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The Histone Methyltransferase Mixed Lineage Leukemia (MLL) 3 May Play a Potential Role on Clinical Dilated Cardiomyopathy.

Tue, 08/15/2017 - 12:45

The Histone Methyltransferase Mixed Lineage Leukemia (MLL) 3 May Play a Potential Role on Clinical Dilated Cardiomyopathy.

Mol Med. 2017 Aug 09;23:

Authors: Jiang DS, Yi X, Li R, Su YS, Wang J, Chen ML, Liu LG, Hu M, Cheng C, Zheng P, Zhu XH, Wei X

Abstract
Histone modifications play a critical role in the pathological processes of dilated cardiomyopathy (DCM). While the role and expression pattern of histone methyltransferases (HMTs), especially mixed lineage leukemia (MLL) families on DCM are unclear. To this end, twelve normal and fifteen DCM heart samples were included in the present study. A murine cardiac remodelling model was induced by transverse aortic constriction (TAC). Real-time PCR was performed to detect the expression levels of MLL families in the mouse and human left ventricles. The mRNA level of MLL3 was significantly increased in the mouse hearts treated by TAC surgery. Compared with normal hearts, higher mRNA and protein level of MLL3 was detected in the DCM hearts, and its expression level was closely associated with left ventricular end systolic diameter (LVEDD) and left ventricular ejection fraction (LVEF). However, the expression level of other MLL families (MLL, MLL2, MLL4, MLL5, SETD1A, and SETD1B) had no obvious change between control and DCM hearts or remodeled mouse hearts. Furthermore, the di-methylated histone H3 lysine 4 (H3K4me2) but not H3K4me3 was significantly increased in the DCM hearts. The protein levels of Smad3, GATA4, EGR1, which might regulate by MLL3, were remarkably elevated in the DCM hearts. Our hitherto unrecognized findings indicate that MLL3 has a potential role on pathological processes of DCM via regulating H3K4me2 and the expression of Smad3, GATA4, and EGR1.

PMID: 28805231 [PubMed - as supplied by publisher]

Changes in patient characteristics following cardiac transplantation: the Montreal Heart Institute experience.

Tue, 08/15/2017 - 12:45

Changes in patient characteristics following cardiac transplantation: the Montreal Heart Institute experience.

Can J Surg. 2017 Aug 03;60(4):5716

Authors: Vistarini N, Nguyen A, White M, Racine N, Perrault LP, Ducharme A, Bouchard D, Demers P, Pellerin M, Lamarche Y, El-Hamamsy I, Giraldeau G, Pelletier G, Carrier M

Abstract
BACKGROUND: Heart transplantation is no longer considered an experimental operation, but rather a standard treatment; nevertheless the context has changed substantially in recent years owing to donor shortage. The aim of this study was to review the heart transplant experience focusing on very long-term survival (≥ 20 years) and to compare the initial results with the current era.
METHODS: From April 1983 through April 1995, 156 consecutive patients underwent heart transplantation. Patients who survived 20 years or longer (group 1) were compared with patients who died within 20 years after surgery (group 2). To compare patient characteristics with the current era, we evaluated our recent 5-year experience (group 3; patients who underwent transplantation between 2010 and 2015), focusing on differences in terms of donor and recipient characteristics.
RESULTS: Group 1 (n = 46, 30%) included younger patients (38 ± 11 v. 48 ± 8 years, p = 0.001), a higher proportion of female recipients (28% v. 8%, p = 0.001) and a lower prevalence of ischemic heart disease (42% v. 65%, p = 0.001) than group 2 (n = 110, 70%). Patients in group 3 (n = 54) were older (52 ± 12 v. 38 ± 11 years, p = 0.001), sicker (hospitalization rate at transplantation 48% v. 20%, p = 0.001) and transplanted with organs from older donors (42 ± 15 v. 29 ± 11 years, p = 0.001) than those in group 1.
CONCLUSION: Very long-term survival ( ≥ 20 years) was observed in 30% of patients transplanted during the first decade of our experience. This outcome will be difficult to duplicate in the current era considering our present population of older and sicker patients transplanted with organs from older donors.

