Procalcitonin (PCT) is used as a biomarker for the diagnosis of sepsis, severe sepsis and septic shock. At the same time, PCT has also been used to guide antibiotic therapy. This review outlines the main indications for PCT measurement and points out possible pitfalls. The classic indications for PCT measurement are: (i) confirmation or exclusion of diagnosis of sepsis, severe sepsis, or septic shock, (ii) severity assessment and follow up of systemic inflammation mainly induced by microbial infection, and (iii) individual, patient adapted guide of antibiotic therapy and focus treatment. Using serially monitored PCT levels, the duration and need of antibiotic therapy can be better adapted to the individual requirements of the patient. This individualized approach has been evaluated in various studies, and it is recommended to be a part of an antibiotic stewardship program.

Objective: The aim of this study was to evaluate the diagnostic and the prognostic value of a laboratory panel consisting of mid-regional pro-atrial natriuretic peptide (MR-proANP), procalcitonin (PCT), and mid-regional pro-adrenomedullin (MR-proADM) for patients presenting to the emergency department (ED) with acute dyspnea.Methods: We prospectively enrolled ED patients who presented with a chief complaint of dyspnea and who had an uncertain diagnosis after physician evaluation. Final primary diagnosis of the cause of shortness of breath was confirmed through additional testing per physician discretion. We recorded inpatient admission and 30-day mortality rates.Results: One hundred fifty-four patients were enrolled in the study. Congestive heart failure exacerbation was the final primary diagnosis in 42.2% of patients, while infectious etiology was diagnosed in 33.1% of patients. For the diagnosis of congestive heart failure exacerbation, MR-proANP had a sensitivity of 92.7% and specificity of 36.8%, with a negative likelihood ratio (LR-) of 0.16 and a positive likelihood ratio (LR+) of 1.44 (cut-off value: 120 pmol/L). For the diagnosis of an infectious etiology, PCT had a 96.5% specificity and 48.8% sensitivity (LR-: 0.58, LR+: 13.8, cutoff value: 0.25 ng/mL). As a prognostic indicator, MR-proADM demonstrated similar values: odds ratio for 30-day mortality was 8.5 (95% CI, 2.5-28.5, cutoff value: 1.5 nmol/L) and the area under the receiver operating characteristic curve in predicting mortality was 0.81 (95% CI, 0.71-0.91).Conclusion: The good negative LR- of MR-proANP and the good positive LR+ of PCT may suggest a role for these markers in the early diagnosis of ED patients with dyspnea. Furthermore, MR-proADM may assist in risk stratification and prognosis in these patients.. (C) 2012 Elsevier Inc. All rights reserved.

Infection and/or sepsis biomarkers should help to make the diagnosis and thus initiate therapy earlier, help to differentiate between infectious and sterile inflammation, allow the use of more-specific antimicrobials, shorten the time of antimicrobial use, and ideally identify distinct phenotypes that may benefit from specific adjunctive sepsis therapies. Procalcitonin (PCT) was proposed as a sepsis and infection marker more than 15 years ago. Meanwhile, PCT has been evaluated in various clinical settings. In this review the present use of PCT on the ICU and in critically ill patients is summarized, included it's role for diagnosis of severe sepsis and septic shock and antibiotic stewardship with PCT.

PurposeThe objective of this study is to define if early changes of procalcitonin (PCT) may inform about prognosis and appropriateness of administered therapy in sepsis.MethodsA prospective multicenter observational study was conducted in 289 patients. Blood samples were drawn on day 1, that is, within less than 24 hours from advent of signs of sepsis, and on days 3, 7, and 10. Procalcitonin was estimated in serum by the ultrasensitive Kryptor assay (BRAHMS GmbH, Hennigsdorf, Germany). Patients were divided into the following 2 groups according to the type of change of PCT: group 1, where PCT on day 3 was decreased by more than 30% or was below 0.25 ng/mL, and group 2, where PCT on day 3 was either increased above 0.25 ng/mL or decreased less than 30%.ResultsDeath occurred in 12.3% of patients of group 1 and in 29.9% of those of group 2 (P < .0001). Odds ratio for death of patients of group 1 was 0.328. Odds ratio for the administration of inappropriate antimicrobials of patients of group 2 was 2.519 (P = .003).ConclusionsChanges of serum PCT within the first 48 hours reflect the benefit or not of the administered antimicrobial therapy. Serial PCT measurements should be used in clinical practice to guide administration of appropriate antimicrobials.

