tbuckley/cabot-search huggingface dataset:
Outcomes of Thrombectomy in Transferred Patients With Ischemic Stroke in the Late Window
Authors: Amrou Sarraj, Michael Mlynash, Sean I. Savitz, Jeremy J. Heit, Maarten G. Lansberg, Michael P. Marks, Gregory W. Albers
Journal: JAMA Neurology (2019)

Although thrombectomy benefit was maintained in transfer patients with ischemic stroke in early-window trials, overall functional independence rates were lower in thrombectomy and medical management-only groups.To evaluate whether the imaging-based selection criteria used in the Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke 3 (DEFUSE 3) trial would lead to comparable outcome rates and treatment benefits in transfer vs direct-admission patients.Subgroup analysis of DEFUSE 3, a prospective, randomized, multicenter, blinded-end point trial. Patients were enrolled between May 2016 and May 2017 and were followed up for 90 days. The trial comprised 38 stroke centers in the United States and 182 patients with stroke with a large-vessel anterior circulation occlusion and initial infarct volume of less than 70 mL, mismatch ratio of at least 1.8, and mismatch volume of at least 15 mL, treated within 6 to 16 hours from last known well. Patients were stratified based on whether they presented directly to the study site or were transferred from a primary center. Data were analyzed between July 2018 and October 2018.Endovascular thrombectomy plus standard medical therapy vs standard medical therapy alone.The primary outcome was the distribution of 90-day modified Rankin Scale scores.Of the 296 patients who consented, 182 patients were randomized (66% were transfer patients and 34% directly presented to a study site). Median age was 71 years (interquartile range [IQR], 60-79 years) vs 70 years (IQR, 59-80 years); 69 transfer patients were women (57%) and 23 of the direct group were women (37%). Transfer patients had longer median times from last known well to study site arrival (9.43 vs 9 hours) and more favorable collateral profiles (based on hypoperfusion intensity ratio): median for transfer, 0.35 (IQR, 0.18-0.47) vs 0.42 (IQR, 0.25-0.56) for direct (P = .05). The primary outcome (90-day modified Rankin Scale score shift) did not differ in the direct vs transfer groups (direct OR, 2.9; 95% CI, 1.2-7.2; P = .01; transfer OR, 2.6; 95% CI, 1.3-4.8; P = .009). The overall functional independence rate (90-day modified Rankin Scale score 0-2) in the thrombectomy group did not differ (direct 44% vs transfer 45%) nor did the treatment effect (direct OR, 2.0; 95% CI, 0.9-4.4 vs transfer OR, 3.1; 95% CI, 1.6-6.1). Thrombectomy reperfusion rates, mortality, and symptomatic intracranial hemorrhage rates did not differ.In late-window patients selected by penumbral mismatch criteria, both the favorable outcome rate and treatment effect did not decline in transfer patients. These results have health care implications indicating transferring potential candidates for late-window thrombectomy is associated with substantial clinical benefits and should be encouraged.ClinicalTrials.gov identifier: NCT02586415.
Abstract IA25: Functional proteomics and site-specific genomic rearrangements of pediatric cancers
Authors: Alex Kentsis
Journal: Cancer Research (2018)

