Associations of Cardiovascular and All-Cause Mortality with Metabolic Syndrome in Hemodialysis Patients: A Prospective Single-Center Study.

Background and objectives: Metabolic syndrome (MetS) is a cluster of risk factors, such as abdominal obesity, insulin resistance, dyslipidemia and hypertension, that together increase the risk of cardiovascular disease. Chronic hemodialysis (HD) patients have multiple comorbidities and many metabolic disorders, causing the frequent occurrence of metabolic syndrome. The goal of this study was to assess the prevalence of MetS in HD patients, and its association with all-cause and cardiovascular (CV) mortality. Patients and methods: A total of 138 HD patients were included in this prospective study. We analyzed demographic, anthropometric and biochemical data. Outcome measures were all-cause and CV mortality during the three-year follow-up. Results: MetS was diagnosed in 57.24% of enrolled patients. During the 36 months of follow-up, 33 patients died. MetS patients showed a significantly higher mortality rate than non-MetS (30.4% versus 16.36%, p < 0.001). The association of different MetS components with cardiovascular mortality reached significance when a minimum of three components were present (1.81 (95% confidence interval CI = 1.21-2.33)), with a grouped increase in effect size for subjects with four or five MetS components. Subjects with MetS exhibited nearly twice as high risk for all-cause (hazard ratio HR = 1.99 (95%CI) = 1.42-2.97) and 2.5 times for CV (HR = 2.51 (95%CI) = 1.25-3.83) mortality compared with those without MetS, after adjustment for age, gender, and cardiovascular disease. Conclusions: The study demonstrates that MetS is widespread in HD patients. In future, the focus must be on an active screening approach, and treatment of cardiometabolic risk factors, aiming to reduce mortality.

Possible health impacts of naturally occurring uptake of aristolochic acids by maize and cucumber roots: links to the etiology of endemic (Balkan) nephropathy.

Aristolochic acids (AAs) are nephrotoxic and carcinogenic derivatives found in several Aristolochia species. To date, the toxicity of AAs has been inferred only from the effects observed in patients suffering from a kidney disease called "aristolochic acid nephropathy" (AAN, formerly known as "Chinese herbs nephropathy"). More recently, the chronic poisoning with Aristolochia seeds has been considered to be the main cause of Balkan endemic nephropathy, another form of chronic renal failure resembling AAN. So far, it was assumed that AAs can enter the human food chain only through ethnobotanical use (intentional or accidental) of herbs containing self-produced AAs. We hypothesized that the roots of some crops growing in fields where Aristolochia species grew over several seasons may take up certain amounts of AAs from the soil, and thus become a secondary source of food poisoning. To verify this possibility, maize plant (Zea mays) and cucumber (Cucumis sativus) were used as a model to substantiate the possible significance of naturally occurring AAs' root uptake in food chain contamination. This study showed that the roots of maize plant and cucumber are capable of absorbing AAs from nutrient solution, consequently producing strong peaks on ultraviolet HPLC chromatograms of plant extracts. This uptake resulted in even higher concentrations of AAs in the roots compared to the nutrient solutions. To further validate the measurement of AA content in the root material, we also measured their concentrations in nutrient solutions before and after the plant treatment. Decreased concentrations of both AAI and AAII were found in nutrient solutions after plant growth. During this short-term experiment, there were much lower concentrations of AAs in the leaves than in the roots. The question is whether these plants are capable of transferring significant amounts of AAs from the roots into edible parts of the plant during prolonged experiments.

The role of lecithin cholesterol acyltransferase and organic substances from coal in the etiology of Balkan endemic nephropathy: a new hypothesis.

Balkan endemic nephropathy (BEN) occurs in Serbia, Bulgaria, Romania, Bosnia and Herzegovina, and Croatia. BEN has been characterized as a chronic, slowly progressive renal disease of unknown etiology. In this study, we examined the influence of soluble organic compounds in drinking water leached from Pliocene lignite from BEN-endemic areas on plasma lecithin-cholesterol acyltransferase (LCAT) activity. We found that changes for all samples were the most prominent for the dilution category containing 90% plasma and 10% of diluting media. Water samples from BEN villages from Serbia and Romania showed higher LCAT inhibiting activity (p=0.02) and (p=0.003), respectively, compared to deionised water and non-endemic water. A secondary LCAT deficiency could result from this inhibitory effect of the organic compounds found in endemic water supplies and provide an ethiopathogenic basis for the development of BEN in the susceptible population.

Spontaneous chronic subdural hematoma in elderly people - Arterial hypertension and other risk factors.

BACKGROUND: The risk factors implicated in the genesis of chronic subdural hematomas include old age, alcoholism, diabetes mellitus, arachnoid cysts, coagulopathy, anticoagulant (ACTh) and antiplatelet drugs. However, no study has reported an association between arterial hypertension (HTA) and chronic subdural hematomas. Therefore, the aim of this study was to investigate whether HTA is a risk factor for spontaneous chronic subdural hematomas (SCSDHs). METHODS: This multicenter study included patients aged over 60 years and was conducted from January 2009 to the end of 2015. One hundred and twenty-two patients with SCSDHs and 111 controls treated for other reasons with no evidence of intracranial hemorrhages on brain computed tomography were enrolled. The patients were separated into three age subgroups to provide a better insight into the role of risk factors with age. RESULTS: The average age in the SCSDH group was 74.45 ± 8.16 years, compared to 71.28 ± 6.69 years in the control group. The SCSDH group was significantly older than the control group (p = 0.0014). The patients in the 60-69 years age group diagnosed with SCSDHs had significantly higher rates of HTA (p = 0.0519), ACTh treatment (p = 0.0292) and alcoholism (p = 0.0300) than the control group. The patients in the 70-79 years age group diagnosed with SCSDHs had significantly higher rates of HTA (p = 0.0071) and ACTh treatment (p = 0.0158) than the control group. In the subgroup of patients older than 80 years, there were no statistical differences. CONCLUSION: The incidence of HTA had borderline significance in the patients aged 60-69 years with SCSDHs and statistical significance in the patients aged 70-79 years with SCSDHs. Anticoagulant therapy was the most significant risk factor. Among the patients with SCSDHs aged 60-69 years, the percentage of heavy drinkers was significantly higher than in the control group.

Aristolochic Acids as Persistent Soil Pollutants: Determination of Risk for Human Exposure and Nephropathy from Plant Uptake.

Exposure to aristolochic acids (AAs) from Aristolochia plants is one of the major global causes of nephropathy, including Balkan endemic nephropathy (BEN); renal failure; and urothelial cancer. The high incidence of BEN on the Balkan Peninsula is assumed to result from consumption of Aristolochia clematitis L. seeds coharvested with crops. Here, we show that AAs are long-lived soil contaminants that enter wheat and maize plants by root uptake with strong pH dependence. Soil and crops from Serbian farms in areas endemic for A. clematitis were found to be extensively contaminated with AAs, with contamination strongly correlated with local incidence of BEN. The persistence of AAs as soil contaminants suggests that weed control for A. clematitis plants is needed to reduce the incidence of BEN and aristolochic acid nephropathy, systematic surveys of soil and crop AA levels would identify high-risk regions, and it is imperative to research soil-remediation methods.

Quantitation of Aristolochic Acids in Corn, Wheat Grain, and Soil Samples Collected in Serbia: Identifying a Novel Exposure Pathway in the Etiology of Balkan Endemic Nephropathy.

While to date investigations provided convincing evidence on the role of aristolochic acids (AAs) in the etiology of Balkan endemic nephropathy (BEN) and upper urothelial cancer (UUC), the exposure pathways by which AAs enter human bodies to cause BEN and UUC remain obscure. The goal of this study is to test the hypothesis that environmental pollution by AAs and root uptake of AAs in the polluted soil may be one of the pathways by which AAs enter the human food chain. The hypothesis driving this study was that the decay of Aristolochia clematitis L., a AA-containing herbaceous plant that is found growing widespread in the endemic regions, could release free AAs to the soil, which could be taken up by food crops growing nearby, thereby transferring this potent human nephrotoxin and carcinogen into their edible parts. Using the highly sensitive and selective high-performance liquid chromatography coupled with fluorescence detection method, we identified and quantitated in this study for the first time AAs in corn, wheat grain, and soil samples collected from the endemic village Kutles in Serbia. Our results provide the first direct evidence that food crops and soil in the Balkans are contaminated with AAs. It is possible that the presence of AAs in edible parts of crops originating from the AA-contaminated soil could be one of the major pathways by which humans become exposed to AAs.

Complications after angiogram-negative subarachnoid haemorrhage: comparative study of pretruncal and nonpretruncal hemorrhage patients.

INTRODUCTION: Subarachnoid haemorrhages (SAH) of unknown aetiology usually have a mild clinical presentation, favourable outcome and low complication rate. OBJECTIVE: The aim of this study was to analyse the complications in two forms of angiogram-negative spontaneous SAH: pretruncal (PNSAH) and nonpretruncal (NPNSAH). METHODS: The study group involved 18 patients with PNSAH and 16 patients with NPNSAH. CT scan was done within 72 hours from bleeding. All patients underwent four-vessel cerebral angiography. Repeat angiography was performed in five PNSAH and all NPNSAH patients. RESULTS: Twenty-nine patients were in grade I or II of the Hunt-Hess Scale (17 PNSAH and 12 NPNSAH). There was one case of rebleeding (NPNSAH patient), 10 cases of transient acute hydrocephalus (4 PNSAH and 6 NPNSAH). Cerebral vasospasm visualized by angiographies in two NPNSAH patients was local and mild, but was not found in PNSAH patients. Acute electrocardiography changes were found in 19 patients (significantly more frequently in NPNSAH than in PNSAH, 12 and 7 patients, respectively; p = 0.037). CONCLUSION: Cardiac problems following these types of SAH are more frequent than expected, and therefore cardiac monitoring is necessary.

[Efficacy of antiviral therapy in patients with hemophilia and hepatitis C virus infection].

INTRODUCTION: HCV infection was common cause of morbidity and mortality in patients with hemophilia before 1986. We wanted to investigate the effect of treatment with combination therapy in HCV positive patients with hemophilia. MATERIAL AND METHODS: The research included totally 13 persons afflicted with hemophilia and HCV infection out of 21 tested. The patients were submitted to laboratory and clinical tests as well as genotypization, whereby a different hepatitis C virus genetic adherence was observed. Parallel with this subcategory the other one was put into comparison, consisting of 12 patients afflicted with chronic C hepatitis, marked as non-hemophilics. The both subcategories were treated with combination antiviral therapy (peginterferon alpha-2a and ribavirin) during 48 weeks for genotype 1 and 4, in reference to 24 weeks for genotype 2 and 3. Within the treatment, clinical and laboratory side-effects were noticed, which did not require therapy interruption. A more frequent hemorrhage during the therapy was found within the hemophilics, rather than before initiliazing it. RESULTS: After the statistical processing of the results (Students' t-test), statistically significant difference among these two subcategories was noticed as values for ALT (***p<0.0001) after 24 weeks of therapy, red blood cells (*p<0.05), haemoglobin and haematocrite (***p<0.0001) 24 weeks after therapy completing By PCR examination of the patients, 6 months after the end of treatment, a sustained viral response (SVR) of the same percentage was registrated within both subcategories, which is even greater than what the other authors have described. DISCUSSION: Main results were without important difference between two subgroups, except for higher number of spontanuous bleeding in group with hemophilia, which was somewhat expected. Most importantly, we didn't find any difference in SVR rates between groups. CONCLUSION: HCV positive patients with hemophilia could be successfully treated with combination therapy of peginterferon alfa-2a and ribavirin.

[Liver damage caused by hepatitis C viral infection and ethyl alcohol consumption].

BACKGROUND/AIM: Hepatitis C virus infection (HCV) is a complex disease, most commonly chronicle (80-85%). The aim of this research was to determinate the level of the liver damage in the patients cansed by HCV in conjunction with consuming ethyl alcohol. METHODS: The research included 15 patients with chronic HCV infection supported by the misuse of ethyl alcohol, as well. The diagnosis of C infection hepatitis was proved using the ELISA test and PCR method. RESULTS: The results of the study showed the liver damage by both HCV infection and ethyl alcohol, which was verified by the presence of biochemical changes and patohystological processing of the patients (liver biopsy and prosection). Patohystological changes were at the level of liver cirrhosis and carcinoma (2 patients). There was a signficant difference between the two subgroups (p < 0.001) regarding the examined values gamma-GT, PLT and PTV. The basic therapeutic procedure was to introduce this category of patients into alcohol abstinence, and, in a few patients, to apply the antivirus therapy, as well. CONCLUSION: Based on the number of the examined patients (n = 15), we could conclude that a prolonged ethyl alcohol misuse with the presence of HCV infection was in a correlation with the liver disease progression.