AIM: Current diagnostics of bone metastatic disease is not satisfactory for early detection or regular process monitoring. The combination of biomarkers and the multiparametric approach was described as effective in other oncology diagnoses. The aim of the study was to improve the difference diagnostics between bone-metastatic disease and solid tumors using mutivariate logistic regression model. METHODS: We assessed the group of 131 patients with the following diagnoses: prostate cancer, breast cancer, lung cancer, and colorectal cancer. According to the results of scintigraphy, the cohort was divided into 2 groups based on the occurrence of bone metastases. Group 0 was a control group of 75 patients with no signs of bone metastases and group 1 included 56 patients with bone metastases. RESULTS: We used stepwise selection multivariate logistic regression for choosing the multimarker formula for calculation of risk score for bone metastases diagnostics. For detection of bone metastasis, it was shown to be most effective measurement of 3 biomarkers: procollagen type 1 N-terminal propeptide, growth differentiation factor-15, and osteonectin and combining with calculation of risk score by designating measured concentrations in mathematical formula: bone risk score = procollagen type 1 N-terminal propeptide × 0.0500 + growth differentiation factor-15 × 1.4179 + osteonectin × 0.00555. CONCLUSION: We identified growth differentiation factor-15 as the best individual marker for bone metastasis diagnostics. The best formula for risk score includes levels of 3 biomarkers-procollagen type 1 N-terminal propeptide, growth differentiation factor-15, and osteonectin. The new score has better performance described by higher area under the curve than individual biomarkers. A further study is necessary to confirm these findings incorporating a larger number of patients.

• Klíčová slova
• biomarkers, bone metastasis, cancer, multivariate analysis, scintigraphy,
• MeSH
• dospělí MeSH
• kohortové studie MeSH
• kosti a kostní tkáň metabolismus   patologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• multivariační analýza MeSH
• nádorové biomarkery metabolismus   MeSH
• nádory kostí metabolismus   patologie   sekundární   MeSH
• osteonektin metabolismus   MeSH
• radioisotopová scintigrafie metody   MeSH
• růstový diferenciační faktor 15 metabolismus   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• 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
• Názvy látek
• nádorové biomarkery MeSH
• osteonektin MeSH
• růstový diferenciační faktor 15 MeSH

The aim of the study was to evaluate the ability of following biomarkers as diagnostic tools and risk predictors of AAA: C-reactive protein, interleukin-6, pentraxin-3, galectin-3, procollagen type III N-terminal peptide, C-terminal telopeptide of type I collagen, high-sensitive troponin I, and brain natriuretic peptide. Seventy-two patients with an AAA and 100 healthy individuals were enrolled into the study. We assessed individual biomarker performance and correlation between the AAA diameter and biomarker levels, and also, a multivariate logistic regression was used to design a possible predictive model of AAA growth and rupture risk. We identified following four parameters with the highest potential to find a useful place in AAA diagnostics: galectin-3, pentraxin-3, interleukin-6, and C-terminal telopeptide of type I. The best biomarkers in our evaluation (galectin-3 and pentraxin-3) were AAA diameter-independent. With the high AUC and AAA diameter correlation, the high-sensitive troponin I can be used as an independent prognostic biomarker of the upcoming heart complications in AAA patients. Authors recommend to add biomarkers as additional parameters to the current AAA patient management. Main addition value of biomarkers is in the assessment of the AAA with the smaller diameter. Elevated biomarkers can change the treatment decision, which would be done only based on AAA diameter size. The best way how to manage the AAA patients is to create a reliable predictive model of AAA growth and rupture risk. A created multiparameter model gives very promising results with the significantly higher efficiency compared with the use of the individual biomarkers.

• Klíčová slova
• Abdominal aortic aneurism, Biomarker panel, Brain natriuretic peptide, C-Terminal telopeptide of type I collagen, Galectin-3, High-sensitive troponin I, Interleukin-6, Multivariate model, Multivariate stepwise logistic regression, Patient stratification, Pentraxin-3, Predictive preventive personalized medicine, Procollagen type III N-terminal peptide,
• Publikační typ
• časopisecké články MeSH

AIM: The first aim of this study was to search for new biomarkers to be used in gastric cancer diagnostics. The second aim was to verify the findings presented in literature on a sample of the local population and investigate the risk of gastric cancer in that population using a multivariant statistical analysis. PATIENTS AND METHODS: We assessed a group of 36 patients with gastric cancer and 69 healthy individuals. We determined carcinoembryonic antigen, cancer antigen 19-9, cancer antigen 72-4, matrix metalloproteinases (-1, -2, -7, -8 and -9), osteoprotegerin, osteopontin, prothrombin induced by vitamin K absence-II, pepsinogen I, pepsinogen II, gastrin and Helicobacter pylori for each sample. RESULTS: The multivariate stepwise logistic regression identified the following biomarkers as the best gastric cancer predictors: CEA, CA72-4, pepsinogen I, Helicobacter pylori presence and MMP7. CONCLUSION: CEA and CA72-4 remain the best markers for gastric cancer diagnostics. We suggest a mathematical model for the assessment of risk of gastric cancer.

• Klíčová slova
• Gastric cancer, biomarkers, gastric cancer index, tumor markers,
• MeSH
• antigeny sacharidové asociované s nádorem krev   MeSH
• dospělí MeSH
• Helicobacter pylori imunologie   MeSH
• imunoglobulin G krev   MeSH
• infekce vyvolané Helicobacter pylori imunologie   MeSH
• karcinoembryonální antigen krev   MeSH
• lidé středního věku MeSH
• lidé MeSH
• matrixová metaloproteinasa 7 krev   MeSH
• multivariační analýza MeSH
• nádorové biomarkery krev   MeSH
• nádory žaludku krev   diagnóza   MeSH
• pepsinogen A krev   MeSH
• protilátky bakteriální krev   MeSH
• rizikové faktory MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• teoretické modely * MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antigeny sacharidové asociované s nádorem MeSH
• CA-72-4 antigen MeSH Prohlížeč
• imunoglobulin G MeSH
• karcinoembryonální antigen MeSH
• matrixová metaloproteinasa 7 MeSH
• MMP7 protein, human MeSH Prohlížeč
• nádorové biomarkery MeSH
• pepsinogen A MeSH
• protilátky bakteriální MeSH

AIM: The aim of this paper was to assess the prevalence of concurrent deep vein thrombosis (DVT) and/or pulmonary embolism (PE) in the patients with superficial vein thrombosis (SVT) of the legs and to find factors significantly and independently associated with coincident DVT/PE. METHODS: In the setting of a tertiary referral hospital, patients with SVT, attending vascular clinic, underwent physical examination, laboratory testing and leg vein ultrasound (in the case of clinically suspected PE also perfusion/ventilation lung scan or/and helical CT pulmonary angiography). In statistical analysis, we used unpaired t-test, non-parametric Wilcoxon rank sum test, stepwise logistic regression and multivariable logistic regression model. RESULTS: We examined 138 patients (age 61.4 ± 13.9 years, 36.2% men), with ST mostly on varicose veins (89.9%). The prevalence of concurrent DVT/PE was 34.1%. Neither the clinical manifestation nor SVT localization differed significantly between the group with isolated SVT and that with coincident DVT/PE. Of all the assessed patients characteristics (age and sex, BMI, history of SVT, DVT or PE, hypercoagulable states, cardiovascular risk factors) only two factors were significantly and independently associated with the presence of concurrent DVT/PE. Log BMI was significantly higher in the patients with isolated SVT. Factor V Leiden (FVL) was proved as an independent risk factor for concomitant DVT/PE with odds ratio 2,531 (95% CI 1,064-6,016). CONCLUSION: The prevalence of concurrent DVT/PE in patients with SVT, referred to hospital vascular clinic was 34.1%. Lower BMI (log BMI, respectively) and the presence of FVL were significantly and independently associated with concurrent DVT/PE. Our results should be further investigated in a larger prospective study.

• MeSH
• centra terciární péče MeSH
• dolní končetina krevní zásobení   MeSH
• faktor V genetika   MeSH
• fyzikální vyšetření MeSH
• index tělesné hmotnosti MeSH
• lidé středního věku MeSH
• lidé MeSH
• logistické modely MeSH
• multivariační analýza MeSH
• obezita diagnóza   epidemiologie   MeSH
• odds ratio MeSH
• plicní embolie diagnóza   epidemiologie   MeSH
• prediktivní hodnota testů MeSH
• prevalence MeSH
• průřezové studie MeSH
• rezistence k aktivovanému proteinu C epidemiologie   genetika   MeSH
• rizikové faktory MeSH
• rozdělení chí kvadrát MeSH
• senioři MeSH
• tomografie spirální počítačová MeSH
• ultrasonografie dopplerovská barevná MeSH
• žilní trombóza diagnóza   epidemiologie   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Česká republika epidemiologie   MeSH
• Názvy látek
• factor V Leiden MeSH Prohlížeč
• faktor V MeSH

BACKGROUND: The aim of our study was to retrospectively analyse the clinical data and the histological findings of 343 patients (pts) followed up with IgA nephropathy (IgAN) in our department of nephrology. We have assessed the main demographic, clinical and histological data, and the medical treatment of IgAN pts. METHODS: Multivariate analysis was used to evaluate the effect of different variables on ≥50% increase of plasma creatinine level from baseline during a median follow-up of 4 years. RESULTS: In our group of IgAN pts, the male gender (68%) predominated over female gender (32%). At the time of renal biopsy, the median age of IgAN pts was 32.3 (18-90) years, the median level of serum creatinine was 119 μmol/L and the median level of proteinuria was 1.8 g/day. Most of the pts were found to have arterial hypertension (56.7%). The majority of the pts with arterial hypertension were treated with inhibitors of angiotensin-converting enzyme (80.4%) and the remaining pts (42.6%) were treated with angiotensin II receptor blockers. Fifty per cent of the pts (170 pts) were treated of corticosteroids, 21% of the pts (71 pts) used a combined immunosuppressive treatment of corticosteroids and cyclophosphamide, 8% of the pts (27 pts) took azathioprine, 1.5% of the pts (5 pts) took cyclosporine and 1.5% of the pts (5 pts) were given mycophenolate mofetil. Hypertension at presentation, fibrointimal proliferation of arterial vessels, interstitial fibrosis and interstitial inflammation were shown to be associated with ≥50% increase of plasma creatinine level from baseline in univariate analysis (P<0.05 for hypertension and fibrointimal proliferation; P<0.01 for interstitial fibrosis and inflammation). Using stepwise logistic regression presenting proteinuria>2 g/day [odds ratio (OR)=2.24, P<0.01], tubular atrophy (OR=4.97, P<0.01) and damage of tubular epithelium (OR=1.78, P<0.05) were found as risk factors for ≥50% increase of plasma creatinine level from baseline. CONCLUSION: Our retrospective analysis found valuable information not only about the clinical, laboratory and histological findings in IgAN pts but also information about the risk factors influencing the progression of renal insufficiency.

• MeSH
• chronické selhání ledvin epidemiologie   etiologie   mortalita   MeSH
• dospělí MeSH
• hodnoty glomerulární filtrace MeSH
• hypertenze epidemiologie   etiologie   mortalita   MeSH
• IgA nefropatie komplikace   mortalita   MeSH
• kreatinin metabolismus   MeSH
• lidé středního věku MeSH
• lidé MeSH
• míra přežití MeSH
• multivariační analýza MeSH
• následné studie MeSH
• prognóza MeSH
• proteinurie epidemiologie   etiologie   mortalita   MeSH
• retrospektivní studie MeSH
• rizikové faktory MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Česká republika epidemiologie   MeSH
• Názvy látek
• kreatinin MeSH

BACKGROUND: Cardiopulmonary exercise testing parameters including ventilatory efficiency (VE/VCO2 slope) are used for risk assessment of lung resection candidates. However, many patients are unable or unwilling to undergo exercise. VE/VCO2 slope is closely related to the partial pressure of end-tidal carbon dioxide (PETCO2). We hypothesized PETCO2 at rest predicts postoperative pulmonary complications. METHODS: Consecutive lung resection candidates were included in this prospective multicenter study. Postoperative respiratory complications were assessed from the first 30 postoperative days or from the hospital stay. Student t test or Mann-Whitney U test was used for comparison. Multivariate stepwise logistic regression analysis was used to analyze association with the development of postoperative pulmonary complications. The De Long test was used to compare area under the curve (AUC). Data are summarized as median (interquartile range). RESULTS: Three hundred fifty-three patients were analyzed, of which 59 (17%) developed postoperative pulmonary complications. PETCO2 at rest was significantly lower (27 [24-30] vs 29 [26-32] mm Hg; P < .01) and VE/VCO2 slope during exercise significantly higher (35 [30-40] vs 29 [25-33]; P < .01) in patients who developed postoperative pulmonary complications. Both rest PETCO2 with odds ratio 0.90 (95% confidence interval [CI] 0.83-0.97); P = .01 and VE/VCO2 slope with odds ratio 1.10 (95% CI 1.05-1.16); P < .01 were independently associated with postoperative pulmonary complications by multivariate stepwise logistic regression analysis. There was no significant difference between AUC of both models (rest PETCO2: AUC = 0.79 (95% CI 0.74-0.85); VE/VCO2 slope: AUC = 0.81 (95% CI 0.75-0.86); P = .48). CONCLUSIONS: PETCO2 at rest has similar prognostic utility as VE/VCO2 slope, suggesting rest PETCO2 may be used for postoperative pulmonary complications prediction in lung resection candidates.

• MeSH
• lidé MeSH
• oxid uhličitý * MeSH
• plíce MeSH
• prospektivní studie MeSH
• spotřeba kyslíku MeSH
• srdeční selhání * MeSH
• zátěžový test MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• Názvy látek
• oxid uhličitý * MeSH

The histological grade is crucial for therapeutic management, and its reliable preoperative detection can significantly influence treatment approach. Lacking established risk factors, this study identifies preoperative predictors of high-grade skull base meningiomas and discusses the implications of non-invasive detection. A multicentric study was conducted on 552 patients with skull base meningiomas who underwent primary surgical resection between 2014 and 2019. Data were gathered from clinical, surgical and pathology records and radiological diagnostics. The predictive factors of higher WHO grade were analysed in univariate analysis and multivariate stepwise selection logistic regression analysis. Histological analysis revealed 511 grade 1 (92.6%) and 41 grade 2 (7.4%) meningiomas. A prognostic model predicting the probability of WHO grade 2 skull base meningioma (AUC 0.79; SE 0.04; 95% Wald Confidence Limits (0.71; 0.86)) based on meningioma diameter, presence of an arachnoid plane and cranial nerve palsy was built. Accurate preoperative detection of WHO grade in skull base meningiomas is essential for effective treatment planning. Our logistic regression model, based on diameter, cranial nerve palsy, and arachnoid plane, is tailored for detecting WHO grade 2 skull base meningiomas, even in outpatient settings.

• Klíčová slova
• Case series, Meningioma, Risk factors, Skull base, Surgery, Tumor grading,
• MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• meningeální nádory * patologie   chirurgie   MeSH
• meningeom * patologie   chirurgie   MeSH
• nádory baze lební * patologie   chirurgie   MeSH
• prognóza MeSH
• retrospektivní studie MeSH
• rizikové faktory MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• stupeň nádoru MeSH
• Světová zdravotnická organizace MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH

BACKGROUND: The rate of immune reconstitution after allogeneic hematopoietic stem cell transplantation (allo-HSCT) plays the principal role in the development of serious post-transplant complications. However, the post-transplantation course has a significant impact on shaping the immune system of the recipient, per se, thus representing risk factors for subsequent unfavorable outcomes. The predictive power of an interferon gamma (IFNγ) release assay (IGRA) on graft-versus-host disease (GVHD) or hematological relapse in recipients of allo-HSCT treated with post-transplantation cyclophosphamide and the impact of these complications on the restoration of cellular immune responsiveness was evaluated. STUDY DESIGN: A prospective observational study in which 62 adult patients with myeloid hematological malignancies who underwent allo-HSCT with a myeloablative conditioning regimen combined with post-transplantation cyclophosphamide were enrolled. Clinical data were collected and the IGRA was performed before commencement of the conditioning regimen and for 12 months post-allo-HSCT. Multivariate Cox regression and logistic regression models with backward stepwise analyses were used to calculate the predictive values for acute or chronic GVHD, or hematological relapse. RESULTS: Pre-transplantation and early post-transplantation IGRA values and other selected covariables (age, diagnosis, relapse risk, conditioning type, pre-T lymphocyte count, and donor sex), enabled prediction of the 12-month incidence of chronic GVHD with positive and negative predictive values of 75 % and 88 %, respectively. However, the IGRA did not improve the predictive value for acute GVHD or hematological relapse. Patients with myelodysplastic syndrome (MDS) had a significantly lower pre-transplant IGRA value (p = 0.021) and a delayed IFNγ response in IGRA, post-HSCT, than patients with acute myeloid leukemia (AML) (p = 0.015 and p = 0.0063 for 3 and 4 months post-HSCT, respectively). CONCLUSIONS: The IGRA can be used to monitor the recovery of total cellular immunity, post-HSCT and it has shown potential for use in personalized post-transplantation care. In the multivariate backward stepwise logistic regression model, pre-and early post-transplantation IGRA values showed potential for predicting chronic GVHD. Patients with MDS had a significantly lower pre-transplantation IGRA value and delayed IFNγ response in IGRA, post-HSCT, than patients with AML.

• Klíčová slova
• Acute myeloid leukemia, Biomarker, GVHD prophylaxis, Graft-versus-host reaction, HSCT, Hematopoietic stem cell transplantation, Interferon γ- release assay, Myelodysplasic syndrome, Relapse,
• MeSH
• chronická nemoc MeSH
• cyklofosfamid * terapeutické užití   MeSH
• dospělí MeSH
• hematologické nádory * terapie   MeSH
• homologní transplantace MeSH
• interferon gama * metabolismus   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• nemoc štěpu proti hostiteli * diagnóza   prevence a kontrola   MeSH
• příprava pacienta k transplantaci * metody   MeSH
• prospektivní studie MeSH
• senioři MeSH
• transplantace hematopoetických kmenových buněk * MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• pozorovací studie MeSH
• Názvy látek
• cyklofosfamid * MeSH
• interferon gama * MeSH

AIM: The aim of the present study was to investigate myocardial perfusion in relation to disease history and laboratory parameters of atherosclerosis risk in asymptomatic patients with breast carcinoma. PATIENTS AND METHODS: One-hundred and eighty-one patients with breast carcinoma were studied. Myocardial perfusion was assessed using single-photon emission computed tomography (SPECT) with 99mtechnetium sestamibi. RESULTS: Perfusion defects were detected in 12 patients (7%). Higher body-mass index, increased concentrations of D-dimers, C-reactive protein, fibrinogen, glucose, triglycerides, and urinary albumin, a history of hypertension and of radiotherapy to the left chest wall were all associated with increased risk of perfusion defects. In a multivariate stepwise selection logistic regression model, body mass index, albuminuria and radiotherapy to the left hemithorax were significantly associated with the presence of perfusion defects. CONCLUSION: In addition to other factors, treatment history may be associated with the presence of perfusion defects in patients with breast cancer.

• Klíčová slova
• Atherosclerosis, breast cancer, single-photon emission computed tomography,
• MeSH
• dospělí MeSH
• jednofotonová emisní výpočetní tomografie metody   MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádory prsu diagnostické zobrazování   patofyziologie   MeSH
• nemoci koronárních tepen diagnostické zobrazování   patofyziologie   MeSH
• radiofarmaka MeSH
• senioři MeSH
• technecium 99mTc sestamibi MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• radiofarmaka MeSH
• technecium 99mTc sestamibi MeSH

INTRODUCTION: Airway management is a critical component of out-of-hospital cardiac arrest (OHCA) resuscitation. The primary aim of this study was to describe pre-hospital airway management in adult patients post-OHCA. Secondary aims were to investigate whether tracheal intubation (TI) versus use of supraglottic airway device (SGA) was associated with patients' outcomes, including ventilator-free days within 26 days of randomization, 6 months neurological outcome and mortality. METHODS: Secondary analysis of the Target Temperature Management-2 (TTM2) trial conducted in 13 countries, including adult patients with OHCA and return of spontaneous circulation, with data available on pre-hospital airway management. A multivariate logistic regression model with backward stepwise selection was employed to assess whether TI versus SGA was associated with outcomes. RESULTS: Of the 1900 TTM2 trial patients, 1702 patients (89.5%) were included, with a mean age of 64 years (Standard Deviation, SD = 13.53); 79.1% were males. Pre-hospital airway management was SGA in 484 (28.4%), and TI in 1218 (71.6%) patients. At hospital admission, 87.8% of patients with SGA and 98.5% with TI were mechanically ventilated (p < 0.001). In the multivariate analysis, TI in comparison with SGA was not independently associated with an increase in ventilator-free days within 26 days of randomization, improved neurological outcomes, or decreased mortality. The hazard ratio for mortality with TI vs. SGA was 1.06, 95%Confidence Interval (CI) 0.88-1.28, p = 0.54. CONCLUSIONS: In the multicentre randomized TTM2-trial including patients with OHCA, most patients received prehospital endotracheal intubation to manage their airway. The choice of pre-hospital airway device was not independently associated with patient clinical outcomes. TRIAL REGISTRATION NUMBER: NCT02908308.

• Klíčová slova
• Airway devices, Airway management, Cardiac arrest, Outcome, endotracheal intubation, Supraglottic device,
• MeSH
• intratracheální intubace * metody   MeSH
• kardiopulmonální resuscitace * metody   MeSH
• lidé středního věku MeSH
• lidé MeSH
• senioři MeSH
• terapeutická hypotermie metody   MeSH
• urgentní zdravotnické služby * metody   MeSH
• zajištění dýchacích cest * metody   MeSH
• zástava srdce mimo nemocnici * terapie   mortalita   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• randomizované kontrolované studie MeSH