THE IMPORTANCE OF DETERMINING PROCALCITONIN AND C REACTIVE PROTEIN IN DIFFERENT STAGES OF SEPSIS

Rapid and early diagnosis of systemic infections is very important for acting on time with an adequate therapy. P e aim of this study is to determine the diagnostic importance of procalcitonin (PCT) and Creactive protein (CRP) of bacterial infections in diff erent stages of sepsis. PCT and CRP have been determined in  newborns, - days of age, with diff erent stages of sepsis, in the centre for prematurely born neonates. P ese parameters have also been determined for control group, in which there were  healthy newborns. Procalcitonin values were signifi cantly increased in neonates with septic shock (, ng/mL; ,- ng/mL) compared to the systemic infl ammatory response syndromeSIRS ( ng/mL; ,- ng/mL), neonatal sepsis (, ng/mL; ,-, ng/mL), neonatal sepsis and purulent meningitis (, ng/mL; ,-, ng/mL). P e control group values were lower than , ng/mL. CRP is increased without statistical diff erences in all stages of sepsis in newborns with septic shock (, mg/L; ,- mg/L) in cases with SIRS (, mg/L; ,- mg/L), neonatal sepsis (, mg/L; - mg/L), neonatal sepsis and purulent meningitis (, mg/L; - mg/L). P e average values for the control group were , mg/L. Procalcitonin is increased in all stages of sepsis with higher values in the septic shock. P e increase of PCT levels is related to the severity, course of infection and prognosis of disease.


Introduction
Infections in newborns are the most often causes of morbidity and mortality.e early and rapid diagnosis of systemic infections is very important to start the right therapy on time.Infections at this age are accompanied by weak subclinical signs.So, they may not be diagnosed on time.As a result of a high activity of cytokines, procalcitonin and C-reactive protein (CRP) are released.C reactive protein is a sensitive and early indicator of systemic infection, but it can also increase at light and local bacterial infections as well as at viral infections ().Procalcitonin (PCT) is an important parameter for bacterial infections.Procalcitonin is a protein which consists of  amino acids out of which  structure the calcitonin hormone (, ).The level of procalcitonin in serum increases during severe systemic bacterial infections, parasites and fungi with systemic manifestations (, , ).In severe viral infections or in infl ammatory reactions with a non infective origin, the levels of procalcitonin don't increase, or there is a moderate increase ().In the conditions of a normal metabolism, the active calcitonin hormone is produced and secreted in C cells of thyroid gland after the intracellular proteolitic process of procalcitonin prohormone.Specific proteases dissolve procalcitonin into calcitonin, katacalcine and in N-terminal residue ().Procalcitonin increase can happen without infections in patients with carcinoma of thyroid gland C cells ().Although new methods of treatments are being used (), mortality in patients with sepsis remains high, often because of late diagnosis and treatment.Infections in newborns and young children in the region of Kosovo are frequent and frequently cause mortality.At these ages, early diagnosis of infections and the differential diagnosis between viral and bacterial infections, present diff erent complications. is study's intention is to prove that the PCT and CRP concentration is diff erent at various stages of sepsis development in newborns.

Study Subjects
PCT and CRP have been determined in  neonates of - days of age with diff erent stages of sepsis, who were patients in the Centre for Prematurely Born Babies, and in  healthy neonates.Patients have been classified into: patients with systemic inflammatory response syndrome (SIRS) ( patients); with neonatal sepsis ( patients); with neonatal sepsis and purulent meningitis ( patients); and patients with septic shock ( patients).There were  cases of healthy children.Anamnesis Some of the criteria to diagnose infections in newborns are hypothermia or hyperthermia, difficulties in diet, signs from the respiratory tract (cyanosis and apnoea), lethargy, jaundice, tachycardia, tachypnoea, changes in skin, hypotony, liver and spleen enlargement.Control group consists of  healthy newborns with normal weight and height, afebrile, normotonic, eupnoic and without evident changes for a disease.

Detailed analysis
The samples have been taken with monovettes of "Sarstedt" company.After serum separation, biochemical parameters were immediately determined.e determination of procalcitonin has been estabilished with the ELFA methods of producer B.R.A.H.M.S Diagnostica GmbH, Berlin, Germany.C reactive protein (CRP) has been determined with the standard turbidimetric methods (Synchron CX-, Beckman Fullerton, CA).

Statistical analysis
The results of this research have been elaborated with the special statistical programme Instat , where the arithmetical average, median, standard deviation, minimal and maximal values as well as p value have been calculated.All these data have been presented in tables and graphics.

Results
In Table 

Discussion
Sepsis is a catabolic acute state, which is caused by cytokines, the role of which can be syner-gic, by inducting or blocking, in which case the normal physiologic balance turns into a pathologic process, including a lot of organs ().Untreated infection may end tragically, newborns with "suspected sepsis" are often subjected to a battery of extensive diagnostic procedures and unguided systemic antibiotic therapy pending further laboratory results ().e clinical signs of the infection and the routine laboratory tests of sepsis, such as CRP and the number of leucocytes are not specifi c and sometimes even false.In cases of a severe infection, most proinflammatory cytokines such as TNF-α, IL-β, increase in a short period of time, or don't increase at all ().In bacterial infections and in various forms of severe systemic inflammation, circulating levels of calcitonin precursors (CTpr), including the pro-hormone procalcitonin (ProCT), increase several -fold to several thousand -fold, and this increase often correlates with the severity of the condition and with mortality (,,,).
Because the clinical diagnosis of sepsis is often subjective and uncertain, there's a difficult task to analyse the markers of infections.In this research, with the analysis of our results, we have reached some conclusions which are of a great value about early diagnosis and about giving the adequate therapy on time at newborns with bacterial infections.
In bacterial infection and other infections ().According to our results the values of PCT correlate with the severity of the disease (Table  and Figure ).Early identifi cation of patients with insidious septic illness allows early therapeutic intervention which may favourably infl uence the outcome ().PCT was identifi ed as a better discriminator than CRP in character-izing the degree of infl ammation related to infection.PCT was more specifi c for sepsis-induced infl ammation than CRP, () but no better than CRP at identifying infection uncomplicated by sepsis or organ failure ().e course and follow up of PCT values is important for assessing both the clinical course of the disease and its prognosis in sepsis or systemic infl ammation (, , ).

Conclusion
Based on our results, we concluded that procalcitonin is increased in all stages of sepsis, with higher values in the septic shock.e increase of PCT levels is related to the severity, course of infection and patient prognosis.
. newborns have been presented according to diseases.casesor of the examinees have suffered from neonatal sepsis,  cases or  have been with SIRS,  have been with neonatal sepsis and purulent meningitis and  with septic shock.eaveragevalues of PCT and CRP in newborns with SIRS have been presented inTable . and Figure .It is noticed that there is an increase of both indicators with an increase rate of PCT, around  times more than CRP.ere is a high statistical diff erence (p<,) values of PCT and CRP in newborns with septic shock have been compared inTable . and Figure .It is seen that the rate of increase is much higher for PCT (around , times higher than reference values), while CRP is increased , times more than the reference values.is diff erence has a high statistical diff erence.
e *Rate of increase, the ratio between average values and reference values, how much it has increased in comparison to the normal value.TABLE 2. e comparison between PTC and CRP values for newborns with SIRS TABLE 4. e comparison between PTC and CRP values for neonates with neonatal sepsis + purulent meningitis -statistical parameters TABLE 3. e comparison between PTC and CRP values for newborns with neonatal sepsis