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Objective Information from critically ill coronavirus disease 2019 (COVID-19) patients is limited and in many cases coming from health systems approaches different from the national public systems existing in most countries in Europe. Besides, patient follow-up remains incomplete in many publications. Our aim is to characterize acute respiratory distress syndrome (ARDS) patients admitted to a medical critical care unit (MCCU) in a referral hospital in Spain. Design Retrospective case series of consecutive ARDS COVID-19 patients admitted and treated in our MCCU. Setting 36-bed MCCU in referral tertiary hospital. Patients and participants SARS-CoV-2 infection confirmed by real-time reverse transcriptase–polymerase chain reaction (RT-PCR) assay of nasal/pharyngeal swabs. Interventions None Main variables of interest Demographic and clinical data were collected, including data on clinical management, respiratory failure, and patient mortality. Results Forty-four ARDS COVID-19 patients were included in the study. Median age was 61.50 (53.25 – 67) years and most of the patients were male (72.7%). Hypertension and dyslipidemia were the most frequent co-morbidities (52.3 and 36.4% respectively). Steroids (1mg/Kg/day) and tocilizumab were administered in almost all patients (95.5%). 77.3% of the patients needed invasive mechanical ventilation for a median of 16 days [11-28]. Prone position ventilation was performed in 33 patients (97%) for a median of 3 sessions [2-5] per patient. Nosocomial infection was diagnosed in 13 patients (29.5%). Tracheostomy was performed in ten patients (29.4%). At study closing all patients had been discharged from the CCU and only two (4.5%) remained in hospital ward. MCCU length of stay was 18 days [10-27]. Mortality at study closing was 20.5% (n 9); 26.5% among ventilated patients. Conclusions The seven-week period in which our MCCU was exclusively dedicated to COVID-19 patients has been challenging. Despite the severity of the patients and the high need for invasive mechanical ventilation, mortality was 20.5%.

Background: Health-care associated infections are a major cause of morbidity and mortality in critical care units. The aim of this study is to evaluate the effectiveness of chlorhexidine gluconate (CHG)-impregnated wipes in the daily bathing of patients in an intensive care unit (ICU) to prevent cross-transmission and colonization by multidrug-resistant organisms (MDROs) Methods: Prospective cohort study with an intervention of 11 months. The intervention consisted of using CHG-impregnated wipes for the daily bathing of patients on mechanical ventilation or colonized by MDROs. Monthly trends in the number of patients colonized by MDROs and the incidence of nosocomial infections were evaluated. Results: A total of 1,675 patients were admitted to the unit during the intervention period, and 430 (25.7%) were bathed with chlorhexidine wipes. A significant decrease was observed in the incidence of colonization by MDROs over the months (beta = -0.209; r(2) = 0.549; P = .027), and in the number of patients colonized compared with the equivalent period of the previous year (22.0% vs 18.4%; P = .01). No significant decrease was observed in the incidence of nosocomial infection between the two periods (4.11% vs 4.57%; P = .355). No dermatologic problems were observed in the treated patients. Conclusions: The use of CHG-impregnated wipes reduces cross-transmission and colonization by MDROs in the ICUs in an endemic situation because of multidrug-resistant Enterobacteriaceae. (C) 2017 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.

Objectives To assess tolvaptan's efficacy and safety in critical care patients with volume overload. Methods Prospective observational study. Twenty-eight patients in the recovery phase from multiple organ failure and with volume overload refractory to conventional therapy treated with tolvaptan were included. Results Patients received an initial daily dose of 3.75 (n=1), 7.5 (n=8) and 15 (n=19) mg of tolvaptan. Median treatment duration was 2 days (range: 1 to 12). All patients presented an increase in 24 hours diuresis after the first dose (median increase from baseline (IQR)=1114 (285-1943) mL), with a median net daily fluid loss of 1007 mL (456-2380) mL after 24 hours. High diuretic efficacy (daily fluid loss higher than 0.5 L with tolvaptan first dose) was detected in 18 patients (64.3%). Initial hyponatraemia was present in 16 (57.1%) patients, while overly rapid correction with tolvaptan treatment occurred in two patients without clinical consequences. Two patients presented hypophosphataemia after treatment. Conclusion Tolvaptan is an effective therapeutic option in critically ill patients with volume overload refractory to conventional diuretics. Further studies are required to evaluate its safety profile and its effect on short-term outcomes and mortality.

