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The monitoring of quality indicators, combined with a detailed risk analysis, validates the process of automated blood culture. Here we report the methodology of 5 years monitoring for 5 indicators at the Biology Department of Foch Hospital: volume sampled, proportion of contaminants, proportion of positive blood cultures in each instrument and drawer, epidemiological indicator and proportion of false-positive instrument signals. The results obtained were outside the expected target for the volume sampled and were acceptable for the other indicators. The analysis of these results leads us to discuss the evolution of quality indicators and more particularly the implementation of corrective measures, their periodicity, their relevance as well as the need to refine their results to carry out targeted actions.

Background: Several studies in internal medicine departments and in intensive care units have shown the interest of eosinopenia in the diagnosis of infected patients. The aim of the present study was to test the value of this marker in the Emergency Department (ED), either alone or associated with other common sepsis markers., Methods: We report on a retrospective and monocentric study. We reviewed the complete blood count (CBC) of all patients visiting the ED during one-week duration (in February 2014). Every element of the CBC and other inflammation markers (such as CRP) were analyzed., Results: During the week of our study, 725 patients had a CBC (33 exclusions) and 692 patients were included for analysis. The median age was 59 years (IQR: 16-100). One hundred and twenty-five patients (18.1%) had a sepsis. The ROC curve demonstrated a cut off level of 10/mm 3 eosinophils for which the specificity for sepsis was 91%. The association of eosinopenia (< 10/mm 3 ) and white blood cells (WBC) or CRP elevation also showed a good specificity in patients with sepsis., Conclusion: In the ED, with a "simple" CBC, a profound eosinopenia appears to be very specific for sepsis, alone or in association with other markers of inflammation. Eosinopenia may become a helpful tool in our daily practice in the ED. Further studies are needed to further evaluate this marker., (Copyright © 2016 Société nationale française de médecine interne (SNFMI). Published by Elsevier SAS. All rights reserved.)

Despite some progress, the mortality of severe sepsis and septic shock remains high. Immunotherapy directed against inflammatory mediators failed, but new treatments more specifically tailored to individual situations are actively investigated. C-reactive protein (CRP) and procalcitonin (PCT) have not demonstrated to be useful for individual prognostic stratification. New biomarkers such as pancreatic stone protein (PSP) or growth arrest specific protein 6 (Gas6) could improve this prediction. Combined with the clinical course, "PCT" allows to tailor individually the duration of antibiotic therapy in ICU patients. This still contested innovative approach significantly reduces overall exposure to antibiotics.

Sepsis is defined as a systemic response to infection, characterized by an intense inflammatory response linked to coagulation activation and fibrinolysis inhibition, two processes which are intimately associated. In a field where mortality remains very high, administration of activated protein C, a physiological coagulation inhibitor with cytoprotective properties, has demonstrated its effectiveness and was able to reduce mortality. Protein C belongs to a system that involves plasma proteins and endothelial cell receptors. In addition to well documented effects on coagulation and fibrinolysis, activated protein C exhibits anti-inflammatory, anti-apoptotic but also anti-histone activities. Indeed, a recent study focusing on the cytoprotective effects of activated protein C showed that extracellular histones are released during severe sepsis and may participate in the pathophysiology of severe sepsis. These histones appear to be new targets of activated protein C., (© 2011 médecine/sciences - Inserm / SRMS.)

The sepsis associated encephalopathy (SAE) is a common cause of delirium, accompanied by hyperthermia or not. It is defined as a diffuse cerebral dysfunction induced by the systemic response to the infection without clinical or laboratory evidence of direct infectious involvement of the central nervous system. It is, thus, a diagnosis of exclusion. The pathogenic mechanisms underlying SAE are now better understood: it involves, at least, an intense inflammation of the central nervous system and a major impairment of the blood brain barrier. At the present time, clinical, biological and radiological characteristics of SAE have been sufficiently described to ensure rapid identification, but prognosis remains severe. Proper management requires treatment as early as possible of the infectious site and accompanying systemic inflammatory response. When appropriately conducted, minimal consequences or complete recovery can be expected., (Copyright © 2010 Elsevier Masson SAS. All rights reserved.)

Human serum albumin is a small (66kD) globular protein representing over 60 % of the total plasma protein content. It is made up of 585 amino 6 acids and contains 35 cysteine residues forming disulfide bridges that contribute to its overall tertiary structure. It has a free cysteine-derived thiol group at Cys-34, which accounts for 80 % of its redox activity. Physiologically, serum albumin exists in a reduced form with a free thiol contributing to its antioxidant properties. It is synthesized primarily in the liver and is an acute-phase protein. It is a multifunctional plasma protein ascribed ligand-binding and transport properties as well as antioxidants and enzymatic functions. It maintains colloid osmotic pressure, modulates inflammatory response and may influence oxidative damage. Hypoalbuminemia is common in the intensive care unit and may be due to decreased synthesis by the liver and/or to increased losses or increased proteolysis and clearance. Although albumin was long used to control vascular collapse in critically ill patients, the evidence suggests that it does not offer a benefit over crystalloid solutions in vascular collapse. However, human serum albumin is an important circulating antioxidant and it may be beneficial in critically ill patients to limit oxidative damage. A number of studies suggest that in specific groups of hypoalbuminemic critically ill patients, albumin administration may have beneficial effects on organ function, although the exact mechanisms remain undefined. Further trials are needed to confirm theses observations and to clearly demonstrate whether albumin should be administered in critically ill patients with hypoalbuminemia., (Copyright (c) 2010 Elsevier Masson SAS. All rights reserved.)

Hyperglycemia is commun in critically ill patients without previously known diabetes. Hyperglycemia occurring in these patients is mainly a consequence of stress associated to complex glucose metabolism abnormalities which have deleterious effects on tissues and vascular function. Several epidemiologic and intervention studies had established that hyperglycemia is related to morbidity and mortality. Maintenance of normoglycemia with intensive insulin therapy seems to decrease morbidity and mortalities in severe acute illnesses. However the benefit of most of these intervention trials remain controversial mainly in stroke, myocardial infarction and severe sepsis. Moreover strict normoglycemia required to obtain an optimal benefit increases the risk of hypoglycaemia which may be particularly harmful in patients in critical state.

Objectives: Determination of the utility of C-reactive protein (CRP) levels when measured 21 days after hip and knee arthroplasties for early diagnosis of infectious complications., Method: This study was performed in two parts: establishment of a reference curve by measurement of CRP levels once a week in a cohort of 94 patients (50 total hip arthroplasties and 44 total or unicondylar knee arthroplasties); study of the diagnostic value of two different CRP cut-offs (25mg/l, the mean CRP level and two standard deviations; 18 mg/l, mean and one standard deviation) at D21 postoperative in a population of 48 patients, of whom 12 presented septic complications (four surgical site infections [SSIs] and eight intercurrent infections)., Results: We observed very high interindividual variations in CRP values two weeks after arthroplasty. These variations decreased strongly in the third week postoperative. In the seven patients with a CRP level above 25mg/l at D21, there were no false-positives. In the 41 patients with a CRP level below 25mg/l at D21, there were five false-negatives and no false-positives. With the CRP threshold set at 18 mg/l, we observed four false-positives and four false-negatives., Discussion-Conclusion: A CRP level threshold of 25mg/l is not sufficiently reliable for early detection of postoperative infections (whether at the surgical site or elsewhere), as judged by a sensitivity of 58.3% and a negative predictive value of 87.8%. However, the 25mg/l threshold displays first-rate specificity and positive predictive values (both 100%). A CRP threshold at 18 mg/l is no better because even though it yields slightly a higher sensitivity value (66.7%), it strongly decreases specificity (88.9%). CRP is an important tool for postoperative monitoring but often appears to be difficult to use. The diagnosis of septic complications is based on clinical and paraclinical arguments. Local discharge, fever over 38 degrees C and local/persistent pain and stiffness are more informative indicators of postoperative infection.

Objectives: The aims of this review are to point out the determinants of oxygen saturation of the haemoglobin of mixed venous blood (SvO(2)), to specify the correlations existing between SvO(2) and central venous saturation in superior vena cava (ScvO(2)), to determine and finally to locate the current place of venous oximetry in clinical practice., Data Sources: A PubMed database research in English and French languages published until December 2006. The keywords were mixed venous blood oxygen saturation; oxygen consumption; oxygen delivery; oxygen extraction; tissue hypoxia; central venous oxygen saturation., Data Extraction: Data in selected articles were reviewed, clinical and basic science research relevant information was extracted., Data Synthesis: The SvO(2) reflects the peripheral extraction of oxygen (O(2)), O(2) delivery and consumption. Its value is related to four determinants: the O(2) consumption (VO(2)), cardiac flow (CF), haemoglobin level (Hb) and O(2) saturation of the haemoglobin of arterial blood (SaO(2)). ScvO(2) is more easily measurable than SvO(2). Under physiological conditions its value is 2 to 3% lower than that of SvO(2). In the critically ill patient, its value is 5% higher than that SvO(2). In most patients, changes in ScvO(2) values parallel those in SvO(2). The clinical interest of the monitoring of venous oximetry was underlined in cases of severe sepsis and septic shock, and during the perioperative period of major surgery., Conclusion: The management of patients in critical states with therapeutic goals integrating the monitoring of venous oximetry may reduce the morbidity and mortality of patients undergoing major surgery or hospitalised in the intensive care unit.

The biphasic waveform (BPW) is an abnormality of the optical transmission waveform obtained during measurement of the activated partial thromboplastin time on a specific photometric haemostasis autoanalyzer. This abnormality is related to calcium-dependent formation of complexes between C reactive protein and very low density lipoprotein. Biphasic waveform had a high sensitivity and negative predictive value for the identification of patients with severe sepsis and septic shock. On day 3, the time course of the biphasic waveform is a marker for the prognosis of sepsis-related mortality. The BPW is not a surrogate marker for C-reactive protein or procalcitonin and provides additional information. Further trials should be necessary using BPW for diagnostic and management procedures. Compared with other laboratory markers such as C reactive protein or procalcitonin, activated partial thromboplastin time waveform analysis is a tool that is rapid, inexpensive, effective and available 24 hours a day. When the analyzer is locally available, waveform analysis of this routine coagulation test provides information for the diagnosis of severe sepsis and the prognosis of septic patients.

Sepsis and trauma lead to a sustained activation of monocytes and endothelium. In the vascular compartment, stimulated cells release microparticles. Circulating MP provide an additional procoagulant phospholipid surface enabling the assembly of the clotting enzymes complexes and thrombin generation. Their procoagulant properties rely on the exposition of phosphatidylserine, made accessible after cell stimulation and on the possible presence of tissue factor, the main cellular initiator of blood coagulation. Microparticles constitute the main reservoir of blood-borne tissue factor activity. At sites of endothelium injury, enhanced release or recruitment of procoagulant MP through P-selectin-PSGL-1 pathway could concentrate TF activity above a threshold allowing blood coagulation to be triggered. Converging evidences from experimental or clinical data highlight a role for MP harboring tissue factor in the initiation of disseminated intravascular coagulopathy. In these settings, the pharmacological modulation of MP levels or biological functions through activated protein C or factor VIIa allows challenging issues.

Purpose: Today, calcitonin assay is used for the diagnosis of thyroid medullary cancer in the context of nodular thyroid disease. Calcitonin is an excellent marker of thyroid medullary cancer but some hypercalcitoninemia can also be related to other diseases, such as renal failure, endocrine tumors other than thyroid medullary cancer and sometimes to C cell hyperplasia, which is a not well-defined situation. Recent studies contributed to define calcitoninemia thresholds, which guide decision and avoid excessive invasive treatment., Current Knowledge and Key Points: After a brief reminder of physiological role of calcitonin and assays, the difficulties encountered in interpreting hypercalcitoninemia and its potential causes other than thyroid medullary cancer are addressed. Recent studies, on large series, now allow a better knowledge of specificity and sensitivity of calcitonin measurement in patients with nodular thyroid disease and a well-argued management., Future Prospects and Projects: In the future, calcitonin dosage will be ordered even more frequently, as some authors recommend it for the diagnosis of thyroid nodule. It is up to us to know how to use this remarkable marker, by considering all possible situations of benign hypercalcitoninemia and reserving aggressive treatments for patients who really need them.

