Immunohistochemical analysis of MMP-9 and COX-2 expression in carotid atherosclerotic plaques among patients undergoing carotid endarterectomy: A prospective study.

BACKGROUND: Matrix metalloproteinase-9 protein (MMP-9) and cyclooxygenase-2 (COX-2) proteins may have a role in remodelling of atherosclerotic plaques. We analysed and compared the radiological, histological and immunohistochemical characteristics of carotid atherosclerotic plaques between symptomatic and asymptomatic patients who underwent carotid endarterectomy (CEA). METHODS: This prospective single-blinded study included 31 patients (70 [64-75] years, 58% males, 42% symptomatic) who underwent CEA and a total of 155 carotid plaque sections that were analysed. Preoperative assessment and multimodality diagnostic imaging with magnetic resonance imaging (MRI) or computed tomography angiography (CTA), histological and immunohistochemical analyses of carotid plaques including the expression of MMP-9 and COX-2 proteins were performed. RESULTS: Symptomatic and asymptomatic patients did not significantly differ in respect to preoperative characteristics. Unstable plaques were detected in 12/13 (92.3%, p = 0.020) symptomatic patients using MRI or CTA. There was no perioperative mortality and perioperative outcomes were comparable in both groups. A significantly higher expression of MMP-9 in macrophages was observed among symptomatic patients (p = 0.020). ROC curve analysis showed statistically significant associations of both the higher intensity of COX-2 staining in CD68 PG-M1 positive macrophages (area under the curve [AUC]=0.701, p = 0.014) and higher MVD (AUC=0.821, p < 0.001) within the plaque with cerebrovascular symptoms. The expression of COX-2 and the intensity of COX-2 staining in macrophages within the unstable carotid plaques detected by preoperative MRI or CTA were significantly higher (76.1% vs. 40.0%, p = 0.038; 76.2% vs. 30.0%, p = 0.01, respectively). CONCLUSIONS: Advanced non-invasive multimodality diagnostic imaging including MRI or CTA is reliable in differentiating unstable from stable carotid plaques. High expression of MMP-9 and COX-2 in macrophages within the symptomatic plaque is associated with increased risk of cerebrovascular complications. TRIAL REGISTRATION: This study has been registered at the ISRCTN registry (ID ISRCTN46536832), isrctn.org Identifier: https://www.isrctn.com/ISRCTN46536832.

Effects of Secondary Porosity on Microstructure and Mechanical Properties of SAP-Containing Lime-Based Plasters.

Despite the many benefits associated with the utilization of superabsorbent polymers (SAPs), several drawbacks have been reported. In particular, the effect of SAPs on microstructure, together with its consequences for mechanical properties, is not fully understood yet for some composite materials. This study analyzes the role of SAPs in the formation of the microstructure of lime composites, taking into account their chemical composition. The obtained experimental results show that the particle size and cross-linking density of used SAPs are crucial parameters affecting both the microstructure and mechanical performance of the analyzed composites. Coarser SAPs with low cross-linking density in the dosage of 0.5 and 1 wt.% are found as the most suitable solution, leading even to a slight improvement of mechanical parameters. The secondary porosity formed by swelled hydrogels is identified as a very significant factor since hydrogel-filled voids do not contribute to the strength parameters. The formation of the affected zone around SAP cores depends on the chemical composition of SAPs considerably as the higher cross-linking density influences the desorption rate. Based on achieved results, utilization of SAPs in building materials should be studied at a more detailed level with particular importance on the definition of SAP-related voids and affected zone around SAP particles.

Cardiomyocytes calpain 2 expression: Diagnostic forensic marker for sudden cardiac death caused by early myocardial ischemia and an indicator of the duration of myocardial agonal period?