In this study, we evaluate the effect of extracorporeal membrane oxygenation (ECMO) and ventricular assist devices (Levitronix) on the pharmacokinetic of amikacin in critically ill patients. Twelve patients with ECMO and three with Levitronix devices who started treatment with amikacin were included. Amikacin pre (Cmax) and post (Cmin) dose serum concentrations were measured during the first 72-96 hours of treatment initiation. Pharmacokinetic parameters were performed by Bayesian adjustment. The median initial dose was 1,000 mg (range: 600-1,400 mg). Mean plasma concentrations were Cmax 58.6 mg/L (17.0 mg/L); Cmin 9.58 mg/L (7.8 mg/L). Patients with an ECMO device had a higher volume of distribution (0.346 [0.033] vs. 0.288 [0.110] L/kg) and a lower plasma clearance (1.58 [0.21] vs. 3.73 [1.03] L/h) than the control group. This phenomenon was also observed in those patients with simultaneous use of ECMO and hemodilafiltration. For patients with Levitronix system, no significant alterations in the volume of distribution were observed, although a lower plasma clearance was noticed. Placement of ECMO devices alters the pharmacokinetic parameters of amikacin in the critically ill patients and should be considered when selecting the initial dose.

Background The aim of this study is to evaluate the risk factors for colonisation by multidrug resistant (MDR) K. pneumoniae in a critical care unit and the relationship between colonisation and the antibiotic pressure exerted by the antimicrobial treatments received by patients. Methods A prospective observational was designed. Patients admitted for more than 48 h to an intensive care unit were included. Samples for surveillance cultures were obtained from all the patients upon admission and once a week. The association between risk factors and colonisation by MDR K. pneumoniae was determined by logistic regression. A Cox regression model was used to evaluate the effect of the use of antimicrobials on the colonisation rate. An ARMIA model was used to investigate the association between the incidence of colonisation by MDR strains and the global consumption of antimicrobials in the unit. Results One thousand seven hundred twenty-five patients were included, from which 308 (17.9%) were positive for MDR K. pneumoniae. In the multivariate analysis, hospitalisation for longer than 7 days together with respiratory infection and administration of any antibiotic was associated with increased MR K. pneumoniae colonisation. Patients who received antibiotics for more than 48 h were colonised earlier than patients who did not receive antibiotic treatment [HR: 2.16 (95%CI:1.55–3.03)]. The ARIMA model found a significant association between the monthly colonisation rate for MR K. pneumoniae and the consumption of cephalosporins and carbapenems in the previous month. Conclusion Individual antibiotic administration and the global antibiotic pressure of cephalosporins and carbapenems are associated to an increased colonisation by MDR K. pneumoniae strains.

What is known and objective Several authors have demonstrated the relationship between voriconazole concentrations and the risk of therapeutic failure and adverse events However, the information about voriconazole concentrations in the critically ill patient is scarce. The aim of this study was to analyse the plasma concentrations and pharmacokinetic behaviour of voriconazole in critically ill patients and their association with the treatment response and development of toxicity. Methods A prospective, observational study was conducted. Patients admitted to an intensive care unit and on treatment with intravenous voriconazole were included. Plasma concentrations were measured between days 4 and 7 from the start of the treatment. The pharmacokinetic analysis was performed using the NONMEM® software. A regression model was used to evaluate the variables associated with the values outside the therapeutic range, as well as the relationship between the plasma concentrations and the treatment response and the development of hepatotoxicity. Results and discussion A total of 33 patients were included. Plasma concentrations outside the therapeutic range (1-5.5 mg/L) were observed in 15 patients, being above the established range in 9 (27.3%) cases, and below it in 6 (18.2%) cases. The presence of a bilirubin value of >1.5 mg/dL and a C-reactive protein >100 mg/dL was associated with supra-therapeutic concentrations. Voriconazole concentrations greater than 5.5 mg/dL were associated with the development of hepatotoxicity. What is new and conclusions There is a wide variation in voriconazole concentrations in critically ill patients, being associated with a high frequency of adverse events. Close monitoring of these values is required in order to decrease the risk of therapeutic failure and toxicity.

