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  1. Article ; Online: Fanning the Fire

    Julie A. Bastarache / James L. Wynn / Lorraine B. Ware

    EBioMedicine, Vol 2, Iss 3, Pp 184-

    Can Methemoglobin Enhance Neutrophil Activation?

    2015  Volume 185

    Keywords Medicine ; R ; Medicine (General) ; R5-920
    Language English
    Publishing date 2015-03-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Protocol for the development of a core outcome set for neonatal sepsis (NESCOS)

    Petek Eylul Taneri / Jamie J. Kirkham / Eleanor J. Molloy / Linda Biesty / Richard A. Polin / James L. Wynn / Barbara J. Stoll / Niranjan Kissoon / Kondwani Kawaza / Mandy Daly / Aoife Branagan / Lívia Nagy Bonnard / Eric Giannoni / Tobias Strunk / Magdalena Ohaja / Kenneth Mugabe / Denise Suguitani / Fiona Quirke / Declan Devane

    PLoS ONE, Vol 18, Iss

    2023  Volume 12

    Keywords Medicine ; R ; Science ; Q
    Language English
    Publishing date 2023-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: Protocol for the development of a core outcome set for neonatal sepsis (NESCOS).

    Petek Eylul Taneri / Jamie J Kirkham / Eleanor J Molloy / Linda Biesty / Richard A Polin / James L Wynn / Barbara J Stoll / Niranjan Kissoon / Kondwani Kawaza / Mandy Daly / Aoife Branagan / Lívia Nagy Bonnard / Eric Giannoni / Tobias Strunk / Magdalena Ohaja / Kenneth Mugabe / Denise Suguitani / Fiona Quirke / Declan Devane

    PLoS ONE, Vol 18, Iss 12, p e

    2023  Volume 0295325

    Abstract: Neonatal sepsis is a serious public health problem; however, there is substantial heterogeneity in the outcomes measured and reported in research evaluating the effectiveness of the treatments. Therefore, we aim to develop a Core Outcome Set (COS) for ... ...

    Abstract Neonatal sepsis is a serious public health problem; however, there is substantial heterogeneity in the outcomes measured and reported in research evaluating the effectiveness of the treatments. Therefore, we aim to develop a Core Outcome Set (COS) for studies evaluating the effectiveness of treatments for neonatal sepsis. Since a systematic review of key outcomes from randomised trials of therapeutic interventions in neonatal sepsis was published recently, we will complement this with a qualitative systematic review of the key outcomes of neonatal sepsis identified by parents, other family members, parent representatives, healthcare providers, policymakers, and researchers. We will interpret the outcomes of both studies using a previously established framework. Stakeholders across three different groups i.e., (1) researchers, (2) healthcare providers, and (3) patients' parents/family members and parent representatives will rate the importance of the outcomes in an online Real-Time Delphi Survey. Afterwards, consensus meetings will be held to agree on the final COS through online discussions with key stakeholders. This COS is expected to minimize outcome heterogeneity in measurements and publications, improve comparability and synthesis, and decrease research waste.
    Keywords Medicine ; R ; Science ; Q
    Subject code 306
    Language English
    Publishing date 2023-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: Survival, bacterial clearance and thrombocytopenia are improved in polymicrobial sepsis by targeting nuclear transport shuttles.

    Ruth Ann Veach / Yan Liu / Jozef Zienkiewicz / Lukasz S Wylezinski / Kelli L Boyd / James L Wynn / Jacek Hawiger

    PLoS ONE, Vol 12, Iss 6, p e

    2017  Volume 0179468

    Abstract: The rising tide of sepsis, a leading cause of death in the US and globally, is not adequately controlled by current antimicrobial therapies and supportive measures, thereby requiring new adjunctive treatments. Severe microvascular injury and multiple ... ...

    Abstract The rising tide of sepsis, a leading cause of death in the US and globally, is not adequately controlled by current antimicrobial therapies and supportive measures, thereby requiring new adjunctive treatments. Severe microvascular injury and multiple organ failure in sepsis are attributed to a "genomic storm" resulting from changes in microbial and host genomes encoding virulence factors and endogenous inflammatory mediators, respectively. This storm is mediated by stress-responsive transcription factors that are ferried to the nucleus by nuclear transport shuttles importins/karyopherins. We studied the impact of simultaneously targeting two of these shuttles, importin alpha 5 (Imp α5) and importin beta 1 (Imp β1), with a cell-penetrating Nuclear Transport Modifier (NTM) in a mouse model of polymicrobial sepsis. NTM reduced nuclear import of stress-responsive transcription factors nuclear factor kappa B, signal transducer and activator of transcription 1 alpha, and activator protein 1 in liver, which was also protected from sepsis-associated metabolic changes. Strikingly, NTM without antimicrobial therapy improved bacterial clearance in blood, spleen, and lungs, wherein a 700-fold reduction in bacterial burden was achieved while production of proinflammatory cytokines and chemokines in blood plasma was suppressed. Furthermore, NTM significantly improved thrombocytopenia, a prominent sign of microvascular injury in sepsis, inhibited neutrophil infiltration in the liver, decreased L-selectin, and normalized plasma levels of E-selectin and P-selectin, indicating reduced microvascular injury. Importantly, NTM combined with antimicrobial therapy extended the median time to death from 42 to 83 hours and increased survival from 30% to 55% (p = 0.022) as compared to antimicrobial therapy alone. This study documents the fundamental role of nuclear signaling mediated by Imp α5 and Imp β1 in the mechanism of polymicrobial sepsis and highlights the potential for targeting nuclear transport as an adjunctive therapy in sepsis ...
    Keywords Medicine ; R ; Science ; Q
    Subject code 610
    Language English
    Publishing date 2017-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article ; Online: Cell-free hemoglobin increases inflammation, lung apoptosis, and microvascular permeability in murine polymicrobial sepsis.

    Jamie E Meegan / Ciara M Shaver / Nathan D Putz / Jordan J Jesse / Stuart R Landstreet / Han Noo Ri Lee / Tatiana N Sidorova / J Brennan McNeil / James L Wynn / Joyce Cheung-Flynn / Padmini Komalavilas / Colleen M Brophy / Lorraine B Ware / Julie A Bastarache

    PLoS ONE, Vol 15, Iss 2, p e

    2020  Volume 0228727

    Abstract: Increased endothelial permeability is central to the pathogenesis of sepsis and leads to organ dysfunction and death but the endogenous mechanisms that drive increased endothelial permeability are not completely understood. We previously reported that ... ...

    Abstract Increased endothelial permeability is central to the pathogenesis of sepsis and leads to organ dysfunction and death but the endogenous mechanisms that drive increased endothelial permeability are not completely understood. We previously reported that cell-free hemoglobin (CFH), elevated in 80% of patients with sepsis, increases lung microvascular permeability in an ex vivo human lung model and cultured endothelial cells. In this study, we augmented a murine model of polymicrobial sepsis with elevated circulating CFH to test the hypothesis that CFH increases microvascular endothelial permeability by inducing endothelial apoptosis. Mice were treated with an intraperitoneal injection of cecal slurry with or without a single intravenous injection of CFH. Severity of illness, mortality, systemic and lung inflammation, endothelial injury and dysfunction and lung apoptosis were measured at selected time points. We found that CFH added to CS increased sepsis mortality, plasma inflammatory cytokines as well as lung apoptosis, edema and inflammation without affecting large vessel reactivity or vascular injury marker concentrations. These results suggest that CFH is an endogenous mediator of increased endothelial permeability and apoptosis in sepsis and may be a promising therapeutic target.
    Keywords Medicine ; R ; Science ; Q
    Subject code 610
    Language English
    Publishing date 2020-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  6. Article ; Online: Unique transcriptomic response to sepsis is observed among patients of different age groups.

    Steven L Raymond / María Cecilia López / Henry V Baker / Shawn D Larson / Philip A Efron / Timothy E Sweeney / Purvesh Khatri / Lyle L Moldawer / James L Wynn

    PLoS ONE, Vol 12, Iss 9, p e

    2017  Volume 0184159

    Abstract: Sepsis is a major cause of morbidity and mortality, especially at the extremes of age. To understand the human age-specific transcriptomic response to sepsis, a multi-cohort, pooled analysis was conducted on adults, children, infants, and neonates with ... ...

    Abstract Sepsis is a major cause of morbidity and mortality, especially at the extremes of age. To understand the human age-specific transcriptomic response to sepsis, a multi-cohort, pooled analysis was conducted on adults, children, infants, and neonates with and without sepsis. Nine public whole-blood gene expression datasets (636 patients) were employed. Age impacted the transcriptomic host response to sepsis. Gene expression from septic neonates and adults was more dissimilar whereas infants and children were more similar. Neonates showed reductions in inflammatory recognition and signaling pathways compared to all other age groups. Likewise, adults demonstrated decreased pathogen sensing, inflammation, and myeloid cell function, as compared to children. This may help to explain the increased incidence of sepsis-related organ failure and death in adults. The number of dysregulated genes in septic patients was proportional to age and significantly differed among septic adults, children, infants, and neonates. Overall, children manifested a greater transcriptomic intensity to sepsis as compared to the other age groups. The transcriptomic magnitude for adults and neonates was dramatically reduced as compared to children and infants. These findings suggest that the transcriptomic response to sepsis is age-dependent, and diagnostic and therapeutic efforts to identify and treat sepsis will have to consider age as an important variable.
    Keywords Medicine ; R ; Science ; Q
    Subject code 610
    Language English
    Publishing date 2017-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    Full text online

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    Inter-library loan at ZB MED

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  7. Article ; Online: Use of a computerized C-reactive protein (CRP) based sepsis evaluation in very low birth weight (VLBW) infants

    Sarah A Coggins / James L Wynn / Melissa L Hill / James C Slaughter / Asli Ozdas-Weitkamp / Osman Jalloh / L Russell Waitman / Randy J Carnevale / Jörn-Hendrik Weitkamp

    PLoS ONE, Vol 8, Iss 11, p e

    a five-year experience.

    2013  Volume 78602

    Abstract: Serial C-reactive protein (CRP) values may be useful for decision-making regarding duration of antibiotics in neonates. However, established standard of practice for its use in preterm very low birth weight (<1500 g, VLBW) infants are lacking.Evaluate ... ...

    Abstract Serial C-reactive protein (CRP) values may be useful for decision-making regarding duration of antibiotics in neonates. However, established standard of practice for its use in preterm very low birth weight (<1500 g, VLBW) infants are lacking.Evaluate compliance with a CRP-guided computerized decision support (CDS) algorithm and compare characteristics and outcomes of compliant versus non-compliant cases. Measure correlation between CRPs and white blood count (WBC) indices.We examined 3 populations: 1) all preterm VLBW infants born at Vanderbilt 2006-2011 - we assessed provider compliance with CDS algorithm and measured relevant outcomes; 2) all patients with positive blood culture results admitted to the Vanderbilt NICU 2006-2012 - we tested the correlation between CRP and WBC results within 7 days of blood culture phlebotomy; 3) 1,000 randomly selected patients out of the 7,062 patients admitted to the NICU 2006-2012 - we correlated time-associated CRP values and absolute neutrophil counts.Of 636 VLBW infants in cohort 1), 569 (89%) received empiric antibiotics for suspected early-onset sepsis. In 409 infants (72%) the CDS algorithm was followed; antibiotics were discontinued ≤48 hours in 311 (55%) with normal serial CRPs and continued in 98 (17%) with positive CRPs, resulting in significant reduction in antibiotic exposure (p<0.001) without increase in complications or subsequent infections. One hundred sixty (28%) were considered non-compliant because antibiotics were continued beyond 48 hours despite negative serial CRPs and blood cultures. Serial CRPs remained negative in 38 (12%) of 308 blood culture-positive infants from cohort 2, but only 4 patients had clinically probable sepsis with single organisms and no immunodeficiency besides extreme prematurity. Leukopenia of any cell type was not linked with CRPs in cohorts 2 and 3.CDS/CRP-guided antibiotic use is safe and effective in culture-negative VLBW infants. CRP results are not affected by low WBC indices.
    Keywords Medicine ; R ; Science ; Q
    Subject code 610
    Language English
    Publishing date 2013-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  8. Article ; Online: Beyond bacteria

    Mariam Susan LaTuga / Joseph Christopher Ellis / Charles Michael Cotton / Ronald N Goldberg / James L Wynn / Robert B Jackson / Patrick C Seed

    PLoS ONE, Vol 6, Iss 12, p e

    a study of the enteric microbial consortium in extremely low birth weight infants.

    2011  Volume 27858

    Abstract: Extremely low birth weight (ELBW) infants have high morbidity and mortality, frequently due to invasive infections from bacteria, fungi, and viruses. The microbial communities present in the gastrointestinal tracts of preterm infants may serve as a ... ...

    Abstract Extremely low birth weight (ELBW) infants have high morbidity and mortality, frequently due to invasive infections from bacteria, fungi, and viruses. The microbial communities present in the gastrointestinal tracts of preterm infants may serve as a reservoir for invasive organisms and remain poorly characterized. We used deep pyrosequencing to examine the gut-associated microbiome of 11 ELBW infants in the first postnatal month, with a first time determination of the eukaryote microbiota such as fungi and nematodes, including bacteria and viruses that have not been previously described. Among the fungi observed, Candida sp. and Clavispora sp. dominated the sequences, but a range of environmental molds were also observed. Surprisingly, seventy-one percent of the infant fecal samples tested contained ribosomal sequences corresponding to the parasitic organism Trichinella. Ribosomal DNA sequences for the roundworm symbiont Xenorhabdus accompanied these sequences in the infant with the greatest proportion of Trichinella sequences. When examining ribosomal DNA sequences in aggregate, Enterobacteriales, Pseudomonas, Staphylococcus, and Enterococcus were the most abundant bacterial taxa in a low diversity bacterial community (mean Shannon-Weaver Index of 1.02 ± 0.69), with relatively little change within individual infants through time. To supplement the ribosomal sequence data, shotgun sequencing was performed on DNA from multiple displacement amplification (MDA) of total fecal genomic DNA from two infants. In addition to the organisms mentioned previously, the metagenome also revealed sequences for gram positive and gram negative bacteriophages, as well as human adenovirus C. Together, these data reveal surprising eukaryotic and viral microbial diversity in ELBW enteric microbiota dominated bytypes of bacteria known to cause invasive disease in these infants.
    Keywords Medicine ; R ; Science ; Q
    Language English
    Publishing date 2011-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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