Direct detection of DNA in complex biological samples bears several challenges regarding the selectivity and sensitivity of analyses. Therefore, DNA pre-extraction from bio-fluids is an emerging tool in biologically related fields. Specifically, a newly developing family of liquid biopsy techniques using PCR detection of circulating tumor DNA from blood serum or blood plasma could be significantly improved by harnessing fast and high-throughput DNA sample preparation. To address these needs, a 3D-printed device and a method based on gel electrophoresis combined with electrodialysis for the time-, cost- and labor-efficient preparative separation of DNA fragments from blood was developed. The proposed system also successfully eliminated large DNA fragments from the samples. Recovery for short DNA fragments was reaching up to 80 %. The method was tested on human genomic DNA and blood and blood serum spiked with DNA standards, and it significantly alleviated the signal of matrix DNA.
- Klíčová slova
- Cancer, Circulating tumor DNA (ctDNA), Liquid biopsy, PCR, Preparative gel electrophoresis,
- MeSH
- 3D tisk * MeSH
- časové faktory MeSH
- DNA * krev izolace a purifikace chemie analýza MeSH
- lidé MeSH
- polymerázová řetězová reakce MeSH
- tekutá biopsie metody MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- DNA * MeSH
BACKGROUND: Prostate Imaging Reporting and Data System (PI-RADS) 3 lesions, identified through multiparametric magnetic resonance imaging (mpMRI), present a clinical challenge due to their equivocal nature in predicting clinically significant prostate cancer (csPCa). Aim of the study is to improve risk stratification of patients with PI-RADS 3 lesions and candidates for prostate biopsy. METHODS: A cohort of 4841 consecutive patients who underwent MRI and subsequent MRI-targeted and systematic biopsies between January 2016 and April 2023 were retrospectively identified from independent prospectively maintained database. Only patients who have PI-RADS 3 lesions were included in the final analysis. A multivariable logistic regression analysis was performed to identify covariables associated with csPCa defined as International Society of Urological Pathology (ISUP) grade group ≥2. Performance of the model was evaluated using the area under the receiver operating characteristic curve (AUC), calibration, and net benefit. Significant predictors were then selected for further exploration using a Chi-squared Automatic Interaction Detection (CHAID) analysis. RESULTS: Overall, 790 patients had PI-RADS 3 lesions and 151 (19%) had csPCa. Significant associations were observed for age (OR: 1.1 [1.0-1.1]; p = 0.01) and PSA density (OR: 1643 [2717-41,997]; p < 0.01). The CHAID analysis identified PSAd as the sole significant factor influencing the decision tree. Cut-offs for PSAd were 0.13 ng/ml/cc (csPCa detection rate of 1% vs. 18%) for the two-nodes model and 0.09 ng/ml/cc and 0.16 ng/ml/cc for the three-nodes model (csPCa detection rate of 0.5% vs. 2% vs. 17%). CONCLUSIONS: For individuals with PI-RADS 3 lesions on prostate mpMRI and a PSAd below 0.13, especially below 0.09, prostate biopsy can be omitted, in order to avoid unnecessary biopsy and overdiagnosis of non-csPCa.
