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Immunological Serum Protein Profiles for Noninvasive Detection of Acute Cellular Rejection After Heart Transplantation.

Sat, 12/09/2017 - 13:45
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Immunological Serum Protein Profiles for Noninvasive Detection of Acute Cellular Rejection After Heart Transplantation.

J Am Coll Cardiol. 2017 Dec 12;70(23):2946-2947

Authors: Sukma Dewi I, Gidlöf O, Hollander Z, Lam KK, Benson MD, Braun OO, Nilsson J, Tebbutt SJ, Ng RT, Öhman J, McManus BM, Smith JG

PMID: 29216990 [PubMed - in process]

Expression of a Chimeric Antigen Receptor Specific for Donor HLA Class I Enhances the Potency of Human Regulatory T Cells in Preventing Human Skin Transplant Rejection.

Sat, 12/09/2017 - 13:45
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Expression of a Chimeric Antigen Receptor Specific for Donor HLA Class I Enhances the Potency of Human Regulatory T Cells in Preventing Human Skin Transplant Rejection.

Am J Transplant. 2017 Apr;17(4):931-943

Authors: Boardman DA, Philippeos C, Fruhwirth GO, Ibrahim MA, Hannen RF, Cooper D, Marelli-Berg FM, Watt FM, Lechler RI, Maher J, Smyth LA, Lombardi G

Abstract
Regulatory T cell (Treg) therapy using recipient-derived Tregs expanded ex vivo is currently being investigated clinically by us and others as a means of reducing allograft rejection following organ transplantation. Data from animal models has demonstrated that adoptive transfer of allospecific Tregs offers greater protection from graft rejection compared to polyclonal Tregs. Chimeric antigen receptors (CAR) are clinically translatable synthetic fusion proteins that can redirect the specificity of T cells toward designated antigens. We used CAR technology to redirect human polyclonal Tregs toward donor-MHC class I molecules, which are ubiquitously expressed in allografts. Two novel HLA-A2-specific CARs were engineered: one comprising a CD28-CD3ζ signaling domain (CAR) and one lacking an intracellular signaling domain (ΔCAR). CAR Tregs were specifically activated and significantly more suppressive than polyclonal or ΔCAR Tregs in the presence of HLA-A2, without eliciting cytotoxic activity. Furthermore, CAR and ΔCAR Tregs preferentially transmigrated across HLA-A2-expressing endothelial cell monolayers. In a human skin xenograft transplant model, adoptive transfer of CAR Tregs alleviated the alloimmune-mediated skin injury caused by transferring allogeneic peripheral blood mononuclear cells more effectively than polyclonal Tregs. Our results demonstrated that the use of CAR technology is a clinically applicable refinement of Treg therapy for organ transplantation.

PMID: 28027623 [PubMed - indexed for MEDLINE]

[Study of migration and distribution of bone marrow cells transplanted animals with B16 melanoma ].

Fri, 12/08/2017 - 13:45

[Study of migration and distribution of bone marrow cells transplanted animals with B16 melanoma ].

Patol Fiziol Eksp Ter. 2017 Apr-Jun;61(2):10-21

Authors: Poveshchenko AF, Solovieva AO, Zubareva KE, Strunkin DN, Gricyk OB, Poveshchenko OV, Shurlygina AV, Konenkov VI

