13 research outputs found
Elevation of C-reactive protein, P-selectin and Resistin as potential inflammatory biomarkers of urogenital Schistosomiasis exposure in preschool children
Diagnostic profiling of MDSCs in sepsis
With 50 million cases and 11 million deaths per year, sepsis is one of the leading causes of death worldwide. Sepsis is caused by a dysregulated host response to an infection, which consists of concurrent inflammatory and immunosuppressive reactions. Myeloid-derived suppressor cells (MDSCs) are immature myeloid cells characterized by their immunosuppressive properties, rising in inflammatory diseases. MDSCs are subdivided into polymorphonuclear MDSCs (PMN-MDSCs) and monocytic MDSCs (M-MDSCs) based on their relationship with mature PMNs and monocytes. It is unknown how their level varies over time in human sepsis. We hypothesized that MDSCs have diagnostic and prognostic potential in sepsis patients. In this thesis, we aimed to illustrate the dynamic profile of MDSCs in critically ill patients in relation to sepsis severity, secondary infections, and mortality.
Four study cohorts were used: 1) healthy subjects infused with endotoxin, 2) non-infectious, critically ill patients without antibiotic therapy (PIPOVAP study), 3) hospitalized coronavirus 2019 (COVID-19) patients and, 4) sepsis patients with multi-organ dysfunction syndrome (MODS) (INCLASS study). Serial samples of peripheral blood were used to quantify MDSCs by flow cytometry and FlowSOM to avoid gating biases. M-MDSCs were defined as HLA-DRlow monocytes, and PMN-MDSCs as CD16low granulocytes. Furthermore, we quantified up to 49 cytokines by multiplex bead assay, and analysed the functionality of monocytes and dendritic cells (DCs) in ex vivo stimulated whole blood by intracellular cytokine staining and flow cytometry.
Endotoxin infusion in healthy subjects induced a quick, massive, and transient accumulation of MDSCs in peripheral blood. PMN-MDSCs increased 40-fold to reach up to 43% of all granulocytes 6-8 hours after infusion. M-MDSCs increased 10-fold 8 hours after endotoxin infusion comprising more than half of total monocytes. After 24 hours, PMN-MDSCs and M-MDSCs returned to baseline levels. In patients enrolled in the PIPOVAP, COVID-19, and INCLASS studies, the blood concentration of PMN-MDSCs and M-MDSCs were high at study inclusion and correlated to disease severity. In the PIPOVAP study, high levels of M-MDSCs also correlated to the development of secondary gram-negative infections. High MDSCs were associated with mortality in non-infectious critically ill patients (PIPOVAP), but with survival in sepsis patients with MODS (INCLASS). MDSCs correlated with the concentrations of blood cytokines, chemokines, and growth factors in the PIPOVAP and COVID-19 studies. Finally, 3 months after the COVID-19 diagnosis, irrespective of initial disease severity, MDSCs were back to normal levels whilst the production of cytokines by blood cells was still largely affected.
Altogether, we report that MDSCs quickly rise during endotoxemia and are associated with sepsis severity. Thus, MDSCs might represent valuable tools to screen vulnerable patients in the intensive care. Additionally, we show for the first time that a high level of MDSCs is associated with improved outcomes in a subset of extremely ill sepsis patients with MODS. Overall, MDSCs may represent sepsis biomarkers and targets of therapy. To pursue clinical development, the quantification method of MDSCs in patients need to be standardized, and the function and plasticity of MDSCs during sepsis should be further explored.
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Avec 50 millions de cas et 11 millions de décès par an, le sepsis est l'une des principales causes de décès dans le monde. Le sepsis est causé par une réponse dérégulée de l'hôte en réponse à une infection, qui consiste en des réactions inflammatoires et immunosuppressives concomitantes. Les cellules suppressives d'origine myéloïde (MDSCs) sont des cellules myéloïdes immatures caractérisées par leurs propriétés immunosuppressives. Les MDSCs sont subdivisées en MDSCs polymorphonucléaires (PMN- MDSCs) et MDSCs monocytaires (M-MDSCs) en fonction de leur relation avec les PMNs et monocytes matures. L’évolution des MDSCs au cours d’un sepsis humain est très peu documentée. Pour combler cette lacune, dans cette thèse nous avons analysé l’expression des MDSCs dans le sang en regard de la sévérité du sepsis et de paramètres immunologiques.
