Search Results (5)

Patients admitted to the intensive care unit (ICU) often experience endotoxemia, nosocomial infections and sepsis. Polymorphonuclear and monocytic myeloid-derived suppressor cells (PMN-MDSCs and M-MDSCs) can have an important impact on the development of infectious diseases, but little is known about their potential predictive value in critically ill patients. Here, we used unsupervised flow cytometry analyses to quantify MDSC-like cells in healthy subjects challenged with endotoxin and in critically ill patients admitted to intensive care units and at risk of developing infections. Cells phenotypically similar to PMN-MDSCs and M-MDSCs increased after endotoxin challenge. Similar cells were elevated in patients at ICU admission and normalized at ICU discharge. A subpopulation of M-MDSC-like cells expressing intermediate levels of CD15 (CD15^int M-MDSCs) was associated with overall mortality (p = 0.02). Interestingly, the high abundance of PMN-MDSCs and CD15^int M-MDSCs was a good predictor of mortality (p = 0.0046 and 0.014), with area under the ROC curve for mortality of 0.70 (95% CI = 0.4–1.0) and 0.86 (0.62–1.0), respectively. Overall, our observations support the idea that MDSCs represent biomarkers for sepsis and that flow cytometry monitoring of MDSCs may be used to risk-stratify ICU patients for targeted therapy. Full article

Objective: The sepsis-induced inflammatory response may potentially affect malignant cells. Recently, a case of spontaneous regression of a histologically confirmed International Federation of Gynecology and Obstetrics (FIGO) stage IIIC epithelial ovarian cancer (EOC) following sepsis was reported. The aim of our study was to assess the impact of sepsis on the oncologic outcomes of advanced-stage EOC patients. Methods: Gynecologic oncologic patients admitted to the Intensive Care Unit of three oncologic centers between 2006 and 2019 were identified and patients who experienced sepsis following advanced-stage EOC diagnosis were selected. Survival outcomes were compared with advanced-stage EOC patients from the Netherlands Cancer Registry (NCR). To correct for case-mix differences, propensity score matching using 1:3 nearest neighbor matching was conducted after which survival analyses were repeated. Results: A total of 18 of 215 patients with advanced-stage EOC experienced sepsis. Sepsis patients had similar distributions of patient, tumor, and treatment characteristics to 3988 patients from the NCR cohort. A total of 3 of 18 patients died from the complications of sepsis. While the remaining patients initially responded to treatment, 14/15 patients relapsed. The median (IQR) overall survival was 31 (24–44) and 35 (20–60) months for the sepsis and unmatched NCR cohort (p = 0.56), respectively. The median (IQR) progression-free survival was 16 (11–21) and 16 (11–27) months (p = 0.90), respectively. Survival outcomes did not differ following propensity matching (overall survival of 31 (24–44) vs. 36 (20–56) months, p = 0.40; progression-free survival of 16 (11–21) and 16 (12–21) months, p = 0.72). Conclusion: In this observational study, the occurrence of sepsis did not affect the oncologic and survival outcomes of advanced-stage EOC patients. Full article

Background: Delirium is a pathobiological brain process that is frequently observed in Intensive Care Unit (ICU) patients, and is associated with longer hospitalization as well as long-term cognitive impairment. In neurological ICU patients, delirium may be more treatment-resistant due to the initial brain injury. This study examined the effects of a multicomponent non-pharmacological nursing intervention program on delirium in neurological ICU patients. Methods: A single-center interrupted time series trial was conducted in adult neurological ICU patients at high risk for developing delirium who were non-delirious at admission. A multicomponent nursing intervention program focusing on modifiable risk factors for delirium, including the optimalization of vision, hearing, orientation and cognition, sleep and mobilization, was implemented as the standard of care, and its effects were studied. The primary outcome was the number of delirium-free and coma-free days alive at 28 days after ICU admission. The secondary outcomes included delirium incidence and duration, ICU and hospital length-of-stay and duration of mechanical ventilation. Results: Of 289 eligible patients admitted to the ICU, 130 patients were included, with a mean age of 68 ± 11 years, a mean APACHE-IV score of 79 ± 25 and a median predicted delirium risk (E-PRE-DELIRIC) score of 42 [IQR 38–50]). Of these, 73 were included in the intervention period and 57 in the control period. The median delirium- and coma-free days alive were 15 days [IQR 0–26] in the intervention group and 10 days [IQR 0–24] in the control group (level change −0.48 days, 95% confidence interval (95%CI) −7 to 6 days, p = 0.87; slope change −0.95 days, 95%CI −2.41 to 0.52 days, p = 0.18). Conclusions: In neurological ICU patients, our multicomponent non-pharmacological nursing intervention program did not change the number of delirium-free and coma-free days alive after 28 days. Full article

SARS-CoV-2 is causing a pandemic resulting in high morbidity and mortality. COVID-19 patients suffering from acute respiratory distress syndrome (ARDS) are often critically ill and show lung injury and hemolysis. Heme is a prosthetic moiety crucial for the function of a wide variety of heme-proteins, including hemoglobin and cytochromes. However, injury-derived free heme promotes adhesion molecule expression, leukocyte recruitment, vascular permeabilization, platelet activation, complement activation, thrombosis, and fibrosis. Heme can be degraded by the anti-inflammatory enzyme heme oxygenase (HO) generating biliverdin/bilirubin, iron/ferritin, and carbon monoxide. We therefore postulate that free heme contributes to many of the inflammatory phenomena witnessed in critically ill COVID-19 patients, whilst induction of HO-1 or harnessing heme may provide protection. HO-activity not only degrades injurious heme, but its effector molecules possess also potent salutary anti-oxidative and anti-inflammatory properties. Until a vaccine against SARS-CoV-2 becomes available, we need to explore novel strategies to attenuate the pro-inflammatory, pro-thrombotic, and pro-fibrotic consequences of SARS-CoV-2 leading to morbidity and mortality. The heme-HO system represents an interesting target for novel “proof of concept” studies in the context of COVID-19. Full article

We recently demonstrated that the sympathetic nervous system can be voluntarily activated following a training program consisting of cold exposure, breathing exercises, and meditation. This resulted in profound attenuation of the systemic inflammatory response elicited by lipopolysaccharide (LPS) administration. Herein, we assessed whether this training program affects the plasma metabolome and if these changes are linked to the immunomodulatory effects observed. A total of 224 metabolites were identified in plasma obtained from 24 healthy male volunteers at six timepoints, of which 98 were significantly altered following LPS administration. Effects of the training program were most prominent shortly after initiation of the acquired breathing exercises but prior to LPS administration, and point towards increased activation of the Cori cycle. Elevated concentrations of lactate and pyruvate in trained individuals correlated with enhanced levels of anti-inflammatory interleukin (IL)-10. In vitro validation experiments revealed that co-incubation with lactate and pyruvate enhances IL-10 production and attenuates the release of pro-inflammatory IL-1β and IL-6 by LPS-stimulated leukocytes. Our results demonstrate that practicing the breathing exercises acquired during the training program results in increased activity of the Cori cycle. Furthermore, this work uncovers an important role of lactate and pyruvate in the anti-inflammatory phenotype observed in trained subjects. Full article