Publications by authors named "Branislav Stefanovic"

33 Publications

Reduced-dose intravenous thrombolysis for acute intermediate high-risk pulmonary embolism: Rationale and design of the PEITHO-3 trial.

Thromb Haemost 2021 Sep 24. Epub 2021 Sep 24.

Hopital Europeen Georges Pompidou, Paris, France.

Intermediate high-risk pulmonary embolism (PE) is characterised by right ventricular (RV) dysfunction and elevated circulating cardiac troponin levels despite apparent haemodynamic stability at presentation. In these patients, full-dose systemic thrombolysis reduced the risk of haemodynamic decompensation or death but increased the risk of life-threatening bleeding. Reduced-dose thrombolysis may be capable of improving safety while maintaining reperfusion efficacy. The Pulmonary Embolism International Trial (PEITHO)-3 study (EudraCT 2018-000816-96) is a randomised, placebo-controlled, double-blind, multicentre, multinational trial with long-term follow-up. We will compare the efficacy and safety of a reduced-dose alteplase regimen with standard heparin anticoagulation. Patients with intermediate high-risk PE will also fulfil at least one clinical criterion of severity: systolic blood pressure ≤ 110 mmHg, respiratory rate >20 breaths/min, or history of heart failure. The primary efficacy outcome is the composite of all-cause death, haemodynamic decompensation or PE recurrence within 30 days of randomisation. Key secondary outcomes, to be included in hierarchical analysis, are fatal or GUSTO severe or life-threatening bleeding; net clinical benefit (primary efficacy outcome plus severe or life-threatening bleeding); and all-cause death, all within 30 days. All outcomes will be adjudicated by an independent committee. Further outcomes include PE-related death, haemodynamic decompensation, or stroke within 30 days; dyspnoea, functional limitation or RV dysfunction at 6 months and 2 years; and utilisation of healthcare resources within 30 days and 2 years. The study is planned to enrol 650 patients. The results are expected to have a major impact on risk-adjusted treatment of acute PE and inform guideline recommendations.
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http://dx.doi.org/10.1055/a-1653-4699DOI Listing
September 2021

Renal dysfunction as intrahospital prognostic indicator in acute pulmonary embolism.

Int J Cardiol 2020 03 13;302:143-149. Epub 2019 Dec 13.

Clinic of Cardiology and Emergency Internal Medicine, School of Medicine, University of Defense, Belgrade, Serbia.

Background: Acute pulmonary embolism (PE), due to hemodynamic disturbances, may lead to multi-organ damage, including acute renal dysfunction. The aim of our study was to investigate the predictive role of renal dysfunction at admission regarding the short-term mortality and bleeding risk in hospitalized PE patients.

Methods: The retrospective cohort study included 1330 consecutive patients with PE. The glomerular filtration rate (GFR) was calculated using the serum creatinine value and Cocroft-Gault formula, at hospital admission. Primary outcomes were all-cause mortality and PE-related mortality in the 30 days following admission, as well as major bleeding events.

Results: Based on the estimated GFR, patients were divided into three groups: the first with GFR < 30 mL/min, the second with GFR 30-60 mL/min, and the third group with GFR > 60 mL/min. A multivariable analysis showed that GFR at admission was strongly associated with all-cause death, as well as with death due to PE. Patients in the first and second group had a significantly higher risk of 30-day all-cause mortality (HR 7.109, 95% CI 4.243-11.911, p < 0.001; HR 2.554, 95% CI 1.598-4.081, p < 0.001). Fatal bleeding was recorded in 1.6%, 0.5% and 0.8% of patients in the first, second and in the third group (p < 0.05). There were no significant differences regarding major bleeding rates among the groups.

Conclusion: Renal dysfunction at admission in patients with acute pulmonary embolism is strongly associated with overall PE mortality.
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http://dx.doi.org/10.1016/j.ijcard.2019.12.025DOI Listing
March 2020

Three-Year Impact of Immediate Invasive Strategy in Patients With Non-ST-Segment Elevation Myocardial Infarction (from the RIDDLE-NSTEMI Study).

Am J Cardiol 2018 07 28;122(1):54-60. Epub 2018 Mar 28.

Department of Cardiology, Clinical Center of Serbia, Belgrade, Serbia; Faculty of Medicine, University of Belgrade, Belgrade, Serbia. Electronic address:

Previous studies compared clinical outcomes of early versus delayed invasive strategy in patients with non-ST-elevation acute coronary syndrome up to 1-year follow-up, but long-term data remain scarce. Our aim was to evaluate the long-term effects of immediate invasive intervention in patients with Non-ST-Segment Elevation Myocardial Infarction (NSTEMI). The Randomized Study of Immediate Versus Delayed Invasive Intervention in Patients With Non-ST-Segment Elevation Myocardial Infarction (RIDDLE-NSTEMI) was a randomized, investigator-initiated, parallel-group trial that assigned 323 patients with NSTEMI (1:1) to either immediate (median time to intervention 1.4 hours) or delayed invasive strategy (61.0 hours). The primary end point was the composite of death or new myocardial infarction (MI). At 3 years, immediate invasive intervention was associated with a lower rate of death or new MI, compared with a delayed invasive strategy (12.3% vs 22.5%, hazard ratio 0.50, 95% confidence interval 0.29 to 0.87, p = 0.014). The observed benefit of immediate intervention was mainly driven by an increased early reinfarction risk in delayed strategy, with similar new MI rates beyond 30 days (4.4% in the immediate and 5.6% in the delayed group, p = 0.61). Three-year mortality was 9.3% in the immediate invasive strategy, and 10.0% in the delayed strategy (p = 0.83). High baseline Global Registry of Acute Coronary Events score (>140) was associated with a significant increase in long-term mortality, regardless of the timing of invasive intervention. In conclusion, whereas immediate invasive intervention significantly reduced the early risk of new MI, the timing of invasive intervention appears to have no significant impact on clinical outcomes beyond 30 days, which seem to mostly be related to the baseline clinical risk profile.
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http://dx.doi.org/10.1016/j.amjcard.2018.03.006DOI Listing
July 2018

Dabigatran after Short Heparin Anticoagulation for Acute Intermediate-Risk Pulmonary Embolism: Rationale and Design of the Single-Arm PEITHO-2 Study.

Thromb Haemost 2017 12 6;117(12):2425-2434. Epub 2017 Dec 6.

Center for Thrombosis and Hemostasis, University Medical Center Mainz, Mainz, Germany.