Quatre études de cohortes ont été utilisées: 1) des sujets sains perfusés avec de l'endotoxine, un composant de bactéries gram-négatives qui permet de mimer une infection bactérienne (étude endotoxin), 2) des patients non infectieux, hospitalisés aux soins intensifs (SI) (étude PIPOVAP),
3) des patients coronavirus 2019 hospitalisés (étude COVID-19) et 4) des patients sepsis présentant un syndrome de défaillance multiviscérale associé à une mortalité d’environ ~70% (étude INCLASS). Des échantillons sériels de sang périphérique ont été collectés pour quantifier les MDSCs. En outre, nous avons mesuré une cinquantaine de cytokines, chimiokines et facteurs de croissances et analysé la fonctionnalité des globules blancs du sang complet.
La perfusion d'endotoxine chez des sujets sains induisait une accumulation rapide, massive (pouvant aller jusqu’à 30-40% de tous les globules blancs) et transitoire de MDSCs. Après 24 heures, les MDSCs étaient revenus à un taux normal. Les MDSCs étaient élevées chez les patients inclus dans les études PIPOVAP, COVID-19 et INCLASS. Cette augmentation corrélait avec la gravité de la maladie et, dans l'étude PIPOVAP, avec le développement d'infections nosocomiales. Des taux élevés de MDSCs étaient associés à la mortalité chez les patients non-infectieux hospitalisés aux SI. Par contre, une accumulation de MDSCs était associée à un devenir favorable chez les patients sepsis ayant développé un syndrome de défaillance multiviscérale. Finalement, chez les patients COVID-19 ré-analysés 3 mois après leur hospitalisation, les MDSCs étaient normales alors que certains dysfonctionnements immunitaires étaient détectés. Ceux-ci qui pourraient être associés au syndrome de « COVID long ».
En résumé, nous rapportons que les MDSCs augmentent rapidement et fortement dans le sang d’individus exposés à un composant de bactérie, et qu’elles sont associées à la sévérité du sepsis. Ainsi, les MDSCs ont un potentiel diagnostique et pronostique chez les patients atteints de sepsis. Par ailleurs, les MDSCs pourraient représenter des cibles d’immunothérapie, d’autant plus que des traitements ciblant les MDSCs sont actuellement testées dans le cadre de cancers.
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The immune system protects the human body against infections caused by microorganisms, like viruses and bacteria. White blood cells are one important part of the immune system. White blood cells kill invading organisms as well as warn and activate other white blood cells to increase host defences. However, sometimes the immune system does not respond appropriately to an infection, or it cannot control it. When that happens, white blood cells injure tissues through collateral damage while trying to contain the infection. This can lead to organ failure, which is associated with a high mortality rate. When this happens, it is called sepsis. With 50 million cases and 11 million deaths per year, sepsis is a global health priority. During sepsis, white blood cells can respond too strongly, stop functioning, or even repress the function of other cells. This is called immunosuppression. Immunosuppression can cause long-term effects in recovered sepsis patients, such as the development of new infections and heart diseases.
In this thesis, we were interested in a particular type of white blood cells called myeloid-derived suppressor cells (MDSCs). MDSCs restrict the function of other white blood cells. In short, they are immunosuppressive. Healthy people have very few MDSCs, but patients with inflammatory diseases such as cancer, have high levels of MDSCs. How fast MDSCs respond after an infection, and what type of impact these cells have during sepsis are largely unknown. We aimed to give an in-depth view of the dynamics of MDSCs in conditions of inflammation and infection.
We set up four studies to address our aim. Blood was collected from individuals at different time intervals to measure MDSCs and other immune parameters. The first study was with healthy volunteers who were injected with bacterial compounds, which trigger white blood cells mimicking bacterial sepsis. We observed that MDSC levels rise strongly 2 hours after infusion and remained high until 8 hours after the injection. MDSCs returned to normal levels after 24 hours. This tells us that MDSCs are very fast responders when the host is triggered by a bacterial compound. In the second study, we tested critically ill patients in the Intensive Care Unit (ICU) without an infection. We noticed that patients with high levels of MDSCs were more likely to become infected and to die. We assume that MDSCs suppressed the function of anti-microbial white blood cells, increasing the risks of infection. In the third study, we looked at COVID-19 patients. COVID-19 patients can develop sepsis, which is one of the reasons why some must be hospitalized. Patients admitted to the ICU had more MDSCs than patients who did not require admission to the ICU. In the fourth study, we analysed severe sepsis patients with multiple organ dysfunctions. Patients with high levels of MDSCs were more likely to survive. Most likely, MDSCs were beneficial in these severe patients because MDSCs were counterbalancing the otherwhite blood cells that were overreacting and damaging.
