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https://www.readbyqxmd.com/read/29353206/dihydroartemisinin-ameliorates-sepsis-induced-hyperpermeability-of-glomerular-endothelium-via-up-regulation-of-occludin-expression
#1
Zuowang Cheng, Ruixia Qi, Liqun Li, Qiang Liu, Wenqian Zhang, Xia Zhou, Dongmei Xu, Thaddeus D Allen, Silin Pan, Ju Liu
Sepsis, the systemic inflammatory responses after infection, remains a serious cause of morbidity and mortality in critically ill patients. The anti-malarial agent dihydroartemisinin (DHA) has been shown to be anti-inflammatory. In this study, we examined the effects of DHA on sepsis-induced acute kidney injury (AKI) and explored the mechanism underlying its mode of action in AKI. In a lipopolysaccharide (LPS)-induced mouse model, we observed that DHA treatment ameliorated glomerular injury, and relieved elevation of the urine albumin to creatinine ratio (UACR) and serum creatinine...
January 17, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29352703/inotuzumab-ozogamicin-in-combination-with-low-intensity-chemotherapy-for-older-patients-with-philadelphia-chromosome-negative-acute-lymphoblastic-leukaemia-a-single-arm-phase-2-study
#2
Hagop Kantarjian, Farhad Ravandi, Nicholas J Short, Xuelin Huang, Nitin Jain, Koji Sasaki, Naval Daver, Naveen Pemmaraju, Joseph D Khoury, Jeffrey Jorgensen, Yesid Alvarado, Marina Konopleva, Guillermo Garcia-Manero, Tapan Kadia, Musa Yilmaz, Gautam Bortakhur, Jan Burger, Steven Kornblau, William Wierda, Courtney DiNardo, Alessandra Ferrajoli, Jovitta Jacob, Rebecca Garris, Susan O'Brien, Elias Jabbour
BACKGROUND: Inotuzumab ozogamicin, an anti-CD22 monoclonal antibody bound to a toxin, calicheamicin, has shown single-agent activity in relapsed or refractory acute lymphoblastic leukaemia. We aimed to assess the activity and safety of inotuzumab ozogamicin in combination with low-intensity chemotherapy in older patients with acute lymphoblastic leukaemia. METHODS: We did a single-arm, phase 2 study at the MD Anderson Cancer Center (Houston, TX, USA). Eligible patients were aged 60 years or older and had newly diagnosed, Philadelphia chromosome-negative, acute lymphoblastic leukaemia, and an Eastern Cooperative Oncology Group performance status of 3 or lower...
January 15, 2018: Lancet Oncology
https://www.readbyqxmd.com/read/29352339/effect-of-time-to-operation-on-value-of-care-in-acute-care-surgery
#3
Tyler J Loftus, Martin D Rosenthal, Chasen A Croft, R Stephen Smith, Philip A Efron, Frederick A Moore, Alicia M Mohr, Scott C Brakenridge
BACKGROUND: As reimbursement models evolve, there is increasing emphasis on maximizing value-based care for inpatient conditions. We hypothesized that longer intervals between admission and surgery would be associated with worse outcomes and increased costs for acute care surgery patients, and that these associations would be strongest among patients with high-risk conditions. METHODS: We performed a 5-year retrospective analysis of three risk cohorts: appendectomy (low-risk for morbidity and mortality, n = 618), urgent hernia repair (intermediate-risk, n = 80), and laparotomy for intra-abdominal sepsis with temporary abdominal closure (sTAC; high-risk, n = 102)...
January 19, 2018: World Journal of Surgery
https://www.readbyqxmd.com/read/29351405/acute-down-regulation-of-mir-199a-attenuates-sepsis-induced-acute-lung-injury-by-targeting-sirt1
#4
Yang Liu, Hao Guan, Ju-Lei Zhang, Zhao Zheng, Hong-Tao Wang, Ke Tao, Shi-Chao Han, Lin-Lin Su, Dahai Hu
MiR-199a is a novel gene regulator with an important role in inflammation and lung injury. However, its role in the pathogenesis of sepsis-induced acute respiratory distress syndrome (ARDS) is currently unknown. Our study explored the role of miR-199a in sepsis-induced ARDS and its mechanism of action. First, we found that LPS could up-regulate miR-199a in alveolar macrophages. Down-regulation of miR-199a inhibited the up-regulation of inflammatory cytokines in alveolar macrophages and induced the remission of histopathologic changes, the reduction of pro-inflammatory cytokines, and the up-regulation of apoptosis protein expression in an ARDS lung, showing a protective role for miR-199a...
January 10, 2018: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/29351007/timing-of-renal-support-and-outcome-of-septic-shock-and-acute-respiratory-distress-syndrome
#5
Stéphane Gaudry, David Hajage, Frédérique Schortgen, Laurent Martin-Lefevre, Charles Verney, Bertrand Pons, Eric Boulet, Alexandre Boyer, Guillaume Chevrel, Nicolas Lerolle, Dorothée Carpentier, Nicolas de Prost, Alexandre Lautrette, Anne Bretagnol, Julien Mayaux, Saad Nseir, Bruno Megarbane, Marina Thirion, Jean-Marie Forel, Julien Maizel, Hodane Yonis, Philippe Markowicz, Guillaume Thiery, Florence Tubach, Jean-Damien Ricard, Didier Dreyfuss
RATIONALE: The optimal strategy for initiation of renal replacement therapy (RRT) in patients with severe acute kidney injury in the context of septic shock and acute respiratory distress syndrome (ARDS) is unknown. OBJECTIVE: To examine the effect of an early compared to a delayed RRT initiation strategy on 60-day mortality according to the baseline sepsis status, ARDS status and severity. METHODS: Post-hoc analysis of the AKIKI (Artificial-Kidney-Initiation in Kidney-Injury) trial...
January 19, 2018: American Journal of Respiratory and Critical Care Medicine
https://www.readbyqxmd.com/read/29350381/macrophage-migration-inhibitory-factor-knockout-attenuates-endotoxin-induced-cardiac-dysfunction-in-mice
#6
Jie Zhang, Xin Zhang, Yuqi Cui, Lianqun Cui, Peng Zhao
BACKGROUND: The accumulated evidence suggests that macrophage migration inhibitory factor (MIF) plays a key role not only in acute and chronic inflammatory diseases but also in cardiovascular disease. The cardiac dysfunction is related to lipopolysaccharide (LPS) in sepsis. AIM: This study was designed to examine whether MIF mediates LPS-induced cardiac dysfunction and address the mechanisms. METHODS: Echocardiography, immunohistochemical analysis, cell shortening/relengthening and intracellular Ca2+ fluorescence evaluation were performed in whole hearts and isolated cardiomyocytes from C57 and MIF knockout mice treated with or without LPS...
January 19, 2018: Kardiologia Polska
https://www.readbyqxmd.com/read/29348412/influence-of-autophagy-on-acute-kidney-injury-in-a-murine-cecal-ligation-and-puncture-sepsis-model
#7
Satoshi Sunahara, Eizo Watanabe, Masahiko Hatano, Paul E Swanson, Takehiko Oami, Lisa Fujimura, Youichi Teratake, Takashi Shimazui, Chiwei Lee, Shigeto Oda
The role of autophagy in the maintenance of renal homeostasis during sepsis is not well understood. We therefore aimed to determine the influence of autophagy on kidney during sepsis using a murine sepsis model, i.e. cecal ligation and puncture (CLP). In CLP treated animals, the number of autolysosomes observed by electron microscopy increased over time. The number of autophagosomes in CLP animals decreased relative sham operated controls at 24 hrs after CLP, indicating that autophagy flux is already diminishing by that time...