Patients with intermediate-risk pulmonary embolism (PE) may, depending on the method and cut-off values used for definition, account for up to 60% of all patients with PE and have an 8% or higher risk of short-term adverse outcome. Although four non-vitamin K-dependent direct oral anticoagulants (NOACs) have been approved for the treatment of venous thromboembolism, their safety and efficacy as well as the optimal anticoagulation regimen using these drugs have not been systematically investigated in intermediate-risk PE. Moreover, it remains unknown how many patients with intermediate-high-risk and intermediate-low-risk PE were included in most of the phase III NOAC trials. The ongoing Pulmonary Embolism International Thrombolysis 2 (PEITHO-2) study is a prospective, multicentre, multinational, single-arm trial investigating whether treatment of acute intermediate-risk PE with parenteral heparin anticoagulation over the first 72 hours, followed by the direct oral thrombin inhibitor dabigatran over 6 months, is effective and safe. The primary efficacy outcome is recurrent symptomatic venous thromboembolism or death related to PE within the first 6 months. The primary safety outcome is major bleeding as defined by the International Society on Thrombosis and Haemostasis. Secondary outcomes include all-cause mortality, the overall duration of hospital stay (index event and repeated hospitalizations) and the temporal pattern of recovery of right ventricular function over the 6-month follow-up period. By applying and evaluating a contemporary risk-tailored treatment strategy for acute PE, PEITHO-2 will implement the recommendations of current guidelines and contribute to their further evolution.
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http://dx.doi.org/10.1160/TH17-06-0434DOI Listing
December 2017

Elevated Serum Protein S100B and Neuron Specific Enolase Values as Predictors of Early Neurological Outcome After Traumatic Brain Injury.

J Med Biochem 2017 Oct 28;36(4):314-321. Epub 2017 Oct 28.

School of Medicine, University of Belgrade, Belgrade, Serbia.

Background: The objective of our study was to determine the serum concentrations of protein S100B and neuron specific enolase (NSE) as well as their ability and accuracy in the prediction of early neurological outcome after a traumatic brain injury.

Methods: A total of 130 polytraumatized patients with the associated traumatic brain injuries were included in this prospective cohort study. Serum protein S100B and NSE levels were measured at 6, 24, 48 and 72 hours after the injury. Early neurological outcome was scored by Glasgow Outcome Scale (GOS) on day 14 after the brain injury.

Results: The protein S100B concentrations were maximal at 6 hours after the injury, which was followed by an abrupt fall, and subsequently slower release in the following two days with continual and significantly increased values (p<0.0001) in patients with poor outcome. Secondary increase in protein S100B at 72 hours was recorded in patients with lethal outcome (GOS 1). Dynamics of NSE changes was characterized by a secondary increase in concentrations at 72 hours after the injury in patients with poor outcome.

Conclusion: Both markers have good predictive ability for poor neurological outcome, although NSE provides better discriminative potential at 72 hours after the brain injury, while protein S100B has better discriminative potential for mortality prediction.
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http://dx.doi.org/10.1515/jomb-2017-0018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6294083PMC
October 2017

Influence of Syrgical Trauma on Nitric Oxide and Nitrotyrosine Serum Levels in Patients Undergoing Laparoscopic Or Conventional Cholecystectomy.

J Med Biochem 2017 Apr 22;36(2):171-176. Epub 2017 Apr 22.

Clinic for Emergency Surgery, Clinical Centre of Serbia, Belgrade, Serbia.

Background: Oxidative stress represents tissue damage caused by reactive forms of oxygen and nitrogen due to the inability of antioxidant mechanisms to reduce reactive forms into more stable ones. The aim of the study was to evaluate the influence of surgical trauma on nitric oxide (NO) and nitrotyrosine (NT) values in patients undergoing conventional and laparoscopic cholecystectomy.

Methods: A prospective study included sixty patients from the Department of Emergency Surgery, Clinical Centre of Serbia who were operated for gallstone related chronic cholecystitis. All the patients enrolled in the study underwent cholecystectomy; the first group was operated conventionally (30 patients - control group), while the second group was operated laparoscopically (30 patients - treatment group).

Results: There were no statistically significant differences in the values of NO and its postoperative changes in both groups, the conventionally operated group (p=0.943) and the laparoscopically operated group (p=0.393). We found an increase in NT values 24 hours postoperatively (p=0.000) in the conventionally operated patients, while in the group operated laparoscopically we didn't find statistically significant changes in the values of NT (conventionally operated group (p=0.943) and laparoscopically operated group (p=0.393)).

Conclusions: In our study, we found a significant increase in NT values 24 hours postoperatively in conventionally operated patients i.e. the control group, vs. the treatment group. Further randomized studies are needed for a better understanding of the impact of surgical trauma on oxidative stress response.
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http://dx.doi.org/10.1515/jomb-2017-0004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5471650PMC
April 2017

Sex and age differences and outcomes in acute coronary syndromes.

Int J Cardiol 2016 Aug 27;217 Suppl:S27-31. Epub 2016 Jun 27.

Department of Experimental, Diagnostics and Specialty Medicine, University of Bologna, Italy.

Background: There is conflicting information about sex differences in presentation, treatment, and outcome after acute coronary syndromes (ACS) in the era of reperfusion therapy and percutaneous coronary intervention. The aim of this study was to examine presentation, acute therapy, and outcomes of men and women with ACS with special emphasis on their relationship with younger age (≤65years).

Methods: From January 2010 to June 2015, we enrolled 5140 patients from 3 primary PCI capable hospitals. Patients were registered according to the International Survey of Acute Coronary Syndrome in Transitional Countries (ISACS-TC) registry protocol (ClinicalTrials.gov: NCT01218776). The primary outcome was the incidence of in-hospital mortality.

Results: The study population was constituted by 2876 patients younger than 65years and 2294 patients older. Women were older than men in both the young (56.2±6.6 vs. 54.1±7.4) and old (74.9±6.4 vs. 73.6±6.0) age groups. There were 3421 (66.2%) patients with ST elevation ACS (STE-ACS) and 1719 (33.8%) patients without ST elevation ACS (NSTE-ACS). In STE-ACS, the percentage of patients who failed to receive reperfusion was higher in women than in men either in the young (21.7% vs. 15.8%) than in the elderly (35.2% vs. 29.6%). There was a significant higher mortality in women in the younger age group (age-adjusted OR 1.52, 95% CI: 1.01-2.29), but there was no sex difference in the older group (age-adjusted OR 1.10, 95% CI: 0.87-1.41). Significantly sex differences in mortality were not seen in NSTE-ACS patients.

Conclusions: In-hospital mortality from ACS is not different between older men and women. A higher short-term mortality can be seen only in women with STEMI and age of 65 or less.
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http://dx.doi.org/10.1016/j.ijcard.2016.06.217DOI Listing
August 2016

Outcome of patients with right heart thrombi: the Right Heart Thrombi European Registry.

Eur Respir J 2016 Mar 21;47(3):869-75. Epub 2016 Jan 21.

Dept of Internal Medicine and Cardiology, The Medical University of Warsaw, Warsaw, Poland

Our aim was the assessment of the prognostic significance of right heart thrombi (RiHT) and their characteristics in pulmonary embolism in relation to established prognostic factors.138 patients (69 females) aged (mean±sd) 62±19 years with RiHT were included into a multicenter registry. A control group of 276 patients without RiHT was created by propensity scoring from a cohort of 963 contemporary patients. The primary end-point was 30-day pulmonary embolism-related mortality; the secondary end-point included 30-day all-cause mortality. In RiHT patients, pulmonary embolism mortality was higher in 31 patients with systolic blood pressure <90 mmHg than in 107 normotensives (42% versus 12%, p=0.0002) and was higher in the 83 normotensives with right ventricular dysfunction (RVD) than in the 24 normotensives without RVD (16% versus 0%, p=0.038). In multivariable analysis the simplified Pulmonary Embolism Severity Index predicted mortality (hazard ratio 2.43, 95% CI 1.58-3.73; p<0.0001), while RiHT characteristics did not. Patients with RiHT had higher pulmonary embolism mortality than controls (19% versus 8%, p=0.003), especially normotensive patients with RVD (16% versus 7%, p=0.02).30-day mortality in patients with RiHT is related to haemodynamic consequences of pulmonary embolism and not to RiHT characteristics. However, patients with RiHT and pulmonary embolism resulting in RVD seem to have worse prognosis than propensity score-matched controls.
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http://dx.doi.org/10.1183/13993003.00819-2015DOI Listing
March 2016

Immediate Versus Delayed Invasive Intervention for Non-STEMI Patients: The RIDDLE-NSTEMI Study.

JACC Cardiovasc Interv 2016 Mar 6;9(6):541-9. Epub 2016 Jan 6.

Department of Cardiology, Clinical Center of Serbia, Belgrade, Serbia; Faculty of Medicine, University of Belgrade, Belgrade, Serbia. Electronic address:

Objectives: This study aimed to assess the clinical impact of immediate versus delayed invasive intervention in patients with non-ST-segment myocardial infarction (NSTEMI).

Background: Previous studies found conflicting results on the effects of earlier invasive intervention in a heterogeneous population of acute coronary syndromes without ST-segment elevation.

Methods: We randomized 323 NSTEMI patients to an immediate-intervention group (<2 h after randomization, n = 162) and a delayed-intervention group (2 to 72 h, n = 161).The primary endpoint was the occurrence of death or new myocardial infarction (MI) at 30-day follow-up.

Results: Median time from randomization to angiography was 1.4 h and 61.0 h in the immediate-intervention group and the delayed-intervention group, respectively (p < 0.001). At 30 days, the primary endpoint was achieved less frequently in patients undergoing immediate intervention (4.3% vs. 13%, hazard ratio: 0.32, 95% confidence interval: 0.13 to 0.74; p = 0.008). At 1 year, this difference persisted (6.8% in the immediate-intervention group vs. 18.8% in delayed-intervention group; hazard ratio: 0.34, 95% confidence interval: 0.17 to 0.67; p = 0.002). The observed results were mainly attributable to the occurrence of new MI in the pre-catheterization period (0 deaths + 0 MIs in the immediate-intervention group vs. 1 death + 10 MIs in the delayed-intervention group). The rate of deaths, new MI, or recurrent ischemia was lower in the immediate-intervention group at both 30 days (6.8% vs. 26.7%; p < 0.001) and 1 year (15.4% vs. 33.1%; p < 0.001).

Conclusions: Immediate invasive strategy in NSTEMI patients is associated with lower rates of death or new MI compared with the delayed invasive strategy at early and midterm follow-up, mainly due to a decrease in the risk of new MI in the pre-catheterization period. (Immediate Versus Delayed Invasive Intervention for Non-STEMI Patients [RIDDLE-NSTEMI]; NCT02419833).
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http://dx.doi.org/10.1016/j.jcin.2015.11.018DOI Listing
March 2016

Surgical management of AAST grades III-V hepatic trauma by Damage control surgery with perihepatic packing and Definitive hepatic repair-single centre experience.

World J Emerg Surg 2015 1;10:34. Epub 2015 Aug 1.

Faculty of Medicine, University of Belgrade and Clinical Center of Serbia, Clinic for Emergency Surgery, University of Belgrade, Serbia, Pasteur Str.2, Belgrade, 11000 Serbia.

Background: Severe liver injury in trauma patients still accounts for significant morbidity and mortality. Operative techniques in liver trauma are some of the most challenging. They include the broad and complex area, from damage control to liver resection.

Material And Method: This is a retrospective study of 121 trauma patients with hepatic trauma American Association for Surgery of Trauma (AAST) grade III-V who have undergone surgery. Indications for surgery include refractory hypotension not responding to resuscitation due to uncontrolled hemorrhage from liver trauma; massive hemoperitonem on Focused assessment by ultrasound for trauma (FAST) and/or Diagnostic peritoneal lavage (DPL) as well as Multislice Computed Tomography (MSCT) findings of the severe liver injury and major vascular injuries with active bleeding.

Results: Non-survivors have significantly higher AAST grade of liver injury and higher Injury Severity Score (ISS) (p = 0.000; p = 0.0001). Non-survivors have significant hypotension on arrival and lower Glasgow Coma Scale (GCS) on admission (p = 0.000; p = 0.0001). Definitive hepatic repair was performed in 62(51.2 %) patient. Damage Control, liver packing and planned re-laparotomy after 48 h were used in 59(48.8 %). There was no statistically significant difference in terms of the surgical approach. There was significant difference in the amount of red blood cells (RBC) transfusion in the first 24 h between survivors and non-survivors (p = 0.001). Overall mortality rate was 33.1 %. Regarding complications non-survivors had significantly prolonged bleeding and higher rate of Acute respiratory distress syndrome (ARDS) (p = 0.0001; p = 0.0001), while survivors had significantly higher rate of pleural effusion (p = 0.0001).

Conclusion: All efforts in the treatment of severe liver injuries should be directed to the rapid and effective control of bleeding, because uncontrollable hemorrhage is the cause of early death and it requires massive blood transfusion, all of which contributes to the late fatal complication.
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http://dx.doi.org/10.1186/s13017-015-0031-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4522150PMC
August 2015

Fibrinolysis for patients with intermediate-risk pulmonary embolism.

N Engl J Med 2014 Apr;370(15):1402-11

The authors' affiliations are listed in the Appendix.

Background: The role of fibrinolytic therapy in patients with intermediate-risk pulmonary embolism is controversial.