The 3 poles of treatment. These are the hemodynamic management, early antibiotherapy and more specific treatments, based on improved physiopathological knowledge. From a hemodynamic point of view The first stage must always be to detect and correct the hypovolemia. The administration of vasopressive amines (or vasoconstricting amines) is mandatory in the case of septic shock. The choice of the antibiotics In the absence of microbiological proof, it is based on the germs most often encountered in infections of the suspected site and community or nosocomial nature of the infection. The antibiotherapy must be set-up as early as possible once the bacteriological samples have been. Treatments based on the physiopathology The activated protein C possesses pro-fibrinolytic, anticoagulant and anti-inflammatory properties; it obtained marketing Authorization in Europe for patients with severe sepsis and at least 2 organ failures or hypotension. Low-dose corticosteroids should be prescribed in the case of septic shock with prolonged use of catecholamines, and if possible following a test with Synacthène(R) (relative adrenal insufficiency). Intensive insulin therapy is aimed at maintaining normal glycemia in the patients for as long as possible.

Objective: To present and discuss the rationale and the results of clinical trials using supplementation with physiologic anticoagulants (Tissue Factor Pathway Inhibitor (TFPI), AntiThrombin (AT), and Protein C (PC) in patients with severe sepsis., Rationale: An early activation of the coagulation cascade occurs in severe sepsis. TFPI, AT, and PC are major inhibitors of the coagulation cascade, and additionally modulate inflammatory and vascular reactions. They are consumed or inhibited in the sepsis pathologic process. Therapeutic supplementation with these inhibitors could improve the sepsis-induced organ failures and mortality., Clinical Results: Randomized controlled studies were recently completed. No effect on the mortality rate could be documented after treatment with recombinant TFPI. AT concentrates neither improve mortality, but a biological interaction with heparin therapy could have biased the study results. Treatment with recombinant activated PC (alpha-drotrecogin) was associated with a significant reduction in the mortality rate of severely ill patients and received recently the approval from FDA and EC authorities in this indication. An increase in the rate of hemorrhagic adverse effects has been observed with these compounds, justifying a strict observance of contraindications and of patients selection. PROSPECTIVE: Additional studies are needed to give confirmation of the positive effects of activated PC supplementation in less severely ill patients, children and specific clinical situations. The effects of new anticoagulant compounds are currently evaluated in preclinical studies.

Purpose: Haptoglobin (H) and orosomucoid (O) are acute phase proteins that increase in a parallel manner. When hemolysis and inflammation are both present, study of the O-H couple on the protein profile may reveal an unknown hemolysis., Methods: To determine if hemolysis is more frequent during infectious endocarditis than during septicemia without valvulopathy or during valvulopathy without septicemia. Study of three groups of patients: 26 patients with infectious endocarditis, 13 patients with septicemia and 36 patients with valvulopathy without septicemia. Studied parameters were the O-H couple, hemoglobin and rate of O., Results: Hemolysis is clear in patients with endocarditis. The difference O-H is significantly more important during endocarditis than during septicemia without valvulopathy (P < 0.001) and during valvulopathy without sepsis (P < 0.001)., Conclusion: Study of the O-H couple may be useful for the diagnosis of endocarditis showing a difficult-to-diagnose hemolysis.

Coagulation and fibrinolysis are not activated in an isolated system but it involves numerous interrelations with the kininogen-kinin pathway and the complement. In severe sepsis, substances released by microorganisms, notably lipopolysaccharides, can activate the contact system, and particularly in such circumstances, contact activation probably plays a role in the occurrence of haemodynamic changes and consumption coagulopathy. Evidence of kininogen-kinin pathway activation as assessed by biological investigations in patients with severe sepsis, could lead to the therapeutical use of natural or synthetic protease inhibitors.

The value of serum bactericidal activity (SBA) determination for assessing the effectiveness of antibiotic therapy was evaluated in a retrospective open study in 168 cases of septicemia. Outcomes in a first group (I) of 67 patients with a SBA of at least 1/4 were compared with outcomes in a second group (II) of 101 patients with a SBA below 1/4 or non-determined. Within these groups, outcomes of 37 septicemias due to Gram negative bacilli (subgroup Ia) and 22 staphylococcal septicemias (subgroup Ib) with a SBA greater than or equal to 1/4 were compared with outcomes in 26 septicemias due to Gram negative bacilli (subgroup IIa) and 22 staphylococcal septicemias (subgroup IIb) with a SBA less than 1/4. Statistical analysis of distribution of age, sex, underlying disease, biologic parameters and antibiotics given demonstrated no significant difference between the various groups. 56 patients (86.1%) recovered in group I, against 76 (79.1%) in group II; corresponding figures are 34 (91.1%) and 21 (84%) in subgroups Ia and IIa respectively. These differences are not significant (p greater than 0.05). Our findings suggest that an "effective" SBA fails to correlate with favorable outcome of septicemia.

In 132 consecutive patients with suspected bacteremic infectious diseases, Gram staining of the buffy coat of blood taken from the ear lobe was performed simultaneously with blood cultures. Out of 132 patients, 7 exhibited intraleukocytic microorganisms among 22 with concomitant positive hemocultures and 21 with concomitant sterile hemocultures. Among this latter group of patients, 8 were severely ill subjects with indwelling intravenous catheters and undergoing treatment with broad spectum antibiotics, while 4 were found to have intraleukocytic yeast forms. Eight presented with a typical history of pneumonia. It is concluded that Gram staining of the buffy coat of the ear lobe blood is a simple technique which is of value in the management of patients with suspected bacteremia and of febrile patients with indwellig catheters or under antibiotic therapy.

There is no uniform agreement about the effects of bacterial endotoxins upon vascular permeability. We presently report some clinical observations indicating an increase in vascular permeability during sepsis and shock related to Neisseria meningitidis in children. 133 children, admitted for a severe infection due to Neisseria m. were separated into three groups according to the severity of the initial clinical picture. The patients presenting with a sepsis or shock had significantly lower mean plasma protein levels on admission. This was not related to any hemodilution or caloric deficiency. Hypoproteinemia worsened during the 24 first hours of treatment, despite hemoconcentration as presented by some patients [12]. The speed of decrease in protein concentrations was inversely related to the molecular weights of the different protein fractions. These observations indicate an increase in vascular permeability with maintainance of vascular membrane selectivity to macromolecules during early meningococcic septicemia and shock.

Changes in serum concentrations versus time of C reactive protein and orosomucoid were investigated in 134 neonates with either materno-foetal infection (group A, n = 111) or nosocomial infection (group B, n = 23). Both proteins were significantly elevated in group A neonates, with mean +/- S.E.M. values of 0.029 +/- 0,003 g/l for C reactive protein (n = 111) and 0.56 +/- 0.003 g/l for orosomucoid (n = 37). In cases with superinfection serum levels of both proteins rose before clinical symptoms developed. Changes in orosomucoid concentrations occurred a few hours after changes in C reactive protein concentrations. Monitoring C reactive protein and orosomucoid levels, in an excellent means of assessing the effectiveness of treatment and of deciding on its withdrawal when both proteins return to normal values.

The variation of Apo SAA has been studied in parallel with HDL disturbances in septic patients to try to define the role of SAA in these lipoproteins abnormalities. 14 septic patients hospitalized in a surgical intensive care unit have been studied. In these patients, the determination of cholesterol, HDL-cholesterol, Apo AI, Apo B, Apo SAA and CRP and lipoprotein electrophoresis have been made between the 4th and the 7th day after admission in the unit. A control group includes 10 patients undergoing an elective knee surgery. Our results show that SAA elevation (480 +/- 250 mg/l) are much greater than CRP ones (137 +/- 38 mg/l) with no correlation between the 2 proteins specially in patients with hepatic failure. As reported by others, we find a diminution of total cholesterol (3.0 +/- 1.2 mmol in our series) and HDL-cholesterol (0.39 +/- 0.18 mmol). Apo AI is dramatically decreased (0.50 +/- 0.29 g/l) such as a negative acute phase protein. The polyacrylamide gel electrophoresis of lipoproteins confirms the HDL decrease and reveals an abnormal migration of this class of lipoprotein in 8 cases/14 cases (4 accelerations and 4 double-bands). From the results, this HDL modification does not seem to correlate with SAA elevation; immunoblotting experiments lead to the same conclusion. The data are discussed and compared to other findings of the literature.

In the search of a fast and simple laboratory test for the diagnosis of neonatal septicemia the blood pictures of 29 cases of septicemia were compared with normal values derived from 390 healthy newborns. In each case the leucocyte count, the neutrophil count, the band count and its percentage, the ratio of band forms to segmented neutrophils and the platelet count were analysed in the blood smear taken on the day of clinical suspicion of septicemia. The leucocyte count, the neutrophil count and the band count are within the pathological range in 70% of the cases. The percentage of band forms and the ratio of bands forms to segmented neutrophils are, with one exception, always abnormally elevated. Thrombocytopenia is present in only 60% of the cases. Among the different criteria the percentage of band forms is evidently the most practical and most significant one. Considering our normal values, the pathological range for this percentage is above 20% on the first day of life, above 15% on the second day and above 8% from the third day on.

The presence of vacuolated polymorphonuclear neutrophils in blood smears of patients suffering from infection appears to be associated with massive bacterial growth and to constitute a very early symptom of rapidly life-threatening septicaemia. When these cells persist for more than 36 hours, the disease may be considered as beyond control.

Plasma fibronectin (pFN) levels were measured in 52 patients throughout their stay in an intensive care unit. At the same time a close watch was kept for signs of sepsis. Low pFN levels regularly accompanied--but did not precede--infectious episodes and were also found in patients without septic complications. These findings indicate that a fall in pFN does not constitute a factor of increased susceptibility to infection.

Among 17 septicemic patients, a statistically decrease of seric oligo-elements is demonstrated. The longitudinal study shows the rapid correction of these perturbations in the surviving group and the lack of correction among the non survivors. The level of phosphorus is the most interesting one. The importance of S.R.E. activity is probably the physiopathologic support of seric oligo-element modifications in sepsis.

The authors studied changes in erythrocyte lipids in severe infectious syndromes, separating healthy individuals (n = 10) from those with hepatic insufficiency (n = 7). No variations in sphingomyelins were seen. By contrast, the fall in cholesterol and other phospholipids studied (phosphatidylcholine and phosphatidylethanolamine) was highly significant. The difference between the two groups remained clear on the fourth day. No relationship could be established with prognosis and the organism responsible. In conclusion, the authors stress the need for study of the relationships between these changes and erythrocyte functions.

Capillary and venous diffusion of bacteria were studied in chickens after intravenous inoculation with Escherichia coli K12. A first group of 35 chickens was inoculated with 10(7) and a second group of 49 chickens with 10(8) E. coli. Bacterial enumeration showed two types of bacterial blood distributions. Early after inoculation, the level of bacteraemia was higher in venous than in capillary blood; later, the level of bacteraemia was higher in capillary than in venous blood. The difference was significant for the two kinds of inoculum. These results showed a slower clearance of E. coli in capillary than in venous blood. These experimental data confirm the greater sensibility of capillary than of venous sampling, already observed in neonates.

We have experimented with a new instrument, "hemopipette", known to reduce the incidence of contamination in small samples of capillary blood for haemoculture. Without altering our usual skin asepsis procedure, we carried out 270 microhaemocultures in 240 neonates. Two haemocultures (0.74%) were contaminated, a significantly lower percentage than the 3.6% observed in a first series of 411 microsamples obtained prior to the introduction of "hemopipette". This fall in contamination rate appears to be associated with the use of this instrument which combines a pipette and a lancet and facilitates capillary blood withdrawal.