tbuckley/cabot-search huggingface dataset:
Abstract 17573: Epinephrine Dosing Interval and Survival Outcomes During Pediatric In-hospital Cardiac Arrest
Authors: Derek B Hoyme, Sonali S Patel, Ricardo A Samson, Tia T Raymond, Vinay M Nadkarni, Dianne L Atkins
Journal: Circulation (2015)

Background: American Heart Association (AHA) guidelines recommend administration of epinephrine (epi) every 3 to 5 minutes during CPR to improve systemic blood pressure and coronary perfusion pressure. In adults with in-hospital cardiac arrest (IHCA), longer dosing intervals are associated with improved survival to hospital discharge. The purpose of this study is to investigate whether longer epi dosing intervals are associated with improved survival to hospital discharge after pediatric IHCA. Methods: A retrospective review of the AHA Get With The Guidelines-Resuscitation registry identified 1,260 pediatric IHCAs that met our inclusion criteria: index IHCA event; no vasoactive infusion in place or alternate vasoactive medication boluses; &gt; 1 dose of epi administered; not located in delivery room, nursery, NICU or obstetrical units. For each arrest, an epi dosing interval was defined by dividing the duration of resuscitation after the first dose of epi by the total doses given. This was necessary as the database does not provide time of individual epi doses. For analysis, epi dosing intervals were categorized as 1 to &lt;5 minutes/dose, 5 to &lt;8 minutes/dose, and 8 to 10 minutes/dose. Multivariable logistic regression models were constructed controlling for age, gender, illness category, location of arrest, and arrest duration to evaluate the relationship of epi dosing intervals on survival to discharge. Odds ratios were calculated using the 1 to &lt;5 minutes/dose interval as the reference. Results: Table 1 displays the descriptive characteristics of the patients and subsequent events. Adjusted odds ratio for survival to hospital discharge for dosing interval of 5 to &lt;8 minutes was 1.454 (95% CI 1.014-2.084) and for 8 to 10 minutes was 1.945 (95% CI 1.094-3.459). Conclusions: Longer dosing intervals than those currently recommended by the AHA guidelines for epinephrine administration during pediatric IHCA are associated with improved survival to hospital discharge.
Device-Related Thrombus After Left Atrial Appendage Closure
Authors: Srinivas R. Dukkipati, Saibal Kar, David R. Holmes, Shephal K. Doshi, Vijendra Swarup, Douglas N. Gibson, Brijeshwar Maini, Nicole T. Gordon, Michael L. Main, Vivek Y. Reddy
Journal: Circulation (2018)

Background: In patients with atrial fibrillation, left atrial appendage closure with the Watchman device prevents thromboembolism from the left atrial appendage; however, thrombus may form on the left atrial face of the device, and then potentially embolize. Herein, we studied the incidence, predictors, and clinical outcome of device-related thrombus (DRT) using a large series of clinical trial cohorts of patients undergoing Watchman implantation. Methods: We studied the device arms of 4 prospective Food and Drug Administration trials: PROTECT-AF (Watchman Left Atrial Appendage System for Embolic Protection in Patients With Atrial Fibrillation) (n=463); PREVAIL (Evaluation of the Watchman LAA Closure Device in Patients With Atrial Fibrillation Versus Long Term Warfarin Therapy) (n=269); CAP (Continued Access to PROTECT AF registry) (n=566); and CAP2 (Continued Access to PREVAIL registry) (n=578). Surveillance transesophageal echocardiographs were performed at 45 days and 12 months in all patients, and also at 6 months in the randomized control trials. We assessed both the incidence of DRT during these transesophageal echocardiographs (and other unscheduled transesophageal echocardiographs), and clinical outcomes of postprocedure stroke or systemic embolism (SSE) and adjusted for CHA 2 DS 2 -VASC and HAS-BLED scores. Results: Of 1739 patients who received an implant (7159 patient-years follow-up; CHA 2 DS 2 -VASc=4.0), DRT was seen in 65 patients (3.74%). The rates of SSE with and without DRT were 7.46 and 1.78 per 100 patient-years (adjusted rate ratio, 3.55; 95% confidence interval [CI], 2.18–5.79; P &lt;0.001), and ischemic SSE rates were 6.28 and 1.65 per 100 patient-years (adjusted rate ratio, 3.22; 95% CI, 1.90–5.45, P &lt;0.001). On multivariable modeling analysis, the predictors of DRT were as follows: history of transient ischemic attack or stroke (odds ratio [OR], 2.31; 95% CI, 1.26–4.25; P =0.007), permanent atrial fibrillation (OR, 2.24; 95% CI, 1.19–4.20; P =0.012); vascular disease (OR, 2.06; 95% CI, 1.08–3.91; P =0.028); left atrial appendage diameter (OR, 1.06 per mm increase; 95% CI, 1.01–1.12; P =0.019); left ventricular ejection fraction (OR, 0.96 per 1% increase; 95% CI, 0.94–0.99; P =0.009). DRT and SSE both occurred in 17 of 65 patients (26.2%). Of the 19 SSE events in these patients with DRT, 9 of 19 (47.4%) and 12 of 19 (63.2%) occurred within 1 and 6 months of DRT detection. Conversely, after left atrial appendage closure, most SSEs (123/142, 86.62%) occurred in patients without DRT. Conclusions: After left atrial appendage closure with Watchman, DRT (≈3.7%) is not frequent but, when present, is associated with a higher rate of stroke and systemic embolism.
An algorythm for screening for liver fibrosis in primary care using population-based data
Authors: Llorenç Caballeria, I. Graupera, G. Pera, I. Arteaga, Lluís Rodríguez, Núria Fabrellas, C. Expósito, P. Torán, J. Caballería, P. Ginès
Journal: Journal of Hepatology (2018)
Real-life experience of ritonavir-boosted paritaprevir, ombitasvir plus ribavirin for treatment of HCV-GT4 in Egyptian patients with severe renal impairment
Authors: H. Omar, M. Said, Z. Abdellatif, Y. Saad, H. Dabes, S. Hamed, M. El-Serafy, K. Elsaeed, Y. Elshazly
Journal: Journal of Hepatology (2018)
Calcium Signaling and Reactive Oxygen Species in Mitochondria
Authors: Edoardo Bertero, Christoph Maack
Journal: Circulation Research (2018)

