tbuckley/cabot-search huggingface dataset:
The global incidence and prevalence of anaphylaxis in children in the general population: A systematic review
Authors: Yichao Wang, Katrina J. Allen, Noor H. A. Suaini, Vicki McWilliam, Rachel L. Peters, Jennifer J. Koplin
Journal: Allergy (2019)

Abstract Background Despite an increasing number of publications from individual countries and regions, there is still no systematic review of the global epidemiology of anaphylaxis in the general paediatric population. Methods We conducted a systematic review, using a protocol registered and published with the international prospective register of systematic reviews ( PROSPERO ). Results were reported following PRISMA guidelines. The search strategy was designed in Medline (ovid) and modified for Embase (ovid) and PubMed. Papers were screened by two independent reviewers following selection and exclusion criteria. Data extraction and risk of bias assessment were completed by the same two reviewers. Studies in adults only or those that did not report data in children separately were excluded. Results A final total of 59 articles were included. Of these, 5 reported cumulative incidence, 39 reported incidence rate and 17 reported prevalence data. The incidence of anaphylaxis in children worldwide varied widely, ranging from 1 to 761 per 100 000 person‐years for total anaphylaxis and 1 to 77 per 100 000 person‐years for food‐induced anaphylaxis. The definition of anaphylaxis from NIAID / FAAN was the most commonly used. Gender and ethnicity were demographic risk factors associated with anaphylaxis in children. Increasing total or food‐induced anaphylaxis incidence over time was reported by 19 studies. Conclusion The reported incidence of anaphylaxis in children varied widely. Studies in developing countries are underrepresented. To accurately compare anaphylaxis incidence between countries and investigate the time trends, further studies using a standardized definition across different countries are required.
Tissue-specific regulation of p53 by PKM2 is redox dependent and provides a therapeutic target for anthracycline-induced cardiotoxicity
Authors: Bruno Saleme, Vikram Gurtu, Yongneng Zhang, Adam Kinnaird, Aristeidis E. Boukouris, Keshav Gopal, John R. Ussher, Gopinath Sutendra
Journal: Science Translational Medicine (2019)

Chemotherapy-induced cardiotoxicity (CIC) is a common clinical problem that compromises effective anticancer therapies. Many chemotherapeutics (including anthracyclines, such as doxorubicin) induce the proapoptotic transcription factor p53 in the tumor and nonspecifically in the heart, promoting heart failure. Although inhibition of p53 shows benefit in preclinical heart failure models, it would not be an attractive adjuvant therapy for CIC, because it would prevent tumor regression. A p53-targeting therapy that would decrease chemotherapy-induced apoptosis in the myocardium and, at the same time, enhance apoptosis in the tumor would be ideal. Here, we propose that differences in oxygen tension between the myocardium and the tumor could provide a platform for redox-dependent tissue-specific therapies. We show by coimmunoprecipitation and mass spectrometry that the redox-regulated pyruvate kinase muscle 2 (PKM2) directly binds with p53 and that the redox status of cysteine-423 of tetrameric (but not monomeric) PKM2 is critical for the differential regulation of p53 transcriptional activity. Tetrameric PKM2 suppresses p53 transcriptional activity and apoptosis in a high oxidation state but enhances them in a low oxidation one. We show that the oxidation state (along with cysteine-423 oxidation) is higher in the heart compared to the tumor of the same animal. Treatment with TEPP-46 (a compound that stabilizes tetrameric PKM2) suppressed doxorubicin-induced cardiomyocyte apoptosis, preventing cardiac dysfunction, but enhanced cancer cell apoptosis and tumor regression in the same animals in lung cancer models. Thus, our work suggests that redox-dependent differences in common proteins expressed in the myocardium and tumor can be exploited therapeutically for tissue selectivity in CIC.
Abstract 21299: Drug of Abuse is Associated With Clinical Aspects and Outcomes of Injection Drug Use Endocarditis
Authors: Erin W Barnes, James E Peacock, Laura Bachmann
Journal: Circulation (2017)

Introduction: Wake Forest Baptist Medical Center has perceived a rise in the number of injection drug use associated endocarditis cases. Many of these patients report injection of the prescription opioid oxymorphone, a drug specifically linked to a microangiopathic hemolytic anemia when injected and large HIV outbreak in Indiana. Hypothesis: 1) The number of IDU-IE cases at our institution is increasing 2) The characteristics of these patients will differ from the classically taught phenotype of a mostly male, right sided predominant, low morbidity and mortality disease process 3) Those who injected oxymorphone will have differing clinical characteristics and clinical outcomes than those who did not inject oxymorphone. Methods: Retrospective analysis of IE cases at an academic medical center from 1/1/2004 to 9/30/2015 stratified by IDU and reported intravenous oxymorphone use. Results: Three hundred seven cases of IE were identified which included 92 IDU cases: 46 oxymorphone-exposed and 46 oxymorphone-unexposed . As compared to the non-IDU group, the IDU group was younger (31.3 +/-9.2 vs 54.2 +/-15.8, p&lt;0.0001), predominantly Caucasian (95.7% vs 78.1%, p=0.0002), and female (58.7% vs 35.4%, p=0.02). When comparing the oxymorphone-exposed to oxymorphone-unexposed group, age (31.3+/-9.2 vs. 33.2+/-9.2, p=.32), race (95.7% Caucasian both groups), and gender (58.7% female vs. 41.3% p=0.1) were equivalent. As compared to the oxymorphone-unexposed group, the oxymorphone exposed group had significantly more MRSA (63% vs 48.9%, p=.007), tricuspid valve involvement (52.2% vs 30.4%, p=.03), and hepatitis C antibody seropositivity (78.3% vs 52.2%, p=.01). The oxymorphone unexposed group had significantly more aortic valve disease (23.9% vs 2.2%, p=.004), cardiac surgery (37% vs 13%, p=.008), and ICU admission (73.9% vs 54.4%, p=.05) than the oxymorphone exposed group. Inpatient mortality was comparable (6.5% exposed vs 8.7% unexposed, p=1.0) whereas one-year mortality was 19.6% in the oxymorphone exposed group and 13% in the oxymorphone unexposed group (p=.06). Conclusions: Our results support the hypothesis that there may be differences in clinical characteristics and outcomes of IDU-IE which are associated with the specific drug of abuse.
Abstract 15424: Endothelial Cells Induce Distal Airway Patterning of Human IPSC-Derived Lung Progenitor Cells by a Paracrine Mechanism Involving Exosome Release
Authors: Miriel Ho, Duncan Stewart
Journal: Circulation (2017)

Introduction: Induced pluripotent stem cells (iPSCs) offer an unprecedented potential for patient-specific tissue regeneration. The regeneration of functional lung tissue requires endothelial cells...
Predicting Responders to Reslizumab after 16 Weeks of Treatment Using an Algorithm Derived from Clinical Studies of Patients with Severe Eosinophilic Asthma
Authors: Eric D. Bateman, Ratko Djukanović, Mario Castro, Janice Canvin, Matthew Germinaro, Robert Noble, Margaret Garin, Roland Buhl
Journal: American Journal of Respiratory and Critical Care Medicine (2018)

Reslizumab is a humanized anti-IL-5 monoclonal antibody used as add-on maintenance treatment for patients with uncontrolled eosinophilic asthma.To predict response and nonresponse to intravenous reslizumab at 52 weeks with an algorithm we developed based on clinical indicators from pivotal clinical trials.Patients aged 18 years and older who met Global Initiative for Asthma 4 or 5 criteria and received intravenous reslizumab (n = 321) in two trials ( www.clinicaltrials.gov identifiers, NCT01287039 and NCT01285323) were selected as the data source. A mathematical model was constructed that was based on change from baseline to 16 weeks in Asthma Control Questionnaire and Asthma Quality of Life Questionnaire scores and FEV1, and number of clinical asthma exacerbations during the year before enrollment and in the first 16 weeks of treatment, and these measures were evaluated for their ability to predict the outcome at 52 weeks: responder, nonresponder, or indeterminate.The algorithm predicted that 276 patients would be classified as responders; in 248 (89.9%), the prediction was correct. In comparison, 26 patients were predicted to be nonresponders; 50.0% of these predictions were correct. Nineteen patients were classified as indeterminate. The algorithm had 95.4-95.5% sensitivity and 40.6-54.1% specificity. Jackknife and cross-study validation confirmed the robustness of the algorithm.Our algorithm enabled prediction at 16 weeks of treatment of the response to intravenous reslizumab treatment at 52 weeks, but it was not suitable for predicting nonresponse. A positive score at 16 weeks should encourage continued treatment, and a negative score should prompt close monitoring to determine whether discontinuation is warranted.
RACK1 Promotes Self-Renewal and Chemoresistance of Cancer Stem Cells in Human Hepatocellular Carcinoma through Stabilizing Nanog
Authors: Junxia Cao, Min Zhao, Jian Liu, Xueying Zhang, Yujun Pei, Jingyang Wang, Xiao Yang, Beifen Shen, Jiyan Zhang
Journal: Theranostics (2019)

Targeting cancer stem cells (CSCs) has been proposed as a new strategy to eradicate malignancies, including hepatocellular carcinoma (HCC). However, the mechanisms by which CSCs sustain their self-renewal and chemoresistance remain elusive. Nanog is a master transcriptional regulator of stemness, especially in CSCs. Its expression is tightly regulated by the ubiquitin-proteasome system in embryonic stem cells (ESCs). Whether the suppression of Nanog ubiquitination contributes to its over-expression in CSCs has not been explored. In addition, the role of receptor for activated C kinase 1 (RACK1), an adaptor protein implicated in HCC growth, in liver CSC-like traits remains to be determined. Methods: In vitro and in vivo assays were performed to investigate the role of RACK1 in liver CSC-like phenotype and murine ESC function. How RACK1 regulates Nanog expression was explored by immunoblotting and immunohistochemistry. The interaction of RACK1 with Nanog and the consequent effects on Nanog ubiquitination and stemness were then analyzed. Results: RACK1 promotes self-renewal and chemoresistance of human liver CSCs and maintains murine ESC function. Consistently, RACK1 enhances the expression of Nanog in human HCC cells and murine ESCs. The protein levels of RACK1 in clinical HCC tissues positively correlate with those of Nanog. Further exploration indicates that RACK1 directly binds to Nanog, which prevents its recruitment of E3 ubiquitin ligase FBXW8 and ubiquitin-dependent degradation. The interaction with Nanog is essential for RACK1 to promote stemness. Conclusions: Our data provide novel insights into the regulation of Nanog protein levels, as well the key role of RACK1 to enhance self-renewal and chemoresistance of CSCs in human HCC.
Abstract 14568: Identification of Laminar Flow Regulated Non-Coding RNAs in Endothelial Cells
Authors: Katharina M Michalik, Xintian You, Anuradha Doddaballapur, Nicolas Jaé, David John, Wei Chen, Shizuka Uchida, Reinier A Boon, Stefanie Dimmeler
Journal: Circulation (2013)

Laminar flow across endothelial cells (ECs) protects against atherosclerotic lesion formation in part via activating the transcription factor KLF2. Previously, it was shown that laminar flow regula...
A Gain of Function Mutation in the NSD2 Histone Methyltransferase Drives Glucocorticoid Resistance of Acute Lymphoblastic Leukemia
Authors: Jianping Li, Catalina Troche, Alok Swaroop, Marta Kulis, Jon Oyer, Christine Will, Daphne Dupere-Richer, Alberto Riva, Crissandra Pipe, Sharon Norton, Richard Lynn Bennett, Jonathan D. Licht
Journal: Blood (2018)
Impact of Chronic Kidney Disease on Outcomes of Myocardial Revascularization in Patients With Diabetes
Authors: Michael E. Farkouh, Mandeep S. Sidhu, Maria M. Brooks, Helen Vlachos, William E. Boden, Robert L. Frye, Pamela Hartigan, F.S. Siami, Vera A. Bittner, Bernard R. Chaitman, G.B. John Mancini, Valentin Fuster
Journal: Journal of the American College of Cardiology (2019)
TCT-326 The Occupational Effects of Interventional Cardiology Results from the WIN for Safety Survey
Authors: Gill Buchanan, Alaide Chieffo, Julinda Mehilli, Ghada Mikhail, Fina Mauri, Patrizia Presbitero, Liliana Grinfeld, Anna Sonia Petronio, Kimberly Skelding, Angela Hoye, Roxana Mehran, Marie-Claude Morice
Journal: Journal of the American College of Cardiology (2012)
Abstract 17116: Incidence and Outcomes of Out-of-hospital Maternal Cardiac Arrest and Compliance With Resuscitation Guidelines
Authors: Alan A Lipowicz, Sheldon Cheskes, Sarah H Gray, Farida Jeejeebhoy, Janice Lee, Damon C Scales, Cathy Zhan, Laurie J Morrison
Journal: Circulation (2015)

Background: Published survival rates after out-of-hospital cardiac arrests (OHCA) are lower than in-hospital cardiac arrest (IHCA). Current estimates for the incidence and rate of survival for maternal cardiac arrest are published only for IHCA. There are no studies that report the incidence and outcomes of maternal OHCA. Current cardiopulmonary resuscitation guidelines contain specific maternal recommendations, although compliance with recommended benchmarks has not been reported. The objective of this study was to report maternal OHCA incidence, outcomes, and compliance with resuscitation and maternal specific guidelines. Methods: This was a population-based cohort study of consecutive maternal OHCA between May 2010 and April 2014. The denominator was estimated from the total regional population of all women of childbearing age obtained from census and age-specific pregnancy rates provided by regional health authorities. Resuscitation performance was measured against the 2010 AHA Guidelines. Results: A total of 6 maternal OHCA occurred amongst 1,085 OHCA occurring in females of child bearing age (15-49) over 4yrs; Incidence-1.85:100,000 (95% CI 1.76 to 1.95) vs. 19.4 per 100,000 (95% CI, 19.37 to 19.43). Maternal and neonatal survival to discharge was 16.7% and 33.3%, respectively. Compliance with CPR quality metrics averaged 83% with a range from 75% to 100%. Compliance with maternal-specific resuscitation guidelines averaged 46.9%, with a range from 0% to 100%. The only performance metrics with 100% compliance was intravenous line insertion above the diaphragm and prehospital activation of the maternal cardiac arrest team. Uterine displacement compliance was low at 0%. Conclusion: The incidence of maternal OHCA was 1.85:100,000, which is lower than the published estimate for maternal IHCA. Survival after OHCA for mother and for child was higher than OHCA occurring in non-pregnant adult females of child bearing age; however, the number of survivors was small (&lt;5). Compliance rates with recommended resuscitation guidelines were high, yet compliance with maternal-specific guidelines were low suggesting targeted training and implementation optimization at the point of care is required to prepare for this rare event involving two lives.
Addressing the complexity of prenatal and postnatal environmental exposures affecting childhood lung function
Authors: Urs Frey, Jakob Usemann
Journal: The Lancet Planetary Health (2019)

Environmental pollution affects morbidity and mortality in children aged 0–5 years, not only in developed countries, but also in low-income and middle-income countries in particular.1 However, environmental exposures during this period of increased susceptibility in infants and children might have long-lasting effects that are often underestimated. Air pollution exposure during pregnancy is associated with reduced postnatal lung function,2 and several studies also show a sustained effect of prenatal air pollution exposure on lung function at age 5 weeks up to age 11 years.
Unexpected Low Expression of Platelet Fibrinogen Receptor in Patients with Chronic Myeloproliferative Neoplasms: How Does It Change with Aspirin?
Authors: Alessandro Lucchesi, Silvia Carloni, Martina Ghetti, Serena De Matteis, Gerardo Musuraca, Accursio Fabio Augello, Pier Paolo Fattori, Giovanni Martinelli, Roberta Napolitano
Journal: Blood (2018)
Whole-Body Staging of Metastatic Atypical Meningioma Using 68Ga-DOTATATE PET/CT
Authors: Marcus Unterrainer, Harun Ilhan, Franziska Vettermann, Clemens C. Cyran, Joerg C. Tonn, Maximilian Niyazi, Peter Bartenstein, Nathalie L. Albert
Journal: Clinical Nuclear Medicine (2019)

A 43-year-old woman with suspected recurrence of atypical meningioma World Health Organization grade II presented extensive intracranial lesions with high Ga-DOTATATE uptake. Moreover, numerous Ga-DOTATATE-positive bone, lung, and liver lesions were seen. For final diagnosis, biopsies taken from a lung lesion revealed distant metastases of the atypical meningioma. This case underlines the high diagnostic power of Ga-DOTATATE PET/CT for the staging of meningioma even beyond cerebral or spinal lesions; in case of distant lesions in patients with known meningioma, differential diagnosis should also contain metastases despite their rare occurrence. Moreover, this case emphasizes radioligand therapy especially in metastatic meningioma.
Safety and Efficacy of Non-Irradiated Granulocyte Transfusions (GTX) in Neutropenic Patients with Severe or Refractory Abdominal Infections: A Single Center Retrospective Analysis of 119 Transfusions in 22 Patients
Authors: Guillaume Richard-Carpentier, Hagop M. Kantarjian, Farhad Ravandi, Tapan M. Kadia, Gautam Borthakur, Guillermo Garcia-Manero, Courtney D. DiNardo, William G. Wierda, Naval G. Daver, Naveen Pemmaraju, Prithviraj Bose, Marina Y. Konopleva, Michael Andreeff, Srdan Verstovsek, Heidi M Krause, Fleur M. Aung, Jorge E. Cortes
Journal: Blood (2018)
Opioid Prescribing Limits for Acute Pain
Authors: Kao-Ping Chua, Chad M. Brummett, Jennifer F. Waljee
Journal: JAMA (2019)

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Enhanced Therapeutic Effect of RGD-Modified Polymeric Micelles Loaded With Low-Dose Methotrexate and Nimesulide on Rheumatoid Arthritis
Authors: Yunlong Wang, Zhongbing Liu, Ting Li, Lin Chen, Jiayao Lyu, Chunhong Li, Yan Lin, Na Hao, Meiling Zhou, Zhirong Zhong
Journal: Theranostics (2019)

Angiogenesis plays an essential role in the progression of rheumatoid arthritis (RA). RGD peptide shows high affinity and selectivity for integrin αvβ3, which is one of the most extensively examined target of angiogenesis. Nimesulide could improve the anti-rheumatic profile of methotrexate. But the clinical application was limited due to water-insolubility of both methotrexate and nimesulide and lacking targeting ability. Therefore, this study aimed to design a targeted drug delivery system of micelles mediated by RGD plus the passive targeting of micelles to solve the application problems of methotrexate and nimesulide (M/N), and thus enhance their combined therapeutic effect on RA. Methods: RGD was conjugated with NHS-PEG-PLA to form RGD-PEG-PLA for the preparation of RGD-modified drug-loaded micelles (R-M/N-PMs). The size and zeta potential of micelles were measured by dynamic light scattering. Morphology was detected by transmission electron microscopy. The inhibition effect of R-M/N-PMs on angiogenesis was assessed by the chick chorioallantoic membrane assay. The real-time fluorescence imaging analysis was conducted to examine the in vivo distribution of the fluorescence-labeled R-M/N-PMs. Rats arthritis model induced by Freund's adjuvant was used to evaluate the in vivo anti-inflammatory efficacy of R-M/N-PMs. Results: The in vitro study indicated successful development of R-M/N-PMs. R-M/N-PMs could markedly suppress the angiogenesis of chick embryos. The fluorescence-labeled R-M/N-PMs mainly accumulated in arthritic joints. RGD enhanced the targeting ability of micelles and thus promoted retention of micelles in arthritic joints. Moreover, R-M/N-PMs significantly alleviated the joint swelling while reducing bone erosion and serum levels of inflammatory cytokines. It helped to recover the bone microstructure of arthritic rats. Conclusion: Our results confirmed that the targeted delivery of the combination of a low dose of methotrexate and nimesulide mediated by RGD-modified polymeric micelles could enhance the therapeutic effect on rheumatoid arthritis. These findings provide a promising potential for the clinical therapy of rheumatoid arthritis.
The gastric cancer survivorship experience: A global perspective.
Authors: Martha Ann Raymond, Craig Lustig
Journal: Journal of Clinical Oncology (2019)

24 Background: The World Health Organization estimates 1.03 million new gastric cancer cases will be diagnosed in 2018. Globally, gastric cancer is the 5th most common cancer and the 3rd most common cause of cancer death. Our study explores the gastric cancer survivorship experience throughout the care continuum. Methods: The Ruesch Center for the Cure of Gastrointestinal Cancers and the GI Cancers Alliance developed a global gastric cancer advocacy initiative (December 2017) to better understand the patient experience. As convener, we facilitated numerous meetings with international advocacy organizations; healthcare professionals; patients and caregivers to gain a global perspective. Based on our goal to help improve patient outcomes, our initiative included analysis to support: efforts to increase earlier detection; provide access to best treatment protocols including clinical trials; enhanced patient education and patient-centered communication. A key element of our research began with a global patient survey, focus groups and interviews. Results: 521 gastric cancer patients (54% female 46% male) participated in the international survey (April-May 2018). 49% indicated a ‘poor’ quality of life; 91% indicated survivorship care gaps; 42% were Stage 4. North and South America, Europe, Asia, and Australia were represented. Follow-up interviews and focus groups (July-September 2018) provided valuable insight and a greater understanding of the patient profile. Conclusions: Additional educational and supportive services are needed to meet patient unmet needs. We will continue providing key stakeholder platforms to address patient concerns; create meaningful and relevant patient education; continue outreach leading to increased patient empowerment; convene and work with global partners improving patient quality of life to ultimately achieve better patient outcomes.
Abstract 16639: Long-Term Outcome of Pulmonary Vein Isolation With and Without Focal Impulse and Rotor Modulation (FIRM) Mapping: Results From a Meta-Analysis
Authors: Sanghamitra Mohanty, Prasant Mohanty, Carola Gianni, Chintan Trivedi, Domenico G Della Rocca, Luigi Di Biase, Andrea Natale
Journal: Circulation (2017)

Background: This meta-analysis systematically evaluated the outcome of pulmonary vein isolation (PVI) with and without FIRM ablation. Methods: An extensive literature search was performed on databa...