tbuckley/cabot-search huggingface dataset:
Abstract MP73: Systolic Blood Pressure Control among Hypertensives and Incident Heart Failure: The Atherosclerosis Risk in Communities Study
Authors: Carlos J Rodriguez, Katrina Swett, Sunil K Agarwal, Aaron R Folsom, Laura R Loehr, Ervin R Fox, Hanyu Ni, Wayne D Rosamond, Patricia P Chang
Journal: Circulation (2013)

Background: Studies document a progressive increase in heart disease risk as systolic blood pressure (SBP) rises above 115mmHg, suggesting a benefit of treatment to a SBP &lt;120mmHg. Hypertension is a major risk factor for heart failure (HF) but whether an SBP &lt;120mmHg lowers HF risk is unknown. Methods: Hypertensive participants at baseline (SBP/DBP &gt;140/90mmHg, report of hypertension or taking BP medication) from ARIC, a prospective population-based study of black and white men and women from 4 US communities, were included. SBP measured at baseline and at three triennial visits was treated as a time-dependent variable and categorized as: Elevated (SBP &gt;140), Standard (SBP 120-139) and Intensive (SBP &lt;120). Prevalent HF at baseline was excluded. Incident HF was defined from HF hospitalization or a death certificate with an ICD-9 or ICD-10 codes. Multivariable Cox regression models included baseline age, sex, diabetes, BMI, high cholesterol, smoking and alcohol intake. Results: After median follow-up of 20.8 years, a total of 1,111 incident HF events occurred in 4,802 hypertensives. Participants with elevated SBP had less HF-free survival compared to those with intensive group (log-rank p&lt;0.001). However, there was no difference in incident HF-free survival among those with standard vs. intensive group (log-rank p=0.08). In adjusted analysis, findings remained similar for elevated SBP (HR: 1.2; 95% CI 1.0-1.5, intensive group as referent); and for standard SBP (HR: 0.9; 95% CI 0.8-1.1, intensive group as referent). There were no differences by race and sex (p for interaction &gt;0.05). Further adjustment for BP medication use at baseline did not significantly affect the results. Conclusion: Hypertension control is necessary to prevent HF. Our results suggest that among hypertensives, having elevated SBP carries the highest risk for HF but in this categorical analysis we observed no risk difference between the standard and intensive SBP groups.
Abstract 14742: Impact of Albuminuria on Left Atrial Function Mediated by Left Ventricular Longitudinal Function in Patients With Diabetic Mellitus
Authors: Yasuhide Mochizuki, Hidekazu Tanaka, Hiroki Takada, Fumitaka Soga, Kumiko Dokuni, Yutaka Hatani, Keiko Hatazawa, Hiroki Matsuzoe, Hiroyuki Shimoura, Junichi Ooka, Hiroyuki Sano, Keiko Ryo Koriyama, Kensuke Matsumoto, Ken-ichi Hirata
Journal: Circulation (2016)

Background:  Diabetic nephropathy is independently associated with left ventricle (LV) longitudinal systolic myocardial dysfunction in asymptomatic diabetes mellitus (DM) patients with preserved LV ejection fraction (LVEF). However, the impact of diabetic nephropathy on left atrial (LA) function remains unknown.   Methods:  We studied 198 asymptomatic DM patients, all of whom had preserved LVEF without coronary artery disease. Diabetic nephropathy was defined as having a protein level higher than for micro-albuminuria. LV global longitudinal strain (GLS) and LA strain were analyzed by measuring two-dimensional speckle-tracking longitudinal strain. Sixty-nine age-, gender-, LVEF-matched normal subjects were also studied.   Results:  GLS and LA strain in systole (LAS-s) decreased significantly from normal controls to DM patients without (n=137) and with nephropathy (n=61), in that order. Furthermore, GLS, LAS-s, and LA strain in late diastole (LAS-a) were significantly lower in DM patients with macro-albuminuria (n=19) than in those with micro-albuminuria (n=42). While one multivariate regression analysis identified albuminuria as an independent determinative factor of LAS-s among other relevant clinical background factors (β=-0.16, p=0.002), another multivariate regression model for LAS-s plus GLS (β=0.40, p   Conclusions:  LA reservoir and contractile function are more impaired in DM patients than in those without albuminuria. The cross-linked association of LA strains with GLS and albuminuria may thus be important for better understanding the development of diabetic cardiomyopathy.
Surgical outcomes and learning curve analysis of robotic gastrectomy for gastric cancer: multidimensional analysis in a comparison with 3D laparoscopic gastrectomy.
Authors: Lin Chen, Jiyang Li, Xin Guo, Hongqing Xi, Yunhe Gao, Jianxin Cui, Zhi Qiao, Kecheng Zhang, Wenquan Liang, Bo Wei, Tianyu Xie
Journal: Journal of Clinical Oncology (2018)

162 Background: There is a lack of supporting evidence regarding the safety, efficacy and surgeon acceptance of robotic versus three-dimensional (3D) laparoscopic surgery for patients with gastric cancer (GC). Methods: An ambispective cohort study was conducted. We compared short-term surgical outcomes including financial cost between robotic and 3D laparoscopic gastrectomy for all GC patients and the GC patients treated by Prof. Chen’s team. The Cumulative Sum (CUSUM) method was developed and used to analyze the learning curves of robotic and 3D laparoscopic gastrectomy performed by Prof. Chen. Results: From August 2011 to June 2017, a total of 517 patients were enrolled for treatment with either robotic (n=408 including n=73 performed by Prof. Chen) or 3D laparoscopic (n=109 including n=71 performed by Prof. Chen) gastrectomy. There were no significant differences between the two operation methods regarding the clinical pathological characteristics, except for smoking habit (p &lt; 0.001). In analysis of all the 517 patients, robotic group had shorter operative time (208 min vs 228 min, p=0.004), less time to first flatus (3 days vs 4 days, p=0.025), longer time to remove drainage and nasogastric tube (12 days vs 9 days, p=0.001, 6 days vs. 4 days, p=0.001, respectively), and more postoperative complications (21.3% vs. 9.2%, p=0.003). While we compared these short-term outcomes of robotic and 3D laparoscopic gastrectomy performed by Prof. Chen, only number of lymph node dissections (robotic 27 vs. 3D 33, p=0.038) and time to remove nasogastric tube (robotic 5 days vs. 3D 3 days, p &lt; 0.001) were significantly different. CUSUM analysis showed that operative time reached a stable state after around 21 cases in robotic gastrectomy and 19 cases in 3D laparoscopic gastrectomy. The cost-effectiveness analysis showed that robotic gastrectomy had significantly higher total cost than 3D laparoscopic gastrectomy (robotic = RMB 124907 vs. 3D-laparoscopic = RMB 94395; p &lt; 0.001). Conclusions: With comparable surgical outcomes, higher surgeon acceptance and less financial cost, 3D laparoscope is a highly recommended minimal invasive surgical method for GC patients.
Your First ENT Job: a Survivor's Guide
Authors: Simon Charlett
Journal: BMJ (2006)

Marie Lyons and Arvind Singh

Radcliffe, 2005, £19.95, 128 pages

ISBN: 1 85775 748 3

Rating: ★★★/5



This first edition text offers a practically oriented overview of ear, nose, and throat medicine (ENT), and is primarily aimed at junior doctors and nurse practitioners who have little or no working knowledge of the specialty. The book is logically arranged and covers the three main subspecialties in turn. Each chapter begins with a short lesson in anatomy, aided …
The Versatile Tanycyte: A Hypothalamic Integrator of Reproduction and Energy Metabolism
Authors: Vincent Prevot, Bénédicte Dehouck, Ariane Sharif, Philippe Ciofi, Paolo Giacobini, Jerome Clasadonte
Journal: Endocrine Reviews (2018)