Einleitung: Patienten und Methodik: Ergebnisse: Zusammenfassung: Introduction: Patients and Methods: Results: Discussion:

BACKGROUND:The present study sought to investigate the correlation of copeptin with the severity of septic status in patients with ventilator-associated pneumonia (VAP), and to analyze the usefulness of copeptin as a predictor of mortality in VAP.METHODS:The prospective observational cohort study was conducted in a teaching hospital. The subjects were 71 patients consecutively admitted to the intensive care unit from October 2003 to August 2005 who developed VAP. Copeptin levels were determined on day 0 and day 4 of VAP. Patients were followed for 28 days after the diagnosis, when they were considered survivors. Patients who died before day 28 were classified as nonsurvivors. There were no interventions.RESULTS:Copeptin levels increased from sepsis to severe sepsis and septic shock both on day 0 and day 4 (P = 0.001 and P = 0.009, respectively). Variables included in the univariable logistic regression analysis for mortality were age, gender, Acute Physiology and Chronic Health Evaluation II score and ln copeptin on day 0 and day 4. Mortality was directly related to ln copeptin levels on day 0 and day 4, with odds ratios of 2.32 (95% confidence interval, 1.25 to 4.29) and 2.31 (95% confidence interval, 1.25 to 4.25), respectively. In a multivariable logistic regression model for mortality, only ln copeptin on day 0 with odds ratio 1.97 (95% confidence interval, 1.06 to 3.69) and ln copeptin on day 4 with odds ratio 2.39 (95% confidence interval, 1.24 to 4.62) remained significant.CONCLUSION:Our data demonstrate that copeptin levels increase progressively with the severity of sepsis and are independent predictors of mortality in VAP.

This study aimed to investigate the correlation of midregional pro-atrial natriuretic peptide (MR-proANP) with severity of septic status in patients with ventilator-associated pneumonia (VAP) and the usefulness of MR-proANP for mortality prediction in VAP.

Timely diagnosis of the different severities of septic inflammation is potentially lifesaving because therapies that have been shown to lower mortality should be initiated early. Sepsis and severe sepsis are accompanied by clinical and laboratory signs of systemic inflammation but patients with inflammation caused by noninfectious causes may present with similar signs and symptoms. It is important to identify markers for an early diagnosis of sepsis and organ dysfunction. This article presents currently interesting sepsis biomarkers. Other novel markers and their potential role are discussed.

BACKGROUND:A comparison of the amount of and the kinetics of induction of procalcitonin (PCT) with that of C-reactive protein (CRP) during various types of and severities of multiple trauma, and their relation to trauma-related complications, was performed.METHODS:Ninety adult trauma patients admitted to the intensive care unit of our tertiary care hospital were evaluated in a prospective case study. During the initial 24 hours after trauma the Injury Severity Score, the Sepsis-related Organ Failure Assessment score, and the Acute Physiology and Chronic Health Evaluation II score were evaluated. PCT, CRP, the sepsis criteria (American College of Chest Physicians/Society of Critical Care Medicine definitions), and the Sepsis-related Organ Failure Assessment score were measured at days 1-7, as well as at days 14 and 21, concluding the observation period with the 28-day survival.RESULTS:The induction of PCT and CRP varied in patients suffering from trauma. PCT increased only moderately in most patients and peaked at day 1-2 after trauma, the concentrations rapidly declining thereafter. CRP ubiquitously increased and its kinetics were much slower. Complications such as sepsis, infection, blood transfusion, prolonged intensive care unit treatment, and poor outcome were more frequent in patients with initially high PCT (>1 ng/ml), whereas increases of CRP showed no positive correlation.CONCLUSION:In patients with multiple trauma due to an accident, the PCT level provides more information than the CRP level since only moderate amounts of PCT are induced, and higher concentrations correlate with more severe trauma and a higher frequency of various complications, including sepsis and infection. Most importantly, the moderate trauma-related increase of PCT and the rapidly declining concentrations provide a baseline value near to the normal range at an earlier time frame than for CRP, thus allowing a faster and more valid prediction of sepsis during the early period after trauma.

This study sought to assess the prognostic value of the kinetics of procalcitonin (PCT), C-reactive protein (CRP) and clinical scores (clinical pulmonary infection score (CPIS), Sequential Organ Failure Assessment (SOFA)) in the outcome of ventilator-associated pneumonia (VAP) at an early time point, when adequacy of antimicrobial treatment is evaluated.

