Cytokine Profiles in Sepsis Have Limited Relevance for Stratifying Patients in the Emergency Department: A Prospective Observational Study

INTRODUCTION: Morbidity, mortality and social cost of sepsis are high. Previous studies have suggested that individual cytokines levels could be used as sepsis markers. Therefore, we assessed whether the multiplex technology could identify useful cytokine profiles in Emergency Department (ED) patients. METHODS: ED patients were included in a single tertiary-care center prospective study. Eligible patients were >18 years and met at least one of the following criteria: fever, suspected systemic infection, ≥ 2 systemic inflammatory response syndrome (SIRS) criteria, hypotension or shock. Multiplex cytokine measurements were performed on serum samples collected at inclusion. Associations between cytokine levels and sepsis were assessed using univariate and multivariate logistic regressions, principal component analysis (PCA) and agglomerative hierarchical clustering (AHC). RESULTS: Among the 126 patients (71 men, 55 women; median age: 54 years [19-96 years]) included, 102 had SIRS (81%), 55 (44%) had severe sepsis and 10 (8%) had septic shock. Univariate analysis revealed weak associations between cytokine levels and sepsis. Multivariate analysis revealed independent association between sIL-2R (p = 0.01) and severe sepsis, as well as between sIL-2R (p = 0.04), IL-1β (p = 0.046), IL-8 (p = 0.02) and septic shock. However, neither PCA nor AHC distinguished profiles characteristic of sepsis. CONCLUSIONS: Previous non-multiparametric studies might have reached inappropriate conclusions. Indeed, well-defined clinical conditions do not translate into particular cytokine profiles. Additional and larger trials are now required to validate the limited interest of expensive multiplex cytokine profiling for staging septic patients

Comparison between B.R.A.H.M.S PCT direct, a new sensitive point-of-care testing device for rapid quantification of procalcitonin in emergency department patients and established reference methods - a prospective multinational trial

BACKGROUND: Procalcitonin (PCT) is increasingly being used for the diagnostic and prognostic work up of patients with suspected infections in the emergency department (ED). Recently, B.R.A.H.M.S PCT direct, the first high sensitive point-of-care test (POCT), has been developed for fast PCT measurement on capillary or venous blood samples. METHODS: This is a prospective, international comparison study conducted in three European EDs. Consecutive patients with suspicion of bacterial infection were included. Duplicate determination of PCT was performed in capillary (fingertip) and venous whole blood (EDTA), and compared to the reference method. The diagnostic accuracy was evaluated by correlation and concordance analyses. RESULTS: Three hundred and three patients were included over a 6-month period (60.4% male, median age 65.2 years). The correlation between capillary or venous whole blood and the reference method was excellent: r2=0.96 and 0.97, sensitivity 88.1% and 93.0%, specificity 96.5% and 96.8%, concordance 93% and 95%, respectively at a 0.25 mug/L threshold. No significant bias was observed (-0.04 and -0.02 for capillary and venous whole blood) although there were 6.8% and 5.1% outliers, respectively. B.R.A.H.M.S PCT direct had a shorter time to result as compared to the reference method (25 vs. 144 min, difference 119 min, 95% CI 110-134 min, p>0.0001). CONCLUSIONS: This study found a high diagnostic accuracy and a faster time to result of B.R.A.H.M.S PCT direct in the ED setting, allowing shortening time to therapy and a more wide-spread use of PCT

Thermal Image Scanning for Influenza Border Screening: Results of an Airport Screening Study

Background: Infrared thermal image scanners (ITIS) appear an attractive option for the mass screening of travellers for influenza, but there are no published data on their performance in airports. Methods: ITIS was used to measure cutaneous temperature in 1275 airline travellers who had agreed to tympanic temperature measurement and respiratory sampling. The prediction by ITIS of tympanic temperature (37.8uC and 37.5uC) and of influenza infection was assessed using Receiver Operating Characteristic (ROC) curves and estimated sensitivity, specificity and positive predictive value (PPV). Findings: Using front of face ITIS for prediction of tympanic temperature $37.8uC, the area under the ROC curve was 0.86 (95$37.8uC at screening (95%CI 0 % to 12%); three had no influenza symptoms. Conclusion: ITIS performed moderately well in detecting fever but in this study, during a seasonal epidemic of predominantly influenza type B, the proportion of influenza-infected travellers who were febrile was low and ITIS were no