Abstract
Purpose. Reveal features migration and distribution of syngeneic bone marrow cells (BMC) and subpopulations (MSC) after transplantation into the recipient carrier B16 melanoma bodies. Methods. We used mouse male and female C57BL/6 mice. Induction of Tumor Growth: B16 melanoma cells implanted subcutaneously into right hind paw of female C57BL/6 mice at a dose of 2.5 x 105 cells / mouse. migration study in vivo distribution and BMC and MSC was performed using genetic markers - Y-chromosome specific sequence line male C57Bl/6 syngeneic intravenous transplantation in females using the polymerase chain reaction (PCR) in real time on Authorized Termal Cycler - Light Cycler 480 II / 96 (Roche). Introduction suspension of unseparated bone marrow cells, mesenchymal stem cells from donor to recipient male mice (syngeneic recipient female C57BL/6), followed by isolation of recipients of organs was performed at regular intervals, then of organ recipients isolated DNA. Results. It was shown that bone marrow cells positive for Y-chromosome in migrate lymphoid (lymph nodes, spleen, bone marrow) or in non-lymphoid organs (liver, heart, brain, skin) syngeneic recipients. In addition to the migration of cells from the bone marrow to other organs, there is a way back migration of cells from the circulation to the bone marrow. B16 melanoma stimulates the migration of transplanted MSCs and BMC in bone marrow. It is found that tumor growth enhanced migration of transplanted bone marrow cells, including populations of MSCs in the bone marrow. In the early stages of tumor formation MSC migration activity higher than the BMC. In the later stages of tumor formation undivided population of bone marrow cells migrate to the intense swelling compared with a population of MSCs. Conclusion. The possibility of using bone marrow MSCs for targeted therapy of tumor diseases, because migration of MSCs in tumor tissue can be used to effectively deliver anticancer drugs.

PMID: 29215830 [PubMed - as supplied by publisher]

Influence of Blood Pressure and Calcineurin Inhibitors on Kidney Function After Heart or Liver Transplantation.

Fri, 12/08/2017 - 13:45

Influence of Blood Pressure and Calcineurin Inhibitors on Kidney Function After Heart or Liver Transplantation.

Transplantation. 2017 Dec 05;:

Authors: Morath C, Opelz G, Döhler B, Zeier M, Süsal C

Abstract
BACKGROUND: Chronic kidney disease is common after heart or liver transplantation, with calcineurin inhibitors (CNI) considered the key contributor. A possible influence of posttransplant blood pressure has not been extensively examined.
METHODS: Data from adult recipients of a first heart or liver transplant were analyzed regarding the relationship between blood pressure at year 1, renal function at year 5, and CNI therapy.
RESULTS: Whereas we confirmed the well-known detrimental effect of increased 1-year systolic blood pressure on 5-year kidney graft survival, heart or liver graft survival were not affected. However, among 2,534 heart transplant recipients with good renal function at year 1, increasing systolic blood pressure at year 1 was associated with higher rates of poor renal function at year 5 posttransplant. This association was confirmed on multivariate analysis overall (odds ratio [OR] 1.25 per 20 mmHg increment, P<0.001) and within subgroups. Similar results were observed in 1,822 liver transplant recipients (OR 1.35, P<0.001). Neither the type of CNI nor CNI dose or trough level at year 1 showed a significant association with kidney function at year 5.
CONCLUSIONS: One-year blood pressure was identified as the major modifiable risk factor associated with deteriorating kidney function between years 1 to 5 after heart or liver transplantation.

PMID: 29215461 [PubMed - as supplied by publisher]

Multi-center Performance Evaluations of Tacrolimus and Cyclosporine Electrochemiluminescence Immunoassays in the Asia-Pacific Region.

Fri, 12/08/2017 - 13:45

Multi-center Performance Evaluations of Tacrolimus and Cyclosporine Electrochemiluminescence Immunoassays in the Asia-Pacific Region.

