tbuckley/cabot-search huggingface dataset:
Interferon regulatory factor 1–Rab27a regulated extracellular vesicles promote liver ischemia/reperfusion injury
Authors: Mu‐qing Yang, Qiang Du, Julie Goswami, Patrick R. Varley, Bin Chen, Rong‐hua Wang, Adrian E. Morelli, Donna B. Stolz, Timothy R. Billiar, Jiyu Li, David A. Geller
Journal: Hepatology (2017)

The role and regulators of extracellular vesicle (EV) secretion in hepatic ischemia/reperfusion (IR) injury have not been defined. Rab27a is a guanosine triphosphatase known to control EV release. Interferon regulatory factor 1 (IRF‐1) is a transcription factor that plays an important role in liver IR and regulates certain guanosine triphosphatases. However, the relationships among IRF‐1, Rab27a, and EV secretion are largely unknown. Here, we show induction of IRF‐1 and Rab27a both in vitro in hypoxic hepatocytes and in vivo in warm IR and orthotopic liver transplantation livers. Interferon γ stimulation, IRF‐1 transduction, or IR promoted Rab27a expression and EV secretion. Meanwhile, silencing of IRF‐1 decreased Rab27a expression and EV secretion. Rab27a silencing decreased EV secretion and liver IR injury. Ten putative IRF‐1 binding motifs in the 1,692‐bp Rab27a promoter region were identified. Chromatin immunoprecipitation and electrophoretic mobility shift assay verified five functional IRF‐1 binding motifs, which were confirmed by a Rab27a promoter luciferase assay. IR‐induced EVs contained higher oxidized phospholipids (OxPL). OxPLs on the EV surface activated neutrophils through the toll‐like receptor 4 pathway. OxPL‐neutralizing E06 antibody blocked the effect of EVs and decreased liver IR injury. Conclusion: These findings provide a novel mechanism by which IRF‐1 regulates Rab27a transcription and EV secretion, leading to OxPL activation of neutrophils and subsequent hepatic IR injury. (H epatology 2018;67:1056–1070)
Moving Toward a Clinically and Fiscally Sound Aeromedical Triage System for Trauma
Authors: Heena P. Santry, Stacy B. Sanders
Journal: JAMA Surgery (2017)

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 Surgery HomeNew OnlineCurrent IssueFor Authors Podcast 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) 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 Surgery journal
Abstract 18631: Delayed Recognition of Cardiac Arrest in Emergency Medical Dispatch - Best Source of Key Information for System Improvement?
Authors: Camilla Hardeland, Linda Soilammi, Andreas E Hansen, Theresa M Olasveengen
Journal: Circulation (2014)

Background: Measuring emergency medical dispatch performance is important for both quality control and clinical outcome. Recognition of cardiac arrest is one of the key metrics when evaluating performance as it is essential for initiation of bystander CPR. It is commonly reported as either recognized or not recognized without any benchmarked definition or time limit. Little is known about the extent of delayed recognition, and if these initial delays lead to clinically relevant delays in CPR. Methods: Prospective, observational study of cardiac arrest calls during a 1 year period in Oslo and Akershus Emergency Services. Dispatch logs, ambulance records and audio files were analyzed. Recognition of cardiac arrest was reported as (1) recognized, (2) not recognized and (3) delayed recognition. Delayed recognition was defined as failure to initially clarify consciousness or abnormal breathing before moving on to further questioning regarding other symptoms or patient history. Calls across all three groups were purposefully selected, and respective dispatchers invited for interviews based on the calls they had experienced. Results: 500 cardiac arrest calls were processed of which 289 calls were included for further analysis as the dispatcher had the opportunity to recognize cardiac arrest and initiate CPR instructions. 74% of cases were recognized, 13% were not recognized and in 13% recognition was delayed. Median time to bystander CPR (first compression performed) was 2,6 (range 0.9,12.3) minutes when cardiac arrest was recognized and 5,1 (range 2.9,9.7) minutes when recognition was delayed. Interviews after calls where cardiac arrest was not recognized or delayed in recognition yielded insight into challenging areas for the dispatchers such as agonal breathing, handling health care workers as callers and non-compliance with protocol that have impacted future training and education. Conclusion: Delayed dispatch recognition of cardiac arrest is common and leads to significant delays in chest compressions. Emergency medical dispatch systems committed to improving cardiac arrest outcomes need to identify and explore all calls that challenge the system, not only those where cardiac arrest is not recognized.
The Lancet Countdown on health and climate change: from 25 years of inaction to a global transformation for public health
Authors: Nick Watts, Markus Amann, Sonja Ayeb-Karlsson, Kristine Belesova, Timothy Bouley, Maxwell Boykoff, Peter Byass, Wenjia Cai, Diarmid Campbell-Lendrum, Jonathan Chambers, Peter M Cox, Meaghan Daly, Niheer Dasandi, Michael Davies, Michael Depledge, Anneliese Depoux, Paula Dominguez-Salas, Paul Drummond, Paul Ekins, Antoine Flahault, Howard Frumkin, Lucien Georgeson, Mostafa Ghanei, Delia Grace, Hilary Graham, Rébecca Grojsman, Andy Haines, Ian Hamilton, Stella Hartinger, Anne Johnson, Ilan Kelman, Gregor Kiesewetter, Dominic Kniveton, Lu Liang, Melissa Lott, Robert Lowe, Georgina Mace, Maquins Odhiambo Sewe, Mark Maslin, Slava Mikhaylov, James Milner, Ali Mohammad Latifi, Maziar Moradi-Lakeh, Karyn Morrissey, Kris Murray, Tara Neville, Maria Nilsson, Tadj Oreszczyn, Fereidoon Owfi, David Pencheon, Steve Pye, Mahnaz Rabbaniha, Elizabeth Robinson, Joacim Rocklöv, Stefanie Schütte, Joy Shumake-Guillemot, Rebecca Steinbach, Meisam Tabatabaei, Nicola Wheeler, Paul Wilkinson, Peng Gong, Hugh Montgomery, Anthony Costello
Journal: The Lancet (2017)
TCT-84 Procedural Strategy and Clinical Outcomes in Patients Undergoing PCI for Left Main Trifurcation Disease: The EXCEL trial
Authors: David Kandzari, Anthony Gershlick, Patrick Serruys, Martin Leon, Marie-Claude Morice, Nicholas Lembo, Adrian Banning, Samer Mansour, Manel Sabate, Joseph Sabik, A. Pieter Kappetein, Ovidiu Dressler, Gregg Stone
Journal: Journal of the American College of Cardiology (2017)
International Expert Consensus on Switching Platelet P2Y <sub>12</sub> Receptor–Inhibiting Therapies
Authors: Dominick J. Angiolillo, Fabiana Rollini, Robert F. Storey, Deepak L. Bhatt, Stefan James, David J. Schneider, Dirk Sibbing, Derek Y.F. So, Dietmar Trenk, Dimitrios Alexopoulos, Paul A. Gurbel, Willibald Hochholzer, Leonardo De Luca, Laurent Bonello, Daniel Aradi, Thomas Cuisset, Udaya S. Tantry, Tracy Y. Wang, Marco Valgimigli, Ron Waksman, Roxana Mehran, Gilles Montalescot, Francesco Franchi, Matthew J. Price
Journal: Circulation (2017)

