tbuckley/cabot-search huggingface dataset:
Abstract 13303: Folic Acid Reverses Nitric Oxide Synthase Uncoupling and Prevents Insulin Resistance-Induced Cardiac Dysfunction: Role Of Ca2+/calmodulin Activated Kinase II (CaMKII)
Authors: Nathan D Roe, Jun Ren
Journal: Circulation (2012)

It has been shown that nitric oxide synthase (NOS) becomes uncoupled in diabetes and switches from producing nitric oxide to superoxide (O 2  - ) enroute to cardiac dysfunction. However, the downstream effector(s) from NOS uncoupling in diabetic cardiomyopathy remain elusive. In this study we examined the impact of folic acid supplement (15mg/kg/d for 4 wks), which reverses NOS uncoupling, on cardiac dysfunction cause by sucrose diet-induced insulin resistance. Insulin resistance was confirmed by glucose tolerance test while whole heart echocardiographic function and isolated cardiomyocyte contractile function were assessed. Tetracaine inhibitable rise in cytosolic Ca 2+  was used to measure ryanodine receptor (RYR) leak. O 2  -  production was monitored using DHE staining in the absence or presence of the NOS inhibitor L-NAME to examine NOS uncoupling and oxidative/phosphorylation state of CaMKII was evaluated by western blot. Our data revealed increased NOS dependent O 2  -  production following sucrose diet feeding, (-2.4±5.7 vs. 30.8±7.1) which was reversed with folic acid administration (p 2+  rise and prolonged intracellular Ca 2+  clearance, which was nullified by folic acid (n=3, p 2+  leak from RYR (1.37±0.45 vs. 3.65±0.64), and spontaneous Ca 2+  transients (0.007±0.003 per sec. vs. 0.087±0.018 per sec.) were observed in insulin resistance, both of which were alleviated by folic acid (n=3, p
Association of Second Allogeneic Hematopoietic Cell Transplant vs Donor Lymphocyte Infusion With Overall Survival in Patients With Acute Myeloid Leukemia Relapse
Authors: Mohamed A. Kharfan-Dabaja, Myriam Labopin, Emmanuelle Polge, Taiga Nishihori, Ali Bazarbachi, Jürgen Finke, Michael Stadler, Gerhard Ehninger, Bruno Lioure, Nicolaas Schaap, Boris Afanasyev, Moshe Yeshurun, Cecilia Isaksson, Johan Maertens, Yves Chalandon, Christoph Schmid, Arnon Nagler, Mohamad Mohty
Journal: JAMA Oncology (2018)

The optimal treatment approach to patients with acute myeloid leukemia (AML) who relapse after an allogeneic hematopoietic cell transplant (allo-HCT) remains elusive. No randomized clinical trial comparing survival outcomes of a second allo-HCT (allo-HCT2) vs donor lymphocyte infusion (DLI) has been conducted to date.To compare overall survival (OS) after an allo-HCT2 or DLI in relapsed AML after a first allo-HCT.A retrospective registry study from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation involving 418 adults who received an allo-HCT2 (n = 137) or DLI (n = 281) for postallograft-relapsed AML. Analysis was assessed on the principle of intent-to-first received intervention. The data were collected from November 21, 2015, to May 15, 2017, and analysis was performed June 1, 2017.Number of patients with relapsed AML who are alive after 2 years and 5 years from receiving an allo-HCT2 or DLI.Of the 418 patients, 228 (54.5%) were men; mean age was 46.2 years (interquartile range, 36.5-56.9 years). There was no apparent difference in OS whether an allo-HCT2 or DLI was prescribed (2-year OS with allo-HCT2, 26%; 5-year OS with allo-HCT2, 19%; 2-year OS with DLI, 25%; 5-year OS with DLI, 15%; P = .86). Overall survival was better if either of these procedures was offered when the patient was in complete remission (hazard ratio, 0.55; 95% CI, 0.41-0.74; P < .001). Conversely, OS was low for patients relapsing within less than 6 months after an allo-HCT1, regardless of the treatment prescribed (5-year OS: allo-HCT2, 9%; 95% CI, 1%-17% vs DLI, 4%; 95% CI, 1%-8%; P = .86).Heterogeneity of the patient-, disease-, and treatment-related characteristics limit the ability to recommend one approach over another. Findings of this study highlight that best outcomes seem to be achieved in patients relapsing 6 or more months from an allo-HCT1 or those in complete remission at the time of either allo-HCT2 or DLI.
Comparación de las características endoscópicas de la esofagitis eosinofílica en niños y adultos
Authors: E Perez Arellano, MI Rodríguez García, AB Galera Rodenas, EJ De La Morena Madrigal
Journal: Endoscopy (2017)

La esofagitis eosinofílica (EE), es una enfermedad frecuente (1/2000), siendo la segunda causa de enfermedad esofágica después de la enfermedad por reflujo y la primera causa de disfagia e impactación en menores de 50 años, con diferencias en cuanto a su presentación clínica en niños y adultos.
Abstract 18848: Pharmacodynamic Effects of in vitro Cangrelor in Patients Treated With Oral P2y12 Receptor Inhibitors
Authors: Fabiana Rollini, Francesco Franchi, Jung Rae Cho, Megha Kureti, Jose Rivas, Martin M Zenni, Theodore A Bass, Dominick J Angiolillo
Journal: Circulation (2016)

Background:  Variability in the onset of platelet inhibitory effects induced by oral P2Y 12  receptor antagonists, including prasugrel and ticagrelor, has been shown in high-risk settings, underscoring the need for intravenous P2Y 12  agents, such as cangrelor, characterized by immediate effects. To date there are no studies comparing the pharmacodynamic (PD) effects induced by cangrelor between ticagrelor and prasugrel-treated patients, which represented the aim of this investigation.   Methods:  In a setting of a prospective randomized study,  in vitro  cangrelor effects were investigated in coronary artery disease (CAD) patients on maintenance aspirin (81mg/qd) and clopidogrel (75mg/qd) therapy, who then were switched to prasugrel or ticagrelor. Patients (n=110) were randomized to prasugrel (60mg LD/10mg MD qd) or ticagrelor (180mg LD/90mg MD bid) for 1 week. PD assessments, using the platelet reactivity index (PRI) by VASP, were performed before and after in vitro incubation with cangrelor (500 nM) during the acute (baseline, 30 min, 2 hrs) and chronic (1 week) phases of treatment.   Results:  In vitro  cangrelor significantly reduced PRI values irrespective of oral P2Y 12  receptor inhibitor, with absolute changes more marked at baseline, while on clopidogrel, compared with prasugrel and ticagrelor. After switching to prasugrel or ticagrelor,  in vitro  cangrelor significantly reduced PRI values at all timepoints in both groups, with the exception of ticagrelor 2 hrs after LD (Fig. A and B). Overall, there were no differences in cangrelor induced antiplatelet effects between prasugrel and ticagrelor with PRI levels consistently low and similar at each time point (Fig. C).   Conclusions:  In CAD patients treated with oral P2Y 12  receptor inhibitors,  in vitro  cangrelor is associated with promptly enhanced platelet inhibition with similar effects in both prasugrel and ticagrelor treated patients during the acute and chronic phases of treatment.
Do Patients With Advanced Cancer Have the Ability to Make Informed Decisions for Participation in Phase I Clinical Trials?
Authors: Fay J. Hlubocky, Greg A. Sachs, Eric R. Larson, Halla S. Nimeiri, David Cella, Kristen E. Wroblewski, Mark J. Ratain, Jeffery M. Peppercorn, Christopher K. Daugherty
Journal: Journal of Clinical Oncology (2018)

Purpose Patients with advanced cancer (ACPs) participating in phase I clinical trials inadequately understand many elements of informed consent (IC); however, the prevalence and impact of cognitive impairment has not been described. Patients and Methods ACPs enrolled onto phase I trials underwent neuropsychological assessment to evaluate cognitive functioning (CF) covering the following domains: memory (Hopkins Verbal Learning Test), executive functioning (Trail Making Test B), language (Boston Naming Test-Short Version and Controlled Oral Word Association Test), attention (Trail Making Test A and Wechsler Adult Intelligenence Scale-IV Digit Span), comprehension (Wechsler Adult Intelligence Scale-IV), and quality of life (Functional Assessment of Cancer Therapy-Cognitive Function). Structured interviews evaluated IC and decisional capacity. Psychological measures included distress (Hospital Anxiety Depression Scale) and depression (Beck Depression Inventory-II). Results One hundred eighteen ACPs on phase I trials were evaluated, with CF ranging from mild impairment to superior performance. Only 45% of ACPs recalled physician disclosure of the phase I trial purpose. The 50% of ACPs who correctly identified the phase I research purpose had greater CF compared with ACPs who did not, as revealed by the mean T scores for memory (37.2 ± 5.6 v 32.5 ± 5.1, respectively; P = .001), attention (29 ± 2.7 v 26.9 ± 2.4, respectively; P < .001), visual attention (35.2 ± 6.6 v 31.5 ± 6.2, respectively; P = .001), and executive function (38.9 ± 7.5 v 34 ± 7.1, respectively; P < .001). Older ACPs (≥ 60 years) were less likely to recall physician disclosure of phase I purpose than younger ACPs (30% v 70%, respectively; P = .02) and had measurable deficits in total memory (34.2 ± 5.0 v 37.3 ± 5.6, respectively; P = .002), attention (24.5 ± 2.6 v 28 ± 2.8, respectively; P < .001), and executive function (32.8 ± 7.3 v 36.4 ± 7.6, respectively; P = .01). Older ACPs, compared with younger ACPs, also had greater depression scores (10.6 ± 9.2 v 8.1 ± 5.2, respectively; P = .03) and lower quality-of-life scores (152 ± 29.6 v 167 ± 20, respectively; P = .03). After adjustment by age, no psychological or neuropsychological variable was further significantly associated with likelihood of purpose identification. Conclusion CF seems to play a role in ACP recall and comprehension of IC for early-phase clinical trials, especially among older ACPs.
Importance of Intelligence and Emotional Intelligence for Physicians
Authors: Bella Nichole Kantor, Jonathan Kantor
Journal: JAMA (2018)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Utilidad de la colonografia por TC para la deteccion preoperatoria de polipos en el colon proximal en pacientes con cancer colorectal estenosante
Authors: A López-Serrano, A Polanco, P Latorre, A Pascual, MJ Suárez, P Besó, MJ Martínez, R Expósito, T Ripollés, E Moreno-Osset
Journal: Endoscopy (2017)

La colonografía por tomografía computarizada (CTC) es útil para excluir tumores sincrónicos en el colon proximal previo a la cirugía en pacientes con cáncer colorrectal (CCR) estenosante. Se recomienda realizar una colonoscopia precoz (3 – 6 meses tras la cirugía) para detectar otras lesiones significativas.
Rational Design of Redox‐Responsive and P‐gp‐Inhibitory Lipid Nanoparticles with High Entrapment of Paclitaxel for Tumor Therapy
Authors: Shao‐Qing Chen, Cheng Wang, Shan Tao, Yun‐Xin Wang, Fu‐Qiang Hu, Hong Yuan
Journal: Advanced Healthcare Materials (2018)

Abstract An insufficient drug concentration at the target site and drug efflux resulting in poor efficacy is recognized as important obstacles in tumor treatment. Herein, novel lipid nanoparticles (LNPs) with redox‐responsive properties based on disulfide bond‐contained, quercetin (Qu)‐grafted glyceryl caprylate‐caprate (Gcc) are introduced (Qu‐SS‐Gcc LNPs). Qu‐SS‐Gcc LNPs show good entrapment of paclitaxel (PTX) due to π–π stacking between the aromatic rings of Qu and PTX. In vitro experiments indicate that Qu‐SS‐Gcc LNPs can selectively respond to high levels of reducing substances by breakdown of disulfide bonds, thus achieving rapid and efficient drug release, and only dissociate rapidly in tumor cells rather than in normal cells. Meanwhile, the Qu released concomitantly with the breakdown of disulfide bonds combines with P‐gp and inhibits the drug efflux triggered by P‐gp. Using an orthotopic 4T1 mouse mammary tumor model in BALB/c mice, PTX/Qu‐SS‐Gcc LNPs exhibit superior antitumor efficacy compared to Taxol, in addition better biosafety and inhibition of chemotherapy‐triggered P‐gp overexpression are achieved. Taken together, this work designs and implements redox‐responsive drug release and drug efflux inhibition in tumor cells via modified LNPs, which not only leads to efficient drug release but also solves the problem of drug efflux that exists in stimulus‐responsive systems.
Advanced breast cancer (ABC): Clinical-pathologic characteristics of long-term survivors after dissemination of the tumor.
Authors: Mario Javier Nacul, Ernesto Gil Deza, Eduardo L. Morgenfeld, Edgardo G. J. Rivarola, Felipe G. Gercovich
Journal: Journal of Clinical Oncology (2012)

e11037 Background: ABC is currently an incurable disease but some patients achieve a longer survival. The following case-control study compared patients suffering from ABC that survived 50 months or more after the onset of metastasis (case) with a group of patients similarly diagnosed treated alongside the case group, whose survival after metastasis was less than 50 months (control). Methods: A search of the IOHM breast cancer tumors registry between September 1997 and April 2010 was carried out. Only those with ABC were included in the paper. The population was divided between cases and controls and both groups were compared. Results: 227 patients meeting the required criteria were found. The population characteristics are detailed in the table below. In 161 pts (70%), a molecular subtype was established: Luminal Type A or B (Cases: 49 pts; Controls: 84 pts), Her2 (Cases: 5 pts; Controls: 9 pts), Triple Negative (Cases: 0 pts; Controls: 14 pts). Systemic and local treatments were similar in both groups, depending on the disease’s stage. Conclusions: 1 – Sixty seven patients (cases) survived 50 or more months after the onset of metastasis. 2 – The Luminal Subtype, long DFS of early stages, compromise of non-visceral organs and the compromise of only one organ were indicative of extended survival of the patients. 3 – No patient with Triple Negative tumors was able to achieve prolonged survival, and so we must continue to research better treatments for these patients. [Table: see text]
Pills are not the answer to unhealthy lifestyles
Authors: Fiona Godlee
Journal: BMJ (2018)

More than half of adults aged over 45 will be labelled as hypertensive if new US guidelines are adopted, concludes a study in The BMJ this week (doi:10.1136/bmj.k2357). This equates to 70 million people in the US and 267 million people in China being eligible for antihypertensive drugs, a marked increase on already high rates of drug treatment for high blood pressure. Furthermore, the study calculates that 7.5 million people in the US and 55 million in China would be advised to start drug treatment, …
Score HandDiCap: una nueva herramienta para la predicción de carcinoma infiltrante profundo oculto en lesiones colónicas referidas para resección endoscópica mucosa
Authors: J Rodríguez Sánchez, M Úbeda Muñoz, P Olivencia Palomar, E De La Santa Belda, J Olmedo Camacho
Journal: Endoscopy (2017)

La identificación de carcinoma infiltrante profundo en lesiones colorrectales resulta en ocasiones una tarea compleja, ya que pueden existir áreas focales de infiltración que pasan desapercibidas incluso al examen detallado con cromoendoscopia. Este evento es de extrema importancia ya que marca el fracaso del tratamiento endoscópico. Por tanto, la sospecha de estas áreas de carcinoma infiltrante oculto profundo (CIOP), debe ser un aspecto a tener en cuenta en la toma de decisiones.
Abstract 18761: Predicting Stroke in Patients With Cancer and Atrial Fibrillation: A Cohort Study
Authors: Alejandra Gutierrez, Rushad Patell, Lisa A Rybicki, Alok A Khorana
Journal: Circulation (2016)

Introduction:  Patients with cancer, a known hypercoagulable state, have a higher prevalence of stroke and atrial fibrillation (AF). Stroke prediction risk scores, developed in general medical populations, have not been validated in patients with cancer and AF and role of cancer-specific factors is unknown.   Objective:  To identify unique risk factors and evaluate validity of CHADS2 and CHA2DS2-VASc scores to predict risk of stroke and mortality.   Methods:  We conducted a retrospective cohort study of patients with cancer and concomitant AF at the Cleveland Clinic from 2008-2014. Data were gathered from tumor registry and electronic medical records. Outcomes, CHADS2 and CHA2DS2-VASc scores were calculated from date of cancer diagnosis. Outcomes included ischemic stroke and mortality. Prognostic factors were identified with Fine & Gray regression for stroke and Cox proportional hazards analysis for survival.   Results:  Study population comprised 2,037 patients. Mean age was 70 ±11 years, 64% were male, 68% had hypertension and 35% had known vascular disease. Genitourinary cancers were the most common (29%) followed by gastrointestinal (GI) (18%). Overall, 52% had CHADS2 ≥ 2. Seventy-four patients (3.6%) developed stroke at a median of 6.4 months after cancer diagnosis (0, 93) with overall stroke risk of 1.9/100 patient years. Increased CHADS2 score was associated with stroke (HR 1.41; 95% CI 1.19-1.67; p    Conclusions:  In patients with cancer and AF each point increase in CHADS2 is associated with nearly 40% greater risk of stroke and has a stronger association than CHA2DS2-VASc score. Primary cancer site is a unique risk factor in this population. Both CHADS2 score and stroke are associated with worsened survival and oncologists need to address impact of cardiovascular disease on mortality.
How Movement Modulates Hearing
Authors: David M. Schneider, Richard Mooney
Journal: Annual Review of Neuroscience (2018)

