Chronic thromboembolic pulmonary hypertension (CTEPH) is successfully treatable with pulmonary endarterectomy (PEA), balloon pulmonary angioplasty, and medical therapy. Registry to Evaluate Early and Long-Term Pulmonary Arterial Hypertension Disease Management risk score (RRS) is able to predict long-term outcome in inoperable patients or in patients with residual PH after surgery. We performed a post hoc analysis of RRS in patients who were enrolled in the CTREPH study (NCT01416636), a randomized, double-blind clinical trial comparing high-dose and low-dose subcutaneous (SC) treprostinil in patients with severe CTEPH that was classified by an interdisciplinary CTEPH team as nonoperable, or as persistent or recurrent pulmonary hypertension after PEA. Baseline mean RRS was similar in both treatment groups (8.7 in high-dose arm vs. 8.6 in low-dose arm), but mean RRS change from baseline to Week 24 was greater in the high-dose treprostinil group than in the low-dose treprostinil group (-0.88 vs. -0.17). The difference in RRS change from baseline to Week 24 between high dose versus low dose was statistically significant with mean difference of -0.70 (95% confidence interval: -1.36 to -0.05, p = 0.0352), and was driven mainly by improvement of World Health Organization functional class and N-terminal pro-brain natriuretic peptide concentration. SC treprostinil therapy administered in standard dose had positive effect on the risk profile measured by RRS in patients with inoperable or persistent/recurrent severe CTEPH. Although our study was limited by the small sample size and post hoc nature, assessment of risk profile is of great importance to this particular patient population with very poor prognosis.

• Klíčová slova
• REVEAL risk score, chronic thromboembolic pulmonary hypertension, treprostinil,
• Publikační typ
• časopisecké články MeSH

Of all kidney transplants, half are still lost in the first decade after transplantation. Here, using genetics, we probed whether interleukin 6 (IL-6) could be a target in kidney transplantation to improve graft survival. Additionally, we investigated if a genetic risk score (GRS) based on IL6 and IL10 variants could improve prognostication of graft loss. In a prospective cohort study, DNA of 1271 donor-recipient kidney transplant pairs was analyzed for the presence of IL6, IL6R, IL10, IL10RA, and IL10RB variants. These polymorphisms and their GRS were then associated with 15-year death-censored allograft survival. The C|C-genotype of the IL6 polymorphism in donor kidneys and the combined C|C-genotype in donor-recipient pairs were both associated with a reduced risk of graft loss (p = .043 and p = .042, respectively). Additionally, the GRS based on IL6, IL6R, IL10, IL10RA, and IL10RB variants was independently associated with the risk of graft loss (HR 1.53, 95%-CI [1.32-1.84]; p < .001). Notably, the GRS improved risk stratification and prediction of graft loss beyond the level of contemporary clinical markers. Our findings reveal the merits of a polygenic IL-6-based risk score strengthened with IL-10- polymorphisms for the prognostication and risk stratification of late graft failure in kidney transplantation.

• Klíčová slova
• interleukins, kidney transplantation, long-term graft survival, polymorphisms,
• MeSH
• alografty MeSH
• interleukin-10 * genetika   MeSH
• interleukin-6 * genetika   MeSH
• ledviny MeSH
• lidé MeSH
• prospektivní studie MeSH
• rizikové faktory MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• interleukin-10 * MeSH
• interleukin-6 * MeSH

Using the method of multi-dimensional statistical analysis in the evaluation of relations between the coronary score and risk factors in 120 men with ischaemic heart disease type stable angine, and in 30 men in a control group the authors revealed: age is a significant negative discriminator of the presence and indicator of the severity of atherosclerotic narrowing of the coronary arteries, cholesterol is a statistically significant positive independent discriminator of the presence and indicator of the severity of atherosclerotic narrowing of the coronary arteries, HDL-cholesterol is a significant negative independent indicator of the severity of the atherosclerotic narrowing of the coronary arteries, triacylglycerols are a positive indicator of the severity of the atherosclerotic narrowing of the coronary arteries only at the borderline of statistical significance, Broca's index of relative body weight is a positive discriminator of atherosclerotic narrowing of the coronary arteries only at the borderline of significance, there is a statistically significant positive additive relationship of quantitative risk factors with the atherosclerotic narrowing of coronary arteries, physical activity is a significant positive discriminator of the presence of atherosclerotic narrowing of the coronary arteries, the oral glucose tolerance test is a positive discriminator of the presence of the atherosclerotic narrowing of the coronary arteries.

• MeSH
• dospělí MeSH
• lidé MeSH
• nemoci koronárních tepen etiologie   MeSH
• rizikové faktory MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• anglický abstrakt MeSH
• časopisecké články MeSH

This study aimed at understanding the predictive potential of genetic risk scores (GRS) for diabetic kidney disease (DKD) progression in patients with type 2 diabetes mellitus (T2DM) and Major Cardiovascular Events (MCVE) and All-Cause Mortality (ACM) as secondary outcomes. We evaluated 30 T2DM and CKD GWAS-derived single nucleotide polymorphisms (SNPs) and their association with clinical outcomes in a central European cohort (n = 400 patients). Our univariate Cox analysis revealed significant associations of age, duration of diabetes, diastolic blood pressure, total cholesterol and eGFR with progression of DKD (all P < 0.05). However, no single SNP was conclusively associated with progression to DKD, with only CERS2 and SHROOM3 approaching statistical significance. While a single SNP was associated with MCVE - WSF1 (P = 0.029), several variants were associated with ACM - specifically CANCAS1, CERS2 and C9 (all P < 0.02). Our GRS did not outperform classical clinical factors in predicting progression to DKD, MCVE or ACM. More precisely, we observed an increase only in the area under the curve (AUC) in the model combining genetic and clinical factors compared to the clinical model alone, with values of 0.582 (95 % CI 0.487-0.676) and 0.645 (95 % CI 0.556-0.735), respectively. However, this difference did not reach statistical significance (P = 0.06). This study highlights the complexity of genetic predictors and their interplay with clinical factors in DKD progression. Despite the promise of personalised medicine through genetic markers, our findings suggest that current clinical factors remain paramount in the prediction of DKD. In conclusion, our results indicate that GWAS-derived GRSs for T2DM and CKD do not offer improved predictive ability over traditional clinical factors in the studied Czech T2DM population.

• Klíčová slova
• Diabetes mellitus, Diabetic kidney disease, Genetic predisposition, Genetic risk score, Single nucleotide polymorphism,
• MeSH
• celogenomová asociační studie MeSH
• chronická renální insuficience * genetika   patologie   MeSH
• diabetes mellitus 2. typu * genetika   komplikace   MeSH
• diabetické nefropatie * genetika   MeSH
• genetická predispozice k nemoci * MeSH
• genetické rizikové skóre MeSH
• jednonukleotidový polymorfismus * MeSH
• lidé středního věku MeSH
• lidé MeSH
• progrese nemoci * MeSH
• rizikové faktory MeSH
• senioři MeSH
• sfingosin-N-acyltransferasa genetika   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• sfingosin-N-acyltransferasa MeSH

Genetic discoveries of Alzheimer's disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study results (discovery n = 409,435 and validation size n = 58,190). Here, we add six variants associated with Alzheimer's disease risk (near APP, CHRNE, PRKD3/NDUFAF7, PLCG2 and two exonic variants in the SHARPIN gene). Assessment of the polygenic risk score and stratifying by APOE reveal a 4 to 5.5 years difference in median age at onset of Alzheimer's disease patients in APOE ɛ4 carriers. Because of this study, the underlying mechanisms of APP can be studied to refine the amyloid cascade and the polygenic risk score provides a tool to select individuals at high risk of Alzheimer's disease.

• MeSH
• Alzheimerova nemoc epidemiologie   genetika   patologie   MeSH
• amyloidový prekurzorový protein beta genetika   metabolismus   MeSH
• apolipoproteiny E genetika   MeSH
• celogenomová asociační studie MeSH
• datové soubory jako téma MeSH
• genetická predispozice k nemoci MeSH
• heterozygot MeSH
• hodnocení rizik metody   MeSH
• jednonukleotidový polymorfismus MeSH
• kohortové studie MeSH
• lidé středního věku MeSH
• lidé MeSH
• multifaktoriální dědičnost * MeSH
• následné studie MeSH
• rizikové faktory MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• studie případů a kontrol MeSH
• věk při počátku nemoci MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• validační studie MeSH
• Názvy látek
• amyloidový prekurzorový protein beta MeSH
• apolipoproteiny E MeSH
• APP protein, human MeSH Prohlížeč

PURPOSE OF THE STUDY Osteoporotic hip fractures commonly associated with comorbid diseases and use of multiple drugs. Polypharmacy status and the comorbidity-polypharmacy score (CPS) are the most common two grading system to predict mortality risk for the trauma patients older than 45 years. The purpose of the study was to determine whether the CPS or polypharmacy can predict the mortality risk in the older patients had a surgery due to an osteoporotic hip fracture. MATERIAL AND METHODS Consecutive patients aged > 65 years had an osteoporotic hip fracture due to a simple trauma were enrolled in the study. Detailed data were collected included comorbid conditions, medications, T-scores and additional fractures. Patients were divided into four groups according to CPS classification and polypharmacy status was indicated in case of using five or more drugs before admission. Overall mortality was assessed using Kaplan-Meier survival testing. Factors influencing 1-year, 2-year and 5-year mortality were evaluated using a multivariate logistic regression model with adjusted odds ratios (AORs) and a threshold significance at p < 0.05. RESULTS A total of 109 patients (65% women) with a mean age 80 ± 8.06 were included in the study. The mean time to death from the surgery was 42.06 ± 34.9 months. The Kaplan-Meier survival curves showed a significant difference in mortality among CPS groups. (Log-Rank test < 0.001). CPS presented a significant prediction in 1-year (AOR: 4.2; p < 0.05) and 2-year mortality (AOR: 2.9; p < 0.05) after adjustment for several covariates (including age, gender, surgical procedure) whereas 5-year mortality did not reveal a significant prediction (p = 0.46) Polypharmacy existence did not independently predict both overall or year-based mortality (p > 0.05) . CONCLUSIONS CPS is a better predictor for mortality risk than polypharmacy existence in the first two years in the patients underwent surgery for an osteoporotic hip fracture. Key words:osteoporotic hip fracture, mortality, polypharmacy, comorbidity.

• MeSH
• fraktury kyčle epidemiologie   etiologie   mortalita   MeSH
• komorbidita MeSH
• lidé MeSH
• osteoporotické fraktury epidemiologie   etiologie   mortalita   MeSH
• polypharmacy * MeSH
• rizikové faktory MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ukazatele zdravotního stavu MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Glioblastoma multiforme (GBM) is the most malignant primary brain tumor. The prognosis of GBM patients varies considerably and the histopathological examination is not sufficient for individual risk estimation. MicroRNAs (miRNAs) are small, non-coding RNAs that function as post-transcriptional regulators of gene expression and were repeatedly proved to play important roles in pathogenesis of GBM. In our study, we performed global miRNA expression profiling of 58 glioblastoma tissue samples obtained during surgical resections and 10 non-tumor brain tissues. The subsequent analysis revealed 28 significantly deregulated miRNAs in GBM tissue, which were able to precisely classify all examined samples. Correlation with clinical data led to identification of six-miRNA signature significantly associated with progression free survival [hazard ratio (HR) 1.98, 95% confidence interval (CI) 1.33-2.94, P < 0.001] and overa+ll survival (HR 2.86, 95% CI 1.91-4.29, P < 0.001). O(6)-methylguanine-DNA methyltransferase methylation status was evaluated as reference method and Risk Score based on six-miRNA signature indicated significant superiority in prediction of clinical outcome in GBM patients. Multivariate Cox analysis indicated that the Risk Score based on six-miRNA signature is an independent prognostic classifier of GBM patients. We suggest that the Risk Score presents promising prognostic algorithm with potential for individualized treatment decisions in clinical management of GBM patients.

• MeSH
• algoritmy MeSH
• DNA modifikační methylasy genetika   MeSH
• enzymy opravy DNA genetika   MeSH
• glioblastom genetika   mortalita   patologie   MeSH
• lidé MeSH
• metylace DNA MeSH
• mikro RNA genetika   MeSH
• míra přežití MeSH
• mozek metabolismus   MeSH
• nádorové biomarkery genetika   MeSH
• nádorové supresorové proteiny genetika   MeSH
• nádory mozku genetika   mortalita   patologie   MeSH
• následné studie MeSH
• prognóza MeSH
• proliferace buněk * MeSH
• promotorové oblasti (genetika) genetika   MeSH
• retrospektivní studie MeSH
• staging nádorů MeSH
• stanovení celkové genové exprese * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• DNA modifikační methylasy MeSH
• enzymy opravy DNA MeSH
• MGMT protein, human MeSH Prohlížeč
• mikro RNA MeSH
• nádorové biomarkery MeSH
• nádorové supresorové proteiny MeSH

Mobile wireless communication technologies have now become an everyday part of our lives, 24 hours a day, 7 days a week. Monitoring the autonomous system under exposition to electromagnetic fields may play an important role in broading of our still limited knowledge on their effect on human body. Thus, we studied the interaction of the high frequency electromagnetic field (HF EMF) with living body and its effect on the autonomic control of heart rate using Heart Rate Variability (HRV) linear and nonlinear analyses in healthy volunteers. A group of young healthy probands (n=30, age mean: 24.2 ± 3.5 years) without any symptoms of disease was exposed to EMF with f=2400 MHz (Wi Fi), and f=2600 MHz (4G) for 5 minutes applied on the chest area. The short-term heart rate variability (HRV) metrics were used as an indicator of complex cardiac autonomic control. The evaluated HRV parameters: RR interval (ms), high frequency spectral power (HF-HRV in [ln(ms2)]) as an index of cardiovagal control, and a symbolic dynamic index of 0V %, indicating cardiac sympathetic activity. The cardiac-linked parasympathetic index HF-HRV was significantly reduced (p =0.036) and sympathetically mediated HRV index 0V % was significantly higher (p=0.002) during EMF exposure at 2400 MHz (Wi-Fi), compared to simulated 4G frequency 2600 MHz. No significant differences were found in the RR intervals. Our results revealed a shift in cardiac autonomic regulation towards sympathetic overactivity and parasympathetic underactivity indexed by HRV parameters during EMF exposure in young healthy persons. It seems that HF EMF exposure results in abnormal complex cardiac autonomic regulatory integrity which may be associated with higher risk of later cardiovascular complications already in healthy probands.

• MeSH
• autonomní nervový systém MeSH
• dospělí MeSH
• elektromagnetická pole * škodlivé účinky   MeSH
• kardiovaskulární nemoci * MeSH
• lidé MeSH
• mladý dospělý MeSH
• rizikové faktory kardiovaskulárních chorob MeSH
• rizikové faktory MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mladý dospělý MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND: Obesity is a growing problem in western societies. The aim of this retrospective cohort study was to determine the association between the overweight and obese polytrauma patients and pneumonia after injury. METHODS: A total of 628 patients with an Injury Severity Score (ISS) of 16 or greater and 16 years or older were included in this retrospective study. The sample was subdivided into three groups as follows: body mass index (BMI) of less than 25 kg/m2; BMI of 25 kg/m2 to 30 kg/m2; and BMI more than 30 kg/m2. The Murray score was assessed at admission and at its maximum during hospitalization to determine pulmonary problems. Pneumonia was defined as bacteriologically positive sputum with appropriate radiologic and laboratory changes (C-reactive protein and interleukin 6). Data are given as mean ± SEM. One-way analysis of variance and the Kruskal-Wallis test were used for the analyses, and the significance level was set at p < 0.05; Bonferroni-Dunn test was performed as post hoc analysis. RESULTS: The Abbreviated Injury Scale (AIS) score for the thorax was 3.2 ± 0.1 in the group with a BMI of less than 25 kg/m2, 3.3 ± 0.1 in the group with a BMI of 25 kg/m2 to 30 kg/m2, and 2.8 ± 0.2 in the group with BMI of more than 30 kg/m2 (p = 0.044). The Murray score at admission was elevated with increasing BMI (0.8 ± 0.8 for BMI < 25 kg/m2, 0.9 ± 0.9 for BMI 25–30 kg/m2, and 1.0 ± 0.8 for BMI > 30 kg/m2; p = 0.137); the maximum Murray score during hospitalization revealed significant differences (1.2 ± 0.9 for BMI < 25 kg/m2, 1.6 ± 1.0 for BMI 25–30 kg/m2, and 1.5 ± 0.9 for BMI > 30 kg/m2; p < 0.001). The incidence of pneumonia also increased with increasing BMI (1.6% for BMI < 25 kg/m2, 2.0% for BMI 25–30 kg/m2, and 3.1% for BMI > 30 kg/m2; p = 0.044). CONCLUSION: Obesity leads to an increased incidence of pneumonia in a polytrauma situation. LEVEL OF EVIDENCE: Prognostic/epidemiologic study, level IV.

