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Updated: 59 min 37 sec ago

Progressive aortic root dilatation in pediatric heart transplant recipients.

59 min 37 sec ago
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Progressive aortic root dilatation in pediatric heart transplant recipients.

Echocardiography. 2017 Jun 23;:

Authors: Sachdeva S, Zhang L, Simpson P, Frommelt PC

Abstract
BACKGROUND: To determine prevalence, clinical implication, and risk factors for aortic root dilation (ARD) in pediatric heart transplant recipients.
METHODS: Serial echocardiograms were reviewed in all pediatric heart transplant recipients from 1999 to 2014 to assess maximal systolic diameter at the aortic annulus, aortic sinus, aortic sino-tubular (ST) junction, and ascending aorta. ARD was defined by a sinus/annulus ratio >1.56, ST junction/annulus ratio >1.28, and/or ascending aorta/annulus ratio >1.35.
RESULTS: A total of 147 subjects (53% male) were evaluated; 50% had congenital heart disease (CHD). Of the 74 with CHD, 38 had prior aortic arch reconstruction. The median age at transplant was 3 years (7 days-20.3 years) with a median duration of follow-up of 3.88 years (3 months-15 years). Prevalence of ARD significantly increased in the cohort from 15.6% at the initial echocardiogram to 49.6% at later follow-up (P<.0001). The median duration to development of ARD was 7.6 months. There were no significant differences in prevalence of ARD or days to maximum ratio based on the pretransplant diagnosis. Aortic regurgitation was very rare (7 with ≤mild) and did not correlate with ARD or require any interventions.
CONCLUSION: During intermediate follow-up, ARD commonly develops in children post-heart transplant, and prevalence increases with time after transplant. Within 1 year after transplant, almost 50% had developed abnormalities in aortic root size that were not apparent at the initial posttransplant echocardiogram. Preexisting CHD or need for prior arch reconstruction did not increase the risk of ARD.

PMID: 28646501 [PubMed - as supplied by publisher]

Combined BTK and PI3Kδ inhibition with acalabrutinib and ACP-319 improves survival and tumor control in CLL mouse model.

59 min 37 sec ago
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Combined BTK and PI3Kδ inhibition with acalabrutinib and ACP-319 improves survival and tumor control in CLL mouse model.

Clin Cancer Res. 2017 Jun 23;:

Authors: Niemann CU, Mora-Jensen HI, Dadashian EL, Krantz F, Covey T, Chen SS, Chiorazzi N, Izumi R, Ulrich R, Lannutti BJ, Wiestner A, Herman SEM

Abstract
Purpose: Targeting the B-cell receptor (BCR) pathway with inhibitors of BTK and PI3K-delta is highly effective for the treatment of chronic lymphocytic leukemia (CLL). However, deep remissions are uncommon and drug resistance with single-agent therapy can occur. In vitro studies support the effectiveness of combing PI3K-delta and BTK inhibitors. <p>Experimental design: As CLL proliferation and survival depends on the microenvironment, we used murine models to assess the efficacy of the BTK inhibitor acalabrutinib combined with the PI3K-delta inhibitor ACP-319 in vivo We compared single-agent with combination therapy in TCL1-192 cell-injected mice, a model of aggressive CLL.</p> <p>Results: We found significantly larger reductions in tumor burden in the peripheral blood and spleen of combination-treated mice. While single-agent therapy improved survival compared with control mice by a few days, combination therapy extended survival by over two weeks compared to either single agent. The combination reduced tumor proliferation, NF-KB signaling and expression of BCL-xL and MCL-1 more potently than single-agent therapy.</p> <p>Conclusion: The combination of acalabrutinib and ACP-319 was superior to single-agent treatment in a murine CLL model, warranting further investigation of this combination in clinical studies.

PMID: 28645939 [PubMed - as supplied by publisher]

Left Ventricular Assist Device Therapy for Destination Therapy: Is Less Invasive Surgery a Safe Alternative?

59 min 37 sec ago
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Left Ventricular Assist Device Therapy for Destination Therapy: Is Less Invasive Surgery a Safe Alternative?

Rev Esp Cardiol (Engl Ed). 2017 Jun 20;:

Authors: Rojas SV, Hanke JS, Avsar M, Ahrens PR, Deutschmann O, Tümler KA, Uribarri A, Rojas-Hernández S, Sánchez PL, González-Santos JM, Haverich A, Schmitto JD

Abstract
INTRODUCTION AND OBJECTIVES: The number of older patients with congestive heart failure has dramatically increased. Because of stagnating cardiac transplantation, there is a need for an alternative therapy, which would solve the problem of insufficient donor organ supply. Left ventricular assist devices (LVADs) have recently become more commonly used as destination therapy (DT). Assuming that older patients show a higher risk-profile for LVAD surgery, it is expected that the increasing use of less invasive surgery (LIS) LVAD implantation will improve postoperative outcomes. Thus, this study aimed to assess the outcomes of LIS-LVAD implantation in DT patients.
METHODS: We performed a prospective analysis of 2-year outcomes in 46 consecutive end-stage heart failure patients older than 60 years, who underwent LVAD implantation (HVAD, HeartWare) for DT in our institution between 2011 and 2013. The patients were divided into 2 groups according to the surgical implantation technique: LIS (n = 20) vs conventional (n = 26).
RESULTS: There was no statistically significant difference in 2-year survival rates between the 2 groups, but the LIS group showed a tendency to improved patient outcome in 85.0% vs 69.2% (P = .302). Moreover, the incidence of postoperative bleeding was minor in LIS patients (0% in the LIS group vs 26.9% in the conventional surgery group, P < .05), who also showed lower rates of postoperative extended inotropic support (15.0% in the LIS group vs 46.2% in the conventional surgery group, P < .05).
CONCLUSIONS: Our data indicate that DT patients with LIS-LVAD implantation showed a lower incidence of postoperative bleeding, a reduced need for inotropic support, and a tendency to lower mortality compared with patients treated with the conventional surgical technique.

PMID: 28645834 [PubMed - as supplied by publisher]

Pulmonary Artery Embolization after Blunt Trauma.

59 min 37 sec ago
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Pulmonary Artery Embolization after Blunt Trauma.

J Vasc Interv Radiol. 2017 Jul;28(7):1011

Authors: Maury JM, Saiedi H, Revel D

PMID: 28645498 [PubMed - in process]

Clinical Characteristics and Outcome of Liver Transplantation for Alagille Syndrome in Children.

Sat, 06/24/2017 - 12:45
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Clinical Characteristics and Outcome of Liver Transplantation for Alagille Syndrome in Children.

J Dig Dis. 2017 Jun 23;:

Authors: Zhou T, Zhang J, Luo Y, Liu Y, Zhuang S, Xue F, Han L, Xia Q

Abstract
AIM: The aim of this study was to analyze clinical characteristics and outcome of liver transplantation for Alagille syndrome in children.
METHOD: By retrospectively reviewing the medical records of 9 Alagille syndrome patients(AGS) with liver transplantation(LT) in Renji Hospital between 2006 and 2015,After operative,the height and weight Z score were compared with preoperative.
RESULT: There were 9 patients included in the study; cholestasis and peculiar faces were seen in all of the patients (100%), heart defect in 8 patients (88.9%), while 6 of them indicated stenosis of pulmonary atria. Complex heart defect(atrial septal defect, pulmonary stenosis and tricuspid insufficiency) existed in 1 patient. Butterfly vertebrae were seen in 4 patients(44.4%) and posterior embryotoxon in 2 patients (22.2%). Liver biopsy after transplantation indicated paucity of interlobular bile in 6 patients(66.7%), intrahepatic cholestasis in 2 patients(22.2%) and biliary proliferation in 1 patient(11.1%). 7 Alagille syndrome patients are still alive with a median follow-up time of 18 month (range: 5 mo. to 31 mo.). 2 patients died due to pulmonary arterial rupture and sepsis. Liver function, serum bilirubin and cholesterol level returned to normal after LT and mass of xanthoma began to decrease. Our results indicate that All 7 survivors showed catch-up growth during follow-up. Mean height Z score improved from -3.7 to -0.8 two years after LT and weight Z score from -3.3 to 0.45.
CONCLUSION: Liver transplantation is an effective treatment for Alagille syndrome with end-stage liver disease, which is better for the patients' growth.

PMID: 28644566 [PubMed - as supplied by publisher]

Mechanical Circulatory Support in the Treatment of Advanced Heart Failure.

Sat, 06/24/2017 - 12:45
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Mechanical Circulatory Support in the Treatment of Advanced Heart Failure.

Am J Transplant. 2017 Jun 22;:

Authors: Cai AW, Islam S, Hankins SR, Fischer W, Eisen HJ

Abstract
According to the Centers for Disease Control (CDC), heart failure (HF) remains a pervasive condition with high morbidity and mortality, affecting 5.8 million people in the United States (US) and 23 million worldwide. For patients with refractory end-stage HF, heart transplantation is the gold standard for definitive treatment. However, the demand for heart transplantation has consistently exceeded the availability of donor hearts, with approximately 2,331 orthotopic heart transplantations performed in the US in 2015 despite an estimated 100,000 to 250,000 patients with New York Heart Association (NYHA) class IIIB or IV symptoms that are refractory to medical treatment and potential transplant candidates. 1, 2, 3 As such, the need for mechanical circulatory support (MCS) to treat patients with end-stage heart failure has become paramount. In this review, we focus on the history, advancements, and current use of durable MCS device therapy in the treatment of advanced heart failure. This article is protected by copyright. All rights reserved.

PMID: 28643428 [PubMed - as supplied by publisher]

Safe and effective administration of T-VEC in a patient with heart transplantation and recurrent locally advanced melanoma.

Sat, 06/24/2017 - 12:45
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Safe and effective administration of T-VEC in a patient with heart transplantation and recurrent locally advanced melanoma.

J Immunother Cancer. 2017;5:45

Authors: Schvartsman G, Perez K, Flynn JE, Myers JN, Tawbi H

Abstract
BACKGROUND: Immunotherapy plays a key role in the treatment of metastatic melanoma. Patients with autoimmune conditions and/or on immunosuppressive therapy due to orthotropic transplants, however, are systematically excluded from clinical trials. Talimogene laherparepvec (T-VEC) is the first oncolytic virus to be approved by the FDA for cancer therapy. To our knowledge, this is the first report of T-VEC being administered in the setting of an organ transplant recipient.
CASE PRESENTATION: Here we present the case of a patient with recurrent locally advanced cutaneous melanoma receiving salvage T-VEC therapy in the setting of orthotropic heart transplantation. After 5 cycles of therapy, no evidence of graft rejection has been observed to date, and the patient achieved a complete remission, and is currently off therapy.
CONCLUSION: This case advocates for further investigation on the safety and efficacy of immunotherapeutic approaches, such as T-VEC, in solid organ transplant recipients.

PMID: 28642816 [PubMed - in process]

Regarding mechanical circulatory support in adults with congenital heart disease: Is it time to lower the threshold for use?

Sat, 06/24/2017 - 12:45
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Regarding mechanical circulatory support in adults with congenital heart disease: Is it time to lower the threshold for use?

J Heart Lung Transplant. 2017 May 29;:

Authors: Bryant R, Morales DLS

PMID: 28642001 [PubMed - as supplied by publisher]

Initial experience with the HeartMate percutaneous heart pump in circulatory failure.

Sat, 06/24/2017 - 12:45
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Initial experience with the HeartMate percutaneous heart pump in circulatory failure.

J Heart Lung Transplant. 2017 May 20;:

Authors: Maly J, Ivak P, Netuka I, Herman A, Kettner J, Sood P, Jorde UP

PMID: 28642000 [PubMed - as supplied by publisher]

Cardiac Sympathetic Denervation for Refractory Ventricular Arrhythmias.

Sat, 06/24/2017 - 12:45
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Cardiac Sympathetic Denervation for Refractory Ventricular Arrhythmias.

J Am Coll Cardiol. 2017 Jun 27;69(25):3070-3080

Authors: Vaseghi M, Barwad P, Malavassi Corrales FJ, Tandri H, Mathuria N, Shah R, Sorg JM, Gima J, Mandal K, Sàenz Morales LC, Lokhandwala Y, Shivkumar K

Abstract
BACKGROUND: Cardiac sympathetic denervation (CSD) has been shown to reduce the burden of implantable cardioverter-defibrillator (ICD) shocks in small series of patients with structural heart disease (SHD) and recurrent ventricular tachyarrhythmias (VT).
OBJECTIVES: This study assessed the value of CSD and the characteristics associated with outcomes in this population.
METHODS: Patients with SHD who underwent CSD for refractory VT or VT storm at 5 international centers were analyzed by the International Cardiac Sympathetic Denervation Collaborative Group. Kaplan-Meier analysis was used to estimate freedom from ICD shock, heart transplantation, and death. Cox proportional hazards models were used to analyze variables associated with ICD shock recurrence and mortality after CSD.
RESULTS: Between 2009 and 2016, 121 patients (age 55 ± 13 years, 26% female, mean ejection fraction of 30 ± 13%) underwent left or bilateral CSD. One-year freedom from sustained VT/ICD shock and ICD shock, transplant, and death were 58% and 50%, respectively. CSD reduced the burden of ICD shocks from a mean of 18 ± 30 (median 10) in the year before study entry to 2.0 ± 4.3 (median 0) at a median follow-up of 1.1 years (p < 0.01). On multivariable analysis, pre-procedure New York Heart Association functional class III and IV heart failure and longer VT cycle lengths were associated with recurrent ICD shocks, whereas advanced New York Heart Association functional class, longer VT cycle lengths, and a left-sided-only procedure predicted the combined endpoint of sustained VT/ICD shock recurrence, death, and transplantation. Of the 120 patients taking antiarrhythmic medications before CSD, 39 (32%) no longer required them at follow-up.
CONCLUSIONS: CSD decreased sustained VT and ICD shock recurrence in patients with refractory VT. Characteristics independently associated with recurrence and mortality were advanced heart failure, VT cycle length, and a left-sided-only procedure.

PMID: 28641796 [PubMed - in process]

Effect of everolimus versus calcineurin inhibitors on quality of life in heart transplant recipients during a 3-year follow up: results of a randomized controlled trial (SCHEDULE).

Sat, 06/24/2017 - 12:45
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Effect of everolimus versus calcineurin inhibitors on quality of life in heart transplant recipients during a 3-year follow up: results of a randomized controlled trial (SCHEDULE).

Clin Transplant. 2017 Jun 22;:

Authors: Relbo Authen A, Grov I, Karason K, Gustafsson F, Eiskjaer H, Rådegran G, Gude E, Jansson K, Dellgren G, Solbu D, Arora S, Andreassen AK, Gullestad L, SCHEDULE investigators

Abstract
The SCHEDULE trial was a 12-month, randomized, open-label, parallel-group trial that compared everolimus (EVR; n=56) to conventional CsA (n=59) immunosuppression. Previously, we reported that EVR outperformed CsA in improving renal function and coronary artery vasculopathy, despite a higher rejection rate with EVR. The present study aimed to compare the effects of these treatments on quality of life (QoL). Within 5 postoperative days, patients (mean age 50±13 years, 27% women) were randomized to EVR or a standard CsA dosage (CsA group). This. study assessed quality of life (QoL), based on the Short Form-36, EuroQol-5D, and Beck Depression Inventory (BDI). Assessments were performed pre-HTx and 12 and 36 months post-HTx. At 12 and 36 months, the groups showed similar improvements in Short Form-36 measures (at pre-HTx, 12 and 36 months the values were: physical component summary: EVR: 31.5±110.9, 49.1±9.7 and 47.9± 10.6; p<0.01; CsA: 32.5±8.2, 48.4±8.5 and 46.5±11.5; p<0.01; mental component summary: EVR: 46.0±12.0, 51.7±11.9 and 52.1±13.0; p<0.01; CsA: 38.2±12.5, 53.4±7.1 and 54.3±13.0; p<0.01); similar decrease in mean BDI (EVE:10.9±10.2, 5.4±4.7 and 8.1±9.0; p<0.01; CsA: 11.8±7.1, 6.3±5.4 and 6.2±6.5; p<0.01); and similar Euro Qol- improvements. Thus, in this small-sized study, EVE-based and conventional CsA immunosuppressive strategies produced similar QoL improvements. This article is protected by copyright. All rights reserved.

PMID: 28640529 [PubMed - as supplied by publisher]

Advancing the field of anti-HLA sensitization management prior to pediatric heart transplantation.

Sat, 06/24/2017 - 12:45
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Advancing the field of anti-HLA sensitization management prior to pediatric heart transplantation.

Pediatr Transplant. 2017 Jun 22;:

Authors: Zuckerman WA

PMID: 28639339 [PubMed - as supplied by publisher]

Effect of ethnicity and socioeconomic status on vascular access provision and performance in an urban NHS hospital.

Sat, 06/24/2017 - 12:45
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Effect of ethnicity and socioeconomic status on vascular access provision and performance in an urban NHS hospital.

Clin Kidney J. 2017 Feb;10(1):62-67

Authors: Wilmink T, Wijewardane A, Lee K, Murley A, Hollingworth L, Powers S, Baharani J

Abstract
BACKGROUND: The aim of this study was to examine the effect of ethnicity, socioeconomic group (SEG) and comorbidities on provision of vascular access for haemodialysis (HD).
METHODS: This was a retrospective review of two databases of HD sessions and access operations from 2003-11. Access modality of first HD session and details of transplanted patients were derived from the renal database. Follow-up was until 1 January 2015. Primary failure (PF) was defined as an arteriovenous fistula (AVF) used for fewer than six consecutive dialysis sessions. AVF survival was defined as being until the date the AVF was abandoned. Ethnicity was coded from hospital records. SEG was calculated from postcodes and 2011 census data from the Office of National Statistics. Comorbidities were calculated with the Charlson Comorbidity Index.
RESULTS: Five hundred incident patients started chronic HD in the study period. Mode of starting HD was not associated with ethnicity (P = 0.27) or SEG (P = 0.45). Patients from ethnic minorities were younger when starting dialysis (P < 0.0001). Some 928 AVF patients' first AVF operations were analysed: 68% Caucasian, 26% Asian and 6% Afro-Caribbean. Half were in the most deprived SEG and 11% in the least deprived SEG. PF did not differ by ethnicity (P = 0.29), SEG (P = 0.75) or comorbidities (P = 0.54). AVF survival was not different according to ethnicity (P = 0.13) or SEG (P = 0.87). AVF survival was better for patients with a low comorbidity score (P = 0.04). The distribution of transplant recipients by ethnic group and SEG was similar to the distributions of all HD starters.
CONCLUSION: Ethnicity and socioeconomic group had no effect on mode of starting HD, primary AVF failure rate or AVF survival. Ethnic minorities were younger at start of dialysis and at their first AVF operation.

PMID: 28638605 [PubMed - in process]

Cardiac Rehabilitation for Patients With Coronary Artery Disease: A Practical Guide to Enhance Patient Outcomes Through Continuity of Care.

Sat, 06/24/2017 - 12:45
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Cardiac Rehabilitation for Patients With Coronary Artery Disease: A Practical Guide to Enhance Patient Outcomes Through Continuity of Care.

Clin Med Insights Cardiol. 2017;11:1179546817710028

Authors: Giuliano C, Parmenter BJ, Baker MK, Mitchell BL, Williams AD, Lyndon K, Mair T, Maiorana A, Smart NA, Levinger I

Abstract
Coronary artery disease (CAD) is a leading cause of disease burden worldwide. Referral to cardiac rehabilitation (CR) is a class I recommendation for all patients with CAD based on findings that participation can reduce cardiovascular and all-cause mortality, as well as improve functional capacity and quality of life. However, programme uptake remains low, systematic progression through the traditional CR phases is often lacking, and communication between health care providers is frequently suboptimal, resulting in fragmented care. Only 30% to 50% of eligible patients are typically referred to outpatient CR and fewer still complete the programme. In contemporary models of CR, patients are no longer treated by a single practitioner, but rather by an array of health professionals, across multiples specialities and health care settings. The risk of fragmented care in CR may be great, and a concerted approach is required to achieve continuity and optimise patient outcomes. 'Continuity of care' has been described as the delivery of services in a coherent, logical, and timely fashion and which entails 3 specific domains: informational, management, and relational continuity. This is examined in the context of CR.

PMID: 28638244 [PubMed - in process]

Paradoxical Suppression of Atherosclerosis in the Absence of microRNA-146a.

Sat, 06/24/2017 - 12:45
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Paradoxical Suppression of Atherosclerosis in the Absence of microRNA-146a.

Circ Res. 2017 Jun 21;:

Authors: Cheng HS, Besla R, Li A, Chen Z, Shikatani EA, Nazari-Jahantigh M, Hammoutène A, Nguyen MA, Geoffrion M, Cai L, Khyzha N, Li T, MacParland SA, Husain M, Cybulsky MI, Boulanger CM, Temel RE, Schober A, Rayner KJ, Robbins C, Fish JE

Abstract
Rationale: Inflammation is a key contributor to atherosclerosis. MicroRNA-146a (miR-146a) has been identified as a critical brake on pro-inflammatory NF-κB signalling in several cell types, including endothelial cells and bone marrow-derived cells. Importantly, miR-146a expression is elevated in human atherosclerotic plaques, and polymorphisms in the miR-146a pre-cursor have been associated with risk of coronary artery disease. Objective: To define the role of endogenous miR-146a during atherogenesis. Methods and Results: Paradoxically, Low-density lipoprotein receptor (Ldlr)(-/-) mice deficient in miR-146a develop less atherosclerosis, despite having highly elevated levels of circulating pro-inflammatory cytokines. In contrast, cytokine levels are normalized in Ldlr(-/-);miR-146a(-/-) mice receiving wild-type bone marrow transplantation, and these mice have enhanced endothelial cell activation and elevated atherosclerotic plaque burden compared to Ldlr(-/-) mice receiving wild-type bone marrow; demonstrating the atheroprotective role of miR-146a in the endothelium. We find that deficiency of miR-146a in bone marrow-derived cells precipitates defects in hematopoietic stem cell function, contributing to extramedullary hematopoiesis, splenomegaly, bone marrow failure and decreased levels of circulating pro-atherogenic cells in mice fed an atherogenic diet. These hematopoietic phenotypes appear to be driven by unrestrained inflammatory signalling that leads to the expansion and eventual exhaustion of hematopoietic cells, and this occurs in the face of lower levels of circulating LDL cholesterol in mice lacking miR-146a in bone marrow-derived cells. Furthermore, we identify Sort1, a known regulator of circulating LDL levels in humans, as a novel target of miR-146a. Conclusions: Our study reveals that miR-146a regulates cholesterol metabolism and tempers chronic inflammatory responses to atherogenic diet by restraining pro-inflammatory signalling in endothelial cells and bone marrow-derived cells.

PMID: 28637783 [PubMed - as supplied by publisher]

Progressive Aortic Stenosis in Homozygous Familial Hypercholesterolemia After Liver Transplant.

Sat, 06/24/2017 - 12:45
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Progressive Aortic Stenosis in Homozygous Familial Hypercholesterolemia After Liver Transplant.

Pediatrics. 2016 Nov;138(5):

Authors: Greco M, Robinson JD, Eltayeb O, Benuck I

Abstract
Early onset coronary artery disease and aortic calcifications are characteristic features of patients with homozygous familial hypercholesterolemia. Standard medical therapy includes dietary modification, pharmacotherapy, and lipoprotein apheresis to lower serum low-density lipoprotein cholesterol (LDL-C). Liver transplant is a surgical option for the treatment of homozygous familial hypercholesterolemia and can lead to normal cholesterol levels. Vascular calcifications are known to progress despite standard medical therapy and have been reported after liver transplant in the setting of rejection. We present the first report of progressive severe aortic valve stenosis in a patient despite liver transplant with normalization of lipid levels and no history of graft rejection.

PMID: 27940769 [PubMed - indexed for MEDLINE]

Short- and Long-Term Mortality Rates of Elderly Acute Kidney Injury Patients Who Underwent Continuous Renal Replacement Therapy.

Sat, 06/24/2017 - 12:45
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Short- and Long-Term Mortality Rates of Elderly Acute Kidney Injury Patients Who Underwent Continuous Renal Replacement Therapy.

PLoS One. 2016;11(11):e0167067

Authors: Rhee H, Jang KS, Park JM, Kang JS, Hwang NK, Kim IY, Song SH, Seong EY, Lee DW, Lee SB, Kwak IS

Abstract
BACKGROUND: The world's population is aging faster and the incidence of acute kidney injury (AKI) needing continuous renal replacement therapy (CRRT) is increasing in elderly population. The outcome of AKI needing CRRT in elderly patients is known to be poor. However, the definitions of elderly used in the previous literatures were diverse and, there were few data that compared the long-term mortality rates of these patients with middle aged patients. This study was aimed to evaluate this issue.
METHODS: This study was a single-center, retrospective cohort study of patients who underwent CRRT from January 2013 to December 2015. The patients were divided into the following four age cohorts: middle-aged (55-64), young-old (65-74), middle-old (75-84), and old-old (≥85). The short- and long-term mortality rates for each age cohort were compared.
RESULTS: A total of 562 patients met the inclusion criteria. The short-term mortality rate was 57.3% in the entire cohort. Compared with the middle-aged cohort, the middle-old cohort (HR 1.48 (1.09-2.02), p = 0.012) and the old-old cohort (HR 2.33 (1.30-4.19), p = 0.005) showed an increased short-term mortality rate along with an increased SOFA score, acidemia and a prolonged prothrombin time. When we analyzed the long-term mortality rate of the 238 survived patients, the middle-old cohort (HR 3.76 (1.84-7.68), p<0.001), the old-old cohort (HR 4.40(1.20-16.10), p = 0.025), a lower BMI, the presence of liver cirrhosis, the presence of congestive heart failure and a history of sepsis were independent risk factors for the prediction of long-term mortality.
CONCLUSION: Compared with the middle-aged cohort, the middle-old and the old-old cohort showed an increased short-term and long-term mortality rate. However, in the young-old cohort, neither the short-term nor the long-term mortality rate was increased.

PMID: 27875571 [PubMed - indexed for MEDLINE]

Towards a Tissue-Engineered Contractile Fontan-Conduit: The Fate of Cardiac Myocytes in the Subpulmonary Circulation.

Sat, 06/24/2017 - 12:45
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Towards a Tissue-Engineered Contractile Fontan-Conduit: The Fate of Cardiac Myocytes in the Subpulmonary Circulation.

PLoS One. 2016;11(11):e0166963

Authors: Biermann D, Eder A, Arndt F, Seoudy H, Reichenspurner H, Mir T, Riso A, Kozlik-Feldmann R, Peldschus K, Kaul MG, Schuler T, Krasemann S, Hansen A, Eschenhagen T, Sachweh JS

Abstract
The long-term outcome of patients with single ventricles improved over time, but remains poor compared to other congenital heart lesions with biventricular circulation. Main cause for this unfavourable outcome is the unphysiological hemodynamic of the Fontan circulation, such as subnormal systemic cardiac output and increased systemic-venous pressure. To overcome this limitation, we are developing the concept of a contractile extracardiac Fontan-tunnel. In this study, we evaluated the survival and structural development of a tissue-engineered conduit under in vivo conditions. Engineered heart tissue was generated from ventricular heart cells of neonatal Wistar rats, fibrinogen and thrombin. Engineered heart tissues started beating around day 8 in vitro and remained contractile in vivo throughout the experiment. After culture for 14 days constructs were implanted around the right superior vena cava of Wistar rats (n = 12). Animals were euthanized after 7, 14, 28 and 56 days postoperatively. Hematoxylin and eosin staining showed cardiomyocytes arranged in thick bundles within the engineered heart tissue-conduit. Immunostaining of sarcomeric actin, alpha-actin and connexin 43 revealed a well -developed cardiac myocyte structure. Magnetic resonance imaging (d14, n = 3) revealed no constriction or stenosis of the superior vena cava by the constructs. Engineered heart tissues survive and contract for extended periods after implantation around the superior vena cava of rats. Generation of larger constructs is warranted to evaluate functional benefits of a contractile Fontan-conduit.

PMID: 27875570 [PubMed - indexed for MEDLINE]

Challenges to success in heart failure: Cardiac cell therapies in patients with heart diseases.

Sat, 06/24/2017 - 12:45
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Challenges to success in heart failure: Cardiac cell therapies in patients with heart diseases.

J Cardiol. 2016 Nov;68(5):361-367

Authors: Oh H, Ito H, Sano S

Abstract
Heart failure remains the leading cause of death worldwide, and is a burgeoning problem in public health due to the limited capacity of postnatal hearts to self-renew. The pathophysiological changes in injured hearts can sometimes be manifested as scar formation or myocardial degradation, rather than supplemental muscle regeneration to replenish lost tissue during the healing processes. Stem cell therapies have been investigated as a possible treatment approach for children and adults with potentially fatal cardiovascular disease that does not respond to current medical therapies. Although the heart is one of the least regenerative organs in mammals, discoveries made during the past few decades have improved our understanding of cardiac development and resident stem/progenitor pools, which may be lineage-restricted subpopulations during the post-neonatal stage of cardiac morphogenesis. Recently, investigation has specifically focused on factors that activate either endogenous progenitor cells or preexisting cardiomyocytes, to regenerate cardiovascular cells and replace the damaged heart tissues. The discovery of induced pluripotent stem cells has advanced our technological capability to direct cardiac reprogramming by essential factors that are crucial for heart field completion in each stage. Cardiac tissue engineering technology has recently shown progress in generating myocardial tissue on human native cardiac extracellular matrix scaffolds. This review summarizes recent advances in the field of cardiac cell therapies with an emphasis on cellular mechanisms, such as bone marrow stem cells and cardiac progenitor cells, which show the high potential for success in preclinical and clinical meta-analysis studies. Expanding our current understanding of mechanisms of self-renewal in the neonatal mammalian heart may lead to the development of novel cardiovascular regenerative medicines for pediatric heart diseases.

PMID: 27341741 [PubMed - indexed for MEDLINE]

The effect of CD34(+) cell telomere length and hTERT expression on the outcome of autologous CD34(+) cell transplantation in patients with chronic heart failure.

Thu, 06/22/2017 - 12:45
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The effect of CD34(+) cell telomere length and hTERT expression on the outcome of autologous CD34(+) cell transplantation in patients with chronic heart failure.

Mech Ageing Dev. 2017 Jun 18;:

Authors: Rozman JZ, Perme MP, Jez M, Malicev E, Krasna M, Novakovic S, Vrtovec B, Rozman P

Abstract
Age-related telomere attrition in stem/progenitor cells may diminish their functional capacity and thereby impair the outcome of cell-based therapies. The aim of the present study was to investigate the effect of CD34(+) cell telomere length and hTERT expression on the clinical outcome of autologous CD34(+) cell transplantation. We studied 43 patients with cardiomyopathy. Their peripheral blood CD34(+) cells were mobilized with granulocyte colony-stimulating factor, enriched by immunoselection and delivered transendocardially. Relative telomere length and expression levels of hTERT were measured using a real-time PCR assay. Immunoselected CD34(+) cells had longer telomere length compared to leukocytes in leukapheresis products (p=0.001). In multivariate analysis, CD34(+) cell telomere length was not associated with the clinical outcome (b=3.306, p=0.540). While hTERT expression was undetectable in all leukapheresis products, 94.4% of the CD34(+) enriched cell products expressed hTERT. Higher CD34(+)hTERT expression was associated with a better clinical outcome on univariate analysis (b=87.911, p=0.047). Our findings demonstrate that CD34(+) cell telomere length may not influence the clinical outcome in cardiomyopathy patients treated with autologous CD34(+) cell transplantation. Larger studies are needed to validate the impact of the CD34(+)hTERT expression on the clinical outcome of autologous CD34(+) cell transplantation.

PMID: 28636901 [PubMed - as supplied by publisher]

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