In heart failure, alterations of Na+ and Ca2+ handling, energetic deficit, and oxidative stress in cardiac myocytes are important pathophysiological hallmarks. Mitochondria are central to these processes because they are the main source for ATP, but also reactive oxygen species (ROS), and their function is critically controlled by Ca2+ During physiological variations of workload, mitochondrial Ca2+ uptake is required to match energy supply to demand but also to keep the antioxidative capacity in a reduced state to prevent excessive emission of ROS. Mitochondria take up Ca2+ via the mitochondrial Ca2+ uniporter, which exists in a multiprotein complex whose molecular components were identified only recently. In heart failure, deterioration of cytosolic Ca2+ and Na+ handling hampers mitochondrial Ca2+ uptake and the ensuing Krebs cycle-induced regeneration of the reduced forms of NADH (nicotinamide adenine dinucleotide) and NADPH (nicotinamide adenine dinucleotide phosphate), giving rise to energetic deficit and oxidative stress. ROS emission from mitochondria can trigger further ROS release from neighboring mitochondria termed ROS-induced ROS release, and cross talk between different ROS sources provides a spatially confined cellular network of redox signaling. Although low levels of ROS may serve physiological roles, higher levels interfere with excitation-contraction coupling, induce maladaptive cardiac remodeling through redox-sensitive kinases, and cell death through mitochondrial permeability transition. Targeting the dysregulated interplay between excitation-contraction coupling and mitochondrial energetics may ameliorate the progression of heart failure.
Abstract 3529: Feasibility, Effectiveness and Safety of Intensive Glucose Control in Critically Ill Hyperglycemic Patients Hospitalized With Acute Coronary Syndromes
Authors: Mikhail Kosiborod, Silvio Inzucchi, Mitchell Hamburg, Lisa Riggs, Sindhu Koshy, Harlan M Krumholz, Lan Xiao, Adnan Khalid, John A Spertus
Journal: Circulation (2007)

Background: Elevated blood glucose (BG) is associated with higher mortality and complications in patients (pts) hospitalized with AMI. While current ACC/AHA guidelines recommend “normalization” of BG in critically ill AMI pts, experience with implementation of intensive BG control protocols in this population is extremely limited. Methods: We implemented an intensive BG control protocol at the Mid America Heart Institute (MAHI) CCU beginning 08/2006, with the purpose of evaluating its feasibility, safety and effectiveness. All ACS patients with admission BG &gt;140 mg/dL received a modified Yale-MAHI intravenous insulin infusion protocol, with a target BG range of 90–120 mg/dL. Demographic, clinical and laboratory data were abstracted from medical records of 94 consecutive pts that received the protocol (post-intervention), and compared with data on 138 consecutive ACS pts with admission BG &gt;140 mg/dL hospitalized in CCU immediately prior to the protocol implementation (pre-intervention). Results: There were no significant differences between pre and post-intervention pts in age (64 vs. 66, p=0.2), female gender (40 vs. 39%, p=0.8), known diabetes (57 vs. 51%, p=0.3), or admission BG (218 vs. 203 mg/dL, p=0.13). Mean 24 hour BG was markedly reduced in post-intervention vs. pre-intervention pts (132 vs. 181 mg/dL, p&lt;0.001). The protocol was very effective in both rapid attainment and maintenance of BG targets (Figure ). The rate of hypoglycemia (BG &lt;60 mg/dL) was 0.72%, and none of the hypoglycemic events were symptomatic. Conclusions: Intensive BG control in critically ill ACS patients with the modified Yale-MAHI protocol is feasible, effective and safe.
Biomedical Informatics on the Cloud
Authors: Peipei Ping, Henning Hermjakob, Jennifer S. Polson, Panagiotis V. Benos, Wei Wang
Journal: Circulation Research (2018)

In the digital age of cardiovascular medicine, the rate of biomedical discovery can be greatly accelerated by the guidance and resources required to unearth potential collections of knowledge. A unified computational platform leverages metadata to not only provide direction but also empower researchers to mine a wealth of biomedical information and forge novel mechanistic insights. This review takes the opportunity to present an overview of the cloud-based computational environment, including the functional roles of metadata, the architecture schema of indexing and search, and the practical scenarios of machine learning–supported molecular signature extraction. By introducing several established resources and state-of-the-art workflows, we share with our readers a broadly defined informatics framework to phenotype cardiovascular health and disease.
Twist promotes tumor metastasis in basal-like breast cancer by transcriptionally upregulating ROR1
Authors: Jingying Cao, Xin Wang, Tao Dai, Yuanzhong Wu, Meifang Zhang, Renxian Cao, Ruhua Zhang, Gang Wang, Rou Jiang, Binhua P. Zhou, Jian Shi, Tiebang Kang
Journal: Theranostics (2018)

Rationale: Twist is a key transcription factor for induction of epithelial-mesenchymal transition (EMT), which promotes cell migration, invasion, and cancer metastasis, confers cancer cells with stem cell-like characteristics, and provides therapeutic resistance. However, the functional roles and targeted genes of Twist in EMT and cancer progression remain elusive. Methods: The potential targeted genes of Twist were identified from the global transcriptomes of T47D/Twist cells by microarray analysis. EMT phenotype was detected by western blotting and immunofluorescence of marker proteins. The dual-luciferase reporter and chromatin immunoprecipitation assays were employed to observe the direct transcriptional induction of ROR1 by Twist. A lung metastasis model was used to study the pro-metastatic role of Twist and ROR1 by injecting MDA-MB-231 cells into tail vein of nude mice. Bio-informatics analysis was utilized to measure the metastasis-free survival of breast cancer patients. Results: Twist protein was proved to directly activate the transcription of ROR1 gene, a receptor of Wnt5a in non-canonical WNT signaling pathway. Silencing of ROR1 inhibited EMT process, cell migration, invasion, and cancer metastasis of basal-like breast cancer (BLBC) cells. Knockdown of ROR1 also ameliorated the pro-metastatic effect of Twist. Furthermore, analyses of clinical specimens indicated that high expression of both ROR1 and Twist tightly correlates with poor metastasis-free survival of breast cancer patients. Conclusion: ROR1 is a targeted gene of Twist. Twist/ROR1 signaling is critical for invasion and metastasis of BLBC cells.
Antibiotic Prophylaxis for Removal of Lower Leg Orthopedic Implants—Reply
Authors: Siem A. Dingemans, Manouk Backes, Tim Schepers
Journal: JAMA (2018)

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National Distribution of Cancer Genetic Testing in the United States
Authors: Kimberly K. Childers, Melinda Maggard-Gibbons, James Macinko, Christopher P. Childers
Journal: JAMA Oncology (2018)

between crizotinib and chemotherapy among responders, owing to the higher objective response rate in the crizotinib arm, it would undermine the treatment benefit with respect to DOR.A caveat for our proposal is that mean DOR depends on a specific time window that can be preselected based on clinical consideration.Empirically one may choose the largest possible time window beyond which a small proportion of patients (eg, 2%) remain at risk for P/D.Like other procedures such as hazard ratio estimation, this time window constraint may not be avoidable without a parametric model for extrapolation.Lastly, it can be quite informative to exam-
Using Indirect Measures to Identify Geographic Hot Spots of Poor Glycemic Control: Cross-sectional Comparisons With an A1C Registry
Authors: David C. Lee, Qun Jiang, Bahman P. Tabaei, Brian Elbel, Christian A. Koziatek, Kevin J. Konty, Winfred Y. Wu
Journal: Diabetes Care (2018)

Focusing health interventions in places with suboptimal glycemic control can help direct resources to neighborhoods with poor diabetes-related outcomes, but finding these areas can be difficult. Our objective was to use indirect measures versus a gold standard, population-based A1C registry to identify areas of poor glycemic control.
P155Cigarette smoke-induced BACH1 regulates the cross talk between NRF2 and AHR through inhibiting microRNA-125b
Authors: M M Almedawar, S Giebe, M Brux, C Brunssen, H Morawietz
Journal: Cardiovascular Research (2018)

genotypes of hemostatic system.One patient (2,3%) had unfavorable heterozygous genotypes according to 5 studied variants predisposing to the development of thrombophilia; 8 (18%) had heterozygous genotypes of 4 SNP, 14 (32%) had heterozygous genotypes of 3 SNP, 14 (32%) had 2 SNPs, 4 (9% ) -1 SNP; only three (7%) individuals did not have adverse heterozygous alleles.The frequency of registration of genotypes predisposing to thromboses shown in table.At the same time, data are available on the prevalence of alleles 5G and 4G polymorphic variant of the PAI-1 gene in healthy adolescents in Russia.In particular, heterozygous genotypes of homozygotes both at the 5G allele and 4G allele are less frequently detected in patients with NOCA, and 5G / 4G are more often detected. Conclusion:The proportion of patients with NOCA among patients with ACS in 2015-2016 was 4.8%.The frequency of adverse allelic variants hemostatic gene polymorphisms associated with risk of thrombophilia in patients with ACS and NOCA was 98%.
Hepatitis C elimination by 2030 is feasible in Brazil: a mathematical modelling approach
Authors: A. Benzaken, E. Catapan, R. Girade, H. Razavi, J. Schmelzer, M. Pessoa, M.L. Ferraz, P. Ferreira, A. Martinelli, M.C.M. Correa
Journal: Journal of Hepatology (2018)
Investigating the effect of adrenomedullin on hepatic NF-kB activation by 2D and 3D hepatic cell cultures
Authors: S.D. Martin, E. Caon, D. Gabbia, G. Zigiotto, Z. Zhang, L. Frenguelli, W. Al-Akkad, S. Sarcognato, G. Maria, G. Mazza, M. Pinzani, K. Rombouts
Journal: Journal of Hepatology (2018)
Are the Globe and UK-PBC scores also effective for predicting risk in patients treated with bezafibrate in addition to ursodeoxycholic acid?: A validation study in Japan
Authors: A. Tanaka, A. Komori, M. Abe, M. Inao, T. Namisaki, N. Hashimoto, K. Kawata, A. Takahashi, M. Ninomiya, A. Honda, K. Jong-Hon, M. Arakawa, S. Yamagiwa, S. Joshita, K. Sato, A. Kaneko, K. Kikuchi, J. Itakura, T. Nomura, K. Kakisaka, T. Masaki, Y. Matsuzaki, H. Ohira, S. Mochida, H. Yoshiji, H. Takikawa
Journal: Journal of Hepatology (2018)
Detection of clinically relevant serrated polyps during screening colonoscopy: results from seven cooperating centers within the German colorectal screening program
Authors: Christoph Schramm, Katharina Janhsen, Jan-Hinnerk Hofer, Hans Toermer, Annette Stelzer, Frank Stenschke, Michael Stollenwerk, Ingo Scheller, Sonja Lang, Tobias Goeser, Hans-Michael Steffen
Journal: Endoscopy (2018)

Abstract Background Serrated polyps have been recognized as precursors of colorectal cancer (CRC) via the serrated pathway. Endoscopic detection and histopathological evaluation of serrated polyps are challenging. The aims of this study were to determine detection rates of the recently proposed entity of clinically relevant serrated polyps (crSPs) and to identify factors that influence their detection in a primary colonoscopy screening cohort. Methods We retrospectively analyzed average-risk screening colonoscopies performed at a tertiary academic hospital and six community-based private practices in Germany between 01/01/2012 and 14/12/2016. Exclusion criteria were age &lt; 50 years, conditions with increased risk for CRC (e. g. inflammatory bowel disease, history of CRC, hereditary cancer syndromes), and incomplete procedures. CrSPs were defined as serrated polyps ≥ 10 mm and/or &gt; 5 mm located proximally to the splenic flexure. Conventional adenomas were defined as adenomas excluding serrated polyps. Results A total of 4161 colonoscopies from average-risk individuals were included (median age 62 years [interquartile range 56 – 69]; 48.6 % male). CrSPs were detected in 6.9 %, with a mean detection rate of 4.7 % (95 % confidence interval 2.3 % – 7.2 %). Detection rates ranged from 0 % to 16.2 %. In multivariate analysis, simultaneous detection of conventional adenomas and an endoscopist adenoma detection rate of ≥ 25 % were significantly associated with increased detection of crSPs, with odds ratios of 1.43 (95 %CI 1.11 – 1.85; P = 0.01) and 7.35 (95 %CI 4.43 – 12.19; P &lt; 0.001). The individual endoscopist’s detection rate for conventional adenomas and crSPs were significantly correlated (r = 0.54, P = 0.02). Conclusion Detection rates for crSPs differed between participating endoscopists. However, individual skills to detect polypoid lesions have a relevant bearing on the detection rate of crSPs.
Utilization and outcomes of elbasvir/grazoprevir in genotype 1B chronic hepatitis C: updated retrospective data analyses from the Trio network
Authors: N. Tsai, B. Bacon, M. Curry, S. Flamm, S. Milligan, C. Nwankwo, N. Wick, Z. Younossi, N. Afdhal
Journal: Journal of Hepatology (2018)
Collocation of Buprenorphine with HCV treatment to improve adherence and reduce harm in PWID with HCV: Preliminary data from the ANCHOR study
Authors: E. Rosenthal, K. Hill, L. Nussdorf, P. Mathur, C. Gross, R. Silk, E. Akoth, D. Sternberg, N. Sidique, C. Chaudhury, B. Emmanuel, H. Masur, S. Kottilil, S. Kattakuzhy
Journal: Journal of Hepatology (2018)
Emergence and long-term persistence of NS3, NS5A, and NS5B resistance associated substitutions after treatment with direct-acting antivirals
Authors: D. Wyles, E. Lawitz, B. Mcnabb, J. Lu, S. Chang, A. Osinusi, E.S. Svarovskaia, D. Brainard, S. Pianko, J. Feld, H. Mo, H. Dvory-Sobol
Journal: Journal of Hepatology (2018)
CD20-TCB with Obinutuzumab Pretreatment as Next-Generation Treatment of Hematologic Malignancies
Authors: Marina Bacac, Sara Colombetti, Sylvia Herter, Johannes Sam, Mario Perro, Stanford Chen, Roberta Bianchi, Marine Richard, Anne Schoenle, Valeria Nicolini, Sarah Diggelmann, Florian Limani, Ramona Schlenker, Tamara Hüsser, Wolfgang Richter, Katharine Bray-French, Heather Hinton, Anna Maria Giusti, Anne Freimoser-Grundschober, Laurent Lariviere, Christiane Neumann, Christian Klein, Pablo Umaña
Journal: Clinical Cancer Research (2018)

Purpose: Despite promising clinical activity, T-cell-engaging therapies including T-cell bispecific antibodies (TCB) are associated with severe side effects requiring the use of step-up-dosing (SUD) regimens to mitigate safety. Here, we present a next-generation CD20-targeting TCB (CD20-TCB) with significantly higher potency and a novel approach enabling safer administration of such potent drug.Experimental Design: We developed CD20-TCB based on the 2:1 TCB molecular format and characterized its activity preclinically. We also applied a single administration of obinutuzumab (Gazyva pretreatment, Gpt; Genentech/Roche) prior to the first infusion of CD20-TCB as a way to safely administer such a potent drug.Results: CD20-TCB is associated with a long half-life and high potency enabled by high-avidity bivalent binding to CD20 and head-to-tail orientation of B- and T-cell-binding domains in a 2:1 molecular format. CD20-TCB displays considerably higher potency than other CD20-TCB antibodies in clinical development and is efficacious on tumor cells expressing low levels of CD20. CD20-TCB also displays potent activity in primary tumor samples with low effector:target ratios. In vivo, CD20-TCB regresses established tumors of aggressive lymphoma models. Gpt enables profound B-cell depletion in peripheral blood and secondary lymphoid organs and reduces T-cell activation and cytokine release in the peripheral blood, thus increasing the safety of CD20-TCB administration. Gpt is more efficacious and safer than SUD.Conclusions: CD20-TCB and Gpt represent a potent and safer approach for treatment of lymphoma patients and are currently being evaluated in phase I, multicenter study in patients with relapsed/refractory non-Hodgkin lymphoma (NCT03075696). Clin Cancer Res; 24(19); 4785-97. ©2018 AACRSee related commentary by Prakash and Diefenbach, p. 4631.