PMID: 28805187 [PubMed - as supplied by publisher]

An integrated approach to coronary heart disease diagnosis and clinical management.

Tue, 08/15/2017 - 12:45
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An integrated approach to coronary heart disease diagnosis and clinical management.

Am J Transl Res. 2017;9(7):3148-3166

Authors: Infante T, Forte E, Schiano C, Cavaliere C, Tedeschi C, Soricelli A, Salvatore M, Napoli C

Abstract
The major issue in coronary heart disease (CHD) diagnosis and management is that symptoms onset in an advanced state of disease. Despite the availability of several clinical risk scores, the prediction of cardiovascular events is lacking, and many patients at risk are not well stratified according to the canonical risk factors alone. Therefore, adequate risk assessment remains the most challenging issue. Recently, the integration of imaging data with biochemical markers in a radiogenomic framework has been proposed in many fields of medicine as well as in cardiology. Multimodal imaging and advanced processing techniques can provide both direct (e.g., remodeling index, calcium score, total plaque volume, plaque burden) and indirect (e.g., myocardial perfusion index, coronary flow reserve) imaging features of CHD. Furthermore, the identification of novel non-invasive biochemical markers, mainly focused on plasma and/or serum samples, has increased the specificity of findings, reflecting several pathophysiological pathways of atherosclerosis, the principal actor in CHD. In this context, a multifaced approach, derived from the strengths of all these modalities, appears promising for finer risk stratification and treatment strategies, facilitating the decision-making and clinical management of patients. This review underlines the role of different imaging modalities in the quantification of coronary atherosclerosis and describes novel blood-based markers that could improve diagnosis and have a better predictive value in CHD.

PMID: 28804537 [PubMed]

Prophylactic use of an intra-aortic balloon pump in a high-risk patient with peripartum cardiomyopathy requiring cesarean delivery.

Tue, 08/15/2017 - 12:45
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Prophylactic use of an intra-aortic balloon pump in a high-risk patient with peripartum cardiomyopathy requiring cesarean delivery.

Int J Obstet Anesth. 2017 Jul 14;:

Authors: Samalavicius RS, Puodziukaite L, Radaviciute I, Norkiene I, Urbonas K, Misiuriene I, Janusauskas V, Zorinas A, Rucinskas K, Serpytis P

Abstract
The use of intra-aortic balloon counter-pulsation for circulatory support in pregnant women with cardiac failure is limited to several case reports. Few publications have addressed the use of intra-aortic balloon counter-pulsation during delivery. We report a case using prophylactic intra-aortic counter-pulsation during the management of a cesarean delivery in a patient with peripartum cardiomyopathy. A 28-year-old primigravid female at 37weeks of gestation was admitted with signs of worsening heart failure, and transthoracic echocardiography revealed a decreased left ventricular ejection fraction of 25%. A plan to proceed with cesarean delivery, using hemodynamic support with intra-aortic balloon counter-pulsation, was made during a multidisciplinary meeting. Shortly after initiation of intra-aortic balloon counter-pulsation, the patient's hemodynamics improved, with a decrease in heart rate and an increase in mean arterial blood pressure. After uneventful cesarean delivery of a healthy 3.2kg infant, the patient was transferred to intensive care and was extubated three hours later. Due to hemodynamic instability, intra-aortic balloon counter-pulsation support and vasopressor infusion were maintained for four postoperative days. The patient was discharged from the hospital on diuretics and beta-blocker treatment after 20days. Heart failure persisted, requiring heart transplantation 25months later. This report highlights the role of a multidisciplinary team approach in the management of delivery in an obstetric patient with peripartum cardiomyopathy.

PMID: 28802997 [PubMed - as supplied by publisher]

Report of the International Society for Heart and Lung Transplantation Working Group on Primary Lung Graft Dysfunction, part II: Epidemiology, risk factors, and outcomes-A 2016 Consensus Group statement of the International Society for Heart and Lung...

Tue, 08/15/2017 - 12:45
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Report of the International Society for Heart and Lung Transplantation Working Group on Primary Lung Graft Dysfunction, part II: Epidemiology, risk factors, and outcomes-A 2016 Consensus Group statement of the International Society for Heart and Lung Transplantation.

