BACKGROUND: There is conflicting evidence on the role of acetylsalicylic acid (ASA) use in the development of cardiac allograft vasculopathy (CAV). METHODS: A nationwide prospective two-center study investigated changes in the coronary artery vasculature by highly automated 3-D optical coherence tomography (OCT) analysis at 1 month and 12 months after heart transplant (HTx). The influence of ASA use on coronary artery microvascular changes was analyzed in the overall study cohort and after propensity score matching for selected clinical CAV risk factors. RESULTS: In total, 175 patients (mean age 52 ± 12 years, 79% male) were recruited. During the 1-year follow-up, both intimal and media thickness progressed, with ASA having no effect on its progression. However, detailed OCT analysis revealed that ASA use was associated with a lower increase in lipid plaque (LP) burden (p = .013), while it did not affect the other observed pathologies. Propensity score matching of 120 patients (60 patient pairs) showed similar results, with ASA use associated with lower progression of LPs (p = .002), while having no impact on layered fibrotic plaque (p = .224), calcification (p = .231), macrophage infiltration (p = .197), or the absolute coronary artery risk score (p = .277). According to Kaplan-Meier analysis, ASA use was not associated with a significant difference in survival (p = .699) CONCLUSION: This study showed a benefit of early ASA use after HTx on LP progression. However, ASA use did not have any impact on the progression of other OCT-observed pathologies or long-term survival.

• MeSH
• alografty patologie   MeSH
• aterosklerotický plát * komplikace   MeSH
• dospělí MeSH
• koronární angiografie MeSH
• lidé středního věku MeSH
• lidé MeSH
• nemoci koronárních tepen * etiologie   MeSH
• optická koherentní tomografie škodlivé účinky   metody   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

BACKGROUND: Galectin-3 (GAL3) is linked to the prognosis of patients with heart failure and after heart transplantation (HTx). We assessed the prognostic role of GAL3 in a long-term follow-up after HTx. METHODS: HTx patients (N = 121) were evaluated in a single-center, noninterventional, prospective, observational study. The median follow-up was 96 months (2942 days, interquartile range (IQR) 2408-3264 days), and 40 patients died. GAL3 was measured before HTx, +10 days after HTx, and during the first posttransplant year. Survival analysis (all-cause mortality) was performed with adjustments for clinical and laboratory variables. RESULTS: The median pretransplant GAL3 level was 18.0 μg/L (IQR 14.0-25.9), and higher values were associated with older age, worse kidney function, left ventricular assist device use before HTx, a higher IMPACT score, and mortality. Increased pretransplant GAL3 predicted shorter survival time (HR 2.05, 95% CI 1.09-3.85, p < .05). Similar prognostic power had GAL3 on the 10th posttransplant day (HR 2.03, 95% CI 1.08-3.82, p < .05). GAL3 was an independent predictor of death after adjustment for clinical variables (age, infection, diabetes, smoking, IMPACT score, and troponin). CONCLUSIONS: GAL3 was significantly associated with all-cause mortality after adjusting for clinical and laboratory variables and may serve as an additional prognostic biomarker.

• MeSH
• galektin 3 * MeSH
• galektiny MeSH
• krevní proteiny MeSH
• lidé MeSH
• mortalita * MeSH
• prognóza MeSH
• prospektivní studie MeSH
• srdeční selhání * diagnóza   MeSH
• transplantace srdce * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• pozorovací studie MeSH
• práce podpořená grantem MeSH

INTRODUCTION: Autosomal dominant tubulointerstitial kidney disease (ADTKD) is a rare genetic cause of chronic kidney disease (CKD) and end-stage renal disease (ESRD). We aimed to compare renal transplant outcomes in people with ESRD due to ADTKD to those with other causes of renal failure. METHODS: Patients with clinical characteristics consistent with ADTKD by the criteria outlined in the 2015 KDIGO consensus were included. We compared ADTKD transplant outcomes with those of 4633 non-ADTKD renal transplant recipients. RESULTS: We included 31 patients who met diagnostic criteria for ADTKD in this analysis, 23 of whom had an identified mutation (28 were categorized as definite-ADTKD and 3 as suspected ADTKD). Five patients received a second transplant during follow-up. In total, 36 grafts were included. We did not identify significant differences between groups in terms of graft or patient survival after transplantation. Twenty-five transplant biopsies were performed during follow-up, and none of these showed signs of recurrent ADTKD post-transplant. CONCLUSION: In patients with ESRD due to ADTKD, we demonstrate that transplant outcomes are comparable with the general transplant population. There is no evidence that ADTKD can recur after transplantation.

• MeSH
• chronické selhání ledvin * chirurgie   MeSH
• lidé MeSH
• mutace MeSH
• polycystické ledviny autozomálně dominantní * MeSH
• přežívání štěpu MeSH
• transplantace ledvin * MeSH
• uromodulin genetika   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

INTRODUCTION: Heart rate slowing agents are frequently prescribed to manage heart transplant (HTx) patients with the assumption that higher heart rate is a risk factor in cardiovascular disease. PATIENTS AND METHODS: This prospective two-center study investigated early progression of cardiac allograft vasculopathy (CAV) in 116 HTx patients. Examinations by coronary optical coherence tomography and 24-hour ambulatory ECG monitoring were performed both at baseline (1 month after HTx) and during follow-up (12 months after HTx). RESULTS: During the first post-HTx year, we observed a significant reduction in the mean coronary luminal area from 9.0 ± 2.5 to 8.0 ± 2.4 mm2 (P < .001), and progression in mean intimal thickness (IT) from 106.5 ± 40.4 to 130.1 ± 53.0 μm (P < .001). No significant relationship was observed between baseline and follow-up mean heart rates and IT progression (R = .02, P = .83; R = -.13, P = .18). We found a mild inverse association between beta-blocker dosage at 12 months and IT progression (R = -.20, P = .035). CONCLUSION: Our study did not confirm a direct association between mean heart rate and progression of CAV. The role of beta blockers warrants further investigation, with our results indicating that they may play a protective role in early CAV development.

• MeSH
• alografty MeSH
• koronární angiografie MeSH
• lidé MeSH
• nemoci koronárních tepen * diagnostické zobrazování   etiologie   MeSH
• optická koherentní tomografie MeSH
• prospektivní studie MeSH
• srdeční frekvence MeSH
• transplantace srdce * škodlivé účinky   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH

BACKGROUND AND AIMS: This multicenter trial compared immediate-release tacrolimus (IR-T) vs prolonged-release tacrolimus (PR-T) in de novo kidney, liver, and heart transplant recipients aged <16 years. Each formulation had similar pharmacokinetic (PK) profiles. Follow-up efficacy and safety results are reported herein. MATERIALS AND METHODS: Patients, randomized 1:1, received once-daily, PR-T or twice-daily, IR-T within 4 days of surgery. After a 4-week PK assessment, patients continued randomized treatment for 48 additional weeks. At Year 1, efficacy assessments included the number of clinical acute rejections, biopsy-confirmed acute rejection (BCAR) episodes (including severity), patient and graft survival, and efficacy failure (composite of death, graft loss, BCAR, or unknown outcome). Adverse events were assessed throughout. RESULTS: The study included 44 children. At Year 1, mean ± standard deviation tacrolimus trough levels were 6.6 ± 2.2 and 5.4 ± 1.6 ng/mL, and there were 2 and 7 acute rejection episodes in the PR-T and IR-T groups, respectively. No cases of graft loss or death were reported during the study. The overall efficacy failure rate was 18.2% (PR-T n = 1; IR-T n = 7). CONCLUSIONS: In pediatric de novo solid organ recipients, the low incidence of BCAR and low efficacy failure rate suggest that PR-T-based immunosuppression is effective and well tolerated to 1-year post-transplantation.

• MeSH
• dítě MeSH
• imunosupresiva terapeutické užití   MeSH
• lidé MeSH
• míra přežití MeSH
• mladiství MeSH
• následné studie MeSH
• pooperační komplikace farmakoterapie   etiologie   MeSH
• předškolní dítě MeSH
• přežívání štěpu účinky léků   MeSH
• příjemce transplantátu statistika a číselné údaje   MeSH
• prognóza MeSH
• rejekce štěpu farmakoterapie   etiologie   MeSH
• retrospektivní studie MeSH
• rizikové faktory MeSH
• takrolimus terapeutické užití   MeSH
• transplantace orgánů škodlivé účinky   MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze II MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH
• srovnávací studie MeSH

Heart transplantation is a relatively common treatment for end-stage heart failure. The major complication of heart transplantation is organ rejection. Epigenetic could play a role in the pathogenesis of organ rejection, and the FTO gene is a mediator of DNA methylation. We analyzed a tagging FTO SNP rs17817449 in both donor and recipient DNA obtained through 370 heart transplantations. Recipient FTO genotypes were not associated with either type of rejection or with the general increase in the risk of rejection. When compared with patients without a history of rejection, carriers of transplanted hearts with the FTO TT genotype exhibited a significantly increased risk (P = 0.02) of suffering from both types of rejection in comparison to carriers of hearts with at least one G allele (OR; 95% CI = 2.56; 1.15-5.69). Our results suggest that the donor, but not the recipient, FTO genotype could be a significant predictor of acute rejection in heart transplant patients.

• MeSH
• gen pro FTO genetika   MeSH
• genotyp MeSH
• jednonukleotidový polymorfismus * MeSH
• lidé středního věku MeSH
• lidé MeSH
• následné studie MeSH
• pooperační komplikace diagnóza   etiologie   genetika   MeSH
• přežívání štěpu MeSH
• prognóza MeSH
• rejekce štěpu diagnóza   etiologie   genetika   MeSH
• rizikové faktory MeSH
• transplantace srdce škodlivé účinky   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem 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

Differentiation between systemic inflammatory response syndrome and sepsis in surgical patients is of crucial significance. Procalcitonin (PCT) and C-reactive protein (CRP) are widely used biomarkers, but PCT becomes compromised after antithymocyte globulin (ATG) administration, and CRP exhibits limited specificity. Presepsin has been suggested as an alternative biomarker of sepsis. This study aimed to demonstrate the role of presepsin in patients after heart transplantation (HTx). Plasma presepsin, PCT, and CRP were measured in 107 patients serially for up to 10 days following HTx. Time responses of biomarkers were evaluated for both noninfected (n=91) and infected (n=16) patients. Areas under the concentration curve differed in the two groups of patients for presepsin (P<.001), PCT (P<.005), and CRP (P<.001). The effect of time and infection was significant for all three biomarkers (P<.05 all). In contrast to PCT, presepsin was not influenced by ATG administration. More than 25% of noninfected patients had PCT above 42 μg/L on the first day, and the peak concentration of CRP in infected patients was reached on the third post-transplant day (median 135 mg/L). Presepsin seems to be as valuable a biomarker as PCT or CRP in the evaluation of infectious complications in patients after HTx.

• MeSH
• antilymfocytární sérum aplikace a dávkování   MeSH
• biologické markery metabolismus   MeSH
• C-reaktivní protein metabolismus   MeSH
• dospělí MeSH
• imunosupresiva aplikace a dávkování   MeSH
• infekční nemoci farmakoterapie   etiologie   metabolismus   MeSH
• kalcitonin metabolismus   MeSH
• lidé středního věku MeSH
• lidé MeSH
• lipopolysacharidové receptory metabolismus   MeSH
• následné studie MeSH
• peptidové fragmenty metabolismus   MeSH
• pooperační komplikace farmakoterapie   etiologie   metabolismus   MeSH
• přežívání štěpu účinky léků   MeSH
• prognóza MeSH
• rizikové faktory MeSH
• studie případů a kontrol 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

BACKGROUND: With the same dose of tacrolimus, lower systemic exposure on the first day of dosing has been reported for prolonged-release tacrolimus compared with immediate-release tacrolimus, prompting investigation of differing initial doses. METHODS: This substudy of a double-blind, randomized, phase III trial in de novo liver transplant recipients compared the pharmacokinetics of once-daily prolonged-release tacrolimus (initial dose: 0.2 mg/kg/day) versus twice-daily immediate-release tacrolimus (initial dose: 0.1 mg/kg/day) during the first 2 weeks post-transplant. RESULTS: Pharmacokinetic data were analyzed from patients receiving prolonged-release tacrolimus (n=13) and immediate-release tacrolimus (n=12). Mean systemic exposure (AUC0-24) was higher with prolonged-release versus immediate-release tacrolimus. Dose-normalized AUC0-24(normalized to 0.1 mg/kg/day) showed generally lower exposure with prolonged-release tacrolimus versus immediate-release tacrolimus. There was good correlation between AUC0-24and concentration at 24 hours after the morning dose (r=.96 and r=.86, respectively), and the slope of the line of best fit was similar for both formulations. CONCLUSIONS: Doubling the initial starting dose of prolonged-release tacrolimus compared with immediate-release tacrolimus overcompensated for lower exposure on Day 1. A 50% higher starting dose of prolonged-release tacrolimus than immediate-release tacrolimus may be required for similar systemic exposure. However, doses of both formulations can be optimized using the same trough-level monitoring system. (ClinicalTrials.gov number: NCT00189826).

• MeSH
• dvojitá slepá metoda MeSH
• imunosupresiva aplikace a dávkování   farmakokinetika   MeSH
• lidé středního věku MeSH
• lidé MeSH
• následné studie MeSH
• plocha pod křivkou MeSH
• pooperační komplikace MeSH
• přežívání štěpu účinky léků   MeSH
• prognóza MeSH
• rejekce štěpu farmakoterapie   etiologie   metabolismus   MeSH
• rizikové faktory MeSH
• takrolimus aplikace a dávkování   farmakokinetika   MeSH
• transplantace jater škodlivé účinky   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze III MeSH
• multicentrická studie MeSH
• randomizované kontrolované studie MeSH
• srovnávací studie MeSH

Vascularized composite tissue allotransplantation is a viable treatment option for injuries and defects that involve multiple layers of functional tissue. In the past 15 yr, more than 150 vascularized composite allotransplantation (VCA) surgeries have been reported for various anatomic locations including - but not limited to - trachea, larynx, abdominal wall, face, and upper and lower extremities. VCA can achieve a level of esthetic and functional restoration that is currently unattainable using conventional reconstructive techniques. Although the risks of lifelong immunosuppression continue to be an important factor when evaluating the benefits of VCA, reported short- and long-term outcomes have been excellent, thus far. Acute rejections are common in the early post-operative period, and immunosuppression-related side effects have been manageable. A multidisciplinary approach to the management of VCA has proven successful. Reports of long-term graft losses have been rare, while several factors may play a role in the pathophysiology of chronic graft deterioration in VCA. Alternative approaches to immunosuppression such as cellular therapies and immunomodulation hold promise, although their role is so far not defined. Experimental protocols for VCA are currently being explored. Moving forward, it will be exciting to see whether VCA-specific aspects of allorecognition and immune responses will be able to help facilitate tolerance induction.

• MeSH
• homologní transplantace MeSH
• lidé MeSH
• transplantační tolerance * MeSH
• vaskularizovaná kompozitní alotransplantace * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Research Support, N.I.H., Extramural MeSH
• Research Support, U.S. Gov't, Non-P.H.S. MeSH