• Klíčová slova
• ribociclib,
• MeSH
• alanintransaminasa analýza   MeSH
• aminopyridiny farmakologie   terapeutické užití   MeSH
• antitumorózní látky terapeutické užití   toxicita   MeSH
• aspartátaminotransferasy analýza   MeSH
• cytomegalovirové infekce diagnóza   terapie   MeSH
• fulvestrant farmakologie   terapeutické užití   MeSH
• infekční mononukleóza diagnóza   terapie   MeSH
• jaterní testy MeSH
• lidé středního věku MeSH
• lidé MeSH
• metastázy nádorů MeSH
• nádory prsu * farmakoterapie   MeSH
• protokoly antitumorózní kombinované chemoterapie MeSH
• puriny farmakologie   terapeutické užití   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• kazuistiky MeSH

• MeSH
• alanintransaminasa krev   MeSH
• aspartátaminotransferasy krev   MeSH
• bilirubin krev   MeSH
• gama-glutamyltransferasa krev   MeSH
• jaterní testy * metody   MeSH
• krevní obraz MeSH
• lidé MeSH
• nemoci jater diagnóza   MeSH
• sérový albumin analýza   MeSH
• Check Tag
• lidé MeSH

• MeSH
• alanintransaminasa krev   MeSH
• alkalická fosfatasa fyziologie   krev   MeSH
• aspartátaminotransferasy krev   MeSH
• bilirubin fyziologie   krev   MeSH
• diferenciální diagnóza MeSH
• gama-glutamyltransferasa fyziologie   krev   MeSH
• hyperbilirubinemie klasifikace   MeSH
• jaterní testy * klasifikace   MeSH
• lidé MeSH
• nemoci jater diagnóza   prevence a kontrola   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• přehledy MeSH

BACKGROUND AND AIMS: Recurrent primary sclerosing cholangitis (rPSC) following liver transplant (LT) has a negative impact on graft and patient survival; little is known about risk factors for rPSC or disease course in children. APPROACH AND RESULTS: We retrospectively evaluated risk factors for rPSC in 140 children from the Pediatric PSC Consortium, a multicenter international registry. Recipients underwent LT for PSC and had >90 days of follow-up. The primary outcome, rPSC, was defined using Graziadei criteria. Median follow-up after LT was 3 years (interquartile range 1.1-6.1). rPSC occurred in 36 children, representing 10% and 27% of the subjects at 2 years and 5 years following LT, respectively. Subjects with rPSC were younger at LT (12.9 vs. 16.2 years), had faster progression from PSC diagnosis to LT (2.5 vs. 4.1 years), and had higher alanine aminotransferase (112 vs. 66 IU/L) at LT (all P < 0.01). Inflammatory bowel disease was more prevalent in the rPSC group (86% vs. 66%; P = 0.025). After LT, rPSC subjects had more episodes of biopsy-proved acute rejection (mean 3 vs. 1; P < 0.001), and higher prevalence of steroid-refractory rejection (41% vs. 20%; P = 0.04). In those with rPSC, 43% developed complications of portal hypertension, were relisted for LT, or died within 2 years of the diagnosis. Mortality was higher in the rPSC group (11.1% vs. 2.9%; P = 0.05). CONCLUSIONS: The incidence of rPSC in this cohort was higher than previously reported, and was associated with increased morbidity and mortality. Patients with rPSC appeared to have a more aggressive, immune-reactive phenotype. These findings underscore the need to understand the immune mechanisms of rPSC, to lay the foundation for developing new therapies and improve outcomes in this challenging population.

• MeSH
• alanintransaminasa krev   MeSH
• aspartátaminotransferasy krev   MeSH
• časové faktory MeSH
• dítě MeSH
• gama-glutamyltransferasa krev   MeSH
• glukokortikoidy terapeutické užití   MeSH
• idiopatické střevní záněty epidemiologie   MeSH
• internacionalita MeSH
• léková rezistence MeSH
• lidé MeSH
• mladiství MeSH
• portální hypertenze epidemiologie   patofyziologie   MeSH
• přežívání štěpu MeSH
• progrese nemoci MeSH
• recidiva MeSH
• registrace MeSH
• rejekce štěpu farmakoterapie   epidemiologie   patologie   MeSH
• rizikové faktory MeSH
• sklerozující cholangitida krev   epidemiologie   chirurgie   MeSH
• transplantace jater * MeSH
• věkové faktory MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• pozorovací studie MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH

PURPOSE: The De Ritis ratio (aspartate aminotransferase/alanine aminotransferase, DRR) has been linked to oncological outcomes in several cancers. We aimed to assess the association of DRR with recurrence-free survival (RFS) and progression-free survival (PFS) in patients with non-muscle-invasive bladder cancer (NMIBC). METHODS: We conducted a retrospective analysis of 1117 patients diagnosed with NMIBC originating from an established multicenter database. To define the optimal pretreatment DRR cut-off value, we determined a value of 1.2 as having a maximum Youden index value. The overall population was therefore divided into two De Ritis ratio groups using this cut-off (lower, < 1.2 vs. higher, ≥ 1.2). Univariable and multivariable Cox regression analyses were used to investigate the association of DRR with RFS and PFS. The discrimination of the model was evaluated with the Harrel's concordance index (C-index). RESULTS: Overall, 405 (36%) patients had a DRR ≥ 1.2. On univariable Cox regression analysis, DRR was significantly associated with RFS (HR: 1.23, 95% CI 1.02-1.47, p = 0.03), but not with PFS (HR: 0.96, 95% CI 0.65-1.44, p = 0.9). On multivariable Cox regression analysis, which adjusted for the effect of established clinicopathologic features, DRR ≥ 1.2 remained significantly associated with worse RFS (HR:1.21, 95% CI 1.00-1.46, p = 0.04). The addition of DRR only minimally improved the discrimination of a base model that included established clinicopathologic features (C-index = 0.683 vs. C-index = 0.681). On DCA the inclusion of DRR did not improve the net-benefit of the prognostic model. CONCLUSION: Despite the statistically significant association of the DRR with RFS in patients with NMIBC, it does not seem to add any prognostic or clinical benefit beyond that of currently available clinical factors.

• MeSH
• alanintransaminasa krev   MeSH
• aspartátaminotransferasy krev   MeSH
• doba přežití bez progrese choroby MeSH
• invazivní růst nádoru MeSH
• lidé středního věku MeSH
• lidé MeSH
• lokální recidiva nádoru epidemiologie   MeSH
• nádory močového měchýře krev   patologie   chirurgie   MeSH
• prognóza MeSH
• retrospektivní studie MeSH
• senioři MeSH
• výsledek terapie MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Cadmium (Cd) is a heavy metal that occurs in all areas of the environment, including the food chain. In the body, it causes oxidative stress by producing free radicals that are harmful to the cells. Grape seed extract (GSE) contains a wide range of biologically active components that help to neutralize the adverse effects of free radicals. In this study, the effects of GSE prepared form semi-resistant grapevine cultivar Cerason, which is rich in phenolics, on biochemical markers of brown rats exposed to the effects of cadmium were monitored. GSE increased the plasma antioxidant activity and, in the kidneys and the liver, Cd content was significantly lowered by GSE co-administration. Accordingly, the increase in creatinine content and alanine aminotransferase activity and the decrease of catalase and superoxide dismutase activities caused by cadmium were slowed down by GSE co-administration. The results of this work reveal that grape seed extract offers a protective effect against the intake of heavy metals into the organism.

• MeSH
• alanintransaminasa krev   MeSH
• antioxidancia analýza   MeSH
• aspartátaminotransferasy krev   MeSH
• biologické markery metabolismus   MeSH
• extrakt ze semen vinné révy farmakologie   MeSH
• fytonutrienty analýza   MeSH
• játra účinky léků   enzymologie   metabolismus   MeSH
• kadmium krev   MeSH
• katalasa metabolismus   MeSH
• kreatinin krev   MeSH
• ledviny účinky léků   metabolismus   MeSH
• metalothionein metabolismus   MeSH
• močovina krev   MeSH
• potkani Wistar MeSH
• semena rostlinná chemie   MeSH
• superoxiddismutasa metabolismus   MeSH
• zdraví * MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Makroenzym aspartátaminotransferáza (dále makro‑AST) je jednou z příčin izolovaného zvýšení aspartátaminotransferázy (AST) v séru. Uvádíme kazuistiku normálně prospívající dívky s náhodně zachycenou přetrvávající izolovanou elevací AST. Podrobným vyšetřením bylo zjištěno, že se jedná o elevaci sérové AST na podkladě cirkulujících makro-AST bez přítomnosti dalšího organického onemocnění.

The macroenzyme of aspartate aminotransferase (macro-AST) is one of the causes of the isolated increase in serum aspartate aminotransferase (AST). We present a case report of a well-thriving girl with an accidentally detected persistent isolated AST elevation. A detailed laboratory analysis revealed this was due to an elevation of serum AST based on circulating macro-AST without the presence of another organic disease.

• MeSH
• aspartátaminotransferasy * analýza   krev   metabolismus   MeSH
• diferenciální diagnóza MeSH
• jaterní testy MeSH
• játra enzymologie   MeSH
• lidé MeSH
• nemoci jater diagnóza   krev   MeSH
• polyethylenglykoly MeSH
• předškolní dítě MeSH
• stabilita enzymů MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• kazuistiky MeSH

BACKGROUND: Predictive markers can help tailor treatment to the individual in metastatic renal cell carcinoma (mRCC). De Ritis ratio (DRR) is associated with oncologic outcomes in various solid tumors. OBJECTIVE: To assess the value of DRR in prognosticating survival in mRCC patients treated with tyrosine-kinase inhibitors (TKI). METHODS: Overall, 220 mRCC patients treated with TKI first-line therapy were analyzed. An optimal cut-off point for DRR was determined with Youden's J. We used multiple strata for DRR, performed descriptive, Kaplan-Meier and multivariable Cox-regression analyses to assess associations of DRR with progression-free (PFS) and overall survival (OS). RESULTS: Patients above the optimal cut-off point for DRR of ≥ 1.58 had fewer liver metastases (p = 0.01). There was no difference in PFS (p > 0.05) between DRR groups. DRR above the median of 1.08 (HR 1.42; p = 0.03), DRR ≥ 1.1(HR 1.44; p = 0.02), ≥ 1.8 (HR 1.56; p = 0.03), ≥ 1.9 (HR 1.59; p = 0.02) and ≥ 2.0 (HR 1.63; p = 0.047) were associated with worse OS. These associations did not remain after multivariable adjustment. In the intermediate MSKCC group, DRR was associated with inferior OS at cut-offs ≥ 1.0 (HR 1.78; p = 0.02), ≥ 1.1 (HR 1.81; p = 0.01) and above median (HR 1.88; p = 0.007) in multivariable analyses. In patients with clear-cell histology, DRR above median (HR 1.54; p = 0.029) and DRR ≥ 1.1 (HR 1.53; p = 0.029) were associated with OS in multivariable analyses. CONCLUSION: There was no independent association between DRR and survival of mRCC patients treated with TKI in the entire cohort. However, OS of patients with intermediate risk and clear-cell histology were affected by DRR. DRR could be used for tailored decision-making in these subgroups.

• MeSH
• alanintransaminasa analýza   krev   MeSH
• analýza přežití MeSH
• aspartátaminotransferasy analýza   krev   MeSH
• cytoredukční chirurgie metody   MeSH
• indazoly * aplikace a dávkování   škodlivé účinky   MeSH
• inhibitory proteinkinas aplikace a dávkování   škodlivé účinky   MeSH
• karcinom z renálních buněk * krev   farmakoterapie   patologie   chirurgie   MeSH
• Karnofského skóre MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádory ledvin * krev   farmakoterapie   patologie   chirurgie   MeSH
• nefrektomie metody   MeSH
• prediktivní hodnota testů MeSH
• prognóza MeSH
• pyrimidiny * aplikace a dávkování   škodlivé účinky   MeSH
• sorafenib aplikace a dávkování   škodlivé účinky   MeSH
• staging nádorů MeSH
• stupeň nádoru MeSH
• sulfonamidy * aplikace a dávkování   škodlivé účinky   MeSH
• sunitinib * aplikace a dávkování   škodlivé účinky   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Nonalcoholic steatohepatitis (NASH) is characterized by hepatic steatosis with inflammation and fibrosis. Membrane endoglin (Eng) expression is shown to participate in fibrosis, and plasma concentrations of soluble endoglin (sEng) are increased in patients with hypercholesterolemia and type 2 diabetes mellitus. We hypothesize that NASH increases both hepatic Eng expression and sEng in blood and that high levels of sEng modulate cholesterol and bile acid (BA) metabolism and affect NASH progression. Three-month-old transgenic male mice overexpressing human sEng and their wild type littermates are fed for six months with either a high-saturated fat, high-fructose high-cholesterol (FFC) diet or a chow diet. Evaluation of NASH, Liquid chromatography-mass spectrometry (LC/MS) analysis of BA, hepatic expression of Eng, inflammation, fibrosis markers, enzymes and transporters involved in hepatic cholesterol and BA metabolism are assessed using Real-Time Quantitative Reverse Transcription Polymerase Chain reaction (qRT-PCR) and Western blot. The FFC diet significantly increases mouse sEng levels and increases hepatic expression of Eng. High levels of human sEng results in increased hepatic deposition of cholesterol due to reduced conversion into BA, as well as redirects the metabolism of triglycerides (TAG) to its accumulation in the liver, via reduced TAG elimination by β-oxidation combined with reduced hepatic efflux. We propose that sEng might be a biomarker of NASH development, and the presence of high levels of sEng might support NASH aggravation by impairing the essential defensive mechanism protecting NASH liver against excessive TAG and cholesterol accumulation, suggesting the importance of high sEng levels in patients prone to develop NASH.

