PURPOSE: Obesity and its related severe comorbidities are increasing rapidly. The duodenal-jejunal bypass is an endoscopically implanted device (mimicking the Roux-en-Y gastric bypass) developed to support weight reduction and improve type 2 diabetes control. MATERIALS AND METHODS: Retrospective data analysis of consecutive patients undergoing duodenal-jejunal bypass (EndoBarrier®, DJB) implantation between 2013 and 2017 was performed to evaluate safety as well as short- and long-term efficacy. RESULTS: One hundred and twenty-one patients (mean BMI of 43.1 ± 7.2 kg/m2 and weight of 138.2 ± 28.6 kg) underwent DJB implantation. The mean dwelling time was 15.5 months, the mean total body weight loss (%TBWL) after explantation was 10.3% ± 7.9% (14.2 kg, p < 0.0001), and the mean BMI was 39.5 ± 7.3 kg/m2 (p < 0.0001). There was no significant weight gain 24 months after the explantation. Seventy-seven patients had type 2 diabetes mellitus (T2DM) with a mean HbA1c before implantation of 5.6% (n = 52). The mean HbA1c after explantation was 5.1% (p = 0.0001). Significant reductions in transaminase and lipid levels before and after explantation were observed. One complication occurred during implantation and another during explantation. In 16 patients, the device had to be extracted earlier than expected (7 for severe adverse events and 9 for adverse events; 13.2%). CONCLUSION: Despite an evident rate of adverse events, the DJB shows promise as a weight-loss procedure. Our results show that some patients implanted with the device maintained reduced weight even 24 months after explantation, while many improved T2DM control.
- MeSH
- diabetes mellitus 2. typu * chirurgie komplikace MeSH
- duodenum chirurgie MeSH
- glykovaný hemoglobin MeSH
- hmotnostní úbytek MeSH
- jejunum chirurgie MeSH
- lidé MeSH
- morbidní obezita * chirurgie MeSH
- obezita chirurgie komplikace MeSH
- retrospektivní studie MeSH
- výsledek terapie MeSH
- žaludeční bypass * metody MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
UNLABELLED: Retinal microcirculation reflects retinal perfusion abnormalities and retinal arterial structural changes at relatively early stages of various cardiovascular diseases. Wall-to-lumen ratio (WLR) may represent the earliest step in hypertension-mediated organ damage.Our objective was to compare functional and structural parameters of retinal microcirculation in a randomly selected urban population sample, in hypertensive and normotensive individuals. DESIGN AND METHOD: A total of 398 randomly selected individuals from an urban population aged 25-65 years, residing in Pilsen, Czech Republic, were screened for major cardiovascular risk factors. Retinal microcirculation was assessed using scanning laser Doppler flowmetry, with data evaluable in 343 patients. Complete data were available for 342 individuals divided into four groups based on blood pressure and control status of hypertension: normotensive individuals ( n = 213), treated controlled hypertensive individuals ( n = 30), treated uncontrolled hypertensive individuals ( n = 26), and newly detected/untreated hypertensive individuals ( n = 73). RESULTS: There was a tendency to higher wall thickness in treated but uncontrolled hypertensive patients (compared to normotensive and treated controlled hypertensive individuals). WLR was significantly increased in treated but uncontrolled hypertensive patients as well as in individuals with newly detected thus untreated hypertension or in patients with known but untreated hypertension. There was no difference in WLR in treated, controlled hypertensive patients compared with normotensive individuals. CONCLUSION: Our results show that an increased WLR, reflecting early vascular damage, was found in newly detected individuals with hypertension and in untreated hypertensive patients, reflecting early hypertension-mediated vascular damage. Early initiation of hypertension treatment may be warranted.
- MeSH
- arterioly MeSH
- hypertenze * MeSH
- krevní tlak MeSH
- lidé MeSH
- mikrocirkulace MeSH
- retinální cévy diagnostické zobrazování MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Česká republika MeSH
BACKGROUND: Familial dysbetalipoproteinemia (FD) is an autosomal recessive (rarely dominant) inherited disorder that is almost exclusively associated with the apolipoprotein E gene (APOE) variability. Nonetheless, only a small proportion of APOE2/E2 subjects develop the phenotype for mixed dyslipidemia; the context of other trigger metabolic or genetic factors remains unknown. METHODS: One hundred and one patients with FD and eighty controls (all APOE2/E2 homozygotes; rs429358) were screened for 18 single-nucleotide polymorphisms (SNPs) within the genes involved in triglyceride metabolism. RESULTS: Two SNPs were significantly associated with the FD phenotype (rs439401 within APOE; P < 0.0005 and rs964184 within ZPR1/APOA5/A4/C3/A1 gene cluster; P < 0.0001). Unweighted genetic risk scores - from these two SNPs (GRS2), and, also, additional 13 SNPs with P-value below 0.9 (GRS15) - were created as an additional tool to improve the risk estimation of FD development in subjects with the APOE2/E2 genotype. Both GRS2 and GRS15 were significantly (P < 0.0001) increased in patients and both GRSs discriminated almost identically between the groups (P = 0.86). Subjects with an unweighted GRS2 of three or more had an almost four-fold higher risk of FD development than other individuals (odds ratio (OR) 3.58, 95% confidence interva (CI): 1.78-7.18, P < 0.0005). CONCLUSIONS: We identified several SNPs that are individual additive factors influencing FD development. The use of unweighted GRS2 is a simple and clinically relevant tool that further improves the prediction of FD in APOE2/E2 homozygotes with corresponding biochemical characteristics.
- MeSH
- apolipoprotein E2 * genetika MeSH
- apolipoproteiny E genetika MeSH
- dospělí MeSH
- genetická predispozice k nemoci * MeSH
- genetické rizikové skóre MeSH
- genotyp * MeSH
- hyperlipoproteinemie typ III genetika MeSH
- jednonukleotidový polymorfismus * MeSH
- lidé středního věku MeSH
- lidé MeSH
- rizikové faktory MeSH
- studie případů a kontrol MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
BACKGROUND: The highest mortality and morbidity worldwide is associated with atherosclerotic cardiovascular disease (ASCVD), which has in background both environmental and genetic risk factors. Apolipoprotein L1 (APOL1) variability influences the risk of ASCVD in Africans, but little is known about the APOL1 and ASCVD in other ethnic groups. METHODS: To investigate the role of APOL1 and ASCVD, we have genotyped four (rs13056427, rs136147, rs10854688 and rs9610473) APOL1 polymorphisms in a group of 1541 male patients with acute coronary syndrome (ACS) and 1338 male controls. RESULTS: Individual APOL1 polymorphisms were not associated with traditional CVD risk factors such as smoking, hypertension or diabetes prevalence, with BMI values or plasma lipid levels. Neither individual polymorphisms nor haplotypes were associated with an increased risk of ACS nor did they predict total or cardiovascular mortality over the 10.2 ± 3.9 years of follow-up. CONCLUSIONS: We conclude that APOL1 genetic variability has no major effect on risk of ACS in Caucasians.
- MeSH
- akutní koronární syndrom * genetika MeSH
- apolipoprotein L1 * genetika MeSH
- apolipoproteiny genetika MeSH
- běloši genetika MeSH
- genetická predispozice k nemoci MeSH
- haplotypy MeSH
- jednonukleotidový polymorfismus MeSH
- lidé středního věku MeSH
- lidé MeSH
- lipoproteiny HDL genetika MeSH
- rizikové faktory MeSH
- senioři MeSH
- studie případů a kontrol MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Česká republika 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.