To conclude, this thesis shows 1) how MDSCs are modulated during sepsis, and 2) that MDSCs can be helpful or hurtful depending on the degree of sepsis severity. We propose to use MDSCs as signals of sepsis severity, and possibly as targets of therapy as currently tested in cancer patients.
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Le système immunitaire protège notre organisme contre les infections par les bactéries et les virus. Les globules blancs présents dans le sang sont des éléments vitaux du système immunitaire car ils peuvent tuer les bactéries et les virus. Par ailleurs ils activent d'autres globules blancs, augmentent les défenses de l'hôte, et confèrent la mémoire immunitaire protégeant de réinfections. Il arrive que le système immunitaire ne réponde pas de façon appropriée ou ne peut pas contrôler l’infection. Dans ce cas, les globules blancs peuvent causer des dommages collatéraux aux tissus. Cela peut entraîner une défaillance d’organe, associée à un taux de mortalité élevé. C'est ce qu'on appelle un sepsis.
Avec 50 millions de cas et 11 millions de décès par an, le sepsis est une priorité sanitaire mondiale. Lors d’un sepsis, les globules blancs peuvent cesser de fonctionner ou empêcher le fonctionnement d'autres cellules. C'est ce qu'on appelle l'immunosuppression. Elle peut avoir des effets à long terme chez les patients ayant guéris d’un sepsis, comme le développement d’infections et ou de maladies cardiaques.
Dans cette thèse, nous nous sommes intéressés aux globules blancs appelés cellules myéloïdes suppressives (MDSCs). Les MDSCs restreignent la fonction des autres globules blancs, elles sont donc immunosuppressives. Les personnes en bonne santé, contrairement à celles atteintes de maladies inflammatoires y compris le cancer, ont très peu de MDSCs dans leur sang. Très peu étant connu quant à l’implication des MDSCs dans le sepsis, notre objectif était de fournir une analyse approfondie de la dynamique des MDSCs dans des conditions d'infection.
Nous avons mis en place quatre études pour répondre à notre objectif. Le sang a été prélevé à intervalles réguliers pour mesurer les MDSCs et d'autres paramètres immunologiques. La première étude portait sur des volontaires sains recevant une injection d’un morceau de bactérie simulant un sepsis à bactérie. Les MDSCs augmentaient rapidement, fortement, et transitoirement revenant à un niveau normal 24 heures après l’injection. Dans la deuxième étude, nous avons testé des patients sans infection, admis aux soins intensifs (SI). Nous avons remarqué que les patients avec beaucoup de MDSCs développaient plus d’infections nosocomiales, dont des infections mortelles. Nous pensons que les MDSCs supprimaient la fonction des globules blancs antimicrobiens, augmentant les risques d'infection. Dans la troisième étude, nous avons examiné des patients atteints de COVID-19. Les patients COVID-19 admis aux SI avaient plus de MDSCs que ceux n’ayant pas besoin d'être admis aux SI. Dans la quatrième étude, nous avons analysé des patients atteints de sepsis grave présentant une défaillance de plusieurs organes. Ceux avec beaucoup de MDSCs avaient un pronostique plus favorable. Nous pensons que, dans ce contexte particulièrement sévère (environ 70% des patients décédaient), les MDSCs contrebalançaient la réponse excessive de globules blancs et les dommages collatéraux subséquents.
Pour conclure, cette thèse décrit comment les MDSCs sont modulées pendant un sepsis, et que les MDSCs peuvent être utiles ou néfastes selon le degré de sévérité des patients infectés. Les MDSCs pourraient être utilisées comme indicateur de gravité du sepsis, et éventuellement comme cibles de traitements tels que ceux ciblant les MDSCs testés actuellement chez les patients cancéreux.
