Nutritional status and risk of malnutrition.

Malnutrition is a global health problem that is not limited to developing countries. So far, it is one of the underdiagnosed and curative medical problems. THE AIM of our observation was to evaluate the nutritional status of patients at risk of malnutrition. METHODS AND PATIENTS: We retrospectively evaluated 140 patients from the Gastroenterology Clinic and the Center for Home Parenteral Nutrition (HPN) at the University Hospital Bratislava, Slovakia. Patients were indicated for examination as part of the entry screening for malnutrition or consultation examination in patients presenting with signs of malnutrition. Based on the determination of the body mass index (BMI), the completed questionnaire of nutritional risk screening (NRS) and the determination of the state of performance, we evaluated the nutritional status of the patient and subsequently started enteral, or parenteral nutrition. RESULTS: We recorded a statistically significant negative correlation between BMI and malnutrition risk (p<0.001), ie. the lower the BMI, the higher the risk of malnutrition. We did not observe a relationship between age, diagnoses and the incidence of BMI-related malnutrition in the study group of patients. CONCLUSION: Properly applied clinical nutrition, whether enteral, parenteral, or a combination thereof, can significantly affect morbidity and mortality in patients with malnutrition or the risk of its development. Unfortunately, Slovakia is still lagging behind developed countries in its implementation as part of a comprehensive treatment of patients (Tab. 2, Fig. 4, Ref. 28).

Risk of chronic thromboembolic pulmonary hypertension after splenectomy.

OBJECTIVES: The purpose of the clinical study was to evaluate the risk of chronic thromboembolic pulmonary hypertension (CTEPH) after splenectomy and to analyze some biochemical and coagulation parameters. BACKGROUND: CTEPH caused by incomplete resolution of thromboemboli and irreversible remodeling of the pulmonary arteries is a progressive, and without treatment a fatal disease. Although the definite etiopathophysiology is not quite perfectly researched, numerous clinical conditions associated with CTEPH as history of pulmonary embolism, infected ventriculoatrial shunts or permanent intravascular devices, high-dose thyroid hormone replacement, malignancy and chronic inflammatory diseases, including osteomyelitis, inflammatory bowel diseases, are well accepted. These factors also include splenectomy. METHODS: We performed a prospective follow-up of patients after splenectomy in the period of 5 years (2017-2022). The study population consisted of 62 adult post-splenectomy patients, who were divided into 3 groups based on the cause of the splenectomy - trauma, haematologic diseases, and others. The study population was analyzed in terms of gender, age, cause of splenectomy, blood group, clinical risk factors and thrombophilic conditions. Some basic haemocoagulation parameters and selected coagulation and biochemical parameters were analyzed. All patients underwent screening echocardiography, symptomatic patients repeatedly. In the presence of pulmonary hypertension (PH) unexplained by other diseases, patients underwent ventilation/perfusion lung scan performed to confirm/exclude perfusion defects typical for CTEPH. If PH and perfusion defects persisted despite effective 3-month anticoagulation therapy, patients underwent right heart catheterization to confirm/exclude CTEPH. RESULTS: The study confirmed a higher incidence of CTEPH after splenectomy compared to published data, the 5-year cumulative incidence was 3.2 %. Other detected clinical risk factors did not affect the incidence of thromboembolism/CTEPH after splenectomy. In our study, the strongest factor in terms of the incidence of thromboembolism/CTEPH after splenectomy was the presence of a thrombophilia detected before the screening echocardiography. Tested haemocoagulation and biochemical parameters in small patient subgroup had no impact on the incidence of thromboembolism/CTEPH - however, the limiting factor was a small patient subgroup. CONCLUSION: The results of the study suggest that the incidence of thromboembolism after splenectomy was consistent with the present data, but the incidence of CTEPH after splenectomy was significantly higher. This suggests that post-splenectomy condition may be an independent risk factor for CTEPH and may imply different management of these patients in the future (Tab. 5, Ref. 18).

The performance and limitations of PCA3, TMPRSS2:ERG, HOXC6 and DLX1 urinary markers combined in the improvement of prostate cancer diagnostics.

