Publications by authors named "Lazar Davidovic"

182 Publications

Application of artificial intelligence for detection of chemico-biological interactions associated with oxidative stress and DNA damage.

Chem Biol Interact 2021 May 27;345:109533. Epub 2021 May 27.

University of Belgrade, Faculty of Medicine, Institute of Medical Physiology, Laboratory for Cellular Physiology, Visegradska 26/II, RS-11129, Belgrade, Serbia; University of Haifa, 199 Abba Hushi Blvd. Mount Carmel, Haifa, IL-3498838, Israel. Electronic address:

In recent years, various AI-based methods have been developed in order to uncover chemico-biological interactions associated with DNA damage and oxidative stress. Various decision trees, bayesian networks, random forests, logistic regression models, support vector machines as well as deep learning tools, have great potential in the area of molecular biology and toxicology, and it is estimated that in the future, they will greatly contribute to our understanding of molecular and cellular mechanisms associated with DNA damage and repair. In this concise review, we discuss recent attempts to build machine learning tools for assessment of radiation - induced DNA damage as well as algorithms that can analyze the data from the most frequently used DNA damage assays in molecular biology. We also review recent works on the detection of antioxidant proteins with machine learning, and the use of AI-related methods for prediction and evaluation of noncoding DNA sequences. Finally, we discuss previously published research on the potential application of machine learning tools in aging research.
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http://dx.doi.org/10.1016/j.cbi.2021.109533DOI Listing
May 2021

Endovascular Treatment of Aortic Bifurcation Occlusive Disease 10 Years After Open Surgical Repair of an Infrarenal Abdominal Aortic Aneurysm.

Eur J Vasc Endovasc Surg 2021 May 9;61(5):850. Epub 2021 Apr 9.

Clinic for Vascular and Endovascular Surgery, Clinical Centre of Serbia, Belgrade, Serbia.

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http://dx.doi.org/10.1016/j.ejvs.2021.02.029DOI Listing
May 2021

Open Surgical Treatment of Acute Spontaneous Isolated Abdominal Aortic Dissection.

Ann Vasc Surg 2021 Apr 6. Epub 2021 Apr 6.

Clinic for Vascular and Endovascular Surgery, Clinical Center of Serbia, Belgrade; Faculty of Medicine, University of Belgrade, Serbia.

Background: The aim of this paper is to report our single-center experience in the open surgical treatment of acute spontaneous infrarenal isolated abdominal aortic dissection (siIAAD).

Methods: This was a single center retrospective study. Between January 2015 and 2020 ten patients were treated due to acute siIAAD with open surgery. There were no patients treated for chronic siIAAD in this time period. Patients who had concomitant thoracic aortic involvement were excluded from this report.

Results: The group consisted of 7 male and 3 female patients. History of hypertension was present in nine patients and six were active smokers. The abdominal/back pain was described in 9 patients, two had acute limb ischemia and three had aortic rupture. Median dissection length was 91 mm (65.7 - 106), median distance from the lowest renal artery was 30 mm (20.7 - 49.3) and median abdominal aortic diameter was 58.5 mm (32.5 - 66.2). Supracoeliac clamp was used in three cases with a ruptured aorta and suprarenal in two patients. The mean duration of proximal clamping time was 24.3 ± 7.49 min. One patient died of postoperative acute myocardial infarction, one suffered nonfatal pulmonary embolism and one had deep venous thrombosis. No aortic-related deaths and/or reinterventions occurred during the median follow-up of 32 months.

Conclusions: Acute siIAAD is a rare event which affects mostly male smokers with hypertension. Open surgery is a technically demanding procedure with acceptable complication rates and should be performed in specialized high-volume centers for the treatment of aortic disease. Future efforts to establish a multicenter registry to evaluate the prevalence of the disease and treatment options could provide better and more comprehensive guidelines for the treatment of acute siIAAAD.
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http://dx.doi.org/10.1016/j.avsg.2021.02.035DOI Listing
April 2021

Impact of Bypass Flow Assessment on Long-Term Outcomes in Patients with Chronic Limb-Threatening Ischemia.

World J Surg 2021 Jul 17;45(7):2280-2289. Epub 2021 Mar 17.

Clinic for Vascular and Endovascular Surgery, Clinical Center of Serbia, Dr Koste Todorovica 8, 11000, Belgrade, Serbia.

Background: Transit time flow meter (TTFM) allows quick and accurate intraoperative graft assessment. The main study goal is to evaluate the influence of graft flow measurements on long-term clinical outcomes in patients with chronic limb-threatening ischemia (CLTI) undergoing bellow the knee (BTK) vein bypass surgery.

Methods: Between January 1st, 1999 and January 1st, 2006, 976 CLTI consecutive patients underwent lower extremity bypass surgery. When applying the exclusion criteria, 249 patients were included in the final analysis. Control measurements were performed at the end of the procedure. Patients were divided according to the mean (more/less than 100 ml/min) and diastolic graft flow (more/less than 40 ml/min) values in four groups. The primary endpoints were a major adverse limb event (male) and primary graft patency.

Results: After the median follow-up of 68 months, a group with the mean graft flow below 100 ml/min and the diastolic graft flow below 40 ml/min had the highest rates of male (χ = 36.60, DF = 1, P < 0.01, log-rank test) and the worst primary graft patency (χ = 53.05, DF = 1, P < 0.01, log-rank test).

Conclusion: In patients with CLTI undergoing BTK vein bypass surgery, TTFM parameters, especially combined impact of mean graft flow less than 100 ml/min and diastolic graft flow less than 40 ml/min, were associated with an increased risk of poor long-term male and primary graft patency.
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http://dx.doi.org/10.1007/s00268-021-06046-yDOI Listing
July 2021

Re "Contemporary Outcomes of Open and Endovascular Intervention for Extracranial Carotid Artery Aneurysms: A Single Centre Experience".

