Browsing by Author "Jenne, Craig N"

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    Closed Or Open after Source Control Laparotomy for Severe Complicated Intra-Abdominal Sepsis (the COOL trial): study protocol for a randomized controlled trial
    (2018-06-22) Kirkpatrick, Andrew W; Coccolini, Federico; Ansaloni, Luca; Roberts, Derek J; Tolonen, Matti; McKee, Jessica L; Leppaniemi, Ari; Faris, Peter; Doig, Christopher J; Catena, Fausto; Fabian, Timothy; Jenne, Craig N; Chiara, Osvaldo; Kubes, Paul; Manns, Braden; Kluger, Yoram; Fraga, Gustavo P; Pereira, Bruno M; Diaz, Jose J; Sugrue, Michael; Moore, Ernest E; Ren, Jianan; Ball, Chad G; Coimbra, Raul; Balogh, Zsolt J; Abu-Zidan, Fikri M; Dixon, Elijah; Biffl, Walter; MacLean, Anthony; Ball, Ian; Drover, John; McBeth, Paul B; Posadas-Calleja, Juan G; Parry, Neil G; Di Saverio, Salomone; Ordonez, Carlos A; Xiao, Jimmy; Sartelli, Massimo
    Abstract Background Severe complicated intra-abdominal sepsis (SCIAS) has an increasing incidence with mortality rates over 80% in some settings. Mortality typically results from disruption of the gastrointestinal tract, progressive and self-perpetuating bio-mediator generation, systemic inflammation, and multiple organ failure. Principles of treatment include early antibiotic administration and operative source control. A further therapeutic option may be open abdomen (OA) management with active negative peritoneal pressure therapy (ANPPT) to remove inflammatory ascites and ameliorate the systemic damage from SCIAS. Although there is now a biologic rationale for such an intervention as well as non-standardized and erratic clinical utilization, this remains a novel therapy with potential side effects and clinical equipoise. Methods The Closed Or Open after Laparotomy (COOL) study will constitute a prospective randomized controlled trial that will randomly allocate eligible surgical patients intra-operatively to either formal closure of the fascia or use of the OA with application of an ANPTT dressing. Patients will be eligible if they have free uncontained intra-peritoneal contamination and physiologic derangements exemplified by septic shock OR a Predisposition-Infection-Response-Organ Dysfunction Score ≥ 3 or a World-Society-of-Emergency-Surgery-Sepsis-Severity-Score ≥ 8. The primary outcome will be 90-day survival. Secondary outcomes will be logistical, physiologic, safety, bio-mediators, microbiological, quality of life, and health-care costs. Secondary outcomes will include days free of ICU, ventilation, renal replacement therapy, and hospital at 30 days from the index laparotomy. Physiologic secondary outcomes will include changes in intensive care unit illness severity scores after laparotomy. Bio-mediator outcomes for participating centers will involve measurement of interleukin (IL)-6 and IL-10, procalcitonin, activated protein C (APC), high-mobility group box protein-1, complement factors, and mitochondrial DNA. Economic outcomes will comprise standard costing for utilization of health-care resources. Discussion Although facial closure after SCIAS is considered the current standard of care, many reports are suggesting that OA management may improve outcomes in these patients. This trial will be powered to demonstrate a mortality difference in this highly lethal and morbid condition to ensure critically ill patients are receiving the best care possible and not being harmed by inappropriate therapies based on opinion only. Trial registration ClinicalTrials.gov , NCT03163095 .
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    Efficacy and safety of active negative pressure peritoneal therapy for reducing the systemic inflammatory response after damage control laparotomy (the Intra- peritoneal Vacuum Trial): study protocol for a randomized controlled trial
    (BioMed Central, 2013-05-16) Roberts, Derek J; Jenne, Craig N; Ball, Chad G; Tiruta, Corina; Léger, Caroline; Xiao, Zhengwen; Faris, Peter D; McBeth, Paul B; Doig, Christopher J; Skinner, Christine R; Ruddell, Stacy G; Kubes, Paul; Kirkpatrick, Andrew W
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    Evaluation of engineered bacterial transferrin binding proteins as vaccine antigens
    (2021-09-14) Chaudhuri, Somshukla; Schryvers, Anthony B; Harrison, Joe J; Savchenko, Alexei; Jenne, Craig N; Wilson, Heather L
    Many important Gram-negative pathogens that cause disease in humans and food production animals have specifically evolved to colonize and reside in the mucosal surfaces of their hosts. A key enabling factor in the survival and the pathogenesis of these bacteria is the bacterial transferrin receptor, which is used by these organisms to acquire iron, an essential micronutrient, from their host environment. The bacterial transferrin receptor is composed of the transferrin binding protein A and B (TbpA and TbpB), which bind exclusively to host protein transferrin and thus, limits the niche for these bacteria exclusively to their host species. TbpA is an outer, transmembrane TonB-dependent transporter, which enables the internalization of iron into the periplasm. TbpB is a surface exposed lipoprotein anchored to the bacterial membrane and aids in capturing iron loaded transferrin in the extracellular milieu. The bacterial transferrin receptor has been considered as a prospective vaccine antigen against these pathogens hence the objective of this thesis is to evaluate these proteins as an antigen. Previous studies have shown that when a TbpB mutant from porcine pathogen Glaesserella parasuis engineered to be defective in binding to porcine transferrin (Y167A TbpB) was used as a vaccine antigen, superior protection was observed in a swine model compared to the wildtype TbpB control. For the first aim, findings from this thesis demonstrated that a murine model of sepsis can be used to evaluate different TbpB mutants, providing a tool to screen different mutants prior to evaluating in a swine model. For the second aim, new TbpB mutants defective in binding to porcine transferrin were generated and evaluated as vaccine antigens. For the third aim, the cross-reactivity of immunizations with either single or multiple TbpB antigens is explored. A combined vaccine formulation with two antigens elicited a broadly cross-reactive response raising the possibility that a final TbpB based vaccine limited to these two antigens may be sufficient in providing protection against the entire repertoire of TbpB variants. Finally, a method for generating chimeric/hybrid antigens using TbpB based scaffolds to display extracellular loops from membrane proteins like TbpA in order to take advantage of TbpA as a vaccine antigen is discussed. Overall, the findings of this thesis adds to our understanding of the bacterial transferrin receptor as a vaccine antigen and brings us closer to the final, optimal vaccine composition for eliciting efficacious and broadly cross-protective coverage.
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    Getting the invite list right: a discussion of sepsis severity scoring systems in severe complicated intra-abdominal sepsis and randomized trial inclusion criteria
    (2018-04-06) Tolonen, Matti; Coccolini, Federico; Ansaloni, Luca; Sartelli, Massimo; Roberts, Derek J; McKee, Jessica L; Leppaniemi, Ari; Doig, Christopher J; Catena, Fausto; Fabian, Timothy; Jenne, Craig N; Chiara, Osvaldo; Kubes, Paul; Kluger, Yoram; Fraga, Gustavo P; Pereira, Bruno M; Diaz, Jose J; Sugrue, Michael; Moore, Ernest E; Ren, Jianan; Ball, Chad G; Coimbra, Raul; Dixon, Elijah; Biffl, Walter; MacLean, Anthony; McBeth, Paul B; Posadas-Calleja, Juan G; Di Saverio, Salomone; Xiao, Jimmy; Kirkpatrick, Andrew W
    Abstract Background Severe complicated intra-abdominal sepsis (SCIAS) is a worldwide challenge with increasing incidence. Open abdomen management with enhanced clearance of fluid and biomediators from the peritoneum is a potential therapy requiring prospective evaluation. Given the complexity of powering multi-center trials, it is essential to recruit an inception cohort sick enough to benefit from the intervention; otherwise, no effect of a potentially beneficial therapy may be apparent. An evaluation of abilities of recognized predictive systems to recognize SCIAS patients was conducted using an existing intra-abdominal sepsis (IAS) database. Methods All consecutive adult patients with a diffuse secondary peritonitis between 2012 and 2013 were collected from a quaternary care hospital in Finland, excluding appendicitis/cholecystitis. From this retrospectively collected database, a target population (93) of those with either ICU admission or mortality were selected. The performance metrics of the Third Consensus Definitions for Sepsis and Septic Shock based on both SOFA and quick SOFA, the World Society of Emergency Surgery Sepsis Severity Score (WSESSSS), the APACHE II score, Manheim Peritonitis Index (MPI), and the Calgary Predisposition, Infection, Response, and Organ dysfunction (CPIRO) score were all tested for their discriminant ability to identify this subgroup with SCIAS and to predict mortality. Results Predictive systems with an area under-the-receiving-operating characteristic (AUC) curve > 0.8 included SOFA, Sepsis-3 definitions, APACHE II, WSESSSS, and CPIRO scores with the overall best for CPIRO. The highest identification rates were SOFA score ≥ 2 (78.4%), followed by the WSESSSS score ≥ 8 (73.1%), SOFA ≥ 3 (75.2%), and APACHE II ≥ 14 (68.8%) identification. Combining the Sepsis-3 septic-shock definition and WSESSS ≥ 8 increased detection to 80%. Including CPIRO score ≥ 3 increased this to 82.8% (Sensitivity-SN; 83% Specificity-SP; 74%. Comparatively, SOFA ≥ 4 and WSESSSS ≥ 8 with or without septic-shock had 83.9% detection (SN; 84%, SP; 75%, 25% mortality). Conclusions No one scoring system behaves perfectly, and all are largely dominated by organ dysfunction. Utilizing combinations of SOFA, CPIRO, and WSESSSS scores in addition to the Sepsis-3 septic shock definition appears to offer the widest “inclusion-criteria” to recognize patients with a high chance of mortality and ICU admission. Trial registration https://clinicaltrials.gov/ct2/show/NCT03163095 ; Registered on May 22, 2017.
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    Integration of metabolic and inflammatory mediator profiles as a potential prognostic approach for septic shock in the intensive care unit
    (Critical Care, BioMed Central, 2015-01-15) Mickiewicz, Beata; Tam, Patrick; Jenne, Craig N; Leger, Caroline; Wong, Josee; Winston, Brent W; Doig, Christopher; Kubes, Paul; Vogel, Hans J
    Introduction Septic shock is a major life-threatening condition in critically ill patients and it is well known that early recognition of septic shock and expedient initiation of appropriate treatment improves patient outcome. Unfortunately, to date no single compound has shown sufficient sensitivity and specificity to be used as a routine biomarker for early diagnosis and prognosis of septic shock in the intensive care unit (ICU). Therefore, the identification of new diagnostic tools remains a priority for increasing the survival rate of ICU patients. In this study, we have evaluated whether a combined nuclear magnetic resonance spectroscopy-based metabolomics and a multiplex cytokine/chemokine profiling approach could be used for diagnosis and prognostic evaluation of septic shock patients in the ICU. Methods Serum and plasma samples were collected from septic shock patients and ICU controls (ICU patients with the systemic inflammatory response syndrome but not suspected of having an infection). 1H Nuclear magnetic resonance spectra were analyzed and quantified using the targeted profiling methodology. The analysis of the inflammatory mediators was performed using human cytokine and chemokine assay kits. Results By using multivariate statistical analysis we were able to distinguish patient groups and detect specific metabolic and cytokine/chemokine patterns associated with septic shock and its mortality. These metabolites and cytokines/chemokines represent candidate biomarkers of the human response to septic shock and have the potential to improve early diagnosis and prognosis of septic shock. Conclusions Our findings show that integration of quantitative metabolic and inflammatory mediator data can be utilized for the diagnosis and prognosis of septic shock in the ICU.
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    The Lyme disease spirochete can hijack the host immune system for extravasation from the microvasculature
    (Wiley, 2021-04-23) Tan, Xi; Petri, Björn; DeVinney, Rebekah; Jenne, Craig N; Chaconas, George
    Lyme disease is the most common tick-transmitted disease in the northern hemisphere and is caused by the spirochete Borrelia burgdorferi and related Borrelia species. The constellation of symptoms attributable to this malady result from vascular dissemination of B. burgdorferi throughout the body to invade various tissue types. However, little is known about the mechanism by which the spirochetes can breach the blood vessel wall to reach distant tissues. We have studied this process by direct observation of spirochetes in the microvasculature of living mice using multilaser spinning-disk intravital microscopy. Our results show that in our experimental system, instead of phagocytizing B. burgdorferi, host neutrophils are involved in the production of specific cytokines that activate the endothelium and potentiate B. burgdorferi escape into the surrounding tissue. Spirochete escape is not induced by paracellular permeability and appears to occur via a transcellular pathway. Neutrophil repurposing to promote bacterial extravasation represents a new and innovative pathogenic strategy.