BACKGROUND: Prostate cancer (PCa) is the second most commonly diagnosed cancer in men. To date, the role of the combined application of long non-coding RNAs (PCA3, DLX1, HOXC6, TMPRSS2:ERG) for obtaining the most accurate method of detection of PCa has not yet been comprehensively investigated. METHODS: In total 240 persons were included in the retrospective study. Among them were 150 patients with confirmed PCa, 30 patients with benign prostatic hyperplasia, 30 patients with active chronic prostatitis and 30 healthy volunteers. In all patients, the urine samples were collected prior to biopsy or treatment. Polymerase chain reaction with reverse transcription was performed to detect the expression level of PCA3, HOXC6, DLX1 and the presence of the TMPRSS2:ERG transcript. RESULTS: PCA3 was detected in urine samples in all cases. Using a PCA3 score of 56 allowed the differentiation between PCa and all other cases with a sensitivity of 61% and specificity of 96% (p < 0.001) while a PCA3 score threshold value of 50 resulted in a differentiation between clinically significant PCa (ISUP grades 2-5) and all other cases with a sensitivity of 93% and specificity of 93% (p < 0.001). The TMPRSS2:ERG expression in urine was detected exclusively in the group of patients with PCa and only in 16% of all cases. CONCLUSIONS: PCA3 score detected in urine demonstrated moderate sensitivity and good specificity in differentiation between PCa and non-PCa and high sensitivity and specificity in differentiation between clinically significant PCa and non-PCa.

Flavonoids attenuate cancer metabolism by modulating Lipid metabolism, amino acids, ketone bodies and redox state mediated by Nrf2.

Metabolic reprogramming of cancer cells is a common hallmark of malignant transformation. The preference for aerobic glycolysis over oxidative phosphorylation in tumors is a well-studied phenomenon known as the Warburg effect. Importantly, metabolic transformation of cancer cells also involves alterations in signaling cascades contributing to lipid metabolism, amino acid flux and synthesis, and utilization of ketone bodies. Also, redox regulation interacts with metabolic reprogramming during malignant transformation. Flavonoids, widely distributed phytochemicals in plants, exert various beneficial effects on human health through modulating molecular cascades altered in the pathological cancer phenotype. Recent evidence has identified numerous flavonoids as modulators of critical components of cancer metabolism and associated pathways interacting with metabolic cascades such as redox balance. Flavonoids affect lipid metabolism by regulating fatty acid synthase, redox balance by modulating nuclear factor-erythroid factor 2-related factor 2 (Nrf2) activity, or amino acid flux and synthesis by phosphoglycerate mutase 1. Here, we discuss recent preclinical evidence evaluating the impact of flavonoids on cancer metabolism, focusing on lipid and amino acid metabolic cascades, redox balance, and ketone bodies.

Additive prognostic value of high baseline coronary flow velocity to ejection fraction during resting echocardiography: 3-year prospective study.

BACKGROUND: There is a lack of information about the prognostic value of high velocity in coronary arteries during echocardiography. The present study was aimed at investigating the three-year prognostic value of coronary velocity assessment in all patients who were referred for echocardiography examination. METHODS: The prospective study comprises 747 consecutive patients. Death, myocardial infarction (MI), acute coronary syndrome (ACS), and/or revascularisation were defined as major adverse cardiac events (MACE). Routine echocardiography was added with coronary velocity assessment in the left main, anterior descending, or circumflex coronary arteries by the Doppler method. RESULTS: During a median follow-up of 36 months, 192 patients experienced MACE. Deaths occurred more frequently in patients with high local velocity in proximal left-sided segments vs. in middle left-sided segments vs. patients without high coronary velocity (9 vs. 3 vs. 1%, p < 0.0001). Death/MI/ACS occurred in 17 vs. 7 vs. 1%, p < 0.0001, respectively. Age (HR 1.04, 95% CI 1.00; 1.06; p < 0.04), a velocity more than 65 cm/s in any proximal segments of the arteries (HR 4.7, 95% CI 1.9; 11.9; p < 0.002), ejection fraction (HR 0.97, 95% CI 0.94; 0.99; p < 0.007) were strong independent prognostic predictors of death/MI/ACS. The maximal velocity of coronary flow velocity had a significant additive prognostic value to ejection fraction. CONCLUSIONS: The coronary velocity parameters give long-term prognostic information that can be used to identify persons with a high risk of MACE in consecutive non-selected patients.

Prognostic value of Doppler echocardiographic coronary flow velocity assessment at rest in elderly patients.

