Gastric cancer is a common oncological disease. Although enormous efforts have been expended, possible therapeutic modalities are still limited. For this reason, new therapeutic approaches and agents are highly requested and intensively developed. One strategy is the application of natural agents, such as curcumin, with proven anticancer effects and low toxicity for patients. Therefore, this review discusses the potential application of curcumin in the therapy of gastric cancer and its potential incorporation in therapeutic regimens. Because one of the largest impediments for widespread curcumin application is its limited bioavailability (caused mainly by its very low water solubility), studied strategies (drug delivery systems and curcumin derivatization) aimed to solve this obstacle are discussed in more detail.

• MeSH
• biologické modely MeSH
• kurkumin chemie   terapeutické užití   MeSH
• lékové transportní systémy MeSH
• lidé MeSH
• nádory žaludku farmakoterapie   MeSH
• výsledek terapie MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

OBJECTIVES: This study aimed to quantify the impact of donor variables on post-heart transplantation mortality and morbidity in recipients with and without a pretransplant left ventricular assist device (LVAD). METHODS: This is a prospective cohort study of the ISHLT Transplant Registry that includes all primary heart transplants in adult recipients (January 2005-June 2013, n = 15 532). All recipients were divided into patients with a durable continuous-flow LVAD (LVAD recipient, n = 3315) and without mechanical support (standard recipient, n = 12 217). Donors were classified as high risk (n = 3751) and low risk (n = 11 781). Transplants were categorized into low-risk donor/standard recipient (n = 9214), high-risk donor/standard recipient (n = 3003), low-risk donor/LVAD recipient (n = 2567) and high-risk donor/LVAD recipient (n = 748). Outcomes prior to discharge, survival at 5 years and freedom from complications were computed for each group. RESULTS: LVAD recipients experienced more episodes of infection, stroke and acute rejection with both low- (P < 0.001, P < 0.001, P < 0.001) and high-risk donors (P < 0.001, P = 0.008, P = 0.028) prior to transplant discharge. Within standard recipients, a higher rate of primary graft failure (P = 0.035), infection (P = 0.001), dialysis (P = 0.012), acute rejection (P = 0.037) and less freedom from cardiac allograft vasculopathy (P < 0.001) and malignancy (P = 0.004) was observed with high-risk donors. Within LVAD recipients, no differences in complications prior to discharge or long-term morbidity were detected between low- and high-risk donors. When compared to standard recipient/low-risk donors, all the 3 remaining categories had an increased probability of death or graft failure within 90 days: LVAD recipient/low-risk donor [hazard ratio (HR) 1.26, confidence interval (CI) 1.05-1.51; P = 0.012], standard recipient/high-risk donor (HR 1.47, CI 1.27-1.71; P < 0.001) and LVAD recipient/high-risk donor (HR 1.72, CI 1.32-2.24; P < 0.001). Between 90 days and 5 years, only standard recipient/high-risk donor had an increased probability of death or graft failure (HR 1.140, CI 1.020-1.274; P = 0.021) when compared to standard recipient/low-risk donor. CONCLUSIONS: LVAD recipients, whether with high- or low-risk donors, have worse early (but not late) survival and more early complications than those of standard recipients. We found that adverse donor characteristics are less predictive for determining the outcome of LVAD-bridged recipients than standard recipients.

