Prognostic Value of Lactate Dehydrogenase in Patients with Melanoma Treated with Pembrolizumab.

INTRODUCTION: Elevated LDH levels have been extensively reported as a biomarker of poorer outcome in patients with melanoma during the chemotherapeutic era. The role of LDH level as a prognostic factor for treatment outcomes in patients with metastatic melanoma treated with immunooncological therapy has also been reported but requires further analysis. OBJECTIVES: In this study, we aimed to evaluate the prognostic value of lactate dehydrogenase (LDH) among patients with metastatic and unresectable melanoma treated with pembrolizumab in terms of progression-free survival (PFS). METHODS: The study included 59 patients with unresectable and metastatic melanoma treated with pembrolizumab. A comparison was performed between patients with normal and elevated levels of LDH in terms of PFS, with subgroup analysis. RESULTS: There was a significant reduction in PFS among patients with elevated levels of LDH compared with patients with normal levels of LDH (NR vs. 5 months; P=0.02). Patients with elevated LDH levels were older (P=0.01), with liver metastasis (P=0.004), and with less frequent CNS deposits (P=0.028). CONCLUSION: Although novel agents improved outcomes in patients with melanoma, high levels of LDH persist as an independent prognostic biomarker of poor prognosis.

Human health risk assessment based on direct and indirect exposure to endocrine disrupting herbicides in drinking, ground, and surface water in Croatia.

The recognition of certain herbicides as endocrine disrupting compounds has raised concerns due to their ability to interfere with the normal functioning of the endocrine system, which regulates various physiological processes in organisms. The objective of this study was to assess the possible human health risks associated with terbuthylazine and endocrine-disrupting herbicides atrazine, acetochlor, and metolachlor in the drinking, surface, and groundwater of the Zagreb city region, Croatia. We relied on advanced statistical methods and principal component analysis (PCA), which revealed higher levels of atrazine and acetochlor in drinking and groundwater samples and higher presence of metolachlor and terbuthylazine in surface waters. To evaluate the danger to human health, various exposure scenarios have been assessed. The risk of direct human exposure to analyzed herbicides through drinking or bathing with drinking (tap) or groundwater, as well as from recreational activities like swimming in rivers, streams, and lakes, has been quantified. In addition to these direct exposure scenarios, indirect ones based on consumer goods, fruits, and vegetables, treated with surface and groundwater for irrigation, were assessed to investigate the danger to human health. Judging by the reported herbicide levels there was no significant risk of carcinogenic (CR ≤ 1 × 10-6) or non-carcinogenic (HI < 1) diseases, not even when we assessed the so-called "cocktail effect" of combined the herbicide exposure in different waters.

Laparoscopic to robotic living donor nephrectomy: Is it time to change surgical technique?

BACKGROUND: We aimed to explore differences in outcomes of robotic and laparoscopic donor nephrectomies (LDN). METHODS: This study compared robotic and laparoscopic surgical techniques for live donor nephrectomies in 153 patients at a single centre. RESULTS: Left nephrectomies were more common in both groups, but with no significant difference between the groups (76.6% vs. 77.6%, p = 0.88). The robotic donor nephrectomies (RDN) group experienced significantly less blood loss (60 vs. 134 mL, p < 0.01), but warm ischaemia time was similar between groups (3.2 vs. 3.7 min, p = 0.54).The RDN group had decreased subjective pain scores (3.54 vs. 4.21, p = 0.04) and shorter length of hospitalisation (2.22 vs. 3.04 days, p < 0.01).There were also fewer complications in the RDN than the LDN group (4 vs. 8, p = 0.186). CONCLUSION: This study demonstrated that RDN is a safe and alternative to LDN. Decreased blood loss and hospital stays and fewer complications may reflect decreased tissue manipulation with robotic assistance.

Review of Active Surveillance in Underrepresented and High-Risk Populations: Feasibility and Safety.

PURPOSE OF REVIEW: The purpose of this review is to investigate the current use and effectiveness of active surveillance (AS) for clinical low-risk prostate cancer (PCa) in men considered to be "high-risk" based on the factors of race, genetics, healthcare access, and socioeconomic status. RECENT FINDINGS: Advances in molecular biomarkers and imaging have improved the detection, risk stratification, and treatment of PCa. Still, overdiagnosis and overtreatment of indolent disease remain a concern. AS is therefore the preferred option for clinical low-risk disease. Yet, because of the variability in PCa presentation based on the aforementioned environmental and genetic factors, the question remains: Is active surveillance a safe option for everyone? Provider hesitancy should not necessarily exclude high-risk men from participating in AS. Rather, clinicians should employ shared decision-making, sound clinical judgment, and stringent follow-up in order to effectively counsel AS candidates and optimize AS-related outcomes in "high-risk" individuals.

Human health risks and benefits assessment based on OCPs, PCBs, toxic elements and fatty acids in the pelagic fish species from the Adriatic Sea.

Benefits and risks of the fish consumption should be assessed to balance the ingestion of healthy omega-3 fatty acids and adverse chemicals. Persistent organic pollutants-POPs (organochlorine pesticides-OCPs and polychlorinated biphenyls-PCB), macro- and micro-elements and fatty acid contents were determined in six fish species from the Adriatic Sea to assess health risks for consumers (worst-case scenario, diseases development risks and benefit-risk). 16 element, 24 POPs and 14 fatty acid contents were determined in six pelagic species which can be used in human diet. Element concentrations were determined by inductively coupled plasma mass spectrometry (ICP-MS), POPs by high-resolution gas chromatography and fatty acid content by gas-liquid chromatography. Diet based on chub mackerel and round sardinella showed lower daily intake (DI) of POPs and highest DI of essential omega-3 fatty acids than other investigated species. Lower ingestion of toxic elements can be observed by consuming anchovy and round sardinella. Based on POP concentrations, there was not observed non-carcinogenic (HI) nor carcinogenic (CR) risks for consumers. Based on element concentrations, there was low HI (0.1 ≥ HI ≥ 1), while the maximum HIs and outlier values (horse mackerel and anchovy samples) implied the presence of HI (HI > 1). The most significant contributor to total non-carcinogenic and carcinogenic risks was inorganic arsenic (inorganic As). Acceptable CR for consumers was assessed, but maximum CR for consumers of horse mackerel and anchovy (CR ≥ 1 × 10-6) showed adverse effects on human health. There were low HIs for developing cardiovascular, nervous, and reproductive diseases, and maximum HIs were higher than 1. Acceptable (1 × 10-4≥CR ≥ 1 × 10-6) risks were observed for developing cancer of nervous system and reproductive organs. Among investigated fish samples, those with higher Æ©BR (benefit-risks) and BR for arsenic (As) than median value have a higher risk than benefits in the human diet.

Pollution and Health Risk Assessments of Potentially Toxic Elements in Soil and Sediment Samples in a Petrochemical Industry and Surrounding Area.

The pollution state and health risk assessment of potentially toxic elements (PTE) in soil and sediment samples of the petrochemical industry and its surrounding area are evaluated in this study. The pseudo-total contents of Ba, Cd, Co, Cu, Cr, Mn, Ni, Pb, V, Zn, As, Hg, and Se were measured by inductively coupled plasma-optical emission spectrometry (ICP/OES) in analyzed samples. Instead of determining total content, we performed aqua regia of the samples. The silicate matrix remained, and the quantities of elements that are within the silicate matrix do not represent an environmental danger. The soils from the chlor-alkali plant are highly polluted by Hg (the enrichment factor values were above 6000), and by Cu, Cd, Pb, and Zn, while the sediment samples from the wastewater channel are polluted with Cr, Cd, and Hg. The measured element contents are used for calculating health risk criteria for a composite worker (a worker who is exposed, long-term, during the work day) and for residential people. Hg is the element that mainly contributes to non-carcinogenic risks within the petrochemical area. The highest value of total carcinogenic risk obtained in the sediment sample from the wastewater channel, and the metal that mostly contributes is Cr. The areas closest to the petrochemical industry have higher values of health risk criteria parameters and pollution indices. The areas that are located further to the north and south from the petrochemical industry are less burdened with the analyzed elements, which is significant because the closest city and village are situated in those directions.

Cadmium retention and distribution in contaminated soil: effects and interactions of soil properties, contamination level, aging time and in situ immobilization agents.

As soil cadmium (Cd) contamination becomes a serious concern and one of the significant environmental pollution issues all over the world, knowledge of the basic chemistry, origin, inputs, sources, quantity, chemical forms, reactions, as well as the fate and transport of Cd in different types of soil is crucial for better understanding Cd bioavailability, health risks and remedial options. This study aimed to increase the current knowledge on the complex interdependence between the factors affecting behavior, transport and fate of Cd in the soil and to test and compare the performance of the stabilization agents in different soil types. Soils demonstrated various sorption affinity and capacity for Cd accumulation, which proved to be positively correlated with soil pH and the cation exchange capacity (CEC). With increasing levels of contamination, sequential extraction analysis showed the highest increase of relative Cd amounts in the exchangeable fraction regardless of the soil properties, suggesting that added Cd is principally associated with the easily accessible and mobile fraction. For different initial Cd concentrations and soil types, Cd sorption reached the quasi-equilibrium within 24 h of contact. Prolonged aging (two months) influenced the natural stabilization of Cd in all types of soil, but only at low contamination level. The application of both, conventional (slaked lime Ca(OH)2) and alternative phosphate-rich (annealed bovine bones B400) amendments, resulted in Cd relocation and reduction of exchangeable Cd content. Although the effect was smaller when apatite amendment was utilized, observed re-distribution of Cd to more stable soil fractions is preferable for achieving long-term stabilization. Cd concentrations extracted in exchangeable and acid soluble fractions after the treatments of contaminated soil samples suggest that the practical applicability of in situ immobilization depends on the soil properties and the level of contamination, as well as that effect, should be monitored for the possible re-mobilization of Cd.