Dual antiplatelet therapy with aspirin and a P2Y 12 inhibitor is the treatment of choice for the prevention of atherothrombotic events in patients with acute coronary syndromes and for those undergoing percutaneous coronary interventions. The availability of different oral P2Y 12 inhibitors (clopidogrel, prasugrel, ticagrelor) has enabled physicians to contemplate switching among therapies because of specific clinical scenarios. The recent introduction of an intravenous P2Y 12 inhibitor (cangrelor) further adds to the multitude of modalities and settings in which switching therapies may occur. In clinical practice, it is not uncommon to switch P2Y 12 inhibitor, and switching may be attributed to a variety of factors. However, concerns about the safety of switching between these agents have emerged. Practice guidelines have not fully elaborated on how to switch therapies, leaving clinicians with limited guidance on when and how to switch therapies when needed. This prompted the development of this expert consensus document by key leaders from North America and Europe with expertise in basic, translational, and clinical sciences in the field of antiplatelet therapy. This expert consensus provides an overview of the pharmacology of P2Y 12 inhibitors, different modalities and definitions of switching, and available literature and recommendations for switching between P2Y 12 inhibitors.
TCT-733 Association Between Hypertension, Platelet Reactivity, and the Risk of Adverse Events After PCI: Analysis from the ADAPT-DES study
Authors: Bjorn Redfors, Xin Huang, Bernhard Witzenbichler, Shmuel Chen, Yangbo Liu, Bruce Brodie, Michael Rinaldi, Timothy Henry, David Cox, Peter L. Duffy, Ernest Mazzaferri, Roxana Mehran, Ajay Jayant Kirtane, Ori Ben-Yehuda, Gregg Stone
Journal: Journal of the American College of Cardiology (2017)
Role of ERBB signaling in RET-rearranged lung cancer and contribution of EGFR amplification to cabozantinib resistance.
Authors: Roger Smith, Alexander E. Drilon, Siddharth Kunte, Ken Suzawa, Takuo Hayashi, Lukas Delasos, Huichun Tai, Tyler Hitchman, Inna Khodos, Marissa Mattar, Shinji Kohsaka, Elisa de Stanchina, William Lockwood, Marc Ladanyi, Romel Somwar
Journal: Journal of Clinical Oncology (2017)

11583 Background: Lung cancers driven by oncogenic RET fusions have lower response rates to targeted monotherapy such as cabozantinib (28%) relative to response rates typically observed in ALK- or ROS1- rearranged lung adenocarcinomas (60-80%). Methods: To identify targetable co-dependencies or cooperating pathways for RET fusion-positive lung cancers, we performed high-throughput chemical and genetic screens to find FDA-approved drugs or genes that when inhibited, would synergize with cabozantinib in RET fusion-positive lung cancer cell lines. In addition we performed NGS of a pair of pre-treatment and post-cabozantinib progression samples. Results: We identified EGFR siRNAs and anti-EGFR drugs as synergistic with cabozantinib. Combinations of drugs that target EGFR (cetuximab, afatinib, erlotinib, gefitinib, neratinib) and RET (cabozantinib, CEP-32496, lenvatinib, vandetanib) were more effective at reducing growth of RET cell lines than any single agent in vitro and in xenograft models. Cabozantinib treatment of RET fusion-positive cell lines inhibited EGFR and RET phosphorylation, an observation not seen in RET wild-type cell lines. Co-immunoprecipitation studies reveal that RET and EGFR interact. Ectopic expression of CCDC6-RET in NIH-3T3 or human bronchial epithelial cells resulted in upregulation of multiple ERBB receptors and ligands (not seen in a ROS1 fusion-positive cell line) and a concomitant increase in EGFR stability. Treatment with ERBB pathway ligands or overexpression of EGFR decreased sensitivity to cabozantinib in two RET fusion-positive cell lines. Finally, sequencing of a pair of pre-treatment and post-progression samples from a lung cancer patient treated with cabozantinib revealed acquired amplification of EGFR in the latter sample. Conclusions: Taken together, these results suggest that the tumorigenic potential of RET fusion oncogenes is dependent on deregulation of ERBB-activated pathways and that a combination of RET and EGFR drugs could be more effective in treating RET fusion-positive tumors. Moreover, amplification of EGFR is a potential driver of resistance to cabozantinib in RET-rearranged lung cancers.
Patterns in provider types and cost of surveillance testing in early-stage breast cancer patients: A regional study.
Authors: Gary H. Lyman, Catherine R. Fedorenko, Julia Rose Walker, Laura Elizabeth Panattoni, Stuart Greenlee, Karma L. Kreizenbeck, Mikael Anne Greenwood-Hickman, Sarah Barger, Sibel Blau, Richard A. McGee, Ted Conklin, Bruce Smith, Scott David Ramsey
Journal: Journal of Clinical Oncology (2017)

6582 Background: Although ASCO Choosing Wisely guidelines recommend against routine surveillance testing or imaging for asymptomatic individuals with early-stage breast cancer (ESBC) treated with curative intent, they are frequently performed. Physician specialty and costs associated with surveillance testing and imaging were examined in ESBC patients. Methods: Cancer registry patient records in Western Washington from 2007 to 2015 were linked with claims from two regional commercial insurers. Selected patients had been diagnosed with stage I/II breast cancer and treated with mastectomy or lumpectomy + radiation. Surveillance was considered from the first 4 month gap in treatment (surgery, chemo, radiation) through 13 months or restart of treatment. Evaluation and Management (E&amp;M) and procedure codes for tumor marker (CEA, CA 15-3, CA 27.29) and advanced imaging (PET, CT, bone scan) were identified. Specialty codes were used to determine provider type. Physician visits were matched to tests using E&amp;M codes in the +/- 7 days around each test. Cost included total reimbursed amount from insurers during the surveillance period. Results: During surveillance, 2,193 patients averaged 13.3 physician visits [median: 11, IQR: 8-17]. Oncologists (91%) and PCPs (83%) were the most common specialties with an average of 3.7 visits each. Overall, 37% of patients received tumor marker tests (avg = 2.8 tests/patient) and 17% received advanced imaging (avg = 1.5 images/patient). The mean total cost during the surveillance period was $18,403 (SD $26,640). Costs were higher for those patients who received tumor marker testing or advanced imaging. Conclusions: Patients frequently see oncologists and PCPs during early surveillance. Targeting oncologists to improve appropriate tumor marker testing could have the largest impact on aligning practice with Choosing Wisely recommendations and potentially reducing the financial burden on patients. [Table: see text]
TCT-608 Contemporary Use and Outcomes Associated with Rotational versus Orbital Atherectomy in Percutaneous Coronary Interventions: Insights from the Blue Cross Blue Shield of Michigan Cardiovascular Consortium (BMC2).
Authors: Emily Perdoncin, Milan Seth, Theodore Schreiber, Akshay Khandelwal, Simon Dixon, Hitinder Gurm
Journal: Journal of the American College of Cardiology (2017)
Amplia diseminación de MRSA epidémico en los hospitales alemanes
Authors: W Witte, C Cuny, C Braulke, D Heuck, I Klare
Journal: Eurosurveillance (1997)

Las cepas de Staphylococcus aureus resistentes a multiples antibioticos, incluyendo las resistentes a la meticilina (MRSA), representan un problema de suma importancia para el control de las infecciones contraidas en el hospital. Algunas de estas cepas tienen la capacidad de propagarse despues de haber sido introducidas en el hospital. Se ha demostrado que varias cepas de MRSA epidemico (EMRSA) identificadas por fenotipo se han propagado de una region a otra en los hospitales britanicos (1). Los estudios realizados en varios centros por la Paul Ehrlich Society for Chemotherapy mostraron que la frecuencia de MRSA entre las infecciones a S. aureus contraidas en los hospitales alemanes habia pasado de un 1,7% a un 8,7% entre 1990 y 1995 (2,3).
Vigilância de doenças sexualmente transmissíveis, por redes de laboratórios, em França
Authors: V Goulet, P Sednaoui
Journal: Eurosurveillance (1998)

A maior parte das doencas sexualmente transmissiveis (DST) sao diagnosticadas, em Franca, por medicos do sector privado (clinicos gerais, ginecologistas, dermatovenereologistas e urologistas) ainda que existam, em todo o territorio, dispensarios antivenereos (DAV) que tem a seu cargo o tratamento gratuito de certas DSTs (gonorreia e sifilis). A reorganizacao, em 1985, do sistema de doencas de declaracao obrigatoria, limitou a lista de doencas a declarar nao incluindo as DSTs. Estas deixaram de ser notificadas pelos medicos do sector privado e, desde 1995, as DSTs diagnosticadas nos DAV deixaram de ser recolhidas pelos servicos estatisticos do Ministerio da Saude.
Abstract 18266: Overactive Tgfβ Signaling in Smooth Muscle Cells Induces Hypertension in Mice Through Increased Myogenic Tone and is Responsible for Increased Myogenic Tone in Resistance Vessels of Hypertensive Patients
Authors: Daniela Carnevale, Manuel Casaburo, Dario Bizzotto, Daniela Cugino, Giulio Selvetella, Gualtiero Innocenzi, Giorgio Bressan, Giuseppe Lembo
Journal: Circulation (2015)

Emilin1 (E1) is a protein of the extracellular matrix that regulates TGFβ activity through proteolysis of the proTGFβ. E1 KO mice are hypertensive, with increased TGFβ activation. As E1 is expressed in blood vessels starting from embryonic life to adulthood, is still unknown whether the E1 KO phenotype results from a developmental defect or lack of a homeostatic role exerted in the adult. To dissect this issue, we inactivated E1 in smooth muscle cells (VSMCs) of adult mice, by the use of floxed E1 and CreERT2 [a tamoxifen (TAM) inducible Cre recombinase] under the control of the smooth muscle myosin heavy chain (Smmhc) promoter. When Smmhc-CreERT2 E1fl/fl mice were given TAM, blood pressure significantly increased (124±1 vs basal condition 106±1 mmHg) as well as myogenic response in resistance arteries (16.3±0.7 vs basal condition 11.4±0.1 % at 125 mmHg). In order to evaluate the relevance of our findings in the human pathology, we enrolled 20 hypertensive and 20 normotensive patients that underwent neurosurgical intervention for primary lumbar hernia repair and dissected out resistance vessels from skeletal muscle biopsies. We analyzed the myogenic tone of human peripheral resistance vessels in a pressure myograph and randomized vessels to receive vehicle, a neutralizing antibody anti-TGFβ or a preimmune non relevant IgG. As first, we found that hypertensive patients had significantly increased myogenic tone as compared to normotensive (16.6±2.1% vs 10.5±0.4% at 125 mmHg). Moreover, the pretreatment of vessels with anti-TGFβ antibody normalized the myogenic tone of hypertensive patients (10.8±0.6%) to the levels of normotensives (11.8±1.3%). A pretreatment with the non relevant IgG did not modify the myogenic tone of hypertensives (17±0.6%), thus demonstrating that the effect was dependent of an increased TGFβ signaling in vessels of hypertensive patients. Overall, our results suggest that the TGFβ pathway in VSMC, is crucial for the myogenic tone of resistance arteries and is linked to the regulation of blood pressure. The data obtained in peripheral resistance vessels from hypertensive patients, that display an increased myogenic tone dependent on overactive TGFβ signaling, highlight the translational potential of our findings to the human pathology.
Evaluación de la clasificación de los casos de encefalitis transmitida por garrapatas en Polonia
Authors: P Stefanoff, M Eidson, D L Morse, A Zielinski
Journal: Eurosurveillance (2005)

