The level of hypotension during hemorrhagic shock is a major determinant of the post-resuscitation systemic inflammatory response: an experimental study

<p>Abstract</p> <p>Background</p> <p>To evaluate whether the level of hypotension during hemorrhagic shock may influence the oxidative and inflammatory responses developed during post-ischemic resuscitation.</p> <p>Methods</p> <p>Fifteen rabbits were equally allocated into three groups: sham-operated (group sham); bled within 30 minutes to mean arterial pressure (MAP) of 40 mmHg (group shock-40); bled within 30 minutes to MAP of 30 mmHg (group shock-30). Shock was maintained for 60 min. Resuscitation was performed by reinfusing shed blood with two volumes of Ringer's lactate and blood was sampled for estimation of serum levels aminotransferases, creatinine, TNF-α, IL-1β, IL-6, malondialdehyde (MDA) and total antioxidant status (TAS) and for the determination of oxidative burst of polymorhonuclears (PMNs) and mononuclear cells (MCs).</p> <p>Results</p> <p>Serum AST of group shock-30 was higher than that of group shock-40 at 60 and 120 minutes after start of resuscitation; serum creatinine of group shock-30 was higher than group shock-40 at 120 minutes. Measured cytokines, MDA and cellular oxidative burst of groups, shock-40 and shock-30 were higher than group sham within the first 60 minutes after start of resuscitation. Serum concentrations of IL-1β, IL-6 and TNF-α of group shock-30 were higher than group shock-40 at 120 minutes (p < 0.05). No differences were found between two groups regarding serum MDA and TAS and oxidative burst on PMNs and MCs but both groups were different to group sham.</p> <p>Conclusion</p> <p>The level of hypotension is a major determinant of the severity of hepatic and renal dysfunction and of the inflammatory response arising during post-ischemic hemorrhagic shock resuscitation. These findings deserve further evaluation in the clinical setting.</p

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

Alterations of innate and adaptive immune system in patients with nosocomial sepsis

Background The present study aimed to investigate changes of the immune response between sepsis due to ventilator-associated pneumonia (VAP) and sepsis due to other types of infections. Methods Peripheral venous blood was sampled from 68 patients with sepsis within 24 hours of diagnosis; 36 suffered from VAP; 32 from other nosocomial infections, all well-matched for severity, age and sex. Blood monocytes were isolated and cultured with/without purified endotoxin (lipopolysaccharide (LPS)). Estimation of tumour necrosis factor alpha (TNFα) and interleukin-6 (IL-6) in cultures’ supernatants was done by an enzyme immunoassay. Flow cytometry was used to determine subpopulations of mononuclear cells and apoptosis. To mimic pathogenesis of VAP, mononuclear cells of healthy volunteers were progressively stimulated with increased inocula of pathogens; apoptosis was determined. Results In patients with VAP, the absolute number of CD3(+)/CD4(+) lymphocytes was significantly lower (p: 0.034) and apoptosis of isolated monocytes was increased (p: 0.007) compared to other infections. TNFα and IL-6 production from LPS-stimulated monocytes was lower in patients with VAP-related sepsis than with sepsis due to other infections. Apoptosis of monocytes was induced after in vitro stimulation of mononuclear cells by a mechanism mimicking VAP. Conclusions Decrease of CD4-lymphocytes and immunoparalysis of monocytes are characteristic alterations of sepsis arising in the field of VAP.Σκοπός της παρούσας μελέτης είναι η διερεύνηση των διαφορών στην ανοσιακή απόκριση ανάμεσα στη σήψη από πνευμονία που σχετίζεται με το μηχανικό αερισμό (ΠΣΜΑ) και στη σήψη εξαιτίας άλλων λοιμώξεων. Μεθοδολογία Στη μελέτη συμμετείχαν 68 ασθενείς με σήψη, 36 εξαιτίας ΠΣΜΑ και 32 εξαιτίας άλλων λοιμώξεων, που δε διέφεραν ως προς το φύλο, την ηλικία και τη σοβαρότητα της κατάστασής τους. Εντός 24 ωρών από τη διάγνωση, ελήφθη δείγμα περιφερικού φλεβικού αίματος. Ο προσδιορισμός των υποπληθυσμών των μονοπυρήνων και της απόπτωσης έγινε με κυτταρομετρία ροής. Πραγματοποιήθηκε απομόνωση των μονοκυττάρων και καλλιέργειά τους απουσία/παρουσία ενδοτοξίνης. Στα υπερκείμενα των καλλιεργειών προσδιορίστηκαν με ανοσοενζυμική μέθοδο οι συγκεντρώσεις του παράγοντα νέκρωσης των όγκων α (TNFα) και της ιντερλευκίνης-6 (IL-6). Σε μια προσπάθεια αναπαραγωγής των συνθηκών παθογένειας της ΠΣΜΑ, μονοπύρηνα κύτταρα υγιών εθελοντών διεγέρθηκαν σταδιακά με αυξανόνενα ενοφθαλμίσματα παθογόνων και προσδιορίστηκε η απόπτωσή τους. Αποτελέσματα Στους ασθενείς με ΠΣΜΑ ο αριθμός των CD3(+)/CD4(+) λεμφοκυττάρων ήταν μικρότερος (p: 0.034) και η απόπτωση των απομονωθέντων μονοκυττάρων αυξημένη (p: 0.007) συγκριτικά με τις άλλες λοιμώξεις. Η παραγωγή TNFα και IL-6 από τα διεγερθέντα με ενδοτοξίνη μονοκύτταρα ήταν σημαντικά μικρότερη στη σήψη από ΠΣΜΑ συγκριτικά με τη σήψη από άλλες λοιμώξεις. Παρατηρήθηκε επαγωγή της απόπτωσης των μονοκυττάρων μετά από in vitro διέγερσή τους με μηχανισμό παρόμοιο με το μηχανισμό παθογένειας της ΠΣΜΑ. Συμπεράσματα Η μείωση των CD4-λεμφοκυττάρων και η ανοσοπαράλυση των μονοκυττάρων αποτελούν χαρακτηριστικά της σήψης που οφείλεται σε πνευμονία που σχετίζεται με το μηχανικό αερισμό

