Publications by authors named "Vera Lanska"

105 Publications

Short-term trajectories of exercise-induced plasma lipid changes in overweight females, with a focus on HDL-cholesterol.

Adv Clin Exp Med 2021 Mar;30(3):239-243

Institute for Clinical and Experimental Medicine (IKEM), Prague, Czech Republic.

Background: Increased levels of plasma lipoproteins are among some of the modifiable risk factors for cardiovascular disease (CVD). Dietary changes and increased physical activity are the most powerful non-pharmacological interventions for achieving optimal plasma lipid levels.

Objectives: To investigate the effect of an intensive short-term lifestyle intervention on plasma lipid trajectories in overweight non-diabetic females.

Material And Methods: A total of 202 healthy overweight (body mass index (BMI) >27.5 kg/m2) females underwent an intensive short-term (ten-week) intervention (at least 4 units of one-hour exercise activity weekly at optimal energy intake) aimed at lowering body weight. Plasma lipid (total cholesterol (TC), low-density-lipoprotein cholesterol (LDL-C), high-density-lipoprotein cholesterol (HDL-C), and triglycerides (TG)) levels were examined at baseline and every 2 weeks over the course of the ten-week intervention.

Results: There was a significant decrease in BMI (Δ -4.7%, p < 0.001) and body weight (Δ -4.9%, p < 0.001) after the intervention. Positive changes (decreases) in TC (Δ -8%, p < 0.001), TG (Δ -9%, p < 0.001) and LDL-C (Δ -11%, p < 0.001) were observed immediately after 2 weeks, but levels did not decrease further thereafter. In contrast, HDL-C did not increase as expected: after 2 weeks of intervention, we observed a significant decrease of about 6% (p < 0.001) followed by a slow return to baseline values. But even after 10 weeks of intervention, HDL-C values had not reached the values detected at baseline.

Conclusions: In overweight females, HDL-C decreased after short-term intensive lifestyle intervention. To confirm the protective effect of increased physical activity, plasma lipids need to be examined over a longer time period.
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http://dx.doi.org/10.17219/acem/129574DOI Listing
March 2021

Liver stiffness measured by two-dimensional shear-wave elastography predicts hepatic vein pressure gradient at high values in liver transplant candidates with advanced liver cirrhosis.

PLoS One 2021 7;16(1):e0244934. Epub 2021 Jan 7.

Department of Hepatogastroenterology, Transplant Centre, Institute for Clinical and Experimental Medicine, Prague, Czech Republic.

Liver stiffness is a reliable non-invasive predictor of Hepatic Venous Pressure Gradient (HVPG) above 10 mm Hg. However, it failed to predict higher thresholds of HVPG. Our aim was to investigate whether liver stiffness and selected previously published non-invasive blood biomarkers could predict higher HVPG thresholds in liver transplant candidates without ongoing alcohol use. One hundred and nine liver transplant candidates with liver cirrhosis of various aetiologies underwent direct HVPG measurement, liver stiffness measurement by 2D shear-wave elastography (Aixplorer Multiwave, Supersonic Imagine, France) and assessment of blood HVPG biomarkers (osteopontin, VCAM-1, IL-6, TNF-α, IL-1ra/IL-1F3 and ELF score). The correlation between liver stiffness and HVPG was linear up to 30 mm Hg of HVPG (r = 0.765, p < 0.0001). The regression lines had similar slopes for HVPG values below and above 16 mm Hg (p > 0.05) and the correlation in patients with HVPG <16 mm Hg (r = 0.456, p = 0.01) was similar to patients with HVPG ≥ 16 mm Hg (r = 0.499, p < 0.0001). The correlation was similar in the subgroup patients with alcoholic (r = 0.718, p < 0.0001), NASH (r = 0.740, p = 0.008), cryptogenic (r = 0.648, p = 0,0377), cholestatic and autoimmune (r = 0.706, p < 0.0001) and viral cirrhosis (r = 0.756, p < 0.0001). Liver stiffness distinguished patients with HVPG above 16, and 20 mm Hg with AUROCs 0.90243, and 0.86824, sensitivity 0.7656, and 0.7027, and specificity 0.9333, and 0.8750. All studied blood biomarkers correlated better with liver stiffness than with HVPG and their AUROCs did not exceed 0.8 at both HVPG thresholds. Therefore, a composite predictor superior to liver stiffness could not be established. We conclude that liver stiffness is a clinically reliable predictor of higher HVPG thresholds in non-drinking subjects with advanced liver cirrhosis.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0244934PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7790429PMC
January 2021

Reference values of retinal microcirculation parameters derived from a population random sample.

Microvasc Res 2021 03 25;134:104117. Epub 2020 Nov 25.

Department of Nephrology and Hypertension, Friedrich-Alexander-University, Erlangen-Nürnberg, Germany.

Retinal microcirculation reflects retinal perfusion abnormalities and retinal arterial structural changes at relatively early stages of various cardiovascular diseases. Our objective has been to establish reference values for major functional and structural parameters of retinal microcirculation in a randomly selected urban population sample. A total of 398 randomly selected individuals from an urban population aged 25 to 65 years, resident in Pilsen, Czech Republic, were screened for major cardiovascular risk factors. Retinal microcirculation was assessed using scanning laser Doppler flowmetry (SLDF), with data evaluable in 343 patients. Of this number, complete data were available for 256 individuals free from manifest cardiovascular disease, diabetes and drug treatment for hypertension and/or dyslipidemia, constituting the reference value population. Juxtapapillary retinal capillary blood flow has increased significantly with age whereas vessel and luminal diameters have decreased. No sex differences in retinal microcirculation parameters have been found. Therefore, reference values for retinal microcirculation parameters have been established by age groups. Unattended automated office systolic BP, after adjusting for age, correlated significantly with wall-to-lumen ratio (WLR) and wall thickness (WT). Moreover, after adjusting for age and mean BP, a positive relationship has been found between carotid femoral pulse wave velocity and WT, WLR and wall cross-sectional area, indicating the interaction between micro- and macro-vasculature. In conclusion, our study is the first to provide reference values of retinal microcirculation parameters in a random Caucasian population sample. Our results have shown that, at the population level, the first structural changes in retinal microcirculation are those in lumen diameters. Of note, a close relationship between BP and vascular remodeling of retinal arterioles and between aortic stiffness and WLR of retinal arterioles suggests an interaction between micro- and macro-vasculature.
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http://dx.doi.org/10.1016/j.mvr.2020.104117DOI Listing
March 2021

Serum Bilirubin in the Czech Population - Relationship to the Risk of Myocardial Infarction in Males.

Circ J 2020 09 26;84(10):1779-1785. Epub 2020 Aug 26.

Institute of Medical Biochemistry and Laboratory Diagnostics, Faculty General Hospital and 1st Faculty of Medicine, Charles University.