Eur J Vasc Endovasc Surg 2021 04 19;61(4):706-707. Epub 2021 Jan 19.

Clinic for Vascular and Endovascular Surgery, Clinical Centre of Serbia, Koste Todorovica, 8, Belgrade, Serbia.

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http://dx.doi.org/10.1016/j.ejvs.2020.12.017DOI Listing
April 2021

Comparison of Long Term Outcomes After Endovascular Treatment Versus Bypass Surgery in Chronic Limb Threatening Ischaemia Patients with Long Femoropopliteal Lesions.

Eur J Vasc Endovasc Surg 2021 02 15;61(2):258-269. Epub 2020 Dec 15.

Clinic for Vascular and Endovascular Surgery, Clinical Centre of Serbia, Belgrade, Serbia; Faculty of Medicine, University of Belgrade, Serbia.

Objective: There are currently two treatments available for patients with chronic limb threatening ischaemia (CLTI): open surgical bypass (OSB) and percutaneous transluminal angioplasty with/without stenting (PTA/S). The aim of this study was to compare short and long term outcomes between PTA/S and OSB in CLTI patients with long (GLASS grade III and IV) femoropopliteal disease.

Methods: This was a two centre retrospective study including all consecutive patients with CLTI undergoing first time lower extremity intervention at two distinct vascular surgical centres. Between 1 January 2012 and 1 January 2018, 1 545 CLTI consecutive limbs were treated for femoropopliteal GLASS grade III and IV lesions at two vascular surgical centres. Using covariables from baseline and angiographic characteristics, a propensity score was calculated for each limb. Thus, comparable patient cohorts (235 in PTA/S and 235 in OSB group) were identified for further analysis. The primary outcomes were freedom from re-intervention in the treated extremity and major amputation. Secondary outcomes were all hospital complications among the two patient groups.

Results: Total overall complication rates were significantly higher in the OSB group (20.42% vs. 5.96%, p < .001), especially wound infection/seroma rate that required prolonged hospitalisation and further treatment (7.65% vs. 0%, p < .001). After the median follow up of 61 months, re-intervention rates were significantly higher in the PTA/S group (log rank test, 44.68% vs. 29.79%, p = .002), but there was no significant difference in terms of major amputation rates between the two group of patients (log rank test, PTA/S 27.23% vs. OSB 22.13%, p = .17).

Conclusion: Bypass surgery seems to be superior to PTA/S for GLASS grade III and IV femoropopliteal lesions in patients with CLTI in terms of long term re-intervention rates, but with considerably higher rates of post-operative complications. A larger cohort of patients in currently ongoing randomised trials, as well as prospective cohort studies are necessary to confirm these findings.
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http://dx.doi.org/10.1016/j.ejvs.2020.11.009DOI Listing
February 2021

Open Vascular Surgery Education: Need for the Second Step.

Eur J Vasc Endovasc Surg 2021 01 14;61(1):155-156. Epub 2020 Nov 14.

Clinic for Vascular and Endovascular Surgery, Clinical Centre of Serbia, Belgrade, Serbia. Electronic address:

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http://dx.doi.org/10.1016/j.ejvs.2020.10.011DOI Listing
January 2021

The TAXINOMISIS Project: A multidisciplinary approach for the development of a new risk stratification model for patients with asymptomatic carotid artery stenosis.

Eur J Clin Invest 2020 Dec 2;50(12):e13411. Epub 2020 Oct 2.

Department of Materials Science and Engineering, Unit of Medical Technology and Intelligent Information Systems, University of Ioannina, Ioannina, Greece.

Introduction: Asymptomatic carotid artery stenosis (ACAS) may cause future stroke and therefore patients with ACAS require best medical treatment. Patients at high risk for stroke may opt for additional revascularization (either surgery or stenting) but the future stroke risk should outweigh the risk for peri/post-operative stroke/death. Current risk stratification for patients with ACAS is largely based on outdated randomized-controlled trials that lack the integration of improved medical therapies and risk factor control. Furthermore, recent circulating and imaging biomarkers for stroke have never been included in a risk stratification model. The TAXINOMISIS Project aims to develop a new risk stratification model for cerebrovascular complications in patients with ACAS and this will be tested through a prospective observational multicentre clinical trial performed in six major European vascular surgery centres.

Methods And Analysis: The risk stratification model will compromise clinical, circulating, plaque and imaging biomarkers. The prospective multicentre observational study will include 300 patients with 50%-99% ACAS. The primary endpoint is the three-year incidence of cerebrovascular complications. Biomarkers will be retrieved from plasma samples, brain MRI, carotid MRA and duplex ultrasound. The TAXINOMISIS Project will serve as a platform for the development of new computer tools that assess plaque progression based on radiology images and a lab-on-chip with genetic variants that could predict medication response in individual patients.

Conclusion: Results from the TAXINOMISIS study could potentially improve future risk stratification in patients with ACAS to assist personalized evidence-based treatment decision-making.
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http://dx.doi.org/10.1111/eci.13411DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7757200PMC
December 2020

Predictors of in-hospital mortality and complications in acute aortic occlusion: a comparative analysis of patients with embolism and in-situ thrombosis.

J Cardiovasc Surg (Torino) 2021 Apr 4;62(2):146-152. Epub 2020 Sep 4.

Clinic for Vascular and Endovascular Surgery, Clinical Center of Serbia, Belgrade, Serbia.

Background: Acute aortic occlusion (AAO) represents potentially fatal acute vascular emergency that requires prompt diagnosis and intervention. Clinical condition of patients with AAO is frequently severely devastated when surgical intervention is questionable. Our objective was to retrospectively review our institutional experience with AAO and assess predictors of intrahospital mortality and morbidity.

Methods: This is a retrospective single-center cohort study with prospectively collected data between January 1, 2005 and January 1, 2018. The total number of 28 consecutive patients with AAO were included in our analysis. Patients with acute aortic thrombosis manifested by bilateral acute limb ischemia were divided in two groups based on potential caues of AAO (embolism or in-situ thrombosis) differentiated according to condition of aortoilical segment.

Results: We identified 28 patients with AAO. All of them underwent either aortobifemoral bypass (N.=20, 71%) or bilateral trans-femoral thrombectomy (N.=8, 29%). The overall in-hospital mortality was 36%. Factors that influenced in-hospital mortality were: paralysis (OR=4.41, 95% CI: 1.88-21.78) and higher lactate values on admission (OR=1.23, 95% CI: 1.09-1.83), postoperative development of severe acute kidney injury (OR=3.08, 95% CI: 1.42-14.66), hemodialysis (OR=10.74, 95% CI: 1.64-109.78) and bowel ischemia (OR=5.19, 95% CI: 1.58-55.63).

Conclusions: Paralysis, higher lactate values, development of acute kidney injury, hemodialysis and bowel ischemia are predictors of worse outcome and may be used for risk stratification of patients with acute aortic occlusion and improve counseling patients and their families about expected postoperative outcomes. Patients with embolism and malignant disease have worse outcome; however, this should be tested in future studies on larger sample.
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http://dx.doi.org/10.23736/S0021-9509.20.11247-3DOI Listing
April 2021

Contemporary Treatment of Popliteal Artery Aneurysms in 14 Countries: A Vascunet Report.

Eur J Vasc Endovasc Surg 2020 Nov 15;60(5):721-729. Epub 2020 Aug 15.

Department of Surgical Sciences, Section of Vascular Surgery, Uppsala, Sweden.

Objective: Popliteal artery aneurysm (PAA) is the second most common arterial aneurysm. Vascunet is an international collaboration of vascular registries. The aim was to study treatment and outcomes.

Methods: This was a retrospective analysis of prospectively registered population based data. Fourteen countries contributed data (Australia, Denmark, Finland, France, Hungary, Iceland, Italy, Malta, New Zealand, Norway, Portugal, Serbia, Sweden, and Switzerland).

Results: During 2012-2018, data from 10 764 PAA repairs were included. Mean values with between countries ranges in parenthesis are given. The incidence was 10.4 cases/million inhabitants/year (2.4-19.3). The mean age was 71.3 years (66.8-75.3). Most patients, 93.3%, were men and 40.0% were active smokers. The operations were elective in 73.2% (60.0%-85.7%). The mean pre-operative PAA diameter was 32.1 mm (27.3-38.3 mm). Open surgery dominated in both elective (79.5%) and acute (83.2%) cases. A medial surgical approach was used in 77.7%, and posterior in 22.3%. Vein grafts were used in 63.8%. Of the emergency procedures, 91% (n = 2 169, 20.2% of all) were for acute thrombosis and 9% for rupture (n = 236, 2.2% of all). Thrombosis patients had larger aneurysms, mean diameter 35.5 mm, and 46.3% were active smokers. Early amputation and death were higher after acute presentation than after elective surgery (5.0% vs. 0.7%; 1.9% vs. 0.5%). This pattern remained one year after surgery (8.5% vs. 1.0%; 6.1% vs. 1.4%). Elective open compared with endovascular surgery had similar one year amputation rates (1.2% vs. 0.2%; p = .095) but superior patency (84.0% vs. 78.4%; p = .005). Veins had higher patency and lower amputation rates, at one year compared with synthetic grafts (86.8% vs. 72.3%; 1.8% vs. 5.2%; both p < .001). The posterior open approach had a lower amputation rate (0.0% vs. 1.6%, p = .009) than the medial approach.

Conclusion: Patients presenting with acute ischaemia had high risk of amputation. The frequent use of endovascular repair and prosthetic grafts should be reconsidered based on these results.
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http://dx.doi.org/10.1016/j.ejvs.2020.07.005DOI Listing
November 2020

Influence of preoperative statins and aspirin administration on biological and magnetic resonance imaging properties in patients with abdominal aortic aneurysm.

Vasa 2021 Feb 16;50(2):116-124. Epub 2020 Jul 16.

School of Medicine, University of Belgrade, Serbia.

: Main objective of this study was to evaluate the influence of statins and/or acetylsalicylic acid on biochemical characteristics of abdominal aortic aneurysm (AAA) wall and intraluminal thrombus (ILT). : Fifty patients with asymptomatic infrarenal AAA were analyzed using magnetic resonance imaging on T1w sequence. Relative ILT signal intensity (SI) was determined as a ratio between ILT and psoas muscle SI. Samples containing the full ILT thickness and aneurysm wall were harvested from the anterior surface at the level of the maximal diameter. The concentration of enzymes such as matrix metalloproteinase (MMP) 9, MMP2 and neutrophil elastase (NE/ELA) were analyzed in ILT and AAA wall; while collagen type III, elastin and proteoglycan 4 were analyzed in harvested AAA wall. Oxidative stress in the AAA wall was assessed by catalase and malondialdehyde activity in tissue samples. : Relative ILT signal intensity (1.09 ± 0.41 vs 0.89 ± 0.21, p = 0.013) were higher in non-statin than in statin group. Patients who were taking aspirin had lower relative ILT area (0.89 ± 0.19 vs 1.13. ± 0.44, p = 0.016), and lower relative ILT signal intensity (0.85 [0.73-1.07] vs 1.01 [0.84-1.19], p = 0.021) compared to non-aspirin group. There were higher concentrations of elastin in AAA wall among patients taking both of aspirin and statins (1.21 [0.77-3.02] vs 0.78 (0.49-1.05) ng/ml, p = 0.044) than in patients who did not take both of these drugs. : Relative ILT SI was lower in patients taking statin and aspirin. Combination of antiplatelet therapy and statins was associated with higher elastin concentrations in AAA wall.
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http://dx.doi.org/10.1024/0301-1526/a000895DOI Listing
February 2021

Long-term Durability and Safety of Carotid Endarterectomy Closure Techniques.

