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Open access

Roxana Buzas, Alexandru Florin Rogobete, Sonia Elena Popovici, Tudor Mateescu, Teodora Hoinoiu, Virgiliu-Bogdan Sorop, Tiberiu Bratu, Marian Ticlea, Calin Marius Popoiu and Dorel Sandesc

Abstract

Worldwide, cardiovascular diseases (CVDs) represent one of the main causes of morbidity and mortality, and acute coronary syndromes are responsible for a large number of sudden cardiac deaths. One of the main challenges that still exist in this area is represented by the early detection and targeted monitoring of the pathophysiology involved in CVDs. During the last couple of years, researchers have highlighted the importance of molecular and epigenetic mechanisms involved in the initiation and augmentation of CVDs, culminating in their most severe form represented by acute myocardial infarction. One of the most studied molecular factors involved in this type of pathology is represented by nuclear transcription factor kappa B (NF-κB), as well as the involvement of microRNAs (miRNAs). It has been suggested that miRNAs can also be involved in the complex process of atheromatous plaque vulnerabilization that leads to an acute cardiac event. In this review paper, we describe the most important molecular mechanisms involved in the pathogenesis of CVDs and atheromatous plaque progression and vulnerabilization, which include molecular mechanisms dependent on NF-κB. For this paper, we used international databases (PubMed and Scopus). The keywords used for the search were “miRNAs biomarkers”, “miRNAs in cardiovascular disease”, “NF-κB in cardiovascular disease”, “molecular mechanism in cardiovascular disease”, and “myocardial NF-κB mechanisms”. Numerous molecular reactions that have NF-κB as a trigger are involved in the pathogenesis of CVDs. Moreover, miRNAs play an important role in initiating and aggravating certain segments of CVDs. Therefore, miRNAs can be used as biomarkers for early evaluation of CVDs. Furthermore, in the future, miRNAs could be used as a targeted molecular therapy in order to block certain mechanisms responsible for inducing CVDs and leading to acute cardiovascular events.

Open access

Tiberiu Nyulas, Emese Marton, Victoria Ancuta Rus, Nora Rat, Mihaela Ratiu, Theodora Benedek and Imre Benedek

Abstract

Background: The independent role of each plaque feature in relation to plaque vulnerability is still the subject of ongoing research. This study aimed to compare the morphologic characteristics of vulnerable atheromatous coronary plaques with the ones of stable, non-vulnerable plaques, and in plaques with different locations in the coronary tree, in order to identify the most relevant imaging-based biomarkers associated with coronary plaque vulnerability.

Material and methods: This was a prospective observational, non-randomized study that included 50 patients with unstable angina who underwent computed tomography angiography for assessment of the entire coronary artery tree followed by complex morphologic analysis of all lesions, divided into two groups: group 1 – 25 patients with vulnerable plaque (VP) and group 2 – 25 age- and gender-matched patients with non-vulnerable plaque (NVP).

Results: Lesions with a stenosis degree >70% were significantly longer than those with a stenosis degree <70% (8.27 ± 2.74 mm vs. 5.56 ± 4.11 mm, p = 0.04). VP presented significantly higher values of plaque thickness (p = 0.0005), plaque burden (p = 0.0004), and higher total plaque volume (p = 0.0005) than NVP. The remodeling index was not significantly different between the groups (p = 0.6), but the eccentricity index was (0.24 ± 0.14 compared to 0.14 ± 0.17, p = 0.023). Linear regression analysis revealed a significant correlation between plaque burden and plaque components in VP (r = 0.76, p <0.0001 for necrotic core; r = 0.62, p = 0.0008 for fibro-fatty tissue; and r = 0.5, p = 0.01 for fibrotic tissue volume). Culprit plaques located in the right coronary artery presented significantly larger plaque burden volumes (91.17 ± 4.88 mm3 vs. 83.35 ± 8.47 mm3, p = 0.04), larger volumes of necrotic core (82.03 ± 47.85 mm3 vs. 45.84 ± 43.72 mm3, p = 0.02) and fibrofatty tissue (53.23 ± 31.92 mm3 vs. 23.76 ± 20.90 mm3, p = 0.02) than the ones situated in the left coronary artery.

Conclusions: VPs from the culprit lesions exhibit a different phenotype than non-vulnerable ones, and vulnerability features are present in a significantly larger extent in VPs from the right coronary artery as compared to those from the left coronary artery.

Open access

Larisa Anghel, Cristina Prisacariu and Cătălina Arsenescu Georgescu

Abstract

Introduction: Cardiovascular disease is the leading cause of death among women irrespective of race or ethnicity, and about half of these deaths are caused by coronary artery disease. Several studies have reported that cardiovascular diseases manifest themself with a delay of about 7–10 years in women and that they have higher in-hospital mortality. It has not yet been established whether female gender itself, through biological and sociocultural differences, represents a risk factor for early in-hospital mortality in ST-segment elevation acute myocardial infarction (STEMI). The aim of our study was to identify the angiographic particularities in women with STEMI from North East Romania.

Material and Methods: For one year, 207 (31.7%) women and 445 (68.3%) men diagnosed with acute myocardial infarction were hospitalized in the Cardiology Clinic of the “Prof. Dr. George I. M. Georgescu” Institute of Cardiovascular Diseases in Iași, Romania.

Results: The highest incidence of symptom onset was between 6:00 a.m. and 12:00 a.m., this morning polarization being more obvious in women. Within the first two hours of admission to the hospital, coronary angiography was performed in 78.1% of men and only 67.3% of women, the difference being statistically significant (p <0.05). We found that a large number of women had multivascular coronary disease (47.9% vs. 42.3%). At the same time, we found that left main disease and multivascular disease were more frequent in women than in men (3.8% vs. 0.7%, p = 0.001 for left main plus two-vessel disease, and 19.4% vs. 14.8%, p = 0.0005 for three-vessel disease).

Conclusions: In women, coronary events began more frequently in the morning, with atypical symptoms; also, fewer women presented to the hospital within the first 12 hours after the onset of the acute event. Compared to men, women from North East Romania present a higher incidence of multivascular atherosclerotic coronary lessions, indicating a higher severity of STEMI in the female population from this geographical area.

Open access

Erna Alukic, Damijan Skrk and Nejc Mekis

Abstract

Background

The aim of the study was to compare patient radiation dose and image quality in planar lumbar spine radiography using the PA and AP projection in a large variety of patients of both sexes and different sizes.

Patients and methods

In the first phase data of image field size, DAP, effective dose and image quality were gathered for AP and PA projection in lumbar spine imaging of anthropomorphic phantom. In the second phase, data of BMI, image field size, diameter of the patient’s abdomen, DAP, effective dose and image quality were gathered for 100 patients of both sexes who were referred to lumbar spine radiography. The patients were divided into two groups of 50 patients, one of which was imaged using the AP projection while the other the PA projection.

Results

The study on the phantom showed no statistically significant difference in image field size, DAP and image quality. However, the calculated effective dose in the PA projection was 25% lower compared to AP projection (p =0.008). Measurements on the patients showed no statistically significant difference between the BMI and the image field size. In the PA projection, the thickness of abdomen was 10% (p < 10–3) lower, DAP 27% lower (p = 0.009) and the effective dose 53% (p < 10–3) lower than in AP projection. There was no statistically significant difference in image quality between the AP and the PA projection.

Conclusions

The study results support the use of the PA projection as the preferred method of choice in planar lumbar spine radiography.

Open access

Christina Eder-Czembirek, Birgit Erlacher, Dietmar Thurnher, Boban M. Erovic, Edgar Selzer and Michael Formanek

Abstract

Background

Results from publications evaluating discrepancies between clinical staging data in relation to pathological findings demonstrate that a significant number of head and neck squamous cell carcinoma (HNSCC) patients are not correctly staged. The aim of this retrospective study was to analyze potential discrepancies of radiological assessment versus pathological data of regional lymph node involvement and to compare the results with data published in the literature.

Patients and methods

In a retrospective analysis we focused on patients with HNSCC routinely treated by surgery plus postoperative radiotherapy between 2002 and 2012. For inclusion, complete pre-operative clinical staging information with lymph node status and patho-histological information on involved lymph node regions as well as survival outcome data were mandatory. We included 87 patients (UICC stage III-IV 90.8%) for which the aforementioned data obtained by CT or MRI were available. Overall survival rates were estimated by the Kaplan–Meier method. The Pearson correlation coefficient and Spearman’s rank correlation coefficient (non-linear relationship) was calculated.

Results

Discrepancies at the level of overall tumour stage assessment were noticed in 27.5% of all cases. Thereof, 5.7% were assigned to patho-histological up-staging or down-staging of the primary tumour. At the lymph node level, 11.5% of the patients were downstaged, and 10.3% were upstaged.

Conclusions

The study showed that in approximately one-fifth (21.8%) of the patients, lymph node assessment by CT or MRI differs from the pathologic staging, an outcome that corresponds well with those published by several other groups in this field.

Open access

Đeni Smilovic Radojcic, David Rajlic, Bozidar Casar, Manda Svabic Kolacio, Nevena Obajdin, Dario Faj and Slaven Jurkovic

Abstract

Background

The accuracy of dose calculation is crucial for success of the radiotherapy treatment. One of the methods that represent the current standard for patient-specific dosimetry is the evaluation of dose distributions measured with an ionization chamber array inside a homogeneous phantom using gamma method. Nevertheless, this method does not replicate the realistic conditions present when a patient is undergoing therapy. Therefore, to more accurately evaluate the treatment planning system (TPS) capabilities, gamma passing rates were examined for beams of different complexity passing through inhomogeneous phantoms.

Materials and methods

The research was performed using Siemens Oncor Expression linear accelerator, Siemens Somatom Open CT simulator and Elekta Monaco TPS. A 2D detector array was used to evaluate dose distribution accuracy in homogeneous, semi-anthropomorphic and anthropomorphic phantoms. Validation was based on gamma analysis with 3%/3mm and 2%/2mm criteria, respectively.

Results

Passing rates of the complex dose distributions degrade depending on the thickness of non-water equivalent material. They also depend on dose reporting mode used. It is observed that the passing rate decreases with plan complexity. Comparison of the data for all set-ups of semi-anthropomorphic and anthropomorphic phantoms shows that passing rates are higher in the anthropomorphic phantom.

Conclusions

Presented results raise a question of possible limits of dose distribution verification in assessment of plan delivery quality. Consequently, good results obtained using standard patient specific dosimetry methodology do not guarantee the accuracy of delivered dose distribution in real clinical cases.

Open access

Chawalit Lertbutsayanukul, Danita Kannarunimit, Anussara Prayongrat, Chakkapong Chakkabat, Sarin Kitpanit and Pokrath Hansasuta

Abstract

Background

Plasma EBV DNA concentrations at the time of diagnosis (pre-EBV) and post treatment (post-EBV) have significant value for predicting the clinical outcome of nasopharyngeal cancer (NPC) patients. However, the prognostic value of the EBV concentration during radiation therapy (mid-EBV) has not been vigorously studied.

Patients and methods

This was a post hoc analysis of 105 detectable pre-EBV NPC patients from a phase II/III study comparing sequential (SEQ) versus simultaneous integrated boost (SIB) intensity-modulated radiation therapy (IMRT). Plasma EBV DNA concentrations were measured by PCR before commencement of IMRT, at the 5th week of radiation therapy and 3 months after the completion of IMRT. The objective was to identify the prognostic value of mid-EBV to predict overall survival (OS), progression-free survival (PFS) and distant metastasis-free survival (DMFS).

Results

A median pre-EBV was 6880 copies/ml. Mid-EBV and post-EBV were detectable in 14.3% and 6.7% of the patients, respectively. The median follow-up time was 45.3 months. The 3-year OS, PFS and DMFS rates were 86.0% vs. 66.7% (p = 0.043), 81.5% vs. 52.5% (p = 0.006), 86.1% vs. 76.6% (p = 0.150), respectively, for those with undetectable mid-EBV vs. persistently detectable mid-EBV. However, in the multivariate analysis, only persistently detectable post-EBV was significantly associated with a worse OS (hazard ratio (HR) = 6.881, 95% confident interval (CI) 1.699-27.867, p = 0.007), PFS (HR = 5.117, 95% CI 1.562–16.768, p = 0.007) and DMFS (HR = 129.071, 95%CI 19.031–875.364, p < 0.001).

Conclusions

Detectable post-EBV was the most powerful adverse prognostic factor for OS, PFS and DMFS; however, detectable mid-EBV was associated with worse OS, PFS especially Local-PFS (LPFS) and may facilitate adaptive treatment during the radiation treatment period.

Open access

Maja Ebert Moltara, Srdjan Novakovic, Marko Boc, Marina Bucic, Martina Rebersek, Vesna Zadnik and Janja Ocvirk

Abstract

Background

BRAF, NRAS and c-KIT mutations are characteristics of tumour tissues that influence on treatment decisions in metastatic melanoma patients. Mutation frequency and their correlation with histological characteristics in Slovenian population have not been investigated yet.

Patients and methods

In our retrospective analysis we analysed mutational status of BRAF, NRAS and c-KIT in 230 pathological samples of patients who were intended to be treated with systemic therapy due to metastatic disease at the Institute of Oncology Ljubljana between 2013 and 2016. We collected also histological characteristics of primary tumours and clinical data of patients and correlated them with mutational status of tumour samples.

Results

The study population consisted of 230 patients with a mean age 59 years (range 25−85). 141 (61.3%) were males and 89 (38.7%) females. BRAF mutations were identified in 129 (56.1%), NRAS in 31 (13.5%) and c-KIT in 3 (1.3%) tissue samples. Among the 129 patients with BRAF mutations, 114 (88.4%) patients had V600E mutation and 15 (11.6%) had V600K mutation. Patients with BRAF mutations tended to be younger at diagnosis (52 vs. 59 years, p < 0.05), patients with NRAS mutations older (61 vs. 55 years, p < 0.05). Number of c-KIT mutations were too low for any statistical correlation, but there was one out of 3 melanoma located in mucus membranes.

Conclusions

The analysis detected high rate of BRAF mutations, low NRAS mutations and low c-KIT mutations compared to previously published studies in Europe and North America. One of the main reasons for this observation is specific characteristics of study population.

Open access

Mateja Vidic, Tina Smuc, Nika Janez, Michael Blank, Tomaz Accetto, Jan Mavri, Isis C. Nascimento, Arthur A. Nery, Henning Ulrich and Tamara T. Lah

Abstract

Background

Detection of circulating lung cancer cells with cancer-stem like characteristics would represent an improved tool for disease prognosis. However, current antibodies based methods have some disadvantages and therefore cell SELEX (Systematic Evolution of Ligands by Exponential Enrichment) was used to develop DNA aptamers, recognizing cell surface markers of non-small lung carcinoma (NSLC) cells.

Materials and methods

The human adenocarcinoma cell line A549 was used for selection in seven cell SELEX cycles. We used human blood leukocytes for negative selection, and lung stem cell protein marker CD90 antibody binding A549 cells for positive selection.

Results

The obtained oligonucleotide sequences after the seventh SELEX cycle were subjected to in silico selection analysis based on three independent types of bioinformatics approaches, selecting two closely related aptamer candidates in terms of consensus sequences, structural motifs, binding affinity (Kd) and stability (ΔG). We selected and identified the aptamer A155_18 with very good binding characteristics to A459 cells, selected for CD90 antibody binding. The calculated phylogenetic tree showed that aptamers A155_18 and the known A549 cell aptamer S6 have a close structural relationship. MEME sequence analysis showed that they share two unique motifs, not present in other sequences.

Conclusions

The novel aptamer A155_18 has strong binding affinity for A549 lung carcinoma cell line subpopulation that is expressing stem cell marker CD90, indicating a possible stemness, characteristic for the A459 line, or a subpopulation present within this cell line. This aptamer can be applied as diagnostic tool, identifying NSLC circulating cells.

Open access

Vencel Somai, David Legrady and Gabor Tolnai

Abstract

Background

In emission tomography maximum likelihood expectation maximization reconstruction technique has replaced the analytical approaches in several applications. The most important drawback of this iterative method is its linear rate of convergence and the corresponding computational burden. Therefore, simplifications are usually required in the Monte Carlo simulation of the back projection step. In order to overcome these problems, a reconstruction code has been developed with graphical processing unit based Monte Carlo engine which enabled full physical modelling in the back projection.

Materials and methods

Code performance was evaluated with simulations on two geometries. One is a sophisticated scanner geometry which consists of a dodecagon with inscribed circle radius of 8.7 cm, packed on each side with an array of 39 × 81 LYSO detector pixels of 1.17 mm sided squares, similar to a Mediso nanoScan PET/CT scanner. The other, simplified geometry contains a 38,4mm long interval as a voxel space, detector pixels are assigned in two parallel sections each containing 81 crystals of a size 1.17×1.17 mm.

Results

We have demonstrated that full Monte Carlo modelling in the back projection step leads to material dependent inhomogeneities in the reconstructed image. The reasons behind this apparently anomalous behaviour was analysed in the simplified system by means of singular value decomposition and explained by different speed of convergence.

Conclusions

To still take advantage of the higher noise stability of the full physical modelling, a new filtering technique is proposed for convergence acceleration. Some theoretical considerations for the practical implementation and for further development are also presented.