Inflammatory parameters predict etiologic patterns but do not allow for individual prediction of etiology in patients with CAP – Results from the German competence network CAPNETZ

<p>Abstract</p> <p>Background</p> <p>Aim of this study was to evaluate the correlation of inflammatory markers procalcitonin (PCT), C-reactive protein (CRP) and leukocyte count (WBC) with microbiological etiology of CAP.</p> <p>Methods</p> <p>We enrolled 1337 patients (62 ± 18 y, 45% f) with proven CAP. Extensive microbiological workup was performed. In all patients PCT, CRP, WBC and CRB-65 score were determined. Patients were classified according to microbial diagnosis and CRB-65 score.</p> <p>Results</p> <p>In patients with typical bacterial CAP, levels of PCT, CRP and WBC were significantly higher compared to CAP of atypical or viral etiology. There were no significant differences in PCT, CRP and WBC in patients with atypical or viral etiology of CAP. In contrast to CRP and WBC, PCT markedly increased with severity of CAP as measured by CRB-65 score (p < 0.0001). In ROC analysis for discrimination of patients with CRB-65 scores > 1, AUC for PCT was 0.69 (95% CI 0.66 to 0.71), which was higher compared to CRP and WBC (p < 0.0001). CRB-65, PCT, CRP and WBC were higher (p < 0.0001) in hospitalised patients in comparison to outpatients.</p> <p>Conclusion</p> <p>PCT, CRP and WBC are highest in typical bacterial etiology in CAP but do not allow individual prediction of etiology. In contrast to CRP and WBC, PCT is useful in severity assessment of CAP.</p

Diagnostic accuracy of procalcitonin in critically ill immunocompromised patients

<p>Abstract</p> <p>Background</p> <p>Recognizing infection is crucial in immunocompromised patients with organ dysfunction. Our objective was to assess the diagnostic accuracy of procalcitonin (PCT) in critically ill immunocompromised patients.</p> <p>Methods</p> <p>This prospective, observational study included patients with suspected sepsis. Patients were classified into one of three diagnostic groups: no infection, bacterial sepsis, and nonbacterial sepsis.</p> <p>Results</p> <p>We included 119 patients with a median age of 54 years (interquartile range [IQR], 42-68 years). The general severity (SAPSII) and organ dysfunction (LOD) scores on day 1 were 45 (35-62.7) and 4 (2-6), respectively, and overall hospital mortality was 32.8%. Causes of immunodepression were hematological disorders (64 patients, 53.8%), HIV infection (31 patients, 26%), and solid cancers (26 patients, 21.8%). Bacterial sepsis was diagnosed in 58 patients and nonbacterial infections in nine patients (7.6%); 52 patients (43.7%) had no infection. PCT concentrations on the first ICU day were higher in the group with bacterial sepsis (4.42 [1.60-22.14] vs. 0.26 [0.09-1.26] ng/ml in patients without bacterial infection, <it>P </it>< 0.0001). PCT concentrations on day 1 that were > 0.5 ng/ml had 100% sensitivity but only 63% specificity for diagnosing bacterial sepsis. The area under the receiver operating characteristic (ROC) curve was 0.851 (0.78-0.92). In multivariate analyses, PCT concentrations > 0.5 ng/ml on day 1 independently predicted bacterial sepsis (odds ratio, 8.6; 95% confidence interval, 2.53-29.3; <it>P </it>= 0.0006). PCT concentrations were not significantly correlated with hospital mortality.</p> <p>Conclusion</p> <p>Despite limited specificity in critically ill immunocompromised patients, PCT concentrations may help to rule out bacterial infection.</p

Predictive value of S100-B and copeptin for outcomes following seizure: the BISTRO International Cohort Study.