World J Surg 2020 10;44(10):3545-3554

Vascular Surgery Department, University Hospital of Larissa, Faculty of Medicine, School of Health Sciences, University of Thessaly, 41110, Larissa, Greece.

Background: Various techniques have been used for the execution of carotid endarterectomy; primary (PC), patch closure (CP) and eversion technique (ET).The superiority of any of them is still unproven. The aim of this study was to compare the long-term outcomes of each technique in terms of cerebrovascular event (CVE), restenosis, survival and major cardiac event (MACE).

Methods: Between 2007 and 2018, a retrospective analysis of prospectively recorded data from three European tertiary centers was undertaken including 1.357 patients. Demographics, comorbidities and medical treatment were analyzed in relation to long-term outcomes. Freedom from CVE, restenosis (> 70%), survival and MACE were estimated with Kaplan-Meier analysis curve.

Results: The mean age was 69.5 ± 8 (72% males;79% asymptomatic). 472 (35%) were treated with PC, 504 (37%) with CP and 381 (28%) with ET. Differences among groups were observed in age (P < 0.001), gender (P < 0.01), hypertension (P = 0.01), dyslipidemia (P < 0.001) and statin treatment (P < 0.001). The mean follow-up was 4.7 ± 3 years (median: 5 years). Seventy-three patients presented a CVE during 8 years of follow-up. The freedom from CVE including all techniques was 96% (SE 0.6%), 93% (SE 1%) and 89% (SE 1.6%), at 2, 5 and 8 years of follow-up, respectively, with no difference between groups (P .289). Freedom from restenosis was at 96% (SE 0.7%) and 89% (SE 5%) at 5 and 10 years, respectively, for all methods without differences. ET was associated with a higher mortality rate (P < 0.001) and MACE rate (P < 0.001).

Conclusions: Excellent outcomes were achieved with all types of closure techniques with low rates of MACE and other adverse events during long-term follow-up after CEA.
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http://dx.doi.org/10.1007/s00268-020-05604-0DOI Listing
October 2020

Vascular Injuries in Intravenous Drug Addicts-A Single-Center Experience.

Ann Vasc Surg 2020 Aug 23;67:185-191. Epub 2020 Apr 23.

Clinic for Vascular and Endovascular Surgery, Clinical Center of Serbia, Belgrade, Serbia; Faculty of Medicine, University of Belgrade, Serbia.

Background: Infected false aneurysms (IFA) caused by intravenous drug abuse are uncommon but challenging lesions. The best approach for the surgical management of this condition is still unknown. The aim is to present a single-center 14-year experience in the IFA treatment in intravenous drug abusers, thus providing additional data regarding the treatment options and outcome in these patients.

Methods: A retrospective analysis of 32 consecutive patients with vascular injuries secondary to intravenous drug abuse, during the period from January 2004 to April 2018, was performed. Data of interest were extracted from patients' medical history records, anesthesia charts, and database implemented in daily practice, or were obtained by personal contact. The diagnosis was set based on history, physical examination and/or color Doppler sonography, multidetector computed tomographic angiography, and digital subtraction angiography. The outcome included graft patency, limb amputation, and mortality.

Results: During study period, 32 heroin abusers, predominantly males (81%), were surgically treated due to vascular injuries, with mean age of 35.2 years. The vast majority of patients have had an injury of the lower extremity blood vessels (84.3%) and the common femoral artery was the most common site of injury (59.4%). Three-quarters of patients underwent resection of the false aneurysm and ligation of the artery without reconstruction of the blood vessel. In 7 cases (21.9%), arterial reconstruction was performed with overall failure rate of 42.86%. The overall mortality rate was 6.25% and the rate of extremity salvage was 96.7%.

Conclusions: The best treatment option is yet to be found, but based on the results of the present study, ligation of affected artery without revascularization seems to be an efficient, safe, and optimal treatment method, with minor risk of the extremity loss.
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http://dx.doi.org/10.1016/j.avsg.2020.02.041DOI Listing
August 2020

Besides complicated and uncomplicated dissections, do we face "potentially complicated" dissections?

J Vasc Surg 2020 05;71(5):1817

Faculty of Medicine, University of Belgrade, Belgrade, Serbia; Clinic for Vascular and Endovascular Surgery, Clinical Center of Serbia, Belgrade, Serbia.

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http://dx.doi.org/10.1016/j.jvs.2019.12.022DOI Listing
May 2020

Early and long-term results of open repair of inflammatory abdominal aortic aneurysms: Comparison with a propensity score-matched cohort.

J Vasc Surg 2020 09 2;72(3):910-917. Epub 2020 Mar 2.

Faculty of Medicine, University of Belgrade, Belgrade, Serbia; Clinic for Vascular and Endovascular Surgery, Clinical Center of Serbia, Belgrade, Serbia.

Objective: The aim of our study was to compare early and long-term results of open repair of patients with inflammatory abdominal aortic aneurysm (IAAA) with matched cohort of patients with abdominal aortic aneurysm (AAA).

