OBJECTIVES: Acute intestinal ischemia is a severe complication of abdominal aortic surgery that is difficult to diagnose early and therefore to treat adequately and timely. In this study the perioperative kinetics of d-lactate and ischemia-modified albumin (IMA) are described and the predictive value of these markers for the early diagnosis of acute intestinal ischemia is assessed. DESIGN & METHODS: This non-randomised, single-centre cohort study enrolled 50 patients with abdominal aortic aneurysm (AAA) and 30 patients with aortoiliac occlusive disease (AOID). Serum d-lactate and IMA were assessed pre-, intra-, and postoperatively at eight defined time points. RESULTS: The highest serum d-lactate was at 6 h after complete declamping of the vascular graft. The highest predictive power of d-lactate was at 3 h after complete declamping (AUC 0.857). IMA was found to be higher in the AAA group in ischemic patients 10 min after complete declamping than in the AOID group. The highest predictive values of IMA were at 1 h after aortic cross-clamping (AUC 0.758) and 3 and 6 h after complete declamping (0.745 and 0.721, respectively). Moreover, the multivariate model with both markers at 3 h after complete declamping improved the detection of intestinal ischemia (AUC 0.894). CONCLUSIONS: Serum levels of IMA and d-lactate seem to be influential predictive markers for postoperative intestinal ischemia, especially after 3 h from complete declamping of vascular reconstruction.
- MeSH
- aneurysma břišní aorty * chirurgie komplikace MeSH
- biologické markery MeSH
- ischemie diagnóza etiologie MeSH
- kohortové studie MeSH
- kyselina mléčná * MeSH
- lidé MeSH
- sérový albumin MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: Prostate cancer (PCa) is the second most commonly diagnosed cancer in men. To date, the role of the combined application of long non-coding RNAs (PCA3, DLX1, HOXC6, TMPRSS2:ERG) for obtaining the most accurate method of detection of PCa has not yet been comprehensively investigated. METHODS: In total 240 persons were included in the retrospective study. Among them were 150 patients with confirmed PCa, 30 patients with benign prostatic hyperplasia, 30 patients with active chronic prostatitis and 30 healthy volunteers. In all patients, the urine samples were collected prior to biopsy or treatment. Polymerase chain reaction with reverse transcription was performed to detect the expression level of PCA3, HOXC6, DLX1 and the presence of the TMPRSS2:ERG transcript. RESULTS: PCA3 was detected in urine samples in all cases. Using a PCA3 score of 56 allowed the differentiation between PCa and all other cases with a sensitivity of 61% and specificity of 96% (p < 0.001) while a PCA3 score threshold value of 50 resulted in a differentiation between clinically significant PCa (ISUP grades 2-5) and all other cases with a sensitivity of 93% and specificity of 93% (p < 0.001). The TMPRSS2:ERG expression in urine was detected exclusively in the group of patients with PCa and only in 16% of all cases. CONCLUSIONS: PCA3 score detected in urine demonstrated moderate sensitivity and good specificity in differentiation between PCa and non-PCa and high sensitivity and specificity in differentiation between clinically significant PCa and non-PCa.
- MeSH
- antigeny nádorové * genetika MeSH
- fúzní onkogenní proteiny genetika moč MeSH
- homeodoménové proteiny genetika MeSH
- lidé MeSH
- nádorové biomarkery moč MeSH
- nádory prostaty * diagnóza genetika MeSH
- prostata patologie MeSH
- prostatický specifický antigen MeSH
- retrospektivní studie MeSH
- serinové endopeptidasy genetika MeSH
- transkripční regulátor ERG MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Neuropathological diagnostic criteria of neurodegenerative disorders are based on the presence of specific inclusions in a specific area of brain tissue that correlate with clinical manifestations. Concomitant neurodegenerative disorders correspond to a combination of two (or more) different fully developed diseases in the same patient. Concomitant neurodegenerative pathology represents the presence of definite neurodegeneration and deposits of pathological proteins specific for another disease, which is not, however, fully developed. Very frequent overlaps include Alzheimer's disease and alpha-synuclein inclusions. Nevertheless, careful neuropathological investigations reveal an increasing frequency of different co-pathologies in examined brains. In Alzheimer's disease, protein TDP-43 may co-aggregate, but it is not clear whether this is atypical isolated Alzheimer's disease or overlap of Alzheimer's disease with early frontotemporal lobar degeneration. Comorbidities of Alzheimer's disease and tauopathies are relatively rare. A combination of vascular pathology with primary neurodegeneration (mostly Alzheimer's disease or dementia with Lewy bodies) is historically called mixed dementia. Overlap of different neuropathologically confirmed neurodegenerations could lead to atypical and unusual clinical presentations and may be responsible for faster disease progression. Several CSF biomarkers have been evaluated for their utility in diagnostic processes in different neurodegenerative dementias; however, evidence regarding their role in neurodegenerative overlaps is still limited.