BACKGROUND: Atherosclerosis and coronary artery disease (CAD) are a common condition and cause of death in the elderly population. There are difficulties with risk assessment in the elderly as the objectification of their symptomatic status can be challenging due to neuromuscular weakness, physical deconditioning or neurological, orthopaedic, peripheral vascular, or respiratory limitations. Non-invasive coronary artery velocity assessment by Doppler method at rest could be helpful in the elderly population. To evaluate the prognostic role of coronary artery ultrasound assessment in a non-selected elderly population in everyday clinical practice. METHODS: One hundred forty-five patients, aged ≥75years (99 women; 80 ± 4 years), formed the study group. Left coronary artery flows were scanned in addition to conventional echocardiography. During a median follow-up of 26 months, 16 deaths and 2 non-fatal MI occurred. RESULTS: In multivariable analysis, maximal coronary velocity was the only independent predictor for mortality (heart rate [HR]: 1.02, 95%, CI: 1.01-1.04, p < .0005) and for mortality/MI (HR: 1.02, 95%, CI: 1.01-1.03, p < .0001). The value of 110 cm/s maximal coronary flow velocity (CFL) in the proximal segments of left arteries was the best predictor for death, sensitivity 50%, specificity 90%, p < .005. The annual mortality rate was 16.6% persons/year for patients with elevated CFL ≥110 cm/s. The value 81 cm/s was the best predictor for death/MI, sensitivity 61%, specificity 80%, p < .0005; annual mortality rate was 11.2% persons/year for patients with elevated CFL ≥81 cm/s (p < .0001). CONCLUSION: Doppler CFL scanning during routine echocardiography is a feasible and valuable tool for assessment of short-term prognosis in elderly patients.

Effect of home parenteral nutrition in malnourished patients.

OBJECTIVE: The goal of our research was to determine the impact of clinical nutrition in the form of home parenteral nutrition (HPN) in patients with nutritional disorders, most often caused by diseases of the digestive tract, with the risk of developing malnutrition. PATIENTS AND METHODS: We retrospectively evaluated 39 patients from the Gastroenterology Clinic and the Home Parenteral Nutrition Center of the University Hospital Bratislava, whose nutritional status was evaluated based on the determination of the body mass index (BMI), the completed nutritional risk screening (NRS) questionnaire and the determination of performance status. Subsequently, after fulfilling the criteria for HPN, the initiation of parenteral nutrition (PN) followed, implemented in a domestic environment for the following two years as HPN. During this period, we did a monthly check-up of the objective condition and laboratory parameters of the enrolled patients, which were the basis for adjusting the nutritional treatment. We also evaluated the occurrence of infectious and thrombotic complications clinically and on the basis of laboratory parameters focused on culture and hemocoagulation examination. After two years, we performed control exit examinations, which we compared with the entrance examinations and statistically evaluated the success of the treatment. We evaluated the obtained data using standard statistical methods. RESULTS: During HPN, there was a statistically significant elevation of the individual monitored values ​​(BMI, absolute lymphocytes count, cholesterol, cholinesterase, total proteins, albumins), which clearly proves correctly indicated and managed HPN. We recorded vein thrombosis in v. subclavia and v. jugularis in 6 (15 %) patients. Subsequent catheter extraction was necessary after unsuccessful catheter insertion. In 13 (33 %) patients, tunneled catheter replacement was required due to infection. The mortality rate in our group was 8 % (3 patients). These were female patients aged 39, 42, and 66 years. The cause of death in all of these patients was the underlying diagnosis (oncohematological disease, systemic connective tissue disease, and repeated resections of the digestive tract for inflammatory GIT disease with the development of severe malnutrition). We recorded a positive effect of applied HPN in all three patients until death.We did not register any factors that would have a relevant influence on the success of administered HPN. CONCLUSION: Based on our results, we can conclude that the patients included in the HPN were correctly indicated, and all of them, based on the monitored parameters (regardless of gender, age, initial diagnosis, or BMI value), benefited from the applied treatment, which was correctly chosen based on their individual needs. Our results clearly document the irreplaceable role of HPN in the management of patients with nutritional intake disorders leading to the development of malnutrition (Tab. 2, Fig. 10, Ref. 44). Text in PDF www.elis.sk Keywords: malnutrition, nutritional risk screening, clinical nutrition, home parenteral nutrition, complications.

Kidney manifestations of mitochondrial disorders.

