Kinetics of progenitor hemopoetic stem cells in sepsis: Correlation with patients survival?

BACKGROUND: Current theories underline the crucial role of pro-inflammatory mediators produced by monocytes for the pathogenesis of sepsis. Since monocytes derive from progenitor hemopoetic cells, the kinetics of stem cells was studied in peripheral blood of patients with sepsis. METHODS: Blood was sampled from 44 patients with septic syndrome due to ventilator-associated pneumonia on days 1, 3, 5 and 7 upon initiation of symptoms. Concentrations of tumour necrosis factor-alpha (TNFα), interleukin (IL)-6, IL-8 and G-CSF were estimated by ELISA. CD34/CD45 cells were determined after incubation with anti-CD45 FITC and anti-CD34 PE monocloncal antibodies and flow cytometric analysis. Samples from eight healthy volunteers served as controls. RESULTS: Median of CD34/CD45 absolute count of controls was 1.0/μl. Respective values of the total study population were 123.4, 112.4, 121.5 and 120.9/μl on days 1, 3, 5 and 7 (p < 0.0001 compared to controls). Positive correlations were found between the absolute CD34/CD45 count and the absolute monocyte count on days 1, 5 and 7. Survival was prolonged among patients with less than 310/μl CD34/CD45 cells on day 1 compared to those with more than 310/μl of CD34/CD45 cells (p: 0.022). Hazard ratio for death due to sepsis was 5.47 (p: 0.039) for CD34/CD45 cells more than 310/μl. Median IL-6 on day 1 was 56.78 and 233.85 pg/ml respectively for patients with less than 310/μl and more than 310/μl CD34/CD45 cells (p: 0.021). CONCLUSION: Stem cells are increased in peripheral blood over all days of follow-up compared to healthy volunteers. Patients with counts on day 1 less than 310/μl are accompanied by increased survival compared to patients with more than 310/μl

Early changes of CD4-positive lymphocytes and NK cells in patients with severe Gram-negative sepsis

Introduction Our aim was to define early changes of lymphocytes and of NK cells in severe sepsis and to correlate them with serum levels of soluble triggering receptor expressed on myeloid cells-1 (sTREM-1). Methods Blood was sampled from 49 patients with proven highly suspected infection by Gram-negative pathogens, within 12 hours of the advent of severe sepsis, and was also sampled from six healthy volunteers. White blood cells were targeted with monoclonal antibodies and were analyzed by flow cytometry. The concentrations of sTREM-1 were estimated by ELISA. Results The presence of CD3/CD4 cells was significantly lower ( P &lt; 0.0001) and that of NK cells significantly higher among patients with sepsis compared with controls ( P = 0.011). The proportions ( median +/- standard error) of ANNEXIN-V/CD4/ CD3-positive cells, of ANNEXIN-V/CD8/CD3-positive cells and of ANNEXIN-V/CD14-positive cells of the patient population were 7.41 +/- 2.26%, 7.69 +/- 3.42% and 1.96 +/- 4.22%, respectively. Patients with NK cells &gt; 20% survived longer compared with those patients with NK cells &lt;= 20% ( P = 0.041), and patients with sTREM-1 concentrations &gt; 180 pg/ml survived longer compared with those patients with sTREM-1 concentrations &lt;= 180 pg/ ml ( P = 0.042). A negative correlation was found between the percentages of ANNEXIN-V/CD4/CD3-positive cells and of CD3/CD4 cells (r(s) = - 0.305, P = 0.049), and a positive correlation was found between the serum sTREM-1 concentration and the percentage of NK cells (r(s) = + 0.395, P = 0.014). NK cells isolated from two healthy volunteers released sTREM-1 upon triggering with endotoxins. Conclusion Early severe sepsis is characterized by CD4-lymphopenia and increased NK cells, providing a survival benefit for the septic patient at percentages &gt; 20%. The survival benefit resulting from elevated NK cells might be connected to elevated serum levels of sTREM-1

In vitro postantibiotic effect of colistin on multidrug-resistant Acinetobacter baumannii