- MeSH
- hodnocení rizik metody MeSH
- lidé středního věku MeSH
- lidé MeSH
- multiparametrická magnetická rezonance * metody MeSH
- nádory prostaty * patologie diagnostické zobrazování diagnóza krev MeSH
- prostata patologie diagnostické zobrazování MeSH
- prostatický specifický antigen * krev MeSH
- retrospektivní studie MeSH
- ROC křivka MeSH
- senioři MeSH
- stupeň nádoru MeSH
- ultrazvukem navigovaná biopsie metody MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- prostatický specifický antigen * MeSH
PURPOSE: This prospective pilot study aims to evaluate the capabilities of novel quantitative ultrasound (QUS) methods based on attenuation (Att.PLUS) and sound speed (SSp.PLUS) for detecting liver fat. PATIENTS AND METHODS: The study included 56 individuals with biopsy-proven steatosis (percutaneous liver biopsy) ranging from 0 % to 90 % of hepatocytes containing intracellular lipid vacuoles. Histopathology was considered reference standard. Abdominal QUS examinations were conducted using Att.PLUS and SSp.PLUS techniques on the Aixplorer MACH 30 system. Comparative assessments were made using the results of liver biopsy and magnetic resonance spectroscopy (MRS) together with magnetic resonance imaging proton density fat fraction (MRI-PDFF). MR examinations were performed on the Siemens VIDA 3 T system. RESULTS: ROC analysis was conducted for two groups: (a) patients without steatosis (S0) versus those with steatosis (S1 + S2 + S3) yielded AUC values of 0.79 for Att.PLUS and 0.78 for SSp.PLUS, in contrast to an AUC > 0.95 for MRS and MRI-PDFF; and (b) patients without or with mild steatosis (S0 + S1) versus those with severe steatosis (S2 + S3), yielded AUC values of 0.93 for Att.PLUS and 0.89 for SSp.PLUS, in contrast to an AUC > 0.99 for MRS and MRI-PDFF. However, MR methods were superior in detecting liver fat content in obese patients and post-liver transplantation individuals. CONCLUSION: Both QUS parameters (Att.PLUS and SSp.PLUS) appear equivalent at differentiating S0 vs. (S1 + S2 + S3) patients, but the Att.PLUS parameter may be more effective at identifying advanced steatosis (S2 + S3). MR techniques outperformed QUS methods, making them more suitable for clinical studies.
- Klíčová slova
- Attenuation, Biopsy, Liver steatosis, Magnetic resonance, Sound speed, Ultrasonography,
- MeSH
- biopsie MeSH
- dospělí MeSH
- játra diagnostické zobrazování patologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- magnetická rezonanční spektroskopie metody MeSH
- magnetická rezonanční tomografie * metody MeSH
- pilotní projekty MeSH
- prospektivní studie MeSH
- reprodukovatelnost výsledků MeSH
- senioři MeSH
- senzitivita a specificita MeSH
- ultrasonografie * metody MeSH
- ztučnělá játra * diagnostické zobrazování patologie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- srovnávací studie MeSH
BACKGROUND: This is a multicentre, European, prospective trial evaluating the diagnostic accuracy of One Step Nucleic Acid Amplification (OSNA) compared to sentinel lymph nodes histopathological ultrastaging in endometrial cancer patients. METHODS: Centres with expertise in sentinel lymph node mapping in endometrial cancer patients in Europe will be invited to participate in the study. Participating units will be trained on the correct usage of the OSNA RD-210 analyser and nucleic acid amplification reagent kit LYNOAMP CK19 E for rapid detection of metastatic nodal involvement, based on the cytokeratin 19 (CK19) mRNA detection. Endometrial cancer patients ≥ 18 years listed for surgical treatment with sentinel lymph node mapping, with no history of other types of cancer and who provide a valid written consent will be considered potentially eligible for the study. However, they will only be enrolled if a successful sentinel lymph node mapping is retrieved. Each node will be processed according to the study protocol and assessed by both OSNA and ultrastaging. DISCUSSION: The accuracy of OSNA (index test) will be assessed against sentinel lymph node histopathological ultrastaging (reference test). This European study has the potential to be the largest study on the use of OSNA in endometrial cancer to date. OSNA could represent a modern diagnostic alternative to sentinel lymph node ultrastaging with the added benefits of standardisation and fast results. TRIAL REGISTRATION: The study was registered in the German Clinical Trial Register - Nr. DRKS00021520, registration date 25th of May 2020, URL of the trial registry record: https://drks.de/search/en/trial/DRKS00021520 .