OBJECTIVE: To evaluate the performance of S100-B protein and copeptin, in addition to clinical variables, in predicting outcomes of patients attending the emergency department (ED) following a seizure. METHODS: We prospectively included adult patients presented with an acute seizure, in four EDs in France and the United Kingdom. Participants were followed up for 28 days. The primary endpoint was a composite of seizure recurrence, all-cause mortality, hospitalization or rehospitalisation, or return visit in the ED within seven days. RESULTS: Among the 389 participants included in the analysis, 156 (40%) experienced the primary endpoint within seven days and 195 (54%) at 28 days. Mean levels of both S100-B (0.11 μg/l [95% CI 0.07-0.20] vs 0.09 μg/l [0.07-0.14]) and copeptin (23 pmol/l [9-104] vs 17 pmol/l [8-43]) were higher in participants meeting the primary endpoint. However, both biomarkers were poorly predictive of the primary outcome with a respective area under the receiving operator characteristic curve of 0.57 [0.51-0.64] and 0.59 [0.54-0.64]. Multivariable logistic regression analysis identified higher age (odds ratio [OR] 1.3 per decade [1.1-1.5]), provoked seizure (OR 4.93 [2.5-9.8]), complex partial seizure (OR 4.09 [1.8-9.1]) and first seizure (OR 1.83 [1.1-3.0]) as independent predictors of the primary outcome. A second regression analysis including the biomarkers showed no additional predictive benefit (S100-B OR 3.89 [0.80-18.9] copeptin OR 1 [1.00-1.00]). CONCLUSION: The plasma biomarkers S100-B and copeptin did not improve prediction of poor outcome following seizure. Higher age, a first seizure, a provoked seizure and a partial complex seizure are independently associated with adverse outcomes

We should not be complacent about our population-based public health response to the first influenza pandemic of the 21st century

Background: More than a year after an influenza pandemic was declared in June 2009, the World Health Organization declared the pandemic to be over. Evaluations of the pandemic response are beginning to appear in the public domain. Discussion. We argue that, despite the enormous effort made to control the pandemic, it is now time to acknowledge that many of the population-based public health interventions may not have been well considered. Prior to the pandemic, there was limited scientific evidence to support border control measures. In particular no border screening measures would have detected prodromal or asymptomatic infections, and asymptomatic infections with pandemic influenza were common. School closures, when they were partial or of short duration, would not have interrupted spread of the virus in school-aged children, the group with the highest rate of infection worldwide. In most countries where they were available, neuraminidase inhibitors were not distributed quickly enough to have had an effect at the population level, although they will have benefited individuals, and prophylaxis within closed communities will have been effective. A pandemic specific vaccine will have protected the people who received it, although in most countries only a small minority was vaccinated, and often a small minority of those most at risk. The pandemic vaccine was generally not available early enough to have influenced the shape of the first pandemic wave and it is likely that any future pandemic vaccine manufactured using current technology will also be available too late, at least in one hemisphere. Summary. Border screening, school closure, widespread anti-viral prophylaxis and a pandemic-specific vaccine were unlikely to have been effective during a pandemic which was less severe than anticipated in the pandemic plans of many countries. These were cornerstones of the population-based public health response. Similar responses would be even less likely to be effective in a more severe pandemic. We agree with the recommendation from the World Health Organisation that pandemic preparedness plans need review

Mating skew in Barbary macaque males: the role of female mating synchrony, female behavior, and male–male coalitions

A fundamental question of sexual selection theory concerns the causes and consequences of reproductive skew among males. The priority of access (PoA) model (Altmann, Ann NY Acad Sci 102:338–435, 1962) has been the most influential framework in primates living in permanent, mixed-sex groups, but to date it has only been tested with the appropriate data on female synchrony in a handful of species. In this paper, we used mating data from one large semi-free ranging group of Barbary macaques: (1) to provide the first test of the priority-of-access model in this species, using mating data from 11 sexually active females (including six females that were implanted with a hormonal contraceptive but who showed levels of sexual activity comparable to those of naturally cycling females) and (2) to determine the proximate mechanism(s) underlying male mating skew. Our results show that the fit of the observed distribution of matings with sexually attractive females to predictions of the PoA model was poor, with lower-ranking males mating more than expected. While our work confirms that female mating synchrony sets an upper limit to monopolization by high-ranking individuals, other factors are also important. Coalitionary activity was the main tactic used by males to lower mating skew in the study group. Coalitions were expressed in a strongly age-related fashion and allowed subordinate, post-prime males to increase their mating success by targeting more dominant, prime males. Conversely, females, while mating promiscuously with several males during a given mating cycle, were more likely to initiate their consortships with prime males, thus reducing the overall effectiveness of coalitions. We conclude that high-ranking Barbary macaque males have a limited ability to monopolize mating access, leading to a modest mating skew among them