Ornithine transcarbamylase deficiency (OTCD) is the most common inborn urea cycle disorder. Patients with OTCD are at risk of acute metabolic decompensation with hyperammonemia and subsequent encephalopathy, coma and death. Symptoms may be triggered by infections, drugs and stress, evoked by trauma, pain, fear, surgery and anaesthesia or by episodes of protein catabolism, i.e. fasting-induced, post partum or during gastrointestinal bleeding. Several specific considerations must be made for anaesthetic and intensive care management in patients with this disease in order to avoid metabolic decompensation. We report the intensive care management of the first manifestation of late-onset OTCD in a 16-year-old girl and a course of inconspicuous general anaesthesia with midazolam, s-ketamine, fentanyl and isoflurane in a 22-year-old girl with known OTCD.

INTRODUCTION:Postoperative infection is a major cause of morbidity and mortality. We investigated two serum markers for their ability to identify patients at risk for postoperative infection. Mannan-binding lectin (MBL) is a central molecule of the innate immune system and MBL deficiency is known to predispose to infection. Procalcitonin (PCT) is a sensitive marker for bacterial infection.METHODS:We investigated 162 patients undergoing elective surgery for cancer of the gastrointestinal tract. Patients were classified as having no complications (group A), having infection for unknown reason (group B) or having sepsis after events like aspiration or anastomotic leakage (group C). Analysis was done pre- and postoperatively for serum levels of MBL, PCT and C-reactive-protein. DNA was preoperatively sampled and stored and later analysed for genetic polymorphisms of MBL.RESULTS:The preoperative serum levels of MBL were significantly lower in group B patients than in group A patients (1332 +/- 466 ng/ml versus 2523 +/- 181 ng/ml). PCT measured on day one post-surgery was significantly higher in group B patients than in group A (3.33 +/- 1.08 ng/ml versus 1.38 +/- 0.17 ng/ml). Patients with an aberrant MBL genotype had a significantly higher risk of postoperative infections than wild-type carriers (p < 0.05).CONCLUSION:Preoperative MBL and early postoperative PCT measurement may help identify patients at risk for postoperative infection.

PURPOSE OF REVIEW:The purpose of this review is to indicate recent developments in biomarkers of sepsis and to evaluate their impact on clinical use. According to the 'surviving sepsis campaign,' diagnosis of sepsis and infection is urgent; early and specific treatment is most effective to reduce complications and to decrease mortality. RECENT FINDINGS:A variety of biomarkers of sepsis is presently available. The diagnostic spectrum of the various markers, however, is different. Some primarily indicate severity of inflammation (e.g. interleukin-6), others respond to infection, but do not indicate the host response well (endotoxin, lipoprotein binding protein, triggering receptor on myeloid cells). There are new markers with limited clinical experience, for example triggering receptor on myeloid cells or mid-pro atrial natriuretic peptide (Seristra, Brahms AG, Hennigsdorf, Germany). Procalcitonin is a well-established biomarker of sepsis that fulfills several criteria of clinical needs: it responds both to infection and severity of inflammation and thus has an impact on therapy. Recent studies indicate that antibiotic treatment can also be guided by procalcitonin. Further indications, including diagnosis of invasive bacterial infections and diagnosis of sepsis in neonates and children have been reported recently. SUMMARY:Recent data and cumulative analyses indicate that biomarkers of sepsis improve diagnosis of sepsis. However, only a few markers have impact on therapy and fulfill the clinical requirements. Procalcitonin is a well-established marker, indicating infection, sepsis, and progression to the more severe stages of the disease. Today, this biomarker should be in the diagnostic portfolio of an intensive care unit or emergency ward.

