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Failure to rescue

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https://www.readbyqxmd.com/read/28549671/the-outcome-of-extracorporeal-life-support-after-general-thoracic-surgery-timing-of-application
#1
Heemoon Lee, Yang Hyun Cho, Hyoung Woo Chang, Ji-Hyuk Yang, Jong Ho Cho, Kiick Sung, Young Tak Lee
BACKGROUND: Extracorporeal life support (ECLS) is widely used in refractory cardiac or pulmonary failure. Because complications of general thoracic surgery frequently involve the heart or lungs, ECLS can be a useful option. Therefore, we retrospectively reviewed our experience with ECLS after general thoracic surgery. METHODS: There were 17,185 adult general thoracic surgery procedures between 2005 and 2013 at our institution, including resection of the lung (n = 10,434; 60...
May 24, 2017: Annals of Thoracic Surgery
https://www.readbyqxmd.com/read/28543100/syndecan-1-limits-the-progression-of-liver-injury-and-promotes-liver-repair-in-acetaminophen-induced-liver-injury
#2
Eon Jeong Nam, Kazutaka Hayashida, Rafael S Aquino, John R Couchman, Rosemary A Kozar, Jian Liu, Pyong Woo Park
Accidental or intentional misuse of acetaminophen (APAP) is the leading cause of acute liver failure in the Western world. While mechanisms that trigger APAP-induced liver injury are well known, those that halt the progression of APAP liver disease and facilitate liver recovery are less understood. Heparan sulfate proteoglycans (HSPGs) bind to and regulate various tissue injury factors through their heparan sulfate (HS) chains, but the importance of HSPGs in liver injury in vivo remains unknown. Here, we examined the role of syndecan-1, the major cell surface HSPG of hepatocytes, in APAP-induced liver injury...
May 22, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28542524/ectopically-expressed-slc34a2a-sense-antisense-transcripts-cause-a-cerebellar-phenotype-in-zebrafish-embryos-depending-on-rna-complementarity-and-dicer
#3
Monica J Piatek, Victoria Henderson, Amy Fearn, Bill Chaudhry, Andreas Werner
Natural antisense transcripts (NATs) are complementary to protein coding genes and potentially regulate their expression. Despite widespread occurrence of NATs in the genomes of higher eukaryotes, their biological role and mechanism of action is poorly understood. Zebrafish embryos offer a unique model system to study sense-antisense transcript interplay at whole organism level. Here, we investigate putative antisense transcript-mediated mechanisms by ectopically co-expressing the complementary transcripts during early zebrafish development...
2017: PloS One
https://www.readbyqxmd.com/read/28542158/identifying-pathogenicity-of-human-variants-via-paralog-based-yeast-complementation
#4
Fan Yang, Song Sun, Guihong Tan, Michael Costanzo, David E Hill, Marc Vidal, Brenda J Andrews, Charles Boone, Frederick P Roth
To better understand the health implications of personal genomes, we now face a largely unmet challenge to identify functional variants within disease-associated genes. Functional variants can be identified by trans-species complementation, e.g., by failure to rescue a yeast strain bearing a mutation in an orthologous human gene. Although orthologous complementation assays are powerful predictors of pathogenic variation, they are available for only a few percent of human disease genes. Here we systematically examine the question of whether complementation assays based on paralogy relationships can expand the number of human disease genes with functional variant detection assays...
May 25, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28538625/a-metric-of-our-own-failure-to-rescue-after-trauma
#5
Daniel N Holena, Elinore J Kaufman, M Kit Delgado, Douglas J Wiebe, Brendan G Carr, Jason D Christie, Patrick M Reilly
BACKGROUND: Failure to rescue (FTR) is defined as death after an adverse event. The original metric was derived in elective surgical populations and reclassifies deaths not preceded by recorded adverse events as FTR cases under the assumption these deaths resulted from missed adverse events. This approach lacks face validity in trauma because patients often die without adverse events as a direct result of injury. Another common approach simply excludes deaths without recorded adverse events, but this approach reduces the reliability of the FTR metric...
May 22, 2017: Journal of Trauma and Acute Care Surgery
https://www.readbyqxmd.com/read/28538237/update-on-postnatal-steroids
#6
Henry L Halliday
Antenatal steroid treatment to enhance fetal lung maturity and surfactant treatment to prevent or treat respiratory distress syndrome have been major advances in perinatal medicine in the past 40 years contributing to improved outcomes for preterm infants. Use of postnatal steroids to prevent or treat chronic lung disease in preterm infants has been less successful and associated with adverse neurodevelopmental outcomes. Although early (in the first week of life) postnatal steroid treatment facilitates earlier extubation and reduces the risk of chronic lung disease, it is associated with adverse effects, such as hyperglycemia, hypertension, gastrointestinal bleeding and perforation, hypertrophic cardiomyopathy, growth failure, and cerebral palsy, and cannot be recommended...