La encefalitis transmitida por garrapatas en Europa central es una enfermedad virica del sistema nervioso central. Aunque existe un Sistema de vigilancia de esta encefalitis en Polonia desde 1970, no hay una definicion de caso estandarizada y las pruebas de diagnostico utilizadas son diferentes dependiendo de las regiones. El objetivo de este estudio es hacer una sintesis de cuatro anos de vigilancia utilizando definiciones de caso estandarizadas. De 1999 a 2002, fueron declarados al sistema nacional de vigilancia 607 casos: 386 (63,6%) eran hombres, 331 (54,5%) vivian en areas rurales y 186 (30,6%) tenian entre 30 y 50 anos. De los 606 casos diagnosticados, 453 (74,7%) tenian una meningitis aseptica, 109 (18,0%) una meningo-encefalitis y 44 (7,3%) una meningo-encefalomielitis. De los 607 casos notificados, 602 (99,2%) se pudieron clasificar como casos confirmados (n=153, 25,4%), probables (343, 57,0%) y posibles (106,17,6%). Se observaron diferencias significativas por sexo: el 28,6% de los casos en hombres fueron confirmados, frente al 19,7% de los casos en mujeres (?2= 10,48 ; p=0,0053). Tambien se observaron diferencias significativas en la clasificacion de los casos por diagnostico clinico : el 32,4% de los casos con meningoencefalitis fueron clasificados como casos confirmados, comparado con el 24,7% de los casos de meningitis aseptica (?2=11,79 ; p=0,019). Tambien se notaron diferencias significativas en la distribucion por grupo de definicion de caso segun regiones geograficas. Una vigilancia apropiada de la encefalitis transmitida por garrapatas necesita una definicion de caso uniforme y valida en toda Europa. Solamente un 25% de los casos declarados responden a la definicion de casos confirmados, lo que requiere un mejor seguimiento y una estandarizacion de las pruebas para los casos sospechosos.
TCT-227 Prognostic impact of obesity on transcatheter valve implantation for severe aortic valve stenosis
Authors: Florian Deuschl, Lisa Voigtländer, Niklas Schofer, Nicole Rübsamen, Daniel Kalbacher, Moritz Seiffert, Yvonne Schneeberger, Johannes Schirmer, Hermann Reichenspurner, Stephan Blankenberg, Lenard Conradi, Ulrich Schäfer
Journal: Journal of the American College of Cardiology (2017)
Abstract 11908: Osteoprotegerin and Myocardial Fibrosis in Patients With Aortic Stenosis
Authors: Vassilis Vassiliou, Claire E Raphael, Tamir Malley, Nikhil Aggarwal, Subothini Selvendran, Helen Berry, Jackie Donovan, Eva Nyktari, Dominique Auger, Dudley J Pennell, Sanjay K Prasad
Journal: Circulation (2015)

Introduction: Understanding the mechanistic role of valve calcification and myocardial fibrosis in patients with aortic stenosis (AS) remains challenging. Osteoprotegerin (OPG), a member of the TNF receptor family, is known to mediate valve calcification in AS; however its role on myocardial fibrosis has not been evaluated. Hypothesis: We hypothesized that OPG stimulates common pathways for valve calcification and myocardial fibrosis and investigated the association of OPG and presence of myocardial fibrosis. Methods: Between 2011 and 2015, consecutive consenting patients with moderate (1.0-1.5cm2) or severe (&lt;1cm2) AS who had cardiovascular magnetic resonance (CMR) with late gadolinium enhancement were included. CMR parameters were analysed by blinded observers and patients characterized into 3 groups according to the pattern of fibrosis: presence of midwall fibrosis, presence of chronic infarction or absence of fibrosis. OPG levels were measured using ELISA and compared between the 3 groups. Results: 113 patients (76±10 years, 78 male) were included. 37 patients had no fibrosis, 40 patients had midwall fibrosis and 34 had chronic infarction. Max OPG level was 23.01 pmol/, min 2.22 pmol/L and mean 7.24± 3.45pmol/L. OPG per group was: no fibrosis= 6.29 pmol/L, midwall fibrosis=7.13 pmol/L and chronic infarction=8.42 pmol/L. There was no association between OPG level and presence of midwall fibrosis compared to no fibrosis (p=0.114). However, patients with chronic myocardial infarction had higher OPG than patients with no fibrosis (p=0.007). Conclusions: OPG is known to promote valve calcification in patients with AS. This is the first study to demonstrate that there is no association between the level of OPG and presence of myocardial midwall fibrosis. However higher OPG was observed in patients with chronic ischemia when compared to patients with no fibrosis.