• MeSH
• alkalická fosfatasa metabolismus   MeSH
• aspartátaminotransferasy metabolismus   MeSH
• biologické markery krev   metabolismus   MeSH
• biologické modely MeSH
• cholesterol krev   metabolismus   MeSH
• dieta s vysokým obsahem tuků MeSH
• endoglin krev   metabolismus   MeSH
• fruktosa MeSH
• jaterní cirhóza krev   komplikace   patologie   MeSH
• játra metabolismus   patologie   MeSH
• lidé MeSH
• modely nemocí na zvířatech MeSH
• myši MeSH
• nealkoholová steatóza jater krev   komplikace   metabolismus   MeSH
• oxidační stres MeSH
• rozpustnost MeSH
• triglyceridy metabolismus   MeSH
• zánět patologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

PURPOSE: Identifying which patients are likely to benefit from cytoreductive nephrectomy (CN) for metastatic renal cell carcinoma (mRCC) is important. We tested the association between preoperative serum De Ritis ratio (DRR, Aspartate Aminotransferase/Alanine Aminotransferase) and overall survival (OS) as well as cancer-specific survival (CSS) in mRCC patients treated with CN. MATERIAL AND METHODS: mRCC patients treated with CN at different institutions were included. After assessing for the optimal pretreatment DRR cut-off value, we found 1.2 to have the maximum Youden index value. The overall population was therefore divided into 2 DRR groups using this cut-off (low, <1.2 vs. high, ≥1.2). Univariable and multivariable Cox regression analyses tested the association between DRR and OS as well as CSS. The discrimination of the model was evaluated with the Harrel's concordance index (C-index). The clinical value of the DRR was evaluated with decision curve analysis. RESULTS: Among 613 mRCC patients, 239 (39%) patients had a DRR ≥1.2. Median follow-up was 31 (IQR 16-58) months. On univariable analysis, high DRR was significantly associated with OS (hazard ratios [HR]: 1.22, 95% confidence interval [CI]: 1.01-1.46, P = 0.04) and CSS (HR: 1.23, 95% CI: 1.02-1.47, P = 0.03). On multivariable analysis, which adjusted for the effect of established clinicopathologic features, high DRR remained significantly associated with both OS (HR: 1.26, 95% CI: 1.04-1.52, P = 0.02) and CSS (HR: 1.26, 95% CI: 1.05-1.53, P = 0.01). The addition of DRR only minimally improved the discrimination of a base model that included established clinicopathologic features (C-index = 0.633 vs. C-index = 0.629). On decision curve analysis, the inclusion of DRR did not improve the net-benefit beyond that obtained by established subgroup analyses stratified by IMDC risk groups, type of systemic therapy, body mass index and sarcomatoid features, did not reveal any prognostic value to DRR. CONCLUSION: Despite the statistically significant association between DRR and OS as well as CSS in mRCC patients treated with CN, DRR does not seem to add any further prognostic value beyond that obtained by currently available features.

• MeSH
• alanintransaminasa krev   MeSH
• aspartátaminotransferasy krev   MeSH
• cytoredukční chirurgie * MeSH
• karcinom z renálních buněk krev   mortalita   sekundární   chirurgie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• míra přežití MeSH
• nádory ledvin krev   mortalita   patologie   chirurgie   MeSH
• nefrektomie metody   MeSH
• předoperační období MeSH
• retrospektivní studie MeSH
• výsledek terapie MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH