Trasplante cardíaco

Evaluation of right ventricular function using liver stiffness in patients with left ventricular assist device†.

Eur J Cardiothorac Surg. 2017 Apr 01;51(4):715-721

Authors: Kashiyama N, Toda K, Nakamura T, Miyagawa S, Nishi H, Yoshikawa Y, Fukushima S, Saito S, Yoshioka D, Sawa Y

Abstract
OBJECTIVES: Although right ventricular failure (RVF) is a major concern after left ventricular assist device (LVAD) implantation, methodologies to evaluate RV function remain limited. Liver stiffness (LS), which is closely related to right-sided filling pressure and may indicate RVF severity, could be non-invasively and repeatedly assessed using transient elastography. Here we investigated the suitability of LS as a parameter of RV function in pre- and post-LVAD periods.
METHODS: The study included 55 patients with LVAD implantation as a bridge to transplantation between 2011 and 2015 whose LS was assessed using transient elastography.
RESULTS: Seventeen patients presented with RVF, defined as requiring inotropic support for ≥30 days, nitric oxygen inhalation for ≥5 days, and/or mechanical RV support following LVAD implantation. Survival of patients with RVF was significantly worse compared with that of patients without RVF. Multivariate logistic regression analysis identified preoperative LS, LV diastolic dimension, RV stroke work index, and dilated phase of hypertrophic cardiomyopathy aetiology as significant risk factors; the combination of these parameters could improve predictive power of post-LVAD RVF with areas under the curve of 0.89. Furthermore, LS was significantly decreased by LV unloading and significantly correlated with right-sided filling pressure.
CONCLUSIONS: In addition to dilated hypertrophic cardiomyopathy aetiology, reduced RV stroke work index and small LV dimension, we demonstrated that non-invasively measured LS was a predictor of post-LVAD RVF and can be used as a parameter for the evaluation and optimization of RV function in the perioperative period.

PMID: 28380632 [PubMed - in process]

Myeloablative Versus Reduced-Intensity Hematopoietic Cell Transplantation for Acute Myeloid Leukemia and Myelodysplastic Syndromes.

J Clin Oncol. 2017 Apr 10;35(11):1154-1161

Authors: Scott BL, Pasquini MC, Logan BR, Wu J, Devine SM, Porter DL, Maziarz RT, Warlick ED, Fernandez HF, Alyea EP, Hamadani M, Bashey A, Giralt S, Geller NL, Leifer E, Le-Rademacher J, Mendizabal AM, Horowitz MM, Deeg HJ, Horwitz ME

Abstract
Purpose The optimal regimen intensity before allogeneic hematopoietic cell transplantation (HCT) is unknown. We hypothesized that lower treatment-related mortality (TRM) with reduced-intensity conditioning (RIC) would result in improved overall survival (OS) compared with myeloablative conditioning (MAC). To test this hypothesis, we performed a phase III randomized trial comparing MAC with RIC in patients with acute myeloid leukemia or myelodysplastic syndromes. Patients and Methods Patients age 18 to 65 years with HCT comorbidity index ≤ 4 and < 5% marrow myeloblasts pre-HCT were randomly assigned to receive MAC (n = 135) or RIC (n = 137) followed by HCT from HLA-matched related or unrelated donors. The primary end point was OS 18 months post-random assignment based on an intent-to-treat analysis. Secondary end points included relapse-free survival (RFS) and TRM. Results Planned enrollment was 356 patients; accrual ceased at 272 because of high relapse incidence with RIC versus MAC (48.3%; 95% CI, 39.6% to 56.4% and 13.5%; 95% CI, 8.3% to 19.8%, respectively; P < .001). At 18 months, OS for patients in the RIC arm was 67.7% (95% CI, 59.1% to 74.9%) versus 77.5% (95% CI, 69.4% to 83.7%) for those in the MAC arm (difference, 9.8%; 95% CI, -0.8% to 20.3%; P = .07). TRM with RIC was 4.4% (95% CI, 1.8% to 8.9%) versus 15.8% (95% CI, 10.2% to 22.5%) with MAC ( P = .002). RFS with RIC was 47.3% (95% CI, 38.7% to 55.4%) versus 67.8% (95% CI, 59.1% to 75%) with MAC ( P < .01). Conclusion OS was higher with MAC, but this was not statistically significant. RIC resulted in lower TRM but higher relapse rates compared with MAC, with a statistically significant advantage in RFS with MAC. These data support the use of MAC as the standard of care for fit patients with acute myeloid leukemia or myelodysplastic syndromes.