Ann Lab Med. 2018 Mar;38(2):85-94

Authors: Qin X, Rui J, Xia Y, Mu H, Song SH, Raja Aziddin RE, Miles G, Sun Y, Chun S

Abstract
BACKGROUND: The immunosuppressant drugs (ISDs), tacrolimus and cyclosporine, are vital for solid organ transplant patients to prevent rejection. However, toxicity is a concern, and absorption is highly variable across patients; therefore, ISD levels need to be precisely monitored. In the Asia-Pacific (APAC) region, tacrolimus and cyclosporine concentrations are typically measured using immunoassays. The objective of this study was to assess the analytical performance of Roche Elecsystacrolimus and cyclosporinee electrochemiluminescence immunoassays (ECLIAs).
METHODS: This evaluation was performed in seven centers across China, South Korea, and Malaysia. Imprecision (repeatability and reproducibility), assay accuracy, and lot-to-lot reagent variability were tested. The Elecsys ECLIAs were compared with commercially available immunoassays (Architect, Dimension, and Viva-E systems) using whole blood samples from patients with various transplant types (kidney, liver, heart, and bone marrow).
RESULTS: Coefficients of variation for repeatability and reproducibility were ≤5.4% and ≤12.4%, respectively, for the tacrolimus ECLIA, and ≤5.1% and ≤7.3%, respectively, for the cyclosporine ECLIA. Method comparisons of the tacrolimus ECLIA with Architect, Dimension, and Viva-E systems yielded slope values of 1.01, 1.14, and 0.897, respectively. The cyclosporine ECLIA showed even closer agreements with the Architect, Dimension, and Viva-E systems (slope values of 1.04, 1.04, and 1.09, respectively). No major differences were observed among the different transplant types.
CONCLUSIONS: The tacrolimus and cyclosporine ECLIAs demonstrated excellent precision and close agreement with other immunoassays tested. These results show that both assays are suitable for ISD monitoring in an APAC population across a range of different transplant types.

PMID: 29214751 [PubMed - in process]

Heart transplantation turns 50 and is going strong.

Fri, 12/08/2017 - 13:45

Heart transplantation turns 50 and is going strong.

Eur J Heart Fail. 2017 Dec 07;:

Authors: Crespo-Leiro MG, Gustafsson F

PMID: 29214698 [PubMed - as supplied by publisher]

PD-L1 Prevents the Development of Autoimmune Heart Disease in Graft-versus-Host Disease.

Fri, 12/08/2017 - 13:45

PD-L1 Prevents the Development of Autoimmune Heart Disease in Graft-versus-Host Disease.

J Immunol. 2017 Dec 06;:

Authors: Juchem KW, Sacirbegovic F, Zhang C, Sharpe AH, Russell K, McNiff JM, Demetris AJ, Shlomchik MJ, Shlomchik WD

Abstract
Effector memory T cells (TEM) are less capable of inducing graft-versus-host disease (GVHD) compared with naive T cells (TN). Previously, in the TS1 TCR transgenic model of GVHD, wherein TS1 CD4 cells specific for a model minor histocompatibility Ag (miHA) induce GVHD in miHA-positive recipients, we found that cell-intrinsic properties of TS1 TEM reduced their GVHD potency relative to TS1 TN Posttransplant, TS1 TEM progeny expressed higher levels of PD-1 than did TS1 TN progeny, leading us to test the hypothesis that TEM induce less GVHD because of increased sensitivity to PD-ligands. In this study, we tested this hypothesis and found that indeed TS1 TEM induced more severe skin and liver GVHD in the absence of PD-ligands. However, lack of PD-ligands did not result in early weight loss and colon GVHD comparable to that induced by TS1 TN, indicating that additional pathways restrain alloreactive TEM TS1 TN also caused more severe GVHD without PD-ligands. The absence of PD-ligands on donor bone marrow was sufficient to augment GVHD caused by either TEM or TN, indicating that donor PD-ligand-expressing APCs critically regulate GVHD. In the absence of PD-ligands, both TS1 TEM and TN induced late-onset myocarditis. Surprisingly, this was an autoimmune manifestation, because its development required non-TS1 polyclonal CD8+ T cells. Myocarditis development also required donor bone marrow to be PD-ligand deficient, demonstrating the importance of donor APC regulatory function. In summary, PD-ligands suppress both miHA-directed GVHD and the development of alloimmunity-induced autoimmunity after allogeneic hematopoietic transplantation.

