• MeSH
• biomedicínský výzkum MeSH
• dechová terapie metody   MeSH
• dospělí MeSH
• ionizace vzduchu metody   přístrojové vybavení   MeSH
• ionty aplikace a dávkování   terapeutické užití   MeSH
• lidé MeSH
• obstrukční plicní nemoci terapie   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH

• MeSH
• zavedení chirurgických vývodů MeSH
• Publikační typ
• periodika MeSH
• populární práce MeSH

• Konspekt
• Sociologie
• NLK Obory
• zdravotně postižení

• MeSH
• poruchy močení MeSH
• Publikační typ
• periodika MeSH
• populární práce MeSH

• Konspekt
• Patologie. Klinická medicína
• NLK Obory
• urologie

Regulatory T cells (Tregs) play a critical role in the maintenance of a pregnancy. While the kinetics of the number of peripheral blood Tregs has been satisfactorily described in mouse models, analysis of these cell populations in human pregnancy is complicated by high variability in the quantity of Tregs and inconsistencies in the markers used for detecting different types of Treg. In the light of this, we set out to investigate the kinetics of various types of Treg, including CD45RA, GARP and PD-1(+) Tregs, in the peripheral blood of pregnant women in the first, second and third trimester, and at the time of delivery. Tregs, defined as a CD4(+)CD25(++)CD127(dim)Foxp3(+) population of leucocytes, were detected using flow cytometry. Natural thymus-derived Tregs and induced Tregs in the peripheral blood were distinguished by the expression or absence of a Helios marker, respectively. Our results showed that during normal pregnancy the sizes of various Treg subpopulations varied across women and also in an individual woman did not remain constant but varied significantly, most notable being the decrease observed at the time of delivery. Helios(-) cells were significantly less frequent in the peripheral blood of healthy pregnant women than Helios(+) cells, and the majority of Tregs were Helios(+)PD-1(+) Tregs.

• MeSH
• buněčná diferenciace MeSH
• forkhead transkripční faktory metabolismus   MeSH
• imunofenotypizace MeSH
• kultivované buňky MeSH
• lidé MeSH
• počet lymfocytů MeSH
• průtoková cytometrie MeSH
• regulační T-lymfocyty imunologie   MeSH
• T-lymfocyty - podskupiny imunologie   MeSH
• těhotenství imunologie   MeSH
• thymus imunologie   MeSH
• transformující růstový faktor beta krev   MeSH
• transkripční faktor Ikaros metabolismus   MeSH
• zdraví dobrovolníci pro lékařské studie MeSH
• Check Tag
• lidé MeSH
• těhotenství imunologie   MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

• MeSH
• infračervené záření MeSH
• terapie ultrafialovými paprsky MeSH
• terapie MeSH
• ultrafialové záření MeSH
• zdravotnické prostředky MeSH
• Publikační typ
• ceníky MeSH

• Konspekt
• Patologie. Klinická medicína
• NLK Obory
• terapie
• technika lékařská, zdravotnický materiál a protetika
• NLK Publikační typ
• informační publikace
• návody

• MeSH
• bronchiální astma terapie   MeSH
• lázně dějiny   MeSH

PURPOSE: Syndrome diGeorge is associated amongst other clinical signs with various degrees of thymic dysplasia, related immunodeficiency and autoimmune disorders. Helios, a transcription factor from Ikaros family, has been proposed as a marker for thymus derived Tregs. We therefore examined Helios + Tregs in a cohort of patients with genetically proven diGeorge syndrome with typical T cell lymphopenia due to the thymic pathology. METHODS: T cells, FoxP3+ Tregs and Helios + FoxP3+ Tregs were examined in 52 samples from 37 patients. One patient with diGeorge/CHARGE syndrome with total thymic aplasia was also included. Statistical analysis was performed using a linear regression comparison. RESULTS: Total absolute Tregs were significantly lower in diGeorge patients as compared to controls in all age groups (0-20 years) (p = 0.0016). The difference was more expressed in the first four years of age. Relative Treg numbers expressed as the percentage of Tregs in CD4+ T-cells, however, were not different in patients and controls in all age groups (p = 0.661), neither could we find any significant difference in the percentage of Helios + Tregs between patients and controls (p = 0.238). Helios + Tregs were still present in a patient with diGeorge/CHARGE syndrome with complete athymia 7 years after partially matched unrelated repeated T lymphocytes infusions. CONCLUSION: Our findings show that while there was a significant decrease in absolute numbers of Tregs in patients with diGeorge syndrome, the relative percentage of this population did not differ between patients and controls. Low absolute Tregs thus reflected typical T cells lymphopenia in patients. Helios expression was not affected in diGeorge syndrome.

• MeSH
• biologické markery metabolismus   MeSH
• DiGeorgeův syndrom imunologie   MeSH
• dítě MeSH
• dospělí MeSH
• forkhead transkripční faktory metabolismus   MeSH
• kohortové studie MeSH
• kojenec MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• novorozenec MeSH
• počet buněk MeSH
• předškolní dítě MeSH
• regulační T-lymfocyty imunologie   MeSH
• thymus imunologie   patologie   MeSH
• transkripční faktor Ikaros genetika   metabolismus   MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• kojenec MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• novorozenec MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

• MeSH
• antihypertenziva MeSH
• diuretika MeSH
• hypertenze farmakoterapie   MeSH
• indapamid farmakologie   MeSH
• Publikační typ
• kongresy MeSH

• Konspekt
• Patologie. Klinická medicína
• NLK Obory
• angiologie
• farmakoterapie

We report follow-up results from the randomized, placebo-controlled, phase 3 HELIOS trial of ibrutinib+bendamustine and rituximab (BR) for previously treated chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) without deletion 17p. Overall, 578 patients were randomized 1:1 to either ibrutinib (420 mg daily) or placebo, in combination with 6 cycles of BR, followed by ibrutinib or placebo alone. Median follow-up was 34.8 months (range: 0.1-45.8). Investigator-assessed median progression-free survival (PFS) was not reached for ibrutinib+BR, versus 14.3 months for placebo+BR (hazard ratio [HR] [95% CI], 0.206 [0.159-0.265]; P < 0.0001); 36-month PFS rates were 68.0% versus 13.9%, respectively. The results are consistent with the primary analysis findings (HR = 0.203, as assessed by independent review committee, with 17-month median follow-up). Median overall survival was not reached in either arm; HR (95% CI) for ibrutinib+BR versus placebo: 0.652 (0.454-0.935; P = 0.019). Minimal residual disease (MRD)-negative response rates were 26.3% for ibrutinib+BR and 6.2% for placebo+BR (P < 0.0001). Incidence of treatment-emergent adverse events (including grades 3-4) were generally consistent with the initial HELIOS report. These long-term data support improved survival outcomes and deepening responses with ibrutinib+BR compared with BR in relapsed CLL/SLL.

• MeSH
• bendamustin hydrochlorid aplikace a dávkování   MeSH
• chronická lymfatická leukemie farmakoterapie   patologie   MeSH
• dospělí MeSH
• dvojitá slepá metoda MeSH
• lidé středního věku MeSH
• lidé MeSH
• míra přežití MeSH
• mladiství MeSH
• mladý dospělý MeSH
• následné studie MeSH
• prognóza MeSH
• protokoly protinádorové kombinované chemoterapie terapeutické užití   MeSH
• pyrazoly aplikace a dávkování   MeSH
• pyrimidiny aplikace a dávkování   MeSH
• rituximab aplikace a dávkování   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze III MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH

We report final analysis outcomes from the phase 3 HELIOS study (NCT01611090). Patients with relapsed/refractory chronic lymphocytic leukemia/small lymphocytic lymphoma without deletion 17p (n = 578) were randomized 1:1 to 420 mg daily ibrutinib or placebo plus ≤6 cycles of bendamustine plus rituximab (BR), followed by ibrutinib or placebo alone. Median follow-up was 63.7 months. Median investigator-assessed progression-free survival was longer with ibrutinib plus BR (65.1 months) than placebo plus BR (14.3 months; hazard ratio [HR] 0.229 [95% confidence interval (CI) 0.183-0.286]; p < .0001). Despite crossover of 63.3% of patients from the placebo plus BR arm to ibrutinib treatment upon disease progression, ibrutinib plus BR versus placebo plus BR demonstrated an overall survival benefit (HR 0.611 [95% CI 0.455-0.822]; p = .0010; median not reached in either arm). Long-term follow-up data confirm the survival benefit of ibrutinib plus BR over BR alone. Safety profiles were consistent with those known for ibrutinib and BR.

• MeSH
• adenin analogy a deriváty   MeSH
• bendamustin hydrochlorid terapeutické užití   MeSH
• chronická lymfatická leukemie * farmakoterapie   MeSH
• lidé MeSH
• piperidiny MeSH
• protokoly protinádorové kombinované chemoterapie škodlivé účinky   MeSH
• rituximab terapeutické užití   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze III MeSH
• randomizované kontrolované studie MeSH