Quantitative analysis of selected genetic markers of induced brain stroke ischemic tolerance detected in human blood.

A brain stroke is a serious disease and the second leading cause of death in the European Union. Carotid stenosis accounts for 15% of all ischemic cerebral strokes. However, there is currently no effective screening for carotid disease. Analysis of the DNA from peripheral blood is increasingly being used for several disease diagnoses. The potentially beneficial therapeutic method of inducing tissue tolerance to ischemia has so far been studied mainly in animal models. The aim of this study is to investigate changes in the gene expression of selected markers of brain ischemia during carotid endarterectomy, considered in this study as an activator of ischemic tolerance. During the carotid endarterectomy, there is a short-term occlusion of the internal carotid artery. Using the RT-qPCR method, we detected changes in the early identified gene markers of brain ischemia (ADM, CDKN1A, GADD45G, IL6, TM4SF1) in peripheral blood during sub lethal cerebral ischemia caused by carotid endarterectomy. Patients underwenting surgical procedure were divided into three groups: asymptomatic, symptomatic, and those who underwent carotid endarterectomy after an acute stroke. The results were compared to a negative/control group. Carotid endarterectomy had an impact on the expression of all monitored biomarkers. We observed statistically significant changes (p value 0.05-0.001) when comparing the groups among themselves, as well as the presence of ischemic tolerance of brain tissue to ischemic attacks. In conclusion, ADM, GADD45G, and TM4SF1 were affected in symptomatic patients, GADD45G and IL6 in acute patients, and CDKN1A and ADM in asymptomatic group after application of carotid endarterectomy.

Modifications of gene expression detected in peripheral blood after brain ischemia treated with remote postconditioning.

BACKGROUND: A stroke is an acute damage to a certain area of a nerve tissue of the brain. In developed countries, it ranks second among the most often causes of death and is also the leading cause of disability. Recent findings emphasize the significant neuroprotective effect of conditioning on the course and rate of recovery after ischemic attack; however the molecular mechanism of ischemic tolerance induced by conditioning is still not completely explored. METHODS AND RESULTS: The purpose of this study is an identification of changes in gene expression induced by stimulation of reaction cascades after activation of the neuroprotective mechanism using an experimental rat model of global ischemia. The induction of neuroprotective cascades was stimulated by the application of early and delayed form of remote ischemic postconditioning. The quantitative qRT-PCR method was used to assess the rate of change in ADM, BDNF, CDKN1A, CREB, GADD45G, IL6, nNOS, and TM4SF1 gene expression levels 72 h after ischemic attack. The detected results confirm the neuroprotective effect of both forms of postconditioning. Participation of neuroprotection-related gene expression changes was observed once as an early one (CREB, GADD45G), once as a delayed one (ADM, IL6), or both (BDNF, CDKN1A, nNOS, TM4SF1) postconditioning forms, depending on the particular gene. CONCLUSIONS: Our results characterize impact of ischemic tolerance on the molecular level. We predict ischemic tolerance to be consisted of complex combination of early and delayed remote postconditioning.

Hypothesis of "stroke-stop" formula: a tool for risk index determination in development of acute cerebrovascular disease in asymptomatic individuals with carotid stenosis.

BACKGROUND: Extracranial carotid artery disease is considered a risk factor for developing acute cerebrovascular diseases. The paper suggests the "Stroke-Stop" formula as hypothesis for the determination of the risk of developing stroke in asymptomatic individuals with carotid stenosis. The formula is based on a mathematical calculation of the major risk factors for stroke: the degree of ICA (internal carotid artery) stenosis, the morphological structure of the atherosclerotic plaque and the level of lipoprotein-associated phospholipase A2 (Lp-PLA2) concentration. METHODS: The cross sectional study included 70 patients with atherosclerotic ICA stenosis. Among vascular inflammatory markers, Lp-PLA2 was determined with concentration 252.7-328.6 mg/l. The obtained results were evaluated using descriptive statistics (the frequency, percentage ratio) as well as the one-way analysis of variance (ANOVA) and chi-square test. RESULTS: The risk of stroke development is eminently increasing with the progression of ICA stenosis and elevation of Lp-PLA2 levels. In patients with echolucent plaque, the risk of stroke development was significantly higher in correlation with patients with echogenic plaque. Based on calculations using "Stroke-Stop" formula, three main groups were generated: low (< 70 points), medium (70-100 points) and high (> 100 points) risk of stroke development. CONCLUSIONS: Hypothesis of "Stroke-Stop" formula is proposed for better selection of patients who should be indicated for surgical treatment and will be evaluated in prospective study. In order to verify this hypothesis, we plan to do prospective study using "Stroke-Stop" formula for ipsilateral annual stroke rate in asymptomatic individuals with carotid stenosis who receive conservative therapy.

Predictors of outcome events and 6-year mortality after carotid endarterectomy and carotid stenting in patients with carotid artery stenosis.