Purpose Information about immunocompromised patients infected with influenza A (H1N1) virus and requiring admission to the ICU is lacking. Our objective was to know the clinical characteristics of these patients and to identify treatment-related variables associated with mortality. Material and methods A prospective multicenter observational cohort study was based on data from a Spanish registry (2009–2015) collected by 148 Spanish ICUs. All patients admitted to the ICU with the diagnosis of influenza A (H1N1) virus infection were included. Immunosuppression was clearly defined. Factors associated with mortality in immunocompromised patients were assessed by conventional logistic regression analysis and by a propensity score (PS) adjusted-multivariable analysis. Results Of 1899 patients with influenza A (H1N1) infection, 238 (12.5%) were classified as immunocompromised. Mortality was significantly higher in immunosuppressed patients. Four variables independently associated with mortality were identified: SOFA score, need of vasopressor, use of corticosteroids, and acute renal failure, AKIN 3 stage. In the PS-adjusted model, corticosteroid therapy remained as an independent factor associated with increased mortality (OR 2.25;95%CI, 1.15–4.38;p = 0.017). In the subgroup of hematological patients (n = 141), corticosteroid therapy was also associated with increased mortality (OR 3.12; 95%CI, 1.32–7.41; p = 0.010). Conclusion Immunocompromised individuals with influenza A (H1N1) admitted to the ICU have a poor outcome. In this population, the use of corticosteroids is strongly discouraged.

Objectives: The aim of this study was to determine the persistence of the adverse prognostic effect of elevated vancomycin minimum inhibitory concentration (MIC) in methicillin-resistant Staphylococcus aureus (MRSA) bacteraemia in a setting with low vancomycin use. Methods: A retrospective study focusing on episodes of bacteraemia due to MRSA diagnosed from January 2010 through December 2015 was designed. The main outcome measures were 30-day mortality and treatment failure. Multivariate logistic regression analysis was used to identify variables associated with patient mortality and treatment outcome. Results: In total, 79 MRSA bacteraemia episodes were included. The vancomycin MIC was >1.0 mu g/mL in 53 episodes (67.1%). The presence of high vancomycin MIC was not associated with a higher mortality rate or treatment success. A daptomycin MIC >= 0.5 mu g/mL was present in 16 (26.2%) of 61 episodes for which the daptomycin MIC was obtained and was associated with 30-day mortality in the multivariate analysis (odds ratio = 4.72, 95% confidence interval 1.19-18.71). None of the antimicrobials used were associated with a lower risk of treatment failure or mortality. Conclusions: The pernicious effect of high vancomycin MIC disappears in the absence of a predominant use of this antibiotic. However, a high daptomycin MIC in MRSA bacteraemia is associated with higher mortality in patients with bacteraemia, irrespective of antimicrobial treatment choice. (C) 2018 International Society for Chemotherapy of Infection and Cancer. Published by Elsevier Ltd. All rights reserved.

Objective: Hospital antimicrobial stewardship programmes have achieved savings and a more rational use of antimicrobial treatments in general wards. The purpose of this report is to evaluate the experience of an antimicrobial stewardship programme in an intensive care unit (ICU). Design: Prospective interventional, before-and-after study. Scope: 24-bed medical ICU in a tertiary hospital. Intervention: Prospective audit and feedback antimicrobial stewardship programme. Endpoints: Antimicrobial consumption, antimicrobial related costs, multi-drug resistant microorganisms (MDRM) prevalence, nosocomial infections incidence, ICU length of stay, and ICU mortality rates were compared before and after one-year intervention. Results: A total of 218 antimicrobial episodes of 182 patients were evaluated in 61 team meetings. Antimicrobial stewardship suggestions were accepted in 91.5% of the cases. Total antimicrobial DDD/100 patient-days consumption was reduced from 380.6 to 295.2 (-22.4%; p = 0.037). Antimicrobial stewardship programme was associated with a significant decrease in the prescription of penicillins plus b-lactamase inhibitors, linezolid, cephalosporins, and aminoglycosides. Overall antimicrobial spending was reduced by (sic) 119,636. MDRM isolation and nosocomial infections per 100 patient-days did not change after the intervention period. No changes in length of stay or mortality rate were observed. Conclusions: An ICU antimicrobial stewardship programme significantly reduced antimicrobial use without affecting inpatient mortality and length of stay. Our results further support the implementation of an antimicrobial stewardship programme in critical care units. (C) 2017 Elsevier Espana, S.L.U. y SEMICYUC. All rights reserved.

Background: To analyse the effect of haemodiafiltration (CVVHDF) flow rate on amikacin pharmacokinetics and blood concentrations. Methods: Prospective observational study. Patients receiving CVVHDF and amikacin treatment were included. Pharmacokinetic parameters were calculated using Bayesian analysis. Spearman correlation test was used in order to assess the influence of CVVHDF flux on amikacin minimum concentration (Cmin) and plasma clearance. Results: Thirty patients undergoing CVVHDF procedures were included. The treatment with amikacin started at an initial mean dose of 12.4 (4.1) mg/kg/day. An association between the flow rate and Cmin value (r = 0.261; p = 0.161) and plasma clearance was found (r = 0.268; p = 0.152). Four patients (13.3%) were not able to achieve peak concentration over MIC value higher than 8. In 4 patients, amikacin had to be discontinued due to a high Cmin value. Conclusions: Amikacin clearance in patients with CVVHDF is affected by the flow rate used. Therefore, CVVHDF dose should be taken into account when dosing amikacin.

What is known and objective Positive volume balance is related with high mortality in critically ill patients. We describe our experience in the use of tolvaptan in patients with fluid overload. Case summary Six patients in the recovery phase from septic shock were included. All patients achieved an increase in diuresis after the first day, with a median fluid balance variation of −2362 (−485 to −3447) mL. At the end of treatment, median fluid balance variation was −9080 (−26 784 to −4395) mL. What is new and Conclusion Tolvaptan could be an option in critically ill patients with fluid overload and resistant or not treatable with conventional diuretics.

The purpose of this study was to assess the effectiveness of silver-embedded surfaces (BactiBlockA (R)) to prevent surface colonization by multi-resistant bacteria (MRB) and to reduce the incidence of MRB colonization and infection in patients admitted to an intensive care unit (ICU). A 6-month prospective observational study in a 24-bed mixed ICU divided into two identical subunits (12 beds each) was designed. Seven solid mobile screens were placed in one of the subunits while in the other cloth screens remained. Solid screens were constructed with high-density polyethylene embedded in BactiblockA (R). To evaluate the effectiveness of screens coated with BactiblockA (R), number of MRB isolates on screens were compared for 6 months. Likewise, numbers of new patients and ICU-stays with MRB colonization in the two subunits were compared. One hundred forty screen samples were collected in 10-point prevalent days. MRB were detected on 28 (20.0%) samples. Over the 70 samples taken on cloth folding screens, MRB were detected in 25 (35.7%), while only 3 (4.3%) of the 70 samples taken on BactiblockA (R) screens were positive for MRB (p < 0.001). The unit with BactiblockA (R) screens presented fewer number of ICU stays with MRB colonization (27.8% vs 47.1%; p < 0.001). No significant differences were found in the global incidence of MRB nosocomial infection. The presence of BactiblockA (R) embedded in solid folding screens avoided MRB surface colonization and reduced MRB transmission to patients admitted to critical care units, proving to be an useful tool in the control of MRB.