2017: Neonatology
https://www.readbyqxmd.com/read/28535186/fxr-gankyrin-axis-is-involved-in-development-of-pediatric-liver-cancer
#7
Leila Valanejad, Kyle Lewis, Mary Wright, Yanjun Jiang, Amber D'Souza, Rebekah Karns, Rachel Sheridan, Anita Gupta, Kevin Bove, David Witte, James Geller, Gregory Tiao, David L Nelson, Lubov Timchenko, Nikolai Timchenko
The development of hepatoblastoma (HBL) is associated with failure of hepatic stem cells (HSC) to differentiate into hepatocytes. Despite intensive investigations, mechanisms of the failure of HSC to differentiate are not known. We found that oncogene Gankyrin (Gank) is involved in the inhibition of differentiation of HSC via triggering degradation of tumor suppressor proteins (TSPs) Rb, p53, C/EBPα and HNF4α. Our data show that the activation of a repressor of Gank, farnesoid X receptor, FXR, after initiation of liver cancer by Diethylnitrosamine (DEN) prevents the development of liver cancer by inhibiting Gank and rescuing tumor suppressor proteins...
May 23, 2017: Carcinogenesis
https://www.readbyqxmd.com/read/28533404/repression-of-phosphatidylinositol-transfer-protein-%C3%AE-ameliorates-the-pathology-of-duchenne-muscular-dystrophy
#8
Natassia M Vieira, Janelle M Spinazzola, Matthew S Alexander, Yuri B Moreira, Genri Kawahara, Devin E Gibbs, Lillian C Mead, Sergio Verjovski-Almeida, Mayana Zatz, Louis M Kunkel
Duchenne muscular dystrophy (DMD) is a progressive muscle wasting disease caused by X-linked inherited mutations in the DYSTROPHIN (DMD) gene. Absence of dystrophin protein from the sarcolemma causes severe muscle degeneration, fibrosis, and inflammation, ultimately leading to cardiorespiratory failure and premature death. Although there are several promising strategies under investigation to restore dystrophin protein expression, there is currently no cure for DMD, and identification of genetic modifiers as potential targets represents an alternative therapeutic strategy...
May 22, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28527830/crispr-cas9-mediated-precise-targeted-integration-in-vivo-using-a-double-cut-donor-with-short-homology-arms
#9
Xuan Yao, Xing Wang, Junlai Liu, Xinde Hu, Linyu Shi, Xiaowen Shen, Wenqin Ying, Xinyao Sun, Xin Wang, Pengyu Huang, Hui Yang
Precisely targeted genome editing is highly desired for clinical applications. However, the widely used homology-directed repair (HDR)-based genome editing strategies remain inefficient for certain in vivo applications. We here demonstrate a microhomology-mediated end-joining (MMEJ)-based strategy for precisely targeted gene integration in transfected neurons and hepatocytes in vivo with efficiencies up to 20%, much higher (up to 10 fold) than HDR-based strategy in adult mouse tissues. As a proof of concept of its therapeutic potential, we demonstrate the efficacy of MMEJ-based strategy in correction of Fah mutation and rescue of Fah(-/-) liver failure mice, offering an efficient approach for precisely targeted gene therapies...
May 11, 2017: EBioMedicine
https://www.readbyqxmd.com/read/28526246/impaired-mitophagy-facilitates-mitochondrial-damage-in-danon-disease
#10
Sherin I Hashem, Anne N Murphy, Ajit S Divakaruni, Matthew L Klos, Bradley C Nelson, Emily C Gault, Teisha J Rowland, Cynthia N Perry, Yusu Gu, Nancy D Dalton, William H Bradford, Eric J Devaney, Kirk L Peterson, Kenneth L Jones, Matthew R G Taylor, Ju Chen, Neil C Chi, Eric D Adler
RATIONALE: Lysosomal associated membrane protein type-2 (LAMP-2) is a highly conserved, ubiquitous protein that is critical for autophagic flux. Loss of function mutations in the LAMP-2 gene cause Danon disease, a rare X-linked disorder characterized by developmental delay, skeletal muscle weakness, and severe cardiomyopathy. We previously found that human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) from Danon patients exhibited significant mitochondrial oxidative stress and apoptosis...
May 16, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/28525886/relationship-between-arterial-access-and-outcomes-in-st-elevation-myocardial-infarction-with-a-pharmacoinvasive-versus-primary-percutaneous-coronary-intervention-strategy-insights-from-the-strategic-reperfusion-early-after-myocardial-infarction-stream-study
#11
Jay Shavadia, Robert Welsh, Anthony Gershlick, Yinggan Zheng, Kurt Huber, Sigrun Halvorsen, Phillipe G Steg, Frans Van de Werf, Paul W Armstrong
BACKGROUND: The effectiveness of radial access (RA) in ST-elevation myocardial infarction (STEMI) has been predominantly established in primary percutaneous coronary intervention (pPCI) with limited exploration of this issue in the early postfibrinolytic patient. The purpose of this study was to compare the effectiveness and safety of RA versus femoral (FA) access in STEMI undergoing either a pharmacoinvasive (PI) strategy or pPCI. METHODS AND RESULTS: Within STrategic Reperfusion Early After Myocardial Infarction (STREAM), we evaluated the relationship between arterial access site and primary outcome (30-day composite of death, shock, congestive heart failure, or reinfarction) and major bleeding according to the treatment strategy received...
June 13, 2016: Journal of the American Heart Association
https://www.readbyqxmd.com/read/28522904/importance-of-antimicrobial-susceptibility-testing-for-the-management-of-eradication-in-helicobacter-pylori-infection
#12
REVIEW
Nazlı Arslan, Özlem Yılmaz, Ebru Demiray-Gürbüz
The management of Helicobacter pylori (H. pylori) infection treatment differs from the common treatment protocol for other infectious diseases. Because culture- or molecular-guided approaches face several practical issues, such as the invasive procedures required to obtain gastric biopsy specimens and the lack of availability of routine laboratory testing in some places, H. pylori treatment includes the administration of two or three empirically selected antibiotics combined with a proton pump inhibitor rather than evidence-based eradication treatment...
April 28, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28522536/a-placental-growth-factor-is-silenced-in-mouse-embryos-by-the-zinc-finger-protein-zfp568
#13
Peng Yang, Yixuan Wang, Don Hoang, Matthew Tinkham, Anamika Patel, Ming-An Sun, Gernot Wolf, Mairead Baker, Huan-Chieh Chien, Kuan-Yu Nick Lai, Xiaodong Cheng, Che-Kun James Shen, Todd S Macfarlan
Insulin-like growth factor 2 (IGF2) is the major fetal growth hormone in mammals. We identify zinc finger protein 568 (ZFP568), a member of the rapidly evolving Kruppel-associated box-zinc finger protein (KRAB-ZFP) family linked primarily to silencing of endogenous retroelements, as a direct repressor of a placental-specific Igf2 transcript (designated Igf2-P0) in mice. Loss of Zfp568, which causes gastrulation failure, or mutation of the ZFP568-binding site at the Igf2-P0 promoter causes inappropriate Igf2-P0 activation...
May 19, 2017: Science
https://www.readbyqxmd.com/read/28521176/incidence-and-prognostic-significance-of-nephrotoxicity-in-patients-receiving-eshap-as-salvage-therapy-for-lymphoma
#14
Marc Sorigue, Juan-Manuel Sancho, Alberto Pineda, Olga Garcia, David Lopez, Miriam Moreno, Gustavo Tapia, Montse Batlle, Christelle Ferra, Susanna Vives, Gladys Ibarra, Evarist Feliu, Josep-Maria Ribera
Nephrotoxicity is a well-known side effect of platinum-based chemotherapy. We retrospectively assessed the incidence and prognostic impact of nephrotoxicity with ESHAP rescue chemotherapy in 74 lymphoma patients (61 aggressive lymphomas). A higher incidence of nephrotoxicity (estimated glomerular filtration rate <60mL/min) was found when ESHAP was administred on an outpatient vs. inpatient basis (14/39 vs. 4/35). Patients submitted to ASCT with renal failure had a lower overall survival (OS) than those with normal renal function (2-yr OS probability [95%CI]: 88% [77%-99%] vs...
May 4, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28518150/cycloheximide-promotes-paraptosis-induced-by-inhibition-of-cyclophilins-in-glioblastoma-multiforme
#15
Lin Wang, Justin H Gundelach, Richard J Bram
Cancer is the second leading cause of death worldwide. Current treatment strategies based on multi-agent chemotherapy and/or radiation regimens have improved overall survival in some cases. However, resistance to apoptosis often develops in cancer cells, and its occurrence is thought to contribute to treatment failure. Non-apoptotic cell death mechanisms have become of great interest, therefore, in hopes that they would bypass tumor cell resistance. Glioblastoma multiforme (GBM), a grade IV astrocytic tumor is the most frequent brain tumor in adults, and has a high rate of mortality...
May 18, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28514527/efficacy-and-safety-of-injectable-robenacoxib-for-the-treatment-of-pain-associated-with-soft-tissue-surgery-in-dogs
#16
G Friton, C Thompson, D Karadzovska, S King, J N King
BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) are used routinely to control pain and inflammation after surgery in dogs. Robenacoxib is a cyclooxygenase-2 selective NSAID. HYPOTHESIS/OBJECTIVE: Assess the clinical efficacy and safety of an injectable formulation of robenacoxib in dogs undergoing surgery. ANIMALS: Three hundred and seventeen client-owned dogs (N = 159 robenacoxib or N = 158 placebo). METHODS: In this prospective, multicenter, randomized, masked, placebo-controlled, parallel-group study, dogs received a SC injection of either robenacoxib, at a target dose of 2...
May 2017: Journal of Veterinary Internal Medicine
https://www.readbyqxmd.com/read/28512217/loss-of-the-homologous-recombination-gene-rad51-leads-to-fanconi-anemia-like-symptoms-in-zebrafish
#17
Jan Gregor Botthof, Ewa Bielczyk-Maczyńska, Lauren Ferreira, Ana Cvejic
RAD51 is an indispensable homologous recombination protein, necessary for strand invasion and crossing over. It has recently been designated as a Fanconi anemia (FA) gene, following the discovery of two patients carrying dominant-negative mutations. FA is a hereditary DNA-repair disorder characterized by various congenital abnormalities, progressive bone marrow failure, and cancer predisposition. In this report, we describe a viable vertebrate model of RAD51 loss. Zebrafish rad51 loss-of-function mutants developed key features of FA, including hypocellular kidney marrow, sensitivity to cross-linking agents, and decreased size...
May 16, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28508586/role-and-regulation-of-autophagy-and-apoptosis-by-nitric-oxide-in-hepatic-stellate-cells-during-acute-liver-failure
#18
Li Jin, Heng Gao, JiuPing Wang, ShuJuan Yang, Jing Wang, JingFeng Liu, Yuan Yang, TaoTao Yan, Tianyan Chen, Yingren Zhao, Yingli He
BACKGROUND & AIMS: We previously found that hepatic stellate cell (HSC) activation induced by autophagy maintains the liver architecture to prevent collapse during acute liver failure (ALF). Nitric oxide (NO) has shown to induce HSC apoptosis. Whether and how NO is involved in ALF and autophagy remains unclear. METHODS: ALF patients were recruited to investigate the correlation between plasma NO levels and clinical features. Liver tissues were collected from chronic hepatitis patients by biopsy and from ALF patients who had undergone liver transplantation...
May 15, 2017: Liver International: Official Journal of the International Association for the Study of the Liver
https://www.readbyqxmd.com/read/28506985/histone-acetyltransferase-kat8-is-essential-for-mouse-oocyte-development-by-regulating-ros-levels
#19
Shi Yin, Xiaohua Jiang, Hanwei Jiang, Qian Gao, Fang Wang, Suixing Fan, Teka Khan, Nazish Jabeen, Manan Khan, Asim Ali, Peng Xu, Tej K Pandita, Heng-Yu Fan, Yuanwei Zhang, Qinghua Shi
Proper oocyte development is critical for female fertility and requires timely and accurate control of gene expression. K (Lysine) Acetyltransferase 8 (KAT8), an important component of the X chromosome dosage compensation system in Drosophila, regulates gene activity by acetylating histone H4 preferentially at lysine 16. To explore the function of Kat8 during mouse oocyte development, we crossed Kat8(flox/flox) mice with Gdf9-Cre mice to specifically delete Kat8 in oocytes. Oocyte Kat8 deletion resulted in female infertility with follicle development failure in the secondary and preantral follicle stages...
May 15, 2017: Development
https://www.readbyqxmd.com/read/28506562/the-impact-of-system-factors-on-quality-and-safety-in-arterial-surgery-a%C3%A2-systematic-review
#20
REVIEW
R Lear, A D Godfrey, C Riga, C Norton, C Vincent, C D Bicknell
OBJECTIVE: A systems approach to patient safety proposes that a wide range of factors contribute to surgical outcome, yet the impact of team, work environment, and organisational factors, is not fully understood in arterial surgery. The aim of this systematic review is to summarize and discuss what is already known about the impact of system factors on quality and safety in arterial surgery. DATA SOURCES: A systematic review of original research papers in English using MEDLINE, Embase, PsycINFO, and Cochrane databases, was performed according to PRISMA guidelines...
May 11, 2017: European Journal of Vascular and Endovascular Surgery
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