovial tissue, which can be analyzed using high‐throughput strategies, must become a reality. This study was undertaken to assess the feasibility of utilizing synovial biopsies as a precision medicine‐based approach for patients with RA. Methods Rheumatologists at 6 US academic sites were trained in minimally invasive ultrasound‐guided synovial tissue biopsy. Biopsy specimens obtained from patients with RA and synovial tissue from patients with osteoarthritis ( OA ) were subjected to histologic analysis, fluorescence‐activated cell sorting, and RNA sequencing ( RNA ‐seq). An optimized protocol for digesting synovial tissue was developed to generate high‐quality RNA ‐seq libraries from isolated macrophage populations. Associations were determined between macrophage transcriptional profiles and clinical parameters in RA patients. Results Patients with RA reported minimal adverse effects in response to synovial biopsy. Comparable RNA quality was observed from synovial tissue and isolated macrophages between patients with RA and patients with OA . Whole tissue samples from patients with RA demonstrated a high degree of transcriptional heterogeneity. In contrast, the transcriptional profile of isolated RA synovial macrophages highlighted different subpopulations of patients and identified 6 novel transcriptional modules that were associated with disease activity and therapy. Conclusion Performance of synovial tissue biopsies by rheumatologists in the US is feasible and generates high‐quality samples for research. Through the use of cutting‐edge technologies to analyze synovial biopsy specimens in conjunction with corresponding clinical information, a precision medicine–based approach for patients with RA is attainable.
RACIAL DISPARITIES AND TRENDS OF THE HUMAN IMMUNODEFICIENCY VIRUS (HIV)-ASSOCIATED INFECTIVE ENDOCARDITIS (IE) HOSPITALIZATION AND COMPLICATIONS: NATIONAL INPATIENT REVIEW
Authors: Rupak Desai, Upenkumar Patel, Sandeep Singh, Bhrugesh Shah, Manan Shah, Smit Patel, Shuba Balan
Journal: Journal of the American College of Cardiology (2018)
Tumor-Associated Fatigue in Cancer Patients Develops Independently of IL1 Signaling
Authors: Aaron J. Grossberg, Elisabeth G. Vichaya, Diana L. Christian, Jessica M. Molkentine, Daniel W. Vermeer, Phillip S. Gross, Paola D. Vermeer, John H. Lee, Robert Dantzer
Journal: Cancer Research (2017)

Fatigue is the most common symptom of cancer at diagnosis, yet causes and effective treatments remain elusive. As tumors can be highly inflammatory, it is generally accepted that inflammation mediates cancer-related fatigue. However, evidence to support this assertion is mostly correlational. In this study, we directly tested the hypothesis that fatigue results from propagation of tumor-induced inflammation to the brain and activation of the central proinflammatory cytokine, IL1. The heterotopic syngeneic murine head and neck cancer model (mEER) caused systemic inflammation and increased expression of Il1b in the brain while inducing fatigue-like behaviors characterized by decreased voluntary wheel running and exploratory activity. Expression of Il1b in the brain was not associated with any alterations in motivation, measured by responding in a progressive ratio schedule of food reinforcement, depression-like behaviors, or energy balance. Decreased wheel running occurred prior to Il1b detection in the brain, when systemic inflammation was minimal. Furthermore, mice null for two components of IL1β signaling, the type 1 IL1 receptor or the receptor adapter protein MyD88, were not protected from tumor-induced decreases in wheel running, despite attenuated cytokine action and expression. Behavioral and inflammatory analysis of four additional syngeneic tumor models revealed that tumors can induce fatigue regardless of their systemic or central nervous system inflammatory potential. Together, our results show that brain IL1 signaling is not necessary for tumor-related fatigue, dissociating this type of cancer sequela from systemic cytokine expression.Significance: These findings challenge the current understanding of fatigue in cancer patients, the most common and debilitating sequela associated with malignancy. Cancer Res; 78(3); 695-705. ©2017 AACR.
Development funding for SAS doctors in England drops by £1.1m
Authors: Helen Jaques
Journal: BMJ (2013)

Professional development funding for staff, associate specialist, and specialty (SAS) doctors in England has fallen by £1.1m (14%) over the past four years (2010-11 to 2013-14), figures from Health Education England show. 