Long-term efficacy of etanercept in hidradenitis suppurativa: results from an open-label phase II prospective trial

Objective: To evaluate the long-term efficacy of etanercept for the management of hidradenitis suppurativa. Methods: Analysis was based on the long-term follow-up (weeks 24-144) of 10 patients enrolled in a prospective open-label phase II study; etanercept was initially administered subcutaneously 50 mg once weekly for 12 weeks in 10 patients. Disease recurrence and the need to restart etanercept were recorded. Results: Three patients did not report any disease recurrence. A second course of treatment with etanercept was needed in seven patients. Favourable responses were found in five; two patients failed treatment. Conclusions: The first treatment course achieved long-term disease remission in almost one-third of patients. The remaining needed a second treatment course but even in that case, their disease severity at restart was significantly lower compared with baseline

Can soluble triggering receptor expressed on myeloid cells (sTREM-1) be considered an anti-inflammatory mediator in the pathogenesis of peptic ulcer disease?

Soluble triggering receptor expressed on myeloid cells (sTREM-1) is a novel mediator involved in the pathogenesis of peptic ulcer disease. To investigate the potential role of sTREM-1 in the anti-inflammatory response in chronic gastritis, sTREM-1 was compared with other anti-inflammatory mediators of gastritis. Forty patients with dyspepsia were enrolled: 20 with peptic ulcer and 20 controls without any macroscopic abnormalities. All patients were examined by endoscopy; gastric juice was aspirated and biopsy specimens were collected from the antrum and corpus of the stomach. sTREM-1, interleukin (IL)-8, and IL-10 were estimated by enzyme immunoassays. Median sTREM-1 in patient controls and in patients with peptic ulcer disease was 3.91 and 44.27 pg/ml, respectively (P=0.006). Respective values of IL-8 were 1856.97 and 2030.66 pg/ml (P=0.023); those of IL-10 were 16.92 and 18.43 pg/ml (NS). The odds ratio for the presence of peptic ulcer in the event of a concentration of sTREM-1 higher than 15 pg/ml was 23.22 (95% CI, 2.58-208.62; P=0.002). A positive correlation was found between the ratios of IL-8/sTREM-1 and IL-8/IL-10 (r (s), + 0.365; P=0.021). In conclusion, sTREM-1 is an independent factor for the generation of peptic ulcer disease and might behave as an anti-inflammatory mediator in chronic gastritis