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Het lichaam wordt door zijn eigen immuunsysteem beschermd tegen indringers zoals virussen en bacteriën. Witte bloedcellen spelen daarbij een belangrijke rol. Ze doden indringers en waarschuwen en activeren andere witte bloedcellen om de afweer te versterken. Soms reageren de witte bloedcellen te sterk of krijgen ze de infectie niet onder controle. In een poging de infectie te bestrijden beschadigen witte bloedcellen dan de weefsels. Deze weefselschade kan leiden tot uitval van organen. De kans op overlijden is hierbij groot. Dit ernstige ziektebeeld wordt sepsis genoemd. Jaarlijks ontwikkelen wereldwijd ongeveer 50 miljoen mensen sepsis waarvan er 11 miljoen overlijden. Na een doorgemaakte sepsis is er kans op langdurige gezondheidsproblemen, zoals bijvoorbeeld nieuwe infecties en hartaandoeningen. Dit komt doordat tijdens sepsis, witte bloedcellen niet alleen te sterk reageren, maar ook stoppen met functioneren en de functie van andere cellen onderdrukken. Dit laatste wordt immunosuppressie genoemd en kan lang aanhouden nadat patiënten van sepsis hersteld zijn.
In dit proefschrift onderzochten we een bepaald type witte bloedcel, namelijk “myeloid-derived suppressor cells” (MDSC's). MDSC's onderdrukken de functie van andere witte bloedcellen en werken dus immunosuppressief. In tegenstelling tot gezonde mensen hebben patiënten met ontstekingsziekten zoals kanker of auto-immuunziekten veel MDSC’s. Het is echter nog onbekend hoe snel MDSC’s reageren op een infectie en welke rol zij spelen tijdens sepsis.
We hebben vier onderzoeken uitgevoerd om hierin meer inzicht te krijgen. De eerste studie betrof gezonde vrijwilligers die stukjes van bacteriën toegediend kregen. Dit activeert witte bloedcellen en is daarom vergelijkbaar met bacteriële sepsis. We constateerden dat de MDSC-waarden in het bloed 2 uur na toediening sterk stegen en vervolgens verhoogd bleven tot 8 uur na toediening. Na 24 uur keerden MDSC-waarden terug naar normaal. Hieruit kunnen we concluderen dat MDSC's zeer snel reageren wanneer het lichaam wordt geïnfecteerd door een bacterie. De tweede studie betrof ernstig zieke patiënten die initieel geen infectie hadden op de intensive care (IC). In deze groep zagen we dat patiënten met hoge MDSC-waarden een grotere kans hadden om een infectie te ontwikkelen en hierdoor te overlijden. Waarschijnlijk onderdrukten MDSC's de functie van andere infectie-bestrijdende witte bloedcellen, waardoor het infectierisico toenam. De derde studie betrof COVID-19-patiënten. Sommige COVID-19-patiënten ontwikkelen sepsis en moeten worden opgenomen in het ziekenhuis. Wij constateerden dat COVID-19-patiënten die op de IC waren opgenomen, meer MDSC's hadden dan patiënten die op de verpleegafdeling konden blijven. Ten slotte, onderzochten we in vierde studie patiënten met ernstige sepsis bij wie meerdere organen waren uitgevallen. Hier constateerden we dat patiënten met hoge MDSC-waarden een grotere overlevingskans hadden. Hoogstwaarschijnlijk waren MDSC's beschermend bij deze ernstig zieke patiënten omdat MDSC’s de te hevig reagerende witte bloedcellen onder controle brachten.
Concluderend toont dit proefschrift hoe MDSC’s zich gedragen tijdens sepsis, en dat MDSC’s therapeutisch of ziekmakend kunnen werken, afhankelijk van de mate van ontsteking in het lichaam. MDSC-waarden kunnen in de toekomst mogelijk gebruikt worden als maat voor ernst van sepsis, en als aangrijpingspunt voor medicatie
Successful treatment of bronchial stenosis after lung transplantation
Treatment of stenotic anastomosis after lung transplantation can be challenging. In this case report, we present a case in which 3D computed tomography reconstructions guided the clinical decision towards operative bronchoplasty after which our patient was treated successfully
Successful treatment of bronchial stenosis after lung transplantation
Treatment of stenotic anastomosis after lung transplantation can be challenging. In this case report, we present a case in which 3D computed tomography reconstructions guided the clinical decision towards operative bronchoplasty after which our patient was treated successfully
Soluble P-selectin as a Biomarker for Infection and Survival in Patients With a Systemic Inflammatory Response Syndrome on the Intensive Care Unit
AIMS: This study investigated the ability of soluble platelet selectin (sP-selectin) to identify infection and predict 30-day mortality in patients with a systemic inflammatory response syndrome (SIRS) on the intensive care unit. METHODS: Soluble platelet selectin levels were measured daily in the first 48 hours in patients presenting with SIRS. The outcome, proven infection, was established using predefined definitions. The 30-day mortality was retrospectively assessed. RESULTS: In a total of 313 patients with SIRS, sP-selectin levels were measured. Of these, 114 patients had proven infection on admission or developing during their intensive care unit (ICU) stay. Patients with proven infection had moderately higher levels of sP-selectin (147 ng/mL; interquartile range [IQR], 93.4-203 ng/mL) compared with noninfected patients (143.8 ng/mL; IQR, 89.6-194.7 ng/mL). This difference was not statistically significant (P = .072). However, in patients who were not admitted for infection (n = 235), sP-selectin levels were significantly related to the subsequent development of infection (P = .013). Soluble platelet selectin levels were particularly high in patients with abdominal sepsis and skin infections. Higher sP-selectin levels were associated with higher mortality (although not statistically significant, P = .08). CONCLUSIONS: This study shows that in patients with SIRS not admitted for infection, sP-selectin levels are significantly related to the subsequent development of infection. Furthermore, patients with higher sP-selectin levels in the first 2 days of admission had higher 30-day mortality, although this association is not statistically significant. Therefore, we conclude that sP-selectin is a potential future biomarker for both mortality and infection in patients with SIRS, but more research is needed to confirm its prognostic role
Myeloperoxidase can differentiate between sepsis and non-infectious SIRS and predicts mortality in intensive care patients with SIRS
BACKGROUND: Systemic inflammatory response syndrome (SIRS) is a clinical syndrome following inflammation. Clinically, it is difficult to distinguish SIRS following an infection, i.e., sepsis, from non-infectious SIRS. Myeloperoxidase is a hemeprotein stored in the neutrophil azurophilic granules and is one of the main pillars of neutrophil attack. Therefore, we hypothesized that myeloperoxidase can differentiate between sepsis and non-infectious SIRS in patients with systemic inflammatory response syndrome in the intensive care unit (ICU). METHODS: An observational single-center cohort study was conducted measuring myeloperoxidase in patients with SIRS in the first 48 h after admission. The outcomes were established using predefined definitions. Thirty-day mortality was retrospectively assessed. RESULTS: We found significantly higher levels of myeloperoxidase in patients with sepsis and septic shock compared to patients without sepsis (60 ng/ml versus 43 ng/ml, P = 0.002). Myeloperoxidase levels were related to 30-day mortality (P = 0.032), and high MPO levels on top of a high APACHE IV score further increased mortality risk. CONCLUSIONS: We show that myeloperoxidase is a potentially novel biomarker for sepsis in the ICU. Myeloperoxidase could eventually help in diagnosing sepsis and predicting mortality. However, more research is necessary to confirm our results
Osteoprotegerin is Higher in Sepsis Than in Noninfectious SIRS and Predicts 30-Day Mortality of SIRS Patients in the Intensive Care