- Klíčová slova
- Endometrial cancer, OSNA, Sentinel lymph nodes, Ultrastaging,
- MeSH
- biopsie sentinelové lymfatické uzliny metody MeSH
- keratin-19 genetika MeSH
- lidé MeSH
- lymfatické metastázy * diagnóza patologie MeSH
- lymfatické uzliny patologie MeSH
- multicentrické studie jako téma MeSH
- nádory endometria * patologie genetika diagnóza MeSH
- prospektivní studie MeSH
- sentinelová uzlina * patologie MeSH
- staging nádorů MeSH
- techniky amplifikace nukleových kyselin * metody MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- protokol klinické studie MeSH
- Geografické názvy
- Evropa MeSH
- Názvy látek
- keratin-19 MeSH
Gliomas are the most common brain tumor type in children and adolescents. To date, diagnosis and therapy monitoring for these tumors rely on magnetic resonance imaging (MRI) and histopathological as well as molecular analyses of tumor tissue. Recently, liquid biopsies (LB) have emerged as promising tool for diagnosis and longitudinal tumor assessment potentially allowing for a more precise therapeutic management. However, the optimal strategy for monitoring gliomas by LB remains to be determined. In this study, we analyzed circulating tumor DNA (ctDNA) from 78 liquid biopsies (plasma n = 44, cerebrospinal fluid n = 34 (CSF)) of 35 glioma patients, determining H3F3A K28M (K27M) and BRAF V600E mutation allele frequency using droplet digital PCR (ddPCR). All results were correlated to clinically relevant parameters including diagnostic imaging and CSF aspiration site (ventricular vs lumbar) with respect to tumor localization. Regarding diagnostic accuracy, the calculated sensitivity score in the H3F3A K27M cohort was 84.61% for CSF and 73.68% for plasma. In the BRAF V600E cohort, we determined a sensitivity of 83.3% in plasma and 80% in CSF. The overall specificity was 100%. With respect to the CSF aspiration, the intra-operatively obtained CSF demonstrated 100% detection rate, followed by ventricular CSF obtained via Ommaya Reservoir/shunt puncture (93%) and CSF obtained via lumbar puncture (66%). Notably, this further correlated with the proximity of the CSF site to tumor localization. Longitudinal CSF monitoring demonstrated a good correlation to clinical and radiological disease evolution. Importantly, we show for the first time that monitoring BRAF V600E by ddPCR could serve as treatment response assessment in gliomas. In summary, our observation may inform recommendations with regard to location of CSF aspiration when incorporating LB into future treatment protocols.
- Klíčová slova
- CSF sampling site, Droplet digital PCR, Glioma, Liquid biopsy, Longitudinal monitoring, Targeted therapy,
- MeSH
- cirkulující nádorová DNA mozkomíšní mok genetika MeSH
- dítě MeSH
- dospělí MeSH
- gliom * genetika patologie diagnóza MeSH
- histony * genetika MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mutace MeSH
- nádorové biomarkery * genetika mozkomíšní mok MeSH
- nádory mozku * genetika diagnóza patologie MeSH
- předškolní dítě MeSH
- protoonkogenní proteiny B-Raf * genetika MeSH
- tekutá biopsie metody MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- předškolní dítě MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- BRAF protein, human MeSH Prohlížeč
- cirkulující nádorová DNA MeSH
- H3-3A protein, human MeSH Prohlížeč
- histony * MeSH
- nádorové biomarkery * MeSH
- protoonkogenní proteiny B-Raf * MeSH
Most kidney transplant patients who undergo biopsies are classified as having no rejection based on consensus thresholds. However, we hypothesized that because these patients have normal adaptive immune systems, T cell-mediated rejection (TCMR) and antibody-mediated rejection (ABMR) may exist as subthreshold activity in some transplants currently classified as no rejection. To examine this question, we studied genome-wide microarray results from 5086 kidney transplant biopsies (from 4170 patients). An updated molecular archetypal analysis designated 56% of biopsies as no rejection. Subthreshold molecular TCMR and/or ABMR activity molecular activity was detectable as elevated classifier scores in many biopsies classified as no rejection, with ABMR activity in many TCMR biopsies and TCMR activity in many ABMR biopsies. In biopsies classified as no rejection histologically and molecularly, molecular TCMR classifier scores correlated with increases in histologic TCMR features and molecular injury, lower estimated glomerular filtration rate, and higher risk of graft loss, and molecular ABMR activity correlated with increased glomerulitis and donor-specific antibody. No rejection biopsies with high subthreshold TCMR or ABMR activity had a higher probability of having TCMR or ABMR, respectively, diagnosed in a future biopsy. We conclude that many kidney transplant recipients have unrecognized subthreshold TCMR or ABMR activity, with significant implications for future problems.