Methods: This retrospective single-center cohort study used prospectively collected data from an institutional registry from 1786 patients between 2009 and 2015. Patients with IAAA and AAA were matched by propensity score analysis controlling for demographics, baseline comorbidities, and AAA parameters in a 1:2 ratio. Patients were followed for 5 years.

Results: There were 76 patients with IAAA and 152 patients with AAA. Patients with IAAA had more common intraoperative lesion of intraabdominal organs (P = .04), longer in-hospital (P = .035) and intensive care (P = .048) stays and a higher in-hospital mortality rate (P = .012). There were four patients (5.26%) with in-hospital lethal outcome in IAAA there were no deaths in the AAA group. During the follow-up, there was no difference in survival (χ = 0.07; DF = 1; P = .80) and overall aortic related complications (χ = 1.25; DF = 1; P = .26); however, aortic graft infection was more frequent in IAAA group (P = .04).

Conclusions: Open repair of IAAA is challenging and comparing to AAA carries a higher perioperative risk and long-term infection rate, even in high-volume centers. The main causes of complications are intraoperative injury of adjacent organs, bleeding, and coronary events. Patients with AAA in a matched cohort showed equal long-term survival, which should be assessed in bigger registries.
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http://dx.doi.org/10.1016/j.jvs.2019.11.040DOI Listing
September 2020

Eversion Carotid Endarterectomy : A Short Review.

J Korean Neurosurg Soc 2020 May 2;63(3):373-379. Epub 2020 Mar 2.

Clinic for Vascular and Endovascular Surgery, Clinical Center of Serbia, Belgrade, Serbia.

Carotid endarterectomy (CEA) is the main procedure in carotid surgery, as well as the most frequent vascular procedure. Two techniques of CEA are available : eversion and conventional plus patch angioplasty. Eversion CEA is anatomic procedure that reduces ischemic and total operative time. Simultaneous correction of the joined carotid kinking and coiling is possible, easy and safe, while the usage of patch is excluded. Thanks to oblique shape of anastomosis, eversion CEA is associated with low risk of long-term restenosis. The false anastomotic aneurysms occurrence is very rare, almost impossible after eversion CEA. However, the usage of carotid shunt during eversion CEA is not always simple, while proximal or distal extension of the carotid plaque can make eversion CEA more difficult and risky. Eversion CEA should be the first choice in carotid surgery. Conventional CEA is indicated in cases when carotid plaque is extended more than usual, as well as, if the usage of carotid shunt is necessary.
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http://dx.doi.org/10.3340/jkns.2019.0201DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7218199PMC
May 2020

Magnetic resonance imaging assessment of proteolytic enzyme concentrations and biologic properties of intraluminal thrombus in abdominal aortic aneurysms.

J Vasc Surg 2020 09 14;72(3):1025-1034. Epub 2020 Feb 14.

School of Medicine, University of Belgrade, Belgrade, Serbia; Clinic for Vascular and Endovascular Surgery, Clinical Center of Serbia, Belgrade, Serbia.

Objective: The aim of the study was to determine whether magnetic resonance imaging (MRI) can be used in assessment of biologic activity of intraluminal thrombus (ILT) and proteolytic processes of the abdominal aortic aneurysm wall.

Methods: Using MRI, 50 patients with asymptomatic infrarenal abdominal aortic aneurysm were analyzed at the maximum aneurysm diameter on T1-weighted images in the arterial phase after administration of contrast material. Relative ILT signal intensity (SI) was determined as the ratio between ILT SI and psoas muscle SI. During surgery, the full thickness of the ILT and the adjacent part of the aneurysm wall were harvested at the maximal diameter for biochemical analysis. The concentrations of matrix metalloproteinase 9 and neutrophil elastase (NE/ELA) were analyzed in harvested thrombi, and the concentrations of collagen type III, elastin, and proteoglycans were analyzed in harvested aneurysm walls.

Results: A significant positive correlation was found between the NE/ELA concentration of the ILT and the relative SI (ρ = 0.309; P = .029). Furthermore, a negative correlation was observed between the elastin content of the aneurysm wall and the relative SI (ρ = -0.300; P = .034). No correlations were found between relative SI and concentration of matrix metalloproteinase 9, NE/ELA, collagen type III, or proteoglycan 4 in the aneurysm wall.

Conclusions: These findings indicate a potential novel use of MRI in prediction of thrombus proteolytic enzyme concentrations and the extracellular matrix content of the aneurysm wall, thus providing additional information for the risk of potential aneurysm rupture.
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http://dx.doi.org/10.1016/j.jvs.2019.11.032DOI Listing
September 2020

Effect of Intra-operative Intra-arterial Thrombolysis on Long Term Clinical Outcomes in Patients with Acute Popliteal Artery Aneurysm Thrombosis.

Eur J Vasc Endovasc Surg 2020 02 6;59(2):255-264. Epub 2020 Jan 6.

Clinic for Vascular and Endovascular Surgery, Clinical Centre of Serbia, Belgrade, Serbia; Faculty of Medicine, University of Belgrade, Belgrade, Serbia.

Objective: Acute lower limb ischaemia (ALI) as a result of popliteal artery aneurysm (PAA) thrombosis represents a significant problem. The aim of this study was to investigate outcome of intra-operative intra-arterial thrombolysis in the treatment of acute ischaemia due to PAA thrombosis in terms of major adverse limb events (MALE), overall survival, and intrahospital complications, especially those associated with bleeding.

Methods: A total of 156 patients with Rutherford grade IIa and IIb acute ischaemia resulting from PAA thrombosis were admitted between 1 January 2011 and 1 January 2017. The patients were divided into two groups, those who underwent additional treatment with intra-operative intra-arterial thrombolysis (20 patients), and those who did not (136 patients). By using covariables from baseline and angiographic characteristics, a propensity score was calculated for each patient. Each patient who underwent intra-operative thrombolysis was matched to four patients from the non-thrombolysis group. Thus, comparable patient cohorts (20 in the thrombolysis and 80 in the non-thrombolysis group) were identified for further analysis. The primary end point was MALE and the secondary endpoint all cause mortality.

Results: After a median follow up of 55 months, the estimated MALE rate was significantly lower in the thrombolysis group (30% vs. 65%, chi square = 10.86, p < .001, log rank test). Also, patients in the thrombolysis group had a significantly lower mortality rate (20% vs. 42.65%, chi square = 3.65, p = .05, log rank test). The thrombolysis group had wound/haematoma related interventions performed more commonly (25% in thrombolysis vs 8%, in non-thrombolysis group), but the difference was not significant (p=.013). There were no cases of major (intracranial and gastrointestinal) bleeding in either group.

Conclusion: The data suggest that intra-operative thrombolysis in the treatment of selected patients with ALI due to PAA thrombosis has long term MALE and overall survival benefits, without a significant risk of major, life threatening bleeding complications.
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http://dx.doi.org/10.1016/j.ejvs.2019.10.013DOI Listing
February 2020

Superior Thyroid Artery Perforation During Carotid Artery Stenting.

Eur J Vasc Endovasc Surg 2020 02 30;59(2):294. Epub 2019 Dec 30.

Clinic for Vascular and Endovascular Surgery, Clinical Centre of Serbia, Serbia; Faculty of Medicine, University of Belgrade, Serbia.

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http://dx.doi.org/10.1016/j.ejvs.2019.11.013DOI Listing
February 2020

Late open conversion after endovascular abdominal aortic aneurysm repair: experience of three-high volume centers.

J Cardiovasc Surg (Torino) 2020 04 18;61(2):183-190. Epub 2019 Nov 18.

Unit of Vascular and Endovascular Surgery, San Martino University Hospital IRCCS, University of Genoa, Genoa, Italy.

Background: Accumulated endovascular aneurysm repair (EVAR) procedures will increase number of patients requiring conversion to open repair of abdominal aortic aneurysms (AAA). In most cases, patients undergo late open surgical conversion (LOSC), many months, or years, after initial EVAR. The aim of this study is to analyze results of LOSC after EVAR in elective and urgent setting, including presenting features, surgical techniques, as well as to review the clinical outcomes and their predictors.

Methods: Retrospective review of all consecutive patients undergoing LOSC after EVAR was performed at three distinct, high volume, vascular centers. Patients that required primary conversion within 30 days after EVAR have not been included in this study. Between January 1st 2010 and January 1st 2017 total of 31 consecutive patients were treated. LOSC were performed either in elective or in urgent setting, thus dividing patients in two groups. Primary outcome was 30-day mortality and secondary postoperative complications.

Results: LOSC rate after EVAR was 4.51%. Most common indication for LOSC was type I endoleak (N.=20, 64.51%). All patients that presented with ruptured AAA had some form of endoleak (type I endoleak was present in five from six cases). Most common site for aortic cross-clamping was infrarenal (51.61%). Stent-graft was removed completely in 18 patients (58.06%) and partially in 13 (41.93%). 30-day mortality rate was 16.12% (5 patients) and most common cause of death was myocardial infarction (60%). Following univariate factors were isolated as predictors for 30-day mortality: preoperative coronary artery disease, chronic obstructive pulmonary disease, urgent LOSC, prolonged time until LOSC, ruptured AAA, supraceliac clamp, higher number of red blood cell transfusion, postoperative myocardial infarction, and prolonged intubation (more than 48 hours).

Conclusions: LOSC seems to be safe and effective procedure when preformed in elective manner. On the other side, urgent LOSC after EVAR is associated with very high postoperative mortality and morbidity. Endoleak remains the main indication for open conversion. Further studies are necessary to standardize timing and treatment options for failing EVAR.
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http://dx.doi.org/10.23736/S0021-9509.19.10972-XDOI Listing
April 2020

Primary Aorto-Appendicular Fistula Accompanied by Infected Penetrating Aortic Ulcer - Case Report.

Ann Vasc Surg 2020 May 31;65:283.e1-283.e5. Epub 2019 Oct 31.

Clinic for vascular and endovascular surgery, Clinical Center of Serbia, Belgrade, Serbia; Faculty of Medicine, University of Belgrade, Belgrade, Serbia.

Primary aorto-appendicular fistulas are extremely rare in clinical practice, and there are only 3 such cases reported in the available literature. The aim of this study is to present the case of a 68-year-old female patient with primary aorto-appendicular fistula accompanied by infected penetrating aortic ulcer (PAU). At the time of her hospital admission, the patient did not demonstrate any typical symptoms. Multidetector computed tomography imaging of aorta was performed during an additional preoperative examination and the PAU of the infrarenal aortic segment was detected. Other pathological changes were not found. The intraoperative findings confirmed the presence of the PAU firmly attached to the appendix and surrounding signs of inflammation. Appendectomy and partial resection of the PAU were performed, along with aortic reconstruction, using a Dacron tube graft and right renal artery reattachment. During the postoperative period, there were no complications, and the patient was discharged on the 10th postoperative day. Control medical examination and color duplex ultrasonography were performed 18 months after the surgery and they provided satisfactory results.
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http://dx.doi.org/10.1016/j.avsg.2019.10.071DOI Listing
May 2020

Endovascular treatment of different types of iliac occlusions-Results from an observational study.