- 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
AIMS/HYPOTHESIS: The aim of this substudy (Eudra CT No:2019-001997-27)was to assess ATB availability in patients with infected diabetic foot ulcers(IDFUs)in the context of microcirculation and macrocirculation status. METHODS: For this substudy, we enrolled 23 patients with IDFU. Patients were treated with boluses of amoxicillin/clavulanic acid(AMC)(12patients) or ceftazidime(CTZ)(11patients). After induction of a steady ATB state, microdialysis was performed near the IDFU. Tissue fluid samples from the foot and blood samples from peripheral blood were taken within 6 hours. ATB potential efficacy was assessed by evaluating the maximum serum and tissue ATB concentrations(Cmax and Cmax-tissue)and the percentage of time the unbound drug tissue concentration exceeds the minimum inhibitory concentration (MIC)(≥100% tissue and ≥50%/60% tissue fT>MIC). Vascular status was assessed by triplex ultrasound, ankle-brachial and toe-brachial index tests, occlusive plethysmography comprising two arterial flow phases, and transcutaneous oxygen pressure(TcPO2). RESULTS: Following bolus administration, the Cmax of AMC was 91.8 ± 52.5 μgmL-1 and the Cmax-tissue of AMC was 7.25 ± 4.5 μgmL-1(P<0.001). The Cmax for CTZ was 186.8 ± 44.1 μgmL-1 and the Cmax-tissue of CTZ was 18.6 ± 7.4 μgmL-1(P<0.0001). Additionally, 67% of patients treated with AMC and 55% of those treated with CTZ achieved tissue fT>MIC levels exceeding 50% and 60%, respectively. We observed positive correlations between both Cmax-tissue and AUCtissue and arterial flow. Specifically, the correlation coefficient for the first phase was r=0.42; (P=0.045), and for the second phase, it was r=0.55(P=0.01)and r=0.5(P=0.021). CONCLUSIONS: Bactericidal activity proved satisfactory in only half to two-thirds of patients with IDFUs, an outcome that appears to correlate primarily with arterial flow.
- MeSH
- antibakteriální látky * farmakokinetika aplikace a dávkování terapeutické užití MeSH
- diabetická noha * farmakoterapie metabolismus MeSH
- intravenózní podání MeSH
- lidé středního věku MeSH
- lidé MeSH
- mikrocirkulace * účinky léků MeSH
- senioři MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: Despite a general decline in mean levels across populations, LDL-cholesterol levels remain a major risk factor for acute coronary syndrome (ACS). The APOB, LDL-R, CILP, and SORT-1 genes have been shown to contain variants that have significant effects on plasma cholesterol levels. METHODS AND RESULTS: We examined polymorphisms within these genes in 1191 controls and 929 patients with ACS. Only rs646776 within SORT-1 was significantly associated with a risk of ACS (P < 0.05, AA vs. + G comparison; OR 1.21; 95% CI 1.01-1.45). With regard to genetic risk score (GRS), the presence of at least 7 alleles associated with elevated cholesterol levels was connected with increased risk (P < 0.01) of ACS (OR 1.26; 95% CI 1.06-1.52). Neither total mortality nor CVD mortality in ACS subjects (follow up-9.84 ± 3.82 years) was associated with the SNPs analysed or cholesterol-associated GRS. CONCLUSIONS: We conclude that, based on only a few potent SNPs known to affect plasma cholesterol, GRS has the potential to predict ACS risk, but not ACS associated mortality.
- MeSH
- akutní koronární syndrom * genetika MeSH
- cholesterol MeSH
- genetické rizikové skóre * MeSH
- jednonukleotidový polymorfismus genetika MeSH
- lidé MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Česká republika MeSH
- Publikační typ
- abstrakt z konference MeSH
- Publikační typ
- abstrakt z konference MeSH
BACKGROUND & AIMS: Severity of portal hypertension is usually quantified by measuring the hepatic venous pressure gradient (HVPG). However, due to its invasiveness, alternative markers are being sought. Bile acids (BA), being synthesized, metabolized, and transported by the liver, seem to have the potential to serve as endogenous markers. The aim of the present study was to determine whether serum BA reflect the severity of portal hypertension. METHODS: We correlated serum concentrations of individual BA with portal pressure (as HVPG) in an exploratory cohort of 21 cirrhotic patients with portal hypertension. The predictive potential of selected candidates was then confirmed in an independent validation cohort (n = 214). Additionally, nine previously published noninvasive markers were added to the stepwise logistic regression model to identify the most relevant ones, which were eventually used to create a prognostic index of portal hypertension. RESULTS: Serum levels of taurochenodeoxycholic acid (TCDCA) significantly correlated with HVPG and showed a high potential to predict clinically significant portal hypertension (HVPG ≥ 10 mm Hg: AUROC = 0.97 ± 0.06). This was confirmed in the validation cohort (AUROC = 0.96 ± 0.01). The predictive index (constructed based on AST/ALT, spleen diameter, and TCDCA concentration) was able to distinguish clinically significant portal hypertension with 95% sensitivity and 76% specificity. CONCLUSIONS: TCDCA seems to be a promising noninvasive marker of clinically significant portal hypertension. Its predictive potential may be further enhanced when it is combined with both the AST/ALT ratio and spleen diameter.