Background: The potential antiatherogenic role of bilirubin is generally acknowledged, so the aim of this study was to determine serum bilirubin concentrations and the prevalence of Gilbert syndrome (GS) in the Czech general population with particular reference to its relationship to the risk of myocardial infarction (MI).Methods and Results:Biochemical markers were analyzed in 2 independent Czech post-MONICA studies (in total, n=3,311), and in 741 male MI patients. TheUGT1A1promoter gene variant (rs81753472) was analyzed in these MI patients and in the first control population cohort (n=717). Medians of serum bilirubin concentrations in the 2 Czech general population cohorts were 9.6 and 9.8 μmol/L (10.7 and 11.3 μmol/L in males, and 8.3 and 8.8 μmol/L in females; P<0.01). The prevalence of GS was 8.9%, twice as high in males compared with females (11.6 vs. 6.1%; P<0.01). TheUGT1A1(TA)promoter repeats significantly influenced serum bilirubin concentrations in the controls, but not in the MI patients. Serum bilirubin concentrations were significantly lower in MI patients (7.7 vs. 10.7 μmol/L; P<0.01), with almost 5-fold lower prevalence of GS.

Conclusions: Serum bilirubin concentrations and the prevalence of GS were determined in the Czech general population. Significantly lower serum bilirubin concentrations were observed in male MI patients.
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http://dx.doi.org/10.1253/circj.CJ-20-0192DOI Listing
September 2020

Post-infarction left ventricular free wall rupture: 12-years experience from the Cardiac Centre of the Institute of Clinical and Experimental Medicine in Prague, Czech Republic.

Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 2020 Aug 18. Epub 2020 Aug 18.

Cardiac Centre, Institute of Clinical and Experimental Medicine, Prague, Czech Republic.

Background: Post-infarction left ventricular free wall rupture (LVFWR) is a feared and catastrophic complication of myocardial infarction that carries a high surgical and hospital mortality. Due to the rarity of this complication, little information exists on surgical treatment and outcomes.Goal and Methods: The goal of this study was to present our experience with LVFWR. We present a retrospective cohort of 19 consecutive patients who were surgically treated in the Cardiac Centre of the Institute of Clinical and Experimental Medicine in Prague between January 2006 and December 2017.

Results: Thirty-day mortality was 26%. Five patients died. Four patients died in the operating theatre and one patient on the ninth postoperative day following re-rupture. Seventy-four percent of the patient cohort survived and were discharged from hospital. The median length of follow-up was 45 months (range 0.75-150). No patient died during follow-up. Median postoperative ejection fraction was 45% (range 25-65%). Angina pectoris and dyspnea were investigated during follow-up and graded according to the Canadian cardiology society (CCS) and the New York Heart Association (NYHA) classifications. Fourteen patients had CCS class I, eight patients had NYHA class I dyspnea and six patients had NYHA class II. Re-rupture occurred after hospital discharge in one patient one month after the original surgery. The patient was treated successfully by urgent surgical intervention.

Conclusion: LVFWR is a catastrophic and challenging complication of myocardial infarction. Good outcomes can be achieved by rapid diagnosis and urgent surgical intervention as shown by our results.
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http://dx.doi.org/10.5507/bp.2020.022DOI Listing
August 2020

Reply.

J Hypertens 2020 09;38(9):1860-1861

Department of Medicine III, Charles University in Prague, First Faculty of Medicine, Prague, Czech Republic.

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http://dx.doi.org/10.1097/HJH.0000000000002498DOI Listing
September 2020

Analysis of incidence and prevalence of cardiovascular risk factors and evaluation of their control in epidemiological survey in the Czech Republic.

Cent Eur J Public Health 2020 Jun;28(2):114-119

Third Department of Internal Medicine, Department of Endocrinology, Metabolism, First Medical Faculty, Charles University, General Faculty Hospital, Prague, Czech Republic.

Objective: The aim of this analysis was to analyze the presence of the most important cardiovascular (CV) risk factors and to discuss patterns of LDL cholesterol management in the population studied.

Methods: We enrolled 961 males, average age of 42.9 ± 4.7, and 851 females, average age of 51.2 ± 3.6. Data on personal, pharmacological and family history, and laboratory examinations were collected. Cardiovascular (CV) risk was calculated using the Systematic Coronary Risk Evaluation (SCORE) algorithm with modifications according to the guidelines.

Results: The distribution of CV risk in the observed cohort was as follows: 24% of the subjects had low, 51% moderate, 17% high and 8% very high risk. The percentage of patients who reached target values of LDL cholesterol was dramatically lower in the groups with very high (1%) and high (3%) risk than in the groups with moderate (14%) or low risk (59%). Dyslipidemia was newly identified in 20% of both sexes. Arterial hypertension was newly diagnosed in 8% of males and 5% of females, and type 2 diabetes mellitus was newly diagnosed in 3% of both the males and females. Dyslipidemia was present in 39% of males and 41% of females; arterial hypertension in 43% of males and 45% of females, and type 2 diabetes mellitus was diagnosed in 11% of the subjects of both sexes. 49% of males and 31% of females were overweight and 32% of both genders were obese. There were 36% of male smokers and 22% of female smokers. 48% of the participants were pharmacologically treated. Non-pharmacological treatment was recommended to 62% of male and to 65% of female participants. Pharmacological intervention was started in 53% of males and 51% of females. In both gender antihypertensive treatment with angiotensin-converting enzyme (ACE) inhibitors (29% of males and 27% of females) and lipid lowering therapy with a statin (28% of males, 27% of females) were the most commonly initiated treatments. In the subgroup of the 101 patients with LDL cholesterol levels > 5 mmol/L 56% were not treated with a statin. The analysis of relationship between the positive family history of any of the followed CV risks showed significant increases of the risk for arterial hypertension, type 2 diabetes mellitus and dyslipidemia.

Conclusion: European guidelines suggest general screening for risk factors, including analysis of lipid profiles in the population of 40-year-old males and 50-year-old or postmenopausal women. Our study documents high prevalence and incidence of CV risk factors together with insufficient control of the risk factors in Czech patients of this age range. This finding suggests that preventive examinations should be undertaken earlier (e.g., in 30-year-old males and 40-year-old women). Exact timing of the preventive check-ups to yield the best cost-benefit ratio needs to be verified.
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http://dx.doi.org/10.21101/cejph.a5730DOI Listing
June 2020

Longitudinal trends in the prevalence of hyperuricaemia and chronic kidney disease in hypertensive and normotensive adults.

Blood Press 2020 10 19;29(5):308-318. Epub 2020 May 19.

Center for Cardiovascular Prevention, First Faculty of Medicine and Thomayer Hospital, Charles University in Prague, Prague, Czech Republic.

To evaluate longitudinal trends in the prevalence of hyperuricaemia and chronic kidney disease (CKD) in Czech adults with and without arterial hypertension (HT). Two independent cross-sectional surveys were performed in 2006-2009 and 2015-2018, each screening involving 1% population random sample of the general population of nine districts of the Czech Republic aged 25-64 years, stratified by age and gender. Hyperuricaemia was defined as serum uric acid ≥ 420 μmol/l in men, and ≥ 360 μmol/l in women. CKD was defined as estimated glomerular filtration rate < 60 ml/min/1.73 m and/or albumin/creatinine ratio ≥ 3 mg/mmol.Results: Final analyses included 3504 individuals examined in 2006-2009, and 2309 in 2015-2018. The overall prevalence of hyperuricaemia increased from 16.4% to 25.2% in men ( < 0.001), and from 7.6% to 10.9% in women ( < 0.001), whereas the overall prevalence of CKD declined from 6.8% to 3.6% in men ( = 0.001), and from 7.6% to 4.8% in women ( < 0.001). There was no interaction between HT and hyperuricaemia in either gender; the increase in hyperuricaemia prevalence was observed both in hypertensive and normotensive adults and was accompanied by the increased prevalence of abdominal obesity. Contrarily, there was an interaction between HT and CKD in both men ( < 0.001) and women ( = 0.011); the CKD prevalence declined only in hypertensive individuals, specifically in those using antihypertensive medication and was accompanied by the increased use of renin-angiotensin-aldosterone system (RAS) inhibitors and calcium channel blockers (CCBs). Over the period of 10 years, the overall prevalence of hyperuricaemia increased, while the prevalence of CKD decreased. An increase in the prevalence of hyperuricaemia was observed both in hypertensive and normotensive individuals and was accompanied by an increase in the prevalence of abdominal obesity. A decline in the prevalence of CKD was only observed in hypertensive individuals and was accompanied by the increased use of RAS inhibitors and CCBs.
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http://dx.doi.org/10.1080/08037051.2020.1763158DOI Listing
October 2020

30-year trends in major cardiovascular risk factors in the Czech population, Czech MONICA and Czech post-MONICA, 1985 - 2016/17.

PLoS One 2020 11;15(5):e0232845. Epub 2020 May 11.

Medical Statistics Unit, Institute for Clinical and Experimental Medicine, Prague, Czech Republic.

Background: Compared with Western Europe, the decline in cardiovascular (CV) mortality has been delayed in former communist countries in Europe, including the Czech Republic. We have assessed longitudinal trends in major CV risk factors in the Czech Republic from 1985 to 2016/17, covering the transition from the totalitarian regime to democracy.

Methods: There were 7 independent cross-sectional surveys for major CV risk factors conducted in the Czech Republic in the same 6 country districts within the WHO MONICA Project (1985, 1988, 1992) and the Czech post-MONICA study (1997/98, 2000/01, 2007/08 and 2016/2017), including a total of 7,606 males and 8,050 females. The population samples were randomly selected (1%, aged 25-64 years).

Results: Over the period of 31/32 years, there was a significant decrease in the prevalence of smoking in males (from 45.0% to 23.9%; p < 0.001) and no change in females. BMI increased only in males. Systolic and diastolic blood pressure decreased significantly in both genders, while the prevalence of hypertension declined only in females. Awareness of hypertension, the proportion of individuals treated by antihypertensive drugs and consequently hypertension control improved in both genders. A substantial decrease in total cholesterol was seen in both sexes (males: from 6.21 ± 1.29 to 5.30 ± 1.05 mmol/L; p < 0.001; females: from 6.18 ± 1.26 to 5.31 ± 1.00 mmol/L; p < 0.001).

Conclusions: The significant improvement in most CV risk factors between 1985 and 2016/17 substantially contributed to the remarkable decrease in CV mortality in the Czech Republic.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0232845PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7213700PMC
August 2020

Which serum uric acid levels are associated with increased cardiovascular risk in the general adult population?

J Clin Hypertens (Greenwich) 2020 05 9;22(5):897-905. Epub 2020 Apr 9.

Center for Cardiovascular Prevention, First Faculty of Medicine and Thomayer Hospital, Charles University in Prague, Prague, Czech Republic.

Our aim was to determine the serum uric acid (SUA) levels associated with an increased risk of cardiovascular (CV) and all-cause death in the general adult population. We analyzed data obtained in two independent cross-sectional surveys performed in the Czech Republic in 2006-09 and 2015-18, involving 1% population random samples in nine districts, aged 25-64 years, stratified by age and gender. Ten-year mortality data were obtained in a cohort with examination in 2006-09. Final analyses included 3542 individuals (48.2% men) examined in 2006-09, and 2304 (47.4% men) examined in 2015-18. From a cohort examined in 2006-09, 122 men and 60 women were reported dead (33% and 27% from CV disease). In men, there was no association of baseline SUA levels with baseline SCORE category or 10-year mortality rates. In women, each 10 µmol/L increase in baseline SUA levels was associated with an increase in baseline SCORE category (P < .001). Receiver operating characteristic curve analyses in women identified the baseline SUA cutoff values discriminating: 1. between low/intermediate and high/very high SCORE categories (309 µmol/L), 2. CV mortality (325 µmol/L), and 3. all-cause mortality (298 µmol/L). After adjusting for confounders including SCORE, Cox regression analysis confirmed that the baseline SUA cutoffs of 309 µmol/L and 325 µmol/L were associated with 4-times (P = .010) and 6-times (P = .036) greater risk of CV mortality, whereas the cutoff of 298 µmol/L was associated with 87% greater risk of all-cause mortality (P = .025). In conclusion, the SUA cutoff value of 309 µmol/L identified women at high/very high SCORE category and was associated with 4-times greater risk of observed CV mortality over 10 years.
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http://dx.doi.org/10.1111/jch.13847DOI Listing
May 2020

Spironolactone-furosemide combination therapy and acid-base disorders in liver cirrhosis patients
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Int J Clin Pharmacol Ther 2020 May;58(5):261-267

Objective: Respiratory alkalosis (RA) and dilutional hyperchloremic acidosis (DHA) are the most common acid-base balance (ABB) disorders in patients with liver cirrhosis. The aims of this study were to clarify whether RA develops in relation to DHA via respiratory compensation of metabolic acidosis and whether spironolactone in combination with low-dose furosemide - diuretics known to ameliorate DHA - positively affects RA in liver cirrhosis patients.

Materials And Methods: 59 patients with advanced cirrhosis were divided into two groups. Group D consisted of individuals (urine sodium concentration (U) > 20 mmol/L) who responded to combination therapy consisting of spironolactone and low-dose furosemide. The non-D group consisted of individuals (U ≤ 20 mmol/L) who either did not respond to the treatment or who were not administered it. In both groups, we examined serum and urine concentrations of electrolytes and ABB parameters, including S-S and S/S values.

Results: In group D, we found a statistically significant relationship between pCO and S: r = 0.756 (p < 0.001) and between pCO and S-S: r = 0.522 (p = 0.001). Neither S nor the corrected anion gap were associated with changes in S or pCO values. Although S values were normal, abnormal pCO values were observed in one third of group D patients. Based on multivariable analysis, S proved to be a statistically significant influencing factor on pCO values.

Conclusion: DHA contributes to the development of RA in individuals with liver cirrhosis. Reducing DHA by means of effective diuretic therapy comprising spironolactone and furosemide has a beneficial effect on RA in such patients.
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http://dx.doi.org/10.5414/CP203624DOI Listing
May 2020

Primary aldosteronism in a general population sample. The Czech post-MONICA study.

Blood Press 2020 06 8;29(3):191-198. Epub 2020 Feb 8.

Center for Cardiovascular Prevention, First Faculty of Medicine, Charles University in Prague, Prague, Czech Republic.

Primary aldosteronism (PA) is considered the most common form of secondary hypertension, however, its prevalence, particularly in a general population, is still a matter of debate. The aim of our study was to evaluate the prevalence of PA in a randomly selected general population sample. A total of 1940 individuals (1% population random sample) aged 25-64 years were screened for major cardiovascular risk factors in six districts of the Czech Republic. Hypertension was defined as a mean of two blood pressure readings ≥140/90 mmHg at one visit or taking antihypertensive medication. Within this population, 740 individuals were labelled as hypertensives and 650 of them sampled for the analysis of direct plasma renin and serum aldosterone. The diagnosis of PA was based on elevated serum aldosterone, low plasma renin and high aldosterone/renin (ARR) ratio and was also verified by a confirmatory test with saline infusion. Positive ARR was found in 52 (8%) individuals (64% women, 36% men, however, due to substatntial proportion of reluctatnt participants to undergo a further work-up (27%), we could confirm the diagnosis of PA only in 13 of them (2%). Aldosterone-producing adenoma was found in one case only, seven patients had idiopathic type and five individuals refused potential surgical treatment therefore, adrenal venous sampling was not performed. Elevated serum aldosterone together with low renin and high ARR were found in 52 (8%) of hypertensives selected from a general population sample, however, the diagnosis of PA was confirmed only in 13 of them (2%). This study based on a general population survey highlighted the difficulty of conducting epidemiological studies on primary aldosteronism in a relatively healthy cohort part of whom did not provide the level of collaboration that is necessary to assess the true prevalence of this condition.
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http://dx.doi.org/10.1080/08037051.2020.1723406DOI Listing
June 2020

SNPs within CHRNA5-A3-B4 and CYP2A6/B6, nicotine metabolite concentrations and nicotine dependence treatment success in smokers.

Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 2021 Mar 29;165(1):84-89. Epub 2019 Nov 29.

Centre for Tobacco-Dependent, 3rd Department of Medicine - Department of Endocrinology and Metabolism, 1st Faculty of Medicine, Charles University and the General University Hospital in Prague, Czech Republic.

Aim: Plasma values of nicotine and its metabolites are highly variable, and this variability has a strong genetic influence. In our study, we analysed the impact of common polymorphisms associated with smoking on the plasma values of nicotine, nicotine metabolites and their ratios and investigated the potential effect of these polymorphisms and nicotine metabolite ratios on the successful treatment of tobacco dependence.

Methods: Five variants (rs16969968, rs6474412, rs578776, rs4105144 and rs3733829) were genotyped in a group of highly dependent adult smokers (n=103). All smokers underwent intensive treatment for tobacco dependence; 33 smokers were still abstinent at the 12-month follow-up.

Results: The rs4105144 (CYP2A6, P<0.005) and rs3733829 (EGLN2, P<0.05) variants were significantly associated with plasma concentrations of 3OH-cotinine and with 3OH-cotinine: cotinine ratios. Similarly, the unweighted gene score was a significant (P<0.05) predictor of both cotinine:nicotine and 3OH-cotinine:cotinine ratios. No associations between the analysed polymorphisms or nicotine metabolite ratios and nicotine abstinence rate were observed.

Conclusion: Although CYP2A6 and EGLN2 polymorphisms were associated with nicotine metabolism ratios, neither these polymorphisms nor the ratios were associated with abstinence rates.
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http://dx.doi.org/10.5507/bp.2019.058DOI Listing
March 2021

The Superiority of Removable Contact Splints in the Healing of Diabetic Foot during Postoperative Care.

J Diabetes Res 2019 15;2019:5945839. Epub 2019 Sep 15.

Diabetes Centre, Institute for Clinical and Experimental Medicine, Prague, Czech Republic.

Objective: Off-loading is one of the crucial components of diabetic foot (DF) therapy. However, there remains a paucity of studies on the most suitable off-loading for DF patients under postoperative care. The aim of our study was to evaluate the effect of different protective off-loading devices on healing and postoperative complications in DF patients following limb preservation surgery.

Methods: This observational study comprised 127 DF patients. All enrolled patients had undergone foot surgery and were off-loaded empirically as follows: wheelchair+removable contact splint (RCS) (group R: 29.2%), wheelchair only (group W: 48%), and wheelchair+removable prefabricated device (group WP: 22.8%). We compared the primary (e.g., the number of healed patients, healing time, and duration of antibiotic (ATB) therapy) and secondary outcomes (e.g., number of reamputations and number and duration of rehospitalizations) with regard to the operation regions across all study groups.

Results: The lowest number of postoperative complications (number of reamputations: = 0.028; rehospitalizations: = 0.0085; and major amputations: = 0.02) was in group R compared to groups W and WP. There was a strong trend toward a higher percentage of healed patients (78.4% vs. 55.7% and 65.5%; = 0.068) over a shorter duration (13.7 vs. 16.5 and 20.3 weeks; = 0.055) in the R group, as well. Furthermore, our subanalysis revealed better primary outcomes in patients operated in the midfoot and better secondary outcomes in patients after forefoot surgery-odds ratios favouring the R group included healing at 2.5 (95% CI, 1.04-6.15; = 0.037), reamputations at 0.32 (95% CI, 0.12-0.84; = 0.018), and rehospitalizations at 0.22 (95% CI, 0.08-0.58; = 0.0013).

Conclusions: This observational study suggests that removable contact splint combined with a wheelchair is better than a wheelchair with or without removable off-loading device for accelerating wound healing after surgical procedures; it also minimises overall postoperative complications, reducing the number of reamputations by up to 77% and the number of rehospitalizations by up to 66%.
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http://dx.doi.org/10.1155/2019/5945839DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6766149PMC
April 2020

Sirolimus vs mycophenolate mofetil (MMF) in primary combined pancreas and kidney transplantation. Results of a long-term prospective randomized study.

Am J Transplant 2020 03 23;20(3):779-787. Epub 2019 Oct 23.

Diabetes Center, Institute for Clinical and Experimental Medicine, Prague, Czech Republic.

The study was intended to compare pancreas graft survival rates in two groups of pancreas and kidney transplant recipients prospectively randomized to treatment either with sirolimus or MMF. From 2002 to 2013, 238 type 1 diabetic recipients with end-stage kidney disease were randomized 1:1 to sirolimus or MMF treatment. Noncensored pancreas survival at 5 years was 76.4 and 71.6% for sirolimus and MMF groups, respectively (P > .05). Death-censored pancreas survival was better in the sirolimus group (P = .037). After removal of early graft losses pancreas survival did not differ between groups (MMF 83.1% vs sirolimus 91.6%, P = .11). Nonsignificantly more grafts were lost due to rejection in the MMF group (10 vs 5; P = .19). Cumulative patient 5-year survival was 96% in the MMF group and 91% in the sirolimus group (P > .05). Five-year cumulative noncensored kidney graft survival rates did not statistically differ (85.6% in the sirolimus group and 88.8% in MMF group). Recipients treated with MMF had significantly more episodes of gastrointestinal bleeding (7 vs 0, P = .007). More recipients in the sirolimus group required corrective surgery due to incisional hernias (21 vs 12, P = .019). ClinicalTrials No.: NCT03582878.
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http://dx.doi.org/10.1111/ajt.15622DOI Listing
March 2020

Donor PNPLA3 and TM6SF2 Variant Alleles Confer Additive Risks for Graft Steatosis After Liver Transplantation.

Transplantation 2020 03;104(3):526-534

Department of Hepatogastroenterology, Institute for Clinical and Experimental Medicine, Prague, Czech Republic.

Background: The rs58542926 polymorphism in transmembrane 6 superfamily member 2 (TM6SF2) is a genetic factor predisposing to nonalcoholic fatty liver disease. We aimed to explore the effect of recipient and donor TM6SF2 rs58542926 genotypes on liver graft fat content after liver transplantation.

Methods: Steatosis was evaluated in liver biopsies from 268 adult recipients. The influence of recipient and donor TM6SF2 genotypes, patatin-like phospholipase domain-containing 3 (PNPLA3) rs738409 genotypes, and nongenetic factors on the steatosis grade assessed 6-30 months after transplantation was analyzed by ordinal logistic regression.

Results: The presence of the TM6SF2 c.499A allele in the donor (P = 0.014), PNPLA3 c.444G allele in the donor (P < 0.001), posttransplant body mass index (P < 0.001), and serum triglycerides (P = 0.047) independently predicted increased liver fat content on multivariable analysis, whereas noncirrhotic liver disease, as an indication for liver transplantation, was associated with lower risk of steatosis (P = 0.003). The effects of the donor TM6SF2 A and PNPLA3 G alleles were additive, with an odds ratio of 4.90 (95% confidence interval, 2.01-13.00; P < 0.001), when both minor alleles were present compared with an odds ratio of 2.22 (95% confidence interval, 1.42-3.61; P = 0.002) when only one of these alleles was present.

Conclusions: The donor TM6SF2 c.499A allele is an independent risk factor of liver graft steatosis after liver transplantation that is additive to the effects of donor PNPLA3 c.444G allele.
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http://dx.doi.org/10.1097/TP.0000000000002876DOI Listing
March 2020

Blood pressure distribution and control in coronary patients from 24 European countries in the European Society of Cardiology EURoObservational Research Programme European survey of cardiovascular disease prevention and diabetes. EUROASPIRE IV Registry.

J Hypertens 2019 10;37(10):2015-2023

Department of Public Health and Primary Care, Ghent University, Ghent, Belgium.

Background: Hypertension is the most prevalent major independent risk factor for developing coronary heart disease (CHD). The present analysis aimed to assess blood pressure (BP) distribution and factors associated with insufficient BP control in coronary patients from 24 countries participating in the European Society of Cardiology (ESC) EURoObservational Research Programme (EORP) EUROASPIRE IV survey.

Methods: EUROASPIRE IV is a cross-sectional study conducted in 2012-2013 in patients aged 80 years or less hospitalized for CHD with a follow-up visit at a median of 16 months later. Logistic regression analysis was applied to confirm factors associated with BP control defined as less than 140/90 mmHg for nondiabetic patients and less than 140/85 mmHg for diabetic patients.

Results: A total of 7998 patients (response rate, 48.7%) attended the follow-up visit. Complete data were available in 7653 participants (mean age 62.5 ± 9.6 years). The BP goal was achieved in 57.6%. Patients failing to achieve the BP goal were older, had higher BMI, had more often a history of coronary artery bypass grafting (CABG) and reported diabetes more frequently. Logistic regression confirmed the following independent significant predictors of not achieving the BP goal: a history of diabetes [odds ratio (OR) 1.75], obesity (OR 1.70 vs. normal BMI), overweight (OR 1.28 vs. normal BMI), age at least 65 years (OR 1.53) and CABG as the index event (OR 1.26 vs. acute MI).

Conclusion: EUROASPIRE IV found insufficient BP control in a large proportion of patients with stable CHD, with diabetes, increased BMI, older age and CABG as the index event being independent predictors of poor BP control.
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http://dx.doi.org/10.1097/HJH.0000000000002130DOI Listing
October 2019

The Gene Score for Predicting Hypertriglyceridemia: New Insights from a Czech Case-Control Study.

Mol Diagn Ther 2019 08;23(4):555-562

3rd Department of Internal Medicine, 1st Faculty of Medicine, Charles University, Prague, Czech Republic.

Background: Plasma triglyceride (TG) values are significant predictors of cardiovascular and total mortality. The plasma levels of TGs have an important genetic background. We analyzed whether 32 single nucleotide polymorphisms (SNPs) identified in genome-wide association studies are discriminators of hypertriglyceridemia (HTG) in the Czech population.

Objectives: The objective of this study was to replicate and test the original findings in an independent study and to re-analyze the gene score leading to HTG.

Methods: In total, we analyzed 32 SNPs in 209 patients with plasma TG levels over 10 mmol/L (HTG group) and compared them in a case-control design with 524 treatment-naïve controls (normotriglyceridemic [NTG] group) with plasma TG values below 1.8 mmol/L.

Results: Sixteen SNPs were significantly associated with an increased risk of HTG development, with odds ratios (ORs) (95% confidence interval [CI]) varying from 1.40 (1.01-1.95) to 4.69 (3.29-6.68) (rs964184 within the APOA5 gene). Both unweighted (sum of the risk alleles) and weighted gene scores (WGS) (log of the achieved ORs per individual genotype) were calculated, and both gene scores were significantly different between groups. The mean score of the risk alleles was significantly increased in the HTG group compared to the NTG group (18.5 ± 2.5 vs. 15.7 ± 2.3, respectively; P < 0.00001). Subjects with a WGS over 9 were significantly more common in the HTG group (44.5%) than in the NTG group, in which such a high score was observed in only 4.7% of subjects (OR 16.3, 95% CI 10.0-36.7; P < 0.0000001).

Conclusions: An increased number of risk genetic variants, calculated both in a weighted or unweighted manner, significantly discriminates between the subjects with HTG and controls. Population-specific sets of SNPs included into the gene score seem to yield better discrimination power.
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http://dx.doi.org/10.1007/s40291-019-00412-2DOI Listing
August 2019

Retrospective Analysis of Bone Metabolism in Patients on Waiting List for Simultaneous Pancreas-Kidney Transplantation.