- MeSH
- alfa-synuklein metabolismus MeSH
- Alzheimerova nemoc metabolismus patologie MeSH
- biologické markery metabolismus MeSH
- demence s Lewyho tělísky metabolismus patologie MeSH
- DNA vazebné proteiny metabolismus MeSH
- lidé MeSH
- patologická konformace proteinů metabolismus patologie MeSH
- proteiny tau metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
During the last two decades, neuropathological examination of the brain has evolved both technically and scientifically. The increasing use of immunohistochemistry to detect protein aggregates paralleled a better understanding of neuroanatomical progression of protein deposition. As a consequence, an international effort was achieved to standardize hyperphosphorylated-Tau (phospho-TAU), ßAmyloid (Aß), alpha syncuclein (alpha-syn), phosphorylated transactive response DNA-binding protein 43 (phospho-TDP43) and vascular pathology detection. Meanwhile harmonized staging systems emerged in order to increase inter rater reproducibility. Therefore, a refined definition of Alzheimer's disease was recommended., a clearer picture of the neuropathological lesions diversity emerged secondarily to the systematic assessment of concomitant pathology highlighting finally a low rate of pure AD pathology. This brings new challenges to laboratory medicine in the field of cerebrospinal fluid (CSF) markers of Alzheimer's disease: how to further validate total Tau, phospho-TAU, Aß40 and Aß42 and new marker level cut-offs while autopsy rates are declining?
- MeSH
- Alzheimerova nemoc diagnóza patologie MeSH
- amyloidní beta-protein normy MeSH
- biologické markery chemie MeSH
- fosforylace MeSH
- lidé MeSH
- mozek patologie MeSH
- progrese nemoci MeSH
- proteiny tau chemie normy MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- MeSH
- Alzheimerova nemoc diagnóza MeSH
- biologické markery MeSH
- lidé MeSH
- metabolomika MeSH
- proteomika MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- úvodníky MeSH
Alzheimer's disease is a progressive, irreversible, incurable, neurodegenerative illness and the most common of the dementing disorders. It starts usually after 60 years of age and may span 8 to 12 years. The continuous and slow decline caused by this disease, is characterized by cognitive deterioration, loss of functional independence, changes in behaviour, and expanding needs for care. In the last three decades, the proteins predominating neuritic plaques and neurofibrillary tangles have been detected and researched: amyloid-beta protein in the plaques and hyperphosphorylated tau in the tangles. Alzheimer's disease is now considered a long-term process with a slow progress and with a prolonged development of pathological changes that precedes symptoms by years. AD is becoming one of the most problematic and expensive illness for the civilization, also known as "silent threat".
- MeSH
- Alzheimerova nemoc diagnóza etiologie MeSH
- behaviorální symptomy MeSH
- lidé MeSH
- rizikové faktory MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
OBJECTIVES: With over 35 million cases worldwide, Alzheimer's disease (AD) represents the main cause of dementia. The differentiation of AD from other types of dementia is challenging and its early diagnosis is complicated. The established biomarkers are not only based on the invasive collection of cerebrospinal fluid, but also lack sufficient sensitivity and specificity. Therefore, much current effort is aimed at the identification of new biomarkers of AD in peripheral blood. DESIGN AND METHODS: We focused on blood-based analyses using chiroptical spectroscopy (Raman optical activity, electronic circular dichroism) supplemented with conventional vibrational spectroscopy (infrared, Raman) and metabolomics (high-performance liquid chromatography with a high-resolution mass detection). RESULTS: This unique approach enabled us to identify the spectral pattern of AD and variations in metabolite levels. Subsequent linear discriminant analysis of the spectral data resulted in differentiation between the AD patients and control subjects. CONCLUSIONS: It may be stated that this less invasive approach has strong potential for the identification of disease-related changes within essential plasmatic biomolecules and metabolites.
- MeSH
- Alzheimerova nemoc krev diagnóza MeSH
- biologické markery krev MeSH
- cirkulární dichroismus MeSH
- diskriminační analýza MeSH
- krevní proteiny analýza MeSH
- lidé středního věku MeSH
- lidé MeSH
- metabolomika MeSH
- Ramanova spektroskopie MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- Publikační typ
- časopisecké články MeSH
OBJECTIVES: Altered amyloid metabolism and mitochondrial dysfunction play key roles in the development of Alzheimer's disease (AD). We asked whether an association exists between disturbed platelet mitochondrial respiration and the plasma concentrations of Aβ40 and Aβ42 in patients with AD. DESIGN AND METHODS: Plasma Aβ40 and Aβ42 concentrations and mitochondrial respiration in intact and permeabilized platelets were measured in 50 patients with AD, 15 patients with vascular dementia and 25 control subjects. A pilot longitudinal study was performed to monitor the progression of AD in a subgroup 11 patients with AD. RESULTS: The mean Aβ40, Aβ42 and Aβ42/Aβ40 levels were not significantly altered in patients with AD compared with controls. The mitochondrial respiratory rate in intact platelets was significantly reduced in patients with AD compared to controls, particularly the basal respiratory rate, maximum respiratory capacity, and respiratory reserve; however, the flux control ratio for basal respiration was increased. A correlation between the plasma Aβ42 concentration and mitochondrial respiration in both intact and permeabilized platelets differs in controls and patients with AD. CONCLUSIONS: Based on our data, (1) mitochondrial respiration in intact platelets, but not the Aβ level itself, may be included in a panel of biomarkers for AD; (2) dysfunctional mitochondrial respiration in platelets is not explained by changes in plasma Aβ concentrations; and (3) the association between mitochondrial respiration in platelets and plasma Aβ levels differs in patients with AD and controls. The results supported the hypothesis that mitochondrial dysfunction is the primary factor contributing to the development of AD.
- MeSH
- Alzheimerova nemoc krev komplikace diagnóza MeSH
- amyloidní beta-protein krev MeSH
- biologické markery krev MeSH
- buněčné dýchání MeSH
- lidé středního věku MeSH
- lidé MeSH
- mitochondriální nemoci krev komplikace diagnóza MeSH
- mitochondrie metabolismus MeSH
- peptidové fragmenty krev MeSH
- senioři MeSH
- spotřeba kyslíku MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Due to the trend of prolonged lifespan leading to higher incidence of age-related diseases, the demand for reliable biomarkers of dementia rises. In this review, we present novel biomarkers of high potential, especially those found in blood, urine or saliva, which could lead to a more comfortable patient experience and better time- and cost-effectivity, compared to the currently used diagnostic methods. We focus on biomarkers that might allow for the detection of Alzheimer's disease before its clinical manifestations. Such biomarkers might be helpful for better understanding the etiology of the disease and identifying its risk factors. Moreover, it could be a base for developing new treatment or at least help to prolong the presymptomatic stage in patients suffering from Alzheimer's disease. As potential candidates, we present, for instance, neurofilament light in both cerebrospinal fluid and blood plasma or amyloid β in plasma. Above all, we provide an overview of different approaches to the diagnostics, analyzing patient's biofluids as a whole using molecular spectroscopy. Infrared and Raman spectroscopy and especially chiroptical methods provide information not only on the chemical composition, but also on molecular structure. Therefore, these techniques are promising for the diagnostics of Alzheimer's disease, as the accumulation of amyloid β in abnormal conformation is one of the hallmarks of this disease.
- MeSH
- Alzheimerova nemoc diagnóza MeSH
- amyloidní beta-protein analýza MeSH
- biologické markery analýza MeSH
- lidé MeSH
- proteiny nervové tkáně analýza MeSH
- sliny chemie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
OBJECTIVES: Molecular screening plays a major role in prognostic categorization and subsequent definition of treatment strategies for acute myeloid leukemia. The possibility of using IDH1/2 mutations as a marker for the monitoring of minimal residual disease (MRD) is still under investigation and remains unclear. METHODS: In this retrospective study, we evaluated 90 patients with de novo AML using Sanger sequencing (exon 4, IDH1 and IDH2). For subsequent MRD monitoring were used both methods, massive parallel sequencing and droplet digital PCR (ddPCR). RESULTS: We identified 22 patients (24%) who harboured mutations in IDH1 or IDH2 genes. Fourteen (64%) of them had other commonly used MRD markers (insertion in NPM1 and partial tandem duplication of MLL, MLL-PTD). Eight of the 22 patients had IDH1 mutations, 13 had IDH2 mutations and 1 had both IDH1 and IDH2 mutations. In our cohort, this IDH1/2 marker responded to the treatment in all of the patients and reflected the onset of the relapse very well. NPM1 mutation based MRD monitoring was more sensitive and predicted relapse earlier but IDH1/2 based monitoring was more sensitive than a method based on MLL-PTD. Both massive parallel sequencing and ddPCR were competent to monitor MRD using IDH1/2. Nevertheless, ddPCR was able to achieve a higher sensitivity in some cases and moreover this method can analyse a single sample without significant price increases. CONCLUSION: Given these data, we conclude that IDH1/2 mutations can be used as a reliable and cost-effective marker for MRD monitoring.
- MeSH
- akutní myeloidní leukemie diagnóza enzymologie genetika terapie MeSH
- dospělí MeSH
- exony MeSH
- genetická predispozice k nemoci * MeSH
- genetické asociační studie MeSH
- indukce remise MeSH
- isocitrátdehydrogenasa chemie genetika metabolismus MeSH
- kohortové studie MeSH
- lidé středního věku MeSH
- lidé MeSH
- mutace * MeSH
- mutační analýza DNA MeSH
- následné studie MeSH
- nemocnice univerzitní MeSH
- prognóza MeSH
- retrospektivní studie MeSH
- reziduální nádor MeSH
- senioři MeSH
- substituce aminokyselin MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Česká republika MeSH