Abstract Despite intense efforts, the cure rates of childhood leukemias and solid tumors are not satisfactory. Resistance to intensive chemotherapy is common, and targets for molecular therapies are largely undefined. In this presentation, I will describe my laboratory’s recent efforts to apply functional proteomic and genomic technologies to identify causal mechanisms of childhood cancer pathogenesis and therapy resistance. I will present functional proteomic studies of pediatric acute myeloid leukemias, identifying kinase-dependent dysregulation of transcription factor control as a determinant of therapy response in AML. I will also present studies of site-specific genomic rearrangements in childhood solid tumors, identifying the PGBD5 DNA transposase as their oncogenic mutator. Lastly, I will present synthetic lethal approaches to leverage functional dependencies of transcription factor control and PGBD5-dependent DNA damage signaling to induce specific antitumor effects while sparing normal cells, including therapeutic strategies suitable for immediate translation to clinical trials. Citation Format: Alex Kentsis. Functional proteomics and site-specific genomic rearrangements of pediatric cancers [abstract]. In: Proceedings of the AACR Special Conference: Pediatric Cancer Research: From Basic Science to the Clinic; 2017 Dec 3-6; Atlanta, Georgia. Philadelphia (PA): AACR; Cancer Res 2018;78(19 Suppl):Abstract nr IA25.
Awareness of Heart Attack Symptoms and Response Among Adults — United States, 2008, 2014, and 2017
Authors: Jing Fang, Cecily Luncheon, Carma Ayala, Erika Odom, Fleetwood Loustalot
Journal: MMWR Morbidity and Mortality Weekly Report (2019)

Heart disease is the leading cause of death in the United States (1). Heart attacks (also known as myocardial infarctions) occur when a portion of the heart muscle does not receive adequate blood flow, and they are major contributors to heart disease, with an estimated 750,000 occurring annually (2). Early intervention is critical for preventing mortality in the event of a heart attack (3). Identification of heart attack signs and symptoms by victims or bystanders, and taking immediate action by calling emergency services (9-1-1), are crucial to ensure timely receipt of emergency care and thereby improve the chance for survival (4). A recent report using National Health Interview Survey (NHIS) data from 2014 found that 47.2% of U.S. adults could state all five common heart attack symptoms (jaw, neck, or back discomfort; weakness or lightheadedness; chest discomfort; arm or shoulder discomfort; and shortness of breath) and knew to call 9-1-1 if someone had a heart attack (5). To assess changes in awareness and response to an apparent heart attack, CDC analyzed data from NHIS to report awareness of heart attack symptoms and calling 9-1-1 among U.S. adults in 2008, 2014, and 2017. The adjusted percentage of persons who knew all five common heart attack symptoms increased from 39.6% in 2008 to 50.0% in 2014 and to 50.2% in 2017. The adjusted percentage of adults who knew to call 9-1-1 if someone was having a heart attack increased from 91.8% in 2008 to 93.4% in 2014 and to 94.9% in 2017. Persistent disparities in awareness of heart attack symptoms were observed by demographic characteristics and cardiovascular risk group. Public health awareness initiatives and systematic integration of appropriate awareness and action in response to a perceived heart attack should be expanded across the health system continuum of care.
Abstract 12233: UPR Effectors PERK and IRE1 Can Contribute to Electrical Remodeling in hiPSC-CMs
Authors: Man Liu, Guangbin Shi, Anyu Zhou, Frederick Williams, Samuel C Dudley
Journal: Circulation (2017)

Background: Heart failure (HF) is associated with endoplasmic reticulum stress and activation of the unfolded protein response (UPR). UPR inhibits protein translation. Ion channel downregulation is associated with arrhythmic risk. We have reported that the PERK branch of the UPR contributes to electrical remodeling in human HF by downregulating Nav1.5 and Kv4.3. Objective: The UPR has been found to be activated in ischemia/reperfusion, hypertrophy, and HF. In this study, we investigated whether the UPR regulates cardiac ion channels in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). Methods: hiPSC-CMs were utilized for channel currents and action potential (AP) measurements with patch clamp recording. Tunicamycin (TM, 5 μg/ml) was used to activate the UPR. GSK2606414 (GSK, 300 nM) and 4μ8C (5 μM) was used to inhibit PERK and IRE1, respectively. All treatment was 24 h at 37 °C in 95%CO2/5%O2 incubator. Results: TM induction of UPR activation was confirmed by elevated protein levels ...
Does Hypogammaglobulinemia at Diagosis Effects Survival and Infection Risk in Chronic Lymphocytic Leukemia (CLL)?
Authors: Erden Atilla, Pinar Ataca Atilla, Sinem Civriz Bozdag, Selami Kocak Toprak, Pervin Topcuoglu, Osman Ilhan, Muhit Ozcan, Onder Arslan
Journal: Blood (2016)
Association of a positive direct antiglobulin test with chronic immune thrombocytopenia and use of second line therapies in children: A multi‐institutional review
Authors: Taylor Olmsted Kim, Amanda B. Grimes, Susan Kirk, Abinaya Arulselvan, Michele P. Lambert, Rachael F. Grace, Jenny M. Despotovic
Journal: American Journal of Hematology (2019)

