Procalcitonin and pneumonia: Is it a useful marker?

An ideal biomarker for pneumonia should allow an early diagnosis and differential diagnosis from noninfectious conditions and should inform about the course and prognosis of the disease. Procalcitonin (PCT) covers these features better as compared to more commonly used biomarkers like C-reactive protein or leukocyte count. PCT complements and improves the assessment of pneumonia based on careful patient history, dedicated physical examination, and appropriate cultures. Importantly, a PCT-based therapeutic strategy can safely and markedly reduce antibiotic courses in community-acquired pneumonia. However, as is the cast with all diagnostic surrogate markers, PCT can be increased in noninfectious conditions and may remain low in bacterial infections, especially localized infections. This stresses the importance of follow-up measurements, because PCT levels in these patients often show a gradual increase during follow-up. Although PCT is better than more common biomarkers for the prognosis of pneumonia and to predict survival and outcome, novel biomarkers show an even better prognostic accurac

Glucorticoids: an investigation into a possible mechanism for their metabolic consequences and their prognostic role in acute illness

PhDBackground: Chronic exposure to glucocorticoids leads to Cushing’s syndrome (CS) with its metabolic consequences. AMPK is involved in many metabolic processes. Cortisol circulates largely bound to binding proteins, with the smaller amount of unbound hormone responsible for its metabolic effects. In acute illness binding proteins fall and total cortisol (TC) no longer reflects free cortisol (FC) levels. Hypothesis: I hypothesized that 1) AMPK has an important role in metabolic consequences of CS and 2) FC, as compared to TC, offers a better reflection of the degree of stress and is a better prognostic measure in acute illness. Methods: Wistar rats were implanted with corticosterone or placebo pellets and tissues collected. Adipose tissue of patients with CS and controls was sampled and AMPK measured by AMPK assay. Experiments were confirmed in vitro. FC was measured by a specially developed assay in two prospective clinical studies in acutely ill patients. Results: In the animal model, AMPK was decreased in adipose tissue and heart, and increased in liver and hypothalamus. This was confirmed in vitro in the respective cell lines. In visceral adipose tissue of patients with CS, AMPK was lower compared to controls. During acute illness, the increase above basal FC was higher than the increase in TC and fell more markedly. After ACTH stimulation, TC increased to a similar and FC to a lesser extent as in major stress. The value of cortisol in predicting outcome was higher as compared to routinely measured parameters. The predictive value of FC was not superior to TC. Conclusion: Glucocorticoid-induced changes in AMPK constitute a novel mechanism possibly explaining some of the metabolic consequences of CS. The more pronounced increase in FC seen during stress as compared to the ACTH test suggests that this test does not adequately anticipate FC levels needed during severe stress. The prognostic accuracy of FC is not superior to TC

Clinical review: The role of biomarkers in the diagnosis and management of community-acquired pneumonia

In patients with community-acquired pneumonia, traditional criteria of infection based on clinical signs and symptoms, clinical scoring systems, and general inflammatory indicators (for example, leukocytosis, fever, C-reactive protein and blood cultures) are often of limited clinical value and remain an unreliable guide to etiology, optimal therapy and prognosis. Procalcitonin is superior to other commonly used markers in its specificity for bacterial infection (allowing alternative diagnoses to be excluded), as an indicator of disease severity and risk of death, and mainly as a guide to the necessity for antibiotic therapy. It can therefore be viewed as a diagnostic, prognostic, and perhaps even theragnostic test. It more closely matches the criteria for usefulness than other candidate biomarkers such as C-reactive protein, which is rather a nonspecific marker of acute phase inflammation, and proinflammatory cytokines such as plasma IL-6 levels that are highly variable, cumbersome to measure, and lack specificity for systemic infection. Elevated levels of pro-adrenomedullin, copeptin (which is produced in equimolar amounts to vasopressin), natriuretic peptides and cortisol are significantly related to mortality in community-acquired pneumonia, as are other prohormones such as pro-atrial natriuretic peptide, coagulation markers, and other combinations of inflammatory cytokine profiles. However, all biomarkers have weaknesses as well as strengths. None should be used on its own; and none is anything more than an aid in the exercise of clinical judgment based upon a synthesis of available clinical, physiologic and laboratory features in each patient

Copeptin: a new and promising diagnostic and prognostic marker

The study conducted by Seligman and coworkers included in the previous issue of Critical Care demonstrates that copeptin is a promising marker to predict outcome in patients with ventilator-associated pneumonia. In recent years, copeptin has emerged as a new prognostic marker in a variety of diseases, such as sepsis, community-acquired pneumonia, chronic obstructive pulmonary failure, heart failure and myocardial infarction. What is the pathophysiological basis for these findings? Copeptin together with vasopressin is co-secreted from the posterior pituitary and therefore mirrors the amount of vasopressin in the circulation. Vaso-pressin is a main secretagogue of the hypothalamo–pituitary–adrenal axis, thereby mirroring the individual stress level. Furthermore, vasopressin is an important hormone in salt and volume regulation. In this context, copeptin is also a diagnostic marker in patients with diabetes insipidus and in patients with disordered water states

Procalcitonin: Importance for the diagnosis of bacterial infections

In contrast to calcitonin which is primarily synthesized in the thyroid, procalcitonin is a prohormone which is synthesized in many different tissues of infected organs. To diagnose mild, localized, or early infections an assay needs to have a functional assay sensivity of approximately 0.02μg/L. We demonstrated that procalcitonin modifies the outcome of respiratory infections with regard to minimizing the use of antibiotics and duration of antibiotic treatment. High concentrations, especially over time, indicate high risk of a severe outcome. In this respect, procalcitonin is superior to other infection markers, such as C-reactive protein. High procalcitonin levels can also be found in non-bacterial diseases, such as malaria, severe trauma, burns, and medullar carcinoma of the thyroid. Procalcitonin, as a marker, has improved the diagnosis of bacterial infections. However, procalcitonin needs to be used in conjunction with other laboratory markers, clinical examination, and medical histor

Procalcitonin und seine Bedeutung für die Diagnose bakterieller Infektionen

Procalcitonin ist das Pro-Hormon von Calcitonin. Im Gegensatz zu Calcitonin, welches primär in der Schilddrüse gebildet wird, wird Procalcitonin bei einer bakteriellen Infektion im Körper von allen infizierten parenchymatösen Organen produzier

Outcome of radioiodine therapy without, on or 3days off carbimazole: a prospective interventional three-group comparison

Purpose: Carbimazole ameliorates hyperthyroidism but reduces radioiodine uptake and adversely affects the outcome of simultaneous radioiodine therapy. We explored whether withdrawal of carbimazole for 3 days can restore the outcome of radioiodine treatment without concurrent exacerbation of hyperthyroidism. By generating three groups with comparable radioiodine uptake, we also investigated whether the effect of carbimazole depends on the radioiodine uptake. Methods: Stratified by a radioiodine uptake >30%, 227 consecutive adult patients were prospectively assigned to radioiodine therapy (target dose 200Gy) without, on or 3days off carbimazole. Patients were clinically (Crooks-Wayne score) and biochemically (T3, fT4, TSH) followed up after 3, 6 and 12months. Primary endpoint was outcome 12months after radioiodine therapy. Results: A total of 207 patients completed follow-up (toxic nodular goitre, n=117; Graves' disease, n=90). The overall success rate was 71.5%. Patients without and 3days off carbimazole had similar biochemical (81.4% and 83.3%, respectively; p=0.82) and clinical outcomes [median (range) Crooks-Wayne score 0 (0-16) and 1 (0-10), respectively; p=0.73], which were both higher than in patients on carbimazole [42.6%, p<0.001; Crooks-Wayne score 3 (0-30), p<0.03]. Time to achieve cure was delayed on carbimazole. No changes in thyroid hormone levels occurred after 3days' discontinuation of carbimazole. Logistic regression revealed that all observed cure rates were independent of entity, sex, age, thyroid volume, radioiodine uptake, radioiodine half-life, fT4, T3 and TSH. Conclusion: Patients under carbimazole treatment can be referred for radioiodine therapy after withdrawal of carbimazole for only 3days. Three days of carbimazole withdrawal is long enough to restore the success of radioiodine therapy and short enough to avoid the risk of exacerbation of hyperthyroidis

Pro-atrial natriuretic peptide is a prognostic marker in sepsis, similar to the APACHE II score: an observational study

INTRODUCTION: Additional biomarkers in sepsis are needed to tackle the challenges of determining prognosis and optimizing selection of high-risk patients for application of therapy. In the present study, conducted in a cohort of medical intensive care unit patients, our aim was to compare the prognostic value of mid-regional pro-atrial natriuretic peptide (ANP) levels with those of other biomarkers and physiological scores. METHODS: Blood samples obtained in a prospective observational study conducted in 101 consecutive critically ill patients admitted to the intensive care unit were analyzed. The prognostic value of pro-ANP levels was compared with that of the Acute Physiology and Chronic Health Evaluation (APACHE) II score and with those of various biomarkers (i.e. C-reactive protein, IL-6 and procalcitonin). Mid-regional pro-ANP was detected in EDTA plasma from all patients using a new sandwich immunoassay. RESULTS: On admission, 53 patients had sepsis, severe sepsis, or septic shock, and 68 had systemic inflammatory response syndrome. The median pro-ANP value in the survivors was 194 pmol/l (range 20–2000 pmol/l), which was significantly lower than in the nonsurvivors (median 853.0 pmol/l, range 100–2000 pmol/l; P < 0.001). On the day of admission, pro-ANP levels, but not levels of other biomarkers, were significantly higher in surviving than in nonsurviving sepsis patients (P = 0.001). In a receiver operating characteristic curve analysis for the survival of patients with sepsis, the area under the curve (AUC) for pro-ANP was 0.88, which was significantly greater than the AUCs for procalcitonin and C-reactive protein, and similar to the AUC for the APACHE II score. CONCLUSION: Pro-ANP appears to be a valuable tool for individual risk assessment in sepsis patients and for stratification of high-risk patients in future intervention trials. Further studies are needed to validate our results