Infections by multi drug-resistant Acinetobacter baumannii constitute an increasing threat for critically ill patients. Colistin is often the only antimicrobial retaining activity against these strains. The postantibiotic effect (PAE) of colistin was studied on 19 isolates of A. baumannii resistant to ampicillin/sulbactam, ciprofloxacin, and carbapenems with the viable count method. The mean PAEs of I X MIC and 4 x MIC concentrations of colistin on the tested isolates were 3.90 and 4.48 h, respectively, indicating that a modified dosage scheme with increased dosing intervals might retain activity whereas minimizing the incidence of adverse effects. (c) 2007 Elsevier Inc. All rights reserved

Oleuropein: A novel immunomodulator conferring prolonged survival in experimental sepsis by Pseudomonas aeruginosa

Oleuropein, a novel immunomodulator derived from olive tree, was assessed in vitro and in experimental sepsis by Pseudomonas aeruginosa. After addition in monocyte and neutrophil cultures, malondialdehyde, TNF-alpha, IL-6, and bacterial counts were estimated in supernatants. Acute pyelonephritis was induced in 70 rabbits after inoculation of pathogen in the renal pelvis. Intravenous therapy was administered in four groups postchallenge by one multidrug-resistant isolate (A, controls; B, oleuropein; C, amikacin; D, both agents) and in three groups postchallenge by one susceptible isolate (E, controls; F, oleuropein; G, amikacin). Survival was recorded; bacterial growth in blood and organs was counted; endotoxins (LPS), malondialdehyde, total antioxidant status, and TNF-alpha in serum were estimated. TNF-alpha and IL-6 of cell supernatants were not increased compared with controls when triggered by LPS and P. aeruginosa. Counts of multidrug-resistant P. aeruginosa were decreased in monocyte supernatants. Median survival of groups A, B, C, D, E, F, and G were 3.00, 6.00, 2.00, 10.00, 1.00, 5.00, and 1.00 days, respectively. Bacteria in blood were lower at 48 h in groups B and D compared with A and in groups F and G compared with E. Total antioxidant status decreased steadily overtime in groups A, C, D, and G, but not in groups B and F. TNF-alpha of groups B, C, and D was lower than A at 48 h. Tissue bacteria decreased in group F compared with E. Oleuropein prolonged survival in experimental sepsis probably by promoting phagocytosis or inhibiting biosynthesis of proinflammatory cytokines

Are neonatal outcomes of triplet pregnancies different from those of singletons according to gestational age?

Objectives: Multiple pregnancies sustain the high pace of extreme prematurity. Little evidence is available about triplet gestation given the evolution in their management during the last decades. The aim of the study was to compare the neonatal outcomes of triplets with those of matched singletons in a cohort study. Methods: An observational retrospective cohort study of triplets and matched singletons born between 2004 and 2017 matched by gestational age was conducted. Additionally, the investigation performed in regard to data from the overall Greek population of interest. The primary outcome was mortality or severe neonatal morbidity based on pregnancy type. Results: A total of 237 triplets of 24-36 weeks’ gestation and 482 matched singletons were included. No differences in the primary outcome between triplets and singletons were found. Rates of severe neonatal morbidities did not differ significantly between triplets and singletons. A threshold of 1000 gr for birthweight and 28 weeks’ gestation for gestational age determined survival on triplets [OR: 0.08 (95% CI: 0.02-0.40, p=0.0020) and OR: 0.13 (95% CI: 0.03-0.57, p=0.0020) for gestational age and birthweight respectively]. In Greece stillbirths in triplets was 8 times higher than that of singletons (OR: 8.5, 95% CI: 6.9-10.5). From 3,375 triplets, 94 were stillborn, whereas in singletons, 4,659 out of 1,388,273. In our center 5 times more triplets than the expected average in Greece were delivered with no significant difference in stillbirths’ rates. Conclusions: No significant differences were identified in mortality or major neonatal morbidities between triplets and matched singletons highlighting the significance of prematurity and birthweight for these outcomes