In 2008 the Department of Health made £12m of recurrent funding available for the professional development of SAS grade doctors and dentists in England. This money supports SAS doctors in training and career development activities, such as leadership training, mentoring, appraisal, and clinical skills acquisition or consolidation.

The amount of development funding available to SAS doctors has fallen over the past four years in eight of 11 regions in England.⇓ The biggest drop in funding was in the East Midlands, …
The application of artificial intelligence and machine learning to automate Gleason grading: Novel tools to develop next generation risk assessment assays.
Authors: Michael Joseph Donovan, Richard Scott, Faisal m Khan, Jack Zeineh, Gerardo Fernandez
Journal: Journal of Clinical Oncology (2018)

170 Background: Postoperative risk assessment remains an important variable in the treatment of prostate cancer (PCA). Advances in genomic risk classifiers have aided clinical-decision making; however, clinical-pathologic variables such as Gleason grade and pathologic stage remain significant comparators for accurate prognostication. We aimed to standardize the descriptive pathology of PCA through automation of Gleason grading with artificial intelligence and image analysis feature selection Methods: Retrospective study using radical prostatectomy (RP) tissue microarrays from Henry Ford Hospital and Roswell Park Cancer Center with 8-year median follow-up. Samples were stained with a multiplex immunofluorescent assay: Androgen Receptor (AR), Ki67, Cytokeratin 18, Cytokeratin 5/6 and Alpha-methylacyl-CoA racemase); imaged with a CRI Nuance FX camera and then analyzed with proprietary software to generate a suite of morphometric - attributes that quantitatively characterize the Gleason spectrum. Derived features were univariately correlated with disease progression using the concordance index (CI) along with the hazards ratio and p-value. Results: Starting with a training cohort of 306 patients and a 15% event rate, MIF PCA images were subjected to a machine learning analysis program which incorporates a graph theory-based approach for characterization of gland / ring fusion and fragmentation of tumor architecture (TA) with biomarker quantitation (BQ) (i.e. AR and Ki67). 19 unique image features with 7 TA and 12 TA+BQ were identified, by univariate CI, all TA features were strongly associated with Gleason grading with CI’s reflecting degree of tumor differentiation (CI 0.29-.33, p-value = 0.005). Four TA+BQ features were selected in a training risk model and effectively replaced the clinical Gleason features. By comparison, dominant RP Gleason had a CI of 0.31. Conclusions: Image-based feature selection guided by principles of machine learning has the potential to automate and replace traditional Gleason grading. Such approaches provide the necessary foundation for next generation risk assessment assays.
The Radial Artery for Percutaneous Coronary Procedures or Surgery?
Authors: Mario Gaudino, Francesco Burzotta, Faisal Bakaeen, Olivier Bertrand, Filippo Crea, Antonino Di Franco, Stephen Fremes, Ferdinand Kiemeneij, Yves Louvard, Sunil V Rao, Thomas A Schwann, James Tatoulis, Robert F Tranbaugh, Carlo Trani, Marco Valgimigli, Pascal Vranckx, David P Taggart
Journal: Journal of the American College of Cardiology (2018)
Capecitabine Efficacy Is Correlated with TYMP and RB1 Expression in PDX Established from Triple-Negative Breast Cancers
Authors: Elisabetta Marangoni, Cécile Laurent, Florence Coussy, Rania El-Botty, Sophie Château-Joubert, Jean-Luc Servely, Ludmilla de Plater, Franck Assayag, Ahmed Dahmani, Elodie Montaudon, Fariba Nemati, Justine Fleury, Sophie Vacher, David Gentien, Audrey Rapinat, Pierre Foidart, Nor Eddine Sounni, Agnès Noel, Anne Vincent-Salomon, Marick Lae, Didier Decaudin, Sergio Roman-Roman, Ivan Bièche, Martine Piccart, Fabien Reyal
Journal: Clinical Cancer Research (2018)

Purpose: Triple-negative breast cancer (TNBC) patients with residual disease after neoadjuvant chemotherapy have a poor outcome. We developed patient-derived xenografts (PDX) from residual tumors to identify efficient chemotherapies and predictive biomarkers in a context of resistance to anthracyclines- and taxanes-based treatments.Experimental Design: PDX were established from residual tumors of primary breast cancer patients treated in neoadjuvant setting. TNBC PDX were treated by anthracyclines, taxanes, platins, and capecitabine. Predictive biomarkers were identified by transcriptomic and immunohistologic analysis. Downregulation of RB1 was performed by siRNA in a cell line established from a PDX.Results: Residual TNBC PDX were characterized by a high tumor take, a short latency, and a poor prognosis of the corresponding patients. With the exception of BRCA1/2-mutated models, residual PDX were resistant to anthracyclines, taxanes, and platins. Capecitabine, the oral prodrug of 5-FU, was highly efficient in 60% of PDX, with two models showing complete responses. Prior treatment of a responder PDX with 5-FU increased expression of thymidylate synthase and decreased efficacy of capecitabine. Transcriptomic and IHC analyses of 32 TNBC PDX, including both residual tumors and treatment-naïve derived tumors, identified RB1 and TYMP proteins as predictive biomarkers for capecitabine response. Finally, RB1 knockdown in a cell line established from a capecitabine-responder PDX decreased sensitivity to 5-FU treatment.Conclusions: We identified capecitabine as efficient chemotherapy in TNBC PDX models established from residual disease and resistant to anthracyclines, taxanes, and platins. RB1 positivity and high expression of TYMP were significantly associated with capecitabine response. Clin Cancer Res; 24(11); 2605-15. ©2018 AACR.
Abstract 13955: Small Conductance Ca2+-activated K+ Current is Upregulated via the Phospholylation of CaMKII in Cardiac Hypertrophy
Authors: Kazuya Mizukami, Hisashi Yokoshiki, Hirofumi Mitsuyama, Masaya Watanabe, Taro Tenma, Rui Kamada, Shingo Takada, Hiroyuki Tsutsui
Journal: Circulation (2015)

Background: Left ventricular hypertrophy is associated with increased risk of ventricular arrhythmias. However, the underlying molecular basis is poorly understood. It has been reported that small-conductance Ca2+-activated K+ (SK) channel is involved in the pathogenesis of ventricular arrhythmias in heart failure. We have recently reported that the activity of calcium/calmodulin-dependent protein kinase II (CaMKII) is increased in hypertensive cardiac hypertrophy. Objective: The aim of this study is to test the hypothesis that SK channels activity is increased via the CaMKII-dependent pathway in hypertensive cardiac hypertrophy. Methods and Results: We used normotensive Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR). Whole cell membrane current was recorded in isolated ventricular myocyte by the patch-clamp method, and apamin-sensitive K+ current (IKAS), inhibited by apamin (100 nM), a blocker of SK channel, was evaluated. IKAS at 40 mV was present in SHR, whereas it was hardly detectable in WKY (0.579±0.046 pA/pF vs 0.022±0.062 pA/pF, both n=6, p&lt;0.05). IKAS was almost completely abolished by 1 μM KN-93, an inhibitor of CaMKII, in SHR. Optical recordings of action potential in left ventricular anterior wall revealed that apamin prolonged the late phase of repolarization only in SHR (APD90 113.07±3.62 vs 124.95±3.62 msec, both n=4, p&lt;0.05, and APD50 37.53±4.21 vs 50.48±4.21 msec, both n=4, p&lt;0.05). Western blot analysis of SK channel protein isoform demonstrated that SK2 was significantly increased in SHR compared to WKY (SK2/GAPDH 0.66±0.07 vs 0.40±0.02, both n=6, p&lt;0.05), whereas SK1 and SK3 did not differ between groups. In addition, autophosphorylated CaMKII was significantly increased in SHR (pCaMKII/GAPDH 0.80±0.06 vs 0.58±0.06, both n=6, p&lt;0.05) despite comparable total amount of CaMKII between groups. Conclusion: SK channels are upregulated via the enhanced activation of CaMKII in hypertensive cardiac hypertrophy.
Lactobacillus gasseri in the Upper Small Intestine Impacts an ACSL3-Dependent Fatty Acid-Sensing Pathway Regulating Whole-Body Glucose Homeostasis
Authors: Paige V. Bauer, Frank A. Duca, T.M. Zaved Waise, Helen J. Dranse, Brittany A. Rasmussen, Akshita Puri, Mozhgan Rasti, Catherine A. O'Brien, Tony K.T. Lam
Journal: Cell Metabolism (2018)
Death Is a Small Thing
Authors: C. Scott Williams
Journal: Annals of Internal Medicine (2018)

Ad Libitum6 March 2018Death Is a Small ThingC. Scott Williams, MDC. Scott Williams, MDFrom Hunstville, Alabama.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/M17-1915 Audio Reading - “Death Is a Small Thing” Audio. Michael A. LaCombe, MD, Annals Associate Editor, reads "Death Is a Small Thing," by C.S. Williams. Your browser does not support the audio element. Audio player progress bar Step backward in current audio track Play current audio trackPause current audio track Step forward in current audio track Mute current audio trackUnmute current audio track 00:00/ SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Somewhere between here and belowI am trying to live,But can only despair and tearfully giveLoops of thought to your memory.Somewhere between here and belowI had plannedMore time to kiss your infant hand,More years to watch you crawlAnd stand—Not sleep beneath the dirt and sand.Somewhere between here and belowI crave,And search my life like a cold black caveFor some happiness I might yet saveBetween now and the solaceOf an adjacent grave. Author, Article, and Disclosure InformationAffiliations: From Hunstville, Alabama.Current Author Address: C. Scott Williams, MD; e-mail, [email protected]net. PreviousarticleNextarticle Advertisement Audio Reading - “Death Is a Small Thing” Audio. Michael A. LaCombe, MD, Annals Associate Editor, reads "Death Is a Small Thing," by C.S. Williams. Your browser does not support the audio element. Audio player progress bar Step backward in current audio track Play current audio trackPause current audio track Step forward in current audio track Mute current audio trackUnmute current audio track 00:00/ FiguresReferencesRelatedDetails Metrics 6 March 2018Volume 168, Issue 5Page: 373-374KeywordsHappinessInfantsMemorySleep ePublished: 6 March 2018 Issue Published: 6 March 2018 Copyright & PermissionsCopyright © 2018 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
LETTER OF THE MONTH Teaching communication skills: should we give up?
Authors: Stephen R Humble
Journal: BMJ (2007)

We welcome your rapid responses, whether in direct response to an article in Career Focus or as a way of sharing your own ideas. As long as it isn9t libellous or offensive, we9ll post it on our website. We print a selection of rapid reponses here and the writer of the best each month wins an <i>Oxford Handbook</i> of their choice. Letter of the month prize is donated by OUP.
An evaluation of the surgical treatment strategy for the adenocarcinoma of the esophagogastric junction: A retrospective single center study in Japan.
Authors: Shizuki Sugita, Masanori Tokunaga, Akio Kaito, Masahiro Watanabe, Akiko Tonouchi, Takahiro Kinoshita
Journal: Journal of Clinical Oncology (2018)