PMID: 29212909 [PubMed - as supplied by publisher]

Genetic Variants Contributing to Circulating Matrix Metalloproteinase 8 Levels and Their Association With Cardiovascular Diseases: A Genome-Wide Analysis.

Fri, 12/08/2017 - 13:45

Genetic Variants Contributing to Circulating Matrix Metalloproteinase 8 Levels and Their Association With Cardiovascular Diseases: A Genome-Wide Analysis.

Circ Cardiovasc Genet. 2017 Dec;10(6):

Authors: Salminen A, Vlachopoulou E, Havulinna AS, Tervahartiala T, Sattler W, Lokki ML, Nieminen MS, Perola M, Salomaa V, Sinisalo J, Meri S, Sorsa T, Pussinen PJ

Abstract
BACKGROUND: Matrix metalloproteinase 8 (MMP-8) is a proinflammatory enzyme expressed mainly by neutrophils. Elevated serum and plasma concentrations of MMP-8 are associated with the risk for and outcome of cardiovascular diseases (CVDs). The origin of circulating MMP-8 is not completely clear.
METHODS AND RESULTS: We performed a genome-wide association study of serum MMP-8 levels in 2 populations comprising altogether 6049 individuals. Moreover, we studied whether MMP-8-associated variants are linked to increased risk of CVDs and overall mortality in >20 000 subjects. The strongest association with serum MMP-8 was found in locus 1q31.3, containing the gene for complement factor H (lead single nucleotide polymorphism: rs800292; P=2.4×10-35). In functional experiments, activation of the alternative pathway of complement in the carriers of rs800292 minor allele (Ile62 in factor H) led to decreased release of MMP-8 from neutrophils compared with the major allele (Val62 in factor H). Another association was detected in 1q21.3, containing genes S100A8, S100A9, and S100A12 (strongest association: rs1560833; P=5.3×10-15). The minor allele of rs1560833 was inversely associated with CVD (odds ratio [95% confidence interval]: 0.90 [0.82-0.99]; P=0.032) and the time to incident CVD event (hazard ratio [95% confidence interval]: 0.91 [0.84-0.99]; P=0.032) in men but not in women.
CONCLUSIONS: According to our results, the activation of the alternative pathway of the complement system strongly contributes to serum MMP-8 concentration. Genetic polymorphism in S100A9-S100A12-S100A8 locus affects serum and plasma MMP-8 and shows a suggestive association with the risk of CVDs. Our results show that genetic variation determines a significant portion of circulating MMP-8 concentrations.

PMID: 29212897 [PubMed - in process]

Low Nasal NO in Congenital Heart Disease With Systemic Right Ventricle and Postcardiac Transplantation.

Fri, 12/08/2017 - 13:45

Low Nasal NO in Congenital Heart Disease With Systemic Right Ventricle and Postcardiac Transplantation.

J Am Heart Assoc. 2017 Dec 06;6(12):

Authors: Adams PS, Zahid M, Khalifa O, Feingold B, Lo CW

Abstract
BACKGROUND: NO bioavailability has not been systematically examined in congenital heart disease (CHD). To assess NO in patients with CHD, we measured nasal NO (nNO) generated by the nasal epithelia, given blood NO is difficult to measure (half-life, <2 ms). Given NO's role in hemodynamic regulation and the association of NO bioavailability with heart failure risk, we hypothesized NO levels may differ with varying severity of CHD physiologic characteristics.
METHODS AND RESULTS: Six-hundred eighteen subjects, 483 with CHD and 135 controls, had nNO measured noninvasively via the nares using American Thoracic Society/European Respiratory Society guidelines. Subjects were dichotomized as having low or normal nNO based on age-specific cutoff values. Prevalence of low nNO was examined by various CHD physiologic feature types. Low nNO was more prevalent with CHD than controls (odds ratio, 2.28; P=0.001). A logistic regression model showed overall significance (P=0.035) for single ventricle, systemic right ventricle, ventricular dysfunction, oxygen desaturation, and heterotaxy predicting low nNO, with systemic right ventricle independently having twice the odds of low nNO (odds ratio, 2.04; P=0.014). Patients with low nNO had a higher risk of experiencing heart transplant or death (hazard ratio, 2.75; P=0.048), and heart transplant recipients (N=16) exhibited 5 times the odds of low nNO (69% versus 30%; odds ratio, 5.1; P=0.001).
CONCLUSIONS: Patients with CHD have increased prevalence of low nNO, with highest odds seen with systemic right ventricle and heart transplant. Further studies are needed to investigate heart failure risks in patients with CHD with left versus right systemic ventricle physiologic characteristics and utility of low nNO for predicting heart failure risk.

PMID: 29212650 [PubMed - in process]

History of Heart Transplantation: a Hard and Glorious Journey.

Thu, 12/07/2017 - 13:45

History of Heart Transplantation: a Hard and Glorious Journey.

Braz J Cardiovasc Surg. 2017 Sep-Oct;32(5):423-427

Authors: Stolf NAG

PMID: 29211224 [PubMed - in process]

The Emblematic Year of 2011, Trials and the 50 Years of Heart Transplantation: Three Relevant Issues.

Thu, 12/07/2017 - 13:45

The Emblematic Year of 2011, Trials and the 50 Years of Heart Transplantation: Three Relevant Issues.

Braz J Cardiovasc Surg. 2017 Sep-Oct;32(5):I-II

Authors: Braile DM, Évora PRB

PMID: 29211211 [PubMed - in process]

Do Psychosocial Factors Have Any Impact on Outcomes After Left Ventricular Assist Device Implantation?

Thu, 12/07/2017 - 13:45

Do Psychosocial Factors Have Any Impact on Outcomes After Left Ventricular Assist Device Implantation?

ASAIO J. 2017 Nov 27;:

Authors: Lundgren S, Lowes BD, Zolty R, Burdorf A, Raichlin E, Um JY, Poon C

Abstract
Psychosocial factors have been show to impact survival and outcomes in a number of different diseases, including heart failure and patients receiving heart transplantation. With the increasing utilization of these devices, it is important to identify risk factors that could impact post-left ventricular assist device (LVAD) outcomes. This study was a single center, retrospective analysis of 238 patients who underwent implantation of a LVAD between July 27, 2004, and July 21, 2016, at The University of Nebraska Medical Center. Data collected include length of stay, number of readmission, alive status at 30 days, 180 days, and 1 year, as well as multiple psychosocial factors including history of drug abuse, history of alcohol abuse, history of noncompliance, history of anxiety, and history of depression, among others. Outcomes were calculated using univariate and multivariate analyses with SAS Version 9.4. None of the psychosocial factors assessed in this study showed statistical significance in predicting 30 day or 6 month mortality, but patients who smoked at the time of admission for LVAD implantation had higher mortality at 1 year (odds ratio 4.6, 95% confidence interval, 1.226-15.898, p = 0.011.) Patients with a diagnosis of depression had higher numbers of readmissions compared with those without depression (p = 0.048) with the number of readmissions further increased in patients with a diagnosis of both depression and anxiety (p = 0.0074). Psychosocial determinants do not appear to have a significant effect on mortality, but can result in increased risk of readmission if not adequately addressed before implantation and continually monitored postimplantation.

PMID: 29210773 [PubMed - as supplied by publisher]

Safety of mTOR inhibitor continuation in pediatric heart transplant recipients undergoing surgical procedures.

Thu, 12/07/2017 - 13:45
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Safety of mTOR inhibitor continuation in pediatric heart transplant recipients undergoing surgical procedures.

Pediatr Transplant. 2017 Dec 06;:

Authors: Heble A, Everitt MD, Gralla J, Miyamoto SD, Lahart M, Eshelman J

Abstract
mTOR inhibitors have been associated with SWC when used in the perioperative period. Limited literature is available to guide providers in managing chronic mTOR inhibitor use in the perioperative period, especially in the pediatric setting. The primary aim of this study was to describe the prevalence of SWC with mTOR inhibitor continuation during the perioperative period for major surgeries. Heart transplant recipients ≤25 years old at the time of primary heart transplant receiving sirolimus maintenance therapy during a surgical procedure and within the study period were included. Surgeries identified within the study period included otolaryngology procedures (46.2%), such as tonsillectomies with or without adenoidectomies, cardiac surgeries (30.8%) including a sternal revision, pulmonary vein repair, and pacemaker placement in two patients, orthopedic surgeries (15.4%) including a posterior spinal fusion and an Achilles tendon lengthening with ankle and subtalar joint release, and a neurosurgery (7.7%), which was a ventriculoperitoneal shunt revision. Thirteen surgical encounters were examined. One SWC was observed, an infected pacemaker requiring systemic antibiotics and removal of the device. The results of this study suggest that sirolimus may be continued in the perioperative period based on the low rate of SWC observed.

PMID: 29210159 [PubMed - as supplied by publisher]

The choice of cryopreservation method affects immune compatibility of human cardiovascular matrices.

Thu, 12/07/2017 - 13:45
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The choice of cryopreservation method affects immune compatibility of human cardiovascular matrices.

Sci Rep. 2017 Dec 05;7(1):17027

Authors: Schneider M, Stamm C, Brockbank KGM, Stock UA, Seifert M

Abstract
Conventional frozen cryopreservation (CFC) is currently the gold standard for cardiovascular allograft preservation. However, inflammation and structural deterioration limit transplant durability. Ice-free cryopreservation (IFC) already demonstrated matrix structure preservation combined with attenuated immune responses. In this study, we aim to explore the mechanisms of this diminished immunogenicity in vitro. First, we characterized factors released by human aortic tissue after CFC and IFC. Secondly, we analyzed co-cultures with human peripheral blood mononuclear cells, purified monocytes, T cells and monocyte-derived macrophages to examine functional immune effects triggered by the tissue or released cues. IFC tissue exhibited significantly lower metabolic activity and release of pro-inflammatory cytokines than CFC tissue, but surprisingly, more active transforming growth factor β. Due to reduced cytokine release by IFC tissue, less monocyte and T cell migration was detected in a chemotaxis system. Moreover, only cues from CFC tissue but not from IFC tissue amplified αCD3 triggered T cell proliferation. In a specifically designed macrophage-tissue assay, we could show that macrophages did not upregulate M1 polarization markers (CD80 or HLA-DR) on either tissue type. In conclusion, IFC selectively modulates tissue characteristics and thereby attenuates immune cell attraction and activation. Therefore, IFC treatment creates improved opportunities for cardiovascular graft preservation.

PMID: 29208929 [PubMed - in process]

Heart transplantation at 50.

Thu, 12/07/2017 - 13:45
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Heart transplantation at 50.

Lancet. 2017 Dec 02;390(10111):e43-e45

Authors: Mehra MR

PMID: 29208305 [PubMed - in process]

Thoracic endovascular aortic repair for type B aortic dissection after renal transplantation.

Thu, 12/07/2017 - 13:45
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Thoracic endovascular aortic repair for type B aortic dissection after renal transplantation.

Oncotarget. 2017 Oct 31;8(53):91628-91635

Authors: Shu C, Xiong Q, Qiu J, Luo M, Fang K

Abstract
Thoracic endovascular repair (TEVAR) is an effective treatment for type B aortic dissection (TBAD). Here, we evaluated the early-midterm effectiveness and safety of TEVAR for treating TBAD patients after renal transplantation. Six patients with TBAD treated with TEVAR after renal transplantation were recruited between February 2012 and December 2016. They were then followed up with clinical examinations and computed tomography angiography (CTA). TEVAR was successfully performed in all patients (100%), and the primary tear sites were well covered by stents with or without coverage of the left subclavian artery. No severe complications occurred in any patient during perioperative period. The one-year survival rate was 100%, one patient died of renal graft failure and heart failure four years after TEVAR; the remaining five patients (83.3%) survived and exhibited no severe complications. Our findings show that TEVAR provides satisfactory short-midterm results for TBAD patients after renal transplantation. Moreover, our experience shows that it need relative longer proximal landing zone to prevent the endoleak and recurrence. However, regular hematodialysis, long-term immunosuppressive therapy, and blood pressure control remain crucial factors to prolong survival. Long-term follow-up studies are needed to evaluate the long-term prognosis in these patients.

PMID: 29207672 [PubMed]

Cellular mechanisms underlying cardiac engraftment of stem cells.

Thu, 12/07/2017 - 13:45
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Cellular mechanisms underlying cardiac engraftment of stem cells.

Expert Opin Biol Ther. 2017 Sep;17(9):1127-1143

Authors: Kanda P, Davis DR

Abstract
INTRODUCTION: Over the past decade, it has become clear that long-term engraftment of any ex vivo expanded cell product transplanted into injured myocardium is modest and all therapeutic regeneration is mediated by stimulation of endogenous repair rather than differentiation of transplanted cells into working myocardium. Given that increasing the retention of transplanted cells boosts myocardial function, focus on the fundamental mechanisms limiting retention and survival of transplanted cells may enable strategies to help to restore normal cardiac function. Areas covered: This review outlines the challenges confronting cardiac engraftment of ex vivo expanded cells and explores means of enhancing cell-mediated repair of injured myocardium. Expert opinion: Stem cell therapy has already come a long way in terms of regenerating damaged hearts though the poor retention of transplanted cells limits the full potential of truly cardiotrophic cell products. Multifaceted strategies directed towards fundamental mechanisms limiting the long-term survival of transplanted cells will be needed to enhance transplanted cell retention and cell-mediated repair of damaged myocardium for cardiac cell therapy to reach its full potential.

PMID: 28670973 [PubMed - indexed for MEDLINE]

Functional engineered human cardiac patches prepared from nature's platform improve heart function after acute myocardial infarction.

Thu, 12/07/2017 - 13:45
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Functional engineered human cardiac patches prepared from nature's platform improve heart function after acute myocardial infarction.

Biomaterials. 2016 10;105:52-65

Authors: Wang Q, Yang H, Bai A, Jiang W, Li X, Wang X, Mao Y, Lu C, Qian R, Guo F, Ding T, Chen H, Chen S, Zhang J, Liu C, Sun N

Abstract
With the advent of induced pluripotent stem cells and directed differentiation techniques, it is now feasible to derive individual-specific cardiac cells for human heart tissue engineering. Here we report the generation of functional engineered human cardiac patches using human induced pluripotent stem cells-derived cardiac cells and decellularized natural heart ECM as scaffolds. The engineered human cardiac patches can be tailored to any desired size and shape and exhibited normal contractile and electrical physiology in vitro. Further, when patching on the infarct area, these patches improved heart function of rats with acute myocardial infarction in vivo. These engineered human cardiac patches can be of great value for normal and disease-specific heart tissue engineering, drug screening, and meet the demands for individual-specific heart tissues for personalized regenerative therapy of myocardial damages in the future.

PMID: 27509303 [PubMed - indexed for MEDLINE]

Outcomes After Concomitant Procedures with Left Ventricular Assist Device Implantation: Implications by Device Type and Indication.

Thu, 12/07/2017 - 13:45
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Outcomes After Concomitant Procedures with Left Ventricular Assist Device Implantation: Implications by Device Type and Indication.

ASAIO J. 2016 Jul-Aug;62(4):403-9

Authors: Maltais S, Haglund NA, Davis ME, Aaronson KD, Pagani FD, Dunlay SM, Stulak JM, Mechanical Circulatory Support Network

Abstract
Guidelines for performing concomitant procedures (CPs) in patients undergoing continuous flow-left ventricular assist device (CF-LVAD) implantation are unclear. The impact of an increased surgical complexity outside the constraint of landmark clinical trials has not been reported. From May 2004 to December 2013, 614 patients (499 males, 81%) underwent CF-LVAD implant at our institutions. Median age was 57 ± 13 years and 364 (59%) were bridge to transplantation (BTT). Survival and device-related complications were analyzed and stratified based on the surgical intervention. A total of 398 patients (65%) underwent CF-LVAD implantation without CPs. The remaining patients (35%, n = 216) were grouped according to various CPs. Survival was comparable between groups and not influenced by the CP, device type, or indication for implant. Time-to-first device-related adverse event was shorter in patients with CPs. Regression analysis revealed only increased age (p = 0.03), increase in baseline creatinine (p = 0.002), cardiopulmonary bypass time (p = 0.03), and decreased body mass index (p = 0.03) were predictors of mortality, whereas only age (p = 0.006) and prior sternotomy (p = 0.02) were related to adverse device-related events. Performing CPs leads to comparable survival and device-related outcomes after implant. The decision to perform CPs should be balanced with age, preoperative renal dysfunction, and projected complexity of surgery.

PMID: 27164038 [PubMed - indexed for MEDLINE]

Liver Transplantation in Patients with Alcoholic Liver Disease: A Retrospective Study.

Wed, 12/06/2017 - 13:45
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Liver Transplantation in Patients with Alcoholic Liver Disease: A Retrospective Study.

Alcohol Alcohol. 2017 Dec 01;:1-6

Authors: Vassallo GA, Tarli C, Rando MM, Mosoni C, Mirijello A, Agyei-Nkansah A, Antonelli M, Sestito L, Perotti G, Di Giuda D, Agnes S, Grieco A, Gasbarrini A, Addolorato G, Gemelli OLT Group

Abstract
Aim: Alcoholic liver disease (ALD) is the most common liver disease in the Western World. Liver transplantation (LT) is the treatment for end-stage ALD. However, many transplant centers are still reluctant to transplant these patients because of the risk of alcohol relapse, recurrence of the primary liver disease and associated post-transplant complications. We examined survival rate, prevalence of primary liver disease recurrence, re-transplantation and post-transplant complications among transplanted patients for alcoholic cirrhosis compared with those transplanted for viral cirrhosis.
Methods: data about patients transplanted for alcoholic and viral cirrhosis at the Gemelli Hospital from January 1995 to April 2016 were retrospectively collected. Survival rate was evaluated according to the Kaplan-Meier method. Recurrence was defined as histological evidence of primary liver disease. Data on the onset of complication, causes of death and graft failure after liver transplant were analyzed.
Results: There was no statistically significant difference regarding survival rate between the two groups. Only patients transplanted for viral cirrhosis presented with primary liver disease recurrence. There was a higher rate of cancer development in patients transplanted for alcoholic cirrhosis. Cancer was the major cause of death in this population. Risk factors associated with the onset of cancer were a high MELD score at the transplant time and smoking after transplantation.
Conclusion: ALD is a good indication for LT. Patients transplanted for alcoholic cirrhosis should receive regular cancer screening and should be advised against smoking.
Short Summary: No difference was found between patients transplanted for alcoholic cirrhosis and viral cirrhosis in term of survival rate. Only patients transplanted for viral cirrhosis presented primary liver disease recurrence. A higher rate of cancer development was found in patients transplanted for alcoholic cirrohosis. This complication was associated with post-trasplant smoking.

PMID: 29206894 [PubMed - as supplied by publisher]

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