TREM-1 expression on neutrophils and monocytes of septic patients: relation to the underlying infection and the implicated pathogen

<p>Abstract</p> <p>Background</p> <p>Current knowledge on the exact ligand causing expression of TREM-1 on neutrophils and monocytes is limited. The present study aimed at the role of underlying infection and of the causative pathogen in the expression of TREM-1 in sepsis.</p> <p>Methods</p> <p>Peripheral venous blood was sampled from 125 patients with sepsis and 88 with severe sepsis/septic shock. The causative pathogen was isolated in 91 patients. Patients were suffering from acute pyelonephritis, community-acquired pneumonia (CAP), intra-abdominal infections (IAIs), primary bacteremia and ventilator-associated pneumonia or hospital-acquired pneumonia (VAP/HAP). Blood monocytes and neutrophils were isolated. Flow cytometry was used to estimate the TREM-1 expression from septic patients.</p> <p>Results</p> <p>Within patients bearing intrabdominal infections, expression of TREM-1 was significantly lower on neutrophils and on monocytes at severe sepsis/shock than at sepsis. That was also the case for severe sepsis/shock developed in the field of VAP/HAP. Among patients who suffered infections by Gram-negative community-acquired pathogens or among patients who suffered polymicrobial infections, expression of TREM-1 on monocytes was significantly lower at the stage of severe sepsis/shock than at the stage of sepsis.</p> <p>Conclusions</p> <p>Decrease of the expression of TREM-1 on the membrane of monocytes and neutrophils upon transition from sepsis to severe sepsis/septic shock depends on the underlying type of infection and the causative pathogen.</p

The importance of sTREM-1 kinetics during the course of septic syndrome

OBJECTIVE: TREM-1 (triggering receptor expressed on myeloid cells), a receptor expressed on neutrophils and monocytes, is upregulated in sepsis and seems to tune the inflammatory response. We explored the expression of TREM-1 at the gene level and on cell membranes of monocytes and association with clinical outcome. METHODS: Peripheral venous blood was sampled from 75 septic patients (41 patients with sepsis, 25 with severe sepsis and 9 with septic shock) on sepsis day 1, 3 and 7. TREM-1 on monocytes was estimated by flow cytometry; gene expression of TREM-1 in circulating monnuclear cells was assessed by real-time PCR. sTREM-1 was measured in serum by an enzyme immunoassay.RESULTS: Although surface TREM-1, sTREM-1 and TREM-1 gene expression did not differ between sepsis, severe sepsis and septic shock on day 1, survivors had greater expression of surface TREM-1 on days 3 and 7 compared to non-survivors. sTREM-1 on non-survivors decreased on day 3 compared to baseline. Patients with increase of monocyte gene expression of TREM-1 from day 1 to day 3 had prolonged survival compared to patients with decrease of gene expression of TREM-1 from day 1 to day 3 (p: 0.031). CONCLUSIONS: Early decrease of gene expression of TREM-1 in monocytes is associated with poor outcome. A reciprocal decrease of the pro-inflammatory surface receptor TREM-1 linked with sepsis-induced immunosuppression may be part of the explanation.ΣΚΟΠΟΣ:Ο TREM-1 (triggering receptor expressed on myeloid cells), ένας υποδοχέας που εκφράζεται στα ουδετερόφιλα και τα μονοκύτταρα, υπερεκφράζεται στη σήψη και φαίνεται ότι παίζει έναρόλο-κλειδί για τη ρύθμιση της φλεγμονώδους απόκρισης. Μελετήσαμε την γονιδιακή και επιφανειακή έκφραση του TREM-1 σε σχέση με την τελική έκβαση. ΜΕΘΟΔΟΙ: Δείγματα περιφερικού φλεβικού αίματος ελήφθησαν από 75 σηπτικούς ασθενείς (41 ασθενείς με σήψη, 25 με σοβαρή σήψη και 9 με σηπτική καταπληξία) εντός είκοσι τεσσάρων ωρών μετά την εισαγωγή τους στη μελέτη και στη συνέχεια κατά την τρίτη και έβδομη μέρα νοσηλείας. Η επιφανειακή έκφραση του TREM-1 επί των μονοκυττάρων εκτιμήθηκε με κυτταρομετρία ροής. Η γονιδιακή έκφραση του TREM-1 στα κυκλοφορούντα μονοκύτταρα αξιολογήθηκε με RT-PCR. Επιπλέον προσδιορίστηκε η συγκέντρωση του sTREM-1 η οποία προσδιορίστηκε στον ορό με μία ανοσοενζυμική μέθοδο. ΑΠΟΤΕΛΕΣΜΑΤΑ: Παρόλο που η επιφανειακή και η γονιδιακή έκφραση του TREM-1, καθώς και η συγκέντρωση του sTREM-1 δεν διέφεραν μεταξύ σήψης, σοβαρής σήψης και σηπτικής καταπληξίας την ημέρα 1, οι επιζώντες είχαν μεγαλύτερη έκφραση στην επιφάνεια TREM-1 στις ημέρες 3 και 7 σε σύγκριση με μη επιζώντες. Η συγκέντρωση του sTREM-1 στους μη επιζώντες μειώθηκε την ημέρα 3 σε σύγκριση με την αρχική τιμή της. Οι ασθενείς με την αύξηση της γονιδιακής έκφρασης του TREM-1 στα μονοκύτταρα από την ημέρα 1 έως την ημέρα 3 είχαν παρατεταμένη επιβίωση σε σύγκριση με ασθενείς με μείωση της έκφρασης του γονιδίου τουTREM-1 από την ημέρα 1 έως την ημέρα 3 (p: 0,031). ΣΥΜΠΕΡΑΣΜΑΤΑ: Η πρώιμη μείωση της έκφρασης του γονιδίου της TREM-1 στα μονοκύτταρα σχετίζεται με κακή έκβαση. Το φαινόμενο αυτό μπορεί να οφείλεται στην ανοσοκαταστολή που προκαλείται από το σηπτικό επεισόδιο μέσω μείωσης του προ-φλεγμονώδους υποδοχέα επιφανείας TREM-1

End-of-Life Health-Care Cost of Patients With Lung Cancer: A Retrospective Study

Introduction: Lung cancer exerts a significant societal and health-care–related economic burden and chemotherapy drugs constitute a major factor of total direct cost. The aim of the present study was to assess the direct health-care cost of lung cancer in Greece by conducting a retrospective analysis on the last 6 months of life. Methods: The present study was based on both the medical data and costs of treatment of deceased adult patients who suffered from terminal stage IIIB/IV lung cancer (non-small cell lung cancer and small cell lung cancer) during the last 6 months of their life. The study’s protocol was approved by the Hospital’s Research Ethics Committee. Costs included outpatient (outpatient services) and inpatient (inpatient services) costs. Descriptive statistics were mainly used for statistical analysis. Results: The files of 144 patients were analyzed. The total cost of health-care services for the study population during the last 6 months of life was attributed by 57% to inpatient services, whereas chemotherapy costs (74%) comprised the largest proportion of the total inpatient cost. The highest expenditure for outpatient services was attributed to concomitant medication (59%), followed by the cost of tests (21%) and radiotherapy (20%). Conclusions: The results of our study indicate that both inpatient and outpatient costs were substantial. The main inpatient and outpatient cost drivers were chemotherapy and concomitant medication, respectively. A more comprehensive nationwide study would be useful to validate our results and to include also indirect costs of cancer care in Greece

End-of-Life Health-Care Cost of Patients With Lung Cancer: A Retrospective Study

Introduction: Lung cancer exerts a significant societal and health-care-related economic burden and chemotherapy drugs constitute a major factor of total direct cost. The aim of the present study was to assess the direct health-care cost of lung cancer in Greece by conducting a retrospective analysis on the last 6 months of life. Methods: The present study was based on both the medical data and costs of treatment of deceased adult patients who suffered from terminal stage IIIB/IV lung cancer (non-small cell lung cancer and small cell lung cancer) during the last 6 months of their life. The study’s protocol was approved by the Hospital’s Research Ethics Committee. Costs included outpatient (outpatient services) and inpatient (inpatient services) costs. Descriptive statistics were mainly used for statistical analysis. Results: The files of 144 patients were analyzed. The total cost of health-care services for the study population during the last 6 months of life was attributed by 57% to inpatient services, whereas chemotherapy costs (74%) comprised the largest proportion of the total inpatient cost. The highest expenditure for outpatient services was attributed to concomitant medication (59%), followed by the cost of tests (21%) and radiotherapy (20%). Conclusions: The results of our study indicate that both inpatient and outpatient costs were substantial. The main inpatient and outpatient cost drivers were chemotherapy and concomitant medication, respectively. A more comprehensive nationwide study would be useful to validate our results and to include also indirect costs of cancer care in Greece

Effect of clarithromycin in patients with suspected Gram-negative sepsis: results of a randomized controlled trial

A previous randomized study showed that clarithromycin decreases the risk of death due to ventilator-associated pneumonia and shortens the time until infection resolution. The efficacy of clarithromycin was tested in a larger population with sepsis. Six hundred patients with systemic inflammatory response syndrome due to acute pyelonephritis, acute intra-abdominal infections or primary Gram-negative bacteraemia were enrolled in a double-blind, randomized, multicentre trial. Clarithromycin (1 g) was administered intravenously once daily for 4 days consecutively in 302 patients; another 298 patients were treated with placebo. Mortality was the primary outcome; resolution of infection and hospitalization costs were the secondary outcomes. The groups were well matched for demographics, disease severity, microbiology and appropriateness of the administered antimicrobials. Overall 28 day mortality was 17.1 (51 deaths) in the placebo arm and 18.5 (56 deaths) in the clarithromycin arm (P0.671). Nineteen out of 26 placebo-treated patients with septic shock and multiple organ dysfunctions died (73.1) compared with 15 out of 28 clarithromycin-treated patients (53.6, P0.020). The median time until resolution of infection was 5 days in both arms. In the subgroup with severe sepsis/shock, this was 10 days in the placebo arm and 6 days in the clarithromycin arm (P0.037). The cost of hospitalization was lower after treatment with clarithromycin (P0.044). Serious adverse events were observed in 1.3 and 0.7 of placebo- and clarithromycin-treated patients, respectively (P0.502). Intravenous clarithromycin did not affect overall mortality; however, administration shortened the time to resolution of infection and decreased the hospitalization costs

Early alterations of the innate and adaptive immune statuses in sepsis according to the type of underlying infection

Introduction: Although major changes of the immune system have been described in sepsis, it has never been studied whether these may differ in relation to the type of underlying infection or not. This was studied for the first time. Methods: The statuses of the innate and adaptive immune systems were prospectively compared in 505 patients. Whole blood was sampled within less than 24 hours of advent of sepsis; white blood cells were stained with monoclonal antibodies and analyzed though a flow cytometer. Results: Expression of HLA-DR was significantly decreased among patients with severe sepsis/shock due to acute pyelonephritis and intraabdominal infections compared with sepsis. The rate of apoptosis of natural killer (NK) cells differed significantly among patients with severe sepsis/shock due to ventilator-associated pneumonia (VAP) and hospital-acquired pneumonia (HAP) compared with sepsis. The rate of apoptosis of NKT cells differed significantly among patients with severe sepsis/shock due to acute pyelonephritis, primary bacteremia and VAP/HAP compared with sepsis. Regarding adaptive immunity, absolute counts of CD4-lymphocytes were significantly decreased among patients with severe sepsis/shock due to community-acquired pneumonia (CAP) and intraabdominal infections compared with sepsis. Absolute counts of B-lymphocytes were significantly decreased among patients with severe sepsis/shock due to CAP compared with sepsis. Conclusions: Major differences of the early statuses of the innate and adaptive immune systems exist between sepsis and severe sepsis/shock in relation to the underlying type of infection. These results may have a major impact on therapeutics