V současné klinické praxi cílenou terapii žaludečního adenokarcinomu představuje použití anti-HER2 monoklonální protilátky trastuzumabu u nádorů s imunohistochemickým skóre 3+ a zároveň s prokázanou amplifikací genu HER2 in situ hybridizací. Na základě současných poznatků o molekulární biologii adenokarcinomu žaludku, roli nádorového mikroprostředí a jeho cévním zásobení se jako slibné možnosti dalšího vývoje cílené terapie jeví zejména ovlivnění PD-1/PD-L1 a inhibice VEGFR2. Studie efektivity nových postupů cílené terapie, stejně jako zavádění metodik prediktivní diagnostiky, jsou však komplikovány nedostatečnou subtypizací nádorů ve studovaných souborech.

Anti-HER2 monoclonal antibody trastuzumab remains the only targeted therapy of gastric carcinoma based on histopathological predictive diagnostics used in current routine clinical practice. In the Czech Republic only the adenocarcinomas with HER2 immunohistochemical score of 3+, together with HER2 amplification detected with in situ hybridization are indicated for treatment with trastuzumab. There has been recent progress in our understanding of the molecular biology of gastric cancer, the role of its tumor microenvironment and vascular supply points to PD-1/PD-L1 and VEGFR2 as possible future targets of targeted therapy. Unfortunately, the interpretation of the results of pharmacological studies, as well as establishing new algorithms of predictive diagnostics are complicated by insufficient molecular stratification of tumors enrolled in the study groups.

• MeSH
• Adenocarcinoma classification   MeSH
• B7-H1 Antigen MeSH
• Programmed Cell Death 1 Receptor MeSH
• Molecular Targeted Therapy MeSH
• Genes, erbB-2 MeSH
• Immunohistochemistry MeSH
• Humans MeSH
• Stomach Neoplasms * diagnosis   drug therapy   classification   MeSH
• Predictive Value of Tests * MeSH
• Antineoplastic Agents, Immunological MeSH
• Vascular Endothelial Growth Factor Receptor-2 antagonists & inhibitors   therapeutic use   MeSH
• Trastuzumab therapeutic use   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Research Support, Non-U.S. Gov't MeSH
• Review MeSH

Současné léčebné algoritmy metastazujícího renálního karcinomu jsou postaveny na sekvenčním použití léků. Je proto vhodné mít k dispozici před zahájením léčby prognostické i prediktivní markery, tak aby mohl být zvolen správný lék pro konkrétního pacienta s konkrétním typem nádoru ledvin. O potenciálních biomarkerech pojednává následující článek.

Current treatment algorithms for metastatic renal cell carcinoma are based on the sequential use of drugs. It is therefore advisable to have prognostic and predictive markers available before starting treatment so that the right drug can be chosen for a particular patient with a particular type of kidney tumor. The following article discusses potential biomarkers.

• MeSH
• B7-H1 Antigen MeSH
• Interleukin-6 MeSH
• Carcinoma, Renal Cell * genetics   blood   pathology   MeSH
• Quality of Life MeSH
• Humans MeSH
• Neoplasm Metastasis MeSH
• Biomarkers, Tumor MeSH
• Von Hippel-Lindau Tumor Suppressor Protein genetics   MeSH
• Predictive Value of Tests MeSH
• Prognosis MeSH
• Tumor Burden MeSH
• Vascular Endothelial Growth Factors MeSH
• Check Tag
• Humans MeSH

Diagnostický algoritmus svalových dystrofií se v uplynulé dekádě výrazně změnil, a to zejména díky rozvoji a zvýšení dostupnosti molekulárně genetických a zobrazovacích metod. Aktuálně, kromě podrobně odebrané anamnézy, detailního klinického vyšetření, biochemického a elektrofyziologického testování, přibylo vyšetření svalů magnetickou rezonancí a nové metody molekulárně genetického vyšetření, naopak svalová biopsie přestala být nezbytnou metodou v diagnostice hereditárních myopatií. Rutinní provádění MRI u pacientů se svalovými dystrofiemi umožnilo odhalení a popsání vzorců svalového postižení (pattern of recognition) charakteristických pro určité klinické jednotky. Molekulárně genetická vyšetření pak, jako jediná, umožňují stanovení definitivní diagnózy na základě detekce kauzální mutace. Pro lepší orientaci v běžné ambulantní praxi popisuje článek hlavní kroky vedoucí k odhalení jednotlivých typů svalových dystrofií s ohledem na úroveň dnešních znalostí a zkušeností.

The diagnostics algorithm of muscular dystrophies has changed significantly over the past decade, mainly due to the development and increase of availability of molecular genetics and imaging methods. The golden standard of detailed medical history, attentive clinical examination, biochemical and electrophysiological testing now includes also magnetic resonance imaging and targeted or more extensive molecular genetic examinations, while muscle biopsy ceased to be the first choice method in the diagnostic process of hereditary myopathies. Routine MRI performance in patients with muscle. dystrophies allowed the detection and description of patterns of recognition characteristic for certain clinical units. Molecular genetic examinations as the only one allow definitive diagnosis to be determined by causal mutation detection. For better orientation in common outpatient practice, the article describes the crucial steps leading to the discovery of individual types of muscular dystrophy with respect to the level of today's knowledge and experience.

• MeSH
• Biopsy MeSH
• Diagnosis, Differential MeSH
• Electromyography methods   MeSH
• Phenotype MeSH
• Genetic Testing methods   MeSH
• Muscle, Skeletal diagnostic imaging   MeSH
• Creatine Kinase blood   MeSH
• Humans MeSH
• Magnetic Resonance Imaging MeSH
• Muscular Diseases diagnostic imaging   diagnosis   metabolism   MeSH
• Muscular Dystrophies * diagnostic imaging   diagnosis   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Review MeSH

This paper presents an adaBoost approach for schizophrenia relapse prediction. The data for the adaBoost are extracted from patients answers to Early Warning Signs questionnaires sent regularly via mobile phone messages. The performance of the adaBoost algorithm is confronted with current ITAREPS system with sensitivity 0.65 and specificity 0.73. AdaBoost has the same sensitivity 0.65 but higher specificity 0.84 and is then ready to became the part of the ITAREPS care program.

• MeSH
• Patient Compliance MeSH
• Algorithms MeSH
• Time Factors MeSH
• Behavior MeSH
• Diagnosis, Computer-Assisted methods   MeSH
• Hospitalization MeSH
• Remote Consultation methods   MeSH
• Humans MeSH
• Text Messaging MeSH
• Recurrence MeSH
• Program Development methods   MeSH
• Schizophrenic Psychology MeSH
• Schizophrenia diagnosis   prevention & control   MeSH
• Software MeSH
• Decision Support Systems, Clinical MeSH
• Telemedicine methods   MeSH
• Patient Readmission MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

Karcinom prsu je nejčastější zhoubné onemocnění u žen v rozvinutých zemích. Základem histopatologického vyšetření je stanovení správné morfologické diagnózy. S nástupem nových terapeutických možností totiž začíná hrát stále důležitější roli molekulární profil nádoru.

Breast carcinoma is the most common malignancy in women in the developed world. The basis of histopathological examination is determining a correct morphological diagnosis. With the emergence of new therapeutic possibilities, the tumour's molecular profile plays an increasingly important role.

• Keywords
• molekulární profil nádoru, protein HER-2/neu, HER2 pozitivita,
• MeSH
• Genetic Predisposition to Disease MeSH
• In Situ Hybridization, Fluorescence methods   MeSH
• Immunochemistry methods   MeSH
• Humans MeSH
• Predictive Value of Tests MeSH
• BRCA2 Protein diagnostic use   genetics   MeSH
• Sensitivity and Specificity MeSH
• Check Tag
• Humans MeSH
• Female MeSH

OBJECTIVES: The objective of this study was to assess the robustness of a novel test bolus (TB)-based computed tomographic angiography (CTA) contrast-enhancement-prediction (CEP) algorithm by retrospectively quantifying the systematic and random errors between the predicted and true enhancements. MATERIALS AND METHODS: All local institutional review boards approved this retrospective study, in which a total of 72 (3 × 24) anonymized cardiac CTA examinations were collected from 3 hospitals. All patients (46 men; median age, 62 years [range, 31-81 years]) underwent a TB scan and a cardiac CTA according to local scan and injection protocols. For each patient, a shorter TB signal and TB signals with lower temporal resolution were derived from the original TB signal. The CEP algorithm predicted the enhancement in the descending aorta (DAo) on the basis of the TB signals in the DAo, the injection protocols and kilovolt settings, as well as population-averaged blood circulation characteristics. The true enhancement was extracted with a region of interest along the DAo centerline. For each patient, the errors in timing and amplitude were calculated; differences between the hospitals were assessed using the 1-way analysis of variance (P < 0.05) and variations between the TB signals were assessed using the within-subject standard deviation. RESULTS: No significant differences were found between the 3 hospitals for any of the TB signals. With errors in the amplitude and timing of 0.3% ± 15.6% and -0.2 ± 2.0 seconds, respectively, no clinically relevant systematic errors existed. Shorter- and coarser-time-sampled TB signals introduced a within-subject standard deviation of 4.0% and 0.5 seconds, respectively. CONCLUSIONS: This TB-based CEP algorithm has no systematic errors in the timing and amplitude of predicted enhancements and is robust against coarser-time-sampled and incomplete TB scans.