Hearing is often viewed as a passive process: Sound enters the ear, triggers a cascade of activity through the auditory system, and culminates in an auditory percept. In contrast to a passive process, motor-related signals strongly modulate the auditory system from the eardrum to the cortex. The motor modulation of auditory activity is most well documented during speech and other vocalizations but also can be detected during a wide variety of other sound-generating behaviors. An influential idea is that these motor-related signals suppress neural responses to predictable movement-generated sounds, thereby enhancing sensitivity to environmental sounds during movement while helping to detect errors in learned acoustic behaviors, including speech and musicianship. Findings in humans, monkeys, songbirds, and mice provide new insights into the circuits that convey motor-related signals to the auditory system, while lending support to the idea that these signals function predictively to facilitate hearing and vocal learning.
Abstract 11069: Sex-Specific Cardio-Protection Against Vulnerable Plaque Composition and Coronary Vascular Dysfunction in Responders to Statin Therapy
Authors: Naser Ahmadi, Vahid Nabavi, Fereshteh hajsadeghi, Micheal Baskett, Michael Fahmy, John Sanchez, Andrew Choi, Matthew Budoff, Ramin Ebrahimi
Journal: Circulation (2011)

Background:  Coronary artery distensibility index (CDI) is an endothelial-dependent process, associated with vulnerable-plaque (VP) composition, and development of coronary artery disease (CAD). The effects of statin-therapy on CDI and VP composition are not well studied. This study evaluates the response to statin therapy through CDI, VP and clinical outcome.   Methods:  Two hundred and forty eight subjects (aged 65±8 years, 46% women, and 100% statin-therapy) underwent computed tomography angiography (CTA) and were prospectively followed. CDI in left anterior descending artery (LAD) was defined as: [(Early diastole - mid diastole lumen cross section area (CSA))/ (lumen CSA in mid diastole x central pulse pressure) x 1000]. Vulnerable-plaque composite-score (VPS) was measured using semi-quantified plaque volume (none, localized, intermediate, or diffuse) and severity of diseased coronaries (normal, mild, moderate, or severe) in non-calcified and mixed plaques based on American Heart Association 15-segment model. Major adverse cardiac event (MACE) was defined as myocardial infarction or cardiovascular-death. Impaired CDI (0) distinguished non-responders from responders to statin therapy.   Results:  During a median of 36-month follow-up, the event Rate was 10.1% (12.1% in men and 6.25% in women). After adjustment for risk factors, the risk of MACE was 628% and 226% higher in impaired CDI and VPS as compared to normal cohort, which were different between genders (p   Conclusions:  Statin therapy is associated with sex-specific cardio-protective effects by improving CDI and decreasing VPS, and reduces MACE independent of conventional risk factors.
Alan David Rogers
Authors: H. Graham
Journal: BMJ (2015)

The human multispecific drug efflux transporter P-glycoprotein (P-gp) causes drug resistance and modulates the pharmacological profile of systemically administered medicines. It has arisen from a homodimeric ancestor by gene duplication. Crystal structures of mouse MDR1A indicate that P-gp shares the overall architecture with two homodimeric bacterial exporters, Sav1866 and MsbA, which have complete rotational symmetry. For ATP-binding cassette transporters, nucleotide binding occurs in two symmetric positions in the motor domains. Based on the homology with entirely symmetric half-transporters, the present study addressed the key question: can biochemical evidence for the existence of dual drug translocation pathways in the transmembrane domains of P-gp be found? P-gp was photolabeled with propafenone analogs, purified, and digested proteolytically, and peptide fragments were identified by high-resolution mass spectrometry. Labeling was assigned to two regions in the protein by projecting data into homology models. Subsequently, symmetric residue pairs in the putative translocation pathways were identified and replaced by site-directed mutagenesis. Transport assays corroborated the existence of two pseudosymmetric translocation pathways. Although rhodamine123 has a preference to take one path, verapamil, propafenones, and vinblastine preferentially use the other. Two major findings ensued from this study: the existence of two solute translocation pathways in P-gp as a reflection of evolutionary origin from a homodimeric ancestor and selective but not exclusive use of one of these pathways by different P-gp solutes. The pseudosymmetric behavior reconciles earlier kinetic and thermodynamic data, suggesting an alternative concept of drug transport by P-gp that will aid in understanding the off-target quantitative structure activity relationships of P-gp interacting drugs.
Impacto de la obesidad en la frecuencia de complicaciones relacionadas con la sedación dirigida por endoscopistas
Authors: A Flores Cucho, L Achecar Justo, M Del Río Izquierdo, I Blázquez Gómez, J Pérez Lasala, M Pichiule Castañeda, M Van Domselaar
Journal: Endoscopy (2017)

El propofol administrado por no anestesistas es un método seguro y eficaz de sedación en endoscopia digestiva. Existen datos limitados sobre el efecto de la obesidad en la aparición de efectos adversos en este grupo de pacientes.