tbuckley/cabot-search huggingface dataset:
Abstract 11060: Regadenoson Positron Emission Tomography (PET) is Safe to Guide Coronary Revascularization In High-risk Patients With Severe Symptomatic Aortic Stenosis (AS) Being Considered for Transcatheter Aortic Valve Replacement (TAVR)
Authors: Paul C Cremer, Shaden Khalaf, Leonardo Rodriguez, Manuel D Cerqueira, Wael A Jaber
Journal: Circulation (2013)

The safety of regadenoson PET stress testing in patients with severe AS has not been ascertained. Moreover, in patients being considered for TAVR, symptoms may be related to coronary artery disease (CAD) and/or AS, and appropriate revascularization prior to TAVR is imperative. We sought to establish the safety of regadenoson PET in this setting from a retrospective cohort at our institution.  Between May 2010 and May 2013, we identified 44 patients from our cardiac PET database who were undergoing evaluation for TAVR. Our patients were high-risk with a median age of 72 ± 17, mean STS mortality of 11.5 ± 7.8%, and a median GFR of 42 ± 27ml/min/1.73m 2 . 93% of patients had a previous diagnosis of CAD; 41% had a previous percutaneous coronary intervention, and 61% had undergone a prior coronary artery bypass grafting.  On echocardiography, mean ejection fraction (EF) was 38 ± 16% with a mean aortic valve area of 0.78 ± 0.26 cm 2 . Peak and mean gradients were 52 ± 19 and 31 ± 12 mmHg, respectively, with a mean dimensionless index of 0.23 ± 0.06.  There were no major adverse events. A significant transient drop in blood pressure, defined as decrease in systolic blood pressure (BP) by 20 mmHg and a nadir less than 90 mmHg, was relatively common (16%). There was a non-significant trend between reduced EF and a significant decrease in BP (mean EF 40 ± 16 v 28 ± 11%, p = 0.07). There was no association between measures of AS severity and a significant decrease in BP. One patient with hypotension became light-headed, but symptoms spontaneously resolved. Another patient had an episode of non-sustained ventricular tachycardia.  PET abnormalities were present in 93%. 68% had ischemia, and 70% had fixed perfusion defects. Average resting and stress EF on PET were 36 ± 18% and 33 ± 16%, respectively. 55% of patients with abnormal tests underwent coronary angiography. 87% of these patients had ischemia or evidence of hibernating myocardium. 34% of our patients underwent revascularization, and 93% of these had revascularization guided by PET results.  In high-risk patients being considered for TAVR, regadenoson PET is safe to guide coronary revascularization. This modality may be particularly useful in patients with renal insufficiency, known CAD, and prior revascularization.
Amplification of the dihydrofolate reductase gene is a mechanism of acquired resistance to methotrexate in patients with acute lymphoblastic leukemia and is correlated with p53 gene mutations
Authors: E Goker, M Waltham, A Kheradpour, T Trippett, M Mazumdar, Y Elisseyeff, B Schnieders, P Steinherz, C Tan, E Berman
Journal: Blood (1995)
Neurobehavioral functioning in a nonconfounded group of asymptomatic HIV-seropositive homosexual men
Authors: R A Stern, N G Singer, S G Silva, H J Rogers, D O Perkins, C D Hall, C M van der Horst, D L Evans
Journal: American Journal of Psychiatry (1992)

Neurobehavioral functioning was tested in 34 asymptomatic HIV-seropositive and 43 HIV-seronegative male homosexual subjects without substance abuse and CNS disorders. The HIV-positive subjects exhibited mild motor slowing compared to the seronegative subjects. These differences remained after controlling for potential cofactors. Early neurobehavioral impairment in HIV infection seems limited to subclinical motor deficits and attributable to HIV rather than possible confounding factors.
The Human FSGS-Causing ANLN R431C Mutation Induces Dysregulated PI3K/AKT/mTOR/Rac1 Signaling in Podocytes
Authors: Gentzon Hall, Brandon M. Lane, Kamal Khan, Igor Pediaditakis, Jianqiu Xiao, Guanghong Wu, Liming Wang, Maria E. Kovalik, Megan Chryst-Stangl, Erica E. Davis, Robert F. Spurney, Rasheed A. Gbadegesin
Journal: Journal of the American Society of Nephrology (2018)

We previously reported that mutations in the anillin (ANLN) gene cause familial forms of FSGS. ANLN is an F-actin binding protein that modulates podocyte cell motility and interacts with the phosphoinositide 3-kinase (PI3K) pathway through the slit diaphragm adaptor protein CD2-associated protein (CD2AP). However, it is unclear how the ANLN mutations cause the FSGS phenotype. We hypothesized that the R431C mutation exerts its pathogenic effects by uncoupling ANLN from CD2AP.We conducted in vivo complementation assays in zebrafish to determine the effect of the previously identified missense ANLN variants, ANLNR431C and ANLNG618C during development. We also performed in vitro functional assays using human podocyte cell lines stably expressing wild-type ANLN (ANLNWT ) or ANLNR431C .Experiments in anln-deficient zebrafish embryos showed a loss-of-function effect for each ANLN variant. In human podocyte lines, expression of ANLNR431C increased cell migration, proliferation, and apoptosis. Biochemical characterization of ANLNR431C -expressing podocytes revealed hyperactivation of the PI3K/AKT/mTOR/p70S6K/Rac1 signaling axis and activation of mTOR-driven endoplasmic reticulum stress in ANLNR431C -expressing podocytes. Inhibition of mTOR, GSK-3β, Rac1, or calcineurin ameliorated the effects of ANLNR431C . Additionally, inhibition of the calcineurin/NFAT pathway reduced the expression of endogenous ANLN and mTOR.The ANLNR431C mutation causes multiple derangements in podocyte function through hyperactivation of PI3K/AKT/mTOR/p70S6K/Rac1 signaling. Our findings suggest that the benefits of calcineurin inhibition in FSGS may be due, in part, to the suppression of ANLN and mTOR. Moreover, these studies illustrate that rational therapeutic targets for familial FSGS can be identified through biochemical characterization of dysregulated podocyte phenotypes.
Abstract 12839: Association of Elevated Blood Glucose Level at Admission in Patients With Acute Decompensated Heart Failure and Long-Term Mortality
Authors: Sharma Kattel, Takatoshi Kasai, Shoichiro Yatsu, Azusa Murata, Takao Kato, Shoko Suda, Masaru Hiki, Kiyoshi Takasu, Tetsuro Miyazaki, Atsutoshi Takagi, Katsumi Miyauchi, Hiroyuki Daida
Journal: Circulation (2014)

Introduction:  Elevated blood glucose (BG) level has been shown to have adverse short-term prognosis in patients with acute decompensated heart failure (ADHF). Relation of this elevated BG level at hospital admission for ADHF in long term has not been well defined.   Hypothesis:  To evaluate the long term prognosis of elevated BG level at the time of admission in ADHF.   Methods:  Cohorts of 1684 patients consecutively admitted to the cardiac intensive-care unit from 2007 to 2011 were studied. Among them, 495 patients eligible for the study meeting criteria for ADHF after exclusion of other life threatening conditions such as neoplasms or acute myocardial infarction were divided into 4 groups based on median of BG level (≥131mg/dl or less ) on admission and presence or absence of diabetes mellitus (DM). The risks of each group for all-cause mortality were assessed by multivariable Cox proportional model including other independent variables that showed P   Results:  At a median follow-up of 1.8 years, 148 patients died (29.9%). There were 168 patients without either BG-elevation or DM, 67 without BG-elevation but with DM, 105 with BG-elevation but no DM and 155 with both BG-elevation and DM. In the multivariable model including other independent variables (age, sex, obesity, history of stroke, ischemic heart disease, atrial fibrillation, renal dysfunction, mean blood pressure, B-type natriuretic peptide, hemoglobin, C-reactive protein, sodium and potassium levels, and use of diuretics) compared with patients without either BG-elevation or DM, those with BG-elevation regardless of presence or absence of DM showed a greater risk of increased mortality (Figure).   Conclusions:  Elevated BG level at the time of admission in ADHF seems to be a powerful prognostic marker independent of the diabetes status. Targeting therapy for this variable may improve the long-term prognosis in patients with heart failure.
Genomic and Transcriptomic Analysis Reveals Incremental Disruption of Key Signaling Pathways during Melanoma Evolution
Authors: A. Hunter Shain, Nancy M. Joseph, Richard Yu, Jamal Benhamida, Shanshan Liu, Tarl Prow, Beth Ruben, Jeffrey North, Laura Pincus, Iwei Yeh, Robert Judson, Boris C. Bastian
Journal: Cancer Cell (2018)
Treatment failure of pharyngeal gonorrhoea with internationally recommended first-line ceftriaxone verified in Slovenia, September 2011
Authors: M Unemo, D Golparian, M Potočnik, S Jeverica
Journal: Eurosurveillance (2012)

We describe the second case in Europe of verified treatment failure of pharyngeal gonorrhoea, caused by an internationally occurring multidrug-resistant gonococcal clone, with recommended first-line ceftriaxone 250 mg in Slovenia. This is of grave concern since ceftriaxone is last remaining option for empirical treatment. Increased awareness of ceftriaxone failures, more frequent test-of-cure, strict adherence to regularly updated treatment guidelines, and thorough verification/falsification of suspected treatment failures are essential globally. New effective treatment options are imperative.
Temporal Trends in the Incidence of and Mortality Associated With Heart Failure With Preserved and Reduced Ejection Fraction
Authors: Connie W Tsao, Asya Lyass, Danielle Enserro, Martin G Larson, Jennifer E Ho, Jorge R Kizer, John S Gottdiener, Bruce M Psaty, Ramachandran S Vasan
Journal: JACC Heart Failure (2018)
MALIGNANT BILIARY OBSTRUCTION AND INITIAL CHOLANGITIS PREDISPOSE TO PLASTIC STENT DYSFUNCTION
Authors: Z Szakács, S Gódi, D Pécsi, P Varjú, B Tinusz, Á Vincze
Journal: Endoscopy (2018)

Cholangitis, obstruction and migration are often seen after biliary plastic stent placement and might shorten stent patency, but the predictors of these complications are poorly defined.
EVALUATION OF CHARACTERISTICS AND INCIDENCE OF INTERVAL COLORECTAL CANCER
Authors: L Monteserín Ron, DJ Matias, L Rodríguez Martín, L Vaquero Ayala, R Díez Rodríguez, C Villar Lucas, R Quiñones Castro, S Vivas Alegre
Journal: Endoscopy (2018)

The development of a colorectal cancer (CRC) after an initial exam before the established revision can be due to non-visualized lesions or the appearance of a new tumour and this is called interval colorectal cancer. Our aim was to know the incidence of colorectal cancer in our health area and the associated risk factors.
Factores de riesgo de complicaciones en disección submucosa endoscópica colorrectal (DSE-CR): Estudio multicéntrico
Authors: JC Marín Gabriel, F Ramos Zabala, F Múgica Aguinaga, E Albéniz Urbizu, J De La Peña García, A Sánchez Yagüe, C Dolz Abadía, MG Fernández Esparrach, A Álvarez Delgado, H Cortés Pérez
Journal: Endoscopy (2017)

La frecuencia de complicaciones asociadas a la DSE-CR es superior, en comparación a las de la resección mucosa, cuando no se realiza por expertos asiáticos.
Clinical and Genomic Characterization of Treatment-Emergent Small-Cell Neuroendocrine Prostate Cancer: A Multi-institutional Prospective Study
Authors: Rahul Aggarwal, Jiaoti Huang, Joshi J. Alumkal, Li Zhang, Felix Y. Feng, George V. Thomas, Alana S. Weinstein, Verena Friedl, Can Zhang, Owen N. Witte, Paul Lloyd, Martin Gleave, Christopher P. Evans, Jack Youngren, Tomasz M. Beer, Matthew Rettig, Christopher K. Wong, Lawrence True, Adam Foye, Denise Playdle, Charles J. Ryan, Primo Lara, Kim N. Chi, Vlado Uzunangelov, Artem Sokolov, Yulia Newton, Himisha Beltran, Francesca Demichelis, Mark A. Rubin, Joshua M. Stuart, Eric J. Small
Journal: Journal of Clinical Oncology (2018)

Purpose The prevalence and features of treatment-emergent small-cell neuroendocrine prostate cancer (t-SCNC) are not well characterized in the era of modern androgen receptor (AR)-targeting therapy. We sought to characterize the clinical and genomic features of t-SCNC in a multi-institutional prospective study. Methods Patients with progressive, metastatic castration-resistant prostate cancer (mCRPC) underwent metastatic tumor biopsy and were followed for survival. Metastatic biopsy specimens underwent independent, blinded pathology review along with RNA/DNA sequencing. Results A total of 202 consecutive patients were enrolled. One hundred forty-eight (73%) had prior disease progression on abiraterone and/or enzalutamide. The biopsy evaluable rate was 79%. The overall incidence of t-SCNC detection was 17%. AR amplification and protein expression were present in 67% and 75%, respectively, of t-SCNC biopsy specimens. t-SCNC was detected at similar proportions in bone, node, and visceral organ biopsy specimens. Genomic alterations in the DNA repair pathway were nearly mutually exclusive with t-SCNC differentiation ( P = .035). Detection of t-SCNC was associated with shortened overall survival among patients with prior AR-targeting therapy for mCRPC (hazard ratio, 2.02; 95% CI, 1.07 to 3.82). Unsupervised hierarchical clustering of the transcriptome identified a small-cell-like cluster that further enriched for adverse survival outcomes (hazard ratio, 3.00; 95% CI, 1.25 to 7.19). A t-SCNC transcriptional signature was developed and validated in multiple external data sets with > 90% accuracy. Multiple transcriptional regulators of t-SCNC were identified, including the pancreatic neuroendocrine marker PDX1. Conclusion t-SCNC is present in nearly one fifth of patients with mCRPC and is associated with shortened survival. The near-mutual exclusivity with DNA repair alterations suggests t-SCNC may be a distinct subset of mCRPC. Transcriptional profiling facilitates the identification of t-SCNC and novel therapeutic targets.
Automated psychological therapy using immersive virtual reality for treatment of fear of heights: a single-blind, parallel-group, randomised controlled trial
Authors: Daniel Freeman, Polly Haselton, Jason Freeman, Bernhard Spanlang, Sameer Kishore, Emily Albery, Megan Denne, Poppy Brown, Mel Slater, Alecia Nickless
Journal: The Lancet Psychiatry (2018)

BackgroundEngaging, interactive, and automated virtual reality (VR) treatments might help solve the unmet needs of individuals with mental health disorders. We tested the efficacy of an automated cognitive intervention for fear of heights guided by an avatar virtual coach (animated using motion and voice capture of an actor) in VR and delivered with the latest consumer equipment.MethodsWe did a randomised trial of automated VR versus usual care. We recruited adults aged older than 18 years with a fear of heights by radio advertisements in Oxfordshire, UK. We diagnosed fear of heights if participants scored more than 29 on the Heights Interpretation Questionnaire (HIQ). We randomly allocated participants by computer in a 1:1 ratio to either automated VR delivered in roughly six 30-min sessions administered about two to three times a week over a 2-week period (intervention group) or to usual care (control group). Randomisation was stratified by severity of fear of heights. The research team, who were unaware of the random allocation, administered three fear-of-height assessments, at baseline (0 weeks), at the end of treatment (2 weeks), and at follow-up (4 weeks). The primary outcome measure was HIQ score (range 16–80, with higher scores indicating greater severity). This trial is registered with the ISRCTN registry, number ISRCTN11898283.FindingsBetween Nov 25, 2017, and Feb 27, 2018, 100 individuals were enrolled and underwent randomisation, of whom 49 were assigned to the VR treatment group and 51 to the control group. All participants completed the 4-week follow-up. The mean total treatment time in VR was 124·43 min (SD 34·23). Compared with participants in the control group, the VR treatment reduced fear of heights at the end of treatment (mean change score −24·5 [SD 13·1] in the VR group vs −1·2 [7·3] in the control group; adjusted difference −24·0, 95% CI −27·7 to −20·3; Cohen's d=2·0; p<0·0001). The benefit was maintained at follow-up (mean change score −25·1 [SD 13·9] in the VR group vs −1·5 [7·8] in the control group; adjusted difference −24·3, 95% CI −27·9 to −20·6; Cohen's d=2·0; p<0·0001). The number needed to treat to at least halve the fear of heights was 1·3. No adverse events were reported.InterpretationPsychological therapy delivered automatically by a VR coach can produce large clinical benefits. Evidence-based VR treatments have the potential to greatly increase treatment provision for mental health disorders.FundingOxford VR, and the National Institute of Health Research Oxford Health Biomedical Research Centre.
Estudio comparativo del drenaje de la vesícula biliar guiado por ecoendoscopia (DVB-USE) mediante prótesis de aposición luminal (PAL) tipo Axios frío y caliente
Authors: R Torres Yuste, S Sevilla Ribota, R Sánchez-Ocaña Hernández, I Peñas Herrero, P Gil Simón, FJ García Alonso, M Cimavilla Román, AY Carbajo López, C De La Serna Higuera, M Pérez-Miranda Castillo
Journal: Endoscopy (2017)

Las PAL permiten el DVB-USE. Las primeras prótesis comercializadas requerían dilatación seriada previo a la inserción de la prótesis sobre guía (tipo frío). Posteriormente aparecieron PAL con un sistema de diatermia que posibilita la inserción directamente sobre la guía (tipo caliente).
Pathologic complete response implies a fewer number of lymph nodes in specimen of rectal cancer patients treated by neoadjuvant therapy and total mesorectal excision
Authors: Leonardo Alfonso Bustamante-Lopez, Caio Sergio Rizkallah Nahas, Sergio Carlos Nahas, Carlos Frederico Sparapan Marques, Rodrigo Ambar Pinto, Guilherme Cutait Cotti, Antonio Rocco Imperiale, Evandro Sobroza de Mello, Ulysses Ribeiro, Ivan Cecconello
Journal: International Journal of Surgery (2018)
Author Correction: Frequent discussion of insomnia and weight gain with glucocorticoid therapy: an analysis of Twitter posts
Authors: Rikesh Patel, Maksim Belousov, Meghna Jani, Nabarun Dasgupta, Carly Winokur, Goran Nenadic, William G. Dixon
Journal: npj Digital Medicine (2018)

[This corrects the article DOI: 10.1038/s41746-017-0007-z.].
Use of Video Review to Investigate Technical Factors That May Be Associated With Delayed Gastric Emptying After Pancreaticoduodenectomy
Authors: Jae Pil Jung, Mazen S. Zenati, Mashaal Dhir, Amer H. Zureikat, Herbert J. Zeh, Richard L. Simmons, Melissa E. Hogg
Journal: JAMA Surgery (2018)

Technical proficiency at robotic pancreaticoduodenectomy (RPD) and video assessment are promising tools for understanding postoperative outcomes. Delayed gastric emptying (DGE) remains a major driver of cost and morbidity after pancreaticoduodenectomy.To determine if technical variables during RPD are associated with postoperative DGE.A retrospective study was conducted of technical assessment performed in all available videos (n = 192) of consecutive RPDs performed at a single academic institution from October 3, 2008, through September 27, 2016.Video review of gastrojejunal anastomosis during RPD.Delayed gastric emptying was classified according to International Study Group of Pancreatic Surgery criteria. Video analysis reviewed technical variables specific in the construction of the gastrojejunal anastomosis. Using multivariate analysis, DGE was correlated with known patient variables and technical variables, individually and combined.Of 410 RPDs performed, video was available for 192 RPDs (80 women and 112 men; mean [SD] age, 65.7 [11.1] years). Delayed gastric emptying occurred in 41 patients (21.4%; grade A, 15; grade B, 14; and grade C, 12). Patient variables contributing to DGE on multivariate analysis were advanced age (odds ratio [OR] 1.11; 95% CI, 1.05-1.16; P < .001), small pancreatic duct size (OR, 0.84; 95% CI, 0.72-0.98; P = .03), and postoperative pseudoaneurysm (OR, 17.29; 95% CI, 2.34-127.78; P = .005). However, technical variables contributing to decreased DGE on multivariate analysis included the flow angle (within 30° of vertical) between the stomach and efferent jejunal limb (OR, 0.25; 95% CI, 0.08-0.79; P = .02), greater length of the gastrojejunal anastomosis (OR, 0.40; 95% CI, 0.20-0.77; P = .006), and a robotic-sewn anastomosis (robotic suture vs stapler: OR, 0.30; 95% CI, 0.09-0.95; P = .04).This study examines modifiable technical factors through the use of review of video obtained at the time of operation and suggests ways by which the surgical construction of the gastrojejunal anastomosis during RPD may reduce the incidence of DGE as a framework for prospective quality improvement.
Abstract 278: PGC1α Activation Corrects Cardiac Dysfunction Caused by Anti-diabetic Dual-PPARα/γ Therapy
Authors: Charikleia Kalliora, Melissa J Lieu, Yujia Yue, Christine Pol, Mesele C Valenti, Ying Tian, Diego Scerbo, Christian Schulze, Muniswamy Madesh, Mete Civelek, Brian N Finck, Ira J Goldberg, Konstantinos Drosatos
Journal: Circulation Research (2017)

Peroxisome proliferator-activated receptor (PPAR) agonists are used in metabolic diseases. PPARα agonists target hyperlipidemia and PPARγ agonists correct hyperglycemia. Dual PPARα/γ agonists were developed to combine the benefits in type 2 diabetes patients. Despite their beneficial effect, PPARα/γ agonists caused cardiac dysfunction. We studied the mechanisms that underlie this toxic effect aiming to improve a failed therapy. Wild type mice were fed with chow and high fat diets containing Tesaglitazar (TESA) a dual PPARα/γ agonist for 6 weeks. Although, TESA lowered plasma triglyceride and glucose levels compared to controls, 2D-echo revealed severe cardiac dysfunction. Assessment of the expression of cardiac fatty acid metabolism genes that are regulated by PPARs showed that mRNA and protein levels of PPARγ-coactivator (PGC1α), a regulator of mitochondrial biogenesis, had the most profound reduction. Furthermore, we observed increased acetylation of PGC1α levels, which indicates lower activation and lower mitochondrial respiration. We then examined the mechanisms that underlie lower expression of PGC1α upon activation of PPARα and PPARγ. Thus, we administered C57BL/6 mice with both single PPARα and PPARγ agonists (WY14643 and rosiglitazone). This treatment reproduced the reduction in PGC1α expression that we observed with TESA. Moreover, mitochondria abundance was lower. Luciferase promoter analysis in a human cardiomyocyte cell line showed that PPARα and PPARγ compete for binding on PPAR elements of the human Pgc1a promoter, as well as that PPARα binding compromises PPARγ-mediated activation of the Pgc1α promoter. Aiming to decipher the mechanism via which dual PPARα/γ activation increases acetylation and thus inhibits PGC1α, we measured cardiac protein levels of the deacetylase sirtuin 1 (SIRT1), which were lower in primary cardiomyocytes from TESA-treated mice. We then treated mice with diet containing TESA and Resveratrol (RSV), which stimulates SIRT1. RSV attenuated TESA-driven cardiac dysfunction and corrected mitochondrial respiratory rates in primary cardiomyocytes. We propose that SIRT1-mediated activation of PGC1α blunts the cardiotoxic effect of dual PPARα/γ agonists and improves their therapeutic potential.
IN VIVO ENDOSCOPIC HEMOSTASIS ON SMALL BOWEL OOZING LESIONS: FIRST EXPERIENCE IN THE EMERGENCY SETTING WITH THE THULIUM/ERBIUM LASER SYSTEM
Authors: GE Tontini, B Marinoni, L Pastorelli, A Rimondi, H Neumann, L Spina, M Vecchi
Journal: Endoscopy (2018)

The Thulium/Erbium laser system (TELS) is a new and promising hemostatic technique in interventional endoscopy, which has been demonstrated successful and safe in the first in vivo hemostatic experiences. The 2-µm wavelength of the Thulium laser provides a confined coagulation depth (0.2 – 0.4 mm) to reduce possible inadvertent injuries.