The impact of fullerenol nanoparticles on the growth of toxigenic Aspergillus flavus and aflatoxins production in vitro and in corn flour.

Antifungal and antimycotoxigenic activity of fullerenol nanoparticles (FNPs) were investigated on Aspergillus flavus growth isolated from a real food sample and aflatoxins (AFs) (AFB1 and AFB2 ) production. The final FNPs concentrations in in vitro and in commercial corn flour after the stationary incubation period of 7 and 14 days were in the range 0.16-80 µg/mL and 0.16-80 µg/g, respectively. Nanocharacterization of FNPs revealed an average size of 5-20 nm and a zeta potential of -35 mV. The highest degree of A. flavus mycelium growth inhibition (28%) after 7 days was observed for applied FNP concentration of 8.0 µg/mL, while after 14 days FNP concentration of 0.32 µg/mL led to the maximal inhibition of A. flavus mycelium growth (36%). Spearman's correlations analysis revealed a strong positive correlation between AFB1 and AFB2 concentrations in YES broth after 7 (R = 0.994, p < 0.05) and 14 days (R = 0.976), as well as between AFs concentrations and A. flavus mycelium mass after 7 (R = 0.786 for AFB1 and R = 0.766 for AFB2 ) and 14 days (R = 0.810 for AFB1 and R = 0.833 for AFB2 ). Paired samples t-test showed the existence of a statistically significant difference (p < 0.05) between the produced AFs concentrations after the incubation of 7 and 14 days. Regarding the artificially inoculated corn flour the lower applied FNP concentrations (0.16-0.8 µg/g) achieved a reduction of AFB1 up to 42% and 60% after 7 and 14 days, respectively.

Acquired von Willebrand syndrome and post-operative drainage: a comparison of patients with aortic stenosis versus coronary artery disease.

OBJECTIVE: Degenerative aortic stenosis and coronary artery disease are considered to be the most prevalent cardiovascular diseases in industrialized countries. This study aims to determine the change over time in von Willebrand factor antigen, von Willebrand factor activity, and factor VIII and where there is a correlation with total post-operative drainage. METHODS: The single-center retrospective study included 203 consecutive patients (64.5% male), undergoing coronary artery bypass surgery between March 1, 2019 and June 30, 2020 at the University Clinical Center of Serbia in the Clinic for Cardiac Surgery in Belgrade, Serbia. All patients 18 years or older who presented with isolated, hemodynamically significant aortic stenosis were included. The control group consisted of patients who presented with only coronary artery disease. RESULTS: Between patients with only coronary artery disease and patients with coronary artery diseases and aortic stenosis, there was a statistically significant difference between pre-op and 1-month post-op fibrinogen, factor VIII, von Willebrand factor antigen, and von Willebrand factor (p < 0.001), post-op drainage, with overall lower drainage in coronary artery disease patients, and consistent increase in von Willebrand factor antigen, von Willebrand factor activity, and Factor VIII post-operatively in patients with coronary artery diseases and aortic stenosis. CONCLUSION: This study has shown that there is a correlation between von Willebrand factor antigen, von Willebrand factor activity and total drainage to the level of statistical significance in aortic stenosis patients and in the overall study population.

Root Resorptions on Adjacent Teeth Associated with Impacted Maxillary Canines.

AIM: Through the use of CBCT images, many unidentified features of impacted canines can be easily resolved. The potential collision of impacted maxillary canines and adjacent teeth could lead to root resorption (RR). The aim of this study is to examine the prevalence, location and severity of RR on adjacent teeth caused by impacted maxillary canines and the association between the adjacent teeth and the features of maxillary impacted canines on CBCT. METHODS: This study examined 89 subjects with 108 maxillary impacted canines, having had no previous orthodontic treatment (mean age: 18.3 ± 4.1 years). The following impacted-canine-related parameters were analyzed on the CBCT images: location; RR levels on adjacent teeth; occlusal line and midline distances of impacted canines; and the angulations of impacted canines to the midline, lateral incisor and occlusal line. Logistic regression was used to evaluate the association between RR and the measured parameters on CBCT. RESULTS: In this study, we found that the majority of our patients with impacted maxillary canines were female (62.5%). Of the total 108 maxillary impacted canines, 60.2% resorbed the adjacent teeth of the affected quadrants. Lateral incisors were the most affected (34.3%). The mean age of subjects with RR was 16.7 ± 3.5 years. The frequency of RR was statistically significantly higher in female subjects (40.4%). Slight RR was the most frequent (30.5%) and the highest incidence noted at the apical third of the root (29.6%). Regarding the impacted maxillary canine angulation to the midline and adjacent tooth, higher values of angulation caused severe forms of RR (p < 0.05). CONCLUSION: The sensitivity of CBCT allows for the accurate diagnosis of the location and the degree of RR, alongside the angulation and distance of impacted canines to adjacent teeth. The association between the linear and angular features of the impacted maxillary canines and RR was confirmed.

