Jadranko Sokolić

Comparative study of frequency of different lymphocytes subpopulation in peripheral blood of patients with prostate cancer and benign prostatic hyperplasia

ZusammenfassungZIEL: Benigne Prostatahyperplasie (BPH) und Prostatakrebs (PC) sind die häufigsten urologischen Erkrankungen bei Männern über fünfzig und sie wurden vor kurzem für das Ergebnis einer gestörten Immunantwort gehalten. Trotz vieler Studien zur auf T-Zellen basierten Anti-Tumor-Immunität, kann die Rolle der angeborenen Immunzellen bei BPH und PC noch immer schlecht verstanden werden. In dieser Studie wurde die Frequenz von verschiedenen Leukozytensubpopulationen im peripheren Blut von sowohl BPH- und PC-Patienten als auch von gesunden Probanden analysiert und gegenseitig verglichen. METHODEN: 60 Probanden wurden in eine Querschnittsstudie eingeschlossen (20 Patienten mit BPH, 20 Patienten mit PC und 20 gesunde Probanden). Mononukleäre Zellen des peripheren Blutes (PBMC) wurden isoliert und sowohl der Prozentsatz von T-Lymphozyten, natürlichen Killerzellen (NK) und natürlichen Killer-T-Zellen (NKT) als auch der Prozentsatz von Subsets der T-Lymphozyten [CD3+CD56–CD4+, TReg (CD4+CD25+FoxP3+) und CD3+CD56–CD8+] und der NK-Zellen (CD3–CD56+dim und CD3–CD56+bright) wurden mit Durchflusszytometrie analysiert. Auch der intrazelluläre Inhalt von Interleukin-4 (IL-4) und Gamma-Interferon (IFN-γ) wurde in T-Lymphozyten, NK- und NKT-Zellen gefunden. ERGEBNISSE: Das Prozent von T-Lymphozyten und deren Subsets in Lymphozyten des peripheren Blutes unterschied sich nicht unter den untersuchten Gruppen, während die Frequenz der regulatorischen T-Zellen (TReg) die höchste bei der PC-Patienten war. Höherer Anteil der B-Lymphozyten und NKT-Zellen wurde in Lymphozyten des peripheren Blutes von BPH-Patienten beobachtet. Der Anteil der NK-Zellen und deren Subsets unterschied sich nicht unter den untersuchten Gruppen. Eine negative Korrelation zwischen dem PSA-Wert und dem Prozentsatz der T-Lymphozyten und NK-Zellen wurde nur bei PC-Patienten bemerkt. Sehr positive Korrelation zwischen dem PSA-Wert und dem Prozentsatz der regulatorischen T-Zellen (TReg) stellte man bei PC-Patienten fest. SCHLUSSFOLGERUNG: Unterschiedliche Frequenz der verschiedenen Lymphozytensubpopulationen im peripheren Blut von gesunden Männern und BPH- und PC-Patienten könnte für das Auftreten und Fortschreiten der Prostatahyperplasie oder des Tumors verantwortlich sein. Aufgrund der Tumorfähigkeit, T-Zell-Immunantwort zu unterdrücken, könnten die Zellen der angeborenen Immunität (NKT-Zellen und regulatorische T-Zellen) die zentrale Rolle in der Immunpathogenese von PC und BPH spielen.SummaryPURPOSE: Benign prostatic hyperplasia (BPH) and prostate cancer (PC) are the most common urologic diseases among men over fifty and, until recently, they were considered to be caused by the impaired immune response. Despite many studies designed to investigate T-cell-based antitumor immunity, the role of innate immune cells in BPH and PC is still poorly understood. In this study the frequency of different leukocytes subpopulation in peripheral blood of BPH, PC patients and in healthy volunteers was analysed and compared. METHODS: In a cross-sectional study 60 subjects were enrolled (20 patients with BPH or with PC and 20 healthy volunteers). Peripheral blood mononuclear cells (PBMC) were isolated and the percentage of T lymphocytes, natural killer (NK) and NKT cells, as well as subsets of T lymphocytes [CD3+CD56–CD4+, Tregs (CD4+CD25+FoxP3+) and CD3+CD56–CD8+] and NK cells (CD3–CD56+dim and CD3–CD56+bright) were analysed by flow cytometry. Intracellular content of interleukin-4 (IL-4) and interferon gamma (IFNγ in T lymphocytes, NK and NKT cells were also detected. RESULTS: The percentage of T lymphocytes and their subsets in peripheral blood lymphocytes did not differ among investigated groups, while the frequency of Tregs was the highest in PC patients. The percentage of NK cell and their subsets did not differ among investigated groups. Negative correlation between PSA value, percentage of T lymphocytes and NK cells was observed only in PC patients. Highly positive correlation between the PSA value and the percentage of Tregs was found in PC patients. CONCLUSION: Different frequencies in distinctly lymphocyte subpopulation in peripheral blood of healthy men, BPH and PC patients could be responsible for occurrence and progression of prostatic hyperplasia or tumour. Due to the ability of tumours to suppress the cognate T cell immune response, the cells of innate immunity (NKT and Tregs) may be playing a key role in the immunopathogenesis of PC and BPH.

Prognostic performance of the Simplified Acute Physiology Score II in major Croatian hospitals: a prospective multicenter study

Aim To perform an external validation of the original Simplified Acute Physiology Score II (SAPS II) system and to assess its performance in a selected group of patients in major Croatian hospitals. Methods A prospective, multicenter study was conducted in five university hospitals and one general hospital during a six-month period between November 1, 2007 and May 1, 2008. Standardized hospital mortality ratio (SMR) was calculated from the mean predicted mortality of all the 2756 patients and the actual mortality for the same group of patients. The validation of SAPS II was made using the area under receiver operating characteristic curve (AUC), 2 × 2 classification tables, and Hosmer-Lemeshow tests. Results The predicted mortality was as low as 14.6% due to a small proportion of medical patients and the SMR being 0.89 (95% confidence interval [CI], 0.78-0.98). The SAPS II system demonstrated a good discriminatory power as measured by the AUC (0.85; standard error [SE] = 0.012; 95% CI = 0.840-0.866; P < 0.001). This system significantly overestimated the actual mortality (Hosmer-Lemeshow goodness-of-fit H statistic: χ2 = 584.4; P < 0.001 and C statistics: χ28 = 313.0; P < 0.001) in the group of patients included in the study. Conclusion The SAPS II had a good discrimination, but it significantly overestimated the observed mortality in comparison with the predicted mortality in this group of patients in Croatia. Therefore, caution is required when an evaluation is performed at the individual level.

Early postoperative gastric enteral nutrition improves gastric emptying after non-complicated cardiac surgery

Background: Postoperative intragastric enteral feeding in cardiac surgery patients is frequently complicated by delayed gastric emptying. Objective: To evaluate how early postoperative gastric enteral nutrition affects gastric emptying in coronary artery by-pass graft (CABG) surgery patients. Methods: In this prospective, randomized study a group of 40 patients treated in the intensive care unit after CABG surgery were studied. Patients were divided in two groups: group E (20 patients: age 59±8 yr.; male 70%) and control group C (20 patients: age 58±10 yr.; male 80%), respectively. The paracetamol absorption test was used to evaluate gastric emptying. In group E gastric enteral nutrition begun 18 hours after surgery and 6 hours later this was stopped and paracetamol solution was administered. The patients in group C received only crystalloid solutions for first 24 hours. Blood samples were obtained at 0 (t 0), 15 (t+15), 30 (t+30), 60 (t+60) and 120 (t+120) min after administration of paracetamol. Results: The values of plasma paracetamol concentration (PPC) at 15 and 120 min were significantly higher in group E when compared with .group C: (t +15) 3.3±2.5 vs. 1.7±1.9 and (t+120) 5.2±2.8 vs. 3.3±1.6 (p <0.05). The PPC values at 30 and 60 min were higher, but not significantly, in group E vs. group C: (t+30) 3.7±2.0 vs. 2.9±2.7 and (t+60) 5.1±3.2 vs. 3.9±3.5 (p = NS). The area under the PPC curve was 429 ± 309 in the E group vs. 293 ± 204 in the group C (p < 0.05). Conclusion: Early postoperative gastric administration of nutritients after CABG surgery stimulates gastric emptying.

Early postoperative gastric enteral nutrition improve gastric emptying after cardiac surgery

Postoperative intragastric enteral feeding in cardiac surgery patients is frequently complicated by delayed gastric emptying. The aim of the study was to evaluate how early postoperative gastric enteral nutrition affects the gastric emptying in coronary artery by-pass graft (CABG) surgery patients.In the prospective, randomized study 40 patients treated at intensive care unit after CABG surgery were studied. Patients were divided in two groups: enteral feeding group E (20 patients: age 59±8 yr.; male 70%) and control group C (20 patients: age 58±10 yr.; male 80%), respectively. Paracetamol absorption test was used to evaluate gastric emptying. In the group E postoperative gastric supply of enteral formula begun 18 hours after surgery and after 6 hours the supply was stopped and paracetamol solution was administrated by nasogastric tube. The patients in group C for.rst 24 hours received only crystalloid solutions intravenously and paracetamol solution by nasogastric tube. Blood samples were obtained at 0 (t0), 15 (t+15), 30 (t+30), 60 (t+60) and 120 (t+120) min after administration of paracetamol.The values of plasma paracetamol concentration (PPC) at 15 and 120 min were significantly higher in group E vs. group C: (t+15) 3.3±2.5vs. 1.7±1.9 and (t+120) 5.2−2.8 vs. 3.3±1.6 (p <0.05). The PPC values at 30 and 60 min were higher, but not signi.cantly, in group E vs. group C: (t+30) 3.7±2.0 vs. 2.9±2.7 and (t+60) 5.1±3.2 vs. 3.9±3.5 (p = NS). The area under the PPC curve was 429 ± 309 in the E group vs. 293 ± 204 in the group C (p < 0.05).In conclusion an early postoperative gastric administration of nutritients after CABG surgery stimulates the gastric emptying.

Acute respiratory distress syndrome in an 11-month-old girl leading to extracorporeal membrane oxygenation

Acute respiratory distress syndrome (ARDS) is a condition recognised for almost fifty years, and is related to high morbidity and mortality in children. From its recognition, medical experts tried to make joint efforts to make recommendations and optimize treatment in children and adult population. The new definition of ARDS suggests treatment by introducing three levels of severity, according to PaO2/ FiO2 and positive end-expiratory pressure. Lung-protective ventilation remains crucial in achieving better outcome in paediatric acute respiratory distress syndrome (PARDS), but promising therapies based on paediatric studies include non-invasive ventilation, endotracheal surfactant, highfrequency oscillatory ventilation (HFOV), and use of ECMO as „rescue“ therapy. Nevertheless, PARDS is a real challenge for the paediatric critical care provider, and even if current state-of-the-art treatment methods are delivered, this disease often leads to fatal outcome. We report the case of an 11-month-old female infant who developed ARDS, was treated by current up-to-date treatment methods, including ECMO, and despite this, succumbed to her illness. With this case report we would like once more to bring to consideration the current knowledge on etiology, epidemiology, diagnosis and treatment of ARDS in children, and emphasize the high morbidity and mortality related to this syndrome.