AIM: The aim of our study was to evaluate the results of CEA and CAS in patients with carotid artery stenosis, and their effect on long-term mortality and morbidity, as well as to identify predictors of long-term mortality in a single-centre observational study. CLINICAL RATIONALE: While data on short-term morbidity and mortality after carotid endarterectomy (CEA) and carotid stenting (CAS) is robust, there is only a limited amount of literature on long-term mortality and its predictors five years-plus post these procedures. MATERIAL AND METHODS: Consecutive patients with symptomatic and asymptomatic internal carotid artery stenosis treated with CEA or CAS in a single centre in eastern Slovakia between 2012 and 2014 were included. We recorded basic sociodemographic data, the presence of co-morbidities and periprocedural complications. Clinical and sonographic follow-up was performed three and 12 months after the procedures. Patient survival data and any stroke data was obtained at the end of a six-year follow-up. RESULTS: We included 259 patients after CEA (mean age 67.4 ± 8.5, 64.5% men) and 321 after CAS (mean age 66.9 ± 8.4, 73.5% men). We did not identify a statistically significant difference in short-term or long-term mortality, survival times, or the presence of short-term or long-term complications between the CEA and CAS groups. Predictors of long-term mortality included age and diabetes mellitus in both cohorts. Repeated interventions were related to increased mortality only in the CAS cohort. CONCLUSIONS: The results of our study show that long-term mortality does not differ between CEA and CAS.

Interdisciplinary Management of Visceral Artery Aneurysms and Visceral Artery Pseudoaneurysms.

The paper presents the results of treating 14 patients, namely eight patients with visceral artery aneurysms and six patients with visceral artery pseudoaneurysms. In 64.3% of the patients, the initial diagnosis was made based on the ultrasound examination. All the patients (100%) underwent CT angiography, while angiography was performed in 71.4% of the cases. Five (35.7%) patients with visceral artery pseudoaneurysms were emergently hospitalized; among them, the signs of bleeding were observed in 2 patients. In 9 patients, pathology was detected during tests for other conditions. Five (35.7%) patients underwent endovascular treatment, while 9 (64.3%) patients received surgical treatment. Endovascular interventions and open surgery demonstrated a nil mortality rate. After endovascular treatment, stent thrombosis was found in 1 patient. In the case of surgical treatment, visceral artery aneurysm was observed in 1 patient who underwent the resection of superior mesenteric artery pseudoaneurysm. Conclusions. The choice of the method of treating visceral artery aneurysms and visceral artery pseudoaneurysms depends on the location, size, anatomic features of the visceral arteries and the clinical course of the disease. Both endovascular and surgical treatment demonstrate good postoperative outcomes. Visceral ischemia is one of the most serious complications in the postoperative period, which can complicate both the diagnosis and the choice of treatment tactics.

[Non-traumatic arteriovenous malformation of the spleen with fatal hemorrhage]. / Non-traumatická arteriovenózna malformácia sleziny s fatálnym krvácaním.

From the medical point of view, splenic rupture developed either as a result of traumatic injury or as a result of any type of splenic disease represents a very severe and life-threatening condition. We describe the case of a 65-year old man without any obvious traumatic injury who was hospitalised because of left abdominal pain. Investigations performed at admission to the hospital (RTG, USG) failed to indicate any signs of intraabdominal bleeding. However, the patient died suddenly after 24 hours of hospitalisation. At autopsy massive intraabdominal bleeding was found. It was caused by rupture of splenic intraparenchymal hematoma developed as a result of an arteriovenous malformation in the lower pole of the spleen. This case shows the necessity of knowledge of all circumstances of death as well as the necessity of consistent histological investigation of the spleen in such cases.

[Traumatic pseudoaneurysm of descendent thoracic aorta solved by aortal stentgraft repair followed by development of fatal aortoesophageal fistula]. / Traumatická pseudoaneuryzma descendentnej torakálnej aorty riesená aortálnym stentgraftom s následnou fatálnou aortoezofageálnou fistulou.

Traumatic pseudoaneurysms are relatively frequently mentioned in textbooks of pathology and forensic medicine but their incidence in pathological reports is seldom documented. Our described case presented a patient who suffered from chronic alcoholism and who was repeatedly hospitalised because of various injuries including epidural and subdural hematomas. We present a case of a 69-year-old man who was hospitalised after nonspecific blunt chest injury with chest pain and dysphagia. By computed tomography the traumatic pseudoaneurysm of the descendent thoracic aorta was diagnosed pressing the oesophageal wall which was solved by implantation of aortal stent graft (TEVAR - thoracic endovascular aortic/aneurysm repair). Since after the implantation there was no blood leak, no progression of the lesion, he was soon discharged from hospital. The patient was hospitalised again after two months for newly developed haemoptysis. On suspicion of bleeding from aortal arch a carotid-carotid bypass from right to left side was performed and then re-TEVAR was implanted proximally to the first one. The man died two days following the implantation after a massive bleeding from oesophagus due to aortoesophageal fistula. The presented case deals with the etiology of the development of pseudoaneurysms, histomorphological picture of pseudoaneurysm resembling not only an isolated thoracic aortitis but slightly also the Takayashu disease. We suppose that in this case the most probable cause of necrosis and perforation of aortal wall was a decubital necrosis caused by stent graft which led to the fatal aortoesophageal necrosis. Aortoesophageal fistula belongs to the most common lethal complications of the TEVAR.

Obturator artery injury after hip fracture surgery.

We present the case of a 55-year-old woman who sustained a left femoral neck fracture which was managed by insertion of a dynamic hip screw. Six hours after surgery, distension appeared in the left lower quadrant of her abdomen associated with a decline in haemoglobin concentration and clinical signs of ongoing bleeding. Computed tomography showed a left retroperitoneal mass without concomitant extravasation of contrast material. Exploratory laparotomy revealed a damaged left obturator artery with a large haematoma in its vicinity. After arterial ligation and retroperitoneal space decompression her postoperative course was uneventful. Reviewing intraoperative C arm images a 0.8 cm protrusion of the threaded guide wire was identified as the cause of obturator artery damage.