Effect of the Mediterranean diet in combination with exercise on metabolic syndrome parameters: 1-year randomized controlled trial.

This work aimed to evaluate and compare the benefits of the energy restricted Mediterranean diet (MD) and Standard hypolipemic diet (SHD) accompanied by exercise on metabolic syndrome parameters. A 12-month, randomized, single-blinded, diet-controlled study was conducted on 124 obese participants in the University Hospital Dubrava. Participants were assigned to the MD (n = 63) or the SHD (n = 61) and received the same amount of nutritional education and guidance on physical activity. The completion rate was 67.7 %. Both diets produced significant beneficial changes in body weight and waist circumference (P < 0.001 for MD and SHD). Compared with the SHD, HDL cholesterol increased (P = 0.031) and systolic blood pressure (SBP) decreased (P = 0.020) in the MD group. Fasting plasma glucose decreased significantly in both diet groups (P < 0.001 for MD; P = 0.026 for SHD). Although both diets accompanied by physical activity yielded similar weight reduction results, adherence to the MD was associated with more prominent reduction of the MetS components, namely HDL level elevation and SBP reduction.

Red blood cell distribution width as a prognostic marker of mortality in patients on chronic dialysis: a single center, prospective longitudinal study.

AIM: To determine if red cell distribution width (RDW) is associated with all-cause mortality in patients on chronic dialysis and to evaluate its prognostic value among validated prognostic biomarkers. METHODS: This is a single center, prospective longitudinal study. At the time of inclusion in January 2011, all patients were physically examined and a routine blood analysis was performed. A sera sample was preserved for determination of NT-pro-brain natriuretic peptide (NT-pro-BNP) and eosinophil cationic protein. Carotid intima media thickness (IMT) was also measured. Following one year, all-cause mortality was evaluated. RESULTS: Of 100 patients, 25 patients died during the follow-up period of one-year. Patients who died had significantly higher median [range] RDW levels (16.7% [14.3-19.5] vs 15.5% [13.2-19.7], P<0.001. They had significantly higher Eastern Cooperative Oncology Group (ECOG) performance status (4 [2-4] vs 2 [1-4], Plt;0.001), increased intima-media thickness (IMT) (0.71 [0.47-1.25] vs 0.63 [0.31-1.55], P=0.011), increased NT-pro-BNP levels (8300 [1108-35000] vs 4837 [413-35000], P=0.043), and increased C-reactive protein (CRP) levels (11.6 [1.3-154.2] vs 4.9 [0.4-92.9], Plt;0.001). For each 1% point increase in RDW level as a continuous variable, one-year all cause mortality risk was increased by 54% in univariate Cox proportional hazard analysis. In the final model, when RDW was entered as a categorical variable, mortality risk was significantly increased (hazard ratio, 5.15, 95% confidence interval, 2.33 to 11.36) and patients with RDW levels above 15.75% had significantly shorter survival time (Log rank Plt;0.001) than others. CONCLUSIONS: RDW could be an additive predictor for all-cause mortality in patients on chronic dialysis. Furthermore, RDW combined with sound clinical judgment improves identification of patients who are at increased risk compared to RDW alone.

Etiology and epidemiology of obstructive jaundice in Continental Croatia.

The etiology and epidemiology of obstructive jaundice in Continental Croatia has been studied in 174 patients. The objective of this research was also to explore the importance and efficiency of endoscopic retrograde cholangiopancreatography (ERCP) as a non-surgical method of treatment of obstructive jaundice in the population of Continental Croatia. Obstructive jaundice is the illness of elderly population which is also confirmed by the information on the average age of our patients. The frequency of illness is higher among female population, and the most frequent cause of obstructive jaundice are gallstones (54.1% of patients). In 29.8% of patients the primary or secondary malignant disease was the cause of blockage in gall flow and subsequent jaundice, and the most frequent malignant cause of obstructive jaundice is pancreas cancer in 11.5% of patients. The mean value of serum concentrations of total bilirubin, alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase and gamma glutamiltransferase 24 hours before the biliary decompression by ERCP has been significantly above the upper referential value, and 24 hours after the ERCP it has dropped to normal with their statistically significant difference (p < 0.0001). The normal values of markers for synthetic liver function (total proteins and prothrombin time) have been noticed as well as elevated values of inflammatory markers in obstructive jaundice independently of etiology. Out of the total number of patients, 37.7% required the surgical treatment while 60.3% of patients were treated by ERCP, i.e. either the stone extraction or the implantation of endobiliary stent was performed.