• MeSH
• Algorithms * MeSH
• Adult MeSH
• Iopamidol analogs & derivatives   diagnostic use   MeSH
• Contrast Media diagnostic use   MeSH
• Coronary Angiography methods   MeSH
• Middle Aged MeSH
• Humans MeSH
• Coronary Artery Disease radiography   MeSH
• Tomography, X-Ray Computed methods   MeSH
• Image Processing, Computer-Assisted methods   MeSH
• Predictive Value of Tests MeSH
• Reproducibility of Results MeSH
• Retrospective Studies MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Radiographic Image Enhancement methods   MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Evaluation Study MeSH

We present a noninvasive Web-based app to help exclude or diagnose myelodysplastic syndrome (MDS), a bone marrow (BM) disorder with cytopenias and leukemic risk, diagnosed by BM examination. A sample of 502 MDS patients from the European MDS (EUMDS) registry (n > 2600) was combined with 502 controls (all BM proven). Gradient-boosted models (GBMs) were used to predict/exclude MDS using demographic, clinical, and laboratory variables. Area under the receiver operating characteristic curve (AUC), sensitivity, and specificity were used to evaluate the models, and performance was validated using 100 times fivefold cross-validation. Model stability was assessed by repeating its fit using different randomly chosen groups of 502 EUMDS cases. AUC was 0.96 (95% confidence interval, 0.95-0.97). MDS is predicted/excluded accurately in 86% of patients with unexplained anemia. A GBM score (range, 0-1) of less than 0.68 (GBM < 0.68) resulted in a negative predictive value of 0.94, that is, MDS was excluded. GBM ≥ 0.82 provided a positive predictive value of 0.88, that is, MDS. The diagnosis of the remaining patients (0.68 ≤ GBM < 0.82) is indeterminate. The discriminating variables: age, sex, hemoglobin, white blood cells, platelets, mean corpuscular volume, neutrophils, monocytes, glucose, and creatinine. A Web-based app was developed; physicians could use it to exclude or predict MDS noninvasively in most patients without a BM examination. Future work will add peripheral blood cytogenetics/genetics, EUMDS-based prospective validation, and prognostication.

• MeSH
• Algorithms MeSH
• Laboratories MeSH
• Humans MeSH
• Myelodysplastic Syndromes * diagnosis   MeSH
• Bone Marrow Diseases * MeSH
• Bone Marrow Examination MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH

Cieľom multicentrickej, otvorenej, observačnej štúdie PREDICTIVE® bolo posúdiť u diabetikov 1. aj 2. typu bezpečnosť a efektivitu inzulínu detemir v podmienkach bežnej klinickej praxe. Výsledky z Európskej kohorty štúdie PREDICTIVE® po 3 mesiacoch liečby inzulínom detemir ukázali, že inzulín detemir je účinný preparát umožňujúci náhradu bazálnej sekrécie inzulínu. Jeho podávanie bolo spojené s minimálnym výskytom nežiaducich účinkov (hlavne ťažkých hypoglykémií) a tiež s nízkou intraindividuálnou variabilitou glykémií nalačno, a teda aj predvídateľnejším terapeutickým účinkom. Európska kohorta štúdie PREDICTIVE® potvrdila výsledky klinických randomizovaných štúdií, že liečba inzulínom detemir nevedie k zvýšeniu telesnej hmotnosti. U mnohých diabetikov 1. aj 2. typu v tejto štúdii došlo dokonca k redukcii telesnej hmotnosti. Šesťmesačná liečba inzulínom detemir v tejto štúdii poskytla dôkaz o dlhodobejšej účinnosti a bezpečnosti tohto inzulínu. Výsledky štúdie TITRATE® ukázali, že pacientom riadená titrácia inzulínu detemir podávaného raz denne na dosiahnutie cieľových hodnôt glykémie nalačno u diabetikov 2. typu predtým neliečených inzulínom je účinná a bezpečná.

The aim of the multicenter, open-label, observational study PREDICTIVE® was to assess safety and efficacy of insulin detemir in both type 1 and 2 diabetes patients in actual clinical practice. The results of the European cohort of PREDICTIVE® after three-month therapy with insulin detemir found it to be an efficacious product allowing substitution of basal insulin secretion. Its administration was associated with a minimal occurrence of adverse events (especially major hypoglycemic episodes) together with a low within-patient fasting glucose variability and more predictable therapeutic effect. The European cohort of the PREDICTIVE® study confirmed the results of clinical randomised trials, that the therapy with insulin detemir does not cause body weight gain. Moreover, body weight reduction in type 1 and 2 diabetes patients was observed within this study. Results from the six-month insulin detemir therapy provide evidence on the long term safety and efficacy of this insulin. Results of the TITRATE® study showed, that lowering the fasting glucose target using a self-directed titration algorithm with once-daily detemir is safe and efficacious.

MOTIVATION: G-quadruplex is a DNA or RNA form in which four guanine-rich regions are held together by base pairing between guanine nucleotides in coordination with potassium ions. G-quadruplexes are increasingly seen as a biologically important component of genomes. Their detection in vivo is problematic; however, sequencing and spectrometric techniques exist for their in vitro detection. We previously devised the pqsfinder algorithm for PQS identification, implemented it in C++ and published as an R/Bioconductor package. We looked for ways to optimize pqsfinder for faster and user-friendly sequence analysis. RESULTS: We identified two weak points where pqsfinder could be optimized. We modified the internals of the recursive algorithm to avoid matching and scoring many sub-optimal PQS conformations that are later discarded. To accommodate the needs of a broader range of users, we created a website for submission of sequence analysis jobs that does not require knowledge of R to use pqsfinder. AVAILABILITY AND IMPLEMENTATION: https://pqsfinder.fi.muni.cz, https://bioconductor.org/packages/pqsfinder. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

• MeSH
• Algorithms MeSH
• G-Quadruplexes * MeSH
• Genome MeSH
• RNA MeSH
• Software MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

BACKGROUND: Prediction of susceptibility to multiple sclerosis (MS) might have important clinical applications, either as part of a diagnostic algorithm or as a means to identify high-risk individuals for prospective studies. We investigated the usefulness of an aggregate measure of risk of MS that is based on genetic susceptibility loci. We also assessed the added effect of environmental risk factors that are associated with susceptibility for MS. METHODS: We created a weighted genetic risk score (wGRS) that includes 16 MS susceptibility loci. We tested our model with data from 2215 individuals with MS and 2189 controls (derivation samples), a validation set of 1340 individuals with MS and 1109 controls taken from several MS therapeutic trials (TT cohort), and a second validation set of 143 individuals with MS and 281 controls from the US Nurses' Health Studies I and II (NHS/NHS II), for whom we also have data on smoking and immune response to Epstein-Barr virus (EBV). FINDINGS: Individuals with a wGRS that was more than 1.25 SD from the mean had a significantly higher odds of MS in all datasets. In the derivation sample, the mean (SD) wGRS was 3.5 (0.7) for individuals with MS and 3.0 (0.6) for controls (p<0.0001); in the TT validation sample, the mean wGRS was 3.4 (0.7) for individuals with MS versus 3.1 (0.7) for controls (p<0.0001); and in the NHS/NHS II dataset, the mean wGRS was 3.4 (0.8) for individuals with MS versus 3.0 (0.7) for controls (p<0.0001). In the derivation cohort, the area under the receiver operating characteristic curve (C statistic; a measure of the ability of a model to discriminate between individuals with MS and controls) for the genetic-only model was 0.70 and for the genetics plus sex model was 0.74 (p<0.0001). In the TT and NHS cohorts, the C statistics for the genetic-only model were both 0.64; adding sex to the TT model increased the C statistic to 0.72 (p<0.0001), whereas adding smoking and immune response to EBV to the NHS model increased the C statistic to 0.68 (p=0.02). However, the wGRS does not seem to be correlated with the conversion of clinically isolated syndrome to MS. INTERPRETATION: The inclusion of 16 susceptibility alleles into a wGRS can modestly predict MS risk, shows consistent discriminatory ability in independent samples, and is enhanced by the inclusion of non-genetic risk factors into the algorithm. Future iterations of the wGRS might therefore make a contribution to algorithms that can predict a diagnosis of MS in a clinical or research setting.

• MeSH
• Alleles MeSH
• Algorithms * MeSH
• Child MeSH
• Adult MeSH
• Genotype MeSH
• Risk Assessment MeSH
• Polymorphism, Single Nucleotide genetics   MeSH
• Cohort Studies MeSH
• Middle Aged MeSH
• Humans MeSH
• Quantitative Trait Loci MeSH
• Adolescent MeSH
• Odds Ratio MeSH
• Predictive Value of Tests MeSH
• Child, Preschool MeSH
• Risk Factors MeSH
• Multiple Sclerosis * epidemiology   genetics   MeSH
• Aged MeSH
• Environment MeSH
• Check Tag
• Child MeSH
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Adolescent MeSH
• Male MeSH
• Child, Preschool MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Research Support, Non-U.S. Gov't MeSH
• Research Support, N.I.H., Extramural MeSH