- Klíčová slova
- ABMR, TCMR, biopsy, gene expression, gradients, kidney transplant, microarray, transplant rejection,
- MeSH
- biopsie MeSH
- dospělí MeSH
- hodnoty glomerulární filtrace MeSH
- isoprotilátky imunologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- následné studie MeSH
- přežívání štěpu imunologie MeSH
- prognóza MeSH
- rejekce štěpu * patologie imunologie etiologie MeSH
- rizikové faktory MeSH
- T-lymfocyty imunologie MeSH
- transplantace ledvin * škodlivé účinky MeSH
- vyšetření funkce ledvin MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- isoprotilátky MeSH
AIM: Transbronchial cryobiopsies are increasingly used for the diagnosis of interstitial lung disease (ILD), but there is a lack of published information on the features of specific ILD in cryobiopsies. Here we attempt to provide pathological guidelines for separating usual interstitial pneumonia (UIP) of idiopathic pulmonary fibrosis (IPF), fibrotic hypersensitivity pneumonitis (FHP) and connective tissue disease-associated ILD (CTD-ILD) in cryobiopsies. METHODS: We examined 120 cryobiopsies from patients with multidisciplinary discussion (MDD)-established CTD-ILD and compared them to a prior series of 121 biopsies from patients with MDD-established IPF or FHP. RESULTS: A non-specific interstitial pneumonia (NSIP) pattern alone was seen in 36 of 120 (30%) CTD-ILD, three of 83 (3.6%) FHP and two of 38 (5.2%) IPF cases, statistically favouring a diagnosis of CTD-ILD. The combination of NSIP + OP was present in 29 of 120 (24%) CTD-ILD, two of 83 (2.4%) FHP and none of 38 (0%) IPF cases, favouring a diagnosis of CTD-ILD. A UIP pattern, defined as fibroblast foci plus any of patchy old fibrosis/fibrosis with architectural distortion/honeycombing, was identified in 28 of 120 (23%) CTD-ILD, 45 of 83 (54%) FHP and 27 of 38 (71%) IPF cases and supported a diagnosis of FHP or IPF. The number of lymphoid aggregates/mm2 and fibroblast foci/mm2 was not different in IPF, CTD-ILD or FHP cases with a UIP pattern. Interstitial giant cells supported a diagnosis of FHP or CTD-ILD over IPF, but were infrequent. CONCLUSIONS: In the correct clinical/radiological context the pathological findings of NSIP, and particularly NSIP plus OP, favour a diagnosis of CTD-ILD in a cryobiopsy, but CTD-ILD with a UIP pattern, FHP with a UIP pattern and IPF generally cannot be distinguished.