Preventive and therapeutic effects of oleuropein against carbon tetrachloride-induced liver damage in mice.

Olives and olive products, an inevitable part of the Mediterranean diet, possess various beneficial effects, such as a decreased risk of cardiovascular disease and cancer. Oleuropein is a non-toxic secoiridoid found in the leaves and fruits of olive (Olea europaea L.). In this study, we have investigated the hepatoprotective activity of oleuropein in carbon tetrachloride (CCl(4))-induced liver injury in male BALB/cN mice. Oleuropein in doses of 100 and 200mg/kg was administered intraperitoneally (ip) once daily for 3 consecutive days, prior to CCl(4) administration (the preventive treatment), or once daily for 2 consecutive days 6h after CCl(4) intoxication (the curative treatment). CCl(4) intoxication resulted in a massive hepatic necrosis and increased plasma transaminases. Liver injury was associated with oxidative/nitrosative stress evidenced by increased nitrotyrosine formation as well as a significant decrease in superoxide dismutase activity and glutathione levels. CCl(4) administration triggered inflammatory response in mice livers by inducing expression of nuclear factor-kappaB, which coincided with the induction of tumor necrosis factor-alpha, cyclooxygenase-2 and inducible nitric oxide synthase. In both treatment protocols, oleuropein significantly attenuated oxidative/nitrosative stress and inflammatory response and improved histological and plasma markers of liver damage. Additionally, in the curative regimen, oleuropein prevented tumor necrosis factor-beta1-mediated activation of hepatic stellate cells, as well as the activation of caspase-3. The hepatoprotective activity of oleuropein was, at least in part, achieved through the NF-E2-related factor 2-mediated induction of heme oxygenase-1. The present study demonstrates antioxidant, anti-inflammatory, antiapoptotic, and antifibrotic activity of oleuropein, with more pronounced therapeutic than prophylactic effects.

Differential hepatoprotective mechanisms of rutin and quercetin in CCl(4)-intoxicated BALB/cN mice.

AIM: To investigate the mechanisms underlying the protective effects of quercetin-rutinoside (rutin) and its aglycone quercetin against CCl(4)-induced liver damage in mice. METHODS: BALB/cN mice were intraperitoneally administered rutin (10, 50, and 150 mg/kg) or quercetin (50 mg/kg) once daily for 5 consecutive days, followed by the intraperitoneal injection of CCl(4) in olive oil (2 mL/kg, 10% v/v). The animals were sacrificed 24 h later. Blood was collected for measuring the activities of ALT and AST, and the liver was excised for assessing Cu/Zn superoxide dismutase (SOD) activity, GSH and protein concentrations and also for immunoblotting. Portions of the livers were used for histology and immunohistochemistry. RESULTS: Pretreatment with rutin and, to a lesser extent, with quercetin significantly reduced the activity of plasma transaminases and improved the histological signs of acute liver damage in CCl(4)-intoxicated mice. Quercetin prevented the decrease in Cu/Zn SOD activity in CCl(4)-intoxicated mice more potently than rutin. However, it was less effective in the suppression of nitrotyrosine formation. Quercetin and, to a lesser extent, rutin attenuated the inflammation in the liver by down-regulating the CCl(4)-induced activation of nuclear factor-kappa B (NF-κB), tumor necrosis factor-α (TNF-α) and cyclooxygenase (COX-2). The expression of inducible nitric oxide synthase (iNOS) was more potently suppressed by rutin than by quercetin. Treatment with both flavonoids significantly increased NF-E2-related factor 2 (Nrf2) and heme oxygenase (HO-1) expression in injured livers, although quercetin was less effective than rutin at an equivalent dose. Quercetin more potently suppressed the expression of transforming growth factor-ß1 (TGF-ß1) than rutin. CONCLUSION: Rutin exerts stronger protection against nitrosative stress and hepatocellular damage but has weaker antioxidant and anti-inflammatory activities and antifibrotic potential than quercetin, which may be attributed to the presence of a rutinoside moiety in position 3 of the C ring.

Atrial fibrillation, atrioventricular blocks and bundle branch blocks in hemodialysis patients.

Atrial fibrillation is one of the most frequent arrhythmias diagnosed in clinical practice and it is also relatively common in dialysis patients. Atrioventricular and intraventricular conduction disturbances are less investigated in hemodialysis patients and data about their prevalence are insufficient. The objective of this study was to determine the prevalence of atrial fibrillation, atrioventricular blocks and bundle branch blocks in hemodialysis patients and to analyze different clinical risk factors. The study included 140 patients on long-term hemodialysis treatment. The presence of atrial fibrillation, atrioventricular blocks and bundle branch blocks was determined by electrocardiogram. Patients were divided into groups depending on the presence or absence of atrial fibrillation/bundle branch blocks and investigated variables were compared. Atrial fibrillation was present in 11 (7.9%) of the 140 patients. In multivariate analysis, age and higher concentration of uric acid were associated with atrial fibrillation. Prevalence of first-degree atrioventricular block was 2.9% (4 patients) and second- and third-degree atrioventricular blocks were not found. Prevalence of bundle branch blocks was 17.1% (24 patients): 5% of patients had a complete right bundle branch block, 6.4% had an incomplete right bundle branch block, 3.6% had a complete left bundle branch block and 2.1% of patients had an incomplete left bundle branch block. The prevalence of atrial fibrillation and bundle branch blocks in this study was relatively high in patients on hemodialysis and greater than that observed in general population. Presence of atrial fibrillation was associated with older age and higher concentration of uric acid.

The antioxidative protecting role of the Mediterranean diet.

Recent meta-analysis shows that adherence to a Mediterranean diet (MD) can significantly decrease the risk of overall mortality, mortality from cardiovascular diseases, as well as incidence of mortality from cancer, and incidence of Parkinson's and Alzheimer's disease. All of these diseases could be linked to oxidative stress (OS) as antioxidative effect of MD is getting more attention nowadays. Although a lot of research has been done in this area and it suggests antioxidative protective role of MD, the presented evidence is still inconclusive. The aim of this paper is to review studies investigating the effect of MD on OS, as well as to identify the areas for further research.

Effect of American ginseng (Panax quinquefolius L.) on glycemic control in type 2 diabetes.

Since diabetes tends to progressively worsen over time, glycemic control often deteriorates in spite of taking regular therapy. Therefore, numerous research studies are by and large focused on finding more efficient therapy, both new medicines for treating type 2 diabetes mellitus, as well as supplements that could serve as an addition to conventional treatment modalities. A variety of herbal preparations have been shown to have modest short-term beneficial effects on glycemia, but of these, the best studied is American ginseng (AG). AG has been shown to be effective in improving glycemic control in type 2 diabetes through increasing post-prandial insulin levels and decreasing postprandial glycemic response. However, high variability in ginsenosides may result in just as high variability in antidiabetic efficacy of over-the-counter ginseng products. Therefore, the availability of standardized extracts of AG could assist greatly in advancing our knowledge on the role of this traditionally used herb and result in a wider application of ginseng product in diabetes management. The aim of this review is to outline the efficacy and safety of American ginseng for AG preparations on glycemic control in patients with type 2 diabetes as well as to increase awareness of the evidence supporting the use of these therapies in diabetes care.