BACKGROUND: Systemic inflammatory response syndrome (SIRS) is a complex disease involving multiple pathways and organs. Biomarkers reflecting these pathways and organ function could correlate with the severity of the disease. Osteoprotegerin (OPG), mainly known for its role in bone metabolism, is also involved in the immune and vascular system and is therefore an interesting biomarker to study in SIRS patients. In this prospective observational study, we investigated the correlation of plasma OPG concentrations, sepsis, and 30-day mortality of SIRS patients in the intensive care unit (ICU). METHODS: This observational, single-center, cohort study included 313 consecutive patients admitted to the ICU, with an anticipated stay of more than 48 h and SIRS on admission. Data from included patients were collected daily until discharge or death for a maximum of 10 days. Thirty-day mortality was retrospectively assessed. OPG concentrations were measured in the first 48 h after admission. The relation of OPG with no sepsis, sepsis, and septic shock was assessed with the Kruskal-Wallis test and the Mann-Whitney U-test. Cox proportional hazards regression was used to study OPG concentrations and 30-day mortality. RESULTS: OPG concentrations were higher in patients with sepsis and septic shock than in patients without sepsis. Furthermore, patients with OPG concentrations in the highest tertile at admission in the ICU have an increased risk of mortality within 30 days when compared to patients with OPG concentrations in the lowest and middle tertiles, independent of acute physiologic and chronic health evaluation (APACHE) and sequential organ failure assessment (SOFA) scores. CONCLUSIONS: We show that OPG is a biomarker that correlates with sepsis and predicts mortality of SIRS patients in the ICU
Osteoprotegerin is Higher in Sepsis Than in Noninfectious SIRS and Predicts 30-Day Mortality of SIRS Patients in the Intensive Care
BACKGROUND: Systemic inflammatory response syndrome (SIRS) is a complex disease involving multiple pathways and organs. Biomarkers reflecting these pathways and organ function could correlate with the severity of the disease. Osteoprotegerin (OPG), mainly known for its role in bone metabolism, is also involved in the immune and vascular system and is therefore an interesting biomarker to study in SIRS patients. In this prospective observational study, we investigated the correlation of plasma OPG concentrations, sepsis, and 30-day mortality of SIRS patients in the intensive care unit (ICU). METHODS: This observational, single-center, cohort study included 313 consecutive patients admitted to the ICU, with an anticipated stay of more than 48 h and SIRS on admission. Data from included patients were collected daily until discharge or death for a maximum of 10 days. Thirty-day mortality was retrospectively assessed. OPG concentrations were measured in the first 48 h after admission. The relation of OPG with no sepsis, sepsis, and septic shock was assessed with the Kruskal-Wallis test and the Mann-Whitney U-test. Cox proportional hazards regression was used to study OPG concentrations and 30-day mortality. RESULTS: OPG concentrations were higher in patients with sepsis and septic shock than in patients without sepsis. Furthermore, patients with OPG concentrations in the highest tertile at admission in the ICU have an increased risk of mortality within 30 days when compared to patients with OPG concentrations in the lowest and middle tertiles, independent of acute physiologic and chronic health evaluation (APACHE) and sequential organ failure assessment (SOFA) scores. CONCLUSIONS: We show that OPG is a biomarker that correlates with sepsis and predicts mortality of SIRS patients in the ICU
High levels of monocytic myeloid-derived suppressor cells are associated with favorable outcome in patients with pneumonia and sepsis with multi-organ failure
Background: Myeloid-derived suppressor cells (MDSCs) are immature
myeloid cells with immunosuppressive functions sub-classified into
monocytic and polymorphonuclear MDSCs (M-MDSCs and PMN-MDSCs). Clinical
studies reported increased levels of MDSCs that were associated with
poor outcome in sepsis patients. Since sepsis patients exhibit signs of
inflammation and immunosuppression, MDSCs may provide benefit by
dampening deleterious inflammation in some patients. To test this
hypothesis, we measured MDSCs in critically ill sepsis patients with
pneumonia and multi-organ dysfunctions and a high likelihood of death.
Methods: This was a prospective multicenter observational cohort study
performed in eight ICUs in Athens and Thessaloniki, Greece, enrolling
critically ill patients with pneumonia and sepsis with multi-organ
dysfunctions. A flow cytometry approach using blood collected at study
inclusion in tubes containing lyophilized antibodies combined to
unsupervised clustering was developed to quantify M-MDSCs and PMN-MDSCs.
Results: Forty-eight patients were included, of whom 34 died within 90
days. At study inclusion, M-MDSCs and PMN-MDSCs were increased in sepsis
patients when compared to healthy subjects (3.07% vs 0.96% and 22% vs
2.1% of leukocytes, respectively; p < 10(-4)). Increased PMN-MDSCs were
associated with secondary infections (p = 0.024) and new sepsis episodes
(p = 0.036). M-MDSCs were more abundant in survivors than in patients
who died within 28 days (p = 0.028). Stratification of patients
according to M-MDSC levels revealed that high levels of M-MDSC were
associated with reduced 90-day mortality (high vs low M-MDSCs: 47% vs
84% mortality, p = 0.003, hazard ratio [HR] = 3.2, 95% CI 1.4-7.2).
Combining high M-MDSC levels with low Acute Physiology and Chronic
Health Evaluation (APACHE) II score improved patient stratification
(M-MDSCshigh/APACHE IIlow vs M-MDSCslow/APACHE IIlow: 20% vs 80%
90-day mortality, p = 0.0096, HR = 7.2, 95% CI 1.6-32). In multivariate
analyses high M-MDSCs remained correlated with improved survival in
patients with low APACHE II score (p = 0.05, HR = 5.26, 95% CI
1.0-27.8).
Conclusion: This is the first study to associate high levels of M-MDSCs
with improved survival in sepsis patients