The fertility and survival of an individual rely on the ability of the periphery to promptly, effectively, and reproducibly communicate with brain neural networks that control reproduction, food intake, and energy homeostasis. Tanycytes, a specialized glial cell type lining the wall of the third ventricle in the median eminence of the hypothalamus, appear to act as the linchpin of these processes by dynamically controlling the secretion of neuropeptides into the portal vasculature by hypothalamic neurons and regulating blood-brain and blood–cerebrospinal fluid exchanges, both processes that depend on the ability of these cells to adapt their morphology to the physiological state of the individual. In addition to their barrier properties, tanycytes possess the ability to sense blood glucose levels, and play a fundamental and active role in shuttling circulating metabolic signals to hypothalamic neurons that control food intake. Moreover, accumulating data suggest that, in keeping with their putative descent from radial glial cells, tanycytes are endowed with neural stem cell properties and may respond to dietary or reproductive cues by modulating hypothalamic neurogenesis. Tanycytes could thus constitute the missing link in the loop connecting behavior, hormonal changes, signal transduction, central neuronal activation and, finally, behavior again. In this article, we will examine these recent advances in the understanding of tanycytic plasticity and function in the hypothalamus and the underlying molecular mechanisms. We will also discuss the putative involvement and therapeutic potential of hypothalamic tanycytes in metabolic and fertility disorders.
Editor’s Choice: Made to measure
Authors: Tom Moberly
Journal: BMJ (2015)

The importance of all doctors having their own individually focused training support and career planning is emphasised in two articles in BMJ Careers this week.

Charlotte Thomas and colleagues look at whether contemporary UK surgical training offers enough experience to allow trainees to meet current training demands (http://careers.bmj.com/careers/advice/view-article.html?id=20022082). They find that, although most trainees had undertaken the necessary numbers of procedures, audits, and publications, only …
Happier as a vet?
Authors: Caroline Elton
Journal: BMJ (2012)

Some sentiments get mentioned again and again when doctors come to me to discuss their career dilemmas. Core medical trainees, for example, often express anxiety about the on-call responsibilities of an acute medical registrar. Other concerns, however, are more idiosyncratic and crop up far less often, such as wondering whether one would have been happier training as a vet. This is something a few doctors have confided in me over the past couple of years, and I started to wonder whether these individuals shared any underlying themes.

The first doctor was on long term sick leave from her trust because of a stress related illness and had been the subject of complaints about her communication and team working skills. This woman (details have been changed to protect client confidentiality) 

was single, isolated from her family, and without close friends, and the most important relationships in her life seemed to be with the horses that she bred and showed competitively. …
Antitumor effect of cationic liposome incorporating keto-mycolic acid from Mycobacterium bovis bacillus Calmette-Guérin in mouse model.
Authors: Takayuki Yoshino, Jun Miyazaki, Takahiro Kojima, Shuya Kandori, Hideyuki Akaza, Ikuya Yano, Hiroyuki Nishiyama
Journal: Journal of Clinical Oncology (2018)

461 Background: Intravesical instillation of live bacillus Calmette-Guérin (BCG) is an established immunotherapy for non-muscle invasive bladder cancer. However, development of non-infectious agents has been expected, because there are several problems due to instillation of live bacteria. BCG cell wall skeleton is known to stimulate host immune system, but the mechanism is still unknown. Mycolic acid (MA), which consist of three subclasses (α, keto, methoxy), is the most abundant lipid component of BCG cell wall and is expected to be one of essential active components. Objective: In order to identify active component from BCG cell wall and develop non-infectious BCG-derived immunotherapy, anti-tumor activities of cationic liposomes incorporating each subclass of MA were assessed using mouse syngeneic graft model. Methods: Heat killed packed cells of M. bovis BCG Tokyo 172 were fully hydrolyzed and MA was obtained. MA was separated to three subclasses by thin layer chromatography. Cationic and hydrophilic liposomes incorporating each subclass of MA were prepared. C57BL/6 mice were subcutaneously inoculated with a mixture of MB49 cells and PBS or liposome with/without MA followed by additional injection of PBS or liposome. Tumor growth was monitored. Infiltration of CD4/8 lymphocytes was examined by immunostaining. Results: Cationic liposomes were internalized into cytoplasm of MB49 cells, a mouse bladder cancer cell line. Cell proliferation was not affected by liposome incorporating MA. Tumor growth was significantly suppressed in mice treated with keto MA-liposome (vs PBS, p = 0.007), but not in mice treated withα-or methoxy-MA liposomes. Number of infiltrating CD8 lymphocytes was higher in tumor treated with keto MA-liposome than control. Antitumor effect of keto MA-liposome disappeared in nude mouse, while the effect existed in beige mouse with NK activity deficiency (vs PBS, p = 0.045). Conclusions: Keto MA-liposome showed the strongest antitumor effects in mouse model among three subclasses. T cell immunity may contribute to those effects.
COMPARISON OF TWO LIPID APHERESIS SYSTEMS IN PATIENTS WITH HOMOZYGOUS FAMILIAL HYPERCHOLESTEROLEMIA: A SINGLE CENTER 3-YEAR EXPERIENCE
Authors: Ahmet Temizhan, Elif Hande Ozcan Cetin, Mehmet S. Cetin, Bahar Tekin Tak
Journal: Journal of the American College of Cardiology (2018)
Health and economic outcomes of two different follow up strategies in effectively cured advanced head and neck cancer patients.
Authors: Lisa F. Licitra, Federica Favales, Enrico Sesenna, Giuseppe Spriano, Mohssen Ansarin, Marco Benazzo, Piero Nicolai, Renzo Corvò, Cesare Grandi, Giuseppe Grando, Massimo Squadrelli, Claudio Marchetti, Franco Ionna, Christian Simon, Antonella Richetti, Livio Presutti, Michela Meregaglia, Luigi Mariani, Carla Rognoni, Paolo Bossi
Journal: Journal of Clinical Oncology (2015)

TPS6625 Background: optimal timing and type of examinations for the follow up (FUP) of head and neck squamous cell cancer (HNSCC) survivors have not been established yet. There is also a need to find out which is the most cost-effective FUP program in this population. The present trial aims at comparing a more intensive radiologic FUP approach with a less intensive one, also evaluating its economical impact on healthcare system. Methods: this is a randomized, phase II, multicenter trial conducted in 15 Centers throughout Italy and Switzerland. Patients with stage III-IV SCC of oral cavity, oropharynx, larynx or hypopharynx having already received radiation therapy as part of their curative treatment and in complete remission at six months are randomized in two arms according to different FUP approaches. A non intensive FUP approach (ARM A) foresees only a radiologic evaluation (locoregional CT scan or MRI) within 6 months since treatment end and subsequently only at signs or symptoms occurrence (according to NCCN guidelines). An intensive FUP approach (ARM B) consists of scheduled radiologic evaluations (CT scan or MRI of head and neck) 2 times/year in the first 2 years and 1 time/year in the third and fourth year; PET scans are requested yearly in the first 3 years for patients with smoking history. FUP visits consist of physical and fiberoptic endoscopic examinations of head and neck district, laboratory tests, quality of life questionnaires and evaluation of out-of-pocket costs and productivity losses; timing of FUP visits is the same in both arms. An estimated 330 patients (randomized 1:1) are being enrolled over the first year; health outcomes and costs will be assessed over the next two years. The percentage of potentially salvageable recurrences or second primaries, as well as the cause-specific survival and the overall survival of recurring patients will be evaluated in both groups. Incremental cost-effectiveness ratio (cost/life year gained) and cost-utility ratios (cost/QALY) will be calculated referring to WHO thresholds of 1-3 times per capita gross domestic product. ClinicalTrials.gov Identifier: NCT02262221. The trial is funded by a grant from the Swiss Bridge Foundation. Clinical trial information: NCT02262221.
Outcomes of serial MRI/ultrasound fusion targeted biopsy in men with very low-risk and low-risk prostate cancer managed with active surveillance.
Authors: Walter Hsiang, Kamyar Ghabili, Jamil Syed, Kevin Nguyen, Alfredo Suarez-Sarmiento, Michael Leapman, Preston Sprenkle
Journal: Journal of Clinical Oncology (2018)

114 Background: The utility of serial magnetic resonance imaging (MRI)/ultrasound (US) fusion targeted prostate biopsy in men with prostate cancer (PCa) on active surveillance (AS) have not been clearly defined. We sought to investigate the rate of Gleason upgrading both on sequential fusion targeted and systematic biopsies among men with low-risk PCa managed with AS. Methods: We retrospectively queried an institutional database of 800 patients undergoing MRI/US fusion biopsy to identify 209 patients on AS with at least two fusion biopsies between December 2013 and November 2016. Men with National Comprehensive Cancer Network (NCCN) very low-risk and low-risk criteria were included. Gleason upgrade was defined as detection of Gleason score &gt;=3+4. The proportion of patients experiencing upgrade on systematic, fusion, or both biopsy techniques was tabulated. Associations of clinical, pathologic, and imaging factors with biopsy upgrade were analyzed by logistic regression. Results: Of 209 patients undergoing MRI/US fusion biopsy, 73 (35.0%) had at least two targeted biopsies (66% very low-risk and 34% low-risk PCa). The time between biopsies was 12.6 months (11.2-17.7). The median PSA and PSA density were 5.4 ng/mL (4.2-7.1) and 0.11 ng/mL/mL (0.07-0.18), respectively. 21 (29%) patients experienced Gleason upgrade on subsequent biopsy. Of those, 6 (8%), 5 (7%), and 10 (14%) had upgrade on systematic biopsy only, fusion biopsy only, and both systematic and fusion biopsy, respectively. Patients with upgrade on subsequent biopsy had higher PSA (p=0.02) and PSA density (p=0.02), and were among low-risk disease population (p=0.03). In logistic regression models, greater number of positive cores in systematic biopsy (OR 1.88; 95% CI 1.23-2.92; p=0.005) was associated with the total Gleason upgrade on repeated biopsy. Conclusions: In men with favorable risk prostate cancer managed with AS, Gleason upgrade was detected in a 29% of patients on a second MRI/US fusion biopsy including both targeted and systematic regions. These findings support the continued use of both MRI fusion and systematic biopsy during surveillance due to risks of reclassification over time.
Novel Self-assembled Organic Nanoprobe for Molecular Imaging and Treatment of Gram-positive Bacterial Infection
Authors: Tang Gao, Hongliang Zeng, Huan Xu, Feng Gao, Wei Li, Shengwang Zhang, Yi Liu, Guifang Luo, Mingdan Li, Dejian Jiang, Zhigao Chen, Yong Wu, Wei Wang, Wenbin Zeng
Journal: Theranostics (2018)

Background: Increasing bacterial infections as well as a rise in bacterial resistance call for the development of novel and safe antimicrobial agents without inducing bacterial resistance.Nanoparticles (NPs) present some advantages in treating bacterial infections and provide an alternative strategy to discover new antibiotics.Here, we report the development of novel self-assembled fluorescent organic nanoparticles (FONs) with excellent antibacterial efficacy and good biocompatibility.Methods: Self-assembly of 1-(12-(pyridin-1-ium-1-yl)dodecyl)-4-(1,4,5-triphenyl-1H-imidazol-2yl)pyridin-1-ium (TPIP) in aqueous solution was investigated using dynamic light scattering (DLS) and transmission electron microscopy (TEM).The bacteria were imaged under a laser scanning confocal microscope.We evaluated the antibacterial efficacy of TPIP-FONs in vitro using sugar plate test.The antimicrobial mechanism was explored by SEM.The biocompatibility of the nanoparticles was examined using cytotoxicity test, hemolysis assay, and histological staining.We further tested the antibacterial efficacy of TPIP-FONs in vivo using the S. aureus-infected rats.Results: In aqueous solution, TPIP could self-assemble into nanoparticles (TPIP-FONs) with characteristic aggregation-induced emission (AIE).TPIP-FONs could simultaneously image gram-positive bacteria without the washing process.In vitro antimicrobial activity suggested that TPIP-FONs had excellent antibacterial activity against S. aureus (MIC = 2.0 µg mL -1 ).Furthermore, TPIP-FONs exhibited intrinsic biocompatibility with mammalian cells, in particular, red blood cells.In vivo studies further demonstrated that TPIP-FONs had excellent antibacterial efficacy and significantly reduced bacterial load in the infectious sites. Conclusion:The integrated design of bacterial imaging and antibacterial functions in the self-assembled small molecules provides a promising strategy for the development of novel antimicrobial nanomaterials.
The aberrant splicing of BAF45d links splicing regulation and transcription in glioblastoma
Authors: Guillermo Aldave, Marisol Gonzalez-Huarriz, Angel Rubio, Juan Pablo Romero, Datta Ravi, Belén Miñana, Mar Cuadrado-Tejedor, Ana García-Osta, Roeland Verhaak, Enric Xipell, Naiara Martinez-Vélez, Arlet Acanda de la Rocha, Montserrat Puigdelloses, Marc García-Moure, Miguel Marigil, Jaime Gállego Pérez-Larraya, Oskar Marín-Bejar, Maite Huarte, Maria Stella Carro, Roberto Ferrarese, Cristobal Belda-Iniesta, Angel Ayuso, Ricardo Prat-Acín, Fernando Pastor, Ricardo Díez-Valle, Sonia Tejada, Marta M Alonso
Journal: Neuro-Oncology (2018)

Glioblastoma, the most aggressive primary brain tumor, is genetically heterogeneous. Alternative splicing (AS) plays a key role in numerous pathologies, including cancer. The objectives of our study were to determine whether aberrant AS could play a role in the malignant phenotype of glioma and to understand the mechanism underlying its aberrant regulation.We obtained surgical samples from patients with glioblastoma who underwent 5-aminolevulinic fluorescence-guided surgery. Biopsies were taken from the tumor center as well as from adjacent normal-appearing tissue. We used a global splicing array to identify candidate genes aberrantly spliced in these glioblastoma samples. Mechanistic and functional studies were performed to elucidate the role of our top candidate splice variant, BAF45d, in glioblastoma.BAF45d is part of the switch/sucrose nonfermentable complex and plays a key role in the development of the CNS. The BAF45d/6A isoform is present in 85% of over 200 glioma samples that have been analyzed and contributes to the malignant glioma phenotype through the maintenance of an undifferentiated cellular state. We demonstrate that BAF45d splicing is mediated by polypyrimidine tract-binding protein 1 (PTBP1) and that BAF45d regulates PTBP1, uncovering a reciprocal interplay between RNA splicing regulation and transcription.Our data indicate that AS is a mechanism that contributes to the malignant phenotype of glioblastoma. Understanding the consequences of this biological process will uncover new therapeutic targets for this devastating disease.
Towards precision medicine in sepsis: a position paper from the European Society of Clinical Microbiology and Infectious Diseases
Authors: J. Rello, T.S.R. van Engelen, E. Alp, T. Calandra, V. Cattoir, W.V. Kern, M.G. Netea, S. Nseir, S.M. Opal, F.L. van de Veerdonk, M.H. Wilcox, W.J. Wiersinga
Journal: Clinical Microbiology and Infection (2018)
A simple diet- and chemical-induced murine NASH model with rapid progression of steatohepatitis, fibrosis and liver cancer
Authors: Takuma Tsuchida, Youngmin A. Lee, Naoto Fujiwara, Maria Ybanez, Brittany Allen, Sebastiao Martins, M. Isabel Fiel, Nicolas Goossens, Hsin-I. Chou, Yujin Hoshida, Scott L. Friedman
Journal: Journal of Hepatology (2018)