J Diabetes Res 2019 14;2019:5143021. Epub 2019 May 14.

Diabetes Center, Institute for Clinical and Experimental Medicine, Prague 140 21, Czech Republic.

Posttransplant osteoporosis, which evolves from preexisting bone pathologies, represents a serious complication with deteriorating consequences. The aim of our study was to evaluate epidemiological data on bone mineral density (BMD) in subjects with type 1 diabetes (T1DM) in advanced stages of diabetic nephropathy indicated for simultaneous pancreas-kidney transplantation (SPK). We retrospectively compiled biochemical and densitometrical data from 177 patients with T1DM at CKD (chronic kidney disease) stages G4-G5 (115 men, 62 women, median age 40 yr, diabetes duration 23 yr) enrolled on waiting list for SPK for the first time between the years 2011 and 2016. Median -scores were as follows: lumbar spine (LS): -0.8 [interquartile range -1.75 to 0.1]; total hip (TH): -1.2 [-1.75 to -0.6]; femoral neck (FN): -1.2 [-1.9 to -0.7]; and distal radius (DR): -0.8 [-1.4 to -0.1]. We noted a gender difference in LS, with worse results for men (-1.1 vs. -0.3) even after adjusting for BMI (body mass index) and glomerular filtration ( < 0.001). Osteoporotic and osteopenic ranges (based on -scores) for all major sites were 27.7% and 56.5%, respectively, with similar results across both genders. Women had a significantly higher proportion of normal BMD in LS than men (67.7 vs. 49.4%, < 0.05). Patients with T1DM at CKD stages G4-G5 exhibited serious BMD impairment despite their young age. Men surprisingly displayed lower -scores and higher percentages of pathological BMD values in LS than women did. The introduction of adequate preventive measures during the advanced stages of diabetic nephropathy to prevent bone loss is recommended.
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http://dx.doi.org/10.1155/2019/5143021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6536959PMC
January 2020

Benefits of Acidifying Agents in Local Therapy of Diabetic Foot Ulcers Infected by sp: A Pilot Study.

Int J Low Extrem Wounds 2019 Sep 3;18(3):262-268. Epub 2019 Jun 3.

Institute for Clinical and Experimental Medicine, Prague, Czech Republic.

Infections caused by Pseudomonas sp are difficult to resolve by antibiotics (ATBs) and local therapy. The aim of our pilot study was to assess the effect of different local agents-particularly acidifying solutions-on the healing of diabetic foot ulcers (DFUs), eradication of pathogens, and economic costs related to DFU therapy. In this case study, we monitored 32 DFU patients infected by species. Patients were divided into 2 groups according to the local therapy provided: group 1 (n = 15)-modern local treatment; group 2 (n = 17)-acidifying antiseptic solutions. The study groups differed only with regard to ATB usage prior to enrolment in the study ( = .004), but did not differ with regard to age, diabetes control, peripheral arterial disease, or microcirculation status. During the follow-up period, DFUs healed in 20% of cases in group 1, but there were no cases of healing in group 2 (NS). The length of ATB therapy, the number of new osteomyelitis, lower limb amputations, and the changes of DFUs status/proportions did not differ significantly between study groups. was eradicated in 67% of cases in group 1 and in 65% of cases in group 2. The local treatment given to group 2 patients was associated with lower costs ( < .0001). . Acidifying agents had the same effect as modern healing agents on wound healing, the number of amputations, and the eradication of . Moreover, therapy performed using acidifying solutions proved in our pilot study markedly cheaper.
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http://dx.doi.org/10.1177/1534734619848573DOI Listing
September 2019

Association between aortic telomere length and cardiac post-transplant allograft function.

Int J Cardiol 2019 09 7;290:129-133. Epub 2019 May 7.

Cardio Centre, Institute for Clinical and Experimental Medicine, Videnska 1958/9, Prague 14021, Czech Republic.

Background: In patients having undergone orthotopic heart transplantation, a number of complications exist that are known to be connected to both telomerase activity and telomere length. The aim of this study was to determine how telomere length in aortic DNA correlates with the subsequent post-transplantation development of the patients.

Materials And Methods: Between 2005 and 2015, we collected aortic samples from 376 heart recipients (age 50.8 ± 11.8 years) and 383 donors (age 38.6 ± 12.2 years). Relative telomere length in aortic tissue DNA was determined using quantitative PCR.

Results: Shorter telomere length was detected in heart allograft recipients compared to donors (P < 0.0001). Patients suffering acute cellular rejection had significantly shorter telomere length (P < 0.01) than patients without rejection. Shorter telomere length was observed in patients with implanted mechanical circulatory support before heart transplantation (P < 0.03), as well as in subjects with cardiac allograft vasculopathy (P < 0.05). Overall survival time after heart transplantation was associated with shorter donor telomeres (P < 0.004).

Conclusions: Telomere length differed between donors and recipients independent of the sex and age of the patients. Our findings suggest a potential new linkage between the aortic telomere length of recipients and post-heart transplant complications. Further studies focusing on epigenetic modifications and gene regulation involved in telomere maintenance in transplanted patients should verify our results.
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http://dx.doi.org/10.1016/j.ijcard.2019.05.006DOI Listing
September 2019

Microbiome and Metabolome Profiles Associated With Different Types of Short Bowel Syndrome: Implications for Treatment.

JPEN J Parenter Enteral Nutr 2020 01 29;44(1):105-118. Epub 2019 Apr 29.

Institute for Clinical and Experimental Medicine, Prague, Czech Republic.

Background: The gut microbiome and metabolome may significantly influence clinical outcomes in patients with short bowel syndrome (SBS). The study aimed to describe specific metagenomic/metabolomics profiles of different SBS types and to identify possible therapeutic targets.

Methods: Fecal microbiome (FM), volatile organic compounds (VOCs), and bile acid (BA) spectrum were analyzed in parenteral nutrition (PN)-dependent SBS I, SBS II, and PN-independent (non-PN) SBS patients.

Results: FM in SBS I, SBS II, and non-PN SBS shared characteristic features (depletion of beneficial anaerobes, high abundance of Lactobacilaceae and Enterobacteriaceae). SBS I patients were characterized by the abundance of oxygen-tolerant microrganisms and depletion of strict anaerobes. Non-PN SBS subjects showed markers of partial FM normalization. FM dysbiosis was translated into VOC and BA profiles characteristic for each SBS cohort. A typical signature of all SBS patients comprised high saturated aldehydes and medium-chain fatty acids and reduced short-chain fatty acid (SCFA) content. Particularly, SBS I and II exhibited low protein metabolism intermediate (indole, p-cresol) content despite the hypothetical presence of relevant metabolism pathways. Distinctive non-PN SBS marker was high phenol content. SBS patients' BA fecal spectrum was enriched by chenodeoxycholic and deoxycholic acids and depleted of lithocholic acid.

Conclusions: Environmental conditions in SBS gut significantly affect FM composition and metabolic activity. The common feature of diverse SBS subjects is the altered VOC/BA profile and the lack of important products of microbial metabolism. Strategies oriented on the microbiome/metabolome reconstitution and targeted delivery of key compounds may represent a promising therapeutic strategy in SBS patients.
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http://dx.doi.org/10.1002/jpen.1595DOI Listing
January 2020

Leukocyte telomere length is not affected by long-term occupational exposure to nano metal oxides.

Ind Health 2019 Nov 28;57(6):741-744. Epub 2019 Mar 28.

Institute of Chemical Process Fundamentals CAS, Czech Republic.

The aim of this study was to ascertain whether long-term occupational exposure to nanoparticles would affect relative leukocyte telomere length (LrTL). We analysed occupational exposure to size-resolved aerosol particles, with special emphasis on nanoparticles at two workshops: i/ the production of nanocomposites containing metal oxides; ii/ laboratory to test experimental exposure of nano-CuO to rodents. Thirty five exposed researchers (age 39.5 ± 12.6 yr; exposure duration 6.0 ± 3.7 yr) and 43 controls (40.4 ± 10.5 yr) were examined. LrTL did not significantly (p=0.14) differ between the exposed researchers (0.92 ± 0.13) and controls (0.86 ± 0.15). In addition, no significant correlation (r=-0.22, p=0.22) was detected between the duration of occupational exposure and LrTL. The results remained non-significant after multiple adjustments for age, sex and smoking status. Our pilot results suggest that relative leukocyte telomere length is not affected by occupational exposure to nanoparticles.
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http://dx.doi.org/10.2486/indhealth.2018-0146DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6885603PMC
November 2019

Preserved Expression of Skin Neurotrophic Factors in Advanced Diabetic Neuropathy Does Not Lead to Neural Regeneration despite Pancreas and Kidney Transplantation.

J Diabetes Res 2018 10;2018:2309108. Epub 2018 Dec 10.

University Hospital of Würzburg, Department of Neurology, 97080 Würzburg, Germany.

Diabetic peripheral neuropathy (DPN) is a common complication of diabetes with potential severe consequences. Its pathogenesis involves hyperglycemia-linked mechanisms, which may include changes in the expression of neurotrophic growth factors. We analyzed the expression of 29 factors potentially related to nerve degeneration and regeneration in skin biopsies from 13 type 1 diabetic pancreas and kidney recipients with severe DPN including severe depletion of intraepidermal nerve fibers (IENF) in lower limb skin biopsies (group Tx1 1st examination). The investigation was repeated after a median 28-month period of normoglycemia achieved by pancreas transplantation (group Tx1 2nd examination). The same tests were performed in 13 stable normoglycemic pancreas and kidney recipients 6-12 years posttransplantation (group Tx2), in 12 matched healthy controls (group HC), and in 12 type 1 diabetic subjects without severe DPN (group DM). Compared to DM and HC groups, we found a significantly higher ( < 0.05-0.001) expression of NGF (nerve growth factor), NGFR (NGF receptor), NTRK1 (neurotrophic receptor tyrosine kinase 1), GDNF (glial cell-derived neurotrophic factor), GFRA1 (GDNF family receptor alpha 1), and GFAP (glial fibrillary acidic protein) in both transplant groups (Tx1 and Tx2). Enhanced expression of these factors was not normalized following the median 28-month period of normoglycemia (Tx1 2nd examination) and negatively correlated with IENF density and with electrophysiological indices of DPN (vibration perception threshold, electromyography, and autonomic tests). In contrast to our expectation, the expression of most of 29 selected factors related to neural regeneration was comparable in subjects with severe peripheral nerve fiber depletion and healthy controls and the expression of six factors was significantly upregulated. These findings may be important for better understanding the pathophysiology of nerve regeneration and for the development of intervention strategies.
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http://dx.doi.org/10.1155/2018/2309108DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6311823PMC
April 2019

The fat mass and obesity related gene polymorphism influences the risk of rejection in heart transplant patients.

Clin Transplant 2018 12 22;32(12):e13443. Epub 2018 Nov 22.

Centre for Experimental Medicine, Institute for Clinical and Experimental Medicine, Prague, Czech Republic.

Heart transplantation is a relatively common treatment for end-stage heart failure. The major complication of heart transplantation is organ rejection. Epigenetic could play a role in the pathogenesis of organ rejection, and the FTO gene is a mediator of DNA methylation. We analyzed a tagging FTO SNP rs17817449 in both donor and recipient DNA obtained through 370 heart transplantations. Recipient FTO genotypes were not associated with either type of rejection or with the general increase in the risk of rejection. When compared with patients without a history of rejection, carriers of transplanted hearts with the FTO TT genotype exhibited a significantly increased risk (P = 0.02) of suffering from both types of rejection in comparison to carriers of hearts with at least one G allele (OR; 95% CI = 2.56; 1.15-5.69). Our results suggest that the donor, but not the recipient, FTO genotype could be a significant predictor of acute rejection in heart transplant patients.
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http://dx.doi.org/10.1111/ctr.13443DOI Listing
December 2018

Body Adiposity Changes After Lifestyle Interventions in Children/Adolescents and the NYD-SP18 and TMEM18 Variants.

Med Sci Monit 2018 Oct 20;24:7493-7498. Epub 2018 Oct 20.

Dr. Filip's Institute for Children, Poděbrady, Czech Republic.

BACKGROUND This study was carried out to determine the relationship between the common TMEM-18 (rs4854344, G>T) and NYD-SP18 (rs6971091, G>A) gene variants and weight loss after lifestyle interventions (increased physical activity in conjunction with optimal dietary intake) in overweight/obese children/adolescents. MATERIAL AND METHODS We genotyped 684 unrelated, white, non-diabetic children (age 12.7±2.1 years, average BMI at baseline 30.66±4.80 kg/m²). Anthropometric and biochemical examinations were performed before and after 4 weeks of an intensive lifestyle intervention. RESULTS The mean weight loss achieved was 5.20±2.02 kg (P<0.001). NYDSP-18 AA homozygotes had significantly higher abdominal skinfold value before and after the intervention (both, P=0.001). No significant associations between BMI decrease and the NYD-SP18 and TMEM18 variants were found. Associations between all anthropometrical and biochemical changes and genes remained non-significant after data were adjusted for sex, age, and baseline values. CONCLUSIONS Decreased body weight in overweight/obese children is not significantly influenced by the NYD-SP18 rs6971091 or TMEM18 rs4854344 polymorphisms.
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http://dx.doi.org/10.12659/MSM.907180DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6204654PMC
October 2018

Falsely elevated human epididymis protein 4 results and Risk of Ovarian Malignancy Algorithm in polymorbid women after solid organ transplantation: A pilot and case-control study.

J Clin Lab Anal 2018 Jul 24;32(6):e22432. Epub 2018 Mar 24.

Department of Laboratory Methods, Institute for Clinical and Experimental Medicine, Prague, Czech Republic.

Background: Cancer prevention is essential after transplantation (Tx). The use of HE4 and Risk of Ovarian Malignancy Algorithm (ROMA) is recommended as a tool for selective ovarian cancer screening; however, creatinine is a known confounder. This study assessed the reliability of HE4, CA125, and ROMA after Tx.

Methods: We matched a total of 202 women without gynecological malignancies and 236 men by age and serum creatinine. Each pair consisted of a patient after Tx (kidney, liver, heart, and pancreas) and a diseased but non-Tx consecutive patient. Serum HE4, CA125 (Roche Cobas 6000), and creatinine (enzymatic, Abbott Architect) were measured in all patients.

Results: Creatinine correlated with HE4 (women: r = .864, P < .0001; men: r = .848, P < .0001). Age correlated slightly with HE4 in women (r = .250, P < .005) and men (r = .240, P < .0005). HE4 in women after Tx (median of 84.8 pmol/L) was significantly higher than non-Tx women (53.7 pmol/L, P < .0001) in the reference range of serum creatinine. Neither HE4 nor CA125 correlated with tacrolimus concentration, but anemia, hyperparathyroidism, kidney, liver, and lung diseases were possible confounders for HE4 after transplantation (P < .05).

Conclusion: Human epididymis protein 4 (HE4) was significantly increased in women after solid organ transplantation compared to levels without transplants matched by age and serum creatinine. HE4 results may be misleading in these patients.
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http://dx.doi.org/10.1002/jcla.22432DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6817055PMC
July 2018

Donor PNPLA3 rs738409 genotype is a risk factor for graft steatosis. A post-transplant biopsy-based study.

Dig Liver Dis 2018 May 9;50(5):490-495. Epub 2018 Jan 9.

Center for Experimental Medicine, Institute for Clinical and Experimental Medicine, Prague, Czech Republic.

Background & Aims: The rs738409 c.444C > G (p.I148M) polymorphism in PNPLA3 is a major factor predisposing to non-alcoholic fatty liver disease. The aim of the study was to clarify the impact of liver and extrahepatic expression of the PNPLA3 p.148M variant on liver graft steatosis after liver transplantation.

Methods: Fat content was assessed in liver biopsies from 176 transplant recipients. During a period of 4 ± 1 years after transplantation, 17 patients developed grade 3 steatosis, 14 patients grade 2 steatosis, 56 patients grade 1 steatosis, and 89 patients grade 0 steatosis. The influence of the recipient and donor rs738409 genotype and clinical and laboratory data on liver fat content were analyzed using ordinal logistic regression.

Results: The PNPLA3 rs738409 CC/CG/GG genotype frequencies, respectively, were 0.494/0.449/0.057 in the graft donors and 0.545/0.330/0.125 in the graft recipients. In the multivariate analysis, the presence of the PNPLA3 c.444G allele in donor (OR 1.62; 95%CI 1.12-2.33), post-transplant BMI (OR 1.14; 95%CI 1.07-1.22), diabetes mellitus (OR 1.99; 95%CI 1.22-3.22), and serum triglycerides (OR 1.40; 95%CI 1.11-1.76) were independent risk factors for increased liver graft fat content.

Conclusions: These data indicate that the liver expression of the PNPLA3 p.148M variant confers a genetic predisposition to liver graft steatosis along with nutritional status and diabetes.
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http://dx.doi.org/10.1016/j.dld.2017.12.030DOI Listing
May 2018

MRAS gene marker rs9818870 is not associated with acute coronary syndrome in the Czech population and does not predict mortality in males after acute coronary syndrome.

Adv Clin Exp Med 2017 Nov;26(8):1213-1217

Center for Experimental Medicine, Institute for Clinical and Experimental Medicine, Prague, Czech Republic.

Background: Genome-wide association studies (GWAs) focused on cardiovascular diseases reveal variants within genes which have not been analyzed through the pre-GWAs era, and whose function is often unknown. One of them is variant rs9818870 at the MRAS gene locus.

Objectives: To analyze if MRAS polymorphism is associated with acute coronary syndrome (ACS) risk in a Czech population and with mortality in male patients after myocardial infarction.

Material And Methods: 1,779 male patients with ACS (aged 55.3 ±7.9 years) and 673 female patients with ACS (aged 64.0 ±8.1 years) were genotyped for rs9818870 polymorphism using the PCR-RFLP method. In a subset of 1,221 patients, detailed diagnoses (901 subjects with STEMI, 280 subjects with NSTEMI, 40 cases with unstable angina pectoris) were recorded. In 1,614 males, records about total and cardiovascular mortality were available.

Results: Whether the entire populations or males and females have been analyzed separately or not, we have not confirmed the described association between DNA marker rs9818870 and ACS in Czechs (30.4% vs 29.4% carriers of the minor T allele [recessive model], p = 0.54; OR 1.05; 95% CI 0.89-1.24 for males and 32.1% vs 29.7% carriers of the minor T allele, p = 0.28; OR 1.12; 95% CI 0.91-1.37 for females). Types of the ACS (STEMI and NSTEMI) or mortality (in males only) were not associated with the analyzed polymorphism (all p > 0.34).

Conclusions: The rs9818870 variant is not associated with ACS or mortality in ACS patients in the Czech Slavonic population.
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http://dx.doi.org/10.17219/acem/67460DOI Listing
November 2017

The FTO variant is associated with chronic complications of diabetes mellitus in Czech population.

Gene 2018 Feb 14;642:220-224. Epub 2017 Nov 14.

Diabetes Centre, Institute for Clinical and Experimental Medicine, Prague, Czech Republic.

Background: Genome-wide association studies have resulted in the identification of the FTO gene as an important genetic determinant of diabetes mellitus. The aim of this study was to confirm the role of this gene in the development of DM in the Czech-Slavonic population and to analyse whether this gene is associated with common DM complications.

Methods: Two groups of patients (814 with T1DM and 848 with T2DM) and a group of healthy controls (2339 individuals) - both of Czech origin - were genotyped for the FTO rs17817449 SNP. ANOVA and logistic regression were used for the statistical evaluations.

Results: The frequency of the GG genotype was significantly higher in T2DM (25.4% vs. 16.7%, P<0.0005) but not in T1DM patients (19.3% vs. 16.7%, P=0.20) than in controls. The increased risk of development of diabetic nephropathy was observed both for T1DM patients (GG vs. TT homozygotes, P<0.01) and T2DM patients (G carriers vs. TT homozygotes, P<0.05). FTO genotype predicted the development of diabetic neuropathy (GG vs. TT comparison; P<0.01) in the T2DM patients only. No association between FTO genotype and development of retinopathy was detected. All presented values are after adjustment for age, sex, BMI and duration of diabetes.

Conclusions: We confirm the association between the FTO rs17817449 SNP and susceptibility to T2DM in the Czech-Slavonic population. The same variant is associated with a spectrum of chronic complications in both types of diabetes.
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http://dx.doi.org/10.1016/j.gene.2017.11.040DOI Listing
February 2018