J Heart Lung Transplant. 2017 Jul 26;:

Authors: Diamond JM, Arcasoy S, Kennedy CC, Eberlein M, Singer JP, Patterson GM, Edelman JD, Dhillon G, Pena T, Kawut SM, Lee JC, Girgis R, Dark J, Thabut G

PMID: 28802530 [PubMed - as supplied by publisher]

A heart-brain-kidney network controls adaptation to cardiac stress through tissue macrophage activation.

Tue, 08/15/2017 - 12:45
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A heart-brain-kidney network controls adaptation to cardiac stress through tissue macrophage activation.

Nat Med. 2017 May;23(5):611-622

Authors: Fujiu K, Shibata M, Nakayama Y, Ogata F, Matsumoto S, Noshita K, Iwami S, Nakae S, Komuro I, Nagai R, Manabe I

Abstract
Heart failure is a complex clinical syndrome characterized by insufficient cardiac function. In addition to abnormalities intrinsic to the heart, dysfunction of other organs and dysregulation of systemic factors greatly affect the development and consequences of heart failure. Here we show that the heart and kidneys function cooperatively in generating an adaptive response to cardiac pressure overload. In mice subjected to pressure overload in the heart, sympathetic nerve activation led to activation of renal collecting-duct (CD) epithelial cells. Cell-cell interactions among activated CD cells, tissue macrophages and endothelial cells within the kidney led to secretion of the cytokine CSF2, which in turn stimulated cardiac-resident Ly6C(lo) macrophages, which are essential for the myocardial adaptive response to pressure overload. The renal response to cardiac pressure overload was disrupted by renal sympathetic denervation, adrenergic β2-receptor blockade or CD-cell-specific deficiency of the transcription factor KLF5. Moreover, we identified amphiregulin as an essential cardioprotective mediator produced by cardiac Ly6C(lo) macrophages. Our results demonstrate a dynamic interplay between the heart, brain and kidneys that is necessary for adaptation to cardiac stress, and they highlight the homeostatic functions of tissue macrophages and the sympathetic nervous system.

PMID: 28394333 [PubMed - indexed for MEDLINE]

Rare variants in GP1BB are responsible for autosomal dominant macrothrombocytopenia.

Tue, 08/15/2017 - 12:45
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Rare variants in GP1BB are responsible for autosomal dominant macrothrombocytopenia.

Blood. 2017 Jan 26;129(4):520-524

Authors: Sivapalaratnam S, Westbury SK, Stephens JC, Greene D, Downes K, Kelly AM, Lentaigne C, Astle WJ, Huizinga EG, Nurden P, Papadia S, Peerlinck K, Penkett CJ, Perry DJ, Roughley C, Simeoni I, Stirrups K, Hart DP, Tait RC, Mumford AD, NIHR BioResource, Laffan MA, Freson K, Ouwehand WH, Kunishima S, Turro E

Abstract
The von Willebrand receptor complex, which is composed of the glycoproteins Ibα, Ibβ, GPV, and GPIX, plays an essential role in the earliest steps in hemostasis. During the last 4 decades, it has become apparent that loss of function of any 1 of 3 of the genes encoding these glycoproteins (namely, GP1BA, GP1BB, and GP9) leads to autosomal recessive macrothrombocytopenia complicated by bleeding. A small number of variants in GP1BA have been reported to cause a milder and dominant form of macrothrombocytopenia, but only 2 tentative reports exist of such a variant in GP1BB By analyzing data from a collection of more than 1000 genome-sequenced patients with a rare bleeding and/or platelet disorder, we have identified a significant association between rare monoallelic variants in GP1BB and macrothrombocytopenia. To strengthen our findings, we sought further cases in 2 additional collections in the United Kingdom and Japan. Across 18 families exhibiting phenotypes consistent with autosomal dominant inheritance of macrothrombocytopenia, we report on 27 affected cases carrying 1 of 9 rare variants in GP1BB.

PMID: 28064200 [PubMed - indexed for MEDLINE]

In-situ split liver splitting under extra-corporeal membrane oxygenation in brain-dead donor.

Sun, 08/13/2017 - 12:45
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In-situ split liver splitting under extra-corporeal membrane oxygenation in brain-dead donor.

Am J Transplant. 2017 Aug 12;:

Authors: Michela A, Majno P, Toso C, Berney T, Giraud R, Dutkowski P, Andres A, Wildhaber B, Elkrief L

Abstract
Hemodynamic instability is generally considered as a contraindication to liver splitting, in particular when using an in-situ technique. We describe the cases of two young donors with brain death in whom refractory cardiac arrest and hemodynamic instability were supported by veno-arterial extracorporeal membrane oxygenation (VA-ECMO), allowing uneventful in situ splitting. Two adult and two pediatric liver recipients were successfully transplanted with immediate graft function. Favorable outcomes were also observed for the other transplanted organs, including one heart, two lungs and four kidneys. Refractory cardiac arrest and hemodynamic instability corrected by VA-ECMO should not be considered as a contraindication to in-situ liver splitting. This article is protected by copyright. All rights reserved.

PMID: 28801937 [PubMed - as supplied by publisher]

Changing our Approach to Stage D Heart Failure.

Sun, 08/13/2017 - 12:45
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Changing our Approach to Stage D Heart Failure.

Prog Cardiovasc Dis. 2017 Aug 08;:

Authors: Becnel M, Ventura HO, Krim SR

Abstract
Despite the tremendous progress made in the management of heart failure (HF), many patients reach advanced stages. This paper aims to present a practical approach to the stage D HF patient who is no longer responding to optimal medical therapy. We discuss all available therapies for this patient population. We also offer some important caveats with regard to identification, risk stratification, evaluation and treatment including early patient referral to a center with an advanced HF program. Given the changing landscape of heart transplantation and an impending change in the allocation system, we also intend to engage a discussion on the need for a paradigm shift towards left ventricular assist device therapy in this population.

PMID: 28801124 [PubMed - as supplied by publisher]

Rational Heart Transplant From Hepatitis C Donor: New Antiviral Weapons Conquer the Trojan.

Sun, 08/13/2017 - 12:45
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Rational Heart Transplant From Hepatitis C Donor: New Antiviral Weapons Conquer the Trojan.

J Card Fail. 2017 Aug 08;:

Authors: Gottlieb RL, Sam T, Wada SY, Trotter JF, Asrani SK, Lima B, Joseph SM, Gonzalez-Stawinski G, Hall SA

Abstract
BACKGROUND: Donors with hepatitis C (HCV) viremia are rarely utilized for orthotopic heart transplantation (OHTx) due to post-transplant risks. New, highly effective HCV antivirals may alter the landscape.
METHODS: An adult patient unsuitable for bridging mechanical support therapy accepted a heart transplant offer from a donor with HCV viremia. Upon daily logarithmic rise in HCV viral load and adequate titers to ensure successful genotyping, once daily sofosbuvir 400 mg / velpatasvir 100 mg (Epclusa) was initiated empirically pending HCV genotype (genotype 3a confirmed after initiation of therapy).
RESULTS: We report the kinetics of acute Hepatitis C viremia and therapeutic response to treatment with a new pangenotypic antiviral agent after donor-derived acute HCV infection transmitted incidental to successful cardiac transplant into a HCV negative OHTx recipient. Prompt resolution of viremia was noted by the first week of a 12 week course of antiviral therapy. Sustained virologic remission continues beyond 12 weeks after completion of HCV therapy (SVR-12).
CONCLUSIONS: The availability of effective pangenotypic therapy for HCV may expand donor availability. The feasibility of early versus late treatment of HCV remains to be determined through formalized protocols. We hypothesize pharmacoeconomics to be the greatest limitation to widespread availability of this promising tool.

PMID: 28801074 [PubMed - as supplied by publisher]

Development and Evaluation of Heartbeat: A Machine Perfusion Heart Preservation System.

Sat, 08/12/2017 - 12:45
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Development and Evaluation of Heartbeat: A Machine Perfusion Heart Preservation System.

Artif Organs. 2017 Aug 11;:

Authors: Li Y, Zeng Q, Liu G, Du J, Gao B, Wang W, Zheng Z, Hu S, Ji B

Abstract
Static cold storage is accompanied with a partial safe ischemic interval for donor hearts. In this current study, a machine perfusion system was built to provide a better preservation for the donor heart and assessment for myocardial function. Chinese mini-swine (weight 30-35 kg, n = 16) were randomly divided into HTK, Celsior, and Heartbeat groups. All donor hearts were respectively preserved for 8 hours under static cold storage or machine perfusion. The perfusion solution is aimed to maintain its homeostasis based on monitoring the Heartbeat group. The ultrastructure of myocardium suggests better myocardial protection in the Heartbeat group compared with HTK or Celsior-preserved hearts. The myocardial and coronary artery structural and functional integrity was evaluated by immunofluorescence and Western blots in the Heartbeat. In the Heartbeat group, donor hearts maintained a high adenosine triphosphate level. Bcl-2 and Beclin-1 protein demonstrates high expression in the Celsior group. The Heartbeat system can be used to preserve donor hearts, and it could guarantee the myocardial and endothelial function of hearts during machine perfusion. Translating Heartbeat into clinical practice, it is such as to impact on donor heart preservation for cardiac transplantation.

PMID: 28800676 [PubMed - as supplied by publisher]

Thrombolysis for acute pulmonary embolism after major hepatic surgery.

Sat, 08/12/2017 - 12:45
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Thrombolysis for acute pulmonary embolism after major hepatic surgery.

J Clin Anesth. 2017 Aug 08;42:44-45

Authors: Siniscalchi A, Gamberini L, Laici C, Loforte A, Ravaioli M

PMID: 28800479 [PubMed - as supplied by publisher]

Acute and mid-term outcomes of stent implantation for recurrent coarctation of the aorta between the Norwood operation and fontan completion: A multi-center Pediatric Interventional Cardiology Early Career Society Investigation.

Sat, 08/12/2017 - 12:45
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Acute and mid-term outcomes of stent implantation for recurrent coarctation of the aorta between the Norwood operation and fontan completion: A multi-center Pediatric Interventional Cardiology Early Career Society Investigation.

Catheter Cardiovasc Interv. 2017 Aug 11;:

Authors: Aldoss O, Goldstein BH, Danon S, Goreczny S, Gray RG, Sathanandam S, Whiteside W, Williams DA, Zampi JD

Abstract
OBJECTIVES: We sought to evaluate outcomes of stent implantation (SI) for recurrent coarctation of the aorta (RC) following the Norwood operation.
BACKGROUND: RC is common following the Norwood operation. Balloon angioplasty (BA) is standard treatment but may result in unsatisfactory relief of RC. SI may improve RC, but outcome data are limited.
METHODS: We performed a multi-center retrospective study of patients who underwent SI for RC between the Norwood operation and Fontan completion. Outcomes were examined, including procedural success, serious adverse events (SAE), and freedom from re-intervention. A core laboratory was utilized to review angiograms. Coarctation Index (CI) was calculated before and after SI. Paired t-test and Wilcoxon signed-rank test were used to compare pre- and post-SI variables.
RESULTS: Thirty-three patients at 8 centers underwent SI for RC at a median age of 5 months (IQR 4.1, 13.3) and weight of 5.9 kg (5.2, 8.6). Aortic arch gradient improved from 20 (15, 24) to 0 (0, 2) mmHg following SI (P < 0.0001). The median CI improved from 0.54 (0.43, 0.62) to 0.97 (0.89, 1.06) following SI (P < 0.0001). There were no procedural deaths but SAEs occurred in 12 (36%) patients. During a median follow-up duration of 29.7 months (6.8, 48.0), freedom from death or heart transplant was 82%, and from re-intervention was 45%, with median time to re-intervention of 20.1 months (11.4, 40.3).
CONCLUSIONS: SI for treatment of RC in patients after the Norwood operation provides excellent acute relief of obstruction. Intraprocedural hemodynamic instability is common and re-intervention is frequent at mid-term follow-up.

PMID: 28799708 [PubMed - as supplied by publisher]

Patient with a total artificial heart maintained on outpatient dialysis while listed for combined organ transplant, a single center experience.

Sat, 08/12/2017 - 12:45
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Patient with a total artificial heart maintained on outpatient dialysis while listed for combined organ transplant, a single center experience.

Hemodial Int. 2017 Aug 11;:

Authors: Hanna RM, Hasnain H, Kamgar M, Hanna M, Minasian R, Wilson J

Abstract
Advanced mechanical circulatory support is increasingly being used with more sophisticated devices that can deliver pulsatile rather than continuous flow. These devices are more portable as well, allowing patients to await cardiac transplantation in an outpatient setting. It is known that patients with renal failure are at increased risk for developing worsening acute kidney injury during implantation of a ventricular assist device (VAD) or more advanced modalities like a total artificial heart (TAH). Dealing with patients who have an implanted TAH who develop renal failure has been a challenge with the majority of such patients having to await a combined cardiac and renal transplant prior to transition to outpatient care. Protocols do exist for VAD implanted patients to be transitioned to outpatient dialysis care, but there are no reported cases of TAH patients with end stage renal disease (ESRD) being successfully transitioned to outpatient dialysis care. In this report, we identify a patient with a TAH and ESRD transitioned successfully to outpatient hemodialysis and maintained for more than 2 years, though he did not survive to transplant. It is hoped that this report will raise awareness of this possibility, and assist in the development of protocols for similar patients to be successfully transitioned to outpatient dialysis care.

PMID: 28799694 [PubMed - as supplied by publisher]

Effect of left ventricular dysfunction on utilization of donor hearts.

Sat, 08/12/2017 - 12:45
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Effect of left ventricular dysfunction on utilization of donor hearts.

J Heart Lung Transplant. 2017 Jul 19;:

Authors: Tryon D, Hasaniya NW, Jabo B, Razzouk AJ, Bailey LL, Rabkin DG

Abstract
BACKGROUND: In this study we investigated modern, non-utilization rates of potential cardiac donors with left ventricular dysfunction (LVD) to clarify this phenomenon's magnitude and the impact of recent studies suggesting these organs can be safely transplanted.
METHODS: Using the United Network for Organ Sharing transplant database, we reviewed all donors evaluated between January 1, 2007 and June 30, 2014. Exclusion criteria included lack of consent and age <13 or >59 years. The number of hearts not transplanted due to non-cardiac causes, structural disease, "other" (previous cardiac surgery, donation after cardiac death, etc.) and isolated LVD was determined and a covariates-adjusted Poisson regression model with robust standard errors was developed to estimate non-utilization relative risk (RR) with 95% confidence interval (CI) for LVD. Heart disposition for potential donor hearts was determined separately for 2 previous eras (1990 to 1999 and 2000 to 2006), and trends were evaluated.
RESULTS: There were 60,789 donors assessed. Of the 44,829 organs meeting the inclusion criteria, 15,654 (34.92%) were transplanted and 29,175 (65.08%) were not. Of the non-utilized hearts, 15,512 (34.60%) were declined for non-cardiac reasons, 1,051 (2.34%) for structural disease, 4,073 (9.09%) for "other" and 8,539 (19.05%) exclusively for LVD. Of this last category, 4,950 (11.04%) lacked documented evidence of LVD. Covariates-adjusted RR for non-utilization showed that, for every 10% increase in LV ejection fraction, the risk of non-utilization decreased by 20% (RR = 0.80, 95% CI 0.79 to 0.81). Analysis of era-effect demonstrated significantly decreased overall utilization of donor hearts, with increases in the number of hearts not transplanted across all categories over time (p < 0.001).
CONCLUSIONS: Roughly 20% of potential cardiac donors are excluded due to LVD. This figure has not been impacted by recent studies indicating that these hearts may be used safely. More complete data are required to understand why 11.04% of hearts that met inclusion criteria were refused for "poor function" without documented evidence.

PMID: 28797760 [PubMed - as supplied by publisher]

Liver grafts procured from donors after circulatory death have no increased risk of microthrombi formation.

Sat, 08/12/2017 - 12:45
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Liver grafts procured from donors after circulatory death have no increased risk of microthrombi formation.

Liver Transpl. 2016 Dec;22(12):1676-1687

Authors: Verhoeven CJ, Simon TC, de Jonge J, Doukas M, Biermann K, Metselaar HJ, Ijzermans JN, Polak WG

Abstract
Microthrombi formation provoked by warm ischemia and vascular stasis is thought to increase the risk of nonanastomotic strictures (NAS) in liver grafts obtained by donation after circulatory death (DCD). Therefore, potentially harmful intraoperative thrombolytic therapy has been suggested as a preventive strategy against NAS. Here, we investigated whether there is histological evidence of microthrombi formation during graft preservation or directly after reperfusion in DCD livers and the development of NAS. Liver biopsies collected at different time points during graft preservation and after reperfusion were triple-stained with hematoxylin-eosin (H & E), von Willebrand factor VIII (VWF), and Fibrin Lendrum (FL) to evaluate the presence of microthrombi. In a first series of 282 sections obtained from multiple liver segments of discarded DCD grafts, microthrombi were only present in 1%-3% of the VWF stainings, without evidence of thrombus formation in paired H & E and FL stainings. Additionally, analysis of 132 sections obtained from matched, transplanted donation after brain death and DCD grafts showed no difference in microthrombi formation (11.3% versus 3.3% respectively; P = 0.082), and no relation to the development of NAS (P = 0.73). Furthermore, no microthrombi were present in perioperative biopsies in recipients who developed early hepatic artery thrombosis. Finally, the presence of microthrombi did not differ before or after additional flushing of the graft with preservation solution. In conclusion, the results of our study derogate from the hypothesis that DCD livers have an increased tendency to form microthrombi. It weakens the explanation that microthrombi formation is a main causal factor in the development of NAS in DCD and that recipients could benefit from intraoperative thrombolytic therapy to prevent NAS following liver transplantation. Liver Transplantation 22 1676-1687 2016 AASLD.

PMID: 27542167 [PubMed - indexed for MEDLINE]

Successful use of equine anti-thymocyte globulin (ATGAM) for fulminant myocarditis secondary to nivolumab therapy.

Fri, 08/11/2017 - 12:45
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Successful use of equine anti-thymocyte globulin (ATGAM) for fulminant myocarditis secondary to nivolumab therapy.

Br J Cancer. 2017 Aug 10;:

Authors: Tay RY, Blackley E, McLean C, Moore M, Bergin P, Gill S, Haydon A

Abstract
BACKGROUND: Immune-mediated myocarditis is an uncommon adverse effect of immune checkpoint inhibition and is associated with a high rate of mortality.
METHODS: In this reported case, a 64-year-old woman with right temporo-parietal glioblastoma IDH-WT was treated with nivolumab, temozolomide and radiation therapy on a clinical trial. She developed malignant arrhythmias secondary to histologically confirmed severe immune-mediated myocarditis. She was treated with equine anti-thymocyte globulin (ATGAM) due to development of malignant arrhythmias refractory to high-dose corticosteroids.
RESULTS: This report describes the only case of immune-mediated myocarditis treated with ATGAM resulting in a favourable outcome.
CONCLUSIONS: Use of ATGAM should be considered in cases of steroid-refractory immune-mediated myocarditis and administered in close consultation with a cardiac transplant team experienced in the use of this agent.British Journal of Cancer advance online publication: 10 August 2017; doi:10.1038/bjc.2017.253 www.bjcancer.com.

PMID: 28797029 [PubMed - as supplied by publisher]

Toxic Myocarditis Caused by Acetaminophen in a Multidrug Overdose.

Fri, 08/11/2017 - 12:45
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Toxic Myocarditis Caused by Acetaminophen in a Multidrug Overdose.

Am J Forensic Med Pathol. 2017 Aug 09;:

Authors: Gosselin M, Dazé Y, Mireault P, Crahes M

Abstract
We report the case of an 18-year-old woman with personality disorders who was hospitalized a few hours after suicidal ingestion of acetaminophen, quetiapine, acetylsalicylic acid, and ethanol. Twelve hours after admission, severe liver damage was evident, but the patient was stable and awaiting hepatic transplantation. Electrolytes were successfully controlled. The condition of the liver stabilized. Cardiac biomarkers then deteriorated unexpectedly. Localized ST-segment elevations were noted on electrocardiogram, but angiography ruled out myocardial infarction. A computed tomographic scan ruled out cerebral edema. The patient died of irreversible cardiac arrest 40 hours after admission. Heart failure remained unexplained, and the body underwent forensic autopsy.At autopsy, histologic findings were indicative of acute toxic myocarditis and were concluded to be caused by acetaminophen intoxication. Acetaminophen overdose is common and typically leads to liver failure requiring supportive treatment and emergency liver transplantation. Toxic myocarditis is an extremely rare complication of acetaminophen overdose. It has only been reported 4 times in the literature despite the widespread use and misuse of acetaminophen. Toxic myocarditis remains a possibility in many cases of overdose but can be overlooked in a clinical picture dominated by hepatorenal failure and encephalopathy. Clinicians and forensic pathologists should be aware of this rare potential complication.

PMID: 28795995 [PubMed - as supplied by publisher]

The reverse metabolic syndrome in the elderly: Is it a "catabolic" syndrome?

Fri, 08/11/2017 - 12:45
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The reverse metabolic syndrome in the elderly: Is it a "catabolic" syndrome?

Aging Clin Exp Res. 2017 Aug 09;:

Authors: Curcio F, Sasso G, Liguori I, Ferro G, Russo G, Cellurale M, Della-Morte D, Gargiulo G, Testa G, Cacciatore F, Bonaduce D, Abete P

Abstract
Traditional risk factors of cardiovascular death in the general population, including body mass index (BMI), serum cholesterol, and blood pressure are also found to relate to outcomes in the geriatric population, but in a differing direction. A higher body mass index, hypercholesterolemia and hypertension are not harmful but even permit better survival at advancing age. This phenomenon is called "reverse epidemiology" or "risk factor paradox" and is also detected in a variety of chronic disease states such as chronic heart failure. Accordingly, a low BMI, blood pressure and cholesterol values are associated with a worse prognosis. Several possible causes are hypothesized to explain this elderly paradox, but this phenomenon remains controversial and its underlying reasons are poorly understood. The aim of this review is to recognize the factors behind this intriguing phenomenon and analyse the consequences that it can bring in the management of the cardiovascular therapy in elderly patient. Finally, a new phenotype identified as "catabolic syndrome" has been postulated.

PMID: 28795337 [PubMed - as supplied by publisher]

Access to Heart Transplantation: A Proper Analysis of the Competing Risks of Death and Transplantation Is Required to Optimize Graft Allocation.

Fri, 08/11/2017 - 12:45
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Access to Heart Transplantation: A Proper Analysis of the Competing Risks of Death and Transplantation Is Required to Optimize Graft Allocation.

Transplant Direct. 2017 Aug;3(8):e198

Authors: Cantrelle C, Legeai C, Latouche A, Tuppin P, Jasseron C, Sebbag L, Bastien O, Dorent R

Abstract
BACKGROUND: Heart allocation systems are usually urgency-based, offering grafts to candidates at high risk of waitlist mortality. In the context of a revision of the heart allocation rules, we determined observed predictors of 1-year waitlist mortality in France, considering the competing risk of transplantation, to determine which candidate subgroups are favored or disadvantaged by the current allocation system.
METHODS: Patients registered on the French heart waitlist between 2010 and 2013 were included. Cox cause-specific hazards and Fine and Gray subdistribution hazards were used to determine candidate characteristics associated with waitlist mortality and access to transplantation.
RESULTS: Of the 2053 candidates, 7 variables were associated with 1-year waitlist mortality by the Fine and Gray method including 4 candidate characteristics related to heart failure severity (hospitalization at listing, serum natriuretic peptide level, systolic pulmonary artery pressure, and glomerular filtration rate) and 3 characteristics not associated with heart failure severity but with lower access to transplantation (blood type, age, and body mass index). Observed waitlist mortality for candidates on mechanical circulatory support was like that of others.
CONCLUSIONS: The heart allocation system strongly modifies the risk of pretransplant mortality related to heart failure severity. An in-depth competing risk analysis is therefore a more appropriate method to evaluate graft allocation systems. This knowledge should help to prioritize candidates in the context of a limited donor pool.

PMID: 28795149 [PubMed]

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