Methods: In a randomized, double-blind trial, we compared tenecteplase plus heparin with placebo plus heparin in normotensive patients with intermediate-risk pulmonary embolism. Eligible patients had right ventricular dysfunction on echocardiography or computed tomography, as well as myocardial injury as indicated by a positive test for cardiac troponin I or troponin T. The primary outcome was death or hemodynamic decompensation (or collapse) within 7 days after randomization. The main safety outcomes were major extracranial bleeding and ischemic or hemorrhagic stroke within 7 days after randomization.

Results: Of 1006 patients who underwent randomization, 1005 were included in the intention-to-treat analysis. Death or hemodynamic decompensation occurred in 13 of 506 patients (2.6%) in the tenecteplase group as compared with 28 of 499 (5.6%) in the placebo group (odds ratio, 0.44; 95% confidence interval, 0.23 to 0.87; P=0.02). Between randomization and day 7, a total of 6 patients (1.2%) in the tenecteplase group and 9 (1.8%) in the placebo group died (P=0.42). Extracranial bleeding occurred in 32 patients (6.3%) in the tenecteplase group and 6 patients (1.2%) in the placebo group (P<0.001). Stroke occurred in 12 patients (2.4%) in the tenecteplase group and was hemorrhagic in 10 patients; 1 patient (0.2%) in the placebo group had a stroke, which was hemorrhagic (P=0.003). By day 30, a total of 12 patients (2.4%) in the tenecteplase group and 16 patients (3.2%) in the placebo group had died (P=0.42).

Conclusions: In patients with intermediate-risk pulmonary embolism, fibrinolytic therapy prevented hemodynamic decompensation but increased the risk of major hemorrhage and stroke. (Funded by the Programme Hospitalier de Recherche Clinique in France and others; PEITHO EudraCT number, 2006-005328-18; ClinicalTrials.gov number, NCT00639743.).
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http://dx.doi.org/10.1056/NEJMoa1302097DOI Listing
April 2014

Spontaneous rupture of giant liver hemangioma: case report.

Srp Arh Celok Lek 2013 Jan-Feb;141(1-2):95-9

Clinic for Emergency Surgery, Clinical Center of Serbia, Belgrade, Serbia.

Introduction: Hemangioma is the most frequent benign solid tumor of the liver. It is well known that a giant liver hemangioma carries the risk of spontaneous rupture, followed by hemoperitoneum and hemorrhagic shock with possible fatal outcome.

Case Outline: This is a case report of the spontaneous rupture of a giant cavernous hemangioma of the liver in an 85-year old patient.The patient was presented with abdominal pain and hemorrhagic shock. Emergency ultrasonography and computed tomography of the abdomen showed a heterogeneous ruptured solid tumor of the right liver lobe, multiple cysts in the left lobe and massive hemoperitoneum. The patient was successfully managed by immediate exploratory laparotomy, surgical enucleation of the hemangioma under intermittent inflow vascular occlusion, temporary perihepatic packing and planned second look relaparotomy.

Conclusion: Immediate surgical procedure is indicated mandatory in unstable patients with a ruptured giant hemangioma of the liver. Surgical enucleation under intermittent inflow vascular occlusion and temporary perihepatic packing could be a life-saving procedure in those patients.
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http://dx.doi.org/10.2298/sarh1302095dDOI Listing
September 2013

The efficacy of three transection techniques of the liver resection: a randomized clinical trial.

Hepatogastroenterology 2012 Jul-Aug;59(117):1501-6

Clinical Center of Serbia, Belgrade, Serbia.

Background/aims: Liver resection is a demanding procedure due to the risk of massive blood loss. Different instruments for liver transection are available today. The aim of this randomized clinical trial was to analyze the efficacy of three different parenchyma transection techniques of liver resection.

Methodology: A total of 60 non-cirrhotic patients undergoing hepatectomy were randomly selected for clamp crushing technique (CRUSH), ultrasonic dissection (CUSA) or bipolar device (LigaSure), n=20 in each group. All patients had liver resection under low central venous pressure anaesthesia (CVP), with ischemic preconditioning and intermittent inflow occlusion. Primary endpoints were surgery duration, transection duration, cumulative pedicle clamping time, intraoperative blood loss and blood transfusion. Secondary endpoints included the postoperative liver injury, postoperative morbidity and mortality.

Results: Overall surgery duration was 295 vs. 270 vs. 240min for LigaSure, CUSA and Clamp Crushing Technique, respectively. The transection duration was 85 vs. 52.5 vs. 40 minutes, respectively. These three different resection techniques of non-cirrhotic liver produced similar outcome in terms of intraoperative blood loss, blood transfusion, postoperative complications and mortality.

Conclusions: The Clump Crushing Technique, CUSA and Liga Sure are equally safe for resection of non-cirrhotic liver. Liver resections can be performed safely if the entire concept is well designed and the choice of dissection device does not affect the outcome of hepatectomy.
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http://dx.doi.org/10.5754/hge11552DOI Listing
October 2012

Early dumping syndrome and reflux esophagitis prevention with pouch reconstruction.

J Surg Res 2012 Jun 5;175(1):56-61. Epub 2011 Mar 5.

Department of Esophago-Gastric Surgery, KBC Bezanijska kosa, Belgrade, Serbia.

Background: Total gastrectomy causes numerous disorders, such as reflux esophagitis, dumping syndrome, malabsorption, and malnutrition. To minimize the consequences, different variants of reconstruction are performed. The aim of our study is the comparison of two reconstructive methods: the standard Roux-en-Y and a new modality of pouch interposition, preduodenal-pouch interposition. This study aims to investigate the advantage of bile reflux prevention and to reduce symptoms of dumping syndrome after 3- and 6-mo follow-up.

Materials And Methods: A total of 60 patients were divided in two groups: (A) 30 patients with Roux-en-Y reconstruction, and (B) 30 patients with the preduodenal-pouch (PDP) type of reconstruction. Endoscopic examination and endoluminal jejunal limb pressure measurements were performed. Scintigraphic measurements of half-emptying time were performed to evaluate meal elimination in the context of reflux esophagitis and early dumping syndrome. The Japan Society of Gastrointestinal Surgery has provided guidelines with which to classify the symptoms of early dumping syndrome. Patients were followed up for periods of 3 and 6 mo after the surgery.

Results: Our study groups did not differ with regard to the level of reflux esophagitis (P = 0.688). Average values of pressure at 10 and 15 cm below the esophago-jejunal junction were significantly lower in the PDP group (P < 0.001). Elimination of the test meal between two groups was not significant (P = 0.222). Evaluation of early dumping syndrome symptoms revealed a significant reduction among PDP patients after 3 and 6 mo.

Conclusion: Our study showed significant superiority of the new pouch reconstruction over the standard Roux-en-Y approach in the treatment of early dumping syndrome.
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http://dx.doi.org/10.1016/j.jss.2011.02.001DOI Listing
June 2012

SIRS score on admission and initial concentration of IL-6 as severe acute pancreatitis outcome predictors.

Hepatogastroenterology 2010 Mar-Apr;57(98):349-53

Center of Emergency Surgery, Clinical Center of Serbia and School of Medicine, University of Belgrade, Belgrade, Serbia.

Background/aims: Early recognition of severe form of acute pancreatitis is important because these patients need more agressive diagnostic and therapeutical approach an can develope systemic complications such as: sepsis, coagulopathy, Acute Lung Injury (ALI), Acute Respiratory Distress Syndrome (ARDS), Multiple Organ Dysfunction Syndrome (MODS), Multiple Organ Failure (MOF). To determine role of the combination of Systemic Inflammatory Response Syndrome (SIRS) score and serum Interleukin-6 (IL-6) level on admission as predictor of illness severity and outcome of Severe Acute Pancreatitis (SAP).

Methodology: We evaluated 234 patients with first onset of SAP appears in last twenty four hours. A total of 77 (33%) patients died. SIRS score and serum IL-6 concentration were measured in first hour after admission.

Results: In 105 patients with SIRS score 3 and higher, initial measured IL-6 levels were significantly higher than in the group of remaining 129 patients (72 +/- 67 pg/mL, vs 18 +/- 15 pg/mL). All nonsurvivals were in the first group, with SIRS score 3 and 4 and initial IL-6 concentration 113 +/- 27 pg/mL. The values of C-reactive Protein (CRP) measured after 48h, Acute Physiology and Chronic Health Evaluation (APACHE II) score on admission and Ranson score showed the similar correlation, but serum amylase level did not correlate significantly with Ranson score, IL-6 concentration and APACHE II score.

Conclusion: The combination of SIRS score on admission and IL-6 serum concentration can be early, predictor of illness severity and outcome in SAP.
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August 2010

[Liver injuries].

Acta Chir Iugosl 2010 ;57(4):57-67

Klinika za urgentnu hirurgiju KCS, Medicinski fakultet u Beogradu.

The liver is the most commonly injured abdominal organ. Severe hepatic trauma continue to be associated with high mortality. Management of liver injuries has changed significantly over the last two decades. Nonoperative management of hemodynamically stable patients has become the first treatment of choice. In unstable patients immediate control of bleeding is critical. In the management of severe injuries of the liver, particularly for patients who had developed a metabolic insult (hypothermia, coagulopathy, and acidosis), perihepatic packing has emerged as the key to effective damage control (DCS). The surgical aim is control of hemorrhage, preservation of sufficient hepatic function and prevention of secondary complications. Currently available surgical methods include hepatorrhaphy, resectional debridement, anatomical/nonanatomical resection, selective hepatic artery ligation, Pringle maneuver, total vascular exclusion, liver transplatation. This review discusses available diagnostic modalities and the best management options for liver injury, based on literature search and authors experience.
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http://dx.doi.org/10.2298/aci1004057kDOI Listing
April 2011

Use of recombinant factor VIIa in the treatment of massive retroperitoneal bleeding due to severe necrotizing pancreatitis.

Vojnosanit Pregl 2009 Nov;66(11):928-32

Clinical Center of Serbia, Emergency Center, Center for Emergency Surgery, Belgrade, Serbia.

Background: Recently, a growing number of case reports and case series have suggested that the use of recombinant activated factor VII (rFVIIa) may be effective in treatment of patients with non-hemophilic acquired coagulopathy not responding to conventional treatment such as major surgery, major trauma, sepsis, necrotizing pancreatitis and bleeding due to cerebral arteriovenous malformations.

Case Report: We presented a septic patient with massive, life-threatening bleeding caused by retroperitoneal necrosis, due to severe acute necrotizing pancreatitis. As conservative treatment (blood, plasma, cryoprecipitates and platelet transfusions) failed to induce cessation of bleeding, the patient was urgently operated on. In spite of usual procedures of surgical hemostasis (ligation, suture, thermocauterisation, fibrin glue, temporary tamponade), hemorrhage could not be stopped. The patient manifested the signs of hypothermia and metabolic acidosis and, therefore, the decision was made to use recombinant activated factor VII (Novo Seven). The application of rFVIIa resulted in significant discontinuation of hemorrhage, restoration to normal blood count as well as other relevant coagulation parameters.

Conclusion: Although application of rFVIIa is still in the initial clinical phase, and the experience is based mainly on uncontrolled series as well as on individual observations, it seems that this drug can be promising, potent and attractive adjunctive prohemostatic agent. This drug may play a beneficial role in the treatment of serious and unresponsive, "nonsurgical", life-threatening bleeding due to severe acute necrotizing pancreatitis.
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http://dx.doi.org/10.2298/vsp0911928sDOI Listing
November 2009

In-hospital and long-term prognosis after myocardial infarction in patients with prior coronary artery bypass surgery; 19-year experience.

ScientificWorldJournal 2009 Oct 1;9:1023-30. Epub 2009 Oct 1.

Division of Emergency Cardiology of the University Institute for Cardiovascular Diseases, Clinical Center of Serbia, School of Medicine, University of Belgrade, 11000 Belgrade, 8 Koste Todorovica, Serbia.

To present a 19-year experience of the prognosis of patients with acute myocardial infarction (AMI) and prior coronary artery bypass surgery (CABS), 748 patients with AMI after prior CABS (postbypass group) and a control group of 1080 patients with AMI, but without prior CABS, were analyzed. All indexes of infarct size were lower in the postbypass group. There was more ventricular fibrillation in the postbypass group. In-hospital mortality was similar (p = 0.3675). In the follow-up period, postbypass patients had more heart failure, recurrent CABS, reinfarction, and unstable angina than did control patients. Cumulative survival was better in the control group than in the postbypass group (p = 0.0403). Multiple logistic regression model showed that previous angina (p = 0.0005), diabetes (p = 0.0058), and age (p = 0.0102) were independent predictor factors for survival. Use of digitalis and diuretics, together with previous angina, also influenced survival (p = 0.0092), as well as male gender, older patients, and diabetes together (p = 0.0420). Patients with AMI after prior CABS had smaller infarct, but more reinfarction, reoperation, heart failure, and angina. Previous angina, diabetes, and age, independently, as well as use of digitalis and diuretics together with angina, and male gender, older patients, and diabetes together, influenced a worse survival rate in these patients.
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http://dx.doi.org/10.1100/tsw.2009.114DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5823101PMC
October 2009

D-dimer in acute pancreatitis: a new approach for an early assessment of organ failure.

Pancreas 2009 Aug;38(6):655-60

Center for Emergency Surgery, School of Medicine, Surgical Department, University of Belgrade, Belgrade, Serbia.