PMID: 28380315 [PubMed - in process]

Donation after circulatory death heart transplantation.

Curr Opin Organ Transplant. 2017 Apr 04;:

Authors: Dhital KK, Chew HC, Macdonald PS

Abstract
PURPOSE OF REVIEW: Despite continued expansion in the use of extended-criteria donor hearts following donation after brain death, there remains an unacceptable discrepancy between the supply of suitable donor hearts and the demand from increasing recipient numbers on transplant wait lists. Until recently, the additional approach of utilizing organs following donation after circulatory death (DCD) had not been possible for clinical heart transplantation in the modern era. This review describes relevant advances in translational research and provides an update on the favourable adoption of this donation pathway for clinical heart transplantation.
RECENT FINDINGS: The use of an ex-situ transportable cardiac perfusion platform together with modified cardioplegia, supplemented with postconditioning agents, has allowed three centres to report successful transplantation of distantly procured human DCD hearts. This has been achieved by utilizing either a method of direct procurement and ex-situ perfusion on the device or through an initial in-situ reanimation with extracorporeal normothermic regional perfusion prior to ex-situ perfusion.
SUMMARY: DCD heart transplantation is feasible with excellent early outcomes. In the face of continued and significant donor organ shortage and inevitable wait list attrition, the rejection of suitable DCD hearts, in jurisdictions permitting this donation pathway, is increasingly difficult to justify.

PMID: 28379853 [PubMed - as supplied by publisher]

Liver transplantation for drug-induced acute liver failure.

Eur Rev Med Pharmacol Sci. 2017 Mar;21(1 Suppl):37-45

Authors: Biolato M, Araneo C, Marrone G, Liguori A, Miele L, Ponziani FR, Gasbarrini A, Grieco A

Abstract
OBJECTIVES: To summarize the different clinical features of drug-induced acute liver failure, the diagnostic work-up, conservative management and the prognostic scores currently used to list patients for liver transplantation.
EVIDENCE AND INFORMATION SOURCES: The current review is based on an analysis of the current literature and the caseload experience of the Authors on this topic.
STATE OF THE ART: Drug-induced liver injury is the leading cause of acute liver failure in the adult population in Western countries, with a transplant-free survival rate of less than 50%. Main subtypes include paracetamol and idiosyncratic drug-induced injury, which differ in epidemiology, clinical course, prognosis and conservative management. In cases of a high likelihood of death, urgent hepatic transplantation is indicated, but the decision whether and when to put a patient with drug-induced acute liver failure on the list for urgent liver transplant is extremely difficult and requires constant interdisciplinary exchange and continuous updating of the clinical picture.
CONCLUSIONS: Intensive management should be done in a clinical tertiary referral center which has a specialized team of hepatologists and a liver transplant center.

PMID: 28379596 [PubMed - in process]

Heart transplantation using a donor with partial anomalous pulmonary venous connection and atrial septal defect.

Interact Cardiovasc Thorac Surg. 2017 Mar 30;:

Authors: de Beco G, Duisit J, Poncelet AJ

Abstract
Over the last decade, the shortage of donors has led to increased waiting time prior to transplantation and its related mortality. Therefore, extended criteria for donor hearts have been proposed. In this report, we describe a successful transplantation despite a diagnosis of partial abnormal pulmonary venous return associated with an atrial septal defect sinus venosus and persisting left-sided superior vena cava. Knowledge in congenital cardiac disease can broaden the definition of 'marginal' donor hearts and allow their use without increasing the risk of transplantation.

PMID: 28379508 [PubMed - as supplied by publisher]

Cancer recurrence and mortality after pediatric heart transplantation for anthracycline cardiomyopathy: A report from the Pediatric Heart Transplant Study (PHTS) group.

Pediatr Transplant. 2017 Apr 04;:

Authors: Bock MJ, Pahl E, Rusconi PG, Boyle GJ, Parent JJ, Twist CJ, Kirklin JK, Pruitt E, Bernstein D

Abstract
We aimed to determine whether malignancy after pediatric HTx for ACM affects overall post-HTx survival. Patients <18y listed for HTx for ACM in the PHTS database between 1993 and 2014 were compared to those with DCM. A 2:1 matched DCM cohort was also compared. Wait-list and post-HTx survival, along with freedom from common HTx complications, were compared. Eighty subjects were listed due to ACM, whereas 1985 were listed for DCM. Although wait-list survival was higher in the ACM group, post-HTx survival was lower for the ACM cohort. Neither difference persisted in the matched cohort analysis. Primary cause of death in the ACM group was infection, which was higher than the DCM group. Malignancy rates were not different. All ACM malignancies were due to PTLD without primary cancer recurrence or SMN. Long-term graft survival after pediatric HTx for ACM is no different than for matched DCM peers, nor is there an increased risk of any malignancy. However, risk of infection and death from infection after HTx are higher in the ACM group. Further studies are needed to assess the effects of prior chemotherapy on susceptibility to infection in this group.

PMID: 28378408 [PubMed - as supplied by publisher]

Mycobacterium tuberculosis in solid organ transplantation: incidence before and after expanded isoniazid prophylaxis.

Ann Saudi Med. 2017 Mar-Apr;37(2):138-143

Authors: Al-Mukhaini SM, Al-Eid H, Alduraibi F, Hakami HI, Talhi HA, Shoukri M, Ahmed AM, Ahmed Y, Alrajhi AA

Abstract
BACKGROUND: The risk of tuberculosis is increased in solid organ transplantation. Rates remain high in developed and developing countries. We developed protocols to better identify transplant recipients at risk of tuberculosis and initiate interventions to prevent tuberculosis.
OBJECTIVES: Report tuberculosis incidence in solid-organ transplant recipients and the results of expanded isoniazid prophylaxis in deceased-donor renal transplantation.
DESIGN: Retrospective cohort study, comparing two time periods.
SETTING: Large transplantation center in a WHO-medium endemicity country for tuberculosis.
METHODS: In a cohort of all solid-organ transplant recipients performed between 2003 and 2012, tuberculosis-free transplantation follow-up is used for incidence calculation. Rates of tuberculosis in renal transplant recipients are compared before and after implementation of expanded isoniazid prophylaxis.
MAIN OUTCOME MEASURE(S): Active tuberculosis post-transplantation.
RESULTS: Of 1966 solid-organ transplant recipients (kidney: 1391, liver: 426, heart: 114, lung: 35), 20 recipients (1.02%) developed tuberculosis. Twelve cases (60%) developed tuberculosis within one year of transplantation. The incidence was 248 cases per 100 000 transplant-years. The proportion of transplant recipients (incidence of tuberculosis per 100 000 transplant-years) for specific organs were kidney 0.58% (127), liver 1.88% (594), heart: 1.75% (570), and lung 5.71% (4750). In the survival analysis, lung transplant recipients had significantly higher rates of tuberculosis compared to recipients of kidneys from living donors (P=.0001) with a rate ratio of 45.3 (95% CI: 7-313). Mortality was 5% among tuberculosis patients. After implementing expanded isoniazid prophylaxis among deceased-donor kidney recipients, no tuberculosis occurred in 177 recipients, compared to 3 out of 155 (2%) recipients before implementation.
CONCLUSIONS: Rates of tuberculosis among our solid transplant recipients are decreasing. Universal iso-niazid prophylaxis in transplant recipients could reduce transplant-associated tuberculosis in endemic areas.
LIMITATIONS: Donor data on tuberculosis exposure and prevention and tuberculosis prevention efforts before referral to our center are not available for all patients.

PMID: 28377543 [PubMed - in process]

Outcomes for primary kidney transplantation from donation after Citizens' death in China: a single center experience of 367 cases.

BMC Health Serv Res. 2017 Apr 04;17(1):250

Authors: Xue W, Tian P, Xiang H, Ding X, Pan X, Yan H, Hou J, Feng X, Liu L, Ding C, Tian X, Li Y, Zheng J

Abstract
BACKGROUND: The cases of donation after brain death followed by circulatory death (DBCD) and donation after cardiac death (DCD) have been increased year by year in China. Further research is needed to understand in the outcomes and risk factors of delayed graft function (DGF) in order to minimize the risk of DGF and ameliorate its potential impact on long-term outcomes. This study was to explore the differences in outcomes between DBCD and DCD transplant and the main risk factors for DGF in DBCD.
METHODS: Retrospective analysis of the clinical data of 367donations after citizens' death kidney transplant procedures (donors and recipients) between July 2012 and August 2015 at our center.
RESULTS: During the study period, the donation success rate was 25.3%. 164 cases of DBCD and 35 cases of DCD had been implemented and 367 kidneys were transplanted. The incidence of DGF in DBCD group were significantly lower than that of DCD group (12.0% vs. 27.0%, p = 0.002). The 1-year percent freedom from acute rejection (AR) was significantly higher in DBCD group compared with it of DCD group (94% vs. 82%, p = 0.036). Multivariate logistic regression analysis of the kidney transplants revealed that the high risk factors for DGF after renal transplantation in DBCD were history of hypertension (Odds Ratio [OR] = 5.88, 95% CI: 1.90 to 18.2, p = 0.002), low blood pressure (BP < 80 mmHg) (OR = 4.86, 95% CI: 1.58 to 14.9, p = 0.006) and serum creatinine of donor (OR = 1.09, 95% CI: 1.03 to 1.16, p = 0.003) before donation.
CONCLUSIONS: The outcomes of DBCD could be better than DCD in DGF and AR. The main risk factors for DGF in DBCD kidney transplants are donors with a history of hypertension, low blood pressure, and serum creatinine of donor before donation.

PMID: 28376778 [PubMed - in process]

A case for using "marginal" hearts.

Pediatr Transplant. 2016 09;20(6):740-1

Authors: Davies RR

PMID: 27545340 [PubMed - indexed for MEDLINE]

Hypoxia inducible factor-1 alpha potentiates Jagged 1-mediated angiogenesis by mesenchymal stem cell-derived exosomes.

Stem Cells. 2017 Apr 04;:

Authors: Gonzalez-King H, García NA, Ontoria-Oviedo I, Ciria M, Montero JA, Sepúlveda P

Abstract
Insufficient vessel growth associated with ischemia remains an unresolved issue in vascular medicine. Mesenchymal stem cells (MSCs) have been shown to promote angiogenesis via a mechanism that is potentiated by hypoxia. Overexpression of hypoxia inducible factor (HIF)-1α in MSCs improves their therapeutic potential by inducing angiogenesis in transplanted tissues. Here we studied the contribution of exosomes released by HIF-1α-overexpressing donor MSCs (HIF-MSC) to angiogenesis by endothelial cells. Exosome secretion was enhanced in HIF-MSC. Omics analysis of miRNAs and proteins incorporated into exosomes pointed to the Notch pathway as a candidate mediator of exosome communication. Interestingly, we found that Jagged1 was the sole Notch ligand packaged into MSC exosomes and was more abundant in HIF-MSC than in MSC controls. The addition of Jagged1-containing exosomes from MSC and HIF-MSC cultures to endothelial cells triggered transcriptional changes in Notch target genes and induced angiogenesis in an in vitro model of capillary-like tube formation, and both processes were stimulated by HIF-1α. Finally, subcutaneous injection of Jagged 1-containing exosomes from MSC and HIF-MSC cultures in the Matrigel plug assay induced angiogenesis in vivo, which was more robust when they were derived from HIF-MSC cultures. All Jagged1-mediated effects could be blocked by prior incubation of exosomes with an anti-Jagged 1 antibody. All together, the results indicate that exosomes derived from MSCs stably overexpressing HIF-1α have an increased angiogenic capacity in part via an increase in the packaging of Jagged1, which could have potential applications for the treatment of ischemia-related disease. This article is protected by copyright. All rights reserved.

PMID: 28376567 [PubMed - as supplied by publisher]

Rapid Discontinuation of Prednisone in Kidney Transplant Recipients: 15-Year Outcomes from the University of Minnesota.

Transplantation. 2017 Apr 03;:

Authors: Serrano OK, Kandaswamy R, Gillingham K, Chinnakotla S, Dunn TB, Finger E, Payne W, Ibrahim H, Kukla A, Spong R, Issa N, Pruett TL, Matas A

Abstract
BACKGROUND: Short- and intermediate-term results have been reported after rapid discontinuation of prednisone (RDP) in kidney transplant recipients. Yet there has been residual concern about late graft failure in the absence of maintenance prednisone.
METHODS: From October 1, 1999, through June 1, 2015, we performed a total of 1553 adult 1st and 2nd kidney transplants-1021 with a living donor (LD), 532 with a deceased donor (DD)-under our RDP protocol. We analyzed the 15-year actuarial overall patient survival (PS), graft survival (GS), death-censored graft survival (DCGS), and acute rejection-free survival (ARFS) rates for RDP compared to historical controls on maintenance prednisone.
RESULTS: For LD recipients, the actuarial 15-year PS rates were similar between groups. But RDP was associated with increased GS (p=0.02) and DCGS (p=0.01). For DD recipients, RDP was associated with significantly better PS (p<0.01), GS (p<0.01) and DCGS (p<0.01). There was no difference between groups in the rate of acute or chronic rejection, or in the mean estimated glomerular filtration rate at 15 years. However, RDP-treated recipients had significantly lower rates of avascular necrosis, CMV, cataracts, NODAT and cardiac complications. Importantly, for recipients with graft survival >5 years, there was no difference between groups in subsequent actuarial PS, GS, and DCGS.
CONCLUSION: In summary, at 15-years post kidney transplant, RDP did not lead to decreased in patient or graft survival, or an increase in graft dysfunction but as associated with reduced complication rates.

PMID: 28376034 [PubMed - as supplied by publisher]

Exercise-based cardiac rehabilitation in heart transplant recipients.

Cochrane Database Syst Rev. 2017 Apr 04;4:CD012264

Authors: Anderson L, Nguyen TT, Dall CH, Burgess L, Bridges C, Taylor RS

Abstract
BACKGROUND: Heart transplantation is considered to be the gold standard treatment for selected patients with end-stage heart disease when medical therapy has been unable to halt progression of the underlying pathology. Evidence suggests that aerobic exercise training may be effective in reversing the pathophysiological consequences associated with cardiac denervation and prevent immunosuppression-induced adverse effects in heart transplant recipients.
OBJECTIVES: To determine the effectiveness and safety of exercise-based rehabilitation on the mortality, hospital admissions, adverse events, exercise capacity, health-related quality of life, return to work and costs for people after heart transplantation.
SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library, MEDLINE (Ovid), Embase (Ovid), CINAHL (EBSCO) and Web of Science Core Collection (Thomson Reuters) to June 2016. We also searched two clinical trials registers and handsearched the reference lists of included studies.
SELECTION CRITERIA: We included randomised controlled trials (RCTs) of parallel group, cross-over or cluster design, which compared exercise-based interventions with (i) no exercise control (ii) a different dose of exercise training (e.g. low- versus high-intensity exercise training); or (iii) an active intervention (i.e. education, psychological intervention). The study population comprised adults aged 18 years or over who had received a heart transplant.
DATA COLLECTION AND ANALYSIS: Two review authors independently screened all identified references for inclusion based on pre-specified inclusion criteria. Disagreements were resolved by consensus or by involving a third person. Two review authors extracted outcome data from the included trials and assessed their risk of bias. One review author extracted study characteristics from included studies and a second author checked them against the trial report for accuracy.
MAIN RESULTS: We included 10 RCTs that involved a total of 300 participants whose mean age was 54.4 years. Women accounted for fewer than 25% of all study participants. Nine trials which randomised 284 participants to receive exercise-based rehabilitation (151 participants) or no exercise (133 participants) were included in the main analysis. One cross-over RCT compared high-intensity interval training with continued moderate-intensity training in 16 participants. We reported findings for all trials at their longest follow-up (median 12 weeks).Exercise-based cardiac rehabilitation increased exercise capacity (VO2peak) compared with no exercise control (MD 2.49 mL/kg/min, 95% CI 1.63 to 3.36; N = 284; studies = 9; moderate quality evidence). There was evidence from one trial that high-intensity interval exercise training was more effective in improving exercise capacity than continuous moderate-intensity exercise (MD 2.30 mL/kg/min, 95% CI 0.59 to 4.01; N = 16; 1 study). Four studies reported health-related quality of life (HRQoL) measured using SF-36, Profile of Quality of Life in the Chronically Ill (PLC) and the World Health Organization Quality Of Life (WHOQoL) - BREF. Due to the variation in HRQoL outcomes and methods of reporting we were unable to meta-analyse results across studies, but there was no evidence of a difference between exercise-based cardiac rehabilitation and control in 18 of 21 HRQoL domains reported, or between high and moderate intensity exercise in any of the 10 HRQoL domains reported. One adverse event was reported by one study.Exercise-based cardiac rehabilitation improves exercise capacity, but exercise was found to have no impact on health-related quality of life in the short-term (median 12 weeks follow-up), in heart transplant recipients whose health is stable.There was no evidence of statistical heterogeneity across trials for exercise capacity and no evidence of small study bias. The overall risk of bias in included studies was judged as low or unclear; more than 50% of included studies were assessed at unclear risk of bias with respect to allocation concealment, blinding of outcome assessors and declaration of conflicts of interest. Evidence quality was assessed as moderate according to GRADE criteria.
AUTHORS' CONCLUSIONS: We found moderate quality evidence suggesting that exercise-based cardiac rehabilitation improves exercise capacity, and that exercise has no impact on health-related quality of life in the short-term (median 12 weeks follow-up), in heart transplant recipients. Cardiac rehabilitation appears to be safe in this population, but long-term follow-up data are incomplete and further good quality and adequately-powered trials are needed to demonstrate the longer-term benefits of exercise on safety and impact on both clinical and patient-related outcomes, such as health-related quality of life, and healthcare costs.

PMID: 28375548 [PubMed - as supplied by publisher]

Systemic Inflammatory Response Syndrome in Acute on Chronic Liver Failure- Relevance of 'Golden Window'- a Prospective Study.

J Gastroenterol Hepatol. 2017 Apr 03;:

Authors: Choudhury A, Kumar M, Sharma BC, Maiwall R, Pamecha V, Moreau R, Chawla YK, Duseja A, Mahtab M, Rahman S, Hamid SS, Butt AS, Jafri W, Tan SS, Devarbhavi H, Amarapurkar D, Ning Q, Eapen CE, Goel A, Kim DJ, Ghazinian H, Shiha G, Lee GH, Abbas Z, Payawal DA, Dokmeci AK, Yuen MF, Lesmana LA, Sood A, Chan A, Lau GK, Jia JI, Duan Z, Chen Y, Yokosuka O, Jain P, Bhadoria AS, Kumar G, Sarin SK, APASL ACLF working party

Abstract
BACKGROUND: SIRS is an early marker of sepsis and ongoing inflammationand has been reported in large proportion of ACLF patients. Whether sepsis is the cause or the result of liver failure is unclear and is vital to know. To address this, we investigated the course and outcome of ACLF patients without SIRS/sepsis.
METHODS: Consecutive ACLF patients were monitored for the development of SIRS/sepsis and associated complications and followed till 90 days, liver transplant or death.
RESULTS: Of 561 patients, 201(35.8%) had no SIRS and 360(64.2%) had SIRS with or without infection. New onset SIRS and sepsis developed in 74.6%and 8% respectively in a median 7(range 4-15) days; at a rate of 11% per day. The cumulative incidence of new SIRS was 29%, 92.8% and 100 % by day 4,7 and 15. Liver failure i.e., bilirubin >12 mg/dl, [(OR = 2.5(95%CI = 1.05-6.19), p = 0.04] at day 0 and 4, renal failure at day 4 [(OR = 6.74(95%CI = 1.50-13.29), p = 0.01] independently predicted new onset SIRS. Absence of SIRS in first week was associated with reduced incidence of organ failure (20% vs.39.4%,p = 0.003), as was the 28 day (17.6%vs.36%,p = 0.02) and 90 day (27.5%vs.51%,p = 0.002) mortality. The 90 day mortality was 61.6% in the total cohort, and that for those having no SIRS and SIRS at presentation were 42.8% and 65% respectively(p < 0.001).
CONCLUSIONS: Liver failure predicts the development of SIRS. New onset SIRS in first week is an important determinant of early sepsis, organ failure and survival. Prompt interventions in this 'Golden window' prior to development of sepsis, may improve outcome of ACLF.

PMID: 28374414 [PubMed - as supplied by publisher]

Disturbances in iron homeostasis result in accelerated rejection after experimental heart transplantation.

J Heart Lung Transplant. 2017 Mar 07;:

Authors: Resch T, Ashraf MI, Ritschl PV, Ebner S, Fabritius C, Brunner A, Schäfer G, Regele H, Günther J, Weiss G, Kotsch K

Abstract
BACKGROUND: Clinical data suggest that iron disturbances deleteriously affect graft survival after heart transplantation (HTx), but immunological mechanisms underlying this phenomenon have not yet been elucidated.
METHODS: To identify the mechanistic influence of iron in a murine model of HTx, fully allogeneic BALB/c donor organs were transplanted into iron-overloaded or iron-deficient C57BL/6 mice, and recipients were analyzed for functional and immunological parameters.
RESULTS: After HTx, iron overload accelerated acute rejection as observed by shortened graft survival (HTx vs HTx + iron; p = 0.01), elevated rejection score (p < 0.01), and induction of troponin T (p < 0.01). Compared with controls, allografts and recipient spleens derived from iron-overloaded recipients were characterized by a pronounced graft infiltration of CD4(+) T cells (p < 0.01), CD3(-)NKp46(+) natural killer cells (p < 0.05), and reduced frequencies of regulatory T cells (p < 0.01). This was accompanied by lower mRNA expression levels of anti-inflammatory cytokines, including interleukin-10, transforming graft factor-β, and Foxp3. Cardiac allograft survival was further tested under co-stimulation blockade (CTLA4-Ig) showing that naïve grafts transplanted into iron-overloaded recipients illustrated restricted graft outcome compared with wild types (p = 0.0051), which was rescued after treatment with the iron chelator deferoxamine. Iron deficiency (ID) also resulted in enhanced intragraft infiltration of inflammatory cells and accelerated rejection in the acute setting (HTx vs HTx + ID; p = 0.02) and after co-stimulation blockade (p = 0.0059).
CONCLUSIONS: We provide novel insights into the understanding of disturbances in iron homeostasis and their consequences after HTX, allowing novel insights regarding improvements in personalized immunosuppression to prolong allograft survival.

PMID: 28372951 [PubMed - as supplied by publisher]

The Gut Microbiota and Alzheimer's Disease.

J Alzheimers Dis. 2017 Mar 29;:

Authors: Jiang C, Li G, Huang P, Liu Z, Zhao B

Abstract
The gut microbiota comprises a complex community of microorganism species that resides in our gastrointestinal ecosystem and whose alterations influence not only various gut disorders but also central nervous system disorders such as Alzheimer's disease (AD). AD, the most common form of dementia, is a neurodegenerative disorder associated with impaired cognition and cerebral accumulation of amyloid-β peptides (Aβ). Most notably, the microbiota-gut-brain axis is a bidirectional communication system that is not fully understood, but includes neural, immune, endocrine, and metabolic pathways. Studies in germ-free animals and in animals exposed to pathogenic microbial infections, antibiotics, probiotics, or fecal microbiota transplantation suggest a role for the gut microbiota in host cognition or AD-related pathogenesis. The increased permeability of the gut and blood-brain barrier induced by microbiota dysbiosis may mediate or affect AD pathogenesis and other neurodegenerative disorders, especially those associated with aging. In addition, bacteria populating the gut microbiota can secrete large amounts of amyloids and lipopolysaccharides, which might contribute to the modulation of signaling pathways and the production of proinflammatory cytokines associated with the pathogenesis of AD. Moreover, imbalances in the gut microbiota can induce inflammation that is associated with the pathogenesis of obesity, type 2 diabetes mellitus, and AD. The purpose of this review is to summarize and discuss the current findings that may elucidate the role of the gut microbiota in the development of AD. Understanding the underlying mechanisms may provide new insights into novel therapeutic strategies for AD.

PMID: 28372330 [PubMed - as supplied by publisher]

Does Declaration of Brain Death Serve the Best Interest of Organ Donors Rather Than Merely Facilitating Organ Transplantation?

Ann Thorac Surg. 2016 Jun;101(6):2053-8

Authors: Clarke MJ, Fenton KN, Sade RM

PMID: 27112652 [PubMed - indexed for MEDLINE]

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Survival after lung transplantation for cystic fibrosis in Sweden†.

Eur J Cardiothorac Surg. 2017 Mar 01;51(3):571-576

Authors: Gilljam M, Nyström U, Dellgren G, Skog I, Hansson L

Abstract
OBJECTIVES: In Sweden, lung transplantation has been performed in patients with end-stage lung disease since 1990. We assessed survival after lung transplantation for cystic fibrosis (CF) with focus on early mortality and outcome for patients infected with certain multiresistant bacteria, considered a relative contraindication for lung transplantation.
METHODS: Review of CF and transplant databases and patient charts. The Kaplan-Meier method and log-rank test were used for survival analysis and group comparison.
RESULTS: From November 1991 to December 2014, 115 transplantations were performed in 106 CF patients (9 retransplantations): 3 heart-lung, 106 double lung-, 1 double lobar- and 5 single lung transplantations, constituting 13% (115/909) of all lung-transplant procedures performed in Sweden. The mean age at surgery was 31 (SD 10, range 10-61) years and there were 48% females. Overall 1-year survival after lung transplantation for CF was 86.4%, 5-year survival was 73.7% and 10-year survival was 62.4%. The mean and median survival after transplantation were 13.1 (95% confidence interval (CI): 11-15.3) and 14.6 (95% CI: 9.3-19.8) years, respectively, and there was no significant difference for gender or transplant centre. Extracorporeal membrane oxygenation was used as a bridge to transplantation in 11 cases and five patients received reconditioned lungs. Vascular and infectious complications contributed to eight deaths within the first three postoperative months. The mean survival for 14 patients infected pretransplant with Mycobacterium abscessus or Burkholderia cepacia complex was 8.8 (95% CI: 6.1-11.6) years compared to 13.2 (95% CI: 10.9-15.8) years for patients negative for these bacteria. Nineteen patients (14% of all listed), of whom three were listed for retransplantation, died while waiting a median time of 94 days (range 4 days-2.5 years) after listing.
CONCLUSION: Survival after lung transplantation in Sweden is good, also for patients with pretransplant infection with M. abscessus or B. cepacia complex, and comparable to international data.

PMID: 28364441 [PubMed - in process]

Serum Galectin-3 and ST2 as predictors of unfavorable outcome in stable dilated cardiomyopathy patients.

Hellenic J Cardiol. 2017 Mar 28;:

Authors: Wojciechowska C, Romuk E, Nowalany-Kozielska E, Jacheć W

Abstract
Dilated cardiomyopathy (DCM) is the third cause of heart failure and the most frequent cause of heart transplantation (HT). The value of biomarkers in prognostic stratification may be important to identification the patients for more advanced treatment. Assessment of serum Galectin-3 (Gal-3) and ST2 as biomarkers of unfavorable outcome (death and combined endpoint :HT or death or left ventricular assist device implantation) in stable DCM patients. 107 DCM patients age 39-56 years were included into the study and followed-up for mean 4.8 years. Gal-3 and ST2 concentrations were measured ELISA tests. Clinical data, treatment, laboratory parameters, NT -proBNP, Gal-3 and ST2 measured at time of inclusion were assessed as risk factors for reaching the study endpoints using log rank test and Cox proportional-hazards model. During follow-up 27 patients died, 40 achieved combined endpoint. ROC curves indicated cutoff value of ST2-17.53 ng/ml, AUC-0.65(0.53-0.76) and of NT-proBNP-669 pg/ml, AUC 0.61(0.50-0.73) for prediction of death. In multivariate analysis ST2 was predictor of death (HR per unit increase in log ST2 2.705, 95% CI 1.324-5.528, P=0.006) and combined endpoint (HR per unit increase in log ST2 2.753, 95% CI 1.542-4.914, P<0.001). NT-proBNP was predictive variable only for death in multivariate analysis. Gal-3 concentration was not associated with adverse outcome. ST2 but not Gal-3 may be useful for predicting adverse outcome in stable dilated cardiomyopathy patients.

PMID: 28363768 [PubMed - as supplied by publisher]

Functional status of United States children supported with a left ventricular assist device at heart transplantation.

J Heart Lung Transplant. 2017 Mar 02;:

Authors: Bulic A, Maeda K, Zhang Y, Chen S, McElhinney DB, Dykes JC, Hollander AM, Hollander SA, Murray J, Reinhartz O, Gowan MA, Rosenthal DN, Almond CS

Abstract
BACKGROUND: As survival with pediatric left ventricular assist devices (LVADs) has improved, decisions regarding the optimal support strategy may depend more on quality of life and functional status (FS) rather than mortality alone. Limited data are available regarding the FS of children supported with LVADs. We sought to compare the FS of children supported with LVADs vs vasoactive infusions to inform decision making around support strategies.
METHODS: Organ Procurement and Transplant Network data were used to identify all United States children aged between 1 and 21 years at heart transplant (HT) between 2006 and 2015 for dilated cardiomyopathy and supported with an LVAD or vasoactive infusions alone at HT. FS was measured using the 10-point Karnofsky and Lansky scale.
RESULTS: Of 701 children who met the inclusion criteria, 430 (61%) were supported with vasoactive infusions, and 271 (39%) were supported with an LVAD at HT. Children in the LVAD group had higher median FS scores at HT than children in the vasoactive infusion group (6 vs 5, p < 0.001) but lower FS scores at listing (4 vs 6, p < 0.001). The effect persisted regardless of patient location at HT (home, hospital, intensive care) or device type. Discharge by HT occurred in 46% of children in the LVAD group compared with 26% of children in the vasoactive infusion cohort (p = 0.001). Stroke was reported at HT in 3% of children in the LVAD cohort and in 1% in the vasoactive infusion cohort (p = 0.04).
CONCLUSIONS: Among children with dilated cardiomyopathy undergoing HT, children supported with LVADs at HT have higher FS than children supported with vasoactive infusions at HT, regardless of device type or hospitalization status. Children supported with LVADs at HT were more likely to be discharged from the hospital but had a higher prevalence of stroke at HT.

PMID: 28363739 [PubMed - as supplied by publisher]