Immune thrombocytopenia (ITP) is the most common autoimmune cytopenia in children. Approximately, 25% of patients develop chronic disease, which may be unpredictable and challenging to treat. It is not currently possible to predict at the time of presentation which patients will have chronic disease or will experience symptoms requiring second‐line therapy defined as treatment beyond corticosteroids, intravenous immunoglobulin, or Rh immune globulin. A multi‐institutional retrospective review of 311 pediatric patients with ITP was performed with the goal of identifying clinical characteristics associated with disease course. In a cohort of 216 patients tested and for whom disease status was known, a positive direct antiglobulin test (DAT) was associated with chronic ITP vs spontaneous resolution of disease (29.2% vs 8.1%, P &lt; 0.001) as well as the need for treatment with second line agents (38.5% vs 11.4%, P &lt; 0.001) in 241 patients. Controlling for the effect of Evans syndrome, defined as having two immune cytopenias, a positive DAT was independently associated with chronic ITP (OR = 2.7, 95% CI: 1.0‐7.2, P = 0.041) and use of second‐line agents (OR: 3.6, 95% CI: 1.7‐7.7, P = 0.001) by multivariate logistic regression model. These findings demonstrate an association with positive DAT and chronic disease, as well as refractory disease requiring second‐line agents.
Abstract 16773: The Influence of Lifestyle Exercise on the Cardiovascular Health of HIV+ Adults
Authors: Allison R Webel, Joseph Perazzo, Trevor Jenkins, Chris T Longenecker, Abdus Sattar, Margaret Rodriguez, Nate Schreiner, Richard A Josephson
Journal: Circulation (2017)

Introduction: Lifestyle exercise (i.e. moderate exercise during routine daily activities most days of the week) may benefit HIV+ adults who are at high risk for cardiovascular disease. Hypothesis: ...
Omadacycline — The Newest Tetracycline
Authors: Henry F. Chambers
Journal: New England Journal of Medicine (2019)

Omadacycline was the second antibiotic of the tetracycline class to be approved by the Food and Drug Administration (FDA) in 2018. Results of two phase 3, double-blind, randomized clinical trials of the drug, one involving acute bacterial skin and skin-structure infections and the other community-acquired bacterial pneumonia, are now reported in the Journal.1,2 Each trial was designed and executed according to FDA guidance.3,4 The primary efficacy end point in each was early clinical response, at 48 to 72 hours for acute bacterial skin and skin-structure infections and at 72 to 120 hours for community-acquired bacterial pneumonia, in an intention-to-treat population. . . .
Mgta-456 Contains Large Numbers of Expanded Cord Blood (CB) CD34+CD90+ Hematopoietic Stem Cells (HSC) Which Confer All Engraftment Activity and Correlate with Accelerated Neutrophil Recovery after Myeloablative Conditioning in Patients with Hematologic Malignancy
Authors: Anthony E. Boitano, Michael P. Cooke, Kevin A. Goncalves, Darin Sumstad, John E. Wagner
Journal: Blood (2018)
Abstract 18302: Left Ventricular Structure by Echocardiography is Associated With Vasopressor Requirements and Severity of Organ Failure After Cardiac Arrest
Authors: Meshe Chonde, Jacob C Jentzer, Hussein Abu-Daya, Asher Shafton, Didier Chalhoub, Andrew Althouse, Jon Rittenberger
Journal: Circulation (2015)

Introduction: Patients resuscitated from cardiac arrest (CA) often require vasopressors for hemodynamic support and frequently have cardiac dysfunction identified on transthoracic echocardiography (TTE). The association between TTE parameters and vasopressor requirements is not well-described. Hypothesis: Echocardiographic findings early after resuscitation from CA will predict vasopressor requirements. Methods: Prospective registry of patients resuscitated from CA underwent TTE within 24 hours after CA. We determined 2D measurements, LVEF, spectral Doppler of mitral inflow (E) and LV outflow and systolic and early diastolic (e’) tissue Doppler of the mitral annulus. Using Pearson correlation coefficients, we examined the association between TTE parameters and number of vasopressor drugs, cumulative vasopressor index (CVI) and Sequential Organ Failure Assessment (SOFA) score. Mean values of TTE parameters were compared in patients with high and low cardiovascular SOFA subscores using t-tests. Results: Among the 55 patients, LV end-diastolic diameter (LVEDD, r = -0.498 to -0.569, p = 0.0001 to 0.0003), LV end-systolic diameter (LVESD, r = -0.392 to -0.463, p = 0.0008 to 0.0053) and LV relative wall thickness (RWT, r = 0.452 to 0.503, p = 0.0002 to 0.0011) correlated significantly with admission and peak 24 hour number of vasopressor drugs and CVI. LVEDD (r = -0.324, p = 0.0229), LVESD (r = -0.290, p = 0.0431), RWT (0.429, p = 0.0021) and septal e’ velocity (r = -0.344, p = 0.037) correlated with admission SOFA score. Other TTE parameters including LVEF did not correlate with vasopressor requirements or SOFA score. Patients with cardiovascular SOFA subscore = 4 had lower LVEDD (4.16cm vs. 5.0cm, p = 0.0008), lower LVESD (3.07cm vs. 4.03cm, p = 0.0008), higher RWT (0.48 vs. 0.65, p = 0.0026) and lower E/e’ ratio (10.84 vs. 18.91, p = 0.0169) compared with patients with cardiovascular SOFA subscore &lt; 4. Conclusions: A smaller, thicker LV cavity by echocardiography at 24 hours after CA is associated with higher vasopressor requirements and more severe organ failure. Patients who required more vasopressor support had smaller, thicker LV cavities and a lower E/e’ ratio. LV systolic dysfunction was not a significant predictor of vasopressor requirements.
Dynamical changes of treatment patterns and outcomes of unresectable pancreatic cancer patients in real-life practice.
Authors: Kazuki Nagai, Takeshi Terashima, Tatsuya Yamashita, Hidenori Kido, Kotaro Hayashi, Hajime Sunagozaka, Ryotaro Nakai, Hideki Mizuno, Hikaru Hayakawa, Yoshimoto Nomura, Yoshiko Takata, Noriaki Orita, Hisashi Takabatake, Masataka Kanno, Masaki Nishitani, Hitoshi Omura, Haruhiko Shugo, Naoki Ooishi, Eishiro Mizukoshi, Shuichi Kaneko
Journal: Journal of Clinical Oncology (2019)