Objectives: Studies on the clinical value of parameters of hemostasis in predicting pancreatitis-associated complications are still scarce. The aim of this prospective study was to identify the useful hemostatic markers for accurate determination of the subsequent development of organ failure (OF) during the very early course of acute pancreatitis (AP).

Methods: In 91 consecutive primarily admitted patients with AP, prothrombin time, activated partial thromboplastin time, fibrinogen, antithrombin III, protein C, plasminogen activator inhibitor 1, D-dimer, and plasminogen were measured in plasma within the first 24 hours of admission and 24 hours thereafter. Two study groups comprising 24 patients with OF and 67 patients without OF were compared.

Results: Levels of prothrombin time, fibrinogen, and D-dimer on admission were significantly different between the OF and non-OF groups, and all these parameters plus antithrombin III were significantly different 24 hours later. A D-dimer value of 414.00 microg/L on admission was the best cutoff value in predicting the development of OF with sensitivity, specificity, and positive and negative predictive values of 90%, 89%, 75%, and 96%, respectively.

Conclusions: Measurement of plasma levels of D-dimer on the admission is an accurate method for the identification of patients who will develop OF in the further course of AP.
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http://dx.doi.org/10.1097/MPA.0b013e3181a66860DOI Listing
August 2009

[Hospital mortality trend analysis of patients with ST elevation myocardial infarction in the Belgrade area coronary care units].

Srp Arh Celok Lek 2008 May;136 Suppl 2:84-96

Introduction: Mortality in ST elevation myocardial infarction (STEMI) ranges from 4-24% and is dependent on the variety of patients' clinical characteristics (CC) that are present prior to and within the first hours of the onset of MI, affecting reliability of the diagnosis. The higher mortality rate of patients with STEMI should be associated with a higher rate of applied reperfusion therapy according to guidelines and randomized study results, which is in opposition to everyday hospital practice.

Objective: The aim of this study was to analyze the mortality of STEMI patients in relationship to their clinical characteristics at presentation, their age, sex, risk factors, prior coronary disease, and time interval from symptom onset to hospital presentation, complications and administered therapy.

Method: The analysis involved patients treated in five coronary care units, four Belgrade Hospital Centres and the Belgrade Emergency Centre of the Clinical Centre of Serbia. Evaluated data was obtained from the Serbian National Registry for Acute Coronary Syndrome (REAKSS) and databases of local coronary care units (CCU).

Results: During 2005 and 2006, a total of 2739 patients with STEMI, of average age 63.3 +/- 11.7, with 64.9% males aged 61.3 +/- 11.7 and 35.1% females aged 67.0 +/- 10.7 (p < 0.01) who underwent treatment. Most of the patients (80.5%) were distributed within the elderly groups of 60, 70 and 80 years of age, with the highest percent of mortality rate (45.9%) noted at age 80 years. Anterior localization of myocardial infarction was observed in 40.2% of patients, with lethal outcome in 21.4% patients, while 59.8% of patients suffered inferiorly localized MI with much lower mortality rate (12.2%, p < 0.01). In 2005, STEMI was registered in 48.7%, while in 2006 in 44.7% of patients. Prior angina pectoris was present in 19.9% of patients, more frequently among women (p < 0.05), prior MI in 14.5% of patients, more often among males (p < 0.05), while aortocoronary revascularization was found in 3.9% of patients. Hospital mortality rate due to STEMI was higher in the group of patients with a history of prior MI (19.1% vs. 15.7%; p > 0.05). Regarding risk factors, hypertension was present in 61.8% of patients, more often among women (69.1% vs.57.9%) (p < 0.01), carrying a higher mortality rate of 18.9% vs. 9.9% among males (p < 0.01). Hyperlipidemia was found in 31.9% of patients; more frequently among women 34.8% vs. 30.4% males (p < 0.05), as well as diabetes mellitus observed in 25.1% of patients; 22.4% males and 30.1% females (p < 0.01). 39.6% of patients were smokers; 46.9% males and 28.0% females (p < 0.01). Heart failure had 33.4% of patients; mortality rate was registered in 28.2% of patients, and was significantly higher than in the non heart failure group (7.9%, p < 0.01). Heart rhythm disorders were registered in 21.3% of patients, more frequently involving posterior MI 55.3% vs 44.7% of anterior MI (p > 0.05), and was significantly higher among females 23.5% vs. 20.1% in males (p < 0.05). In 2005 in Belgrade hospitals, reperfusion therapy (RT) was performed in 34.6% of patients, mostly as thrombolytic therapy (TT) (in 99.0% of patients), and as percutaneous coronary intervention (PCI) in 1.0% of patients. STEMI mortality rate was 12.8%. In 2006, in the CCU of the In the Emergency Center RT was applied in 48.0% of patients, TT in 13.8% and PCI in 34.2%, while classical therapy without RT was applied in 52.0% of patients.

Conclusion: Clinical characteristics significantly influence mortality in STEMI; a significantly higher mortality is among women, patients in their 80's and 90's, anterior MI localization and prior coronary disease. RT significantly lowers mortality in STEMI compared to the use of classical therapeutic approach and therefore STEMI patients with a higher mortality determined by their prehospital charactheristics, i.e. higher risk, are those who have higher benefit of RT, which should be taken into consideration when making decision about the therapy of choice.
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http://dx.doi.org/10.2298/sarh08s2084vDOI Listing
May 2008

The timing of infarction pain in patients with acute myocardial infarction after previous revascularization.

ScientificWorldJournal 2008 Jun 13;8:598-603. Epub 2008 Jun 13.

Division of Emergency Cardiology of The University Institute for Cardiovascular Diseases, Clinical Center of Serbia, 11000 Belgrade, 8 Koste Todorovica, Serbia.

Circadian variation of onset of acute myocardial infarction (AMI) has been noted in many studies, but there are no data about subgroups of patients with previous coronary artery bypass grafting (CABG). Because of abnormalities in the circadian rhythm of autonomic tone after surgery, it was very interesting to analyze the circadian patterns in the onset of symptoms of AMI in various subgroups of 1784 patients with previous CABG. As in the other studies, a peak occurred in the morning hours with 26.3% of the patients, but there was a second nearly equal, but higher, peak (26.4%) in the evening hours. The subgroups with specific clinical characteristics exhibited different patterns that determined these peaks in all populations. In patients older than 70 years of age, in both sexes, in smokers, diabetics, in patients with hypertension, in those undergoing beta-blocker therapy, and in patients without previous angina, two nearly equal peaks were observed, with higher evening peaks, except in those patients with hypertension and without angina. Only one peak in the evening hours was observed in a subgroup of patients with previous congestive heart failure (CHF) and non-STEMI. The subgroup of patients with previous angina and previous AMI exhibited no discernible peaks. The distribution of time of onset within the four intervals was not uniform, and the difference was statistically significant only for patients undergoing beta-blocker therapy at time of onset (p = 0.0013), nonsmokers (p = 0.0283), and patients with non-STEMI (p = 0.0412). It is well known that patients with AMI have a dominant morning peak of circadian variation of onset. However, analyzing a different subgroup of patients with AMI after previous CABG, it was found that some subgroups had two peaks of onset, but a higher evening peak (patients older than 70 years of age, smokers, diabetics, and a group of patients who were taking beta-blocker therapy). This subgroup of patients, together with the subgroups of patients with a dominant evening peak (patients with CHF and those with non-STEMI) and with patients with no peak (patients with previous angina and previous AMI), probably appear to modify characteristic circadian variation of infarction onset, expressing a higher evening peak, respectively to the previous CABG, with adverse consequences for central nervous system functioning.
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http://dx.doi.org/10.1100/tsw.2008.88DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5848734PMC
June 2008

Immunoscintigraphy of colorectal carcinomas with radiolabeled monoclonal antibody fragments.

Hepatogastroenterology 2006 Jul-Aug;53(70):526-30

Institute for Nuclear Medicine, Clinical Center of Serbia, Belgrade, Serbia, & Montenegro.

Background/aims: The aim was evaluation of the accuracy and clinical impact of the immunoscintigraphy for the detection of metastases and recurrences of colorectal carcinomas using two different radiolabeled antibody fragments.

Methodology: The study was performed in 5 patients with IMACIS 1 containing the cocktail of 111MBq 131I MoAb 19-9 F(ab')2 and MoAb anti-CEA F(ab')2 and 8 patients with INDIMACIS 19-9 containing 150MBq of 111In-labeled MoAb 19-9 F(ab')2.

Results: With IMACIS 1, in all the patients, both tumor marker values were elevated. The number of TN was 3/5 and TP 2/5. From 2 TP, one had recurrence of the diseases with peritoneal carcinosis and one with liver metastases. In one patient, the results influenced the therapeutical management. With INDIMACIS 19-9, there were 2/8 TN, with borderline value of CEA and CA 19-9. TP were 6/8 (all with elevated tumor marker values, five of them many times; 3 with recurrences, 1 with recurrence and liver metastases and two with only liver metastases. In three patients, immunoscintigraphy influenced patient management.

Conclusions: With both radiopharmaceuticals, immunoscintigraphy significantly influenced the patient management or it was complementary. It would be performed in the detection of recurrence, assessment of viability and follow-up of the therapy.
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December 2006

Simultaneous dynamic study of gastric emptying and changes of serum levels of gut hormones in patients after peptic ulcer surgery.

Nucl Med Rev Cent East Eur 2006 ;9(1):51-5

Institute for Nuclear Medicine, Clinical Centre of Serbia, Beograd, Serbia and Montenegro.

Background: The aim was to examine the influence of different modalities of peptic ulcer surgery on the gastric emptying (GE) pattern and related serum level changes of selected gut hormones.

Material And Methods: Fifty eight subjects were examined. In 48 of them peptic ulcer surgery was performed at least six months before the examination: Billroth I (B1) in 11, Billroth II (B2) in 16, B1 with the selective vagotomy--Harkins 1 (H1) in 9 and B2 with the selective vagotomy--Harkins 2 (H2) in 12. Ten healthy volunteers (C) were also examined.

Results: The results of gastric emptying showed that the lag phase duration was inversely related to the GE rates, and the GE pattern was linear in both controls (C) and in operated patients, except in B2 group, in which the GE pattern was exponential. In comparison with C group, GE was slower in B1, H1 and H2 groups, and faster in B2 group. The plasma gastrin values in C group, showing two peaks, were higher in relation to other groups. In relation to C group, higher values of motilin were obtained in patients after the selective vagotomy. The plasma somatostatin values recorded in B1 and H1 groups, showing the marked peaks, were higher in relation to C group. In relation to C group the highest plasma neurotensin values were obtained in B2 group.

Conclusions: In order to understand entirely the influence of peptic ulcer surgery on the GI function, further research of the role of specific hormones and neuropeptides is needed, which would enable more precise selection of the therapy in order to prevent postvagotomy and postgastrectomy syndromes.
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August 2006

Thrombolytic therapy for massive pulmonary embolism 12 hours after cesarean delivery despite contraindication?

Am J Emerg Med 2006 Jul;24(4):502-4

Institute of Cardiovascular Diseases, Cardiology Clinic, Clinical Center of Serbia, 11000 Belgrade, Serbia and Montenegro.

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http://dx.doi.org/10.1016/j.ajem.2005.12.003DOI Listing
July 2006

Predictive value of biphasic response during dipyridamole echocardiography test in the low-risk group of patients after acute myocardial infarction.

J Am Soc Echocardiogr 2005 Dec;18(12):1355-61

Institute of Cardiovascular Diseases, Clinical Center of Serbia, Belgrade, Serbia and Montenegro.

To investigate whether biphasic response during dipyridamole echocardiography test (DET), which represents viable but potentially ischemic myocardium in the infarcted region, affects prognosis of patients after uncomplicated acute myocardial infarction, we performed high-dose DET in 80 consecutive patients younger than 65 years with first acute myocardial infarction and preserved left ventricular function. Patients were followed up for 27 +/- 12 months for new coronary events. According to DET results all patients were classified into 4 groups: group 1 consisted of 20 patients with biphasic response; group 2 included 14 patients with sustained improvement in regional contractility; group 3 consisted of 24 patients showing no change in contractility; and group 4 included 22 patients with worsening response. Cumulative survival free of total coronary events was significantly lower in group 1 patients compared with all other groups (P < .05). By multivariate Cox analysis biphasic response was the strongest independent predictor of stable angina pectoris (odds ratio = 12.1, P = .0002), followed by hyperlipoproteinemia (odds ratio = 5.9, P = .006). On the other hand, development of acute coronary syndromes could not have been predicted by actual clinical or DET parameters.
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http://dx.doi.org/10.1016/j.echo.2005.05.003DOI Listing
December 2005

Effects of glucose-insulin-potassium infusion on ST-elevation myocardial infarction in patients treated with thrombolytic therapy.

Am J Cardiol 2005 Oct 24;96(8):1053-8. Epub 2005 Aug 24.

Medical Faculty, University Institute of Cardiovascular Disease Belgrade, Serbia and Montenegro.

