Title:

Evaluation of the diagnostic and prognostic accuracy of angiopoietin-2 (Ang-2) and neutrophil gelatinase-associated lipocalin (NGAL) as markers of the severity and complications of acute pancreatitis in the early phase of the disease

Author:

Sporek, Mateusz

Subject:

NGAL ; acute pancreatitis ; Ang-2

Abstract:

Despite intense studies, prognosis and early diagnosis of SAP is still a challenge. In every day practice, careful observation of a patient and frequent evaluation by attending physician is necessary. Nowadays, it is routinely supported by advanced, wider accessible imaging, application of prognostic scales (Ranson, Glasgow, APACHE II) and measurement of certain laboratory biomarkers, mainly associated with inflammation (CRP, procalcitonin). The aim of the PhD thesis was the estimation of diagnostic usefulness of new biomarkers in prediction of severe and complicated course of AP. Analysis of correlations between concentrations of NGAL (in serum and urine), Ang-2 and selected microRNAs and the severity of AP in early phase of the disease was performed. Author tried to answer the following questions: 1. Do concentrations of Ang-2 and NGAL in serum as well as NGAL in urine increase in the early phase of AP? What is the dynamics of changes in concentrations of the analyzed markers in patients with severe form of AP comparing to other early markers of inflammation? 2. Do concentrations of Ang-2, uNGAL and sNGAL allow early prognosis of severity of AP and early diagnosis of organ complications in the course of this disease? Particularly is determination of uNGAL and Ang-2 useful in recognition of AKI as a complication of AP? 3. Is determination of microRNA useful in early evalua ; tion of AP severity? The doctoral dissertation is based on monothematic series of articles, which consists of 4 original papers and review papers 1 with a total value IF = 6,073 and 85 points Ministry of Science and Higher Education. The studies regarding NGAL in serum and urine and Ang-2 in serum included 65 patients diagnosed with AP hospitalized and treated in Surgical Ward of District Hospital in Sucha Beskidzka. In the publication on microRNA, the studied group consisted of 88 patients, including 65 treated in Surgical Ward of District Hospital in Sucha Beskidzka, and 23 hospitalized in Surgical Ward of Clinic of General, Oncologic and Gastroenterologic Surgery of University Hospital in Krakow. Characteristics of the papers included into PhD thesis Article no 1 published in Przegląd Lekarski 2015;72(5):1-5 is an introduction into the thesis, which guides through the issues related to AP. The article presents definition of AP, and describes in details the prognostic scales and laboratory biomarkers useful in early phase of the disease. Basic data from world literature relevant to biomarkers studied in this thesis (NGAL, Ang-2) were also summarized. Article no 2 published in Mediators of Inflammation (Doi: 10.1155/2016/5780903) evaluates the usefulness of angiopoetin-2 (Ang-2) serum concentrations for prognosis of severity of AP and early diagnosis of complications, es ; pecially acute kidney injury (AKI following KDIGO) and renal failure recognized on the basis of Marshall score. Correlations were reported between Ang-2 concentrations and laboratory indicators used for monitoring the course of AP, including markers of renal function. Article no 3 published in Folia Medica Cracoviensia 2016; 56(2) deals with diagnostic usefulness of sNGAL in recognition of SAP in early phase of the disease. The paper shows how sNGAL concentrations change depending on the severity of the disease, and reports correlations between sNGAL and BISAP score and certain markers of inflammation. Also, the prognostic value of sNGAL was estimated. Article no 4 published in Folia Medica Cracoviensia 2016; 56(1): 13¬25 compares the diagnostic utility of urine and serum NGAL concentrations in early phase of AP. Particularly, the usefulness of these measurements in prediction of AKI complicatingAP was evaluated. Correlations were reported between uNGAL, sNGAL and markers of kidney function (urea, creatinine, albuminuria). Article no 5 published in Pancreatology 2015; 15: 344-351 describes concentrations of selected microRNA, that in the literature are associated with pancreatic, hepatic and endothelial damage, in patients in early phase of AP. Especially, associations are reported between serum concentrations of microRNAs of endothelial origin (hsa-miR- 126-5p and has-miR- ; 551b-5p) and severity of AP. Presented PhD thesis aimed at evaluating the diagnostic and prognostic usefulness of angiopoetin-2 and NGAL as markers of the severity and complications of AP in the early phase of the disease (first 72 hours). Despite intense studies on the patomechanism of AP and searching for optimal markers of severity of the disease, obtained results are original and unique depiction of the problem. Studies on the concentration of Ang-2 and microRNA in the serum of patients in the early phase of AP were carried out for the first time in Polish population and delivered new information on the scope and dynamics of changes of concentrations of these markers in course of AP of various severity. The observations regarding sNGAL and uNGAL confirmed the findings of another authors. However, the evaluation of diagnostic usefulness of these markers enables their better use in clinical practice. It is concerned especially to uNGAL as routine laboratory test. The presented results provide a supplement to clinical data regarding the diagnostic tools that may be used at the early stage of qualification patients with AP to the most appropriate group of disease severity. In the future, it might be helpful in creation of certain treatment strategy, dictated by significantly worse prognoses in patients with SAP. However, obtained results should be confirmed by studies carrie ; d out on a larger groups of patients.

Place of publishing:

Kraków

Level of degree:

2 - studia doktoranckie

Degree discipline:

choroby układu trawiennego

Degree grantor:

Wydział Lekarski

Promoter:

Kuśnierz-Cabala, Beata

Date:

2016

Date issued:

2016

Type:

Praca doktorska

Call number:

ZB-126422

Language:

pol; eng

Access rights:

tylko w bibliotece

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