Ventilator-associated pneumonia (VAP) can have a clear onset or may be a result of the gradual appearance of symptoms and signs of VAP (gradual VAP). The aim of this paper is to describe the VAP development process with the intention of discriminating between those pneumonias with a clear beginning and those that are diagnosed after a period of maturation. In addition, we evaluate the effect of the starting time of antibiotic treatment in both situations.Consecutive ventilated patients fulfilling VAP criteria were included. The patients were monitored for clinical, microbiological, and inflammatory signs. Patients with VAP were classified into two groups: (1) nongradual VAP (patients in whom all VAP criteria were detected for the first time on the day of diagnosis) and (2) gradual VAP (progressive appearance of signs and symptoms throughout the pre-VAP period [96 h to24 h before VAP diagnosis]).A total of 71 patients with VAP were identified, of whom 43 (61 %) had gradual VAP, most of whom (n = 38, 88 %) had late-onset VAP. Antibiotic treatment was given to 34 (79 %) patients with gradual VAP in the pre-VAP period, and empirical antibiotic treatment was appropriate in 22 patients (51 %). The patients with an appropriate empirical treatment had a higher percentage of early clinical response to treatment (68 % [n = 15] vs. 28 % [n = 7]; p = 0.009). An attempt was made to find a diagnostic test capable of identifying the infectious process underway, but clinical scales and biomarkers of inflammation helped us to achieve acceptable results.Gradual emergence of VAP, mainly of late onset, is a common condition. Clinicians should be aware of this gradual onset of the infection to establish an early antibiotic treatment, even before the classic diagnostic criteria for VAP are applied.

Introduction: External ventricular drainage (EVD)-related ventriculitis is one of the most severe complications associated with the use of EVDs. Establishing an early and certain diagnosis can be difficult in critically ill patients. We performed this prospective study to evaluate the usefulness of soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) determination in cerebrospinal fluid (CSF) in the diagnosis of ventriculitis. Methods: A prospective observational study was conducted of 73 consecutive patients with EVD. Samples of CSF for culture, cytobiochemical analysis and sTREM-1 determination were extracted three times a week. Ventriculitis diagnosis required a combination of microbiological, cytobiochemical and clinical criteria. Results: Seventy-three consecutive patients were included. EVD-related ventriculitis was diagnosed in six patients and EVD-colonization in ten patients. Patients without clinical or microbiological findings were considered controls. The median CSF sTREM-1 was 4,320 pg/ml (interquartile range (IQR): 2,987 to 4,886) versus 266 pg/ml (118 to 689); P

Summary Objectives The objective of this study was to assess surveillance cultures (SC) prediction accuracy in two periods and settings of the same Department with a different microbiological epidemiology (high and low prevalence of multi-drug resistant microorganisms (MDRM)). Methods Prospective and observational study. SC were obtained twice a week in consecutive mechanically ventilated patients. Patients fulfilling VAP criteria were analyzed. Results 440 patients were followed up, 71 patients had VAP (50 in period I and 21 in period II). MDRM causing VAP were more prevalent in the first period (48% vs. 19%; p = 0.033). The rate of empirical appropriate treatment in period I was lower than in period II (52% vs. 76%; p = 0.031). SC prediction accuracy was similar in the two periods (80% vs. 81%; p = 0.744). However, if antibiotic treatment had been guided by SC, the percentage of appropriate treatment would have increased by 28% in the first period but only by 5% in the second; p = 0.024. Conclusions SC were able to predict VAP etiology in 80% of cases regardless the prevalence of MDRM. However, the potential benefit of SC in terms of appropriate empirical treatment could be only observed when MDRM were prevalent.

Little is known on the participation of immunoglobulin isotypes and subclasses in the pathogenesis of the severe disease caused by the pandemic influenza virus (influenza A(H1N1)pdm09).(1) To evaluate the association between plasma levels of IgG1, IgG2, IgG3, IgG4, IgA, IgM, IgE and outcome in patients with severe pandemic influenza. (2) To evaluate the association between immunoglobulin and cytokine levels in these patients.40 critically ill patients with community acquired pneumonia and influenza A(H1N1)pdm09 infection were recruited from November 2010 to February 2011. Plasma samples were collected during the first 24h following admission to the ICU. Immunoglobulins and 17 major cytokines were profiled in plasma.15 patients died (37.5%). When the association between clinical variables and prognosis was assessed, prior immunosuppression, APACHE II score, levels of IgG2 and levels of IgM were associated with outcome in a univariate Cox regression analysis. Kaplan Meier analysis showed that patients with levels of IgG2 and IgM59 and58 mg/dl respectively died earlier. Multivariate Cox regression analysis showed that APACHE II score and levels of IgM were the best predictors of outcome, being levels of IgM a protective factor against mortality. IgM was the immunoglobulin showing the largest number of negative correlations with cytokine levels.Our results support a central role of IgM in preventing uncontrolled inflammatory response and mortality in severe pandemic influenza. Early assessment of IgM could contribute to guide clinical decisions in these patients.

Biofilm formation on external ventricular drainages (EVDs) has been postulated as the main pathogenic mechanism for EVD-associated ventriculitis. However, biofilm on EVDs has never been systematically studied and the in vivo effect of antibiotic-impregnated EVDs on biofilm has not been assessed. The aim of this study was to measure the prevalence of biofilm formation on EVDs and to analyze the influence of antibiotic-impregnated EVD on the risk of biofilm formation and ventriculitis. Consecutive patients with EVDs were included in the study. Surveillance cerebrospinal fluid (CSF) cultures were performed twice a week. Withdrawn EVDs were cultured using standard bacteriologic techniques and examined under a scanning electron microscope. We collected 32 EVDs, 18 of which (56 %) were antibiotic-impregnated EVDs. Biofilm was present on 24 EVDs (75 %), ventriculitis was diagnosed in 6 patients (19 %), and colonization occurred in 12 patients (38 %). All cases of ventriculitis were due to Gram-negative bacteria. Biofilm was more frequent on EVDs originating from patients with ventriculitis or bacterial colonization. Impregnated EVDs did not avoid ventriculitis or colonization, but biofilm development on these devices depended on the time from insertion and varied from 67 % for those used for

Background: Severe disease caused by 2009 pandemic influenza A/H1N1virus is characterized by the presence of hypercytokinemia. The origin of the exacerbated cytokine response is unclear. As observed previously, uncontrolled influenza virus replication could strongly influence cytokine production. The objective of the present study was to evaluate the relationship between host cytokine responses and viral levels in pandemic influenza critically ill patients. Methods: Twenty three patients admitted to the ICU with primary viral pneumonia were included in this study. A quantitative PCR based method targeting the M1 influenza gene was developed to quantify pharyngeal viral load. In addition, by using a multiplex based assay, we systematically evaluated host cytokine responses to the viral infection at admission to the ICU. Correlation studies between cytokine levels and viral load were done by calculating the Spearman correlation coefficient. Results: Fifteen patients needed of intubation and ventilation, while eight did not need of mechanical ventilation during ICU hospitalization. Viral load in pharyngeal swabs was 300 fold higher in the group of patients with the worst respiratory condition at admission to the ICU. Pharyngeal viral load directly correlated with plasma levels of the pro-inflammatory cytokines IL-6, IL-12p70, IFN-gamma, the chemotactic factors MIP-1 beta, GM-CSF, the angiogenic mediator VEGF and also of the immuno-modulatory cytokine IL-1ra ( p < 0.05). Correlation studies demonstrated also the existence of a significant positive association between the levels of these mediators, evidencing that they are simultaneously regulated in response to the virus. Conclusions: Severe respiratory disease caused by the 2009 pandemic influenza virus is characterized by the existence of a direct association between viral replication and host cytokine response, revealing a potential pathogenic link with the severe disease caused by other influenza subtypes such as H5N1., The authors would like to thank also to the Nursery teams who kindly collected the samples and to Lucia Rico and Veronica Iglesias for their precious laboratory assistance. The study was scientifically supported by the Spanish Society for Critical Care Medicine (SEMICYUC). Funding: MICCIN-FIS/JCYL-IECSCYL-SACYL (Spain): Programa de Investigacion Comisionada en Gripe, GR09/0021-EMER07/050-PI081236-RD07/0067. This work was also supported by Grants or Contracts from ATCC/CDC USA, and University Health Network and IDR Canada (DJK).

Introduction: Pandemic A/H1N1/2009 influenza causes severe lower respiratory complications in rare cases. The association between host immune responses and clinical outcome in severe cases is unknown. Methods: We utilized gene expression, cytokine profiles and generation of antibody responses following hospitalization in 19 critically ill patients with primary pandemic A/H1N1/2009 influenza pneumonia for identifying host immune responses associated with clinical outcome. Ingenuity pathway analysis 8.5 (IPA) (Ingenuity Systems, Redwood City, CA) was used to select, annotate and visualize genes by function and pathway (gene ontology). IPA analysis identified those canonical pathways differentially expressed (P < 0.05) between comparison groups. Hierarchical clustering of those genes differentially expressed between groups by IPA analysis was performed using BRB-Array Tools v.3.8.1. Results: The majority of patients were characterized by the presence of comorbidities and the absence of immunosuppressive conditions. pH1N1 specific antibody production was observed around day 9 from disease onset and defined an early period of innate immune response and a late period of adaptive immune response to the virus. The most severe patients (n = 12) showed persistence of viral secretion. Seven of the most severe patients died. During the late phase, the most severe patient group had impaired expression of a number of genes participating in adaptive immune responses when compared to less severe patients. These genes were involved in antigen presentation, B-cell development, T-helper cell differentiation, CD28, granzyme B signaling, apoptosis and protein ubiquitination. Patients with the poorest outcomes were characterized by proinflammatory hypercytokinemia, along with elevated levels of immunosuppressory cytokines (interleukin (IL)-10 and IL-1ra) in serum. Conclusions: Our findings suggest an impaired development of adaptive immunity in the most severe cases of pandemic influenza, leading to an unremitting cycle of viral replication and innate cytokine-chemokine release. Interruption of this deleterious cycle may improve disease outcome., This work has been developed by an international team pertaining to the Spanish-Canadian Consortium for the Study of Influenza Immunopathogenesis. The authors would like to thank also to the Nursery teams who kindly collected the samples. The authors would like to thank Nikki Kelvin for language revision of this article. The study was scientifically sponsored by the Spanish Society for Critical Care Medicine (SEMICYUC). Funding: MICCIN-FIS/JCYL-IECSCYL-SACYL (Spain): Programa de Investigacion Comisionada en Gripe, GR09/0021 EMER07/050 PI081236 RD07/0067. CIHR NIH-Sardinia Recherche-LKSF Canada support DJK.

Objective: In cardiogenic shock (CS), presence of fever, leukocytosis, relatively low systemic vascular resistances, and high serum procalcitonin levels are quite frequent and recurrently involve the search for an infectious complication. We hypothesized that endotoxin exposure in CS could explain this sepsis-like syndrome. Design and Setting: Prospective observational study of consecutive CS patients admitted to our intensive care unit (ICU). Patients were followed during the first 3 days after CS onset. All clinical, hemodynamic, and microbiological data were collected. Inflammatory biomarkers and anti-endotoxin antibodies (IgM EndoCAb) were daily measured. Patients: We included 37 consecutive CS patients. Measurements and Main Results: Twenty-two patients (60%) had body temperature >38.3 degrees C or 14,000/mm(3) or