tbuckley/cabot-search huggingface dataset:
Abstract 023: Left Ventricular Hypertrophy and Elevated Biomarkers of Chronic Myocardial Injury May Identify African Americans With a Very High Risk for Heart Failure Development: Findings From The Jackson Heart Study
Authors: Ambarish PANDEY, Neil Keshvani, Colby Ayers, Adolfo Correa, Mark Drazner, Carlos Rodriguez, Michael Hall, Robert Mentz, James de Lemos, Jarett Berry
Journal: Circulation (2018)

Introduction: African Americans (AA) have a disproportionate greater burden of risk factors and higher risk of HF than Whites. However, the factors underlying the transition from at-risk to clinical HF in AA is not well understood. We aimed to examine the independent and joint effects of subclinical myocardial injury, as measured by highly sensitive assays for cardiac troponin (hs-TnI) and left ventricular hypertrophy (LVH), on risk of HF in AA. Methods: Participants from the Jackson Heart Study, a prospective study of AA adults, without prevalent HF at baseline (2000-2004) were stratified into categories based on elevation in hs-cTnI (&gt;6 ng/L) and presence of LVH (LV mass &gt; 96 g/m 2 in women and &gt; 116 g/m 2 in men). The risk of incident HF across different LVH and hs-cTnI groups was assessed using adjusted Cox models. Results: We included 3,796 participants (54 y, 64% women, 17.2% with elevated hs-TnI &amp; 6.1% with LVH) with median follow up of 9.8 y and 285 incident HF events. In adjusted analyses, LVH and higher hs-TnI at baseline were independently associated with risk of HF [HR (95% CI): LVH (vs. no LVH) = 2.2(1.6 - 2.9); Log hs-cTnI (per unit higher)=1.6(1.5 - 1.8)]. A significant interaction was observed between LVH and hs-TnI for the risk of HF (p-int &lt; 0.0001) with the highest risk among individuals with both LVH and elevated hs-TnI [43% incidence, HR (95% CI): 5.7(3.9 - 8.2)]. In contrast, LVH in absence of hs-TnI elevation was not associated with HF risk [ Figure ]. Among 2,367 participants with repeat assessment of hs-TnI at 5 year follow-up, increase in hs-TnI levels on follow-up was also associated with significantly higher risk of HF [HR (95% CI) per 1 unit increase = 1.03 (1.02 - 1.06)] Conclusions: The combination of LVH and elevated hs-TnI levels identifies a malignant preclinical HF phenotype in AAs with a remarkably high absolute risk of HF over a 10-year f/u period. Longitudinal increase in hs-TnI levels is also associated with significant risk of HF. Targeting these high-risk subsets may be an important strategy to mitigate HF risk in blacks.
Human Organ Miniaturization: 3D Miniaturization of Human Organs for Drug Discovery (Adv. Healthcare Mater. 2/2018)
Authors: Joseph Park, Isaac Wetzel, Didier Dréau, Hansang Cho
Journal: Advanced Healthcare Materials (2018)

The cover artwork for the article number 1700551 by Hansang Cho and co-workers reviews the current state-of-the-art in engineering and miniaturizing human organ 3D models and overviews the major engineering technologies: organoids, microfabrication, 3D bioprinting, used for the organ construction. Cover illustration by You Jung Kang. CT images of organs kindly provided by NIH.
Epigenetic modification in histone deacetylase deletion strain of Calcarisporium arbuscula leads to diverse diterpenoids
Authors: Jian Bai, Rong Mu, Man Dou, Daojiang Yan, Bingyu Liu, Qian Wei, Jun Wan, Yi Tang, Youcai Hu
Journal: Acta Pharmaceutica Sinica B (2018)

Epigenetic modifications have been proved to be a powerful way to activate silent gene clusters and lead to diverse secondary metabolites in fungi. Previously, inactivation of a histone H3 deacetylase in Calcarisporium arbuscula had led to pleiotropic activation and overexpression of more than 75% of the biosynthetic genes and isolation of ten compounds. Further investigation of the crude extract of C. arbuscula ΔhdaA strain resulted in the isolation of twelve new diterpenoids including three cassanes (1-3), one cleistanthane (4), six pimaranes (5-10), and two isopimaranes (11 and 12) along with two know cleistanthane analogues. Their structures were elucidated by extensive NMR spectroscopic data analysis. Compounds 2 and 4 showed potent inhibitory effects on the expression of MMP1 and MMP2 (matrix metalloproteinases family) in human breast cancer (MCF-7) cells.
Association of Hypercapnia and Hypercapnic Acidosis With Clinical Outcomes in Mechanically Ventilated Patients With Cerebral Injury
Authors: Ravindranath Tiruvoipati, David Pilcher, John Botha, Hergen Buscher, Robert Simister, Michael Bailey
Journal: JAMA Neurology (2018)

Clinical studies investigating the effects of hypercapnia and hypercapnic acidosis in acute cerebral injury are limited. The studies performed so far have mainly focused on the outcomes in relation to the changes in partial pressure of carbon dioxide and pH in isolation and have not evaluated the effects of partial pressure of carbon dioxide and pH in conjunction.To review the association of compensated hypercapnia and hypercapnic acidosis during the first 24 hours of intensive care unit admission on hospital mortality in adult mechanically ventilated patients with cerebral injury.Multicenter, binational retrospective review of patients with cerebral injury (traumatic brain injury, cardiac arrest, and stroke) admitted to 167 intensive care units in Australia and New Zealand between January 2000 and December 2015. Patients were classified into 3 groups based on combination of arterial pH and arterial carbon dioxide (normocapnia and normal pH, compensated hypercapnia, and hypercapnic acidosis) during the first 24 hours of intensive care unit stay.Hospital mortality.A total of 30 742 patients (mean age, 55 years; 21 827 men [71%]) were included. Unadjusted hospital mortality rates were highest in patients with hypercapnic acidosis. Multivariable logistic regression analysis and Cox proportional hazards analysis in 3 diagnostic categories showed increased odds of hospital mortality (cardiac arrest odds ratio [OR], 1.51; 95% CI, 1.34-1.71; stroke OR, 1.43; 95% CI, 1.27-1.6; and traumatic brain injury OR, 1.22; 95% CI, 1.06-1.42; P <.001) and hazard ratios (HR) (cardiac arrest HR, 1.23; 95% CI, 1.14-1.34; stroke HR, 1.3; 95% CI, 1.21-1.4; traumatic brain injury HR, 1.13; 95% CI, 1-1.27), in patients with hypercapnic acidosis compared with normocapnia and normal pH. There was no difference in mortality between patients who had compensated hypercapnia compared with patients who had normocapnia and normal pH. In patients with hypercapnic acidosis, the adjusted OR of hospital mortality increased with increasing partial pressure of carbon dioxide, while no such increase was noted in patients with compensated hypercapnia.Hypercapnic acidosis was associated with increased risk of hospital mortality in patients with cerebral injury. Hypercapnia, when compensated to normal pH during the first 24 hours of intensive care unit admission, may not be harmful in mechanically ventilated patients with cerebral injury.
Beyond Concurrent Chemoradiation: The Emerging Role of PD-1/PD-L1 Inhibitors in Stage III Lung Cancer
Authors: Neal S. McCall, Adam P. Dicker, Bo Lu
Journal: Clinical Cancer Research (2018)

Concurrent chemoradiation (cCRT) with platinum-based chemotherapy is standard-of-care therapy for patients with stage III unresectable non-small cell lung cancer (NSCLC). Although cCRT is potentially curative, 5-year overall survival has hovered around 20%, despite extensive efforts to improve outcomes with increasing doses of conformal radiation and intensification of systemic therapy with either induction or consolidation chemotherapy. PD-1/PD-L1 immune checkpoint inhibitors have demonstrated unprecedented efficacy in patients with stage IV NSCLC. In addition, preclinical and early clinical evidence suggests that chemotherapy and radiation may work synergistically with anti-PD-1/PD-L1 therapy to promote antitumor immunity, which has led to the initiation of clinical trials testing these drugs in patients with stage III NSCLC. A preliminary report of a randomized phase III trial, the PACIFIC trial, demonstrated an impressive increase in median progression-free survival with consolidative durvalumab, a PD-L1 inhibitor, compared with observation after cCRT. Here, we discuss the clinical and translational implications of integrating PD-1/PD-L1 inhibitors in the management of patients with unresectable stage III NSCLC. Clin Cancer Res; 24(6); 1271-6. ©2018 AACR.
Identifying a consensus sample type to test for Chlamydia trachomatis, Neisseria gonorrhoeae, Mycoplasma genitalium, Trichomonas vaginalis and human papillomavirus
Authors: L. Coorevits, A. Traen, L. Bingé, J. Van Dorpe, M. Praet, J. Boelens, E. Padalko
Journal: Clinical Microbiology and Infection (2018)
Identification and characterization of circulating tumor cells in post prostatectomy patients with localized high risk prostate cancer.
Authors: Terence W. Friedlander, Christopher J. Welty, Archana Anantharaman, Jeffrey Hough, Matthew Edwards, Alise Stromlund, Jeff Simko, Ryon Graf, Angel Rodriquez, Yipeng Wang, Peter Carroll, Matthew R. Cooperberg, Ryan Vance Dittamore, Pamela Paris
Journal: Journal of Clinical Oncology (2018)

69 Background: Over 15% of men with newly diagnosed prostate cancer (PCa) have high-risk features that raise the recurrence risk. Better biomarkers could allow for even earlier detection of biochemical recurrence (BCR) and inform adjuvant treatment decisions. Circulating tumor cells (CTCs) may represent the earliest form of metastases, however their role as biomarkers in men with localized PCa is not well defined. Here, we aim to enumerate and molecularly and genomically analyze CTCs using an enrichment-free, unbiased CTC identification technology from men with high-risk, localized PCa after radical prostatectomy (RP) and correlate the analysis with clinical outcomes. Methods: Blood samples from 37 patients with high-risk, localized PCa were obtained 2-5 mos post RP and shipped to Epic. All nucleated cells were subjected to immunofluorescent staining for cytokeratin (CK), CD45, and AR. CTCs were identified using algorithmic analysis. CK + CTCs were enumerated and subsequently analyzed for AR expression and individually sequenced for copy number alterations (CNA). Patients were followed for BCR, defined as detectable PSA &gt; 0.2ng/dL. Progression free survival (PFS) was calculated using Kaplan-Meier and Cox proportional hazards. Results: CTCs were detected in 81.1%(30/37) of patients with an average of 5.2 CTCs/ml (range: 0 – 22.9) detected per patient. AR expression was detected in 18.9% (7/37) of patients. Ninety nine CTCs from 14 patients were picked and sequenced. CNAs were identified in CTCs in commonly mutated genes in PCa, including MYC amplification and CHD1 deletions. Patients with higher traditional CTC (CK+) burdens exhibited a trend towards shorter PFS (hazard ratio: 1.65; 95% confidence interval: 0.7-3.86; p = 0.13). Conclusions: There was a high incidence of CTC detection after RP in patients with high-risk, localized PCa. A trend toward shorter PFS was seen in those with higher CTC burden. Genomic alterations were detectable in CTCs and consistent with established CNAs in PCa. With further testing in appropriately powered cohorts early CTC detection after primary therapy could represent an informative biomarker to stratify patients with high risk PCa.
Prognosis of hepatic failure with the albumin-bilirubin model for hepatocellular carcinoma after stereotactic body radiotherapy with and without transplant.
Authors: Shaakir Hasan, Alexander V. Kirichenko, Paul Renz, Vijay Kudithipudi, Molly Vincent, Lorenzo Machado, Tadahiro Uemura, Ngoc Thai
Journal: Journal of Clinical Oncology (2018)

384 Background: The Albumin-Bilirubin (ALBI) model is a validated prognostic assessment of cirrhosis in hepatocellular carcinoma (HCC), stratifying patients to grades 1(ALBI-1), 2(ALBI-2), or 3(ALBI-3). We reported that ALBI distinguishes patients at higher risk for hepatic failure(HF) after stereotactic body radiotherapy (SBRT) within the Child Pugh(CP) A population. We now apply the ALBI model to both CP-A and CP-B patients after SBRT with or without orthotropic liver transplant (OLT), and assess its prognostic capability of overall survival (OS) and HF relative to the CP model. Methods: From 2009-2017, 68 patients with 81 HCC lesions and CP-A (45) or CP-B (23) cirrhosis completed SBRT in this IRB approved study. The median dose was 45 Gy (35 - 57 Gy) in 4-7 fractions. Initial ALBI and CP scores were measured against OS and progression of CP class, which was recorded every 3-4 months. Median follow-up = 18 months. Results: The median age = 62 and tumor size = 3.5 cm (1.1 Ð 11 cm). 26 patients were ALBI-1, 31 ALBI-2, and 11 ALBI-3 prior to SBRT. For all patients, 2-year local control was 96%. 1 and 2 year OS was 77% and 54%, disease free survival was 71% and 40%, and freedom from CP progression was 71% and 56%, respectively. OS was significantly different between ALBI-1, ALBI-2, and ALBI-3 patients (P = 0.01), as was progression of CP class (P&lt;0.001). When stratified by initial CP class, there were no significant differences in survival or CP progression [Table 1]. In a subset of 37 CP-A and 15 CP-B without OLT, rates of progressive cirrhosis were better predicted by ALBI (P&lt;0.001) than CP class (P=0.09). Conclusions: Compared to the CP model, the ALBI index more precisely predicted HF and OS in HCC patients for both early and intermediate cirrhosis. Its application may help better select candidates for OLT after SBRT, who may be at higher risk for HF than initially predicted. [Table: see text]
Plasma ghrelin is probably not a useful biomarker for risk prediction or early detection of colorectal cancer
Authors: Anneli Sundkvist, Robin Myte, Richard Palmqvist, Sophia Harlid, Bethany Van Guelpen
Journal: Gut (2018)

Table 1 Characteristics of colorectal cancer cases and matched control participants, all of whom provided repeated blood samples at 10-year intervals Time period prior to diagnosis of cases >10 years <5 years Cases Controls Cases Controls N 60 60 60 60 Males (%) 34 (57) 34 (57) 34 (57) 34 (57) Age (years) 50.0 (40.3 -50.2) 50.0 (40.2 -50.2) 59.8 (50.3 -60.1) 59.9 (50.2 -60.1)BMI 25.5 (23.6 -27.0) 24.6 (22.8 -28.1) 26.1 (24.4 -28.9) 25.5 (23.3 -29.0)Ever smoker, N (%) 36 (60) 34 (57) 38 (63) 35 (58) Alcohol intake (g/day) 3.0 (0.9 -6.3) 3.4 (1.6 -6.7) 4.6 (1.7 -8.1) 3.2 (0.9 -6.3)No physical activity* (%) 28 (47) 23 (38) 27 (45) 25 (42) Ghrelin † (pg/mL) 556 (323 -772)
How can I become a life coach and is this compatible with a career in general practice?
Authors: Susan Kersley
Journal: BMJ (2004)

Got a career or related problem that needs answering? Can't 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.
P123 The IFN type I gene expression in a cardiovascular disease continuum of rheumatoid arthritis
Authors: AN Burska, G Harrison, EM Hensor, L-A Bissell, G Fent, I Sadreev, YM El Sherbiny, H Donica, EM Vital, S Plein, MH Buch
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Introduction</h3> Rheumatoid Arthritis (RA) patients have a prominent increase in cardiovascular (CV) comorbidity not fully explained by traditional risk factors.<sup>1</sup> Interferons type 1 (IFN-1) have been associated with premature CV disease (CVD) in SLE<sup>2</sup> and are implicated in several aspects of atherosclerosis and acute coronary syndromes.<sup>3</sup> In RA a subpopulation of patients also display an IFN-1 signature in the blood,<sup>4</sup> which is associated with response to biologics. The IFN- 1 signature association with CVD in RA remains unclear. <h3>Objectives</h3> To analyse expression of interferon type 1 response genes (ISGs) along a CVD continuum in patients with RA using a well phenotyped cohort of RA patients whereby cardiovascular changes were assessed by Cardiac Magnetic Resonance Imaging (CMR). <h3>Methods</h3> PBMCs samples from 60 RA patients (mean (90% CI)) age 62.4 (60.2, 64.6)y.o, sex F/M 42/18, disease duration 153.3 (121.3, 185.2) mths and n=18 healthy controls (HC); age 42 (37.8,46.0) y, F/M 12/6 were obtained. RA patients were stratified based on CMR into: no CVD (RA CMRneg n=13) and abnormal CMR (RA CMRpos n=26), and RA with clinical CVD (no CMR, defined as history of cerebrovascular disease or ischaemic heart disease) (RA CVD n=21). qPCR of ISGs was performed using TaqMan Gene Expression Assays on Biomark (Fluidigm). Factor scores were created using the set of 51 genes measured in 78 subjects. <h3>Results</h3> All routinely used biomarkers were associated with RA diagnosis (ACPA, RF, TJC, SJC, CRP, DAS28). Total cholesterol and LDL levels were higher in RA than in HC group (p=0.051 and p=0.015). Three IFN-1 scores were present in the dataset (IFN Score 1, 2 and 3) and were composed of 19, 21 and 7 genes respectively. IFN-1 score 2 showed significant differences between HC and RA CMRpos groups (mean difference and 90% CI: 0.52 (0.09, 0.96)) and HC and RA CVD (0.57 (0.10, 1.03)) as well as all RA patients with CVD (CMRpos and RA CVD) ((0.54 (0.16, 0.93); p&lt;0.05 for all comparisons). IFN-1 Score 3 showed trend for a difference between RA CMRneg and CMRpos patients (0.37 (0.03, 0.70); p=0.071). There was no statistical difference between HC and RA CMRneg groups. <h3>Conclusions</h3> An IFN-1 score 2 emerged as a possible factor characterising progression along a CVD continuum in RA patients, from no CVD to subclinical and clinical CVD; also distinguishing between HC and RA with subclinical and clinical CVD. These results warrant further evaluation in a larger cohort to confirm the findings. <h3>References</h3> . Kaplan MJ. Curr. Opin. Rheumatol2006;18(3):289–297. . Somers EC, et al. PloS One2012;7(5):e37000. . de Winther MPJ. Arterioscler. Thromb. Vasc. Biol2016;36(2):217–218. . van der Pouw Kraan TC, et al. Ann. Rheum. Dis2007;66(8):1008–1014. <h3>Disclosure of interest</h3> None declared
Abstract P5-18-04: Bridging gaps in breast cancer care: A pilot forum for mental health professionals
Authors: R Yang, B Rabinowitz, M Frank, L Schapira, I Wapnir
Journal: Cancer Research (2018)

Abstract Introduction: Supporting the emotional needs of women diagnosed with breast cancer is a recognized priority for cancer clinicians and a core component of high quality care and survivorship programs. We hypothesized that mental health professionals would benefit from an educational program directed to enhance their practical knowledge of breast cancer. Methods: We designed an innovative educational forum for mental health professionals to broaden their practical knowledge regarding the physical and psychosocial effects of breast cancer. Diverse mental health professionals working in the Bay Area were invited. The day-long forum consisted of presentations and interactive discussion led by breast cancer physicians, mental health providers and patient advocates. An evaluation survey was administered at the end of the program. Descriptive statistics were performed of categorical results and open response items were aggregated. Results: Of 40 local pre-registrants, 18 mental health professionals (8 social workers, 6 psychologists, 3 other mental health professionals) attended. 88.2% of participants worked in a medical-based practice; 64.7% worked in an oncology-based practice. The majority of participants agreed the forum was relevant to their practice (82.3%), was well-organized (88.2%), would improve their care of patients (76.5%), and that they would recommend it to others (76.5%). The overall rating of the forum was positive (94.0%). Conclusion: The format and content of this forum represents a multidisciplinary educational model to enhance mental health professionals' understanding of breast cancer in order to better serve this unique patient population. Breast cancer clinicians, advocates and psychotherapists generated much enthusiasm and broad insights about meeting the psycho-emotional needs of breast cancer patients. This model can be replicated and extended to a national audience and to other cancer subpopulations. Citation Format: Yang R, Rabinowitz B, Frank M, Schapira L, Wapnir I. Bridging gaps in breast cancer care: A pilot forum for mental health professionals [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 P5-18-04.
The Francis and Keogh reviews have made junior doctors powerful agents for change
Authors: Craig Winthrop, Iain Wilkinson, James George
Journal: BMJ (2013)

The Francis and Keogh reviews emphasised the important role that junior doctors have in improving care in the health service. <b>Craig Winthrop</b>, <b>Iain Wilkinson</b>, and <b>James George</b> reflect on what has changed for junior doctors in the wake of the reviews
Case 8-2018: A 55-Year-Old Woman with Shock and Labile Blood Pressure
Authors: Joseph Loscalzo, Nathalie Roy, Ravi V. Shah, Joy N. Tsai, Alexis M. Cahalane, Johannes Steiner, James R. Stone
Journal: New England Journal of Medicine (2018)

A 55-year-old woman presented with cardiogenic shock. Echocardiography revealed a left ventricular ejection fraction of 15% and apical ballooning; angiography revealed normal coronary arteries. She had episodes of hypotension and hypertension. A diagnosis was made.
PERCUTANEOUS CORONARY INTERVENTION IN PATIENTS WITH PREVIOUS CORONARY ARTERY BYPASS GRAFT SURGERY: INSIGHTS FROM A MULTICENTER REGISTRY
Authors: Peter Tajti, Dimitrios I. Karmpaliotis, Khaldoon Alaswad, Farouc Jaffer, Robert Yeh, Mitul Patel, Ehtisham Mahmud, James Choi, M. Nicholas Burke, Anthony Doing, Catalin Toma, Barry Uretsky, Elizabeth Holper, David Kandzari, Nicholas Lembo, Santiago Garcia, Oleg Krestyaninov, Dmitrii Khelimskii, Michalis Koutouzis, Jeffrey Moses, Ajay Kirtane, Ziad Ali, Bavana Rangan, Subhash Banerjee, Emmanouil Brilakis
Journal: Journal of the American College of Cardiology (2018)