177 Background: The incidence of Siewert type II adenocarcinoma of the esophagogastric junction (AEG II) has been increasing in the East, and total gastrectomy (TG) has been a standard treatment procedure. However, it is reported that the incidence of distal perigastric lymph node (LN) metastasis is low, and thus proximal gastrectomy (PG) could be a treatment option. The aim of this study was to demonstrate the oncological safety of PG for patients with AEG II. Methods: This study included 99 patients with AEG II who underwent gastrectomy with lower esophagectomy from Jan. 2008 to June 2017. Patients with esophageal invasion over 30 mm, and those with positive LN in the upper/middle mediastinum were excluded. PG was selected when more than half of the stomach could be preserved, and no obvious distal perigastric LN metastasis was found. Surgical approach was selected at the patients’ discretion. Short- and long-term outcomes were compared between patients who underwent TG (N = 43) and PG (N = 56). Results: Laparoscopic surgery was the predominant procedure (75.0%) in the PG group while open surgery was most frequently selected (79.1%) in the TG group. Intraoperative and short-term surgical outcomes were not different between the groups except for intraoperative blood loss, which was less in the PG group than in the TG group. Survival outcomes tended to be better in the PG group than in the TG group (3-/5-year OS, 91.1%/ 91.1% vs 67.4%/ 65.1%), presumably due to the predominance of early stage cancers in the PG group. After stratification by pStage, however, survival outcomes were not significantly different between the groups in any pStage. In the PG group, distal perigastric LN reccurence was not found during the follow-up period. In the TG group, 2 patients (4.7%) had distal perigastric LN metastasis, and both died within 2 years of surgery. Conclusions: Therapeutic value of distal perigastric LN dissection is quite limited in patients with AEG II. PG seems to be as oncologically safe as TG, and could be a suitable treatment strategy for patients with AEG II.
Interim analysis of a prospective randomized trial of dietary carbohydrate restriction for men with a rising PSA after failed primary treatment: Carbohydrate and Prostate Study 2 (CAPS2).
Authors: Stephen J. Freedland, Jenifer Allen, Andrew J. Armstrong, Judd W. Moul, Howard M. Sandler, Dana Levin, Lauren E. Howard, Pao-hwa Lin
Journal: Journal of Clinical Oncology (2018)

382 Background: Nearly one third of men treated with curative intent for localized prostate cancer (PC) will develop a rising PSA. The rate of PSA rise (PSA doubling time aka PSASDT) is a predictor metastases and PC death. In laboratory mice, an extreme low carbohydrate diet slows PC growth. We tested whether this diet could slow PSADT in men with recurrent PC. Methods: We are conducting a 6-month multi-center randomized phase II trial of dietary carbohydrate restriction vs. no diet intervention control. Men had to have a BMI ≥24 kg/m2, received radical prostatectomy or definitive local radiation for PC, had a PSA 0.4-20.0 ng/ml (3-20 if prior radiation therapy) within the past 3 months, and current PSADT 3-36 months. The intervention arm was instructed to eat &lt; 20 grams/carbs/day with no other limits. The control arm was told to make no diet. In this interim analysis, we present the efficacy of the dietary intervention with regards to weight loss. Arms were compared using rank-sum. Total anticipated enrollment is 60. The primary outcome is differences in PSADT between arms. Secondary outcomes include weight loss, and dietary make-up. Results: To date, 28 patients (14 in each study arm) have completed the study. Characteristics were well-balanced at baseline. At the 6-month dietary assessment, calorie consumption was similar between the two study arms (p = 0.090) among the 16 patients (7 low-carb, 9 control) with diet information. Subjects in the low-carb arm ate fewer carbs (29 vs. 188 g, p = 0.008) and more protein (125 vs. 73 g, p = 0.044) but similar amounts of fat (75 vs. 67 g, p = 0.672) vs. subjects in the control arm. Six months on the low carb diet resulted in greater weight loss (median: 31.7 vs. 0.8 lbs, p &lt; 0.001), lower BMI (24.4 vs. 29.6 kg/m 2 , p &lt; 0.001), and smaller waist circumference (95.7 vs. 108.9 cm, p = 0.002). Conclusions: In this interim analysis of an on-going dietary study for men with a rising PSA after definitive local treatment, an extreme low carbohydrate diet results in dramatic weight loss in 6 months. Whether this weight loss slows PC growth is an on-going question. Clinical trial information: NCT01763944.
ASSOCIATIONS AMONG CUMULATIVE SOCIAL RISK, IDEAL CARDIOVASCULAR HEALTH AND EXPOSURE TO ENVIRONMENTAL POLLUTANTS
Authors: Ann Canterbury, Sebhat Erqou, Jane Clougherty, Claudia Bambs, Ellen J. Kinnee, Sheila Tripathy, Daniel Shpilsky, Jared Magnani, Aryan Aiyer, Steven Reis
Journal: Journal of the American College of Cardiology (2018)