Methods and kits for the rapid determination of patients at high risk of death during severe sepsis and septic shock

A technology for septic shock and sepsis, applied in disease diagnosis, biological testing, material inspection, etc., can solve problems such as useless life support, difficult and expensive for clinicians

Inactive Publication Date: 2011-11-23
巴黎公众助理医院
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The absence of an early, specific, and sensitive marker for determining prognosis creates difficulties not only for clinicians in terms of expensive drug prescriptions and useless life support, but also in terms of patient selection for study program enrolment also create difficulties for experimental researchers
Some promising markers have been tested, such as procalcitonin (Clec'h et al., 2004), HLA-DR (Monneret et al., 2006), IL-6 (Abraham et al., 2001) and soluble myeloid Cell triggering receptor (sTREM) (Gibot et al., 2005); however results are conflicting

Method used

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  • Methods and kits for the rapid determination of patients at high risk of death during severe sepsis and septic shock
  • Methods and kits for the rapid determination of patients at high risk of death during severe sepsis and septic shock
  • Methods and kits for the rapid determination of patients at high risk of death during severe sepsis and septic shock

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0084] Example 1: Multicenter Evaluation of Plasma S100A8 / A9 Complex as an Early Prognostic Marker in Septic Shock

[0085] Materials and methods

[0086] All experiments reported below were performed using the materials and methods described below.

[0087] patient

[0088] This multicentre study was approved by the Cochin Hospital Ethics Committee (#CCPPRB 2061) and patients were recruited from 4 intensive care units (two medical, two surgical). Only patients meeting the criteria for septic shock as defined by the ACCP / SCCM joint meeting (Bone et al., 1992) were selected. Inclusion criteria required patients with septic shock to have at least two organ failures as defined by SOFA (Vincent et al., 1998). The first blood sample was collected on day 0 (D0), defined as within 24 hours of the onset of second organ failure.

[0089] Blood samples were obtained from these patients recruited to the training cohort who met the inclusion criteria for the determination of gene ...

Embodiment 2

[0138] Example 2: Trend of plasma S100A8 / A9 complex levels over time in septic shock patients

[0139] As in example 1, for experiments performed on day 0 and day 1, it has been completed in 28 days (days 0, 1, 7, 14, 28)

[0140] Results from 111 patients (49 training group, 62 test group in Example 1) showed that plasma protein levels decreased over time in survivors but not in non-survivors ( Figure 5 ). Plasma S100A8 / A9 was still high at day 28 in survivors compared to controls (median 2.65 μg / ml (IQR 2.60)).

[0141] Only one patient with a good final outcome showed surprisingly high levels of the S100A8 / A9 complex at day 14. In this patient, the S100A8 / A9 values ​​were 4.7 μg / ml on day 0, 4.0 μg / ml on day 1, 4.5 μg / ml on day 7, and 20.1 μg / ml on day 14, although its progression was smooth And had a good final outcome (discharged by day 28). But S100A8 / A9 levels at day 14 were not controlled, and this surprising outcome may be a measurement artifact.

[0142] Both...

Embodiment 3

[0150] Example 3: Trends of S100A8 and S100A9 gene expression levels over time in patients with septic shock

[0151] Image 6 and Figure 7 Gene expression of S100A8 and S100A9 in 32 patients is shown. These data were collected from microarray analysis performed on an Affymetrix HG-U133 Plus 2.0 array using the same method as described in EP 2085486A1.

[0152] There was a slight decrease in S100A8 gene expression among survivors between day 0 and day 7, even though it was not significant as 28 days passed. This trend was not observed in the non-survivors. S100A8 gene expression statistics are as follows:

[0153] Friedman's test among survivors, Day 0-Day 28, n=11: not significant

[0154] Day 0-Day 7, n=18: p=0.0421

[0155] Wilcoxon test among survivors, day 0-day 1, n=17: not significant

[0156] Wilcoxon test among non-survivors, day 0-day 1, n=9: not significant

[0157] Mann Whitney test, Survivors vs. Non-survivors: Significant at day 1, p=0.035.

[0158] S...

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Abstract

The present invention provides methods and kits to obtain an early evaluation of mortality risk and help therapeutic decisions for patients in severe sepsis with two organ failures, for example for patients in septic shock. The invention is based on the measure of the level of S100A8 / A9 complex in plasma, since a level of S100A8 / A9 above a predetermined threshold is indicative of a bad prognosis and a level of S100A8 / A9 below said predetermined threshold is indicative of a good prognosis.

Description

technical field [0001] The present invention relates to the field of treatment of severe medical syndromes such as severe sepsis or septic shock. In particular, the present invention provides methods and kits to obtain early assessment of lethal risk and adjuvant treatment decisions for severe sepsis patients with two organ failures, such as for patients with septic shock. Background technique [0002] Septic shock, the most severe clinical manifestation of sepsis, has a poor prognosis despite strong therapeutic support and anti-infective strategies to eradicate infectious foci. Sepsis syndromes are defined as symptoms associated with host responses to the abnormal presence of microorganisms (bacteria, viruses or parasites) or their antigenic components. Local infection may spread throughout the body for different reasons, with specific activation of blood immune cells controlling innate immunity in the early phase and adaptive immunity in the second phase. Such a strong i...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): G01N33/50G01N33/68
CPCG01N2800/26G01N33/5091G01N33/6893
Inventor D·帕扬·德拉加朗代里A·C·卢卡谢维奇
Owner 巴黎公众助理医院
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