The role of glucose-insulin-potassium (GIK) infusion in the management of acute myocardial infarction is not well established. This prospective, randomized study comprised 120 patients who had ST-elevation myocardial infarction that was treated within 12 hours from symptom onset with a high dose of GIK (25% glucose, 50 IU of soluble insulin per liter, and 80 mmol of potassium chloride per liter at 1 ml/kg/hour over 24 hours) as adjunct to thrombolytic therapy (1.5 MU of streptokinase/30 to 60 minutes; GIK group) or thrombolytic therapy alone (control group). The primary end point of the study was the rate of major adverse cardiac events (MACEs) at 1 month, defined as a composite of cardiac death, reinfarction, serious arrhythmias (ventricular fibrillation and/or tachycardia), and severe heart failure. The secondary end points were the rate of MACEs at 1 year and improvement in left ventricular systolic function. The incidence of MACEs at 1 month was significantly lower in the GIK group (10% vs 32.5%, relative risk 0.24, 95% confidence interval 0.09 to 0.63, p = 0.0043). Patients in the GIK group had significant decreases in ventricular tachycardia and/or fibrillation (1.3% vs 15.0%, p = 0.003) and severe heart failure (3% vs 12.5%, p = 0.031). The rate of MACEs at 1 year was also significantly lower in the GIK group (13% vs 40.0%, relative risk 0.22, 95% confidence interval 0.09 to 0.55, p = 0.0012). After 1 year, there was a significant improvement in left ventricular ejection fraction in the GIK group (from 48 +/- 8% to 51 +/- 10%, p <0.01), which was not observed in the control group. In conclusion, high-dose GIK, used as an adjunct to thrombolytic therapy, was safe and improved clinical outcome at 1 month. The beneficial effect of GIK infusion was maintained up to 1 year.
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http://dx.doi.org/10.1016/j.amjcard.2005.05.068DOI Listing
October 2005

Planned staged reoperative necrosectomy using an abdominal zipper in the treatment of necrotizing pancreatitis.

Surg Today 2005 ;35(10):833-40

Center of Emergency Surgery, Clinical Center of Serbia and School of Medicine, University of Belgrade, 2 Pasterova Street, 11000, Belgrade, Serbia and Montenegro.

Purpose: The optimal operative treatment for severe necrotizing pancreatitis (SNP) still remains controversial. This article describes the operative approach with a planned staged necrosectomy using the "zipper" technique.

Methods: Between 1996 and 2000, 35 patients with SNP were treated with this approach. The patient demographics, etiology and severity of SNP, hospital course, and outcome were recorded and comparisons of several parameters were made between the patients who survived and those who died.

Results: Hospital mortality was 34%. A total of 16 fistulae developed in 11 patients (31%), recurrent intra-abdominal abscesses in 4 (11%), and hemorrhaging in 5 (14%). The patients who died compared with those who survived had a higher Acute Physiology and Chronic Health Evaluation (APACHE)-II score on admission (14.5 vs 9, P < 0.001), extrapancreatic extension of necrosis more often (100% vs 65%, P = 0.02), and developed postoperative hemorrhaging more often (33% vs 4%, P = 0.038). A multivariate logistic analysis revealed an APACHE-II score of > 13 on admission (P = 0.018) and an extension of necrosis behind both paracolic gutters (P < 0.001) to both be prognostic factors for mortality.

Conclusions: Severe necrotizing pancreatitis still carries significant morbidity and mortality. This surgical approach facilitates the removal of all devitalized tissue and seems to decrease the incidence of recurrent intra-abdominal infection requiring reoperation. An APACHE-II score of > or = 13 and an extension of necrosis behind both paracolic gutters was thus found to signify a worse outcome.
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http://dx.doi.org/10.1007/s00595-005-3045-0DOI Listing
April 2006

High-resolution phylogenetic analysis of southeastern Europe traces major episodes of paternal gene flow among Slavic populations.

Mol Biol Evol 2005 Oct 8;22(10):1964-75. Epub 2005 Jun 8.

Institute for Anthropological Research, Amruseva 8, 10000 Zagreb, Croatia.

The extent and nature of southeastern Europe (SEE) paternal genetic contribution to the European genetic landscape were explored based on a high-resolution Y chromosome analysis involving 681 males from seven populations in the region. Paternal lineages present in SEE were compared with previously published data from 81 western Eurasian populations and 5,017 Y chromosome samples. The finding that five major haplogroups (E3b1, I1b* (xM26), J2, R1a, and R1b) comprise more than 70% of SEE total genetic variation is consistent with the typical European Y chromosome gene pool. However, distribution of major Y chromosomal lineages and estimated expansion signals clarify the specific role of this region in structuring of European, and particularly Slavic, paternal genetic heritage. Contemporary Slavic paternal gene pool, mostly characterized by the predominance of R1a and I1b* (xM26) and scarcity of E3b1 lineages, is a result of two major prehistoric gene flows with opposite directions: the post-Last Glacial Maximum R1a expansion from east to west, the Younger Dryas-Holocene I1b* (xM26) diffusion out of SEE in addition to subsequent R1a and I1b* (xM26) putative gene flows between eastern Europe and SEE, and a rather weak extent of E3b1 diffusion toward regions nowadays occupied by Slavic-speaking populations.
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http://dx.doi.org/10.1093/molbev/msi185DOI Listing
October 2005

Protein C as an early marker of severe septic complications in diffuse secondary peritonitis.

World J Surg 2005 Jun;29(6):759-65

Center for Emergency Surgery, Clinical Center of Serbia, School of Medicine, University of Belgrade, Pasteur 2 str., 11000, Belgrade, Serbia & Montenegro.

To evaluate the predictive value of protein C as a marker of severity in patients with diffuse peritonitis and abdominal sepsis, protein C levels were repeatedly determined and compared with serum levels of antithrombin III, plasminogen, alpha(2)-antiplasmin, Plasminogen activator inhibitor, D-dimer, C1-inhibitor, high molecular weight kininogen, and the C5a, C5b-9 fragments of the complement system. We carried out a prospective study from 44 patients with severe peritonitis confirmed by laparotomy and 15 patients undergoing elective ventral hernia repair who acted as controls. Analyzed biochemical parameters were determined before operations and on days 1, 2, 3, 5, 7, 10, and 14 after operations. For the study group, preoperative average protein C level was significantly lower in the patients who developed septic shock in the late course of the disease, with lethal outcome, than in the patients with severe peritonitis and sepsis who survived (p = 0.0001). In non-survivors, protein C activity remained decreased below 70%, whereas the course of survivors was characterized by increased values that were significantly higher (p < 0.03) at every time point than in those patients who died. Protein C was of excellent predictive value and achieved a sensitivity of 80% and a specificity of 87.5% in discriminating survivors from non-survivors within the first 48 hours of the study (AUC-0.917; p < 0.001), with a "cut-off" level of 66.0%. As for the control group, throughout the study period, protein C activity was permanently maintained within the range of normal, with significant differences with reference to the study group (p < 0.01). These results suggest that protein C represents a sensitive and early marker for the prediction of severe septic complications during diffuse peritonitis, and of outcome.
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http://dx.doi.org/10.1007/s00268-005-7771-7DOI Listing
June 2005
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