Correlation of endothelin-1 concentration and angiotensin-converting enzyme activity with the staging of liver fibrosis.

Increased serum angiotensin-converting enzyme (SACE) activity and serum concentration of endothelin-1 (ET-1) were found in liver cirrhosis. We investigated a correlation between the different stages of liver fibrosis and SACE activity and serum ET-1 concentration. Seventy patients with pathohistologically established chronic liver disease were divided in three groups according to Ishak criteria for liver fibrosis: minimal fibrosis (Ishak score 0-1, n =20), medium fibrosis (Ishak score 2-5, n=20) and cirrhosis (Ishak score 6, n=30). SACE activity and ET-1 concentration were determined using commercial ELISA kits. SACE activity and ET-1 concentrations were proportional to the severity of disease, the highest being in patients with liver cirrhosis. Maximal increase in SACE activity was found between minimal and medium fibrosis while maximal increase in ET-1 concentration was revealed between medium fibrosis and cirrhosis. The analysis of the Receiver Operating Characteristic (ROC) curve for SACE activity suggested a cut-off value to separate minimal from medium fibrosis at 59.00 U/L (sensitivity 100%, specificity 64.7%). The cut-off value for serum ET-1 concentration to separate medium fibrosis from cirrhosis was 12.4 pg/mL (sensitivity 96.8%, specificity 94.4%). A positive correlation between SACE activity and ET-1 concentration was registered (Spearman's ñ = 0.438, p = 0.004). Both SACE activity and ET-1 concentration were increased in all stages of liver fibrosis. Cut-off points for SACE activity and ET-1 concentration could be a biochemical marker for the progression of fibrosis. Positive correlation between SACE activity and ET-1 concentration might indicate their interaction in the development of liver cirrhosis.

Anti-cyclic citrullinated peptide and rheumatoid factor in HIV positive patients.

The aim of this study was to determine the difference of anti-CCP and RF between HIV positive patients and a healthy control group. The rheumatological complications in HIV positive patients are rather common and are recognized as a serious problem that requires more attention. Anti-CCP and RF are the only laboratory tools for rheumatoid disorder diagnostics and predictors of the course of the disease. We determined anti-CCP and RF in sera of 35 healthy volunteers and 45 HIV positive patients. Data were compared using chi-square test, Mann-Whitney test and ROC curve statistics. Both parameters were significantly higher in HIV positive patients, and significant differences between areas under the anti-CCP and RF curves were observed. Median value for anti-CCP in HIV positive patients was higher than the reference interval, and RF values were, in the reference interval, suggested by the manufacturer. Both anti-CCP and RF are significantly higher in HIV positive patients. ROC analysis showed that anti-CCP distinguishes the two groups better than RF. Because of that, it would be of a great interest to investigate the HIV positive patients after the detailed rheumatological examination.

Oxidative stress markers in patients with post-traumatic stress disorder.

Recent study data support the role of oxidative stress in diverse psychiatric disorders. Oxidative stress results from an oxidant/antioxidant imbalance, an excess of oxidants and/or a depletion of antioxidants. There are numerous studies that indicate that free radicals (FRs) damage neurons, and then play an important role in the pathophysiology of schizophrenia and depression. Active oxygen can cause considerable damage and disrupt the important physiological functions of proteins, lipids, enzymes and DNA. The aim of our study was to investigate the possible differences in the concentration of tromboxane B2, 8-OHdG and protein carbonyls, as significant markers of oxidative damage, and urate, albumin and total protein concentrations as antioxidative molecules in PTSD patients in comparison to the healthy control group. The study included 74 male participants who were active soldiers in the Croatian armed forces from 1991 to 1995. 46 subjects with chronic and current PTSD were recruited from the Department of Psychiatry of Dubrava University Hospital during 2010, 28 healthy subjects were recruited in the same period during the regular medical examination at the Dubrava University Hospital. Study results have shown that there is no statistically significant difference in urinary concentrations of 8-OHdG, serum thromboxane B2, and serum urates between two studied groups. Statistically significant difference of the protein carbonyl concentrations was examined. Concentrations were significantly lower in the PTSD group than in the control group. The clinical significance of these results was examined using ROC analysis. The obtained ROC curves did not separate the groups in a satisfactory manner.

Metastatic prostate cancer in an asymptomatic patient with an initial prostate-specific antigen (PSA) serum concentration of 21,380 ng/ml.

BACKGROUND: Prostate cancer is the second most common cause of cancer death in men, being responsible for approximately 13% of all cancer deaths. Due to the high specificity for prostate tissue, prostate-specific antigen (PSA) is the primary serum tumor marker for prostate cancer. To our knowledge, in published data, the highest reported PSA level on initial presentation was 5,666 ng/ml. CASE REPORT: We present a 64-year-old Caucasian man with no specific urologic or pain symptoms and with an initial PSA serum value of 21,380 ng/ml. Initial laboratory studies showed chronic anemia and elevated alkaline phosphatase, most likely from bone marrow infiltration due to metastatic disease. Prostate biopsies diagnosed an adenocarcinoma of the prostate (Gleason score 9). Computed tomography (CT) showed multiple liver metastases with retroperitoneal lymph nodes of up to 1 cm. The prostate was moderately enlarged (estimated weight 35 g). Both kidneys were normal (no hydronephrosis present). A bone scintigraphy demonstrated diffuse osseous metastasis. Treatment was initiated with bilateral subcapsular orchiectomy and bicalutamide therapy in an effort to create total androgen blockade. After 3 months of follow-up, the serum concentration of PSA was 29 ng/ml. CONCLUSION: This case presents an asymptomatic prostate cancer patient with bone and liver metastasis, enlarged retroperitoneal lymph nodes and the highest PSA level published to date.

Homocysteine and serum lipids concentration in male war veterans with posttraumatic stress disorder.

The evidence of increased cardiovascular disease (CVD) risk in posttraumatic stress disorder (PTSD) is accumulating. The present study aimed to determine whether chronic, combat-related PTSD is associated with serum lipid and homocysteine concentrations that could indicate higher CVD risk. The authors tested 66 war veterans with PTSD, 33 war veterans without PTSD, and 42 healthy volunteers for serum concentrations of homocysteine, total cholesterol, high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C) and triglycerides. All the subjects were men and the analyses were adjusted for age, body mass index and smoking. Potential influences of depression, anxiety, and psychotic symptoms on the outcome measures were checked by introducing the scores from the Hamilton Depression Rating Scale (HAM-D-17), the Hamilton Anxiety Scale (HAMA), and the Positive and Negative Syndrome Scale (PANSS) into the overall statistical model. No differences in total cholesterol, LDL-C, HDL-C and triglycerides were found between the groups. Non-smoking PTSD war veterans had higher homocysteine concentrations (mean=10.4 micromol/L, SD=1.7) when compared to non-smoking war veterans without PTSD (mean=8.2 micromol/L, SD=4.0, P=0.014) and both smoking (mean=8.7 micromol/L, SD=2.3, P=0.008) and non-smoking healthy volunteers (mean=8.8 micromol/L, SD=2.2, P=0.021). The results of our cross-sectional study are possibly confounded by many factors, especially behavioral and life-style related which are difficult to control comprehensively and might have influenced serum lipids and homocysteine concentration in a complex manner. An increase in the homocysteine concentration observed in the non-smoking PTSD patients needs further investigation with a carefully designed prospective study to confirm associated, possibly enhanced CVD risk.

Anti-citrullinated protein antibody and rheumatoid factor in patients with end-stage renal disease.

BACKGROUND: Patients with end-stage renal disease (ESRD) and on hemodialysis (HD) are at increased risk for developing rheumatoid arthritis (RA), as a result of defective immunity. Our aim was to examine if ESRD and the length of HD treatment impact the clinical utility of antibodies to cyclic citrullinated peptides (anti-CCP) and rheumatoid factor (RF) as diagnostic tools for RA. METHODS: We included 94 subjects in our study: 37 healthy volunteers and 57 patients with ESRD who had been undergoing HD for 1-12 years, and without confirmed RA. In order to test our hypothesis, we measured and correlated anti-CCP and RF as laboratory markers of RA. RESULTS: Our study showed that there is no significant difference between values for anti-CCP (p=0.11) and RF (p=0.98) in control subjects as well as in patients undergoing HD, regardless of the length of time that patients had been undergoing HD treatment. CONCLUSIONS: Our study indicates that HD does not impair the specificity of anti-CCP and RF for RA in patients where the disease has not yet developed. Future prospective studies may show whether there is any use in determinating RF, and especially anti-CCP, as early predictors of RA in patients with ESRD who are at greater risk of developing this condition.

The association between upper gastrointestinal lesions and high-sensitivity C-reactive protein in coronary artery disease patients.

BACKGROUND: Although high-sensitivity C-reactive protein (hs-CRP) testing is not specific for coronary atherosclerosis, elevated hs-CRP is recently accepted as an independent predictor of future cardiovascular events. Also, a connection between upper gastrointestinal lesions (UGILs) and coronary artery disease (CAD) has been observed. The authors hypothesized that UGILs increase hs-CRP in CAD patients. MATERIAL/METHODS: One hundred fifty patients with stable CAD were enrolled in the study. Demographic and clinical variables and chronic medication used were gathered from a structured questionnaire. UGIL severity was determined by a modified Lanza score, H. pylori status by histology of the gastric mucosa, and the severity of CAD by a modified Gensini score. Independent correlation between hs-CRP and UGIL was tested by logistic regression analysis. RESULTS: The overall hs-CRP value was higher in patients with UGIL than in those with normal endoscopic results (8.14+/-4.53 mg/l vs. 4.64+/-3.06 mg/l, P<0.0001). hs-CRP level positively correlated with UGIL severity (r=0.434, P<0.0001). Correlation between UGIL and hs-CRP level remained significant after adjustment for coronary risk factors, medication used, CAD severity, and H. pylori status (standardized coefficient beta=1.272, P<0.0001). However, when hs-CRP level was used as a categorical variable, multivariate analysis revealed independent correlation only between UGIL and hs-CRP categories > or =6.1 mg/l. CONCLUSIONS: Elevated hs-CRP levels may be predictive of UGIL; thus endoscopy should be considered in CAD patients with elevated hs-CRP even with no dyspeptic symptoms. Because CRP plays an active role in atherothrombosis, UGILs with subsequent elevated CRP levels could increase cardiovascular risk in those patients.

Endothelin-1, big endothelin-1, and nitric oxide in patients with chronic renal disease and hypertension.

The complex pathogenesis of chronic renal disease (CRD) depends on endothelin (ET) axis (ETs and ET receptors) and nitric oxide (NO) because of their vasoactive effects and their role in general modulation of vascular homeostasis. Various renal cells synthesize ETs and NO that play a significant role in renal hemodynamics as well as in water and salt excretion via urine. ET-1 is a strong vasoconstrictor. Besides its vasoactive effects, ET-1 modulates mitosis and apoptosis in a cell type-dependent manner, and may play an important role in CRD pathogenesis. The aims of this study were to emphasize the role and interactions of ET-1, Big ET-1, and NO in CRD. Concentrations of these vasoactive molecules were measured in plasma/serum and/or urine of 57 patients with diabetic nephropathy (subgroup 1), arterial hypertension (subgroup 2) or CRD with chronic renal insufficiency (subgroup 3), and in healthy control subjects (n=18). In comparison with control group, urine concentration of Big ET-1 was significantly increased (13.13 pmol/L vs. 11.34 pmol/L; P<0.001) in CRD patients, whereas plasma and urine concentrations of ET-1 did not differ significantly. NO concentrations were also significantly increased in CRD patients (serum, 72.55 micromol/L; P<0.001, and urine 141.74 micromol/L; P<0.05) as compared to control group. Study results indicated that Big ET-1 and NO could be useful diagnostic parameters in CRD for their diagnostic sensitivity and diagnostic specificity (Big ET-1 in urine: 56.1 and 88.9%, and NO in serum: 66.7 and 83.3%, respectively). In addition, Big ET-1 may prove useful in the differential diagnosis of diabetic nephropathy (78.6% diagnostic sensitivity and 88.9% diagnostic specificity).

The role of endothelin-1 and nitric oxide in the pathogenesis of hypertension in diabetic patients.

The pathogenesis of renal hypertension has not yet been fully clarified. As the potential role of endothelin-1 (ET-1) and nitric oxide (NO) has been postulated, their concentrations were determined in plasma and urine of diabetic patients. The study included 30 diabetic patients (both IDDM and NIDDM) with initial or advanced diabetic nephropathy (decreased endogenous creatinine clearance, proteinuria) and 20 healthy control subjects. The correlation with blood pressure and other renal function parameters was monitored and compared with the control group. Also, the effect of ACE inhibitors (ACEI) on ET-1 and NO patterns was monitored in correlation with arterial hypertension. In diabetic patients that did not receive ACEI therapy, the increase in plasma ET-1 was associated with both systolic and diastolic blood pressure elevation, whereas in those administered ACEI the increase in plasma ET-1 was associated with a systolic blood pressure decline. In addition, the increase in plasma NO was accompanied by a statistically significant decline of both systolic and diastolic blood pressure in diabetic patients receiving ACEI.

[Gastroduodenal mucosal lesions and coronary atherosclerosis severity in patients with coronary artery disease]. / Ostecenje gastroduodenalne sluznice i tezina koronarne ateroskleroze u bolesnika s koronarnom bolescu srca.

AIM: Due to high metabolic activity and oxygen demands, ischemia of gastroduodenal (GD) mucosa is an important factor in the pathogenesis of its impairment. Comparing the degree of coronary atherosclerosis, for evaluation of severity of atherosclerosis, with the prevalence and severity of GD mucosal lesions, we wanted to investigate the possible ischemia of GD mucosa could contribute to its impairment. PATIENTS AND METHODS: This prospective study included 150 coronary artery disease (CAD) patients, 109 (72.7%) male and 41 (27.3%) female, average age 62.61 +/- 10.23 years. We noted clinical and anthropometric parameters, standard laboratory findings, treatment until inclusion into the study and standard cardiovascular risk factors. The severity of CAD was assessed by several parameters: 1) number of coronary arteries affected with atherosclerosis, 2) modified Gensa score, and 3) number of coronary arteries with stenosis > 50%. The severity of GD mucosal lesions was assessed by modified Lanza score, and Helicobacter pylori infection was confirmed by biopsy and pathohistological analysis of GD mucosa. Predictive value of different independent factors regarding the presence of GD mucosal lesions was assessed by multivariate analysis. RESULTS: The severity of CAD in patients with or without GD mucosal lesions did not differ by any of used scoring methods: 1) number of coronary arteries affected by atherosclerosis (2.15 +/- 0.85 vs. 2.00 +/- 0.87, p = 0.292), 2) modified Gensa score (71.22 +/- 51.78 vs. 69.89 +/- 54.18, p = 0.881), 3) number of coronary arteries with stenosis > 50% (3.89 +/- 2.05 vs. 3.47 +/- 2.25, p = 0.244). We also noticed that there had been no correlation between severity of CAD and severity of GD mucosal lesions. Correlation of number of coronary arteries affected with atherosclerosis with Lanza score resulted in r = 0.029, p = 0.721, correlation of Genza score with Lanza score resulted in r = 0.019, p = 0.082, and correlation of the number of coronary arteries with stenosis > 50% with Lanza score resulted in r = 0.079, p = 0.337. CONCLUSION: According to available method for evaluating the severity of CAD, in CAD patients ischemia has no or very minor role in pathogenesis of GD mucosa impairment.

High absolute basophil count is a powerful independent predictor of inferior overall survival in patients with primary myelofibrosis.

OBJECTIVES: To investigate the clinical and prognostic significance of absolute basophil count (ABC) in patients with primary myelofibrosis (PMF). METHODS: We retrospectively investigated 58 patients with PMF treated in our institution in the period from 2006 to 2017. ABC was obtained in addition to other hematological and clinical parameters. Patients were separated into high and low ABC groups using the Receiver operating characteristic curve analysis. RESULTS: ABC was higher in PMF patients than in healthy controls (P < 0.001). Patients with high ABC had higher white blood cells (P < 0.001), higher red cell distribution width (P = 0.035), higher lactate dehydrogenase (P < 0.001), more frequently had circulatory blasts (P < 0.001), constitutional symptoms (P = 0.030) and massive splenomegaly (P = 0.014). ABC was also positively correlated with absolute monocyte count (AMC) (P < 0.001) and other components of differential blood count. There was no difference in ABC regarding driver mutations or degree of bone marrow fibrosis. Univariately, high ABC was significantly associated with inferior overall survival (hazard ratio (HR) 4.79, P < 0.001). This effect remained statistically significant (HR 4.27, P = 0.009) in a multivariate Cox regression model adjusted for age, gender, Dynamic International Prognostic Scoring System (HR 2.6, P = 0.001) and AMC (HR 8.45, P = 0.002). DISCUSSION: High ABC reflects higher disease activity and stronger proliferative potential of disease. ABC and AMC independently predict survival and therefore seem to reflect different underlying pathophysiologic processes. Hence, both have a potential for improvement of current prognostic scores. CONCLUSION: Basophils represent a part of malignant clone in PMF and are associated with unfavorable disease features and poor prognosis which is independent of currently established prognostic scoring system and monocytosis.

Effect of timing of levothyroxine administration on the treatment of hypothyroidism: a three-period crossover randomized study.

AIM: Hypothyroidism is a common clinical problem that is successfully treated with hormone substitutes in the form of levothyroxine (LT4). LT4 is a drug with a narrow therapeutic index and is usually administered by strict rules, standardly at least half an hour before breakfast. The aim of this study was to investigate a possible effect of different timings of administration on thyroid function status and lipid profile. METHODS: The study included patients with the diagnosis of primary hypothyroidism, which were using a stable dose of levothyroxine. They were randomized into three different groups regarding the timing of LT4 administration in a crossover fashion. Each timing regimen lasted for at least 8 weeks; timing regimen A-half an hour before breakfast; timing regimen B-an hour before the main meal of the day; timing regimen C-at bedtime (minimally 2 h after dinner). The hormones (TSH, fT3, fT4) and lipid profile (triglycerides, HDL-, LDL-, and total cholesterol) were measured before the study, at the beginning of every timing regimen and at the end of the study. RESULTS: Altogether, 84 patients finished the study. Different timings of LT4 administration were non-inferior in comparison to the standard one and between each other. Median differences in TSH level between baseline and timing regimens were: baseline vs. A = -0.017 95% C.I. (-0.400-0.192); baseline vs. B = -0.325 95% C.I. (-0.562-0.023); baseline vs. C = -0.260 95% C.I. (-0.475-0.000). There were no statistically significant differences in either TSH, fT4, or fT3 when compared between all three timing regimens of LT4 administration and the baseline. There were no statistically significant differences in any of the lipid profile parameters (triglycerides, HDL-, LDL-, and total cholesterol) when compared between all three timing regimens of LT4 administration and the baseline. CONCLUSION: The three investigated timing regimens of LT4 administration were equally efficient and offer additional options regarding the treatment individualization.