tbuckley/cabot-search huggingface dataset:
Abstract 049: Mitochondrial DNA Copy Number and Incident Atrial Fibrillation: The Atherosclerosis Risk in Communities Study (ARIC)
Authors: Di Zhao, Eliseo Guallar, Ryan Longchamps, Christina Castellani, Yunsoo Hong, Alvaro Alonso, Nathan Pankratz, John Lane, Dan Arking
Journal: Circulation (2018)

Background: Atrial fibrillation (AF) is the most common clinical arrhythmia. Molecular studies suggest that mitochondrial dysfunction is associated with increased risk of AF through reduced production of adenosine triphosphate and increased production of reactive oxidative species. Mitochondrial DNA copy number (mtDNA CN), a marker of mitochondrial function, has been found to be associated with sudden cardiac death and cardiovascular disease (CVD) in ARIC. However, the association between mtDNA CN and incident AF in the general population is unknown. Objective: To examine the prospective association between mtDNA CN and the risk of incident AF. Methods: Cohort study of 10,764 ARIC participants without AF at baseline (1987-89) and followed through December 31, 2014. AF were identified through electrocardiograms, review of hospital discharge codes, and death certificates. DNA samples were isolated from buffy coat. mtDNA CN was calculated from probe intensities on the Affymetrix Genome-Wide Human single nucleotide polymorphisms (SNP) Array and standardized using the residual method. Cox proportional hazards models adjusted for demographics and CVD risk factors were used to estimate hazard ratios (HR) for AF comparing the four lowest quintiles of mtDNA CN to the highest quintile. Results: The mean (SD) age was 57.4 (6.0) years. During 21 years of median follow-up, 1,946 participants developed AF. In fully-adjusted models, the HRs (95% CI) for AF comparing quintiles 1 - 4 to quintile 5 of mtDNA CN were 1.17 (1.00, 1.37), 1.17 (0.99, 1.37), 0.92 (0.78, 1.10) and 1.05 (0.89, 1.24), respectively (p-trend 0.044; Figure). The HR for AF comparing 10 th vs 90 th percentile of mtDNA-CN was 1.16 (1.04, 1.30). Conclusions: mtDNA CN was inversely associated with the risk of AF independent of traditional CVD risk factors. Decline in mitochondrial function may be a novel mechanism underlying biological changes that increase the risk of AF in the general population. mtDNA CN may provide potential for novel AF prevention strategies.
Utility of next-generation sequencing in clinical decision making in hepatocellular carcinoma (HCC).
Authors: Ramya Thota, Mark Andrew Lewis, Sharanya Raghunath, Derrick S. Haslem, Lincoln Nadauld, Terence Duane Rhodes, Bryce Moulton, Tyler Abraham, Robin Romero, Gail Fulde, Bryce Christensen, Tyler Barker
Journal: Journal of Clinical Oncology (2018)

295 Background: HCC is a heterogeneous disease with diverse genomic alterations. The prior genomic studies have identified common alterations in TERT, P53, WNT pathways. However, most of these alterations are not targetable with current FDA approved targeted agents. In this study, we determine the clinical impact of targeted next generation sequencing in patients with advanced HCC. Methods: We retrospectively assessed all patients with gastrointestinal (GI) malignancies who have undergone next generation sequencing (NGS) between January 2013 and August 2017. The primary endpoint is to determine the frequency of clinically actionable mutations in HCC. Secondary endpoint is to identify number of patients eligible for current FDA approved targeted agents. Results: Of the 299 consecutive GI tumors sequenced, 29 cases were identified as HCC. Clinically actionable mutations were noted in 22 of 29 patients (pts) (76%). Most pts (52%) were found to harbor more than one potentially actionable genetic alterations (n = 15). The common pathways involved: P53 in 9 pts (22%), cell-cycle regulation in 7 pts (17.1%) and mitogen-activated protein kinase in 6 pts (14.6%). Other pathways involved were DNA repair in 4 pts (9.8%), WNT in 3 pts (7.3%), MYC in 3 pts (7.3%), NOTCH in 2 pts (4.9%), HNPCC in 2 pts (4.9%), APC in 2 pts (4.9%), phosphatidylinositol 3-kinase-AKT-mTOR in 1 patient (pt) (2.4%), BRINP in 1 pt (2.4%) and angiogenesis in 1 pt (2.4%). We noted 10 pts (34.5%) harbor alterations that could potentially be targeted with FDA approved treatments such as palbociclib (for CCND1/2 amplification), PARP inhibitors (for DNA repair defects), and immunotherapy (for MMR defects) on precision medicine clinical trials such as TAPUR or MATCH. Conclusions: Mutational profiling using a targeted NGS panel identified clinically actionable alterations in nearly 75% of advanced HCC patients. Almost one third of these patients were potential candidates for current FDA approved treatments. NGS and enrollment in clinical trials should be considered in all fit patients with HCC who had progression on current standard of care treatments.
TWO-DIMENSIONAL GRADIENT GEL ELECTROPHORESIS OF HDL AND SMALL DENSE LDL, REVEAL BEHAVIORAL-RELATED HEART DISEASE RISK IMPROVEMENTS MISSED BY THE TRADITIONAL HDL-C AND LDL-C MEASUREMENTS
Authors: H. Robert Superko, Rosalynn Gill, Megan McCarthy, Kepra Jack, Debanjali Ghosh, Briana E. Jones, Joi Gleason, Paul T. Williams, Michael Dansinger
Journal: Journal of the American College of Cardiology (2018)
Results of a multi-institutional, randomized, non-inferiority, phase III trial of accelerated fractionation versus standard fractionation in radiation therapy for T1-2N0M0 glottic cancer: Japan Clinical Oncology Group Study (JCOG0701)
Authors: T. Kodaira, Y. Kagami, T. Shibata, N. Shikama, Y. Nishimura, S. Ishikura, K. Nakamura, Y. Saito, Y. Matsumoto, T. Teshima, Y. Ito, T. Akimoto, K. Nakata, T. Toshiyasu, K. Nakagawa, Y. Nagata, T. Nishimura, T. Uno, M. Kataoka, A. Yorozu, M. Hiraoka
Journal: Annals of Oncology (2018)
High Frequency of Systemic Corticosteroid Use for Acute Respiratory Tract Illnesses in Ambulatory Settings
Authors: Evan L. Dvorin, Marie Claire Lamb, Dominique J. Monlezun, Austin C. Boese, Lydia A. Bazzano, Eboni G. Price-Haywood
Journal: JAMA Internal Medicine (2018)

HighFrequencyofSystemicCorticosteroidUseforAcute Respiratory Tract Illnesses in Ambulatory SettingsClinical practice guidelines do not recommend systemic steroids in the treatment of acute respiratory tract infections (ARTIs). 1 While some studies have shown earlier symptom resolution with steroids given for pharyngitis, 2 clinical trials show no efficacy of systemic steroids for sinusitis 3 and bronchitis. 4Adverse events can develop within 30 days of short-term steroid use, which raises concern about the safety of systemic steroids for ARTIs. 5We conducted the present study to examine the frequency of steroid use for ARTIs in Louisiana and nationally and to examine factors associated with this clinical practice.
Medical education needs more central control, medical bodies say
Authors: Helen Jaques
Journal: BMJ (2013)

Health Education England (HEE) should provide greater national oversight of medical education and training than is currently set out in draft legislation, medical organisations have told MPs.

From April 2013 medical education and training in England will be run by 13 local education and training boards. HEE, a new national body, will oversee these boards.

Representatives of the BMA, the Royal College of Surgeons, and the Academy of Medical Sciences raised concerns about HEE’s remit at a hearing about the legislation creating these organisations. The representatives told MPs on the Joint Committee on the Draft Care and Support …
Erratum. Metformin Use in Prediabetes Among U.S. Adults, 2005–2012. Diabetes Care 2017;40:887–893
Authors: Eva Tseng, Hsin-Chieh Yeh, Nisa M. Maruthur
Journal: Diabetes Care (2018)

In the article cited above, the authors neglected to multiple the SEs by 100 to correspond …
Which patients with localized prostate cancer account for the greatest proportion of prostate cancer deaths?
Authors: Michelle Nezolosky, Paul L. Nguyen, David Dewei Yang
Journal: Journal of Clinical Oncology (2018)

130 Background: We sought to determine which groups of patients, stratified by risk group and age, account for the greatest absolute number of deaths due to prostate cancer. Methods: Using the Surveillance, Epidemiology, and End Results (SEER) database, we identified 437,150 men diagnosed with prostate cancer from 2004 to 2014. Men were excluded if they had N1 or M1 disease, risk group could not be determined, or if prostate cancer was not their first malignancy. Men were categorized as having low (Gleason ≤6, prostate-specific antigen [PSA] &lt; 10 ng/mL, and cT1-T2a), intermediate (Gleason 7, PSA 10-20 ng/mL, or cT2b-T2c), or high risk disease (Gleason 8-10, PSA &gt; 20 ng/mL, or cT3-T4). We calculated the cumulative incidence of prostate cancer-specific mortality (PCSM). Results: Median follow-up was 4.8 years. The overall incidences of diagnosis of low, intermediate, and high risk disease were 29.7% (n = 129,925), 48.0% (n = 209,643), and 22.3% (n = 97,582), respectively. 5-year PCSM for men with low, intermediate, and high risk disease was 0.5%, 1.4%, and 9.4%, respectively, and the 10-year PCSM was 1.6%, 4.0%, and 16.8%. Within 10 years of diagnosis, 6.5% (n = 905) of patients who died of prostate cancer were low risk, 27.4% (n = 3,834) were intermediate risk, and 66.2% (n = 9,278) were high risk. In particular, patients age 70 or older accounted for 49.9% of all high risk prostate cancer diagnoses, but 65.3% of deaths due to high risk prostate cancer. Conclusions: While high risk disease accounted for only 22.3% of the diagnoses, it accounted for 66.2% of the prostate cancer deaths within 10 years of diagnosis. Therefore, high risk patients account for the vast majority of prostate cancer deaths and should remain the focus of the majority of our research efforts. In addition, older patients with high risk disease die of prostate cancer at a disproportionately high rate, which runs counter to the notion that the disease is less of a threat to survival in older men.
Neonatal gut-microbiome-derived 12,13 DiHOME suppresses immune tolerance via PPARγ
Authors: Sophia R. Levan, Kei E. Fujimura, Din L. Lin, Kelsey A. Stamnes, Edward M. Zoratti, Nicholas W. Lukacs, Dennis Ownby, Homer A. Boushey, Christine Cole Johnson, Susan V. Lynch
Journal: Journal of Allergy and Clinical Immunology (2018)
BMA raises alarm over GMC texts as hundreds of doctors have their revalidation deferred
Authors: Helen Jaques
Journal: BMJ (2013)

A 10th of the doctors who have been up for revalidation since the system launched last December have had their revalidation recommendation deferred, the GMC has confirmed.

In addition, many doctors have been told about their revalidation decision in ambiguous text messages, a scenario the BMA called “inhumane.”

Responsible officers are able to request to defer making a doctor’s revalidation recommendation if the doctor is involved in a disciplinary process or is on a sabbatical, a career break, long term sick leave, or maternity …
Abstract 19641: Community Pharmacist Led Atrial Fibrillation Screening Program Has the Potential to Improve Atrial Fibrillation Detection Rates and Reduce Stroke Risk
Authors: Zainab M Khanbhai, Sally E Manning, Wajid Hussain
Journal: Circulation (2016)

Introduction: The prevalence of atrial fibrillation (AF) in the UK is around 2%, affecting more than 10% of people aged over 80 years. AF is associated with a high risk of stroke which is preventab...
Clinical excellence awards reinstated in Northern Ireland
Authors: Helen Jaques
Journal: BMJ (2013)

Clinical excellence awards (CEAs) will be reintroduced for consultants in Northern Ireland for 2012-13 and 2013-14, Northern Ireland’s health, social services, and public safety minister Edwin Poots has announced.

CEAs were not distributed in Northern Ireland in 2010-11 and 2011-12 …
RIGHT VENTRICULAR DYSFUNCTION DETERMINED BY 2D- SPECKLE TRACKING ECHOCARDIOGRAPHY AFTER ST-SEGMENT ELEVATION MYOCARDIAL INFARCTION IN PATIENTS WITH CHRONIC OBSTRUCTIVE PULMONARY DISEASE
Authors: Laurien Goedemans, Georgette Hoogslag, Rachid Abou, Martin Schalij, Nina Marsan, Jeroen J. Bax, Victoria Delgado
Journal: Journal of the American College of Cardiology (2018)
A CRISPR-based screen for Hedgehog signaling provides insights into ciliary function and ciliopathies
Authors: David K. Breslow, Sascha Hoogendoorn, Adam R. Kopp, David W. Morgens, Brandon K. Vu, Margaret C. Kennedy, Kyuho Han, Amy Li, Gaelen T. Hess, Michael C. Bassik, James K. Chen, Maxence V. Nachury
Journal: Nature Genetics (2018)
Histone Deacetylases 1 and 2 Regulate Microglia Function during Development, Homeostasis, and Neurodegeneration in a Context-Dependent Manner
Authors: Moumita Datta, Ori Staszewski, Elena Raschi, Maximilian Frosch, Nora Hagemeyer, Tuan Leng Tay, Thomas Blank, Mario Kreutzfeldt, Doron Merkler, Stephanie Ziegler-Waldkirch, Patrick Matthias, Melanie Meyer-Luehmann, Marco Prinz
Journal: Immunity (2018)
Time to Endovascular Treatment and Outcome in Acute Ischemic Stroke
Authors: Maxim J.H.L. Mulder, Ivo G.H. Jansen, Robert-Jan B. Goldhoorn, Esmee Venema, Vicky Chalos, Kars C.J. Compagne, Bob Roozenbeek, Hester F. Lingsma, Wouter J. Schonewille, Ido R. van den Wijngaard, Jelis Boiten, Jan Albert Vos, Yvo B.W.EM. Roos, Robert J. van Oostenbrugge, Wim H. van Zwam, Charles B.L.M. Majoie, Aad van der Lugt, Diederik W.J. Dippel
Journal: Circulation (2018)

Background: Randomized, clinical trials in selected acute ischemic stroke patients reported that for every hour delay of endovascular treatment (EVT), chances of functional independence diminish by up to 3.4%. These findings may not be fully generalizable to clinical practice because of strict in- and exclusion criteria in these trials. Therefore, we aim to assess the association of time to EVT with functional outcome in current, everyday clinical practice. Methods: The MR CLEAN Registry (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in The Netherlands) is an ongoing, prospective, observational study in all centers that perform EVT in The Netherlands. Data were analyzed from patients treated between March 2014 and June 2016. In the primary analysis we assessed the association of time from stroke onset to start of EVT and time from stroke onset to successful reperfusion with functional outcome (measured with the modified Rankin Scale), by means of ordinal logistic regression. Results: We analyzed 1488 patients with acute ischemic stroke who underwent EVT. An increased time to start of EVT was associated with worse functional outcome (adjusted common odds ratio, 0.83 per hour; 95% confidence interval, 0.77–0.89) and a 2.2% increase in mortality. Every hour increase from stroke onset to EVT start resulted in a 5.3% decreased probability of functional independence (modified Rankin Scale, 0–2). In the 742 patients with successful reperfusion, every hour increase from stroke onset to reperfusion was associated with a 7.7% decreased probability of functional independence. Conclusions: Time to EVT for acute ischemic stroke in current clinical practice is strongly associated with functional outcome. Our data suggest that this association might be even stronger than previously suggested in reports on more selected patient populations from randomized, controlled trials. These findings emphasize that functional outcome of EVT patients can be greatly improved by shortening onset to treatment times.
Is it possible to leave a specialist registrar job after signing a contract? How many months' notice should someone give, and what are the consequences?
Authors: Sarah Burnett
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.
Long-Term Prognostic Factors after Hepatic Resection for Hepatitis C Virus-Related Hepatocellular Carcinoma, with a Special Reference to Viral Status
Authors: Masaki Koda, Shogo Tanaka, Shigekazu Takemura, Hiroji Shinkawa, Masahiko Kinoshita, Genya Hamano, Tokuji Ito, Norifumi Kawada, Toshihiko Shibata, Shoji Kubo
Journal: Liver Cancer (2018)

Although studies have reported on long-term (10-year) survival after hepatic resection for hepatocellular carcinoma (HCC), they did not focus on patients with hepatitis C virus (HCV)-related HCC, and the contribution of antiviral therapy to long-term survival (especially ≥15 years) has not been adequately examined. We investigated the long-term outcome after hepatic resection for HCV-related HCC, including the effects of interferon (IFN) therapy, and the changes in prognostic factors according to postoperative duration.The data of 207 patients who underwent hepatic resection for HCV-related HCC between January 1992 and December 2001 were retrospectively reviewed. We investigated the disease-free and overall survival rates after surgery and analyzed the prognostic factors at 5, 10, and 15 years postoperatively.The proportion of patients who survived at 5, 10, and 15 years after hepatic resection was 52% (n = 107), 18% (n = 38), and 9% (n = 19). The overall survival rate was significantly higher in patients who achieved sustained virological response (SVR) with IFN therapy than in those without SVR. Tumor-related factors such as multiple tumor, microscopic vascular invasion, and a high indocyanine green retention rate at 15 min (ICGR15) were unfavorable prognostic factors for 5-year survival. Conversely, a low ICGR15 and SVR were favorable prognostic factors at 10 years, and SVR alone was a favorable prognostic factor at 15 years postoperatively; no tumor-related factors were prognostic factors at 10 and 15 years postoperatively.The prognostic factors varied according to the duration after hepatic resection for HCV-related HCC. Tumor-related factors were unfavorable prognostic factors in the early postoperative period, whereas SVR and good liver function were favorable prognostic factors at 10 and 15 years postoperatively. Achievement of SVR with IFN therapy is essential for long-term (≥15 years) survival after hepatic resection for HCV-related HCC.
PREDICTORS OF 6-MONTH HEART FAILURE READMISSION AND DEATH IN OLDER PATIENTS WITH HEART FAILURE WITH PRESERVED VERSUS REDUCED EJECTION FRACTION
Authors: Cherinne Arundel, Helen Sheriff, Fahad K. Lodhi, Charity Morgan, Steven Singh, Phillip H. Lam, Selma Mohammed, Charles Faselis, Gregg C. Fonarow, Ali Ahmed
Journal: Journal of the American College of Cardiology (2018)
Transforming Growth Factor β Activation Primes Canonical Wnt Signaling Through Down‐Regulation of Axin‐2
Authors: Justin Gillespie, Rebecca L. Ross, Clarissa Corinaldesi, Filomena Esteves, Emma Derrett‐Smith, Michael F. McDermott, Gina M. Doody, Christopher P. Denton, Paul Emery, Francesco Del Galdo
Journal: Arthritis & Rheumatology (2018)

Aberrant activation of Wnt signaling has been observed in tissues from patients with systemic sclerosis (SSc). This study aimed to determine the role of transforming growth factor β (TGFβ) in driving the increased Wnt signaling, through modulation of axis inhibition protein 2 (Axin-2), a critical regulator of the Wnt canonical pathway. Canonical Wnt signaling activation was analyzed by TOPflash T cell factor/lymphoid enhancer factor promoter assays. Axin-2 was evaluated in vitro by analysis of Axin-2 primary/mature transcript expression and decay, TGFβ receptor type I (TGFβRI) blockade, small interfering RNA-mediated depletion of tristetraprolin 1, and XAV-939-mediated Axin-2 stabilization. In vivo, Axin-2 messenger RNA (mRNA) and protein expression was determined in skin and lung biopsy samples from mice that express a kinase-deficient TGFβRII specifically on fibroblasts (TβRIIΔk-fib-transgenic mice) and from littermate controls. SSc fibroblasts displayed an increased response to canonical Wnt ligands despite basal levels of Wnt signaling that were comparable to those in healthy control fibroblasts in vitro. Notably, we showed that SSc fibroblasts had reduced basal expression of Axin-2, which was caused by an endogenous TGFβ-dependent increase in Axin-2 mRNA decay. Accordingly, we observed that TGFβ decreased Axin-2 expression both in vitro in healthy control fibroblasts and in vivo in TβRIIΔk-fib-transgenic mice. Additionally, using Axin-2 gain- and loss-of-function experiments, we demonstrated that the TGFβ-induced increased response to Wnt activation characteristic of SSc fibroblasts depended on reduced bioavailability of Axin-2. This study highlights the importance of reduced bioavailability of Axin-2 in mediating the increased canonical Wnt response observed in SSc fibroblasts. This novel mechanism extends our understanding of the processes involved in Wnt/β-catenin-driven pathology and supports the rationale for targeting the TGFβ pathway to regulate the aberrant Wnt signaling observed during fibrosis.
OBJECTIVELY MEASURED PHYSICAL ACTIVITY AND THE RISK OF ATRIAL FIBRILLATION: THE REASONS FOR GEOGRAPHIC AND RACIAL DIFFERENCES IN STROKE (REGARDS) STUDY
Authors: Wesley O'Neal, Aleena Bennet, Matthew J. Singleton, Suzanne Judd, George Howard, Virginia Howard, Steven Hooker, Elsayed Soliman
Journal: Journal of the American College of Cardiology (2018)
REGIONAL DISPARITIES AND NATIONAL TRENDS IN MORTALITY RATES AMONG CARDIAC ARREST PATIENTS MANAGED WITH EXTRACORPOREAL MEMBRANE OXYGENATION
Authors: Ayush Arora, Adamantios Tsangaris, Akhtar Amin, David Song, Pratik Agrawal, Richard Hajjar, Mirela Feurdean, Alfonso Waller, James Maher
Journal: Journal of the American College of Cardiology (2018)
Diabetic Kidney Disease: A Determinant of Cardiovascular Risk in Type 1 Diabetes
Authors: Ian H. de Boer, George L. Bakris
Journal: Diabetes Care (2018)

Diabetes, regardless of type, has well-accepted vascular consequences. In fact, atherosclerotic cardiovascular disease (CVD) is the most important cause of death attributable to diabetes (1). Acute complications of diabetes such as hypoglycemia, hyperglycemia, and diabetic ketoacidosis are important causes of morbidity and mortality beginning early in its course. However, microvascular and macrovascular complications drive excess mortality over the long term (2–4).

Diabetic kidney disease (DKD) is strongly associated with CVD (5). DKD may be a marker of cumulative vascular damage due to diabetes or may causally promote CVD through several mechanisms, such as blood pressure dysregulation, retention of uremic toxins, anemia, and altered mineral metabolism. Provocative studies suggest that the preponderance of excess CVD risk in both types 1 and 2 diabetes is restricted to people with DKD (6–8).

The question posed by Groop et al. (9) in this issue of Diabetes Care was whether patients with type 1 diabetes have heightened CVD mortality risk in the absence of DKD compared with people without diabetes. To examine this question, they looked at two different databases. The first was a registry of 10,737 Finnish children followed for 10 years after the initial diagnosis of type 1 diabetes, a period considered generally too early for DKD development. The mortality rate of children in the Finnish registry was compared with that of the general population as a standardized mortality ratio (SMR) that adjusts for demographic characteristics. Children with diabetes had a mortality rate of 8 per 10,000 person-years, yielding an SMR of 2.6. (An SMR …