PLoS One 2019 2;14(10):e0222893. Epub 2019 Oct 2.

School of Medicine, Belgrade University, Belgrade, Serbia.

Objective: The aim of this study was to evaluate the results of endovascular therapy on the treatment of different types of iliac occlusions.

Materials And Methods: A bi-center prospective, non-randomized study was conducted on 100 patients (mean age 59.14 ± 8.53; 64 men) who underwent endovascular treatment of iliac occlusive disease between January 2013 and November 2017. We evaluated baseline data, procedure, and follow-up results for the entire group, and according to Trans-Atlantic Inter-Society Consensus (TASC II) classification. The majority of patients (60%) were treated for severe claudication; 56 (56%) patients had TASC B occlusions, 28 patients TASC C, and 16 patients TASC D.

Results: The mean length of the occluded segments was 61.41 ± 35.15 mm. Procedural complications developed in 6 patients (6%). Mean ankle-brachial pressure index increased from 0.40 ± 0.12 preoperatively to 0.82 ± 0.16 postoperatively. The mean follow-up was 33.18 ± 15.03 months. After 1 and 5 years, the primary patency rates were 98% and 75.1%, and the secondary patency rate was 97% respectively. Regarding occlusion complexity there were no statistical significant differences in primary patency rates (TASC B vs. C vs. D: p = 0.19). There were no statistically significant differences in primary patency rates between patients in different clinical stages, as well as between the type of stents, and location of the occlusion.

Conclusion: In our study, endovascular treatment for iliac artery occlusions proved to be a safe and efficient approach with excellent primary and secondary patency rates regardless of the complexity of occlusions defined by TASC II classification. This study is aligned with the notion that in well selected patients, endovascular therapy can be the treatment of choice even in complex iliac lesions if performed by experienced endovascular interventionists in high volume centers.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0222893PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6774573PMC
March 2020

Potential Application of Diffusion-Weighted Whole-Body Imaging with Background Body Signal Suppression for Disease Activity Assessment in Takayasu Arteritis-In Search of the "Golden Mean": Case Report.

Ann Vasc Surg 2019 Nov 31;61:468.e9-468.e12. Epub 2019 Jul 31.

Department of Vascular Surgery, Tashkent Medical Academy, Tashkent, Uzbekistan. Electronic address:

The case report describes our first experience of "diffusion-weighted whole-body imaging with background body signal suppression" (DWIBS) application for disease activity assessment in a young female patient with Takayasu arteritis (TA). Despite the normal level of inflammatory markers, clinical signs of disease recurrence were present. In our case, DWIBS did not only help to identify the disease recurrence in the patient with false-negative inflammatory markers but also revealed new foci involved in the TA process. DWIBS can be a potentially new imaging method, useful during the follow-up in patients with TA.
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http://dx.doi.org/10.1016/j.avsg.2019.04.044DOI Listing
November 2019

Single center experience in the management of a case series of subclavian artery aneurysms.

Asian J Surg 2020 Jan 18;43(1):139-147. Epub 2019 May 18.

Clinic for Vascular and Endovascular Surgery, Clinical Center of Serbia, Belgrade, Serbia.

Objective: Subclavian artery aneurysms (SAAs) are rare, but they may cause life- and limb-threatening complications.

Methods: Retrospective review was performed of all SAA patients that underwent treatment at the Clinic for Vascular and Endovascular Surgery, Clinical Center of Serbia, Belgrade between January 1st 2006 and January 1st 2018. The paper includes analysis of etiology and therapeutic options based on the experience from our institution.

Results: Twenty (80%) of SAAs involved extrathoracic (ET), while five (20%) intrathoracic (IT) segment. Out of total five IT SAAs, two were asymptomatic (40%), one had dyspnea (20%), while two (40%) had hematothorax due to rupture. Seven (35%) patients with ET SAA had shoulder pain and pulsatile mass, five (25%) acute, seven (35%) had chronic limb ischemia, while one was asymptomatic (5%). Two IT SAAs were treated with open surgery (OS). Other three cases underwent hybrid procedure. One case with ET SAA was treated endovascularly due to hostile anatomy, while in all other 19 cases of ET SAAs open repair was performed, which included: graft interposition in 10 (52.63%), end-to-end anastomosis in 7 (36.84%) cases, while bypass procedure in 2 (10.52%) patients. One of our patients (4%) died during the first 30 postoperative days.

Conclusions: SAAs are rare, however because of their natural history they have huge clinical significance. OS is the method of choice in cases of ET SAAs caused by TOS. Endovascular and hybrid treatment decrease significantly perioperative morbidity and mortality rates in cases of intrathoracic SAAs and thus should be the first option.
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http://dx.doi.org/10.1016/j.asjsur.2019.04.012DOI Listing
January 2020

Phase 2, randomized, open-label study on catheter-directed thrombolysis with plasmin versus rtPA and placebo in acute peripheral arterial occlusion.

J Drug Assess 2019 9;8(1):43-54. Epub 2019 Apr 9.

Department of Radiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.

Patients with acute peripheral arterial occlusion (aPAO) are candidates for operative thrombectomy, bypass, or catheter-directed thrombolysis (CDT) using a plasminogen activator. Human plasma-derived plasmin may offer another CDT option. To evaluate the efficacy, safety, and tolerability of two intrathrombus delivery methods and two doses of plasmin compared with recombinant tissue plasminogen activator (rtPA) and placebo in patients with aPAO. This was a phase 2, randomized, open-label study of intra-arterial CDT of plasmin in patients with aPAO. The study used infusion catheters with or without balloon occlusion (BOC) to evaluate 150 mg plasmin (2 and 5 h post-infusion) and 250 mg plasmin (5 h post-infusion). The efficacy of plasmin, rtPA and placebo was assessed. One hundred and seventy-four subjects were enrolled. Overall, the thrombolytic efficacy (>50% thrombolysis) was 59% (58/99) for 150 mg plasmin without BOC, which is comparable to 89% (8/9) for rtPA without BOC ( = 0.149) and 40% (2/5) for placebo control ( 0.648). The thrombolytic efficacy was 33% of the 250 mg plasmin group. There was no difference ( > 0.999) in thrombolytic efficacy with BOC (59%, 58/99) or without BOC (59%, 17/29). Plasmin-treated groups experienced treatment-emergent adverse events (TEAEs) at 71% (76/107) without BOC and 63% (24/38) with BOC; 78% (7/9) of the rtPA-treated group and 89% (8/9) of the placebo group had TEAEs. Serious AEs (SAEs) occurred in 29% (31/107) of the 150 mg plasmin group without BOC and 24% (9/38) with BOC. No SAEs occurred in the 250 mg plasmin group. Plasmin demonstrated less bleeding during catheter-directed administration at 150 mg and 250 mg doses compared to rtPA. BOC utilization did not improve efficacy. CDT with plasmin has a potential thrombolytic benefit in patients presenting with aPAO. NCT01222117.
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http://dx.doi.org/10.1080/21556660.2019.1586402DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6493290PMC
April 2019

Treatment of pediatric vascular injuries: the experience of a single non-pediatric referral center.

Int Angiol 2019 Jun 15;38(3):250-255. Epub 2019 Apr 15.

Faculty of Medicine, University of Belgrade, Belgrade, Serbia.

Background: Pediatric peripheral vascular trauma carries significant risk of complications including limb loss and long-term invalidity. Mechanisms and types of morphological lesions are very diverse. The objectives of this study are to present the experience of a single vascular center in the surgical approach to pediatric vascular injuries, and to analyze the main challenges related to this clinical entity.

Methods: Over a period of 25 years, 17 pediatric peripheral vascular injuries were treated in our institution. Patient's age ranged between one day (newborn) and 15 years (mean: 10.7 years). There were five injuries of upper and 12 injuries of the lower extremity. Preoperative diagnosis was established by clinical examination (N.=4), ultrasonography (N.=1) and angiography (N.=12). Blunt trauma mainly caused arterial thrombosis while penetrating trauma caused arterial laceration or complete transection. Five patients had associated orthopedic injuries (29,4%). There were two posttraumatic pseudoaneurysms and two arterio-venous fistulas.

Results: There was no perioperative mortality. Vascular reconstructions included arterial suture (N.=4), thrombectomy + patch angioplasty (N.=1), termino-terminal anastomosis (N.=3), venous anatomic bypass (N.=6), PTFE graft reconstruction (N.=2), and venous extra-anatomic reconstruction (N.=1). Two patients had associated venous injury demanding both arterial and venous reconstruction. In the only case of war trauma treatment ended with limb loss. Other reconstructions presented good early and long-term patency.

Conclusions: Pediatric vascular injuries are extremely challenging issues. Treatment includes broad spectrum of different types of vascular reconstructions. It should be performed by vascular surgeon trained in open vascular treatment or pediatric surgeon with significant experience in vascular surgery.
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http://dx.doi.org/10.23736/S0392-9590.19.04124-5DOI Listing
June 2019

Transesophageal Echocardiography-Guided Thrombectomy of Level IV Renal Cell Carcinoma without Cardiopulmonary Bypass.

Braz J Cardiovasc Surg 2019 Mar-Apr;34(2):229-232

Clinic for Vascular and Endovascular Surgery, Clinical Center of Serbia, Belgrade, Serbia.

Advanced renal cell carcinoma accompanied by tumor thrombus in the venous system is present in up to 10% of cases. Extension of tumor thrombus above the diaphragm or into the right atrium represents level IV disease. Level IV tumors are typically treated with sterno-laparotomy approach with or without deep hypothermic circulatory arrest and veno-venous bypass. In this case report, the surgical technique for the resection of advanced RCC were described, with the concomitant use of transesophageal echocardiography for thrombus extraction without the veno-venous or cardiopulmonary bypass.
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http://dx.doi.org/10.21470/1678-9741-2018-0216DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6436781PMC
June 2019

An Isolated Aneurysm of the Abdominal Aorta in a Patient with Marfan Syndrome-A Case Report.

Ann Vasc Surg 2020 Feb 11;63:454.e1-454.e4. Epub 2019 Feb 11.

Clinic for Vascular and Endovascular Surgery, Clinical Center of Serbia, Belgrade, Serbia; School of Medicine, University of Belgrade, Serbia.

We present a case of successfully treated abdominal aortic aneurysm in a 24-year-old patient with Marfan syndrome. After initial physical and ultrasound examination, the multislice computed tomography (MSCT) scan revealed infrarenal aortic aneurysm of 6 cm in diameter, 10 cm long, along with slightly dilated iliac arteries. However, dimensions of aortic root, aortic arch, and descending suprarenal aorta were within normal limits. Further on, because the patient presented with signs of impending rupture, an urgent surgical intervention was performed. The patient was discharged in good general medical condition 7 days after surgery. After 6 months of follow-up, the patient's condition was satisfying and no MSCT signs of further aortic dissection/aneurysm were identified. To the best of our knowledge, a case of successful management of a patient with Marfans syndrome and truly isolated infrarenal and symptomatic abdominal aortic aneurysm has not been described in the literature before.
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http://dx.doi.org/10.1016/j.avsg.2018.11.019DOI Listing
February 2020