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Dysregulated activities of proline-specific enzymes in septic shock patients (sepsis-2).

ABSTRACT: The proline-specific enzymes dipeptidyl peptidase 4 (DPP4), prolylcarboxypeptidase (PRCP), fibroblast activation protein ? (FAP) and prolyl oligopeptidase (PREP) are known for their involvement in the immune system and blood pressure regulation. Only very limited information is currently available on their enzymatic activity and possible involvement in patients with sepsis and septic-shock. The activity of the enzymes was measured in EDTA-plasma of patients admitted to the intensive care unit (ICU): 40 septic shock patients (sepsis-2) and 22 ICU control patients after major intracranial surgery. These data were used to generate receiver operating characteristic (ROC) curves. A survival analysis (at 90 days) and an association study with other parameters was performed. PRCP (day 1) and PREP (all days) enzymatic activities were higher in septic shock patients compared to controls. In contrast, FAP and DPP4 were lower in these patients on all studied time points. Since large differences were found, ROC curves were generated and these yielded area under the curve (AUC) values for PREP, FAP and DPP4 of 0.88 (CI: 0.80-0.96), 0.94 (CI: 0.89-0.99) and 0.86 (CI: 0.77-0.95), respectively. PRCP had a lower predicting value with an AUC of 0.71 (CI: 0.58-0.83). A nominally significant association was observed between survival and the DPP4 enzymatic activity at day 1 (p<0.05), with a higher DPP4 activity being associated with an increase in survival. All four enzymes were dysregulated in septic shock patients. DPP4, FAP and PREP are good in discriminating between septic shock patients and ICU controls and should be further explored to see whether they are already dysregulated in earlier stages, opening perspectives for their further investigation as biomarkers in sepsis. DPP4 also shows potential as a prognostic biomarker. Additionally, the associations found warrant further research.

SUBMITTER: Vliegen G

PROVIDER: S-EPMC7173796 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Dysregulated activities of proline-specific enzymes in septic shock patients (sepsis-2).

Vliegen Gwendolyn G Kehoe Kaat K Bracke An A De Hert Emilie E Verkerk Robert R Fransen Erik E Jongers Bart 's B' Peters Esther E Lambeir Anne-Marie AM Kumar-Singh Samir S Pickkers Peter P Jorens Philippe G PG De Meester Ingrid I

PloS one 20200421 4

The proline-specific enzymes dipeptidyl peptidase 4 (DPP4), prolylcarboxypeptidase (PRCP), fibroblast activation protein α (FAP) and prolyl oligopeptidase (PREP) are known for their involvement in the immune system and blood pressure regulation. Only very limited information is currently available on their enzymatic activity and possible involvement in patients with sepsis and septic-shock. The activity of the enzymes was measured in EDTA-plasma of patients admitted to the intensive care unit (I ...[more]

PMID: 32315321

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Project description:ObjectiveTo identify research priorities in the management, epidemiology, outcome and underlying causes of sepsis and septic shock.DesignA consensus committee of 16 international experts representing the European Society of Intensive Care Medicine and Society of Critical Care Medicine was convened at the annual meetings of both societies. Subgroups had teleconference and electronic-based discussion. The entire committee iteratively developed the entire document and recommendations.MethodsEach committee member independently gave their top five priorities for sepsis research. A total of 88 suggestions (ESM 1 - supplemental table 1) were grouped into categories by the committee co-chairs, leading to the formation of seven subgroups: infection, fluids and vasoactive agents, adjunctive therapy, administration/epidemiology, scoring/identification, post-intensive care unit, and basic/translational science. Each subgroup had teleconferences to go over each priority followed by formal voting within each subgroup. The entire committee also voted on top priorities across all subgroups except for basic/translational science.ResultsThe Surviving Sepsis Research Committee provides 26 priorities for sepsis and septic shock. Of these, the top six clinical priorities were identified and include the following questions: (1) can targeted/personalized/precision medicine approaches determine which therapies will work for which patients at which times?; (2) what are ideal endpoints for volume resuscitation and how should volume resuscitation be titrated?; (3) should rapid diagnostic tests be implemented in clinical practice?; (4) should empiric antibiotic combination therapy be used in sepsis or septic shock?; (5) what are the predictors of sepsis long-term morbidity and mortality?; and (6) what information identifies organ dysfunction?ConclusionsWhile the Surviving Sepsis Campaign guidelines give multiple recommendations on the treatment of sepsis, significant knowledge gaps remain, both in bedside issues directly applicable to clinicians, as well as understanding the fundamental mechanisms underlying the development and progression of sepsis. The priorities identified represent a roadmap for research in sepsis and septic shock.

Project description:BackgroundDespite growing interest in treatment strategies that limit oxygen exposure in ICU patients, no studies have compared conservative oxygen with standard oxygen in postsurgical patients with sepsis/septic shock, although there are indications that it may improve outcomes. It has been proven that high partial pressure of oxygen in arterial blood (PaO2) reduces the rate of surgical-wound infections and mortality in patients under major surgery. The aim of this study is to examine whether PaO2 is associated with risk of death in adult patients with sepsis/septic shock after major surgery.MethodsWe performed a secondary analysis of a prospective observational study in 454 patients who underwent major surgery admitted into a single ICU. Patients were stratified in two groups whether they had hyperoxemia, defined as PaO2 > 100 mmHg (n = 216), or PaO2 ≤ 100 mmHg (n = 238) at the day of sepsis/septic shock onset according to SEPSIS-3 criteria maintained during 48 h. Primary end-point was 90-day mortality after diagnosis of sepsis. Secondary endpoints were ICU length of stay and time to extubation.ResultsIn patients with PaO2 ≤ 100 mmHg, we found prolonged mechanical ventilation (2 [8] vs. 1 [4] days, p < 0.001), higher ICU stay (8 [13] vs. 5 [9] days, p < 0.001), higher organ dysfunction as assessed by SOFA score (9 [3] vs. 7 [5], p < 0.001), higher prevalence of septic shock (200/238, 84.0% vs 145/216) 67.1%, p < 0.001), and higher 90-day mortality (37.0% [88] vs. 25.5% [55], p = 0.008). Hyperoxemia was associated with higher probability of 90-day survival in a multivariate analysis (OR 0.61, 95%CI: 0.39-0.95, p = 0.029), independent of age, chronic renal failure, procalcitonin levels, and APACHE II score > 19. These findings were confirmed when patients with severe hypoxemia at the time of study inclusion were excluded.ConclusionsOxygenation with a PaO2 above 100 mmHg was independently associated with lower 90-day mortality, shorter ICU stay and intubation time in critically ill postsurgical sepsis/septic shock patients. Our findings open a new venue for designing clinical trials to evaluate the boundaries of PaO2 in postsurgical patients with severe infections.

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Dysregulated activities of proline-specific enzymes in septic shock patients (sepsis-2).

Publications

Dysregulated activities of proline-specific enzymes in septic shock patients (sepsis-2).

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