tbuckley/cabot-search huggingface dataset:
Abstract 294: A Machine Learning Approach in Using Capnography to Predict Resuscitation Interventions Required in Hypoxic Pseudo-Pulseless Electrical Activity Resuscitation
Authors: Alexander L Lindqwister, Alexander Ivanov, Yiyuan D Hu, Samuel B Klein, Karen L Moodie, Norman A Paradis
Journal: Circulation (2020)

Introduction: Pseudo-Pulseless Electrical Activity (p-PEA) is a lifeless form of profound cardiac shock characterized by measurable cardiac mechanical activity without clinically detectable pulses. Patients in pseudo-PEA carry different prognoses than those in true PEA and may require different therapies. End-tidal carbon dioxide (ET-CO 2 ) has been studied in ventricular fibrillation and true PEA, but not in p-PEA. We evaluated the ability of capnography to predict the need for CPR in p-PEA. Methods: Female swine (N = 14) under intravenous anesthesia were instrumented with aortic and central venous micromanometer pressure catheters. ECG and ET-CO 2 were measured continuously. p-PEA was induced by ventilation with 6% oxygen in 94% nitrogen and was defined as a systolic aortic pressure less than 40 mmHg. Pigs were grouped into cohorts based on the interventions required to achieve ROSC: 100% O 2 , 100% O 2 + CPR, 100% O 2 + CPR + epinephrine. One hundred 4 sec. snippets of ET-CO 2 data were randomly sampled during the p-PEA state, and the mean, maximum, slope, and r-value of each epoch was used to train 7 machine learning algorithms to predict which intervention cohort they belonged to. Data was split randomly into 60% training and 40% testing sets. Results: Ensemble approaches were highly successful, with the gradient boosting model achieving an AUC of 0.91 on ROC curves (Figure 1), with an accuracy 0.83, sensitivity 0.86, specificity 0.78. Conclusions: In porcine hypoxic p-PEA, machine learning derived models of ET-CO2 appeared able to predict the degree of interventions needed for ROSC. If confirmed clinically, such an approach may be useful in guiding treatment of this increasingly common type of cardiac arrest.
Abstract 347: The Effect of Targeted Temperature Management at 34 °C and 36 °C on Day-30 Neurological Outcomes in Out-of-hospital Cardiac Arrest Patients
Authors: Takeshi Iyonaga, Ken-ichi Hiasa, Nobuyuki Enzan, Masaaki A Nishihara, Kenzo Ichimura, Yuji Shono, Takanari Kitazono, Hiroyuki Tsutsui
Journal: Circulation (2020)

Introduction: Targeted temperature management (TTM) has established evidence for improving neurological outcomes in cardiac arrest patients who sustained coma after return of spontaneous circulation (ROSC). The target temperature has been recommended to be between 32 and 36 °C. However optimal temperature remains unestablished. This study aimed to assess the relationship between target temperature and neurological outcome by using the Japanese nationwide registry. Methods: This retrospective observational cohort study was based on the Japanese association for acute medicine - out-of-hospital cardiac arrest (JAAM-OHCA) registry during 2014 to 2017. Our study included all initial rhythms and any cause of OHCA patients and excluded age &lt; 18 and Glasgow Coma Scale score &gt; 8. The primary outcome was 30 day favorable neurological outcome, defined as cerebral performance category (CPC) scale 1 and 2. First, to clarify the efficacy of TTM, the neurological outcome was compared whether patients received TTM or not. Next, to evaluate the relationship between neurological outcome and target temperature on TTM, the neurological outcome was compared hypothermia (34 °C) group with normothermia (36 °C) group . Single and multivariable logistic regression analysis was performed. Results: The study included 9930 patients. Of these, 1184 (11.9%) patients received TTM. Favorable neurological outcome was more present in TTM group than in no TTM group (39.7% vs. 4.3%, odds ratio [OR] 14.6, 95% confidence interval [CI] 12.5-17.1, p&lt;0.001). Multivariable analysis showed TTM was associated with favorable neurological outcome (OR 1.6, 95%CI 1.1-2.3, p&lt;0.001). Of TTM group, 801 (68.5%) patients received hypothermia management and 242 (20.7%) patients received normothermia management. Favorable neurological outcome was more present in the hypothermia group than in the normothermia group (42.6% vs. 34.3%, OR 1.42, 95% CI 1.1-1.9, p=0.022). However, the neurological outcome did not differ between these two groups (OR 0.84, 95%CI 0.46-1.5, p&lt;0.57). Conclusions: TTM was significantly associated with favorable neurological outcome. However, neurological outcome was not associated with target temperature on TTM.
Abstract 12872: Machine Learning on Dual-isotope Myocardial Semiconductor SPECT Can Predict Cardiac Prognosis in Patients With Congestive Heart Failure
Authors: Masato Shimizu, shummo cho, Yoshiki Misu, Mari Ohmori, Ryo Tateishi, Toshio Kaneda, Yosuke Yamakami, Hiroshi Shimada, Tomoko Manno, Ami Isshiki, Shigeki Kimura, Hiroyuki Fujii, Makoto Suzuki, Mitsuhiro Nishizaki, Tetsuo Sasano
Journal: Circulation (2020)

Introduction: Dual-isotope (201TlCl and 123I-β-methyl-P-iodophenyl-pentadecanoic acid (BMIPP) ) single photon emission computed tomography (SPECT) is utilized to estimate not only in patients with ischemic heart disease but with congestive heart failure (CHF). We tried to construct predictive model for cardiac prognosis on the SPECT for cardiac death by machine learning. Hypothesis: Machine learning is a powerful tool to predict cardiac prognosis in patients with CHF Methods: Consecutive 310 patients who admitted with CHF (77.1±3.1 years, 164 males) were enrolled. After initial treatment, they underwent electrocardiography gated SPECT and observed in median 507 days [IQR: 165, 1032]. Multivariate Cox regression analysis for cardiac death was performed, and predictive model was constructed by ROC curve analysis and machine learning (Random Forest and Deep Learning). The accuracies (= [True positive + True negative] / Total) of the prediction models were compared with ROC curve model. Results: Thirty-six patients fell into cardiac death. Cox analysis showed Age, left ventricular ejection fraction (LVEF), summed rest score (SRS) of BMIPP, and mismatch score were significant predictors (Hazard ratio: 1.068, 0.970, 1.032, 1.092, P value: &lt;0.001, 0.014, 0.002, &lt;0.001, respectively). ROC curve analysis of them revealed the accuracy of the cut-off value was 0.479-0.773. Conversely, machine learning model demonstrated higher accuracy for cardiac death (Random Forest: 0.895, Deep Learning: 0.935). The top 4 feature importance of the random forest were LVEF (0.299), SRS BMIPP (0.263), Age (0.262), and mismatch score (0.160). Conclusions: Machine learning model on SPECT had powerful predictive value for predicting cardiac death in patients with CHF.
Tumor Targeted Delivery of an Anti‐Cancer Therapeutic: An In Vitro and In Vivo Evaluation
Authors: You Jung Kang, Claire K. Holley, Mohammad Reza Abidian, Achuthamangalam B. Madhankumar, James Connor, Sheereen Majd
Journal: Advanced Healthcare Materials (2020)

Abstract The limited effectiveness of current therapeutics against malignant brain gliomas has led to an urgent need for development of new formulations against these tumors. Chelator Dp44mT (di‐2‐pyridylketone‐4,4‐dimethyl‐3‐thiosemicarbazone) presents a promising candidate to defeat gliomas due to its exceptional anti‐tumor activity and its unique ability to overcome multidrug resistance. The goal of this study is to develop a targeted nano‐carrier for Dp44mT delivery to glioma tumors and to assess its therapeutic efficacy in vitro and in vivo. Dp44mT is loaded into poly(ethylene glycol) (PEG)ylated poly(lactic‐co‐glycolic acid) (PLGA) nanoparticles (NPs) decorated with glioma‐targeting ligand Interlukin 13 (IL13). IL13‐conjugation enhanced the NP uptake by glioma cells and also improved their transport across an in vitro blood‐brain‐barrier (BBB) model. This targeted formulation showed an outstanding toxicity towards glioma cell lines and patient‐derived stem cells in vitro, with IC 50 values less than 125 nM, and caused no significant death in healthy brain microvascular endothelial cells. In vivo, when tested on a xenograft mouse model, IL13‐conjugated Dp44mT‐NPs reduced the glioma tumor growth by ≈62% while their untargeted counterparts reduced the tumor growth by only ≈16%. Notably, this formulation does not cause any significant weight loss or kidney/liver toxicity in mice, demonstrating its great therapeutic potential.
Associations of Plasma Phospho-Tau217 Levels With Tau Positron Emission Tomography in Early Alzheimer Disease
Authors: Shorena Janelidze, David Berron, Ruben Smith, Olof Strandberg, Nicholas K. Proctor, Jeffrey L. Dage, Erik Stomrud, Sebastian Palmqvist, Niklas Mattsson-Carlgren, Oskar Hansson
Journal: JAMA Neurology (2020)

There is an urgent need for inexpensive and minimally invasive blood biomarkers for Alzheimer disease (AD) that could be used to detect early disease changes.To assess how early in the course of AD plasma levels of tau phosphorylated at threonine 217 (P-tau217) start to change compared with levels of established cerebrospinal fluid (CSF) and positron emission tomography (PET) biomarkers of AD pathology.This cohort study included cognitively healthy control individuals (n = 225) and participants with subjective cognitive decline (n = 89) or mild cognitive impairment (n = 176) from the BioFINDER-2 study. Participants were enrolled at 2 different hospitals in Sweden from January 2017 to October 2019. All study participants underwent plasma P-tau217 assessments and tau- and amyloid-β (Aβ)-PET imaging. A subcohort of 111 participants had 2 or 3 tau-PET scans.Changes in plasma P-tau217 levels in preclinical and prodromal AD compared with changes in CSF P-tau217 and PET measures.Of 490 participants, 251 were women (51.2%) and the mean (SD) age was 65.9 (13.1) years. Plasma P-tau217 levels were increased in cognitively unimpaired participants with abnormal Aβ-PET but normal tau-PET in the entorhinal cortex (Aβ-PET+/ tau-PET- group vs Aβ-PET-/ tau-PET- group: median, 2.2 pg/mL [interquartile range (IQR), 1.5-2.9 pg/mL] vs 0.7 pg/mL [IQR, 0.3-1.4 pg/mL]). Most cognitively unimpaired participants who were discordant for plasma P-tau217 and tau-PET were positive for plasma P-tau217 and negative for tau-PET (P-tau217+/tau-PET-: 36 [94.7%]; P-tau217-/tau-PET+: 2 [5.3%]). Event-based modeling of cross-sectional data predicted that in cognitively unimpaired participants and in those with mild cognitive impairment, both plasma and CSF P-tau217 would change before the tau-PET signal in the entorhinal cortex, followed by more widespread cortical tau-PET changes. When testing the association with global Aβ load in nonlinear spline models, both plasma and CSF P-tau217 were increased at lower Aβ-PET values compared with tau-PET measures. Among participants with normal baseline tau-PET, the rates of longitudinal increase in tau-PET in the entorhinal cortex were higher in those with abnormal plasma P-tau217 at baseline (median standardized uptake value ratio, 0.029 [IQR, -0.006 to 0.041] vs -0.001 [IQR, -0.021 to 0.020]; Mann-Whitney U, P = .02).In this cohort study, plasma P-tau217 levels were increased during the early preclinical stages of AD when insoluble tau aggregates were not yet detectable by tau-PET. Plasma P-tau217 may hold promise as a biomarker for early AD brain pathology.
Abstract IA-01: Role of the gut-tumor microbial axis in pancreatic ductal adenocarcinoma (PDAC)
Authors: Florencia McAllister
Journal: Cancer Research (2020)

Abstract Even though Pancreatic Ductal Adenocarcinoma (PDAC) has a 5-year survival rate of 9%, there is a minority of patients that survive more than 5 years (Long Term Survivors, LTS). Genomic studies have not shown a particular signature on those patients, suggesting the potential relevance of extrinsic non-genetic factors in survival. Also, higher number of tumor infiltrating CD8+T cells and neoantigens with similarities to microbes are predictive of better outcomes. Studies have linked microbiome with tumorigenesis and treatment responses in many cancers, including PDAC, a tumor that contains bacteria. We have analyzed intratumoral microbial content and found that LTS have higher microbial diversity and a unique microbial signature. We have also found that some of the intra-tumoral bacteria originates in the intestines. Fecal microbial transplants resulted in modulation of tumoral microbiome, immune infiltration and tumor growth. Direct bacterial immune activation or indirect effect by bacterial metabolites may be some of the mechanisms implicated. Future clinical work is needed to further understand how to modulate tumors immune status by manipulating bacteria. A clinical trial with this goal is now being developed. Citation Format: Florencia McAllister. Role of the gut-tumor microbial axis in pancreatic ductal adenocarcinoma (PDAC) [abstract]. In: Proceedings of the AACR Virtual Special Conference on Pancreatic Cancer; 2020 Sep 29-30. Philadelphia (PA): AACR; Cancer Res 2020;80(22 Suppl):Abstract nr IA-01.
Once-per-week selinexor, bortezomib, and dexamethasone versus twice-per-week bortezomib and dexamethasone in patients with multiple myeloma (BOSTON): a randomised, open-label, phase 3 trial
Authors: Sebastian Grosicki, Maryana Simonova, Ivan Spicka, Ludek Pour, Iryrna Kriachok, Maria Gavriatopoulou, Halyna Pylypenko, Holger W Auner, Xavier Leleu, Vadim Doronin, Ganna Usenko, Nizar J Bahlis, Roman Hajek, Reuben Benjamin, Tuphan K Dolai, Dinesh K Sinha, Christopher P Venner, Mamta Garg, Mercedes Gironella, Artur Jurczyszyn, Pawel Robak, Monica Galli, Craig Wallington-Beddoe, Atanas Radinoff, Galina Salogub, Don A Stevens, Supratik Basu, Anna M Liberati, Hang Quach, Vesselina S Goranova-Marinova, Jelena Bila, Eirini Katodritou, Hanna Oliynyk, Sybiryna Korenkova, Jeevan Kumar, Sundar Jagannath, Phillipe Moreau, Moshe Levy, Darrell White, Moshe E Gatt, Thierry Facon, Maria V Mateos, Michele Cavo, Donna Reece, Larry D Anderson, Jean-Richard Saint-Martin, Jacqueline Jeha, Anita A Joshi, Yi Chai, Lingling Li, Vishnuvardhan Peddagali, Melina Arazy, Jatin Shah, Sharon Shacham, Michael G Kauffman, Meletios A Dimopoulos, Paul G Richardson, Sosana Delimpasi
Journal: The Lancet (2020)
Midostaurin Shows Efficacy in Refractory Multiple Myeloma with TP53 Mutation and Elevated Expression of NTRK1, NTRK3 and AURKA
Authors: Muntasir M Majumder, David Tamborero, Pekka Anttila, Raija Helena Silvennoinen, Samuli Eldfors, Juha Lievonen, Ashwini Kumar, Alun Parsons, Minna Suvela, Esa Jantunen, Kimmo Porkka, Caroline A Heckman
Journal: Blood (2017)
A knockout combination for MPN stem cells
Authors: Megan Bywater, Steven W. Lane
Journal: The Journal of Experimental Medicine (2020)

Myeloproliferative neoplasms (MPNs) are a group of blood cancers that are maintained by stem cell populations. In this issue of JEM, Dagher et al. (https://doi.org/10.1084/jem.20201268) combine arsenic and interferon α to deliver a knockout punch to MPN stem cells and provide new hope to cure patients with MPNs.
Abstract 13291: Impact of VAD Support Duration on Pediatric Heart Transplant Outcomes
Authors: Arene Butto, Chad Y Mao, Lydia Wright, Martha Wetzel, Michael Kelleman, Michael P Carboni, Anne I Dipchand, Kenneth R Knecht, Zdenka Reinhardt, Joshua D Sparks, Chet Villa, William T Mahle
Journal: Circulation (2020)

Introduction: There is wide variability in the timing of heart transplant (HT) listing and consideration of organ offers after ventricular assist device (VAD) implant in children. While some centers wait weeks or months before proceeding with HT, others accept donor hearts within days of VAD surgery. We sought to determine if HT within 30 days of VAD implant impacts post-HT outcomes when compared to HT after ≥30 days of VAD support. Methods: Patients on VAD support prior to HT were extracted from the Pediatric Heart Transplant Study database. The primary endpoints were post-HT length of hospital stay (LOS) and one-year survival. Confounding was addressed by propensity score weighting using inverse probability of treatment. Propensity scores were calculated based on age at VAD implant, blood type, primary cardiac diagnosis, decade, VAD type, and allosensitization status. Group balance was verified with standardized differences. Results: A total of 1138 children underwent VAD implant prior to HT between 2000-2019 (Table 1). Most underwent HT ≥30 days after VAD (71%). The majority (70%) had an LVAD alone. Infants accounted for 22% of both groups, while those 1-11 years were 46% of the ≥30-day group and patients ≥12 years made up 42% of &lt;30-day group (p=0.001). There was no difference in the prevalence of congenital heart disease vs. cardiomyopathy (p=0.7) or high allosensitization status (p=0.8) between groups. Post-HT LOS was similar between groups (23 vs. 21 days in &lt;30 vs. ≥30 days, p=0.07). One-year survival was 90.5% in the &lt;30-day group vs. 94.5% in ≥30 days (adjusted mortality HR 1.81, 95% CI 1.15-2.86, p=0.01). Conclusions: In this large study of children undergoing HT after VAD, we found lower one-year survival in patients on VAD support for &lt;30 days prior to HT compared to those on VAD for ≥30 days before HT. These findings suggest that a strategy of delayed HT listing following VAD implant may favorably impact post-HT survival in the pediatric population.
Guidelines for Opioid Prescribing in Children and Adolescents After Surgery
Authors: Lorraine I. Kelley-Quon, Matthew G. Kirkpatrick, Robert L. Ricca, Robert Baird, Calista M. Harbaugh, Ashley Brady, Paula Garrett, Hale Wills, Jonathan Argo, Karen A. Diefenbach, Marion C.W. Henry, Juan E. Sola, Elaa M. Mahdi, Adam B. Goldin, Shawn D. St Peter, Cynthia D. Downard, Kenneth S. Azarow, Tracy Shields, Eugene Kim
Journal: JAMA Surgery (2020)

<h3>Importance</h3> Opioids are frequently prescribed to children and adolescents after surgery. Prescription opioid misuse is associated with high-risk behavior in youth. Evidence-based guidelines for opioid prescribing practices in children are lacking. <h3>Objective</h3> To assemble a multidisciplinary team of health care experts and leaders in opioid stewardship, review current literature regarding opioid use and risks unique to pediatric populations, and develop a broad framework for evidence-based opioid prescribing guidelines for children who require surgery. <h3>Evidence Review</h3> Reviews of relevant literature were performed including all English-language articles published from January 1, 1988, to February 28, 2019, found via searches of the PubMed (MEDLINE), CINAHL, Embase, and Cochrane databases. Pediatric was defined as children younger than 18 years. Animal and experimental studies, case reports, review articles, and editorials were excluded. Selected articles were graded using tools from the Oxford Centre for Evidence-based Medicine 2011 levels of evidence. The Appraisal of Guidelines for Research &amp; Evaluation (AGREE) II instrument was applied throughout guideline creation. Consensus was determined using a modified Delphi technique. <h3>Findings</h3> Overall, 14 574 articles were screened for inclusion, with 217 unique articles included for qualitative synthesis. Twenty guideline statements were generated from a 2-day in-person meeting and subsequently reviewed, edited, and endorsed externally by pediatric surgical specialists, the American Pediatric Surgery Association Board of Governors, and the American College of Surgeons Board of Regents. Review of the literature and guideline statements underscored 3 primary themes: (1) health care professionals caring for children who require surgery must recognize the risks of opioid misuse associated with prescription opioids, (2) nonopioid analgesic use should be optimized in the perioperative period, and (3) patient and family education regarding perioperative pain management and safe opioid use practices must occur both before and after surgery. <h3>Conclusions and Relevance</h3> These are the first opioid-prescribing guidelines to address the unique needs of children who require surgery. Health care professionals caring for children and adolescents in the perioperative period should optimize pain management and minimize risks associated with opioid use by engaging patients and families in opioid stewardship efforts.
PARE0021 TARGETED INITIATIVE TO FACILITATE THE IMPLEMENTATION OF EXISTING EFFECTIVE GOUT TREATMENT IN SWEDEN
Authors: L. Alemo Munters, I. Loell, S. Jansson, L. T. H. Jacobsson, M. Dehlin
Journal: Annals of the Rheumatic Diseases (2020)

Background: Gout is a very painful rheumatic condition origin from excess uric acid in the bloodstream, which results in an accumulation of uric acid crystals in the joints and a severe local inflammatory response. Gout is treated in primary care and the current treatment has satisfactory results on disease management, thus patients can expect a controlled disease without flares. In Sweden however, only 30-40 % (1) of the patients receives adequate urate lowering treatment and prevent the disabling flares. Objectives: As a patient association, the Swedish Rheumatism Association (SRA) has identified an opportunity to use scientific evidence and data to improve awareness in both patients and physicians in order to make the existing treatment available and to shift the gout treatment from flare management to prevention. Methods: With SRA funding we created the Gout network, consisting of researchers, health professionals and patient research partners. Through meetings and operational support developed strategies to educate patients suffering from gout and to alert physicians in the primary care of the most recent research to aid the management of gout. We also fund a specific research project aimed to create an implementation plan to establish a treatment routine for gout in primary care with already existing resources. Results: A high quality patient education material is under development and consists of an information video lecture and a comprehensive online patient school providing information about the diagnosis, preventive treatment, possible life style change along with other resources that will support the gout patient, both for self-care and in relation to healthcare. For the healthcare profession we have together with a clinical research expert and a patient research partner developed a fact sheet with the latest scientific updates on gout. Conclusion: Accessible, high quality diagnosis information about gout is currently missing in Sweden. This collaboration initiative provides high quality facts to raise the general awareness and to educate and empower patients to get the effective therapy that is available today. References: [1] Incidence and prevalence of gout in Western Sweden Dehlin M, Drivelegka P, Sigurdardottir V, Svärd A &amp; Jacobsson LTH. Arthritis Research &amp; Therapy 18,: 164 (2016 ) Disclosure of Interests: Li Alemo Munters: None declared, Ingela Loell: None declared, Suzanna Jansson: None declared, Lennart T.H. Jacobsson Consultant of: AbbVie, Eli Lilly, Janssen, Novartis and Pfizer, Mats Dehlin: None declared