Organochlorine pesticides (OCPs) and polychlorinated biphenyls (PCBs) in Cyprinidae fish: Towards hints of their arrangements using advanced classification methods.

To tackle the ever-present global concern regarding human exposure to persistent organic pollutants (POPs) via food products, this study strived to indicate associations between organochlorine pesticides (OCPs) and polychlorinated biphenyls (PCBs) in lake-fish tissue depending on the species and sampling season. Apart from the monitoring initiatives recommended in the Global Monitoring Plan for POPs, the study discussed 7 OCPs and 18 PCB congeners determined in three Cyprinidae species (rudd, carp, and Prussian carp) from Vransko Lake (Croatia), which are widely domesticated and reared as food fish across Europe and Asia. We exploit advanced classification algorithms, the Kohonen self-organizing maps (SOM) and Decision Trees (DT), to search for POP patterns typical for the investigated species. As indicated by SOM, some of the dioxin-like and non-dioxin-like PCBs (PCB-28, PCB-74, PCB-52, PCB-101, PCB-105, PCB-114, PCB-118, PCB-156 and PCB-157), α-HCH and ß-HCH caused dissimilarities among fish species, but regardless of their weight and length. To support these suggestions, DT analysis sequenced the fish species and seasons based on the concentration of heavier congeners. The presented assumptions indicated that the supplemental application of SOM and DT offers advantageous features over the usually rough interpretation of POPs pattern and over the single use of the methods.

Canned sea fish marketed in Serbia: their zinc, copper, and iron levels and contribution to the dietary intake.

The aim of this study was to determine the levels of Zn, Cu, and Fe in three canned fish species marketed Serbia to see if they meet recommended daily intake requirements or exceed safety limits. We collected a total of 207 samples of canned tuna, sardine, and mackerel, in oil or tomato sauce and analysed them with inductively coupled plasma mass spectrometry (ICP-MS) after acid digestion. The highest levels were obtained for Zn (15.1 mg kg-1) and Cu (1.37 mg kg-1) in sardine in oil and tomato sauce, respectively, and for Fe (18.98 mg kg-1) in mackerel in tomato sauce. Our results keep within the ranges reported by several national food databases and available literature data, with a few exceptions. Our findings also single out canned sardines as the richest source of the three essential elements combined. The estimated daily intake (EDI) of the three essential elements, however, was subpar, and ranged between 0.14 % and 0.72 % of the recommended dietary allowance (RDA) for Zn, Cu, and Fe.

Estimation of Cadmium uptake by tobacco plants from laboratory leaching tests.

The objective of the present study was to determine the impact of cadmium (Cd) concentration in the soil on its uptake by tobacco plants, and to compare the ability of diverse extraction procedures for determining Cd bioavailability and predicting soil-to-plant transfer and Cd plant concentrations. The pseudo-total digestion procedure, modified Tessier sequential extraction and six standard single-extraction tests for estimation of metal mobility and bioavailability were used for the leaching of Cd from a native soil, as well as samples artificially contaminated over a wide range of Cd concentrations. The results of various leaching tests were compared between each other, as well as with the amounts of Cd taken up by tobacco plants in pot experiments. In the native soil sample, most of the Cd was found in fractions not readily available under natural conditions, but with increasing pollution level, Cd amounts in readily available forms increased. With increasing concentrations of Cd in the soil, the quantity of pollutant taken up in tobacco also increased, while the transfer factor (TF) decreased. Linear and non-linear empirical models were developed for predicting the uptake of Cd by tobacco plants based on the results of selected leaching tests. The non-linear equations for ISO 14870 (diethylenetriaminepentaacetic acid extraction - DTPA), ISO/TS 21268-2 (CaCl2 leaching procedure), US EPA 1311 (toxicity characteristic leaching procedure - TCLP) single step extractions, and the sum of the first two fractions of the sequential extraction, exhibited the best correlation with the experimentally determined concentrations of Cd in plants over the entire range of pollutant concentrations. This approach can improve and facilitate the assessment of human exposure to Cd by tobacco smoking, but may also have wider applicability in predicting soil-to-plant transfer.

Pollution by Urticaceae pollen-influence of selected air pollutants and meteorological parameters.

The goal of this study was to analyze the influence of pollutants (concentrations of NO2, SO2, and soot in the air) and meteorological parameters (air temperature, humidity, wind speed, air pressure, cloud index) on Urticaceae pollen type emission measured in the region of Subotica, Serbia. The concentrations of the air pollutants, Urticaceae pollen, and meteorological parameters were measured over a 5-year period (2009-2013), followed by a statistical analysis of the values obtained. For most of the years examined, the concentration of NO2 correlates significantly with the concentration of Urticaceae pollen type. It was also established that air temperature, humidity, wind speed, atmospheric pressure, and cloud index have an influence on Urticaceae pollen type emission, while SO2 and soot do not contribute.

Interpretative optimization and artificial neural network modeling of the gas chromatographic separation of polycyclic aromatic hydrocarbons.

An interpretative strategy (factorial design experimentation+total resolution analysis+chromatogram simulation) was employed to optimize the separation of 16 polycyclic aromatic hydrocarbons (PAHs) (naphthalene, acenaphthylene, acenaphthene, fluorene, phenanthrene, anthracene, fluoranthene, pyrene, chrysene, benzo(a)anthracene, benzo(k)fluoranthene, benzo(b)fluoranthene, benzo(a)pyrene, indeno(1,2,3-c,d)pyrene, dibenzo(a,h)anthracene, benzo(g,h,i)perylene) in temperature-programmed gas chromatography (GC). Also, the retention behavior of PAHs in the same GC system was studied by a feed-forward artificial neural network (ANN). GC separation was investigated as a function of one (linear temperature ramp) or two (linear temperature ramp+the final hold temperature) variables. The applied interpretative approach resulted in rather good agreement between the measured and the predicted retention times for PAHs in both one and two variable modeling. The ANN model, strongly affected by the number of input experiments, was shown to be less effective for one variable used, but quite successful when two input variables were used. All PAHs, including difficult to separate peak pairs (benzo(k)fluoranthene/benzo(b)fluoranthene and indeno(1,2,3-c,d)pyrene/dibenzo(a,h)anthracene), were separated in a standard (5% phenyl-95% dimethylpolysiloxane) capillary column at an optimum temperature ramp of 8.0 degrees C/min and final hold temperature in the range of 260-320 degrees C.

Polycyclic aromatic hydrocarbons (PAHs) in different types of smoked meat products from Serbia.

The contents of the16 EU priority PAHs in six different meat products from Serbia (beef ham, pork ham, bacon without skin, bacon with skin, cajna sausage and sremska sausage) were examined during the process of smoking. All these meat products from meat industry Zlatiborac, Mackat, Serbia presented in this study, have not previously been analysed concerning to their contents of PAH compounds. Determination and quantification of PAHs in meat products were performed by a Fast GC/HRMS method. The maximum level for benzo[a]pyrene (BaP) of 5µg/kg in smoked meat products was not exceeded in any samples. BaP comprises in general 4.6% of the total sum of the 16 EU priority PAHs and 15.2% of the total sum of the 12 IARC PAH compounds. The suitability of BaP as a marker both for 16 EU priority PAHs and 12 IARC probably and possibly carcinogenic PAHs was checked by applying correlation analysis.

Speciations of trace metals in the Danube alluvial sediments within an oil refinery.

A sequential extraction procedure was applied to identify forms of Ni, Zn, Pb and Cu with Fe- and Mn-oxides associated in alluvial sediments of the River Danube within Pancevo Oil Refinery (Serbia). The five steps of the sequential extraction procedure partitioned metals into: CH(3)COONH(4) extractable (S1); NH(2)OH.HCl carbonate extractable and easily reducible (S2); (NH(4))(2)C(2)O(2)/H(2)C(2)O(2) moderately reducible (S3); H(2)O(2)-HNO(3) organic extractable (S4); and HCl acid soluble residue (S5). Extracted concentrations of trace metals, analyzed after all five steps, were found to be (mg kg(-1)) for Mn: 656, Fe: 26734, Ni: 32.3, Zn: 72.8, Pb: 13.4 and Cu: 27.0. Most of the elements were found in acid soluble residue, characterizing stable compounds in sediments. Non-residual fractions of trace metals (sum of the first four fractions) were analyzed because they are more bioavailable than the residual amount. Correlation analysis and two multivariate analysis methods (principal component and cluster analysis) were used to understand and visualize the associations between the non-residual fractions of trace metals and certain forms, more or less crystalline of Fe- and Mn-oxides within the analyzed sediments, since Fe- and Mn-oxides play an important role in trace metal sorption within aquatic systems, especially within the Danube alluvium where the fluctuations of groundwater are very frequent and the level of groundwater could come close to surface.