January 18, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29346183/near-infrared-spectroscopy-to-predict-organ-failure-and-outcome-in-sepsis-the-assessing-risk-in-sepsis-using-a-tissue-oxygen-saturation-aristos-study
#8
Stephen P J Macdonald, Frances B Kinnear, Glenn Arendts, Kwok M Ho, Daniel M Fatovich
OBJECTIVES: Sepsis is acute organ dysfunction in the setting of infection. An accurate diagnosis is important to guide treatment and disposition. Tissue oxygen saturation (StO2) can be estimated noninvasively by near-infrared spectroscopy (NIRS), and may be an indicator of microcirculatory dysfunction in early sepsis. We aimed to determine the utility of StO2 for sepsis recognition and outcome prediction among patients presenting to the emergency department (ED) with infection. PATIENTS AND METHODS: A multicentre, prospective, observational cohort study recruited patients who were being admitted to hospital with infection...
January 17, 2018: European Journal of Emergency Medicine: Official Journal of the European Society for Emergency Medicine
https://www.readbyqxmd.com/read/29344053/an-overview-of-exposure-to-ethanol-containing-substances-and-ethanol-intoxication-in-children-based-on-three-illustrated-cases
#9
REVIEW
Kam Lun Hon, Alexander Kc Leung, Eddie Cheung, Bryan Lee, Michelle Mc Tsang, Alcy R Torres
Alcohol addiction and intoxication are major health problems worldwide. Acute alcohol intoxication is well reported in adults and adolescents but less frequently reported in children of younger ages. We report three anonymized cases of pediatric ethanol exposure and illustrate the different mechanisms of intoxication. In all cases, a focused history is the key to prompt diagnosis and timely management. Physicians should be aware of this potential poison in children presented with acute confusional or encephalopathic state...
2018: Drugs in Context
https://www.readbyqxmd.com/read/29343314/cell-free-dna-the-role-in-pathophysiology-and-as-a-biomarker-in-kidney-diseases
#10
Peter Celec, Barbora Vlková, Lucia Lauková, Janka Bábíčková, Peter Boor
Cell-free DNA (cfDNA) is present in various body fluids and originates mostly from blood cells. In specific conditions, circulating cfDNA might be derived from tumours, donor organs after transplantation or from the foetus during pregnancy. The analysis of cfDNA is mainly used for genetic analyses of the source tissue -tumour, foetus or for the early detection of graft rejection. It might serve also as a nonspecific biomarker of tissue damage in critical care medicine. In kidney diseases, cfDNA increases during haemodialysis and indicates cell damage...
January 18, 2018: Expert Reviews in Molecular Medicine
https://www.readbyqxmd.com/read/29341864/comparison-of-acute-kidney-injury-of-different-aetiology-reveals-in-common-mechanisms-of-tissue-damage
#11
Michael Hultström, Mediha Becirovic-Agic, Sofia Jönsson
Acute kidney injury (AKI) is a syndrome of reduced glomerular filtration rate (GFR) and urine production caused by a number of different diseases. It is associated with renal tissue damage. This tissue damage can cause tubular atrophy and interstitial fibrosis that leads to nephron loss and progression of chronic kidney disease (CKD). This review describes the in-common mechanisms behind tissue damage in AKI caused by different underlying diseases. Comparing six high-quality microarray studies of renal gene expression after AKI in disease models (gram-negative sepsis, gram-positive sepsis, ischemia-reperfusion, malignant hypertension, rhabdomyolysis and cisplatin toxicity) identified 5254 differentially expressed genes in at least one of the AKI models...
December 20, 2017: Physiological Genomics
https://www.readbyqxmd.com/read/29339097/safety-and-preliminary-efficacy-of-venetoclax-with-decitabine-or-azacitidine-in-elderly-patients-with-previously-untreated-acute-myeloid-leukaemia-a-non-randomised-open-label-phase-1b-study
#12
Courtney D DiNardo, Keith W Pratz, Anthony Letai, Brian A Jonas, Andrew H Wei, Michael Thirman, Martha Arellano, Mark G Frattini, Hagop Kantarjian, Relja Popovic, Brenda Chyla, Tu Xu, Martin Dunbar, Suresh K Agarwal, Rod Humerickhouse, Mack Mabry, Jalaja Potluri, Marina Konopleva, Daniel A Pollyea
BACKGROUND: Elderly patients (aged ≥65 years) with acute myeloid leukaemia have poor outcomes and no effective standard-of-care therapy exists. Treatment with hypomethylating agents such as azacitidine and decitabine is common, but responses are modest and typically short-lived. The oral anti-apoptotic B-cell lymphoma 2 protein inhibitor, venetoclax, has shown promising single-agent activity in patients with relapsed or refractory acute myeloid leukaemia and preclinical data suggested synergy between hypomethylating agents and venetoclax, which led to this combination phase 1b study...
January 12, 2018: Lancet Oncology
https://www.readbyqxmd.com/read/29337789/multicohort-analysis-of-whole-blood-gene-expression-data-does-not-form-a-robust-diagnostic-for-acute-respiratory-distress-syndrome
#13
Timothy E Sweeney, Neal J Thomas, Judie A Howrylak, Hector R Wong, Angela J Rogers, Purvesh Khatri
OBJECTIVES: To identify a novel, generalizable diagnostic for acute respiratory distress syndrome using whole-blood gene expression arrays from multiple acute respiratory distress syndrome cohorts of varying etiologies. DATA SOURCES: We performed a systematic search for human whole-blood gene expression arrays of acute respiratory distress syndrome in National Institutes of Health Gene Expression Omnibus and ArrayExpress. We also included the Glue Grant gene expression cohorts...
February 2018: Critical Care Medicine
https://www.readbyqxmd.com/read/29334583/effects-of-carnosine-beta-alanyl-l-histidine-in-an-experimental-rat-model-of-acute-kidney-injury-due-to-septic-shock
#14
Sabiha Sahin, Dilek Burukoglu Donmez
BACKGROUND Acute kidney injury (AKI) secondary to sepsis is a major cause of morbidity and mortality in the human intensive care unit (ICU). Kidney function and the histological findings of AKI were investigated in an experimental rat model with sepsis induced by cecal ligation and puncture (CLP) and compared with and without treatment with carnosine (beta-alanyl-L-histidine). MATERIAL AND METHODS Twenty-four Sprague-Dawley rats were randomly divided into three groups consisting eight rats in each: Group 1 - control; Group 2 - septic shock; and Group 3 - septic shock treated with carnosine...
January 15, 2018: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/29332614/serelaxin-for-infant-heart-failure-in-congenital-dilated-cardiomyopathy
#15
Patrick O Myers, Alice Bordessoule, Cécile Tissot
Serelaxin has been studied in trials in adults with acute heart failure, but not in children. We report the first compassionate use of serelaxin in an infant. A 6-month-old girl with dilated cardiomyopathy was placed on extracorporeal membrane oxygenation following cardiac arrest unresponsive to medical treatment. Extracorporeal membrane oxygenation weaning failed despite maximal ino-dilator therapy. During the 48-hour infusion of serelaxin, we observed marked improvement in brain natriuretic peptide, left ventricular systolic function, and dilatation...
January 15, 2018: Cardiology in the Young
https://www.readbyqxmd.com/read/29330126/recent-progress-in-the-discovery-of-myeloid-differentiation-2-md2-modulators-for-inflammatory-diseases
#16
REVIEW
Lingfeng Chen, Weitao Fu, Lulu Zheng, Yi Wang, Guang Liang
Myeloid differentiation protein 2 (MD2), together with Toll-like receptor 4 (TLR4), binds lipopolysaccharide (LPS) with high affinity, inducing the formation of the activated homodimer LPS-MD2-TLR4. MD2 directly recognizes the Lipid A domain of LPS, leading to the activation of downstream signaling of cytokine and chemokine production, and initiation of inflammatory and immune responses. However, excessive activation and potent host responses generate severe inflammatory syndromes such as acute sepsis and septic shock...
January 9, 2018: Drug Discovery Today
https://www.readbyqxmd.com/read/29327522/clinical-profile-and-outcome-of-pregnant-patients-with-acute-hev-hepatitis-during-water-borne-epidemic-in-himachal-pradesh-a-hospital-based-study
#17
Asha Ranjan, Surinder Thakur, Jatinder Mokta, Rajesh Bhawani, Varsha Ranjan
Background: Recent outbreak of HEV hepatitis epidemic in Himachal Pradesh in Shimla caused significant morbidity and mortality especially among pregnant patients. Overall mortality is 0.5- 4% in patients developing acute hepatic failure (ALF) and is significantly higher in pregnant patients (20%). Present study conducted to observe clinical profile and outcome in pregnant patients. Methodology: this is a retrospective observational study done on admitted pregnant and post partum patients with acute HEV hepatitis during 3 months periods...
December 2017: Journal of the Association of Physicians of India
https://www.readbyqxmd.com/read/29327282/ziziphus-spina-christi-leaf-extract-pretreatment-inhibits-liver-and-spleen-injury-in-a-mouse-model-of-sepsis-via-anti-oxidant-and-anti-inflammatory-effects
#18
Mohamed A Dkhil, Saleh Al-Quraishy, Ahmed E Abdel Moneim
Sepsis is a systemic response to infection that can result in acute hepatic and splenic damage. Ziziphus spina-christi (L.) is a wild tree used as a medicinal plant by ancient Egyptians. However, little is known about the mechanism underlying its effects on sepsis. The current study investigated the protective effects of a Z. spina-christi leaf extract (ZSCLE) on liver and spleen damage in a male C57BL/6 mouse model of sepsis, induced by cecal ligation and puncture (CLP). Prior to CLP, ZSCLE was administered daily for five consecutive days via oral gavage at doses of 100, 200, or 300 mg/kg...
January 11, 2018: Inflammopharmacology
https://www.readbyqxmd.com/read/29327152/the-prevalence-and-impact-of-status-epilepticus-secondary-to-intracerebral-hemorrhage-results-from-the-us-nationwide-inpatient-sample
#19
Amol Mehta, Benjamin E Zusman, Lori A Shutter, Ravi Choxi, Ahmed Yassin, Arun Antony, Parthasarathy D Thirumala
BACKGROUND: Status epilepticus (SE) has been identified as a predictor of morbidity and mortality in many acute brain injury patient populations. We aimed to assess the prevalence and impact of SE after intracerebral hemorrhage (ICH) in a large patient sample to overcome limitations in previous small patient sample studies. METHODS: We queried the Nationwide Inpatient Sample for patients admitted for ICH from 1999 to 2011, excluding patients with other acute brain injuries...
January 11, 2018: Neurocritical Care
https://www.readbyqxmd.com/read/29325753/induced-hypothermia-in-patients-with-septic-shock-and-respiratory-failure-cass-a-randomised-controlled-open-label-trial
#20
Theis Skovsgaard Itenov, Maria Egede Johansen, Morten Bestle, Katrin Thormar, Lars Hein, Louise Gyldensted, Anne Lindhardt, Henrik Christensen, Stine Estrup, Henrik Planck Pedersen, Matthew Harmon, Uday Kant Soni, Silvia Perez-Protto, Nicolai Wesche, Ulrik Skram, John Asger Petersen, Thomas Mohr, Tina Waldau, Lone Musaeus Poulsen, Ditte Strange, Nicole P Juffermans, Daniel I Sessler, Else Tønnesen, Kirsten Møller, Dennis Karsten Kristensen, Alessandro Cozzi-Lepri, Jens D Lundgren, Jens-Ulrik Jensen
BACKGROUND: Animal models of serious infection suggest that 24 h of induced hypothermia improves circulatory and respiratory function and reduces mortality. We tested the hypothesis that a reduction of core temperature to 32-34°C attenuates organ dysfunction and reduces mortality in ventilator-dependent patients with septic shock. METHODS: In this randomised, controlled, open-label trial, we recruited patients from ten intensive care units (ICUs) in three countries in Europe and North America...
January 8, 2018: Lancet Respiratory Medicine
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