Mitochondria are intracellular organelles involved in a number of key biologic processes in the cell, including energy production, redox signaling, calcium homeostasis, inflammation, senescence, innate immune response, and mitophagy. Mitochondrial cytopathies include a heterogeneous group of diseases that are characterized by impaired oxidative phosphorylation, leading to multi-organ involvement and progressive clinical deterioration. Mitochondrial cytopathies can result from mitochondrial or nuclear DNA mutations. Mitochondrial defects play an important role in the pathogenesis of nephropathies as tubular syndromes, interstitial nephritis, focal and segmental glomerulosclerosis and diabetic nephropathy. The role of mitochondria in a pathogenesis of nephrotoxicity and kidney carcinogenesis is also discussed (Tab. 2, Fig. 7, Ref. 100). Keywords: mitochondrial nephropathy, interstitial nephritis, glomerulosclerosis, diabetic nephropathy, nephrotoxicity, mitochondrial cytopathies.

Should we routinely assess coronary artery Doppler in daily echocardiography practice?

A lot of people with coronary artery disease do not have specific symptoms, and myocardial infarction or death are the first manifestation of the disease. New accurate, non-invasive and safe screening methods are required that can assess the prognosis of patients during routine examinations performed on millions of people. The aim of this review was to discuss the current literature regarding the utility of non-invasive ultrasound imaging of the coronary artery in assessing a patient's prognosis in daily practice. Assessment of coronary artery flow during common stress echocardiography or echocardiography can provide additive incremental prognostic information without the burden of radiation. Exercise or pharmacologic stress echocardiography tests combined with coronary flow velocity reserve assessment has advantages over stress tests based only on regional wall motion abnormalities. Scanning of main coronary arteries as an addition to routine echocardiography can reveal patients at high risk of adverse cardiac events in the near future.

Health implication of vitamin D on the cardiovascular and the renal system.

Vitamin D regulates the calcium and phosphorus balance in the body. The activated form of vitamin D (1 α,25-dihydroxyvitamin D) binds to vitamin D receptor which regulates genes that control cell proliferation, differentiation and apoptosis. In the cardiovascular system, the vitamin D receptor is present in cardiomyocytes and the arterial wall. A clear correlation between vitamin D level and cardiovascular diseases is established. Vitamin D deficiency affects the renin-angiotensin system leading to ventricular hypertrophy and eventually to stroke. While clinical trials highlighted the positive effects of vitamin D supplements on cardiovascular disease these still need to be confirmed. This review outlines the association between vitamin D and cardiovascular and renal disease summarising the experimental data of selective cardiovascular disorders.

Peak Responses during Exercise Treadmill Testing using Individualized Ramp Protocol and Modified Bruce Protocol in Elderly Patients.

BACKGROUND: Exercise capacity is well known to be an important prognostic factor in patients with cardiovascular disease and among healthy persons. AIM: To determine if there are any differences between the peak exercise response during exercise treadmill testing with the individualized ramp protocol and the modified Bruce protocol in elderly patients. MATERIALS AND METHODS: The study included 40 patients (both male and female), aged 70 years and older, who had not had a baseline history of the confirmed coronary artery disease or heart failure diagnoses. All patients underwent exercise treadmill testing using modified Bruce protocol and individualized ramp protocol for 2 consecutive days. Peak heart rate, peak systolic and diastolic blood pressure, peak pressure-rate double product, exercise duration, and peak metabolic equivalents were recorded in both tests. Perceived level of exertion was evaluated using the Borg 10-point scale. RESULTS: The average duration of exercise was longer for the ramp protocol than for the modified Bruce protocol. When the modified Bruce protocol was used, patients achieved a lower workload than they did in using the ramp protocol. The rating of perceived exertion using the revised Borg scale (0 to 10) was 5.6±1.4 for the ramp protocol and 8.7±1.4 for the modified Bruce protocol, which indicates that the patients found the ramp protocol easier. CONCLUSION: In elderly patients the individualized ramp treadmill protocol allows to achieve the optimal test duration with higher degrees of workload and greater patient comfort during the test more often than does the modified Bruce protocol.

Systemic treatment of the metastatic renal cell carcinoma: usefulness of the apparent diffusion coefficient of diffusion-weighted MRI in prediction of early therapeutic response.