INTRODUCTION:Both C-reactive protein (CRP) and procalcitonin (PCT) are accepted sepsis markers. However, there is still some debate concerning the correlation between their serum concentrations and sepsis severity. We hypothesised that PCT and CRP concentrations are different in patients with infection or with no infection at a similar severity of organ dysfunction or of systemic inflammatory response. PATIENTS AND METHODS:One hundred and fifty adult intensive care unit patients were observed consecutively over a period of 10 days. PCT, CRP and infection parameters were compared among the following groups: no systemic inflammatory response syndrome (SIRS) (n = 15), SIRS (n = 15), sepsis/SS (n = 71) (including sepsis, severe sepsis and septic shock [n = 34, n = 22 and n = 15]), and trauma patients (n = 49, no infection). RESULTS:PCT and CRP concentrations were higher in patients in whom infection was diagnosed at comparable levels of organ dysfunction (infected patients, regression of median [ng/ml] PCT = -0.848 + 1.526 sequential organ failure assessment [SOFA] score, median [mg/l] CRP = 105.58 + 0.72 SOFA score; non-infected patients, PCT = 0.27 + 0.02 SOFA score, P < 0.0001; CRP = 84.53 - 0.19 SOFA score, P < 0.005), although correlation with the SOFA score was weak (R = 0.254, P < 0.001 for PCT, and R = 0.292, P < 0.001 for CRP). CRP levels were near their maximum already during lower SOFA scores, whereas maximum PCT concentrations were found at higher score levels (SOFA score > 12).PCT and CRP concentrations were 1.58 ng/ml and 150 mg/l in patients with sepsis, 0.38 ng/ml and 51 mg/l in the SIRS patients (P < 0.05, Mann-Whitney U-test), and 0.14 ng/ml and 72 mg/l in the patients with no SIRS (P < 0.05). The kinetics of both parameters were also different, and PCT concentrations reacted more quickly than CRP. CONCLUSIONS:PCT and CRP levels are related to the severity of organ dysfunction, but concentrations are still higher during infection. Different sensitivities and kinetics indicate a different clinical use for both parameters.

α-Fetoprotein (AFP) is a fetal glycoprotein produced by most human hepatocellular carcinoma tumors. Research has focused on its immunosuppressive properties in pregnancy, autoimmunity, and cancer, and human AFP directly limits the viability and functionality of human natural killer (NK) cells, monocytes, and dendritic cells (DCs). AFP-altered DCs can promote the differentiation of naïve T cells into regulatory T cells. These properties may work to shield tumors from the immune system. Recent efforts to define the molecular characteristics of AFP identified key structural immunoregulatory domains and bioactive roles of AFP-bound ligands in immunomodulation. We propose that a key mechanism of AFP immunomodulation skews DC function through cellular metabolism. Delineating differences between fetal ‘normal’ AFP (nAFP) and tumor-derived AFP (tAFP) has uncovered a novel role for tAFP in altering metabolism via lipid-binding partners.

Our objective was to evaluate the role of the liver for procalcitonin (PCT) and cytokine induction in a baboon endotoxin shock model. Complete liver resection with portocaval anastomosis was established in a baboon prior to the induction of endotoxin shock by intravenous administration of endotoxin (100 microg/kg LPS Escherichia coli). Two baboons without surgical intervention were used as controls. Plasma concentrations of PCT, tumor necrosis factor (TNF)-alpha, interleukin (IL) 6, IL-8, endotoxin, and hemodynamic and metabolic parameters were measured pre- and postoperatively and until 6 h after endotoxin administration. PCT concentrations increased to 1.2 and 4.6 ng/mL in control animals at 6 h, but remained below 0.3 ng/mL in the anhepatic baboon. IL-6 and IL-8 increased only for few hours in controls, but remained elevated in the hepatectomized animal near their maximum (IL-6, 2-6 ng/mL) or several-fold higher (IL-8, 30-35 ng/mL), whereas TNF-alpha response was only a small fraction (0.3 ng/mL) of the controls. Endotoxin was much higher and longer persisting in the hepatectomized animal compared with controls. The near absence of PCT production in the anhepatic baboon suggests a primary role for the liver as a source of PCT production during endotoxin shock. Furthermore, the liver also seems to be an important source of TNF-alpha, but not IL-6 or IL-8.

Induction of the protein procalcitonin during infection and inflammation was first described approximately 10 years ago. A large number of publications, primarily clinical studies, demonstrate the increasing use of procalcitonin in modern clinical practice. However, data on the biological function and origin of procalcitonin is scarce. Findings regarding the possible role and source of procalcitonin in sepsis and infection were recently published, and the pathophysiology of the protein has meanwhile been investigated in various experimental models. Procalcitonin obviously has certain biological functions, and it is also known to be specifically induced. Given the hormonal origin of the mature protein and the inflammation-related functions of its propeptides, some investigators suggest that procalcitonin should be referred to as a "hormokine," although its biological functions should be studied in more detail. This review will survey the data now available in recent publications on the induction, production sources, possible biological functions and clinical uses of procalcitonin.