The adaptive immune system is involved in tumor establishment and aggressiveness. Tumors of the ovaries, an immune-privileged organ, spread via transceolomic routes and rarely to distant organs. This is contrary to tumors of non-immune privileged organs, which often disseminate hematogenously to distant organs. Epigenetics-based immune cell quantification allows direct comparison of the immune status in benign and malignant tissues and in blood. Here, we introduce the "cellular ratio of immune tolerance" (immunoCRIT) as defined by the ratio of regulatory T cells to total T lymphocytes. The immunoCRIT was analyzed on 273 benign tissue samples of colorectal, bronchial, renal and ovarian origin as well as in 808 samples from primary colorectal, bronchial, mammary and ovarian cancers. ImmunoCRIT is strongly increased in all cancerous tissues and gradually augmented strictly dependent on tumor aggressiveness. In peripheral blood of ovarian cancer patients, immunoCRIT incrementally increases from primary diagnosis to disease recurrence, at which distant metastases frequently occur. We postulate that non-pathological immunoCRIT values observed in peripheral blood of immune privileged ovarian tumor patients are sufficient to prevent hematogenous spread at primary diagnosis. Contrarily, non-immune privileged tumors establish high immunoCRIT in an immunological environment equivalent to the bloodstream and thus spread hematogenously to distant organs. In summary, our data suggest that the immunoCRIT is a powerful marker for tumor aggressiveness and disease dissemination.

• MeSH
• dospělí MeSH
• epigeneze genetická MeSH
• imunologická tolerance * MeSH
• kolorektální nádory imunologie   patologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• metastázy nádorů MeSH
• mladý dospělý MeSH
• nádorové biomarkery imunologie   MeSH
• nádory ledvin imunologie   patologie   MeSH
• nádory plic imunologie   patologie   MeSH
• nádory prsu imunologie   patologie   MeSH
• nádory vaječníků imunologie   patologie   MeSH
• nádory imunologie   patologie   MeSH
• senioři MeSH
• studie případů a kontrol MeSH
• T-lymfocyty imunologie   patologie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND: Long-term outcomes following percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) might be changing because of improved techniques and better medical therapy. This final prespecified analysis of the Fractional Flow Reserve (FFR) versus Angiography for Multivessel Evaluation (FAME) 3 trial aimed to reassess their comparative effectiveness at 5 years. METHODS: FAME 3 was a multicentre, randomised trial comparing FFR-guided PCI using current-generation zotarolimus-eluting stents versus CABG in patients with three-vessel coronary artery disease not involving the left main coronary artery. 48 hospitals in Europe, USA and Canada, Australia, and Asia participated in the trial. Patients (aged ≥21 years with no cardiogenic shock, no recent ST segment elevation myocardial infarction, no severe left ventricular dysfunction, and no previous CABG) were randomly assigned to either PCI or CABG using a web-based system. At 1 year, FFR-guided PCI did not meet the prespecified threshold for non-inferiority for the outcome of death, stroke, myocardial infarction, or repeat revascularisation versus CABG. The primary endpoint for this intention-to-treat analysis was the 5-year incidence of the prespecified composite outcome of death, stroke, or myocardial infarction. The trial was registered at ClinicalTrials.gov, NCT02100722, and is completed; this is the final report. FINDINGS: Between Aug 25, 2014 and Nov 28, 2019, 757 of 1500 participants were assigned to PCI and 743 to CABG. 5-year follow-up was achieved in 724 (96%) patients assigned to PCI and 696 (94%) assigned to CABG. At 5 years, there was no significant difference in the composite of death, stroke, or myocardial infarction between the two groups, with 119 (16%) events in the PCI group and 101 (14%) in the CABG group (hazard ratio 1·16 [95% CI 0·89-1·52]; p=0·27). There were no differences in the rates of death (53 [7%] vs 51 [7%]; 0·99 [0·67-1·46]) or stroke (14 [2%] vs 21 [3%], 0·65 [0·33-1·28]), but myocardial infarction was higher in the PCI group than in the CABG group (60 [8%] vs 38 [5%], 1·57 [1·04-2·36]), as was repeat revascularisation (112 [16%] vs 55 [8%], 2·02 [1·46-2·79]). INTERPRETATION: At the 5-year follow-up, there was no significant difference in a composite outcome of death, stroke, or myocardial infarction after FFR-guided PCI versus CABG, although myocardial infarction and repeat revascularisation were higher with PCI. These results provide contemporary evidence to allow improved shared decision making between physicians and patients. FUNDING: Medtronic and Abbott Vascular.

• MeSH
• frakční průtoková rezerva myokardu * MeSH
• infarkt myokardu epidemiologie   MeSH
• koronární angiografie MeSH
• koronární angioplastika * metody   MeSH
• koronární bypass * metody   MeSH
• lidé středního věku MeSH
• lidé MeSH
• následné studie MeSH
• nemoci koronárních tepen * chirurgie   mortalita   MeSH
• senioři MeSH
• sirolimus analogy a deriváty   aplikace a dávkování   MeSH
• stenty uvolňující léky 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
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH
• srovnávací studie MeSH

The last decade has seen a sharp increase in the number of scientific publications describing physiological and pathological functions of extracellular vesicles (EVs), a collective term covering various subtypes of cell-released, membranous structures, called exosomes, microvesicles, microparticles, ectosomes, oncosomes, apoptotic bodies, and many other names. However, specific issues arise when working with these entities, whose size and amount often make them difficult to obtain as relatively pure preparations, and to characterize properly. The International Society for Extracellular Vesicles (ISEV) proposed Minimal Information for Studies of Extracellular Vesicles ("MISEV") guidelines for the field in 2014. We now update these "MISEV2014" guidelines based on evolution of the collective knowledge in the last four years. An important point to consider is that ascribing a specific function to EVs in general, or to subtypes of EVs, requires reporting of specific information beyond mere description of function in a crude, potentially contaminated, and heterogeneous preparation. For example, claims that exosomes are endowed with exquisite and specific activities remain difficult to support experimentally, given our still limited knowledge of their specific molecular machineries of biogenesis and release, as compared with other biophysically similar EVs. The MISEV2018 guidelines include tables and outlines of suggested protocols and steps to follow to document specific EV-associated functional activities. Finally, a checklist is provided with summaries of key points.

• Publikační typ
• časopisecké články MeSH

• MeSH
• duševně nemocní MeSH
• psychiatrie MeSH
• zodpovědnost duševně nemocného MeSH
• Publikační typ
• monografie MeSH

• Konspekt
• Psychiatrie
• NLK Obory
• psychiatrie