Perceval Sutureless Bioprosthesis for Degenerative Aortic Valve Stenosis: Initial Experience With 67 Patients.

OBJECTIVE: The objective of this prospective study was to evaluate the characteristics (positive and negative) of Perceval S valve in patients undergoing aortic valve replacement with a biological prosthesis. The study included 67 patients operated on at our institution and a mean follow-up period of 18 months. METHODS: From June 2016 to November 2019, 209 patients underwent aortic valve replacement with a biological prosthesis. Of these, 67 patients were included in the study based on the exclusion and inclusion criteria set before the study began. Their data were recorded during their hospital stay (preoperative, intraoperative, and early and late postoperative time). RESULTS: Fifty-four patients underwent isolated aortic valve replacement (group I) with a Perceval S prosthesis, and 13 patients had combined aortic valve replacement procedures and CABG procedures (group II). Patients were implanted with the following prosthesis sizes: S (N = 12), M (N = 18), L (N = 28), or XL (N = 9). The Perceval S valve successfully was implanted in 67 (91.8%) patients (in 6 patients, the preoperative transthoracic echocardiographic data did not coincide with intraoperative TEE and surgical measurement of the size of the annulus in the suture). Surgical approaches in patients were medial sternotomy (N = 48), mini sternotomy (N = 15), and thoracotomy through the second intercostal space to the right (N = 4). The mean clamping time of the aorta and CPB length for isolated cases was 54 and 82 minutes, respectively, and 96 and 120 minutes for combined procedures. Four (5.9%) patients died within 30 days. CONCLUSION: Early postoperative results showed that the Perceval S valve was safe. Further follow up is required to evaluate the long-term duration of patients with this bioprosthesis.

COVID-19 cases prediction by using hybrid machine learning and beetle antennae search approach.

The main objective of this paper is to further improve the current time-series prediction (forecasting) algorithms based on hybrids between machine learning and nature-inspired algorithms. After the recent COVID-19 outbreak, almost all countries were forced to impose strict measures and regulations in order to control the virus spread. Predicting the number of new cases is crucial when evaluating which measures should be implemented. The improved forecasting approach was then used to predict the number of the COVID-19 cases. The proposed prediction model represents a hybridized approach between machine learning, adaptive neuro-fuzzy inference system and enhanced beetle antennae search swarm intelligence metaheuristics. The enhanced beetle antennae search is utilized to determine the parameters of the adaptive neuro-fuzzy inference system and to improve the overall performance of the prediction model. First, an enhanced beetle antennae search algorithm has been implemented that overcomes deficiencies of its original version. The enhanced algorithm was tested and validated against a wider set of benchmark functions and proved that it substantially outperforms original implementation. Afterwards, the proposed hybrid method for COVID-19 cases prediction was then evaluated using the World Health Organization's official data on the COVID-19 outbreak in China. The proposed method has been compared against several existing state-of-the-art approaches that were tested on the same datasets. The proposed CESBAS-ANFIS achieved R 2 score of 0.9763, which is relatively high when compared to the R 2 value of 0.9645, achieved by FPASSA-ANFIS. To further evaluate the robustness of the proposed method, it has also been validated against two different datasets of weekly influenza confirmed cases in China and the USA. Simulation results and the comparative analysis show that the proposed hybrid method managed to outscore other sophisticated approaches that were tested on the same datasets and proved to be a useful tool for time-series prediction.

Diabetic Cardiomyopathy: Clinical and Metabolic Approach.

BACKGROUND: Having in mind that diabetes mellitus (DM) and obesity are some of the greatest health challenges of the modern era, diabetic cardiomyopathy (DCM) is becoming more and more recognized in clinical practice. Main Text: Initially, DM is asymptomatic, but it may progress to diastolic and then systolic left ventricular dysfunction, which results in congestive heart failure. A basic feature of this DM complication is the absence of hemodynamically significant stenosis of the coronary blood vessels. Clinical manifestations are the result of several metabolic disorders that are present during DM progression. The complexity of metabolic processes, along with numerous regulatory mechanisms, has been the subject of research that aims at discovering new diagnostic (e.g. myocardial strain with echocardiography and cardiac magnetic resonance) and treatment options. Adequate glycaemic control is not sufficient to prevent or reduce the progression of DCM. Contemporary hypoglycemic medications, such as sodium-glucose transport protein 2 inhibitors, significantly reduce the frequency of cardiovascular complications in patients with DM. Several studies have shown that, unlike the above-stated medications, thiazolidinediones and dipeptidyl peptidase-4 inhibitors are associated with deterioration of heart failure. CONCLUSION: Imaging procedures, especially myocardial strain with echocardiography and cardiac magnetic resonance, are useful to identify the early signs of DCM. Research and studies regarding new treatment options are still "in progress".

Comparison of the Diagnostic Value of Phosphatidylethanol and Carbohydrate-Deficient Transferrin as Biomarkers of Alcohol Consumption.

BACKGROUND: The aim of this study was to compare the results of Phosphatidylethanol (PEth) and carbohydrate-deficient transferrin (CDT) in blood as biomarkers of alcohol consumption in a large clinical cohort and to evaluate concentrations in relation to age and sex. METHODS: Results of PEth 16:0/18:1 in blood and CDT in serum were included, together with information of age and sex, which were extracted from a clinical chemistry database containing samples mostly from patients of primary care physicians and social care institutions. PEth concentrations were determined using Ultra Performance Convergence chromatography mass spectrometer. CDT was quantified by electrophoretic Capillary System. CDT values ≥ 1.7 %-units and PEth values ≥ 0.31 µmol/L were considered to indicate heavy alcohol consumption. RESULTS: Samples from 6705 patients were included. The median age was 54.5 years, and 34 % were females. Only 47 % of the patients with PEth ≥ 0.31 µmol/L had increased CDT ≥ 1.7 %-units examined in the same specimen (Cohen's kappa was 0.43, p < 0.001). Patients above 50 years had significantly higher concentrations for both CDT (1.0 %-units vs. 0.9 %-units, p < 0.001) and PEth (0.340 µmol/L vs. 0.200 µmol/L, p < 0.001) compared with younger patients. Concentrations of CDT were significantly higher in males compared with females (p = 0.002), while no significant sex differences were seen for PEth (p = 0.465). CONCLUSIONS: A high fraction of the patients had PEth values above the suggested cutoff for heavy drinking and normal CDT values, verifying the superior sensitivity of PEth compared with CDT. The effect of age seems to be minor for both markers. Higher concentrations of CDT, but not PEth, were seen in males, indicating that PEth, as opposed to CDT, might be formed equally in men and women. Therefore, the bias due to sex is possibly present only for CDT, not for PEth.

Potential of TiO2 with Various Au Nanoparticles for Catalyzing Mesotrione Removal from Wastewaters under Sunlight.

Nowadays, great focus is given to the contamination of surface and groundwater because of the extensive usage of pesticides in agriculture. The improvements of commercial catalyst TiO2 activity using different Au nanoparticles were investigated for mesotrione photocatalytic degradation under simulated sunlight. The selected system was 2.43 × 10-3% Au-S-CH2-CH2-OH/TiO2 (0.5 g/L) that was studied by transmission electron microscopy and ultraviolet-visible (UV-Vis) spectroscopy. It was found that TiO2 particles size was ~20 nm and ~50 nm, respectively. The Au nanoparticles were below 10 nm and were well distributed within the framework of TiO2. For 2.43 × 10-3% Au-S-CH2-CH2-OH/TiO2 (0.5 g/L), band gap energy was 2.45 eV. In comparison to the pure TiO2, addition of Au nanoparticles generally enhanced photocatalytic removal of mesotrione. By examining the degree of mineralization, it was found that 2.43 × 10-3% Au-S-CH2-CH2-OH/TiO2 (0.5 g/L) system was the most efficient for the removal of the mesotrione and intermediates. The effect of tert-butanol, NaF and ethylenediaminetetraacetic acid disodium salt on the transformation rate suggested that the relative contribution of various reactive species changed in following order: h+ > ●OHads > ●OHbulk. Finally, several intermediates that were formed during the photocatalytic treatment of mesotrione were identified.

The Puzzling Potential of Carbon Nanomaterials: General Properties, Application, and Toxicity.

Being a member of the nanofamily, carbon nanomaterials exhibit specific properties that mostly arise from their small size. They have proved to be very promising for application in the technical and biomedical field. A wide spectrum of use implies the inevitable presence of carbon nanomaterials in the environment, thus potentially endangering their whole nature. Although scientists worldwide have conducted research investigating the impact of these materials, it is evident that there are still significant gaps concerning the knowledge of their mechanisms, as well as the prolonged and chronic exposure and effects. This manuscript summarizes the most prominent representatives of carbon nanomaterial groups, giving a brief review of their general physico-chemical properties, the most common use, and toxicity profiles. Toxicity was presented through genotoxicity and the activation of the cell signaling pathways, both including in vitro and in vivo models, mechanisms, and the consequential outcomes. Moreover, the acute toxicity of fullerenol, as one of the most commonly investigated members, was briefly presented in the final part of this review. Thinking small can greatly help us improve our lives, but also obliges us to deeply and comprehensively investigate all the possible consequences that could arise from our pure-hearted scientific ambitions and work.

Surgical Challenges of Heart Mate 3 Pump Implantation in Aneurysmally Changed Heart Ventricles.

We presented surgical treatment of three patients indicated for implantation of a permanent mechanical circulatory support device and with the associated left ventricular aneurysms. In order to evade the left ventricular rupture, adverse thromboembolic events and provide safe implantation of the inflow cannula, LVAD HM3 implantation together with the reconstruction of the left ventricular aneurysmal wall was performed in two patients. Regarding the third patient, LVAD implantation upon the reconstruction of the left ventricular wall was abandoned because there was no safe location for placement of the inflow cannula.

Fullerol C60(OH)24 Nanoparticles Affect Secondary Metabolite Profile of Important Foodborne Mycotoxigenic Fungi In Vitro.

Despite the efforts to control mycotoxin contamination worldwide, extensive contamination has been reported to occur in food and feed. The contamination is even more intense due to climate changes and different stressors. This study examined the impact of fullerol C60(OH)24 nanoparticles (FNP) (at 0, 1, 10, 100, and 1000 ng mL-1) on the secondary metabolite profile of the most relevant foodborne mycotoxigenic fungi from genera Aspergillus, Fusarium, Alternaria and Penicillium, during growth in vitro. Fungi were grown in liquid RPMI 1640 media for 72 h at 29 °C, and metabolites were investigated by the LC-MS/MS dilute and shoot multimycotoxin method. Exposure to FNP showed great potential in decreasing the concentrations of 35 secondary metabolites; the decreases were dependent on FNP concentration and fungal genus. These results are a relevant guide for future examination of fungi-FNP interactions in environmental conditions. The aim is to establish the exact mechanism of FNP action and determine the impact such interactions have on food and feed safety.

Impact of fullerol C60(OH)24 nanoparticles on the production of emerging toxins by Aspergillus flavus.

The impact of fullerene C60 water soluble daughter molecules - fullerols C60(OH)24 nanoparticles (FNP) on emerging (non-aflatoxin biosynthetic pathway) toxins production in mycelia and yeast extract sucrose (YES) media of A. flavus was investigated under growth conditions of 29 °C in the dark for a 168 h period. The FNP solution (10, 100 and 1000 ng mL-1) contained predominantly nanoparticles of 8 nm diameter and with zeta potential mean value of -33 mV. Ten emerging metabolites were produced at concentrations reaching 1,745,035 ng 50 mL-1 YES medium. Seven of the metabolites were found in mycelia and media, while three were only in mycelia. Majority of the metabolites were detected in higher quantity in mycelia than in media, at a ratio of 99:1 (m/m). However, higher metabolite quantities were found in media following FNP application, while FNP caused a decrease of total metabolite quantities in mycelia. The concentrations of the metabolites in media increased in the presence of 1000 ng mL-1 FNP while mycelial quantities of the metabolites decreased with increased applied FNP dose. The impacts of global climate changes on FNP availability in the environment and on mycotoxin occurrence in crops increase the relevance of this study for risk assessment of nanoparticles. Cordycepin is reported for the first time as metabolite of A. flavus.

Effect of fullerenol nanoparticles on oxidative stress induced by paraquat in honey bees.

The enormous progress in nanomaterials development and their use, followed by their inevitable environmental print, has arisen the emerging questions concerning their influence to the living systems. Honey bees are considered to be quite a suitable model system for the risk assessment and prediction of various external influences. To the best of our knowledge, this is the first study dealing with the influence of fullerenol nanoparticles (FNP), a biodegradable carbon nanomaterials' representative, to honey bees. This investigation was conducted with an aim to merge two different open-ended questions: the potential toxic effect of FNP to the bees on the one hand and antioxidative effect of FNP on the other hand. Since FNP antioxidative properties were proved in a number of in vivo models, we hypothesized the similar outcomes, and according to this assumption, we opted for paraquat as a well-known oxidative stress inducer. FNP did not have toxic effect in none of investigated concentrations. The results also confirmed the potential of FNP to reduce oxidative stress through the gene expression of antioxidative enzymes and the change in the redox state of the cells. Additional experiments are needed for a better understanding of the exact mechanism and complex patterns of FNP's activity.

Investigation of the Postoperative Complications Rate and Predictors in Patients Undergoing Surgery due to Associated Carotid and Coronary Occlusive Disease.

BACKGROUND: The aim of this study was to evaluate the frequency of postoperative complications in patients who underwent coronary artery bypass grafting (CABG) and simultaneous carotid endarterectomy (CEA) and find predictors of postoperative complications. METHODS: We retrospectively evaluated 86 patients after simultaneous CABG and CEA. Inclusion criteria were: patients with asymptomatic carotid stenosis with a reduction of the carotid lumen diameter of more than 70% detected with Doppler ultrasound and diagnosed with one, two, or three vessel coronary artery disease with coronary stenosis more than 75% and hemodynamic significant stenosis of the left main artery. Exclusion criteria were patients with urgent and previous cardiac surgery and patients with myocardial infarction and stroke in the past one month. We monitored preoperative (ejection fraction, coronarography status), operative (number of grafts, on-pump or off-pump technique) and postoperative (extubation, unit care and hospital stay, bleeding and reoperation) details and complications (myocardial infarction, neurological events, inotropic agents and transfusion requiry, infection, arrhythmic complication, renal failure, mortality). RESULTS: Postoperative complications were observed in 18 (29.9%) patients. Two patients (2.3%) had postoperative stroke and one patient (1.2%) had transient ischemic attack (TIA). Previous stroke was a predictor for increased postoperative neurological events (P < .05). Intrahospital mortality was 8.1%. CONCLUSION: Simultaneous CEA and CABG were performed with low rates of stroke and TIA. Previous stroke was identified as a predictor for increased postoperative neurological complications.

Nanoformulations of doxorubicin: how far have we come and where do we go from here?

Nanotechnology, focused on discovery and development of new pharmaceutical products is known as nanopharmacology, and one research area this branch is engaged in are nanopharmaceuticals. The importance of being nano has been particularly emphasized in scientific areas dealing with nanomedicine and nanopharmaceuticals. Nanopharmaceuticals, their routes of administration, obstacles and solutions concerning their improved application and enhanced efficacy have been briefly yet comprehensively described. Cancer is one of the leading causes of death worldwide and evergrowing number of scientific research on the topic only confirms that the needs have not been completed yet and that there is a wide platform for improvement. This is undoubtedly true for nanoformulations of an anticancer drug doxorubicin, where various nanocarrriers were given an important role to reduce the drug toxicity, while the efficacy of the drug was supposed to be retained or preferably enhanced. Therefore, we present an interdisciplinary comprehensive overview of interdisciplinary nature on nanopharmaceuticals based on doxorubicin and its nanoformulations with valuable information concerning trends, obstacles and prospective of nanopharmaceuticals development, mode of activity of sole drug doxorubicin and its nanoformulations based on different nanocarriers, their brief descriptions of biological activity through assessing in vitro and in vivo behavior.

Hepatoprotective effect of fullerenol/doxorubicin nanocomposite in acute treatment of healthy rats.

In our recent studies we have designed fullerenol/doxorubicin nanocomposite (FNP/DOX) as the new drug nanocarrier. This research has demonstrated that this novel nanocomposite has had better implications on the liver tissue in vivo (Wistar rats treated intraperitoneally), than treatment based only on DOX. FNP/DOX has been characterised by DLS, TEM and AFM measurements which have shown that DOX loaded onto FNP did not influence fullerenol nanoparticle's size. FNP/DOX affected oxidative status in blood causing a significant decrease of catalase and SOD activity in comparison to DOX, implicating the reduction in oxidative stress. qRT-PCR results on the mRNA level of antioxidative enzymes (catalase and MnSOD) revealed that the effect of oxidative stress is significantly reduced by the treatment with FNP/DOX (p < .05). The ultrastructural analysis of the liver tissue has revealed that FNP/DOX nanocomposite generated considerably less damage in the liver tissue, than DOX applied at the same dose. Hence, our results have indicated that FNP, within FNP/DOX nanocomposite, exhibits protective effects to the liver tissue of the healthy rats.

Significance of asymptomatic hyperuricemia in patients after coronary events.

The goal of the present study was to determine the prevalence of hyperuricemia in patients with coronary artery disease (CAD), within three months after coronary events. Also, we aimed to determine whether the presence of hyperuricemia holds correlation with severe CAD, overall heart functioning and risk factors for CAD. The study included 505 consecutive CAD patients, 385 males and 120 females, aged 60.9 ± 9.6 years, with a mean body mass index (BMI) 28.0 ± 3.7 kg/m2. All patients were admitted to specialized cardiovascular rehabilitation within three months post-acute myocardial infarction (AMI) without revascularization (32.6%), percutaneous coronary intervention (PCI) with myocardial infarction (32.1%) and with coronary bypass graft (35.3%). The mean value of serum acidum uricum (SUA) was 345.5 ± 100.3 µmol/L, where 115 (22.8%) patients had asymptomatic hyperuricemia. Patients with asymptomatic hyperuricemia had significantly higher average number of risk factors, lower HDL cholesterol and higher creatinine and triglycerides levels, lower ejection fraction (EF). Multivariate stepwise analysis revealed that five parameters were capable to predict SUA levels. We can conclude that in patients with CAD, SUA levels are independently associated with BMI, triglyceride and creatinine levels and negatively with EF. Thus, one can say that asymptomatic hyperuricemia is not significantly associated with the severity of CAD.

Enhancement of nano titanium dioxide coatings by fullerene and polyhydroxy fullerene in the photocatalytic degradation of the herbicide mesotrione.

The surface modification of commercial TiO2 Hombikat (TiO2) using nanoparticles of fullerene C60 with tetrahydrofuran (THF-nC60), as well as fullerenol C60(OH)24 nanoparticles (FNP) was investigated in this study. Characterization of THF-nC60, FNP, TiO2, TiO2/THF-nC60, and TiO2/FNP was studied by using DES, ELS, TEM, SEM, DRS and BET measurements and their photoactivity has been examined on the mesotrione degradation under simulated sunlight. It was found that FNP in self-assembled nanocomposite TiO2/FNP increased negatively charge, as well as catalytic surface of TiO2. In addition, TiO2/FNP exhibits a shift of band gap energy to lower values compared to TiO2 and TiO2/THF-nC60. BET surface area has not showed significant differences among catalysts. Furthermore, it was found that the highest photoactivity was obtained for TiO2/FNP system. Besides, influence of different concentrations of electron acceptors (H2O2 and KBrO3), as well as scavengers on the kinetics of mesotrione removal in aqueous solution with/without TiO2 and FNP under simulated sunlight was investigated. Namely, addition of mentioned electron acceptors has resulted in higher mesotrione degradation efficiency compared to O2 alone. Besides, in the first period substrate degradation probably takes place via hydroxyl radicals and after 60 min of irradiation the reaction mechanism proceeds mainly via holes. The most efficient system for mesotrione degradation and mineralization were TiO2/7 mM KBrO3 and TiO2/7 mM KBrO3/40 µl FNP, respectively.

Evaluation of predictive value of 1H MR spectroscopy for response of neoadjuvant chemotherapy in musculoskeletal tumors.

PURPOSE: Bone and soft tissue tumors are rare. There is a variety of types and each one has its own particular behavior, treatment and patient outcome. The assessment of treatment response following the 3rd cycle of chemotherapy is one of the most important aspects of patient care, as therapeutic options and the timing of surgery may vary depending on the achievement of response. Hence, we focused on the advanced imaging technique, proton magnetic resonance spectroscopy (1H MRS), aiming at improving the diagnostic accuracy and the tumor response to therapy, based on the absolute concentration of choline (Cho) as biomarker of malignancy. METHODS: Twenty patients were studied. All of them had a pathological diagnosis after biopsy. MRI examinations were performed using a 1.5 T MR scanner (Avanto; Siemens, Erlangen, Germany). Single-voxel 1H MR spectroscopy was performed by using a PRESS with TR/TE 1530/100 ms, before chemotherapy and after the 3rd cycle. 1H MRS was processed in LCmodel. RESULTS: Of 20 patients, 7 responded to neoadjuvant chemotherapy and 13 did not. In responders, the mean concentration of tCho before therapy was 4.7±2.5 mmol/kg, which showed statistically significant reduction after therapy. In non-responders, the mean tCho concentration before therapy was 2.9±0.9 mmol/kg which remained the same or increased after the 3rd cycle of neoadjuvant chemotherapy (2.7±2.5 mmol/kg; range from 2.05 to 5.79 with no statistical significance). Compared to reference healthy group, tCho concentrations were increased in all cases. CONCLUSIONS: 1H MRS appears to be valuable technique for evaluation of response to neoadjuvant chemotherapy of patients with musculoskeletal tumors (MSK).

Treatment results of childhood Ewing's sarcoma of the bone in Serbia.

PURPOSE: The purpose of this study was to present treatment results of childhood Ewing's sarcoma (ES) of the bone in Serbia and to analyze prognostic factors. METHODS: We performed a detailed analysis on a series of 107 patients with ES of the bone treated at the Institute for Oncology and Radiology of Serbia between 2000 and 2014, using modern multimodal therapy. RESULTS: Median age at the time of diagnosis was 14 years, with 56.07% of the patients being ≤14 years. There was a male predominance (59.81%). The most common primary sites were pelvis (25.23%), femur (17.76%) and tibia (12.15%). Thirty-four patients (31.78%) had metastatic disease, 17 of which had isolated lung metastases, 9 bone metastases and 8 patients had both. Tumor size ≤ 8 cm had 38.32% and >8 cm had 61.68% patients. Overall, 51.4% patients underwent surgery and radiotherapy as a local treatment modality after neoadjuvant chemotherapy. Radiotherapy alone was performed in 24 patients. The 5-year overall survival (OS) was 43.8%. For patients with localized disease, the 5-year OS was 56.4% and for patients with metastatic disease 17.6%. In patients with initially nonmetastatic disease, age under 14 years, with tumor size <8 cm and a good response to the neoadjuvant chemotherapy, the OS correlated with better outcome. CONCLUSIONS: Modern multidisciplinary approach in treatment of childhood ES of the bone in accordance with the recommended pediatric protocols, gives good treatment results. Therapy should be performed in referral centers.