Andrzej Siemiatkowski

Early enteral nutrition is superior to delayed enteral nutrition for the prevention of infected necrosis and mortality in acute pancreatitis.

Objectives The exact time of initiation of total enteral nutrition (TEN) in severe acute pancreatitis (SAP) and its influence on the disease outcome are not well known. Methods An analysis of 197 cases with predicted SAP allocated to: group A (n = 97), early TEN (started within the first 48 hours after admission to hospital); and group B (n = 100), delayed TEN (started after 48 hours). Results Infection of necrosis/fluid collections occurred in 4 patients in group A and 18 patients in group B (P < 0.05). Respiratory failure and transfer to intensive care unit occurred more frequently in group B than in group A (15 vs 5 and 15 vs 3 patients; P < 0.05). Multiple-organ failure was observed in 9 patients in group A and 16 patients in group B (P > 0.05). Seven patients in group A and 11 patients in group B underwent surgery (P > 0.05). All 9 reported deaths occurred in group B (P < 0.05). The time to start TEN was a predictor of infected necrosis/fluid collection (odds ratio, 4.09; P = 0.028). Conclusions Delayed compared to early TEN is associated with higher mortality, increased frequency of infected necrosis/fluid collections, respiratory failure, and a need for intensive care unit hospitalization. Enteral nutrition in SAP should be started within 48 hours after admission to hospital.

The importance of interleukin 18, glutathione peroxidase, and selenium concentration changes in acute pancreatitis

Cytokinemia and oxidative stress are important factors responsible for an inadequate immune response in the early course of acute pancreatitis (AP). The aim of the study was to evaluate the profiles of interleukin 18 (IL-18), glutathione peroxidase (GPx), and selenium concentrations in serum with respect to AP severity and to study the relationships between these parameters and recognized prognostic indicators of AP severity. Prospective clinical analyses were performed on 61 patients with mild and severe forms of AP and for 15 healthy volunteers. In both forms of AP severity, the IL-18 concentration in the serum was significantly higher than in healthy controls. In the severe form of AP, the IL-18 concentration was the highest and exceeded significantly the values recorded on the 1st, 2nd, 3rd, 5th, and 10th days of mild AP. A significantly lower GPx concentration in the serum was recorded in severe AP compared to the mild form and in the control group. There was a significantly lower selenium concentration in the severe form of AP. Significant correlations between GPx and selenium, between IL-18 and GPx, and between IL-18 and selenium were recorded. The ROC analysis shows a high prognostic accuracy of IL-18 and GPx concentrations in the determination of AP severity. IL-18 is released early in the course of AP and may be a key immunomodulator of the inflammatory response in the severe form of this disease. Low GPx and selenium concentrations in severe AP reflect the lower antioxidative ability in this form of AP. IL-18 and GPx may represent new indicators of AP severity.

Serum profiles of E-selectin, interleukin-10, and interleukin-6 and oxidative stress parameters in patients with acute pancreatitis and nonpancreatic acute abdominal pain.

Introduction Excessive inflammatory response is one of the major causes of early mortality in acute pancreatitis (AP). Aim To evaluate the serum profiles of E-selectin, interleukin (IL)–6, and IL-10 along with their correlation to the markers of oxidative stress and neutrophil activation in patients with AP and patients with nonpancreatic acute abdominal pain (NPAAP). Methodology This prospective clinical study included 56 patients with AP (28 with mild AP and 28 with severe AP) as well as 15 patients with NPAAP. Results Serum concentrations of E-selectin, IL-10, and IL-6 and plasma concentrations of polymorphonuclear leukocyte elastase (determined on days 1–3, 5, and 10 after admission) were the highest in severe AP during the first 3 days and then declined. At day 10, the E-selectin level in severe AP was still higher than that in mild AP, and the IL-10 concentration increased again. There was no elevation in the E-selectin concentration in NPAAP patients, and IL-10 levels remained unchanged in mild AP. Oxidative stress, measured by serum malondialdehyde and 4-hydroxyalkenals levels, was the most pronounced in severe AP. Conclusions The serum E-selectin concentration is markedly elevated in severe AP and is less in mild AP but not in NPAAP. It may result from stimulation with different inflammatory mediators or indicate vascular endothelium injury mediated by oxidative stress, especially in the severe form of AP.

Lysosomal activity of pulmonary alveolar macro phages in acute experimental pancreatitis in rats with reference to positive PAF-antagonist (BN 52021) effect

The activation of pulmonary alveolar macrophages (PAMs), might play an important role in severe complications of acute pancreatitis. The aim of our study was to assess the labilization of macrophage lysosomal membranes and release of lysosomal cathepsin B (CB) and N-acetyl-beta-D-hexosaminidase (NAH) into bronchoalveolar lavage fluid (BALF) during taurocholate acute pancreatitis (AP) in rats treated with PAF-antagonist--BN 52021. Total activity of CB increased by 374% after 6 h and by 237% after 12 h of AP in lysosomal enriched fraction of PAMs. Fractional free activity of CB increased to 40% after 6 h and to 38% after 12 h of AP. Free activity of CB was increased 5 fold in the supernatant of macrophage homogenate, and 10 fold in the supernatant of BALF after 6 h of AP. The values of NAH activity roughly paralleled that of CB. Treatment with BN 52021 (5 mg x kg(-1) every 6 h i.v.) partially normalized the measured parameters. Our results indicate that the PAF-antagonist BN 52021 reduced the increase of total and free activity of lysosomal hydrolases of PAMs and partly prevented the labilization of their lysosomal membranes. Therefore, an important mechanism of BN 52021 beneficial effect in pulmonary complications of acute pancreatitis could be dependent on the stabilization of PAMs lysosomes.

von Willebrand factor antigen as a prognostic marker in posttraumatic acute lung injury.

The specific endothelial cell product von Willebrand factor antigen (vWf:Ag) was measured in plasma and lung function tests were carried out and the following lung injury parameters measured: PaO2/FiO2 ratio, static respiratory compliance and Murray’s lung injury score (LIS) in a follow-up study of 36 severely traumatized patients. Injury severity score (ISS) and APACHE II scores were calculated. Patients were classified according to the presence or absence of acute respiratory distress syndrome (ARDS) complications and survival versus death. Data collection was performed on admission to hospital and after 1–3, 5, 7, 10 days of ICU stay. On all of the occasions investigated, plasma vWf:Ag levels in ARDS patients and nonsurvivors were significantly greater than those in patients without ARDS and survivors, respectively. Significant correlations were observed between initial vWf:Ag concentration and ISS, APACHE II, LIS. Our study suggests that increased concentrations of vWf:Ag in plasma are predictive of the development of ARDS and signal poor prognosis in patients following severe trauma.

Circulating endothelial mediators in human pancreatitis-associated lung injury.

Objectives To investigate the role of endothelial cell mediators, E-selectin (ES), intercellular adhesion molecule-1 (ICAM-1), tissue factor (TF), and von Willebrand factor (vWF), in the early phase of severe acute pancreatitis (SAP) complicated with respiratory failure [pancreatitis-associated lung injury (PALI)]. Patients and methods This study included 30 patients with SAP and 39 patients with PALI. Blood samples were taken from SAP and PALI patients on presenting to the hospital (day 1), and days 2, 3, 5, and 10. The relationship between blood concentrations of the studied endothelial mediators and lung function tests was analyzed. Results PALI patients had significantly higher ES, ICAM-1, TF, and vWF blood levels than those with SAP as early as at admission and throughout the period studied. We found the highest concentration of ES on the second day, ICAM-1 and TF at admission, and vWF level on the fifth day. There were adverse correlations between ES, ICAM-1, TF, vWF concentrations, and the index of oxygenation – PaO2/FiO2 ratio (Rs=−0.385, Rs=−0.523, Rs=−0.505, Rs=−0.408, P<0.001, respectively). The most accurate prediction of PALI was provided by ICAM-1 and TF levels on the day of admission [areas under curve (AUCs): ES, 0.704; ICAM-1, 0.787; TF, 0.757; and vWF, 0.686]. Conclusion Endothelium-related mediators ES, ICAM-1, TF, and vWF appear to participate in pancreatitis-associated lung injury. In SAP, the measurement of endothelial mediator levels (especially ICAM-1 and TF) may be used as an early prognostic indicator that would predict the development of respiratory failure and to monitor the severity of lung dysfunction.

Endothelin 1 and transforming growth factor-β1 correlate with liver function and portal pressure in cirrhotic patients.

OBJECTIVE The invasive measurement of hepatic venous pressure gradient is the recommended method for the assessment of portal hypertension. We assessed if the mediators that regulate portal hypertension may be used as noninvasive markers of portal hypertension and liver insufficiency. MATERIALS AND METHODS We explored in prospective, observational study the concentration of endothelin-1, nitric oxide, and transforming growth factor-β1/2 in peripheral and hepatic venous blood; their relationship with the values of portal hypertension and liver insufficiency; and their level changes 4-6 months after non-selective beta-blocker therapy in cirrhotic patients with non-bleeding esophageal varices. RESULTS (1) Cirrhotics have significantly increased peripheral endothelin 1 and decreased transforming growth factor-β1 levels; (2) peripheral levels of all factors correlated significantly with their hepatic levels; (3) after therapy, peripheral endothelin-1 levels significantly increased, but transforming growth factor-β2 levels decreased and were lower in patients with pressure gradient value normalization; (4) before and after therapy, peripheral and hepatic endothelin-1, transforming growth factor-β1/2 levels correlated significantly with liver failure indicators (laboratory parameters, Child-Pough and MELD scores) and pressure gradient values. CONCLUSIONS Peripheral endothelin-1 and transforming growth factor-β1 levels, which strongly correlate with their hepatic levels, reflect the stage of portal hypertension and liver insufficiency in cirrhosis.

Creatinine or cystatin C - which is a better index of renal function in morbid obesity?

PURPOSE The most important index of renal function is estimated glomerular filtration rate (eGFR) which can be calculated from creatinine or cystatin C concentration in serum. There is uncertainty, which formula is best suited to assess renal function in morbidly obese patients. The aim of this study was to evaluate eGFR in patients with morbid obesity using formulas: Modification of Diet in Renal Disease (MDRD), Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI), Grubb, Le Bricon, Hoek, Larsson, and to compare the obtained results. MATERIAL AND METHODS In 40 morbidly obese patients, serum concentration of cystatin C and creatinine were assayed. Values of eGFR were calculated using the above-mentioned formulas. RESULTS The mean value of eGFR ranged from 85.9 to 111.1 ml/min/1.73 m², depending on the formula. The biggest difference between the obtained values was 29% (Grubb vs. Hoek p<0.01). After calculation of eGFR from creatinine concentration (MDRD), 7 patients were qualified to the 2nd and 3rd stage of chronic renal disease, while application of Hoeks formula, based on cystatin C concentration, allotted 27 patients to 2nd and 3rd stage of chronic renal disease. Le Bricon formula gave eGFR values, that correlated best with albuminuria. CONCLUSION eGFR calculated using Le Bricon formula based on the cystatin C concentration was significantly lower than eGFR calculated from creatinine concentration and was more closely associated with albuminuria. Relying only on creatinine concentration to estimate glomerular filtration rate can lead to underestimation of renal malfunction in obese patients.

The imbalance between matrix metalloproteinase 9 and tissue inhibitor of metalloproteinase 1 in acute pancreatitis.

BACKGROUND The balanced activity of matrix metalloproteinases and their tissue inhibitors is an important, albeit still not completely understood, determinant of extracellular matrix homeostasis, a factor involved in the pathogenesis of acute pancreatitis (AP). AIMS The aim of this study was to compare serum concentrations of matrix metalloproteinase 9 (MMP-9) and its tissue inhibitor (TIMP-1) in patients with AP of various severity and to investigate their relationship with prognostic indicators of AP severity, e.g., polymorphonuclear leukocyte elastase (PMN-E). PATIENTS AND METHODS The study included 37 patients with mild (n = 18) or severe AP (n = 19) and 15 healthy controls. Serum concentrations of MMP-9 and TIMP-1 were determined on admission (day 1) and on days 2, 3, 5 and 10. RESULTS Throughout the study period, the serum MMP-9 concentration in patients with severe AP was significantly higher than those in individuals with mild AP and in healthy controls. In turn, the serum MMP-9 concentrations in persons with mild AP did not differ significantly from those of the controls. The serum TIMP-1 concentrations in both groups were significantly higher than in the controls. Beginning from the 2(nd) day of hospital stay, the serum TIMP-1 concentration in patients with severe AP was significantly higher than in individuals with mild AP. There were significant correlations between: MMP-9 and PMN-E, TIMP-1 and PMN-E, and MMP-9 and TIMP-1. CONCLUSION A disturbed balance between MMP-9 and TIMP-1 observed during the early stages of severe AP suggests that endogenous TIMP-1 is unable to prevent excessive activation and release of MMP-9. MMP-9 may represent a new marker of AP severity.

C-terminal and intact FGF23 in critical illness and their associations with acute kidney injury and in-hospital mortality

Background FGF23 proved its value in prognostication of cardiovascular events and mortality among renal patients and general population. Limited data exist whether FGF23 may have any use in prediction of negative outcomes among critically ill patients admitted to intensive care unit (ICU). Methods Single center cohort study performed among patients admitted to ICU. The primary exposure was FGF23 plasma concentration measured within 24 h of ICU admission. The primary outcome was incident Acute Kidney Injury (AKI) and in‐hospital mortality during the ICU stay. Results The study enrolled 79 patients admitted to ICU. C‐terminal FGF23 (cFGF23) but not intact FGF23 (iFGF23) concentration was significantly elevated in patients, who acquired AKI and non‐survivors (p < .001). ROC analysis of cFGF23 yielded an AUC of 0.81 and 0.85 for prediction of incident AKI and death during ICU stay, respectively. Multivariate analysis showed higher odds for AKI (OR 1.80; 95% CI 1.10–2.96) and in‐hospital mortality (OR 2.85; 95% CI 1.60–5.06) for one unit increase of log transformed cFGF23. Conclusions cFGF23 measurement may serve as a novel biomarker for incident AKI and death among critically ill patients.