407 Background: Several new combination therapies, including GEM plus nab-paclitaxel (GnP) and FOLFIRINOX (FFX) has been developed for treating pancreatic ductal adenocarcinoma (PDAC) in these ten years. We investigated trends in characteristics, treatment patterns, and outcomes of unselected patients with unresectable PDAC in real-life practice in Japan. Methods: We retrospectively reviewed the medical records of 1917 patients diagnosed as having unresectable or recurrent PDAC in multiple centers in our local area between January 2009 and April 2018. Results: The median age was 74, and 53.1% were men; 27.2% had locally advanced and 67.2% metastatic disease, and 5.6% had recurrences. Oncological therapy was administered to 1295 patients (67.6%): chemotherapy (n = 1161), chemo-radiotherapy (n = 117), or radiotherapy (n = 17); the remaining patients were treated with best supportive care. Of 100 patients diagnosed in 2009, 62.0% received GEM as first-line chemotherapy; whereas 56.8% of the 266 patients diagnosed in 2017 or 2018 received GnP, 20.3% GEM, and 15.4% FFX. The objective response rates of patients treated with GnP, FFX and GEM were 16.8%, 17.6%, and 5.1%, respectively. The median time to treatment failures were 3.9, 3.6, and 2.8 months, and the overall survivals were 11.5, 11.7, and 6.5 months after GnP, FFX, and GEM, respectively. Grade 3 or greater any hematological toxicity occurred in 53.7%, 64.7%, and 34.6% of the patients treated with GnP, FFX, and GEM, respectively. The treatment discontinuation rates due to adverse events were 17.2%, 14.9% and 22.9% in the patients treated with GnP, FFX and GEM, respectively. Conclusions: Chemotherapeutic protocols changed dramatically between 2009 and 2018 in Japan. Both GnP and FFX are well-tolerable and effective in real-life practice despite high frequent adverse events.
The Mentor–Protégé Program in health research in Cameroon
Authors: Pierrette Essama Mekongo, Sylvie Kwedi Nolna, Marceline Djuidje Ngounoue, Judith Torimiro Ndongo, Mireille Ndje Ndje, Celine Nkenfou Nguefeu, Julienne Nguefack, Evelyn Mah, Amani Adjidja, Barbara Atogho Tiedeu, Marielle Paty Ngassa, Veronique Penlap Beng, Rose Gana Fomban Leke
Journal: The Lancet (2019)
Updates Regarding Biomarker Testing for Non–Small Cell Lung Cancer: Considerations from the National Lung Cancer Roundtable
Authors: Edward S. Kim, Upal Basu Roy, Jennifer L. Ersek, Jennifer King, Robert A. Smith, Nicole Martin, Renato Martins, Amy Moore, Gerard A. Silvestri, James Jett
Journal: Journal of Thoracic Oncology (2019)
Abstract 16404: Troponin is the Predominant Risk Factor for Mortality in Patients With Ischemic Heart Failure With Reduced or Preserved Ejection Fraction
Authors: Cassandra Freitas, Bing Yu, Heather J Ross, Peter C Austin, Dennis T Ko, Michael E Farkouh, Jack V Tu, Therese A Stukel, Douglas S Lee
Journal: Circulation (2017)

Introduction: Heart failure (HF) is a major public health concern with substantial morbidity and mortality burden. HF patients with ischemic heart disease may be a particularly high-risk group. How...
Correlation of Clinical Atopic Dermatitis Scores with Levels of Eosinophil Progenitors in Skin after Intradermal Allergen Challenge
Authors: Roma Sehmi, Emma Price, Dhuha Al-Sajee, Sai Sakktee Krisna, Michael J. Aw, Karen J. Howie, Caroline Munoz, Paul M. O'Byrne, Hermenio Lima, Gail M. Gauvreau
Journal: Journal of Allergy and Clinical Immunology (2019)
OrthoMaM v10: Scaling-Up Orthologous Coding Sequence and Exon Alignments with More than One Hundred Mammalian Genomes
Authors: Celine Scornavacca, Khalid Belkhir, Jimmy Lopez, Rémy Dernat, Frédéric Delsuc, Emmanuel J P Douzery, Vincent Ranwez
Journal: Molecular Biology and Evolution (2019)

Abstract We present version 10 of OrthoMaM, a database of orthologous mammalian markers. OrthoMaM is already 11 years old and since the outset it has kept on improving, providing alignments and phylogenetic trees of high-quality computed with state-of-the-art methods on up-to-date data. The main contribution of this version is the increase in the number of taxa: 116 mammalian genomes for 14,509 one-to-one orthologous genes. This has been made possible by the combination of genomic data deposited in Ensembl complemented by additional good-quality genomes only available in NCBI. Version 10 users will benefit from pipeline improvements and a completely redesigned web-interface.
DP <sub>2</sub> antagonism reduces airway smooth muscle mass in asthma by decreasing eosinophilia and myofibroblast recruitment
Authors: Ruth Saunders, Himanshu Kaul, Rachid Berair, Sherif Gonem, Amisha Singapuri, Amanda J. Sutcliffe, Latifa Chachi, Michael S. Biddle, Davinder Kaur, Michelle Bourne, Ian D. Pavord, Andrew J. Wardlaw, Salman H. Siddiqui, Richard A. Kay, Bindi S. Brook, Rod H. Smallwood, Christopher E. Brightling
Journal: Science Translational Medicine (2019)

Cellular and computational models and bronchial biopsies from asthma patients show that a DP 2 antagonist reduces airway smooth muscle mass in asthma.
Complete Transposition of the Great Vessels
Authors: LAURENCE P. STERNS, ROY M. BAKER, JESSE E. EDWARDS
Journal: Circulation (1964)

A case of survival to the age of 11 years is reported in a patient with complete transposition of the great vessels. Additional malformations in the form of subpulmonary stenosis, ventricular septal defect, and patent ductcus arteriosus may have contributed to the unusually long period of survival. Surgical creation of an atrial septal defect and of a subclavian-pulmonary arterial anastomosis when the patient was 3 years old may have augmented the beneficial effects of the existing associated malformations.
Technology will improve doctors’ relationships with patients, says Topol review
Authors: Abi Rimmer
Journal: BMJ (2019)

Doctors should be trained in genomics, artificial intelligence (AI), and digital healthcare technologies, the government commissioned Topol review has said.

The review, led by Eric Topol of the Scripps Research Institute in California, was commissioned by Jeremy Hunt, former health secretary, to explore how NHS staff can make the most of technology to improve services and help ensure a sustainable NHS.

The final report said that the UK has the potential to become a world leader in healthcare technologies and that these would affect the way doctors and other clinicians work.1

It added that, while technology will not replace healthcare professionals, it can “enhance them” and give them more …
Mutation Landscape in Myelofibrosis: Assessment of Frequency and Correlation with Clinical Factors and Outcomes
Authors: Andrew Kuykendall, Chetasi Talati, Najla H Al Ali, Eric Padron, David Sallman, Jinming Song, Ling Zhang, Jeffrey E. Lancet, Kendra L. Sweet, Alan F. List, Kenneth S. Zuckerman, Rami S. Komrokji
Journal: Blood (2016)
Report of prenatal exposure to pesticide predicts infant rhinitis and watery eyes without a cold
Authors: Matthew S. Perzanowski, Virginia Rauh, Laura Conrad, Lori Hoepner, Luis M. Acosta, Frederica P. Perera, Andrew G. Rundle, Emilio Arteaga-Solis, Rachel L. Miller
Journal: Journal of Allergy and Clinical Immunology (2019)
Abstract 19439: Acute Biventricular Hemodynamic Effects of Cardiac Resynchronization Therapy in Right Bundle Branch Block
Authors: Brian A Houston, J. L Sturdivant, Yinghong Yu, Michael R Gold
Journal: Circulation (2017)

Introduction: Equipoise remains regarding the utility of cardiac resynchronization therapy (CRT) in heart failure (HF) patients with right bundle branch block (RBBB) and reduced left ventricular ejection fraction (LVEF). Moreover, little is known regarding the acute hemodynamic changes with CRT in such patients. Hypotheses: HF patients with a RBBB and reduced LVEF demonstrate a diminished LV hemodynamic response to biventricular pacing compared to LBBB patients. However, RBBB patients will demonstrate an improved RV hemodynamic response by correcting RV conduction delay. Methods: Forty patients (9 with RBBB and 31 with LBBB) undergoing clinically-indicated CRT implantation underwent temporary pacing with varying configurations and AV delay. Acute hemodynamic response was assessed via invasive measurements of dP/dtmax in the LV as well as the RV in RBBB subjects. Results: LBBB patients had a greater LV dP/dtmax response to CRT than the RBBB patients (11.3±11.1% vs 6.1±4.0%, p<0.05) during biventricular pac...