Sudden cardiac death (SCD) is an unexpected natural death of cardiac etiology and occurs within one hour of the onset of cardiac symptoms in an apparently healthy subject or within 24 h if death is not witnessed. The diagnosis of early myocardial ischemia (EMI) or acute myocardial infarction (AMI) after death is a challenge for forensic pathologists especially when death occurs in a short period of time after the onset of myocardial ischemia. Disorder of cardiomyocytes Ca2+ homeostasis caused by myocardial ischemia during SCD can lead to the activation of calcium-activated non-lysosomal cysteine protease, including calpains. They serve as a proteolytic unit for cell balance and also participate in the processes of apoptosis and necrosis. Agony is a period that precedes somatic death that differs from cellular agony which may evolve for hours after somatic death lasting differently depending on the cell type and mechanism of death. We hypothesize that the expression of calpain 2 in cardiomyocytes could be a specific and sensitive diagnostic forensic marker for SCD caused by EMI and an indicator of the duration of myocardial agonal period. We will conduct a retrospective study that will prove this hypothesis on the respondents who died of SCD by EMI and AMI, instant death by head gunshot and hanging. There is no data on such an analysis in the available literature. The standard hematoxylin-eosin staining will be used to detect cardiac tissue damage. The expression of calpain 2 in cardiomyocytes will be analyzed immunohistochemically. In SCD caused by EMI we expect lower level of calpain 2 expressionin comparison to AMI due to shorter duration of dying. Similar, we predict in the remote region lower calpain 2 expression than in the region of ischemia for both EMI and AMI. In instant death caused by perforating traumatic brain injury we expect mild or no calpain 2 expression throughout the whole myocardium because of very short (immediate) duration of dying. In death caused by hanging calpain 2 expression throughout the whole myocardium should be strong because of longer cellular agonal period. We expect that our results would indicate the immediate activation of calpain 2 in different causes of cardiomyocytes death. From the degree of expression of calpain 2 we could conclude about the duration of cardiomyocytes agony so calpain 2 could be used as a marker for the assessment the duration of somatic and cellular agony.

Decrease of Perforin Expressing Lymphocytes after On-Pump Coronary Artery Bypass Grafting Surgery Irrespective of Carbohydrate Preoperative Oral Feeding.

BACKGROUND: Coronary artery bypass grafting (CABG) surgery continues to be the gold standard for treating the patients with coronary artery disease. CABG surgery can be performed on or off cardiopulmonary bypass, termed as on-pump or off-pump CABG, respectively. It has been shown that CABG surgery, preferably on-pump CABG surgery, leads to the changes of cell immunity during perioperative and early postoperative period. The mechanisms of regulation of the immune response in patients during and early after surgical revascularization are not fully understood. The aim of this study was to investigate the influence of carbohydrate preoperative oral feeding on frequency and perforin expression in peripheral blood lymphocytes in patients after on- or off-pump CABG surgery in early postoperative period. PATIENTS AND METHODS: In this prospective clinical study, 80 patients scheduled for CABG surgery were included in the study. The patients were randomly allocated into four groups (20 in each group): patients in Group 1 underwent on-pump CABG and did not receive carbohydrate preoperative oral feeding; patients in Group 2 underwent on-pump CABG and were preoperatively fed; patients in Group 3 underwent off-pump CABG and did not receive carbohydrate preoperative oral feeding; while patients in Group 4 underwent off-pump CABG and received carbohydrate preoperative oral feeding. Blood samples were collected immediately before (T1), 24 (T2) and 72 (T3) hours after the surgery. Peripheral blood mononuclear cells were isolated by gradient centrifugation and simultaneously labelled by antigens using fluorochrome-conjugated monoclonal antibodies. Frequency of T lymphocytes, NK and NKT cells, their subsets as well as their perforin expression were detected, and analyzed by flow cytometry. RESULTS: There was significant decrease in frequency of CD3+ and CD3+CD4+ cells, as well as perforin expressing CD3+CD8+ cells in patients who underwent on-pump CABG in comparison to patients who underwent off-pump CABG 24 hours after the surgery. Carbohydrate preoperative oral feeding did not effect changes in lymphocytes subpopulations and perforin expression at any time point. CONCLUSION: Decreases of CD3+ cells on account of CD3+CD4+ subsets, and perforin expressing cells on account of CD3+CD8+ perforin+ cells were found in patients who had undergone on-pump CABG, but not in patients who had undergone off-pump CABG surgery, irrespectively of carbohydrate preoperative oral feeding.

Endothelial dysfunction mediated by interleukin-18 in patients with ischemic heart disease undergoing coronary artery bypass grafting surgery.

When medication management or percutaneous coronary intervention is not successful in patients with advanced ischemic heart disease, surgical revascularisation-predominantly coronary artery bypass grafting (CABG)-is considered the gold standard. However, CABG surgery can lead to ischemia/reperfusion injury, which is characterized by a strong inflammatory response. Interleukin (IL)-18, is a strong inflammatory mediator, that is released from cardiomyocytes and can be found in the systemic circulation of patients during and immediately after CABG surgery. The existing damage of endothelial glycocalyx in patients with ischemic heart disease is further impaired concurrently during the surgery due to the anaesthesia-surgical technique used and intravascular fluid loading. This results in the increased incidence of adverse events, including myocardial infarction. IL-18 leads to the activation of lymphocyte cytotoxicity via cytotoxic mediators (Fas ligand, Tumour necrosis factor (TNF)-related apoptosis-inducing ligand, perforin, and granulysin). We hypothesize that IL-18 is released locally in the heart and the systemic circulation in patients undergoing CABG surgery and may be correlated with the level of activity of circulating lymphocytes. In turn, this may lead to lymphocyte-mediated cytotoxicity directed toward damaged and activated endothelial cells. Shear stress glycocalyx, as well as damaged and activated endothelial cells then become the main the source of pro-inflammatory cytokines, chemokines, and adhesion molecules. These attract activated lymphocytes to adhere to the endothelium or enter the subintimal layer, increasing existing or initiating the formation of new plaques, which leads to the development of myocardial infarction during or shortly after surgery. To evaluate our hypothesis, we will measure the local concentration of IL-18 in the sinus coronarius and systemic circulation. These values will then be correlated with immunological and biochemical parameters, predominantly with the concentration of degradation products of glycocalyx and cytotoxic mediators in activated lymphocytes. If our hypothesis is correct, measuring the IL-18 concentration that is responsible for glycocalyx deterioration, may become a useful tool for predicting myocardial infarction occurrence in patients undergoing CABG surgery.

Successful treatment of fulminant Lyme myocarditis with mechanical circulatory support in a young male adult: a case report.

We describe the case of fulminant myocarditis due to Lyme disease and use of mechanical circulatory support (MCS) for the treatment of the Lyme carditis associated with refractory cardiogenic shock. Fulminant Lyme myocarditis in young adult male patient led to a sudden onset of acute, severe biventricular heart failure with progressive cardiogenic shock, and multiorgan failure immediately after admission.

Muscle strength differ between patients with diabetes and controls following heart surgery.

BACKGROUND: The aim of our study was to analyze muscle strength in patients with recent surgical treatment for ischemic and combined ischemic-valvular heart disease, based on existence of diabetes mellitus. Connections existing between muscle strength and patient characteristics or conventional diagnostic tests were analyzed as well. METHODS: Study prospectively included consecutive patients scheduled for cardiovascular rehabilitation 0-3months after heart surgery. Diagnostics covered drug utilization, anthropometrics, demographics, echocardiography, conventional laboratory, echocardiography, bioelectrical impedance analysis (BIA), and hand grip test (HGT). HGT was analyzed for dominant hand. RESULTS: Patients with diabetes had significantly weaker muscle strength on HGT than controls; 29.4±12.2kg vs. 38.2±14.7kg (p=0.029), respectively. ROC analysis for HGT and existence of diabetes mellitus were significant; ≤40kg had sensitivity of 89.7% (95%CI: 72.6-97.8), specificity 43.7% (31.9-56.0); AUC 0.669 (0.568-0.760); p=0.002. HGT significantly correlated with hematocrit (Rho CC=0.247; p=0.013), whilst other laboratory or echocardiographic parameters were insignificant (all p>0.05). HGT also correlated with body weight (Rho CC=0.510; p<0.001); height (Rho CC=0.632; p<0.001); waist circumference (Rho CC=0.388; p<0.001); waist-to-hip ratio (Rho CC=0.274; p=0.006) and BIA (Rho CC=-0.412; p<0.001). CONCLUSIONS: In postoperative recovery of patients with diabetes, muscle strength assessed by HGT is decreased and in relation with nutritional status. Clinically resourceful connections of HGT were also found to hematocrit and utilization of loop diuretics.

Prolonged utilization of proton pump inhibitors in patients with ischemic and valvular heart disease is associated with surgical treatments, weight loss and aggravates anemia.

BACKGROUND: Proton pump inhibitors (PPIs) are among the commonest drugs used nowadays. The aim of our study was to analyze prolonged utilization of proton pump inhibitors in medical therapy of patients with ischemic and valvular heart disease. Secondly, profile of utilization was scrutinized to patient characteristics and type of cardiovascular treatments. METHODS: The study included consecutive patients scheduled for cardiovascular rehabilitation 2-6months after index cardiovascular treatment. RESULTS: Two hundred ninety-four patients (n=294/604; 48.7%) have been using proton pump inhibitor in their therapy after index cardiovascular treatment. Cardiovascular treatments were powerfully connected with utilization of PPIs; surgery 5.77 (95%-confidence intervals [CI]: 4.05-8.22; p<0.001) and PCI 0.15 (CI: 0.10-0.22; p<0.001). The odds for having proton pump inhibitor in their chronic therapy were increased for atrial fibrillation 1.87 (CI: 1.08-3.23; p=0.025) and decreased for obesity 0.65 (CI: 0.45-0.96; p=0.035); surviving myocardial infarction 0.49 (CI: 0.29-0.83; p=0.035). Multinomial logistic regression controlled for existence of chronic renal disease found no significant association of renal dysfunction and PPI therapy. The existence of anemia was significantly increased in patients taking PPIs than controls; 6.00 (CI: 3.85-9.33; p<0.001). The use of PPI was also associated with worsening of metabolic profile, in part due to decreased utilization of ACE-inhibitors and statins. PPI consumption correlated with age of patients (Rho=0.216; p<0.001). CONCLUSIONS: High proportion of cardiovascular, particularly surgical patients with ischemic and valvular heart disease utilized proton pump inhibitor in prolonged courses. Prolonged courses of PPIs were connected with existence and worsening of red blood count indexes, older age, lesser weight of patients and underutilization of cardioprotective drugs.

Successful Treatment of Acute Aortic Dissection Type Stanford A Presenting as Limb Ischemia, Successfully Treated with Operative and Endovascular Procedures.

We report a successful treatment of unusual case of a 48 year old male patient with acute aortic dissection type Stanford A that expanded into left common and external iliac artery diagnosed by MSCT angiography, presenting as a single leg paresis, without symptoms of a chest or back pain. Patient was operated with conventional ascending aortic replacement. Patient had no known prior medical condition. He has been treated for acute thrombosis of the left popliteal artery developing one day after ascending aortic replacement surgery, embolectomy was performed. Critical limb ischemia developed due to preocclusive stenosis of the left common and left external iliac artery and was treated by endovascular procedure of iliac artery stenting performed on the fifth postoperative day. After 17 days patient was discharged form hospital, showing no neurological or vascular deficit. For successful treatment of acute aortic dissection type Stanford A complicated with limb ischemia, rapid and accurate diagnosis is essential, together with close cooperation of cardio surgeons, vascular surgeons and invasive radiologists and individual approach to these demanding patients.

Unexpectedly elevated cardiac troponin I level in the patient without acute coronary syndrome.

BACKGROUND: Since cTnI assay is leading test in diagnostic of myocardial infarctions, and it is used for risk assessment in patients with ACS as well as unstable angina pectoris, it is very important to measure its concentration accurately and precisely. METHODS: Here we report a case in which there was a significant difference in the cTnI concentrations measured by three different methods, which was detected in one patient's sera during preoperative evaluation for cardiac surgery. RESULTS: Due to variations in the results for the cTnI concentrations (0.62; 0.13; 0.89 microg/L), the question was raised about the possibility of an interference known to occur in especially rare situations. A 76-year-old male was operated, temporal elevation and subsequent decrease in the concentrations of cTnI were monitored. CONCLUSIONS: It was observed that results obtain with different assays are not comparable.

Many-particle surface diffusion coefficients near first-order phase transitions at low temperatures.

We analyze the chemical and jump surface diffusion coefficients, D(c) and D(J), near a first-order phase transition at which two phases coexist and the surface coverage, θ, jumps between single-phase values θ(-)(*) and θ(+)(*). Contrary to other studies, we consider temperatures that are sufficiently subcritical. Using the local equilibrium approximation, we obtain approximate analytical formulas for the dependences of D(c) and D(J) on the coverage and system size, N, near such a transition. In the two-phase regime, when θ ranges between θ-* and θ+*, the diffusion coefficients behave as the sums of two hyperbolas, D(c) ≈ A-/N|θ-θ(-)(*)| + A+/N|θ-θ(+)(*)| and D(J) ≈ A(-)|θ-θ(+)(*)|/θ+A(+)|θ-θ(-)(*)|/θ. This behavior rapidly changes as the system goes from the two-phase regime to either of the single-phase regimes (when θ goes below θ(-)(*) or above θ(+)(*)). The crossover behavior of D(c)(θ) and D(J)(θ) between the two-phase and single-phase regimes is described by rather complex formulas involving the Lambert function. We consider a lattice-gas model on a triangular lattice to illustrate these general results, applying them to four specific examples of transitions exhibited by the model.

Is mitral valve repair safe procedure in elderly patients?

The aim of this randomized, prospective, study was to evaluate postoperative hospital mortality and morbidity after mitral valve repair by comparing two surgical techniques for resolving mitral valve insufficiency in elderly patients. In comparison were: mitral valve repair vs. mitral valve replacement in patients older than 70 years. In period from January 1st 2006 until August 30th 2009. Eighty patients with mitral valve disease, isolated or associated with other comorbidities, were scheduled for mitral valve repair or mitral valve replacement in our institution. Patients were randomized in two groups, one scheduled for mitral valve repair and another one for mitral valve replacement using the envelope method with random numbers. Results show no difference in hospital mortality and morbidity postoperatively in both groups. In group undergoing valve replacement we had one significant complication of ventricle rupture in emphatically calcified posterior part of mitral valve annulus. In conclusion we found no distinction in postoperative hospital mortality and morbidity after using one of two surgical techniques.

Perioperative and early postoperative neurological deficit in older patients during carotid artery thrombendarterectomy.

Cerebrovascular accidents, strokes in particular, are among the most frequent causes of death today in developed countries. In the last two decades, stroke was the second most frequent cause of death in Primorsko-Goranska Region in Croatia. In older patients, individuals older than 65 years of age have an increased risk of stroke, mainly because the degree of carotid artery stenosis increases with age. The most frequent complication of the high percent stenosis of the carotid arteries is thrombosis in the area of atherosclerotic changes of blood vessels. With the increase in the age of the population, there is also an increase in the number of risk factors of cerebrovascular accident. Doppler ultrasound sonography and Multi Slice CT scans have the most prominent role in the early detection of atherosclerotic changes and in the assessment of the degree of carotid artery narrowing. Today, in Croatia as well as worldwide, thrombendarterectomy holds the most important place in stroke prevention. Between 2006 and 2009, 209 patients underwent surgical intervention at the Clinical Hospital Center in Rijeka for high degree of carotid artery narrowing. In the group younger than 65 years of age, which consisted of 53 patients, a neurological deficit was noted in 4 patients (7.54%) in the perioperative and early postoperative course. In the group of individuals older than 65 years of age, which consisted of 156 patients, a neurological deficit was noted in 9 patients (5.76%). There was no significant statistical difference in the incidence of neurological deficit, nor in the mortality in individuals older than 65 years of age during carotid arteries thrombendarterectomy.

Application of wound closure Molndal technique after laparoscopic cholecystectomy--initial comparative study.

Because of a possible delayed wound healing, critical colonization and infection of wounds present a problem for surgeons. Colonized and infected wounds are a potential source for cross-infection. Molndal technique of wound dressing has proven to be effective in prevention of infection. Also the wound heal better and faster. In our study we wanted to describe the benefits of the Molndal technique wound dressing after laparoscopic cholecistectomy compared to traditional wound dressing technique. Molndal technique consisted of wound dressing with Aquacel Ag--Hydrofiber (ConvaTec, Dublin, Ireland). Traditional technique was performed using gauze compresses and hypoallergic adhesives. We analyzed the results of 100 patients after laparoscopic cholecystectomy. 50 patients were treated by Molndal technique and 50 patients by the traditional technique of wound dressing. In the group treated by Molndal technique only 1 (2%) patient has revealed a wound infection, proven by positive microbiological examination and suppuration, mostly in the subumbilical incision. In the traditional technique group 7 (14%) patients developed wound infection also predominantly in the subumbilical incision. The difference was statistically significant (p < 0.01). Our results are clearly showing that Molndal technique is effective in preventing the infection of subumbilical incision wound and is to by recommend for regular use at designated site after laparoscopic cholecistectomy.

Chiral segregation in three microscopic statistical-mechanical models.

We consider three microscopic model molecular systems, each containing an equimolar mixture of a chiral molecule and its nonsuperimposable mirror image. The molecules in each model are assumed to lie on a thin film in such a way that they occupy the sites of a honeycomb lattice. Although neither enantiomorph is externally favored at low temperatures, we prove that for one range of interactions, chiral segregation into ordered phases containing a single enantiomorph occurs for two of the models and, in a second range of interactions, ordered racemic phases (containing equal numbers of each enantiomorph) occur for the two models. For a third range of interactions, each of the two models has an infinite number of ground-state configurations and, moreover, an associated residual entropy. In all three ranges of interactions considered, the third model has an infinite number of ground-state configurations and a residual entropy.

Off-pump versus on-pump--intermittent aortic cross clamping--myocardial revascularisation: single center expirience.

The aim of this randomised, prospective study was to evaluate hospital mortality and morbidity after myocardial revascularisation, comparing on-pump coronary artery bypass graft (CABG) myocardial revascularisation versus off-pump coronary artery bypass graft (OPCAB) myocardial revascularisation in population with multivessels coronary artery disease. Sixty patients with multivessels coronary artery diseases were scheduled to undergo coronary artery bypass grafting from January 15, 2006 to June 30, 2007 in our institution. Patients were randomized to off-pump or on-pump surgery with intermittent cross-clamping of aorta and ventricular fibrillation, using the envelope method with random numbers. In the results only difference we did find postoperatively was in Creatine Kinase-MB (CK-MB) release, the amount of bleeding and intensive care unit (ICU) stay (p<0.05). There was no diference between the two groups of patients regarding incidence of main morbidity and hospital moratlity. In summary, we didn't find no superiority in any of the two techniques regarding on hospital mortality and morbidity.

Low temperature phases of the Andelman-de Gennes model of chiral discrimination: rigorous results.

We determine the ordered low temperature phases of the Andelman-de Gennes model of chiral discrimination, using rigorous statistical mechanical methods. The system is considered in the close-packed regime, equivalent to placing the molecules at every site of a honeycomb lattice. If the system contains an equimolar mixture of each of a pair of enantiomers, we prove in general that a heterochiral phase (disfavoring enantiomeric segregation) as well as a homochiral phase (favoring the segregation) is possible, depending on the types of intermolecular interactions. We apply our general results to the specific examples of the interactions considered by Andelman and de Gennes and provide a comparison with their conjectures that were based on two-molecule partition functions.

Ochronosis of the aortic valve and aorta.

A 64-year-old male patient with unknown alkaptonuria and severe aortic stenosis and ischemic heart disease was admitted to the authors' institution for elective surgery. The patient underwent aortic valve replacement with a 25-mm aortic valve (ATS Medical, Inc.) and single venous aortocoronary artery bypass grafting for a right coronary artery. Aortotomy revealed typical ochronotic pigmentation of a severely calcified aortic valve and aortic intima. A diagnosis of alkaptonuria was confirmed by evidence of homogentisic acid in the patient's urine, together with histopathological analysis.

Chronic heart perforation with 13.5 cm long Kirschner wire without pericardial tamponade: an unusual sequelae after shoulder fracture.

We report a unique case of cardiac embolization with the Kirschner wire that has been used for osteosynthesis for 24 months previously. According to the complete analysis of medical records and autopsy report, the wire had migrated from the right humeroscapular joint to the heart. Although migration of a Kirschner wire has been reported in the literature, migration of the wire with a total length of 13.5 cm with no pericardial tamponade, despite myocardial perforation, has not been previously described.

Heart embolization with the Kirschner wire without cardiac tamponade.

The case of the heart embolization with the Kirschner wire that was used for shoulder trauma fixation, 2 years previously in a 67-year-old female, is reported. This case is unique; although embolization of foreign bodies to the heart is not a novel occurrence, heart embolization with non-broken Kirschner wire with a total length of 13.5 cm without cardiac tamponade was not described in medical literature so far.