Accurate prediction of early treatment response to systemic therapy (ST) with tyrosine kinase inhibitors (TKI) in patients with metastatic renal cell carcinoma (mRCC) could help avoid ineffective and expensive treatment with serious side effects. Neither RECIST v.1.1 nor Choi criteria successfully discriminate between patients with mRCC who received ST having a short or long time to progression (TTP). There is no biomarker, which is able to predict early therapeutic response to TKIs application in patients with mRCC. The goal of our study was to investigate the potential of apparent diffusion coefficient (ADC) of diffusion-weighted imaging (DWI) of MRI in prediction of early therapeutic response to ST with pazopanib in patients with mRCC. The retrospective study enrolled 32 adult patients with conventional mRCC who received pazopanib (mean duration-7.5 ± 3.45). The mean duration of follow-up was 11.85 ± 4.34 months. In all patients as baseline examination and 1 month after treatment, 1.5T MRI including DWI sequence was performed followed by ADC measurement of the main renal lesion. For assessment of the therapeutic response, RECIST 1.1 is used. Partial response (PR), stable disease (SD) and progressive disease (PD) were observed in 12 (37.50%), 10 (31.25%) and 10 (31.25%) cases with mean TTP of 10.33 ± 2.06 months (95% confidence interval, CI = 9.05-11.61), 7.40 ± 2.50 months (95% CI = 5.61-9.19) and 4.20 ± 1.99 months (95% CI = 2.78-5.62) accordingly (p < 0.05). There was no difference in change of main lesions' longest size 1 month after ST in patients with PR, SD and PD. Comparison of mean ADC values before and 1 month after systemic treatment showed significant decrease by 19.11 ± 10.64% (95% CI = 12.35-25.87) and by 7.66 ± 6.72% (95% CI = 2.86-12.47) in subgroups with PR and SD, respectively (p < 0.05). There was shorter TTP in patients with mRCC if ADC of the main renal lesion 1 month after the ST increased from the baseline less than 1.73% compared to patients with ADC levels above this threshold: 5.29 ± 3.45 versus 9.50 ± 2.04 months accordingly (p < 0.001). Overall, our findings highlighted the use of ADC as a predictive biomarker for early therapeutic response assessment. Use of ADC will be effective and useful for reliable prediction of responders and non-responders to systemic treatment with pazopanib.

The therapeutic effect of B-type natriuretic peptides in acute decompensated heart failure.

B-type natriuretic peptide (BNP) exhibits roles in natriuresis and diuresis, making it an ideal drug that may aid in diuresing a fluid-overloaded patient with poor or worsening renal function. Several randomized clinical trials have tested the hypothesis that infusions of pharmacological doses of BNP to acute heart failure (HF) patients may enhance decongestion and preserve renal function in this clinical setting. Unfortunately, none of these have demonstrated beneficial outcomes. The current challenge for BNP research in acute HF lies in addressing a failure of concept and a reluctance to abandon an ineffective research model. Future success will necessitate a detailed understanding of the mechanism of action of BNP, as well as better integration of basic and clinical science.

MicroRNA-15a tissue expression is a prognostic marker for survival in patients with clear cell renal cell carcinoma.

None of the currently investigated molecular markers demonstrated sufficient accuracy in prognostication of the renal cell carcinoma (RCC) oncologic outcomes; thus, none of them has been recommended for the application in the routine clinical practice. The role of miR-15a as a potential prognostic marker for RCC is still not unveiled. The aim of our study was to assess the expression of miR-15a in tumor tissues of the patients with RCC and to evaluate the possibility of its usage as a prognostic molecular biomarker of this disease. The retrospective included 64 adult patients with clear cell RCC (ccRCC) in whom radical or partial nephrectomy was conducted. After deparaffinization of formalin-fixed paraffin-embedded (FFPE) ccRCC specimens, the tissue expression of miR-15a was measured using the reverse transcription and quantitative polymerase chain reaction in the real time. For the reference, the expression of miR-15a was estimated in 15 FFPE tissue specimens of the normal renal parenchyma. Survival analysis involved all cases of non-metastatic RCCs (n = 57). Five-year cancer-specific survival (CSS) was estimated by means of the Kaplan-Meier method and was calculated from the date of surgery to the date of death. Patients with the RCC were characterized by significantly upregulated tumor tissue mean levels of miR-15a compared to the healthy controls: 0.10 ± 2.62 relative units (RU) versus 4.84E - 03 ± 3.11E - 03 RU (p < 0.001). Overexpression of miR-15a was strongly associated with poor histologic prognostic features of ccRCC. Poorly differentiated tumors tend to have more pronounced upregulation of miR-15a compared to highly differentiated lesions: Mean expression values were 4.57 ± 3.19 RU for Fuhrman grade 4 versus 0.02 ± 0.01 RU for Fuhrman grade 1 (p < 0.001). The metastatic involvement of the regional lymphatic nodules (N +) was associated with significantly upregulated miRNA-15a in comparison with N - cases: Mean expression values were 4.92 ± 2.80 RU versus 1.10 ± 2.29 RU, respectively (p < 0.001). In patients with miR-15a expression in RCC tissues ≤ 0.10 RU, mean 5-year CSS was significantly longer compared to patients with expression levels above this threshold: 92.31% (mean duration of survival-59.88 ± 0.12 months) versus 54.8% (mean duration of survival-49.74 ± 2.16 months), respectively (p < 0.001). The tissue expression of miR-15a could be used as a potential prognostic molecular biomarker for conventional RCC.

Latest Updates on Lipid Management.

Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of death worldwide. Despite the clinical long-term and near-term benefits of lowering cholesterol in, respectively, primary and secondary prevention of ASCVD, cholesterol levels remain under-treated, with many patients not achieving their recommended targets. The present article will review the latest updates on lipid management with emphases on the different classes of cholesterol-lowering agents and their clinical uses.

Markers of Atherosclerosis: Part 1 - Serological Markers.

Atherosclerosis is a major contributor to morbidity and mortality worldwide. With therapeutic consequences in mind, several risk scores are being used to differentiate individuals with low, intermediate or high cardiovascular (CV) event risk. The most appropriate management of intermediate risk individuals is still not known, therefore, novel biomarkers are being sought to help re-stratify them as low or high risk. This narrative review is presented in two parts. Here, in Part 1, we summarise current knowledge on serum (serological) biomarkers of atherosclerosis. Among novel biomarkers, high sensitivity C-reactive protein (hsCRP) has emerged as the most promising in chronic situations, others need further clinical studies. However, it seems that a combination of serum biomarkers offers more to risk stratification than either biomarker alone. In Part 2, we address genetic and imaging markers of atherosclerosis, as well as other developments relevant to risk prediction.

Markers of Atherosclerosis: Part 2 - Genetic and Imaging Markers.

This is Part 2 of a two-part review summarising current knowledge on biomarkers of atherosclerosis. Part 1 addressed serological biomarkers. Here, in part 2 we address genetic and imaging markers, and other developments in predicting risk. Further improvements in risk stratification are expected with the addition of genetic risk scores. In addition to single nucleotide polymorphisms (SNPs), recent advances in epigenetics offer DNA methylation profiles, histone chemical modifications, and micro-RNAs as other promising indicators of atherosclerosis. Imaging biomarkers are better studied and already have a higher degree of clinical applicability in cardiovascular (CV) event prediction and detection of preclinical atherosclerosis. With new methodologies, such as proteomics and metabolomics, discoveries of new clinically applicable biomarkers are expected.

MicroRNA-15a expression measured in urine samples as a potential biomarker of renal cell carcinoma.

INTRODUCTION: Currently, there is no accurate diagnostic molecular biomarker for renal cell carcinoma (RCC). The aim of this study was to assess the expression of microRNA-15a (miR-15a) in urine of patients with RCC and to evaluate its potential as a diagnostic molecular biomarker. MATERIALS AND METHODS: In total, 67 patients with solid renal tumors were enrolled: clear-cell RCC (ccRCC, n = 22), papillary RCC (pRCC, n = 16), chromophobe RCC (chRCC, n = 14), oncocytoma (n = 8), papillary adenoma (n = 2) and angiomyolipoma (n = 5). MiRNA-15a expression levels measurement in urine were performed using qPCR. Urine of 15 healthy volunteers without kidney pathology was used as control. RESULTS: We observed a difference in mean miR-15a expression values in groups of pre-operative patients with RCC, benign renal tumors and healthy persons (2.50E-01 ± 2.72E-01 vs 1.32E-03 ± 3.90E-03 vs 3.36E-07 ± 1.04E-07 RFU, respectively, p < 0.01). There was no difference in miR-15a expression between ccRCC, pRCC and chRCC (p > 0.05). Direct association between RCC size and miR-15a expression values was obtained (Pearson correlation coefficient-0.873). On the 8th day after nephrectomy, mean expression value in patients with RCC decreased by 99.53% (p < 0.01). MiR-15a expression differentiated RCC from benign renal tumors with 98.1% specificity, 100% sensitivity at a cut-off value of 5.00E-06 RFU, with AUC-0.955. CONCLUSIONS: MiR-15a expression measured in urine may be used as diagnostic molecular biomarker for RCC.

Melatonin and breast cancer: Evidences from preclinical and human studies.

The breast cancer affects women with high mortality and morbidity worldwide. The risk is highest in the most developed world but also is markedly rising in the developing countries. It is well documented that melatonin has a significant anti-tumor activities demonstrated on various cancer types in a plethora of preclinical studies. In breast cancer, melatonin is capable to disrupt estrogen-dependent cell signaling, resulting in a reduction of estrogen-stimulated cells, moreover, it's obvious neuro-immunomodulatory effect in organism was described. Several prospective studies have demonstrated the inverse correlation between melatonin metabolites and the risk of breast cancer. This correlation was confirmed by observational studies that found lower melatonin levels in breast cancer patients. Moreover, clinical studies have showed that circadian disruption of melatonin synthesis, specifically night shift work, is linked to increased breast cancer risk. In this regard, proper light/dark exposure with more selective use of light at night along with oral supplementation of melatonin may have benefits for high-risk women. The results of current preclinical studies, the mechanism of action, and clinical efficacy of melatonin in breast cancer are reviewed in this paper. Melatonin alone or in combined administration seems to be appropriate drug for the treatment of early stages of breast cancer with documented low toxicity over a wide range of doses. These and other issues are also discussed.

Differential diagnosis of the small renal masses: role of the apparent diffusion coefficient of the diffusion-weighted MRI.

INTRODUCTION: Renal cell carcinoma (RCC) accounts for approximately 3% of adult malignancies and more than 90% of neoplasms arising from the kidney. Uninformative percutaneous kidney biopsies vary from 10 to 23%. As a result, 7.5-33.6% of partial nephrectomies in patients with small renal masses (SRM) are performed on benign renal tumors. The aim of this study was to assess the feasibility of the apparent diffusion coefficient (ADC) of the diffusion-weighted imaging (DWI) of MRI, as RCC imaging biomarker for differentiation of SRM. METHOD: Adult patients (n = 158) with 170 SRM were enrolled into this study. The control group were healthy volunteers with normal clinical and radiologic findings (n = 15). All participants underwent MRI with DWI sequence included. RESULTS: Mean ADC values of solid RCC (1.65 ± 0.38 × 10-3 mm2/s) were lower than healthy renal parenchyma (2.47 ± 0.12 × 10-3 mm2/s, p < 0.05). There was no difference between mean ADC values of ccRCC, pRCC and chRCC (1.82 ± 0.22 × 10-3 vs 1.61 ± 0.07 × 10-3 vs 1.46 ± 0.09 × 10-3 mm2/s, respectively, p = ns). An inverse relationship between mean ADC values and Fuhrman grade of nuclear atypia of solid ccRCCs was observed: grade I-1.92 ± 0.11 × 10-3 mm2/s, grade II-1.84 ± 0.14 × 10-3 mm2/s, grade III-1.79 ± 0.10 × 10-3 mm2/s, grade IV-1.72 ± 0.06 × 10-3 mm2/s. This was significant (p < 0.05) only between tumors of I and IV grades. Significant difference (p < 0.05) between mean ADC values of solid RCCs, benign renal tumors and renal cysts was observed (1.65 ± 0.38 × 10-3 vs 2.23 ± 0.18 × 10-3 vs 3.15 ± 0.51 × 10-3 mm2/s, respectively). In addition, there was a significant difference (p < 0.05) in mean ADC values between benign cysts and cystic RCC (3.36 ± 0.35 × 10-3 vs 2.83 ± 0.21 × 10-3 mm2/s, respectively). CONCLUSION: ADC maps with b values of 0 and 800 s/mm2 can be used as an imaging biomarker, to differentiate benign SRM from malignant SRM. Using ADC value threshold of 1.75 × 10-3 mm2/s allows to differentiate solid RCC from solid benign kidney tumors with 91% sensitivity and 89% specificity; ADC value threshold of 2.96 × 10-3 mm2/s distinguishes cystic RCC from benign renal cysts with 90% sensitivity and 88% specificity. However, the possibility of differentiation between ccRCC histologic subtypes and grades, utilizing ADC values, is limited.