tbuckley/cabot-search huggingface dataset:
Outcomes and Effect of Treatment According to Etiology in HFrEF
Authors: Craig Balmforth, Joanne Simpson, Li Shen, Pardeep S. Jhund, Martin Lefkowitz, Adel R. Rizkala, Jean L. Rouleau, Victor Shi, Scott D. Solomon, Karl Swedberg, Michael R. Zile, Milton Packer, John J.V. McMurray
Journal: JACC Heart Failure (2019)

The purpose of this study was to compare outcomes (and the effect of sacubitril/valsartan) according to etiology in the PARADIGM-HF (Prospective comparison of angiotensin-receptor-neprilysin inhibitor [ARNI] with angiotensin-converting-enzyme inhibitor [ACEI] to Determine Impact on Global Mortality and morbidity in Heart Failure) trial. Etiology of heart failure (HF) has changed over time in more developed countries and is also evolving in non-Western societies. Outcomes may vary according to etiology, as may the effects of therapy. We examined outcomes and the effect of sacubtril/valsartan according to investigator-reported etiology in PARADIGM-HF. The outcomes analyzed were the primary composite of cardiovascular death or HF hospitalization, and components, and death from any cause. Outcomes were adjusted for known prognostic variables including N terminal pro-B type natriuretic peptide. Among the 8,399 patients randomized, 5,036 patients (60.0%) had an ischemic etiology. Among the 3,363 patients (40.0%) with a nonischemic etiology, 1,595 (19.0% of all patients; 47% of nonischemic patients) had idiopathic dilated cardiomyopathy, 968 (11.5% of all patients; 28.8% of nonischemic patients) had a hypertensive cause, and 800 (9.5% of all patients, 23.8% of nonischemic patients) another cause (185 infective/viral, 158 alcoholic, 110 valvular, 66 diabetes, 30 drug-related, 14 peripartum–related, and 237 other). Whereas the unadjusted rates of all outcomes were highest in patients with an ischemic etiology, the adjusted hazard ratios (HRs) were not different from patients in the 2 major nonischemic etiology categories; for example, for the primary outcome, compared with ischemic (HR: 1.00), hypertensive 0.87 (95% confidence interval [CI]: 0.75 to 1.02), idiopathic 0.92 (95% CI: 0.82 to 1.04) and other 1.00 (95% CI: 0.85 to 1.17). The benefit of sacubitril/valsartan over enalapril was consistent across etiologic categories (interaction for primary outcome; p = 0.11). Just under one-half of patients in this global trial had nonischemic HF with reduced ejection fraction, with idiopathic and hypertensive the most commonly ascribed etiologies. Adjusted outcomes were similar across etiologic categories, as was the benefit of sacubitril/valsartan over enalapril. (Efficacy and Safety of LCZ696 Compared to Enalapril on Morbidity and Mortality of Patients With Chronic Heart Failure; NCT01035255)
Coaxial Bioprinting: Bioprinting of Cell‐Laden Microfiber: Can It Become a Standard Product? (Adv. Healthcare Mater. 9/2019)
Authors: Lei Shao, Qing Gao, Chaoqi Xie, Jianzhong Fu, Meixiang Xiang, Yong He
Journal: Advanced Healthcare Materials (2019)

In the desert of organ shortage, could cell-laden microfibers become a solution? Technically, to be a propagable cell-laden product, three necessary elements are systematically discussed. In article number 1900014, Qing Gao, Yong He, and co-workers prove that bioprinting could be the magic flute of Chinese Apsaras to help fibers acting as clinical products for tissue regeneration in the future.
Abstract 3836: A tracking and feedback registry to reduce disparities in breast cancer care
Authors: Nina Bickell, Kruti Shastri, Kezhen Fei, Soji Oluwole, Henry Godfrey, Anitha Srinivasan, Karen Hiotis, Amber Guth
Journal: Cancer Research (2008)

Abstract Background: Despite the existence of effective adjuvant treatment for early stage breast cancer, women do not always receive it, particularly, minority women. Primary treatment for breast cancer, surgery and varying combinations of radio-, chemo- and hormonal therapy, is delivered by different specialists and is often fragmented. Underuse of post-surgical adjuvant treatment occurs more commonly among women who do not see a medical oncologist despite surgeons’ referral request. To reduce underuse of adjuvant treatment due to failed connections, we tracked and fedback to surgeons information about whether their newly diagnosed breast cancer patients connected with an oncologist. Methods: We compared oncology referral rates and underuse among pre-intervention (N=677) and intervention (N=300) patients undergoing breast cancer surgery at 6 NYC hospitals. All surgeons consented to the intervention. Each surgeon chose an office person to verify eligibility and identify patient’s oncology referrals. Patients identified upcoming oncology appointment sites and times. Following scheduled visits, oncologists were called to verify patients’ connection &amp; these data were fedback to surgeons &amp; their office staff. Six months later, we abstracted in- &amp; outpatient charts. We compared rates of: completed oncology consultations and underuse of radiotherapy after breast conserving surgery, of chemotherapy for ER negative and hormonal therapy for ER positive tumors &amp;gt;1cm between pre- and intervention women with newly diagnosed early-stage breast cancer. Results: There was a significant increase in oncology consultations completed (83% to 97%; p&amp;lt;0.0001) and decrease in underuse of adjuvant treatment (21% to 14%; p&amp;lt;0.001); specifically, underuse of chemotherapy (22% to 11%; p=0.05) and hormonal therapy (20% to 8%; p=0.0004) declined. Among black and Hispanic women, underuse of radiotherapy significantly decreased (23% to 10%; p=0.02). Multivariate models, adjusting for clustering by hospital, patient age, race, stage and insurance, found the intervention increased rates of oncology consultation (OR=5.33; 95%CI: 2.68-10.60), and reduced adjuvant underuse (OR= 0.62; 95%CI: 0.42-0.93). Minority race was no longer a risk factor for an oncology consultation (OR=1.20; 95%CI: 0.69-2.08) or underuse of adjuvant therapy (OR= 1.13; 95%CI: 0.73-1.75). Conclusions: A tracking and feedback registry which closes the referral loop between surgeons and oncologists appears to improve rates of medical oncology consultation, reduces rates of adjuvant treatment underuse and eliminates the racial disparity in treatment.
Occurrence of mental health symptoms and disorders in current and former elite athletes: a systematic review and meta-analysis
Authors: Vincent Gouttebarge, João Mauricio Castaldelli-Maia, Paul Gorczynski, Brian Hainline, Mary E Hitchcock, Gino M Kerkhoffs, Simon M Rice, Claudia L Reardon
Journal: British Journal of Sports Medicine (2019)

Objectives To present an overview of the existing epidemiological evidence regarding the occurrence of mental health symptoms and disorders among current and former elite athletes. Design Systematic review and meta-analysis. Data sources Five electronic databases were searched from inception to November 2018: PubMed (MEDLINE), SportDiscus via EBSCO, PSycINFO via ProQuest, Scopus and Cochrane. Eligibility criteria for selecting studies We included original quantitative studies that were written in English, were conducted exclusively among current or former elite athletes, and presented incidence or prevalence rates of symptoms of mental disorders. Results Twenty-two relevant original studies about mental health symptoms and disorders among current elite athletes were included: they presented data especially on symptoms of distress, sleep disturbance, anxiety/depression and alcohol misuse. Meta-analyses comprising 2895 to 5555 current elite athletes showed that the prevalence of mental health symptoms and disorders ranged from 19% for alcohol misuse to 34% for anxiety/depression. Fifteen relevant original studies about mental health symptoms and disorders among former elite athletes were included: they similarly presented data especially about symptoms of distress, sleep disturbance, anxiety/depression and alcohol misuse. Meta-analyses comprising 1579 to 1686 former elite athletes showed that the prevalence of mental health symptoms and disorders ranged from 16% for distress to 26% for anxiety/depression. Conclusions Our meta-analyses showed that the prevalence of mental health symptoms and disorders ranged from 19% for alcohol misuse to 34% for anxiety/depression for current elite athletes, and from 16% for distress to 26% for anxiety/depression for former elite athletes.
How important is it to publish during your time at medical school?
Authors: Caroline Elton
Journal: BMJ (2015)

Dear Caroline

How important is it to publish during your time at medical school?

Aaron Dale, second year graduate entry medical student, University of Oxford

Caroline replies . . . 

In professional life—whether as a doctor or a psychologist—it is vital that you are clear about the limits of your knowledge. So when this question landed in my inbox, although I had a few thoughts, I wanted to garner the opinion of an academic clinician who would have a much more nuanced understanding of the key issues.

The old adage “if you want to get something done, ask a busy person” came to mind, so I emailed Jeremy Levy, consultant nephrologist, director of clinical academic training for Imperial College Academic Health science centre and clinical lead for Health Education North West London (among many other responsibilities). As expected—he came up …
Technology in medicine
Authors: Peysh Patel
Journal: BMJ (2011)

“What are the cardinal signs of cardiac tamponade?” I often begin my student supervisions with a clinical question, and this day was no exception.

“Just a second,” a student said. Without hesitation, he reached into his pocket, extracted his phone, and did a rapid search on the topic. “Raised jugular venous pressure, hypotension, and muffled heart …
Abstract P6-02-01: Not presented
Authors: J Luo, Q Chen, L Tang, L Yang, E Han, Y Chen, L Yuan
Journal: Cancer Research (2019)

Abstract This abstract was not presented at the conference. Citation Format: Luo J, Chen Q, Tang L, Yang L, Han E, Chen Y, Yuan L. Not presented [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P6-02-01.
Patent Foramen Ovale and Ischemic Stroke in Patients With Pulmonary Embolism
Authors: Emmanuelle Le Moigne, Serge Timsit, Douraied Ben Salem, Romain Didier, Yannick Jobic, Nicolas Paleiron, Raphael Le Mao, Thierry Joseph, Clément Hoffmann, Angelina Dion, Jean Rousset, Grégoire Le Gal, Karine Lacut, Christophe Leroyer, Dominique Mottier, Francis Couturaud
Journal: Annals of Internal Medicine (2019)

Background: Pulmonary embolism (PE) is associated with increased risk for ischemic stroke, but the underlying mechanism remains unclear. The authors hypothesized that paradoxical embolism through patent foramen ovale (PFO) should be the main mechanism. Objective: To determine the frequency of recent ischemic stroke in patients with symptomatic PE according to whether PFO was detected. Design: Prospective cohort study with masked assessment of stroke outcomes. (ClinicalTrials.gov: NCT01216423) Setting: 4 French hospital centers. Participants: 361 consecutive patients with symptomatic acute PE from 13 November 2009 through 21 December 2015. Intervention: Systematic contrast transthoracic echocardiography (TTE) and cerebral magnetic resonance imaging (MRI) within 7 days after enrollment. Measurements: Recent symptomatic or silent ischemic stroke was diagnosed on the basis of clinical examination and cerebral MRI showing a hypersignal on the trace diffusion-weighted image with reduction or pseudonormalization of apparent diffusion coefficient. Results: Contrast TTE was conclusive in 324 of 361 patients and showed PFO in 43 patients (13%). The median age was 66 years (interquartile range, 54 to 77 years). In total, 51% of patients (145/284) had associated deep venous thrombosis, 91% (279/306) had cardiovascular risk factors, and 10% (16/151) presented with arrhythmia (no difference between PFO and non-PFO groups). Cerebral MRI was conclusive in 315 patients. Recent ischemic stroke was more frequent in the PFO group than in the non-PFO group (9 of 42 patients [21.4%] vs. 15 of 273 patients [5.5%]; difference in proportions, 15.9 percentage points [95% CI, 4.7 to 30.7 percentage points]). Limitation: Because of inconclusive contrast TTE or MRI, 46 patients were excluded from analysis. Conclusion: Frequency of recent ischemic stroke in patients with symptomatic PE was higher in patients with PFO than in those without PFO. This finding supports the hypothesis that paradoxical embolism is an important mechanism of ischemic stroke in patients with PFO. Primary Funding Source: French Ministry of Health.
Open dissection for resection of a large submucosal tumor in the esophagus
Authors: Liansong Ye, Malay Sharma, Dan Yang, Chuncheng Wu, Xianglei Yuan, Bing Hu
Journal: Endoscopy (2019)

Endoscopic submucosal tunnel dissection (ESTD) is commonly used for resecting esophageal submucosal tumors (SMT) [1] [2]. However, it is difficult to resect many large SMTs using ESTD because the endoscopic view is obscured and the cutting line is unclear. We present here a method of open dissection for resecting a large and irregular SMT in the distal esophagus.
<i>NRG1</i> Gene Fusions Are Recurrent, Clinically Actionable Gene Rearrangements in <i>KRAS</i> Wild-Type Pancreatic Ductal Adenocarcinoma
Authors: Martin R. Jones, Laura M. Williamson, James T. Topham, Michael K.C. Lee, Angela Goytain, Julie Ho, Robert E. Denroche, GunHo Jang, Erin Pleasance, Yaoquing Shen, Joanna M. Karasinska, John P. McGhie, Sharlene Gill, Howard J. Lim, Malcolm J. Moore, Hui-li Wong, Tony Ng, Stephen Yip, Wei Zhang, Sara Sadeghi, Carolyn Reisle, Andrew J. Mungall, Karen L. Mungall, Richard A. Moore, Yussanne Ma, Jennifer J. Knox, Steven Gallinger, Janessa Laskin, Marco A. Marra, David F. Schaeffer, Steven J.M. Jones, Daniel J. Renouf
Journal: Clinical Cancer Research (2019)

Gene fusions involving neuregulin 1 (NRG1) have been noted in multiple cancer types and have potential therapeutic implications. Although varying results have been reported in other cancer types, the efficacy of the HER-family kinase inhibitor afatinib in the treatment of NRG1 fusion-positive pancreatic ductal adenocarcinoma is not fully understood.Forty-seven patients with pancreatic ductal adenocarcinoma received comprehensive whole-genome and transcriptome sequencing and analysis. Two patients with gene fusions involving NRG1 received afatinib treatment, with response measured by pretreatment and posttreatment PET/CT imaging.Three of 47 (6%) patients with advanced pancreatic ductal adenocarcinoma were identified as KRAS wild type by whole-genome sequencing. All KRAS wild-type tumors were positive for gene fusions involving the ERBB3 ligand NRG1. Two of 3 patients with NRG1 fusion-positive tumors were treated with afatinib and demonstrated a significant and rapid response while on therapy.This work adds to a growing body of evidence that NRG1 gene fusions are recurrent, therapeutically actionable genomic events in pancreatic cancers. Based on the clinical outcomes described here, patients with KRAS wild-type tumors harboring NRG1 gene fusions may benefit from treatment with afatinib.See related commentary by Aguirre, p. 4589.
An arty look at global health
Authors: Naina McCann
Journal: BMJ (2014)

At the Wellcome Collection in Euston, London a new exhibition—Foreign Bodies: Common Ground—explores the connection between global health, research and art. It’s a thought provoking project showcasing the work of six different artists who were placed in six different research centres around the world, with their brief being to learn about the ongoing research at the centre and its relationship with the local community. The art produced in response is a moving yet fun exhibition highlighting the wide areas of global research that exist, and the ideas and challenges posed by the local communities surrounding them.

As you enter the exhibition you are welcomed by three Malawian songs that deal with some of …
Microfluidic Model for Evaluation of Immune Checkpoint Inhibitors in Human Tumors
Authors: Ashley L. Beckwith, Luis F. Velásquez‐García, Jeffrey T. Borenstein
Journal: Advanced Healthcare Materials (2019)

Abstract Presented is the first demonstration of real‐time monitoring of the response of resident lymphocyte populations in biopsied tumor tissue to immunotherapeutic agents in a perfused tumor microenvironment. This technology comprises a microfluidic tumor trapping device constructed from a novel 3D‐printed, transparent, noncytotoxic substrate. The 3D‐printed device sustains viability of biopsied tissue fragments under dynamic perfusion for at least 72 h while enabling simultaneous administration of various drug treatments, illustrating a useful tool for drug development and precision medicine for immunotherapy. Confocal microscopy of the tumor tissue and resident lymphocytes in the presence of fluorescent tracers provides real‐time monitoring of tumor response to various immunotherapies. Devices are additively manufactured in Pro3dure GR‐10 (i.e., a relatively new, high‐resolution stereolithographic resin with properties suitable for biomedical applications), allowing integration of a set of finely featured functional components into a monolithically constructed platform. The presented platform comprises a new methodology for modeling and analyzing tumor response for the improved prediction of patient‐specific immunotherapy efficacy. It is acknowledged that this is the first report of human tumor fragments cultured in a dynamic perfusion system capable of testing the effect of circulating immune checkpoint inhibitors on resident tumor‐infiltrating lymphocytes.
Trends in the incidence of physician-diagnosed posttraumatic stress disorder among active-duty U.S. military personnel between 1999 and 2008
Authors: Kenneth L. Cameron, Rodney X. Sturdivant, Susan P. Baker
Journal: Military Medical Research (2019)

The impact of combat operations in Iraq and Afghanistan on the incidence of post-traumatic stress disorder (PTSD) in military service members has been poorly quantified. The purpose of this study was to examine trends in the incidence rate of physician-diagnosed PTSD in active-duty military personnel between 1999 and 2008. We conducted a retrospective cohort study utilizing data extracted from the Defense Medical Surveillance System to identify incident cases of PTSD within the study population. The incidence rate of physician-diagnosed PTSD was the primary outcome of interest. Multivariable Poisson regression was used to analyze the data. The overall incidence rate of PTSD among all active-duty US military personnel was 3.84 (95% CI: 3.81, 3.87) cases per 1000 person-years. The adjusted average annual percentage increase in the incidence rate of PTSD prior to the initiation of Operation Iraqi Freedom (OIF) was a modest 5.02% (95% CI: 1.85, 8.29%). Following the initiation of OIF, the average annual percentage increase in the rate of PTSD was 43.03% (95% CI: 40.55, 45.56%). Compared to the baseline period between 1999 and 2002, the incidence rate of PTSD in 2008 was nearly 7 times higher (RR = 6.85, 95% CI: 6.49, 7.24). Significant increases in the incidence rate of PTSD were observed following the initiation of OIF regardless of sex, age, race, marital status, military rank, or branch of military service. Notably, the rate of PTSD among females was 6–7 times higher prior to OIF, but there was no difference by gender by 2008. Overall, these data quantify the significant increase in the incidence rate of PTSD following the initiation of combat operations in Iraq and Afghanistan within the active-duty military population during the study period.
You’ve been bleeped: patient with a fever
Authors: Lucie Weatherall, James Bonnington, Andrew Clarke
Journal: BMJ (2015)

Patients with a fever on the ward might have been admitted with infection that is not improving or admitted for another reason and developed a hospital acquired infection. An infection is not the only differential for a patient with fever so keep an open diagnostic mind. Whatever the cause of the patient’s fever, a high temperature is often the first presentation of a serious illness or serious deterioration so you need to be adept with your clinical assessment and speedy when instigating an initial management plan. #### Scenario It is Sunday morning. You are the foundation year one doctor (FY1) on call covering the general medical wards at a busy district general hospital. You are finishing the insertion of an intravenous cannula for a patient, when you are bleeped by ward 15. Bleep “Is that the FY1 on call for medicine? My name is Nicole, I’m a nurse on ward 15. I’m calling about a woman called Peggy Lee who I’m worried about because she has spiked a temperature of 39ºC. She is 61 years old and has pneumonia. Can you come and review her?” ### How should you react to this bleep on the phone? A new or recurring fever is a common bleep. The definition of a fever is a temperature greater than 37.8°C measured with an oral or auricular thermometer, or 38.2°C measured with a rectal thermometer. Fever is one part of the systemic inflammatory response syndrome (SIRS). This syndrome is the body’s reaction to a large number of insults, and is a potential signal of major disease. Fever on its own is not enough to diagnose SIRS—two or more of the following features must be present1:
Immune Suppression by PD-L2 against Spontaneous and Treatment-Related Antitumor Immunity
Authors: Tokiyoshi Tanegashima, Yosuke Togashi, Koichi Azuma, Akihiko Kawahara, Ko Ideguchi, Daisuke Sugiyama, Fumio Kinoshita, Jun Akiba, Eiji Kashiwagi, Ario Takeuchi, Takuma Irie, Katsunori Tatsugami, Tomoaki Hoshino, Masatoshi Eto, Hiroyoshi Nishikawa
Journal: Clinical Cancer Research (2019)

To evaluate the detailed immunosuppressive role(s) of PD-L2 given that its detailed role(s) remains unclear in PD-1 signal blockade therapy in animal models and humans.We generated mouse cell lines harboring various status of PD-L1/PD-L2 and evaluated the tumor growth and phenotypes of tumor-infiltrated lymphocytes using several PD-1 signal blockades in animal models. In humans, the correlation between immune-related gene expression and CD274 (encoding PD-L1) or PDCD1LG2 (encoding PD-L2) was investigated using The Cancer Genome Atlas (TCGA) datasets. In addition, PD-L1 or PD-L2 expression in tumor cells and CD8+ T-cell infiltration were assessed by IHC.In animal models, we showed that PD-L2 expression alone or simultaneously expressed with PD-L1 in tumor cells significantly suppressed antitumor immune responses, such as tumor antigen-specific CD8+ T cells, and was involved in the resistance to treatment with anti-PD-L1 mAb alone. This resistance was overcome by anti-PD-1 mAb or combined treatment with anti-PD-L2 mAb. In clinical settings, antitumor immune responses were significantly correlated with PD-L2 expression in the tumor microenvironment in renal cell carcinoma (RCC) and lung squamous cell carcinoma (LUSC).We propose that PD-L2 as well as PD-L1 play important roles in evading antitumor immunity, suggesting that PD-1/PD-L2 blockade must be considered for optimal immunotherapy in PD-L2-expressing cancers, such as RCC and LUSC.
Abstract P3-03-04: Withdrawn
Authors: S Wu, Y Wang, J Li, N Zhang, G Liu
Journal: Cancer Research (2019)

Abstract This abstract was withdrawn by the authors. Citation Format: Wu S, Wang Y, Li J, Zhang N, Liu G. Withdrawn [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P3-03-04.