Browsing by Subject "CRITICALLY-ILL"

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  • Lankelma, Jacqueline M.; Belzer, Clara; Hoogendijk, Arie J.; de Vos, Alex F.; de Vos, Willem M.; van der Poll, Tom; Wiersinga, W. Joost (2016)
    OBJECTIVES: Broad-spectrum antibiotics disrupt the intestinal microbiota. The microbiota is essential for physiological processes, such as the development of the gut immune system. Recent murine data suggest that the intestinal microbiota also modulates systemic innate immune responses; however, evidence in humans is lacking. METHODS: Twelve healthy young men were given oral broad-spectrum antibiotics (ciprofloxacin 500 mg bid, vancomycin 500 mg tid and metronidazole 500 mg tid) for 7 days. At baseline, 1 day, and 6 weeks after antibiotics, blood and feces were sampled. Whole blood and isolated mononuclear cells were stimulated with selected Toll-like receptor agonists and heat-killed bacteria. Microbiota diversity and composition was determined using bacterial 16S rDNA sequencing. RESULTS: One day after the antibiotic course, microbial diversity was significantly lower compared with baseline. After antibiotic therapy, systemic mononuclear cells produced lower levels of tumor necrosis factor (TNF)-alpha after ex vivo stimulation with lipopolysaccharide (LPS). This diminished capacity to produce TNF-alpha was restored 6 weeks after cessation of antibiotic therapy. In whole blood, a reduced capacity to release interleukin (IL)-1 beta and IL-6 was observed after LPS stimulation. Antibiotic treatment did not impact on differential leukocyte counts, phagocytosis, and cell surface markers of neutrophils and monocytes. CONCLUSIONS: In this proof-of-principle study of healthy subjects, microbiota disruption by broad-spectrum antibiotics is reversibly associated with decreased systemic cellular responsiveness towards LPS. The implications of these findings in a clinical setting remain to be determined.
  • Pettilä, Ville; Kyhälä, Lea; Kylänpää, Marja-Leena; Leppäniemi, Ari; Tallgren, Minna; Markkola, Antti Thor Olavi; Puolakkainen, Pauli; Repo, Heikki; Kemppainen, Esko (2010)
  • 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 (2018)
    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 selfperpetuating 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.
  • Rasilainen, S. K.; Mentula, P. J.; Leppaniemi, A. K. (2016)
    Background and aims: The goal after open abdomen treatment is to reach primary fascial closure. Modern negative pressure wound therapy systems are sometimes inefficient for this purpose. This retrospective chart analysis describes the use of the components separation' method in facilitating primary fascial closure after open abdomen. Material and methods: A total of 16 consecutive critically ill surgical patients treated with components separation during open abdomen management were analyzed. No patients were excluded. Results: Primary fascial closure was achieved in 75% (12/16). Components separation was performed during ongoing open abdomen treatment in 7 patients and at the time of delayed primary fascial closure in 9 patients. Of the former, 3/7 (43%) patients reached primary fascial closure, whereas all 9 patients in the latter group had successful fascial closure without major complications (p=0.019). Conclusion: Components separation is a useful method in contributing to successful primary fascial closure in patients treated for open abdomen. Best results were obtained when components separation was performed simultaneously with primary fascial closure at the end of the open abdomen treatment.
  • Annane, Djillali; Fuchs-Buder, Thomas; Zoellner, Christian; Kaukonen, Maija; Scheeren, Thomas W. L. (2018)
  • Wiersema, Renske; Jukarainen, Sakari; Vaara, Suvi T.; Poukkanen, Meri; Lakkisto, Päivi; Wong, Hector; Linder, Adam; van der Horst, Iwan C. C.; Pettilä, Ville (2020)
    Background The pathophysiology of septic acute kidney injury is inadequately understood. Recently, subphenotypes for sepsis and AKI have been derived. The objective of this study was to assess whether a combination of comorbidities, baseline clinical data, and biomarkers could classify meaningful subphenotypes in septic AKI with different outcomes. Methods We performed a post hoc analysis of the prospective Finnish Acute Kidney Injury (FINNAKI) study cohort. We included patients admitted with sepsis and acute kidney injury during the first 48 h from admission to intensive care (according to Kidney Disease Improving Global Outcome criteria). Primary outcomes were 90-day mortality and renal recovery on day 5. We performed latent class analysis using 30 variables obtained on admission to classify subphenotypes. Second, we used logistic regression to assess the association of derived subphenotypes with 90-day mortality and renal recovery on day 5. Results In total, 301 patients with septic acute kidney injury were included. Based on the latent class analysis, a two-class model was chosen. Subphenotype 1 was assigned to 133 patients (44%) and subphenotype 2 to 168 patients (56%). Increased levels of inflammatory and endothelial injury markers characterized subphenotype 2. At 90 days, 29% of patients in subphenotype 1 and 41% of patients in subphenotype 2 had died. Subphenotype 2 was associated with a lower probability of short-term renal recovery and increased 90-day mortality. Conclusions In this post hoc analysis, we identified two subphenotypes of septic acute kidney injury with different clinical outcomes. Future studies are warranted to validate the suggested subphenotypes of septic acute kidney injury.