• MeSH
• bakteriální pneumonie etiologie   MeSH
• C-reaktivní protein analýza   MeSH
• dospělí MeSH
• index tělesné hmotnosti MeSH
• interleukin-6 krev   MeSH
• kalcitonin krev   MeSH
• lidé MeSH
• nadváha komplikace   MeSH
• neparametrická statistika MeSH
• obezita komplikace   MeSH
• polytrauma komplikace   MeSH
• proteinové prekurzory krev   MeSH
• retrospektivní studie MeSH
• rizikové faktory MeSH
• skóre závažnosti úrazu MeSH
• zkrácená stupnice závažnosti úrazů MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• C-reaktivní protein MeSH
• interleukin-6 MeSH
• kalcitonin MeSH
• proteinové prekurzory MeSH

Previous studies of non-histocompatibility leukocyte antigen (HLA) gene single-nucleotide polymorphisms (SNPs) on subgroups of patients undergoing allogeneic haematopoietic stem cell transplantation (HSCT) revealed an association with transplant outcome. This study further evaluated the association of non-HLA polymorphisms with overall survival in a cohort of 762 HSCT patients using data on 26 polymorphisms in 16 non-HLA genes. When viewed in addition to an already established clinical risk score (EBMT-score), three polymorphisms: rs8177374 in the gene for MyD88-adapter-like (MAL; P=0.026), rs9340799 in the oestrogen receptor gene (ESR; P=0.003) and rs1800795 in interleukin-6 (IL-6; P=0.007) were found to be associated with reduced overall survival, whereas the haplo-genotype (ACC/ACC) in IL-10 was protective (P=0.02). The addition of these non-HLA polymorphisms in a Cox regression model alongside the EBMT-score improved discrimination between risk groups and increased the level of prediction compared with the EBMT-score alone (gain in prediction capability for EBMT-genetic-score 10.8%). Results also demonstrated how changes in clinical practice through time have altered the effects of non-HLA analysis. The study illustrates the significance of non-HLA genotyping prior to HSCT and the importance of further investigation into non-HLA gene polymorphisms in risk prediction.

• MeSH
• alfa receptor estrogenů genetika   MeSH
• alografty MeSH
• dítě MeSH
• dospělí MeSH
• genotyp MeSH
• haplotypy MeSH
• hematologické nádory mortalita   terapie   MeSH
• histokompatibilita MeSH
• hodnocení rizik metody   MeSH
• infekce mortalita   MeSH
• interleukin-10 genetika   MeSH
• interleukin-6 genetika   MeSH
• jednonukleotidový polymorfismus * MeSH
• Kaplanův-Meierův odhad MeSH
• lidé středního věku MeSH
• lidé MeSH
• membránové glykoproteiny genetika   MeSH
• mladiství MeSH
• multiorgánové selhání mortalita   MeSH
• následné studie MeSH
• nemoc štěpu proti hostiteli mortalita   MeSH
• příčina smrti MeSH
• příprava pacienta k transplantaci škodlivé účinky   MeSH
• prognóza MeSH
• proporcionální rizikové modely MeSH
• receptory interleukinu-1 genetika   MeSH
• senioři MeSH
• transplantace hematopoetických kmenových buněk mortalita   MeSH
• výsledek terapie MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• alfa receptor estrogenů MeSH
• ESR1 protein, human MeSH Prohlížeč
• IL10 protein, human MeSH Prohlížeč
• IL6 protein, human MeSH Prohlížeč
• interleukin-10 MeSH
• interleukin-6 MeSH
• membránové glykoproteiny MeSH
• receptory interleukinu-1 MeSH
• TIRAP protein, human MeSH Prohlížeč