- Klíčová slova
- connective tissue disease‐associated interstitial lung disease, cryobiopsy, hypersensitivity pneumonitis, usual interstitial pneumonia,
- MeSH
- biopsie metody MeSH
- dospělí MeSH
- idiopatická plicní fibróza patologie komplikace diagnóza MeSH
- intersticiální plicní nemoci * patologie diagnóza komplikace MeSH
- lidé středního věku MeSH
- lidé MeSH
- nemoci pojiva * komplikace patologie diagnóza MeSH
- plíce patologie 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
The main aim of our study was to investigate the specific contribution of a 9-valent human papillomavirus vaccine (9vHPV) to the recurrence risk of cervical intraepithelial neoplasia grade 2 or worse (CIN2+) in women vaccinated post-excision. Therefore, we conducted a retrospective monocentric cohort study in women aged 22-49 years undergoing conization between 2014 and 2023. The 9vHPV-vaccinated women were matched to unvaccinated women for age and follow-up duration in a 1:2 ratio to eliminate allocation bias. The risk of CIN2+ recurrence was estimated by the incidence rate ratio using Poisson regression with adjustment for comorbidities, smoking status, nulliparity, CIN grade, positive cone margin, and HPV genotypes. The CIN2+ recurrence rates in 147 women enrolled in the analysis were 18 and 2 cases per 100,000 person-days for unvaccinated and vaccinated women, respectively, during a mean follow-up period of 30 months (±22 months). A reduction in CIN2+ recurrences by 90% (95% confidence interval: 12-99%) was documented in 9vHPV-vaccinated participants compared to women undergoing only surgical excision. Moreover, vaccinated women with a positive cone margin showed a 42% (though non-significant) reduction in relapse (p = .661). Full post-conization vaccination with the 9vHPV contributed to an additional reduction in the risk of CIN2+ recurrence. This finding is consistent with current knowledge and suggests a high adjuvant effect of the 9vHPV vaccine.
- Klíčová slova
- Human papillomavirus, cervical intraepithelial neoplasia, conization, recurrence reduction, vaccination,
- MeSH
- dospělí MeSH
- dysplazie děložního hrdla * prevence a kontrola virologie MeSH
- infekce papilomavirem * prevence a kontrola MeSH
- konizace děložního čípku metody MeSH
- lidé středního věku MeSH
- lidé MeSH
- lokální recidiva nádoru * prevence a kontrola MeSH
- mladý dospělý MeSH
- nádory děložního čípku * prevence a kontrola virologie MeSH
- retrospektivní studie MeSH
- vakcinace MeSH
- vakcíny proti papilomavirům * aplikace a dávkování imunologie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- vakcíny proti papilomavirům * MeSH
BACKGROUND: Idiopathic normal pressure hydrocephalus (iNPH) is a progressive disease characterized by disproportionate ventricular enlargement at brain imaging with gait disturbance and an increased risk of falling. Gait assessment is a key feature in the diagnosis of iNPH and characterization of post-surgical outcomes. RESEARCH QUESTION: How do gait parameters change 24 h after CSF tap test (CSFTT) and after ventriculoperitoneal shunt surgery? METHODS: The PRISMA guidelines were used to perform the systematic review. We conducted a search of the following electronic databases: PubMed, Medline, Web of Science and EBSCO. We included studies focusing on gait changes occurring 24 h after a CSFTT or after ventriculoperitoneal shunt surgery in patients with iNPH. All articles were assessed for methodological quality using an adapted version of The Standard Quality Assessment Criteria for Evaluating Primary Research Papers checklist. RESULTS: Twenty-seven studies were included in the systematic review. Studies were highly heterogeneous due to lack of standardization of CSFTT or shunt surgery methodology, with varying amounts of CSF removed during the tap test (20-50 ml) and varying time of outcome assessment after shunt surgery. Dynamic equilibrium measurements are generally used to assess preoperative levels of cardinal symptoms and postoperative outcomes in iNPH. The most sensitive spatio-temporal parameter assessed 24 h after CSFTT was self-selected walking speed followed by stride length, which increased significantly. Cadence is hence not suitable to consider in the evaluation of effect of CSFTT and shunt surgery. Changes in balance-related gait parameters after CSFTT and shunt surgery are still a controversial area of research. CONCLUSION: Gait assessment is a key feature in the diagnosis of iNPH and characterization of post-surgical outcomes. Dynamic equilibrium measurements are generally used to assess preoperative levels of cardinal symptoms and postoperative outcomes in iNPH, but quantitative and standardized gait analysis procedures are missing. Changes in balance-related gait parameters after CSFTT might be useful in deciding whether to perform shunt surgery in iNPH patients who hope for improvement in gait ability. The dual-task paradigm after CSFTT could improve the clinical evaluation of higher level frontal gait disturbances in patients with suspected iNPH before shunting.
- Klíčová slova
- CSF tap test, Gait analysis, Hydrocephalus, Shunt,
- MeSH
- chůze (způsob) * fyziologie MeSH
- lidé MeSH
- normotenzní hydrocefalus * chirurgie patofyziologie mozkomíšní mok diagnóza MeSH
- shunty pro odvod mozkomíšního moku MeSH
- spinální punkce metody MeSH
- ventrikuloperitoneální zkrat MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- systematický přehled MeSH
BACKGROUND: Systematic biopsy (SB) combined with magnetic resonance imaging (MRI)-targeted biopsy is still recommended considering the risk of missing clinically significant prostate cancer (csPCa). OBJECTIVE: To evaluate the added value in csPCa detection on side-specific SB relative to MRI lesion and to externally validate the Noujeim risk stratification model that predicts the risk of csPCa on distant SB cores relative to the index MRI lesion. DESIGN, SETTING, AND PARTICIPANTS: Overall, 4841 consecutive patients diagnosed by MRI-targeted biopsy and SB for Prostate Imaging Reporting and Data System score ≥3 lesions were identified from a prospectively maintained database between January 2016 and April 2023 at 15 European referral centers. A total of 2387 patients met the inclusion criteria and were included in the analysis. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: McNemar's test was used to compare the csPCa detection rate between several biopsy strategies including MRI-targeted biopsy, side-specific SB, and a combination of both. Model performance was evaluated in terms of discrimination using area under the receiver operation characteristic curve (AUC), calibration plots, and decision curve analysis. Clinically significant prostate cancer was defined as International Society of Urological Pathology grade group ≥2. RESULTS AND LIMITATIONS: Overall, the csPCa detection rate was 49%. Considering MRI-targeted biopsy as reference, the added values in terms of csPCa detection were 5.8% (relative increase of 13%), 4.2% (relative increase of 9.8%), and 2.8% (relative increase of 6.1%) for SB, ipsilateral SB, and contralateral SB, respectively. Only 35 patients (1.5%) exclusively had csPCa on contralateral SB (p < 0.001). Considering patients with csPCa on MRI-targeted biopsy and ipsilateral SB, the upgrading rate was 2% (20/961) using contralateral SB (p < 0.001). The Noujeim model exhibited modest performance (AUC of 0.63) when tested using our validation set. CONCLUSIONS: The added value of contralateral SB was negligible in terms of cancer detection and upgrading rates. The Noujeim model could be included in the decision-making process regarding the appropriate prostate biopsy strategy. PATIENT SUMMARY: In the present study, we collected a set of patients who underwent magnetic resonance imaging (MRI)-targeted and systematic biopsies for the detection of prostate cancer. We found that biopsies taken at the opposite side of the MRI suspicious lesion have a negligible impact on cancer detection. We also validate a risk stratification model that predicts the risk of cancer on biopsies beyond 10 mm from the initial lesion, which could be used in daily practice to improve the personalization of the prostate biopsy.
- Klíčová slova
- Cancer detection, Magnetic resonance imaging–targeted biopsy, Prostate cancer, Systematic biopsy,
- MeSH
- lidé středního věku MeSH
- lidé MeSH
- magnetická rezonanční tomografie * metody MeSH
- nádory prostaty * patologie diagnostické zobrazování MeSH
- prostata * patologie diagnostické zobrazování MeSH
- senioři MeSH
- ultrazvukem navigovaná biopsie * metody MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH