Browsing by Subject "ORGAN FAILURE"

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  • FINNAKI Study Grp (2019)
    Background Injury to endothelium and glycocalyx predisposes to vascular leak, which may subsequently lead to increased fluid requirements and worse outcomes. In this post hoc study of the prospective multicenter observational Finnish Acute Kidney Injury (FINNAKI) cohort study conducted in 17 Finnish intensive care units, we studied the association of Syndecan-1 (SDC-1), Angiopoetin-2 (Ang-2), soluble thrombomodulin (sTM), vascular adhesion protein-1 (VAP-1) and interleukin-6 (IL-6) with fluid administration and balance among septic critical care patients and their association with development of acute kidney injury (AKI) and 90-day mortality. Results SDC-1, Ang-2, sTM, VAP-1 and IL-6 levels were measured at ICU admission from 619 patients with sepsis. VAP-1 decreased (p <0.001) and IL-6 increased (p <0.001) with increasing amounts of administered fluid, but other biomarkers did not show differences according to fluid administration. In linear regression models adjusted for IL-6, only VAP-1 was significantly associated with fluid administration on day 1 (p <0.001) and the cumulative fluid balance on day 5/ICU discharge (p = 0.001). Of 415 patients admitted without AKI, altogether 112 patients (27.0%) developed AKI > 12 h from ICU admission (AKI(>12 h)). They had higher sTM levels than patients without AKI, and after multivariable adjustment log, sTM level was associated with AKI(>12 h) with OR (95% CI) of 12.71 (2.96-54.67), p = 0.001). Ninety-day non-survivors (n = 180; 29.1%) had higher SDC-1 and sTM levels compared to survivors. After adjustment for known confounders, log SDC-1 (OR [95% CI] 2.13 [1.31-3.49], p = 0.002), log sTM (OR [95% CI] 7.35 [2.29-23.57], p <0.001), and log Ang-2 (OR [95% CI] 2.47 [1.44-4.14], p = 0.001) associated with an increased risk for 90-day mortality. Finally, patients who had high levels of all three markers, namely, SDC-1, Ang-2 and sTM, had an adjusted OR of 5.61 (95% CI 2.67-11.79; p <0.001) for 90-day mortality. Conclusions VAP-1 and IL-6 associated with fluid administration on the first ICU day. After adjusting for confounders, sTM was associated with development of AKI after 12 h from ICU admission. SDC-1, Ang-2 and sTM were independently associated with an increased risk for 90-day mortality.
  • Turunen, Antti; Kuuliala, Antti; Mustonen, Harri; Puolakkainen, Pauli; Kylänpää, Leena; Kuuliala, Krista (2021)
    Objectives Clinical practice lacks biomarkers to predict the severity of acute pancreatitis (AP). We studied if intracellular signaling of circulating leukocytes could predict persistent organ dysfunction (OD) and secondary infections in AP. Methods A venous blood sample was taken from 174 patients with AP 72 hours or less from onset of symptoms and 31 healthy controls. Phosphorylation levels (p) of appropriately stimulated signal transducer and activator of transcription 1 (STAT1), STAT6, nuclear factor-kappa B (NF-kappa B), Akt, and nonstimulated STAT3 in monocytes, neutrophils, and lymphocytes was measured using phosphospecific flow cytometry. Results The patients showed higher pSTAT3 and lower pSTAT1, pSTAT6, pNF-kappa B, and pAkt than healthy controls. pSTAT3 in all leukocyte subtypes studied increased, and pSTAT1 in monocytes and T cells decreased in an AP severity-wise manner. In patients without OD at sampling, high pSTAT3 in monocytes and T lymphocytes were associated with development of persistent OD. In patients with OD, low interleukin-4-stimulated pSTAT6 in monocytes and neutrophils and Escherichia coli-stimulated pNF-kappa B in neutrophils predicted OD persistence. High pSTAT3 in monocytes, CD8(+) T cells, and neutrophils; low pSTAT1 in monocytes and T cells; and low pNF-kappa B in lymphocytes predicted secondary infections. Conclusions Leukocyte STAT3, STAT1, STAT6, and NF-kappa Beta phosphorylations are potential predictors of AP severity.
  • Kuusela, Pentti I; Saraswat, Mayank; Joenväärä, Sakari; Kaartinen, Johanna; Järvinen, Asko; Renkonen, Risto (2017)
    Blood culture is the primary diagnostic test performed in a suspicion of bloodstream infection to detect the presence of microorganisms and direct the treatment. However, blood culture is slow and time consuming method to detect blood stream infections or separate septic and/or bacteremic patients from others with less serious febrile disease. Plasma proteomics, despite its challenges, remains an important source for early biomarkers for systemic diseases and might show changes before direct evidence from bacteria can be obtained. We have performed a plasma proteomic analysis, simultaneously at the time of blood culture sampling from ten blood culture positive and ten blood culture negative patients, and quantified 172 proteins with two or more unique peptides. Principal components analysis, Orthogonal Projections to Latent Structures Discriminant Analysis (OPLS-DA) and ROC curve analysis were performed to select protein(s) features which can classify the two groups of samples. We propose a number of candidates which qualify as potential biomarkers to select the blood culture positive cases from negative ones. Pathway analysis by two methods revealed complement activation, phagocytosis pathway and alterations in lipid metabolism as enriched pathways which are relevant for the condition. Data are available via ProteomeXchange with identifier PXD005022.
  • Nieminen, Anne; Maksimow, Mikael; Mentula, Panu; Kyhala, Lea; Kylänpää, Leena; Puolakkainen, Pauli; Kemppainen, Esko; Repo, Heikki; Salmi, Marko (2014)
  • Perner, Anders; Haase, Nicolai; Wetterslev, Jorn; Aneman, Anders; Tenhunen, Jyrki; Guttormsen, Anne Berit; Klemenzson, Gudmundur; Pott, Frank; Bodker, Karen Doris; Badstolokken, Per Martin; Bendtsen, Asger; Soe-Jensen, Peter; Tousi, Hamid; Bestle, Morten; Pawlowicz, Malgorzata; Winding, Robert; Bulow, Hans-Henrik; Kancir, Claude; Steensen, Morten; Nielsen, Jonas; Fogh, Bjarne; Madsen, Kristian R.; Larsen, Nils H.; Carlsson, Marcela; Wiis, Jorgen; Petersen, John Asger; Iversen, Susanne; Schoidt, Ole; Leivdal, Siv; Berezowicz, Pawel; Pettilä, Ville; Ruokonen, Esko; Klepstad, Pal; Karlsson, Sari; Kaukonen, Maija; Rutanen, Juha; Karason, Sigurbergur; Kjaelgaard, Anne Lene; Holst, Lars Brokso; Wernerman, Jan; Scandinavian Critical Care Trials (2011)
  • 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. (2018)
    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 (AUQ 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 (752%), 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.
  • Kylänpää, Marja-Leena; Repo, Heikki; Puolakkainen, Pauli Antero (2010)
  • Gaddnas, Fiia P.; Sutinen, Meeri M.; Koskela, Marjo; Tervahartiala, Taina; Sorsa, Timo; Salo, Tuula A.; Laurila, Jouko J.; Koivukangas, Vesa; Ala-Kokko, Tero I.; Oikarinen, Aarne (2010)
  • Husu, HL; Valkonen, MM; Leppaniemi, AK; Mentula, PJ (2021)
    Background In patients with severe acute pancreatitis (SAP), infected pancreatic necrosis (IPN) is associated with a worsened outcome. We studied risk factors and consequences of IPN in patients with necrotizing SAP. Methods The study consisted of a retrospective cohort of 163 consecutive patients treated for necrotizing SAP at a university hospital intensive care unit (ICU) between 2010 and 2018. Results All patients had experienced at least one persistent organ failure and approximately 60% had multiple organ failure within the first 24 h from admission to the ICU. Forty-seven (28.8%) patients had IPN within 90 days. Independent risk factors for IPN were more extensive anatomical spread of necrotic collections (unilateral paracolic or retromesenteric (OR 5.7, 95% CI 1.5-21.1) and widespread (OR 21.8, 95% CI 6.1-77.8)) compared to local collections around the pancreas, postinterventional pancreatitis (OR 13.5, 95% CI 2.4-76.5), preceding bacteremia (OR 4.8, 95% CI 1.3-17.6), and preceding open abdomen treatment for abdominal compartment syndrome (OR 3.6, 95% CI 1.4-9.3). Patients with IPN had longer ICU and overall hospital lengths of stay, higher risk for necrosectomy, and higher readmission rate to ICU. Conclusions Wide anatomical spread of necrotic collections, postinterventional etiology, preceding bacteremia, and preceding open abdomen treatment were identified as independent risk factors for IPN.
  • Peake, Sandra L.; Delaney, Anthony; Bailey, Michael; Bellomo, Rinaldo; ARISE Investigators; Pettilä, Ville (2017)
    Study objective: The influence of the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3) on the conduct of future sepsis research is unknown. We seek to examine the potential effect of the new definitions on the identification and outcomes of patients enrolled in a sepsis trial. Methods: This was a post hoc analysis of the Australasian Resuscitation in Sepsis Evaluation (ARISE) trial of early goal-directed therapy that recruited 1,591 adult patients presenting to the emergency department (ED) with early septic shock diagnosed by greater than or equal to 2 systemic inflammatory response syndrome criteria and either refractory hypotension or hyperlactatemia. The proportion of participants who would have met the Sepsis-3 criteria for quick Sequential Organ Failure Assessment (qS0FA) score, sepsis (an increased Sequential Organ Failure Assessment score >= 2 because of infection) and septic shock before randomization, their baseline characteristics, interventions delivered, and mortality were determined. Results: There were 1,139 participants who had a qSOFA score of greater than or equal to 2 at baseline (71.6% [95% confidence interval [Cl) 69.4% to 73.8%]). In contrast, 1,347 participants (84.7% [95% CI 82.9% to 86.4%]) met the Sepsis-3 criteria for sepsis. Only 1,010 participants were both qSOFA positive and met the Sepsis-3 criteria for sepsis (63.5% [95% CI 61.1% to 65.8%]). The Sepsis-3 definition for septic shock was met at baseline by 203 participants (12.8% [95% CI 11.2% to 14.5%]), of whom 175 (86.2% [95% CI 81.5% to 91.0%]) were also qSOFA positive. Ninety-day mortality for participants fulfilling the Sepsis-3 criteria for sepsis and septic shock was 20.4% (95% CI 18.2% to 22.5%) (274/1,344) and 29.6% (95% CI 23.3% to 35.8% [60/203]) versus 9.4% (95% CI 5.8% to 13.1%) (23/244) and 17.1% (95% CI 15.1% to 19.1% [237/1,388]), respectively, for participants not meeting the criteria (risk differences 11.0% [95% CI 6.2% to 14.8%] and 12.5% [95% CI 6.3% to 19.4%], respectively). Conclusion: Most ARISE participants did not meet the Sepsis-3 definition for septic shock at baseline. However, the majority fulfilled the new sepsis definition and mortality was higher than for participants not fulfilling the criteria. A quarter of participants meeting the new sepsis definition did not fulfill the qSOFA screening criteria, potentially limiting its utility as a screening tool for sepsis trials with patients with suspected infection in the ED. The implications of the new definitions for patients not eligible for recruitment into the ARISE trial are unknown.
  • Vaara, Suvi T.; Hollmen, Maija; Korhonen, Anna-Maija; Maksimow, Mikael; Ala-Kokko, Tero; Salmi, Marko; Jalkanen, Sirpa; Pettilä, Ville; FINNAKI Study Grp (2016)
    Background CD73 dephosphorylates adenosine monophosphate to adenosine that is an anti-inflammatory molecule inhibiting immune activation and vascular leakage. Therefore, CD73 could be an interesting mediator both in sepsis and acute kidney injury (AKI). We aimed to explore the soluble CD73 (sCD73) levels and their evolution in critically ill patients with severe sepsis and, second, to scrutinize the potential association of sCD73 levels with AKI and 90-day mortality. Methods This was a post-hoc laboratory analysis of the prospective, observational FINNAKI study conducted in 17 Finnish ICU during 5 months in 2011-2012. Plasma samples of 588 patients admitted with severe sepsis/shock or with developing severe sepsis were analyzed at 0h (ICU admission) and 24h, and additionally, on day 3 or day 5 from a subset of the patients. Results The median [IQR] sCD73 levels at 0h were 5.11 [3.29-8.28] ng/mL and they decreased significantly from 0h to 4.14 [2.88-7.11] ng/mL at 24h, P Conclusions Compared to normal population, the sCD73 levels were generally low at 0h, showed a decrease to 24h, and later an increase by day 5. The sCD73 levels do not seem useful in predicting the development of AKI or 90-day mortality among patients with severe sepsis or shock.
  • Turunen, Antti; Kuuliala, Antti; Penttilä, Anne; Kaukonen, Kirsi-Maija; Mustonen, Harri; Pettilä, Ville; Puolakkainen, Pauli; Kylänpää, Leena; Kuuliala, Krista (2020)
    Activation of intracellular signaling pathways in circulating leukocytes represents an early step in systemic immune-inflammatory response occurring e.g. in acute pancreatitis (AP) and sepsis. Previously, we found aberrations in the phosphorylation of leukocyte signaling proteins in patients with sepsis or AP (measured
  • Poukkanen, Meri; Koskenkari, Juha; Vaara, Suvi T.; Pettila, Ville; Karlsson, Sari; Korhonen, Anna-Maija; Laurila, Jouko J.; Kaukonen, Kirsi-Maija; Lund, Vesa; Ala-Kokko, Tero I.; FINNAKI Study Grp (2014)