• MeSH
• dárci tkání statistika a číselné údaje   MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• míra přežití trendy   MeSH
• mladý dospělý MeSH
• nemoci srdce chirurgie   MeSH
• podpůrné srdeční systémy * MeSH
• příjemce transplantátu * MeSH
• prospektivní studie MeSH
• registrace * MeSH
• transplantace srdce metody   mortalita   MeSH
• výběr dárců MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Evropa MeSH
• Spojené státy americké MeSH

Filamentous ascomycetes (Neurospora and Monascus) have been studied for a long time because of their production of secondary metabolites such as microbial pigments. The ascomycetes represent an interesting group of compounds with high potential for medicinal applications. Many recent studies have shown their efficacy in the treatment of serious pathological states such as oncological diseases, neurodegenerative diseases and hyperlipidaemia. Nevertheless, the clinical usability of ascomycetes is still limited. However, this problem can be solved by the use of these compounds with combinations of other therapeutic agents. This strategy can suppress their side effects and improve their therapeutic efficacy. Moreover, their co-application can significantly enhance conventional therapies that are used. This review summarizes and discusses the general principles of this approach, introduced and supported by numerous examples. In addition, the prediction of the future potential application of this methodology is included.

• MeSH
• Ascomycota chemie   metabolismus   MeSH
• biologické pigmenty metabolismus   terapeutické užití   MeSH
• kombinovaná farmakoterapie MeSH
• lidé MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

The study objective is to quantify the impact of donor and recipient variables on heart transplant survival in recipients with a significant proportion of implanted continuous-flow left ventricular assist devices (LVADs). This is a prospective cohort study of International Society for Heart and Lung Transplantation (ISHLT) Registry that includes all primary heart-alone transplants in adult recipients (January 2005 and June 2013, N = 15 532, 27% LVADs). Donor and recipient characteristics were assessed for association with death or graft failure within 90 days and between 90 days and 5 years after transplantation. On Cox proportional hazard model donor cause of death other than head trauma (hazard ratio [HR] 1.985, P < 0.0001), recipient congenital (HR 2.7555, P < 0.0001) and ischemic (HR 1.165, P = 0.0383) vs dilated etiology and female donor heart transplanted into male recipient (HR 1.207, P = 0.0354) were predictors of death or graft failure within 90 days. Between 90 days and 5 years, donor cigarette use (HR 1.232, P = 0.0001), recipient cigarette use (HR 1.193, P = 0.0003), diabetes (HR 1.159, P = 0.0050), arterial hypertension (HR 1.129, P = 0.0115), and ischemic vs dilative cardiomyopathy had an increased probability of death or graft failure.

• MeSH
• dárci tkání zásobování a distribuce   MeSH
• dospělí MeSH
• faktorová analýza statistická MeSH
• hodnocení rizik metody   MeSH
• lidé středního věku MeSH
• lidé MeSH
• míra přežití MeSH
• mladý dospělý MeSH
• následné studie MeSH
• podpůrné srdeční systémy statistika a číselné údaje   MeSH
• pooperační komplikace mortalita   MeSH
• přežívání štěpu MeSH
• příjemce transplantátu statistika a číselné údaje   MeSH
• prognóza MeSH
• prospektivní studie MeSH
• rejekce štěpu mortalita   MeSH
• rizikové faktory MeSH
• transplantace srdce mortalita   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

OBJECTIVES: Antibodies targeting angiotensin II type 1 receptor (AT1R) have been associated with malignant hypertension, autoimmune diseases and acute rejection and graft loss in solid organ transplantation. The aim of our study was to assess the impact of anti-AT1R antibodies on survival and incidence of acute cellular rejection (ACR) and pathology antibody-mediated rejection (pAMR) in a population of heart transplant recipients who were bridged to transplantation with a durable mechanical assist device Heart Mate II. METHODS: Sera of 69 consecutive heart transplant recipients transplanted between October 2008 and August 2014 were tested for the presence of angiotensin II type 1 receptor antibodies before Heart Mate II device implantation and at the time of transplantation. Overall survival and post-transplant rejection-free survival were compared between antibody-negative and antibody-positive recipients using Kaplan-Meier and log-rank tests. RESULTS: Anti-AT1R antibodies were present in 8 patients (11.6%) before Heart Mate II implantation. During the left ventricular assist device (LVAD) bridging, 44 patients (63.8%) who were initially anti-AT1R antibody-negative became positive, leaving 17 (24.6%) anti-AT1R antibody-negative patients at the time of transplantation for all comparisons. One- and 5-year survival was 88 ± 8 and 76 ± 10% for anti-AT1R antibody-negative and 87 ± 5 and 81 ± 7% for anti-AT1R antibody-positive patients, respectively (P = 0.582). Freedom from ACR at 1 year was 68 ± 12% for anti-AT1R-negative and 75 ± 6% for anti-AT1R-positive recipients (P = 0.218). None of the anti-AT1R-negative patients developed AMR 1 year post-transplantation, whereas freedom from pAMR in anti-AT1R-positive recipients was 98 ± 2% (P = 0.198). CONCLUSIONS: Our data showed no difference in the overall post-heart transplant survival and freedom from acute cellular and antibody-mediated rejection between anti-AT1R-negative and anti-AT1R-positive recipients. Further research is needed to assess the role of anti-AT1R antibodies in the risk stratification of LVAD-bridged recipients on the post-heart transplantation outcomes.

• MeSH
• akutní nemoc MeSH
• autoprotilátky krev   MeSH
• buněčná imunita MeSH
• časové faktory MeSH
• dospělí MeSH
• humorální imunita MeSH
• Kaplanův-Meierův odhad MeSH
• lidé středního věku MeSH
• lidé MeSH
• podpůrné srdeční systémy * MeSH
• přežívání štěpu MeSH
• receptor angiotensinu typ 1 imunologie   MeSH
• rejekce štěpu imunologie   MeSH
• retrospektivní studie MeSH
• rizikové faktory MeSH
• srdeční selhání krev   diagnóza   imunologie   chirurgie   terapie   MeSH
• transplantace srdce * škodlivé účinky   mortalita   MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• pozorovací studie MeSH

Primary graft dysfunction (PGD) is a life-threatening complication among heart transplant recipients and a major cause of early mortality. Although the pathogenesis of PGD is still unclear, ischemia/reperfusion injury has been identified as a predominant factor. Both necrosis and apoptosis contribute to the loss of cardiomyocytes during ischemia/reperfusion injury, and this loss of cells can ultimately lead to PGD. The aim of our prospective study was to find out whether cell death, necrosis and apoptosis markers present in the donor myocardium can predict PGD. The prospective study involved 64 consecutive patients who underwent orthotopic heart transplantation at our institute between September 2010 and January 2013. High-sensitive cardiac troponin T (hs-cTnT) as a marker of minor myocardial necrosis was detected from arterial blood samples before the donor's pericardium was opened. Apoptosis (caspase-3, active + pro-caspase-3, bcl-2, TUNEL) was assessed from bioptic samples taken from the right ventricle prior graft harvesting. In our study, 14 % of transplant recipients developed PGD classified according to the standardized definition proposed by the ISHLT Working Group. We did not find differences between the groups in regard to hs-cTnT serum levels. The mean hs-cTnT value for the PGD group was 57.4+/-22.9 ng/l, compared to 68.4+/-10.8 ng/l in the group without PGD. The presence and severity of apoptosis in grafted hearts did not differ between grafts without PGD and hearts that subsequently developed PGD. In conclusion, our findings did not demonstrate any association between measured myocardial cell death, necrosis or apoptosis markers in donor myocardium and PGD in allograft recipients. More detailed investigations of cell death signaling pathways in transplanted hearts are required.

• MeSH
• apoptóza fyziologie   MeSH
• dárci tkání * MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• myokard metabolismus   patologie   MeSH
• nekróza diagnóza   metabolismus   MeSH
• prediktivní hodnota testů MeSH
• primární dysfunkce štěpu diagnóza   metabolismus   MeSH
• prospektivní studie MeSH
• transplantace srdce škodlivé účinky   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Solid-phase assays (SPA) have facilitated detection and definition of antibodies to human leukocyte antigens (HLA) and major histocompatibility complex class I chain-related antigen A (MICA). However, clinical consequences of pretransplant SPA results in heart transplantation have been studied insufficiently in the current era of immunosuppression and rejection surveillance. Pretransplant sera, panel-reactive antibodies (PRA), pretransplant crossmatch, and clinical data were retrospectively analyzed in 264 adult heart transplant recipients. The specificity of HLA and MICA antibodies and C1q-binding activity of donor-specific antibodies (DSA) were defined using SPA. Pretransplant HLA antibodies were detected in 57 (22%) individuals, in 28 individuals (11%); these antibodies were DSA after transplant. Preformed DSA and elevated peak PRA were independent predictors of pathologic AMR, which occurred in 19 individuals (7%). The increasing number of DSA and the cumulative mean fluorescence intensity of DSA were associated with AMR. C1q-binding assay was a suboptimal predictor of AMR in our cohort. Pretransplant allosensitization and MICA antibodies were related neither to impaired graft survival nor to other adverse clinical events during a median follow-up of 39 months. Identification of preformed DSA by SPA, in addition to PRA monitoring, may predict AMR in the contemporary era of heart transplantation.

• MeSH
• analýza rozptylu MeSH
• dospělí MeSH
• HLA antigeny krev   imunologie   MeSH
• hodnocení rizik MeSH
• homologní transplantace škodlivé účinky   metody   MeSH
• imunizace metody   MeSH
• imunologická tolerance fyziologie   MeSH
• imunosupresivní léčba metody   MeSH
• Kaplanův-Meierův odhad MeSH
• kohortové studie MeSH
• lidé středního věku MeSH
• lidé MeSH
• míra přežití MeSH
• následné studie MeSH
• prediktivní hodnota testů MeSH
• předoperační péče metody   MeSH
• přežívání štěpu imunologie   MeSH
• proporcionální rizikové modely MeSH
• rejekce štěpu imunologie   MeSH
• retrospektivní studie MeSH
• ROC křivka MeSH
• rozdělení chí kvadrát MeSH
• specificita protilátek MeSH
• testování histokompatibility MeSH
• transplantace srdce škodlivé účinky   metody   mortalita   MeSH
• transplantační imunologie fyziologie   MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• srovnávací studie MeSH

AIMS: One of the proposed limitations of left ventricular assist device (LVAD) therapy is high degree of sensitization. Apart from human leukocyte antigen (HLA), antibodies against Angiotensin II Type 1 Receptor (AT1R) have been associated with adverse outcomes. The purpose of this study was to compare complications and survival of anti - AT1R positive versus negative Heart Mate II (HMII) recipients. METHODS: Altogether 96 patients received HMII at our institution between 2008 and 2012. These were stratified into three groups: antibody positive before implantation (AT1R+), antibody conversion during support (AT1R-/+) and patients who remained antibody negative (AT1R-). Survival, major on-device adverse events and post-transplant rejections were assessed with Kaplan-Meier and log-rank tests. RESULTS: Two year on-device and overall survival was 78 ± 12% and 75 ± 10% in AT1R-, 60 ± 23% and 60 ± 15% in AT1R+ and 92 ± 6% and 87 ± 5% in AT1R-/+ group (P = 0.409, P = 0.185). Freedom from major adverse event at two years for AT1R-, AT1R+ and AT1R-/+ was 49 ± 14%, 53 ± 16% and 41 ± 11% (P = 0.875). Freedom from rejection was 63 ± 17% in patients who were both anti-AT1R and HLA negative and 65 ± 13% in those who were antibody positive (P = 0.788). CONCLUSION: Patients who were anti-AT1R antibody positive had similar on-device survival and rate of complications in comparison to those who were antibody negative. In transplanted patients, there were no differences in the overall survival and rejection between the groups.

• MeSH
• dospělí MeSH
• HLA antigeny imunologie   MeSH
• infekce spojené s protézou etiologie   mortalita   MeSH
• lidé středního věku MeSH
• lidé MeSH
• nemoci nervového systému etiologie   mortalita   MeSH
• podpůrné srdeční systémy škodlivé účinky   MeSH
• pooperační krvácení etiologie   MeSH
• protilátky metabolismus   MeSH
• receptor angiotensinu typ 1 imunologie   MeSH
• rejekce štěpu imunologie   MeSH
• selhání protézy MeSH
• srdeční selhání imunologie   mortalita   terapie   MeSH
• transplantace srdce mortalita   MeSH
• transplantační imunologie imunologie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• pozorovací studie MeSH

OBJECTIVES: Second-generation axial-flow left ventricular assist devices (LVADs) have become an established therapy in bridging end-stage heart failure patients to cardiac transplantation. Despite the proven clinical success of these devices, some patients develop right ventricular (RV) failure after LVAD implantation. We sought to determine post-heart transplantation outcomes of HeartMate II (HMII)-bridged patients who developed postimplantation right ventricular failure and received Levitronix CentriMag for RV support in addition to LVAD. METHODS: This was a single-centre institutional report of 64 patients transplanted during 2007-2013 from a HeartMate II device. Patients were divided into two groups according to whether they received an isolated LVAD (n = 56) or required additional RV mechanical support (n = 8). These two groups were compared for early graft loss (death before discharge or retransplantation), major early post-transplant complications and 3-year graft survival. RESULTS: Early graft loss was 10.7% in isolated HMII and 25% in HMII + RVAD patients (P = 0.26). There were no observed differences in the rates of primary graft dysfunction (7.3 vs 0%, P = NS), renal failure (16.7 vs 12.5%, P = NS) and stroke (11.1 vs 25%, P = 0.273) between the two groups. Pulmonary artery resistance (odds ratio: 3.286, 95% confidence interval: 1.063-10.157, P = 0.039) was identified as a significant predictor for adverse outcome of mechanically-bridged heart transplant recipients. The 3-year graft survival rate was 86 ± 5% in isolated HMII and 75 ± 15% in HMII + RVAD patients, P = 0.326. CONCLUSIONS: Our data demonstrate that heart transplant recipients who required unplanned RV mechanical support after LVAD implantation achieved comparable rates of early graft loss, post-transplant renal failure and stroke rate in comparison with patients bridged with an isolated HeartMate II assist device. Three-year graft survival was equivalent between those two groups. Given the small sample size, further studies involving more patients are needed to support or challenge our conclusions.

• MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• míra přežití trendy   MeSH
• podpůrné srdeční systémy * MeSH
• přežívání štěpu MeSH
• retrospektivní studie MeSH
• srdeční komory MeSH
• srdeční selhání mortalita   terapie   MeSH
• transplantace srdce metody   MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika MeSH

We describe a minimally invasive technique for the removal of a temporary right ventricular assist device (RVAD) that provided support concomitant with durable left ventricular assist device support. The RVAD cannulas are mobilized through a small subxiphoid incision at the cannula exit site. Both cannulas are transected subcutaneously, then occluded with plugs made of rolled bovine pericardium, and the skin is closed. The cannula remnants are left in place until heart transplantation is accomplished. To minimize risk of thrombus formation at the cannula tips and subsequent embolization into the right atrium or pulmonary artery, anticoagulation is increased to achieve an international normalized ratio (INR) in the range of 2.5-3.0.

• MeSH
• biokompatibilní materiály MeSH
• katétry MeSH
• lidé středního věku MeSH
• lidé MeSH
• miniinvazivní chirurgické výkony metody   MeSH
• odstranění implantátu metody   MeSH
• perikard MeSH
• podpůrné srdeční systémy * MeSH
• skot MeSH
• srdeční selhání chirurgie   MeSH
• transplantace srdce MeSH
• výsledek terapie MeSH
• zvířata MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• skot MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH