tbuckley/cabot-search huggingface dataset:
Heat-Stable Carbetocin versus Oxytocin to Prevent Hemorrhage after Vaginal Birth
Authors: Mariana Widmer, Gilda Piaggio, Thi M.H. Nguyen, Alfred Osoti, Olorunfemi O. Owa, Sujata Misra, Arri Coomarasamy, Hany Abdel-Aleem, Ashalata A. Mallapur, Zahida Qureshi, Pisake Lumbiganon, Archana B. Patel, Guillermo Carroli, Bukola Fawole, Shivaprasad S. Goudar, Yeshita V. Pujar, James Neilson, G. Justus Hofmeyr, Lin L. Su, Jose Ferreira de Carvalho, Uma Pandey, Kidza Mugerwa, Shobha S. Shiragur, Josaphat Byamugisha, Daniel Giordano, A. Metin Gülmezoglu
Journal: New England Journal of Medicine (2018)

Postpartum hemorrhage is the most common cause of maternal death. Oxytocin is the standard therapy for the prevention of postpartum hemorrhage, but it requires cold storage, which is not available in many countries. In a large trial, we compared a novel formulation of heat-stable carbetocin with oxytocin.We enrolled women across 23 sites in 10 countries in a randomized, double-blind, noninferiority trial comparing intramuscular injections of heat-stable carbetocin (at a dose of 100 μg) with oxytocin (at a dose of 10 IU) administered immediately after vaginal birth. Both drugs were kept in cold storage (2 to 8°C) to maintain double-blinding. There were two primary outcomes: the proportion of women with blood loss of at least 500 ml or the use of additional uterotonic agents, and the proportion of women with blood loss of at least 1000 ml. The noninferiority margins for the relative risks of these outcomes were 1.16 and 1.23, respectively.A total of 29,645 women underwent randomization. The frequency of blood loss of at least 500 ml or the use of additional uterotonic agents was 14.5% in the carbetocin group and 14.4% in the oxytocin group (relative risk, 1.01; 95% confidence interval [CI], 0.95 to 1.06), a finding that was consistent with noninferiority. The frequency of blood loss of at least 1000 ml was 1.51% in the carbetocin group and 1.45% in the oxytocin group (relative risk, 1.04; 95% CI, 0.87 to 1.25), with the confidence interval crossing the margin of noninferiority. The use of additional uterotonic agents, interventions to stop bleeding, and adverse effects did not differ significantly between the two groups.Heat-stable carbetocin was noninferior to oxytocin for the prevention of blood loss of at least 500 ml or the use of additional uterotonic agents. Noninferiority was not shown for the outcome of blood loss of at least 1000 ml; low event rates for this outcome reduced the power of the trial. (Funded by Merck Sharpe & Dohme; CHAMPION Australian New Zealand Clinical Trials Registry number, ACTRN12614000870651 ; EudraCT number, 2014-004445-26 ; and Clinical Trials Registry-India number, CTRI/2016/05/006969 .).
ESPACOMP Medication Adherence Reporting Guideline (EMERGE)
Authors: Sabina De Geest, Leah L. Zullig, Jacqueline Dunbar-Jacob, Remon Helmy, Dyfrig A. Hughes, Ira B. Wilson, Bernard Vrijens
Journal: Annals of Internal Medicine (2018)

Research on assessing or managing medication adherence applies approaches from observational, interventional, and implementation science that spans many disciplines and demands coherent conceptualization, valid methods, appropriate analyses, and complete and accurate reporting. To ensure such reporting, the European Society for Patient Adherence, COMpliance, and Persistence (ESPACOMP) Medication Adherence Reporting Guideline (EMERGE) recommends standard reporting approaches based on an accepted taxonomy. This guideline is derived from a literature review, a reactive Delphi study with 26 medication adherence experts from many countries and disciplines, and feedback from ESPACOMP members. It is designed to supplement existing guidelines for health research reporting and is structured around 4 minimum reporting criteria and 17 items reflecting best reporting practice. By enhancing and harmonizing research reporting, EMERGE aims to advance research and, ultimately, patient outcomes.
Abstract 9363: Intervention for Re-coarctation in the Single Ventricle Reconstruction Trial: Incidence, Risk and Outcomes
Authors: Kevin D Hill, John F Rhodes, Ranjit Aiyagari, G. H Baker, Lisa Bergersen, Paul J Chai, Gregory A Fleming, J. C Fudge, Matthew J Gillespie, Robert G Gray, Russel Hirsch, Kyong-Jin Lee, Jennifer S Li, Richard G Ohye, Matthew E Oster, Sara K Pasquali, Andrew M Pelech, Wolfgang A Radtke, Cheryl M Takao, Julie A Vincent, Christoph P Hornik
Journal: Circulation (2012)

Hill Kevin D 2012 Finalist and Presenting Author
Effectiveness of Live Attenuated vs Inactivated Influenza Vaccines in Children During the 2012-2013 Through 2015-2016 Influenza Seasons in Alberta, Canada
Authors: Sarah A. Buchan, Stephanie Booth, Allison N. Scott, Kimberley A. Simmonds, Lawrence W. Svenson, Steven J. Drews, Margaret L. Russell, Natasha S. Crowcroft, Mark Loeb, Bryna F. Warshawsky, Jeffrey C. Kwong
Journal: JAMA Pediatrics (2018)

<h3>Importance</h3> Recent observational studies report conflicting results regarding the effectiveness of live attenuated influenza vaccine (LAIV), particularly against influenza A(H1N1)pdm09. <h3>Objective</h3> To compare the effectiveness of LAIV and inactivated influenza vaccine (IIV) against laboratory-confirmed influenza. <h3>Design, Setting, and Participants</h3> A test-negative study to estimate influenza vaccine effectiveness (VE) using population-based, linked, individual-level laboratory, health administrative, and immunization data. Data were obtained from 10 169 children and adolescents aged 2 to 17 years (children) who were tested for influenza in inpatient or outpatient settings during periods when influenza was circulating based on a threshold level of 5% weekly test positivity for the province during the 4 influenza seasons spanning from November 11, 2012, to April 30, 2016, in Alberta, Canada. Logistic regression was used to estimate VE by vaccine type, influenza season, and influenza type and subtype. The relative effectiveness of each vaccine type was assessed by comparing the odds of laboratory-confirmed influenza infection for LAIV recipients with that for IIV recipients. <h3>Exposures</h3> The primary exposure was receipt of LAIV or IIV before testing for influenza. <h3>Main Outcomes and Measures</h3> The primary outcome was influenza case status as determined by reverse-transcriptase polymerase chain reaction testing. <h3>Results</h3> A total of 10 779 respiratory specimens (from 10 169 children) collected and tested for influenza during the 4 influenza seasons were included, with 53.4% from males; the mean (SD) age was 7.0 (4.6) years. Across the 4 influenza seasons, 3161 children tested positive for influenza. Combining the 4 influenza seasons, the adjusted VE against influenza A(H1N1)pdm09 was 69% (95% CI, 56%-78%) for LAIV compared with 79% (95% CI, 70%-86%) for IIV. Vaccine effectiveness against influenza A(H3N2) was 36% (95% CI, 14%-53%) for LAIV and 43% (95% CI, 22%-59%) for IIV. Against influenza B, VE was 74% (95% CI, 62%-82%) for LAIV and 56% (95% CI, 41%-66%) for IIV. There were no significant differences in the odds of influenza infection for LAIV recipients compared with IIV recipients except for influenza B during the 2015-2016 season, when LAIV recipients had lower odds of infection than IIV recipients (odds ratio, 0.36; 95% CI, 0.17-0.76). <h3>Conclusions and Relevance</h3> There was no evidence to support the lack of effectiveness of LAIV against influenza A(H1N1)pdm09. These results support administration of either vaccine type in this age group.
Abstract 12681: Secretory Factor(s) Derived From Human Pulmonary Artery Endothelial Cells Induce Pseudo-hypoxic Activation of HIF-1α Signaling and Metabolic Reprogramming in Human Pulmonary Artery Smooth Muscle Cells
Authors: Wusheng Xiao, William Oldham, Joseph Loscalzo
Journal: Circulation (2016)

Cell-cell communication is required for maintaining physiological functions of the vasculature, and is also involved in the development of vascular disorders, including pulmonary arterial hypertension. Yet, how heterologous cell-cell crosstalk influences cellular metabolism in pulmonary vascular cells is not well understood. Objective: We studied how the interaction of heterologous pulmonary vascular cells regulates vascular metabolism. Methods and Results: Human pulmonary artery endothelial cells (PAEC) and smooth muscle cells (PASMC) were cultured in a transwell coculture system with or without conditioned medium (CM) under ambient oxygen levels. Results from the Seahorse XF24 analyzer showed an increase in extracellular acidification rate (indicative of glycolysis), and a decrease in oxygen consumption rate (indicative of mitochondrial respiration) in PASMC cultured in CM from PAEC, suggesting a metabolic shift toward glycolysis induced by an endothelial product. This metabolic shift correlated with activation of HIF-1α signaling, as demonstrated by normoxic stabilization of HIF-1α protein and upregulation of its target gene expression ( GLUT1 , HK2 , and PDK1 ) in PASMC. Interestingly, these effects were not observed in PAEC cultured with PASMC or in CM from PASMC. We also found that HIF-1α stabilization is independent of its transcription and of the protein levels of prolyl hydroxylase domain protein 2 (PHD2) and pVHL; however, PHD activity decreased in PASMC cultured in CM from PAEC, suggesting that factor(s) secreted by PAEC could suppress PHD activity in PASMC. To identify the potential factor(s), CM from PAEC were pretreated by heat inactivation or with proteinase K and fractionated by filtration column. Results from these experiments suggested that the inhibitor(s) is(are) a small molecule (&lt;10 kDa). We then tested known PHD inhibitors and found that pyruvate, succinate, fumarate, lactate, glutamate, and reactive oxygen species were unlikely to be the mediators. Overall, our study indicates that cellular metabolism of PASMC can be reprogrammed by PAEC through a paracrine mechanism. These results may provide novel insights into mechanisms of vascular cell-cell crosstalk and its consequences for vascular metabolism and disease.
Abstract 3112: Distinct oncogenic events induce different DNA methylation and copy number changes in human mammary epithelial cells
Authors: Stan P. du manoir, Claire Fonti, Anne Saumet, Amanda Abi-Khalil, Béatrice Orsetti, Cleroux Elouan, Ambre Bender, Michael Dumas, Jacques Colinge, Michael Weber, Charles Theillet
Journal: Cancer Research (2018)

Abstract Gene expression differences, combined with distinct patterns of genomic rearrangements and epigenetic modifications constitute the bases of molecular classification of breast cancer. Molecular subtypes may originate from different cell lineages in the mammary gland, but also from the early activation of oncogenes that may drive the establishment of these molecular subtypes. However, in the natural history of human cancer, it is difficult to discriminate between these two factors : cell lineage and initial oncogenic alterations. In this work, we designed an experimental strategy aiming at determining whether activation of distinct oncogenic pathways in human mammary epithelial cells (HMEC) could lead to different patterns of genetic and epigenetic changes. We show that initial activation of CCNE1, WNT1 and RASv12 in shp53 immortalized HMECs results in different and reproducible profiles of mRNA and miR expression, copy number alterations (CNA) and DNA methylation modifications. Interestingly, first the extend of CNA measured as fraction of the genome altered was lower in HMECs transformed by RAS than CCNE1 and WNT1 transformed HMECs revealing a lower genetic instability. This was confirmed by less numerous γH2Ax and 53BP1 nuclear foci in HMECs transformed by RAS. Second, HMECs transformed by RAS bore specific profiles of CNAs and DNA methylation, clearly distinct of those shown by CCNE1 and WNT1 transformed HMECs. Genes differentially expressed in the RAS and the CCNE1/WNT1 clusters and included in CNAs or with variable CpG methylation were mostly different, depicting the activation of distinct signaling pathways in these two clusters. These data indicate that early activation of distinct oncogenic pathways may leads to adaptive events resulting in specific pattern of CNAs and DNA methylation changes. We postulated that the early activation of oncogenes may be an important determinant of the establishment of breast cancer molecular subtypes along with cell lineage origin. Citation Format: Stan P. du manoir, Claire Fonti, Anne Saumet, Amanda Abi-Khalil, Béatrice Orsetti, Cleroux Elouan, Ambre Bender, Michael Dumas, Jacques Colinge, Michael Weber, Charles Theillet. Distinct oncogenic events induce different DNA methylation and copy number changes in human mammary epithelial cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3112.
High Diabetes Distress Among Ethnic Minorities Is Not Explained by Metabolic, Cardiovascular, or Lifestyle Factors: Findings From the Dutch Diabetes Pearl Cohort
Authors: Behiye Özcan, Femke Rutters, Frank J. Snoek, Mandy Roosendaal, Eric J. Sijbrands, Petra J.M. Elders, Frits Holleman, Hanno Pijl, Cees J. Tack, Evertine J. Abbink, Harold W. de Valk, Bruce H.R. Wolffenbuttel, Coen D.A. Stehouwer, Nicholas C. Schaper, Jacqueline M. Dekker, Miranda T. Schram
Journal: Diabetes Care (2018)

OBJECTIVE Diabetes distress among patients from ethnic minorities is still poorly understood. We investigated the association between ethnicity and diabetes distress among ethnic minority groups of people with type 2 diabetes in the Netherlands, focusing on the possible effects of glycemic control, lifestyle factors, cardiovascular risk factors, and diabetes complications. RESEARCH DESIGN AND METHODS Cross-sectional data from the Dutch Diabetes Pearl cohort included people with type 2 diabetes from primary, secondary, and tertiary diabetes care programs. We used the 20-item Problem Areas in Diabetes Survey (PAID) scale to assess diabetes distress; a score ≥40 is considered to represent high distress. Ethnicity was estimated on the basis of country of birth. Sociodemographic and lifestyle data were self-reported; cardiovascular and metabolic data were retrieved from medical charts. Logistic regression analysis determined the association between ethnicity and diabetes distress, with Caucasians as the reference group. RESULTS Diabetes distress scores and ethnicity were available for 4,191 people with type 2 diabetes: 3,684 were Caucasian, 83 were Asian, 51 were Moroccan, 92 were African, 134 were Latin American, 46 were Turkish, and 101 were Hindustani-Surinamese. Overall, participants in minority groups had worse health outcomes than those of Caucasian descent, and diabetes distress was more prevalent (ranging from 9.6 to 31.7%, compared with 5.8% among Caucasians), even after adjusting for age, sex, education level, alcohol use, smoking, BMI, lipid profile, HbA1c, medication use, and the presence of diabetes complications. CONCLUSIONS Among people with type 2 diabetes in the Netherlands, ethnicity is independently associated with high diabetes distress. Further research is warranted to explain the higher prevalence of diabetes distress in minority groups and to develop effective interventions.
Mutation burden and other molecular markers of prognosis in colorectal cancer treated with curative intent: results from the QUASAR 2 clinical trial and an Australian community-based series
Authors: Enric Domingo, Carme Camps, Pamela J Kaisaki, Marie J Parsons, Dmitri Mouradov, Melissa M Pentony, Seiko Makino, Michelle Palmieri, Robyn L Ward, Nicholas J Hawkins, Peter Gibbs, Hanne Askautrud, Dahmane Oukrif, Haitao Wang, Joe Wood, Evie Tomlinson, Yasmine Bark, Kulvinder Kaur, Elaine C Johnstone, Claire Palles, David N Church, Marco Novelli, Havard E Danielsen, Jon Sherlock, David Kerr, Rachel Kerr, Oliver Sieber, Jenny C Taylor, Ian Tomlinson
Journal: The Lancet. Gastroenterology & hepatology (2018)

Molecular indicators of colorectal cancer prognosis have been assessed in several studies, but most analyses have been restricted to a handful of markers. We aimed to identify prognostic biomarkers for colorectal cancer by sequencing panels of multiple driver genes.
Identification of genomic and molecular traits that present therapeutic vulnerability to HGF-targeted therapy in glioblastoma
Authors: Jason K Sa, Sung Heon Kim, Jin-Ku Lee, Hee Jin Cho, Yong Jae Shin, Hyemi Shin, Harim Koo, Donggeon Kim, Mijeong Lee, Wonyoung Kang, Sung Hee Hong, Jung Yong Kim, Young-Whan Park, Seong-Won Song, Song-Jae Lee, Kyeung Min Joo, Do-Hyun Nam
Journal: Neuro-Oncology (2018)

Cancer is a complex disease with profound genomic alterations and extensive heterogeneity. Recent studies on large-scale genomics have shed light on the impact of core oncogenic pathways, which are frequently dysregulated in a wide spectrum of cancer types. Aberrant activation of the hepatocyte growth factor (HGF) signaling axis has been associated with promoting various oncogenic programs during tumor initiation, progression, and treatment resistance. As a result, HGF-targeted therapy has emerged as an attractive therapeutic approach. However, recent clinical trials involving HGF-targeted therapies have demonstrated rather disappointing results. Thus, an alternative, in-depth assessment of new patient stratification is necessary to shift the current clinical course.To address such challenges, we have evaluated the therapeutic efficacy of YYB-101, an HGF-neutralizing antibody, in a series of primary glioblastoma stem cells (GSCs) both in vitro and in vivo. Furthermore, we performed genome and transcriptome analysis to determine genetic and molecular traits that exhibit therapeutic susceptibility to HGF-mediated therapy.We have identified several differentially expressed genes, including MET, KDR, and SOX3, which are associated with tumor invasiveness, malignancy, and unfavorable prognosis in glioblastoma patients. We also demonstrated the HGF-MET signaling axis as a key molecular determinant in GSC invasion, and we discovered that a significant association in HGF expression existed between mesenchymal phenotype and immune cell recruitment.Upregulation of MET and mesenchymal cellular state are essential in generating HGF-mediated therapeutic responses. Our results provide an important framework for evaluating HGF-targeted therapy in future clinical settings.
Chinese expert consensus on echelons treatment of pelvic fractures in modern war
Authors: Zhao-wen Zong, Si-xu Chen, Hao Qin, Hua-ping Liang, Lei Yang, Yu-feng Zhao
Journal: Military Medical Research (2018)

The characteristics and treatment of pelvic fractures vary between general conditions and modern war. An expert consensus has been reached based on pelvic injury epidemiology and the concepts of battlefield treatment combined with the existing levels of military medical care in modern warfare. According to this consensus, first aid, emergency treatment and early treatment of pelvic fractures are introduced in three separate levels. In Level I facilities, simple triage and rapid treatment following the principles of advanced trauma life support are recommended to evaluate combat casualties during the first-aid stage. Re-evaluation, further immobilization and fixation, and hemostasis are recommended at Level II facilities. At Level III facilities, the main components of damage control surgery are recommended, including comprehensive hemostasis, a proper resuscitation strategy, the treatment of concurrent visceral and blood vessel damage, and battlefield intensive care. The grading standard for evidence evaluation and recommendation was used to reach this expert consensus.
Reduction of CD83 Expression on B Cells and the Genetic Basis for Rheumatoid Arthritis: Comment on the Article by Thalayasingam et al
Authors: Yumi Tsuchida, Shuji Sumitomo, Mineto Ota, Haruka Tsuchiya, Yasuo Nagafuchi, Hirofumi Shoda, Keishi Fujio, Kazuyoshi Ishigaki, Kensuke Yamaguchi, Akari Suzuki, Yuta Kochi, Kazuhiko Yamamoto
Journal: Arthritis & Rheumatology (2018)
Characteristics and Outcomes of Surgical Patients With Solid Cancers Admitted to the Intensive Care Unit
Authors: Kathryn Puxty, Philip McLoone, Tara Quasim, Billy Sloan, John Kinsella, David S. Morrison
Journal: JAMA Surgery (2018)

<h3>Importance</h3> Within the surgical population admitted to intensive care units (ICUs), cancer is a common condition. However, clinicians can be reluctant to admit patients with cancer to ICUs owing to concerns about survival. <h3>Objective</h3> To compare the clinical characteristics and outcomes of surgical patients with and without cancer who are admitted to ICUs. <h3>Design, Setting, and Participants</h3> An observational retrospective cohort study using ICU audit records linked to hospitalization discharge summaries, cancer registrations, and death records of all 16 general adult ICUs in the West of Scotland was conducted. All 25 017 surgical ICU admissions between January 1, 2000, and December 31, 2011, were included, and data analysis was conducted during that time. <h3>Exposures</h3> Patients were dichotomized based on a diagnosis of a solid malignant tumor as determined by its documentation in the Scottish Cancer Registry within the 2 years prior to ICU admission. <h3>Main Outcomes and Measures</h3> Intensive care unit patients with cancer were compared with ICU patients without cancer in terms of patient characteristics (age, sex, severity of illness, reason for admission, and organ support) and survival (ICU, hospital, 6 months, and 4 years). <h3>Results</h3> Within the 25 017 surgical ICU patients, 13 684 (54.7%) were male, the median (interquartile range [IQR]) age was 64 (50-74), and 5462 (21.8%) had an underlying solid tumor diagnosis. Patients with cancer were older (median [IQR] age, 68 [60-76] vs 62 [45-74] years;<i>P</i> &lt; .001) with a higher proportion of elective hospitalizations (60.5% vs 19.8%;<i>P</i> &lt; .001), similar Acute Physiology and Chronic Health Evaluation II scores (median for both, 17), but lower use of multiorgan support (57.9% vs 66.7%;<i>P</i> &lt; .001). Intensive care unit and hospital mortality were lower for the cancer group, at 12.2% (95% CI, 11.3%-13.1%) vs 16.8% (95% CI, 16.3%-17.4%) (<i>P</i> &lt; .001) and 22.9% (95% CI, 21.8%-24.1%) vs 28.1% (27.4%-28.7%) (<i>P</i> &lt; .001). Patients with cancer had an adjusted odds ratio for hospital mortality of 1.09 (95% CI, 1.00-1.19). By 6 months, mortality in the cancer group was higher than that in the noncancer group at 31.3% compared with 28.2% (<i>P</i> &lt; .001). Four years after ICU admission, mortality for those with and without cancer was 60.9% vs 39.7% (<i>P</i> &lt; .001) respectively. <h3>Conclusions and Relevance</h3> Cancer is a common diagnosis among surgical ICU patients and this study suggests that initial outcomes compare favorably with those of ICU patients with other conditions. Consideration that a diagnosis of cancer should not preclude admission to the ICU in patients with surgical disease is suggested.
Endoscopic submucosal dissection with triangulated traction with clip and rubber band: the “wallet” strategy
Authors: Alexandru Lupu, Jérémie Jacques, Jérôme Rivory, Florian Rostain, Frédéric Pontette, Thierry Ponchon, Mathieu Pioche
Journal: Endoscopy (2018)

Endoscopic submucosal dissection (ESD) is the reference method for the curative endoscopic resection of colorectal tumors [1] [2]. Nevertheless, it is technically challenging, and new strategies to facilitate the procedure are requested. Counter-traction strategies, such as the clip and rubber band approaches, allow the enlargement of the submucosal space [3] [4]. In the colon, line traction makes a tangential traction without triangulation, and is not really adaptive as the dissection progresses [5]. We report a case of ESD for a colonic laterally spreading tumor in a patient with a history of pancolonic ulcerative colitis.