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Bariatric surgery for a patient with a HeartMate II ventricular assist device for destination therapy.

Sat, 03/02/2013 - 12:48

Bariatric surgery for a patient with a HeartMate II ventricular assist device for destination therapy.

Prog Transplant. 2013 Mar;23(1):28-32

Authors: Lockard KL, Allen C, Lohmann D, Severyn DA, Schaub RD, Kauffman KE, Hodges JR, Woodhall L, Ramanathan R, Teuteberg JJ, Eckert CE, Kormos RL

Abstract
A patient with a HeartMate II left ventricular assist device who had a body mass index of 52 needed gastric bypass surgery in order to qualify for a heart transplant. Unlike previous experience in which the surgery was performed at the implant hospital, the gastric bypass surgery in this case was performed at a bariatric center of excellence that was a separate facility from the implant hospital. The artificial heart program of the University of Pittsburgh Medical Center worked with the bariatric center of excellence in scheduling the gastric bypass surgery using a multidisciplinary team approach at 2 hospitals to coordinate safe, high-quality patient care in a unique situation.

PMID: 23448817 [PubMed - in process]

Survey of transplant-related pharmacy services at large comprehensive transplant centers in the United States.

Sat, 03/02/2013 - 12:48

Survey of transplant-related pharmacy services at large comprehensive transplant centers in the United States.

Prog Transplant. 2013 Mar;23(1):23-7

Authors: Staino C, Lewin JJ, Nesbit TW, Sullivan B, Ensor CR

Abstract
Context-United Network for Organ Sharing (UNOS) 2011 bylaws and Centers for Medicare and Medicaid Services (CMS) regulations require a transplant pharmacist to be an active participant in the care of transplant patients. Transplant centers must be members in good standing with UNOS in order to perform transplants and must be certified by CMS to participate with Medicare.Objective-To identify characteristics of transplant-related pharmacy services at comprehensive transplant centers.Design-Survey regarding number of full-time equivalent (FTE) transplant pharmacists relative to number of annual transplants, transplant pharmacy model, roles in inpatient and clinic environments, training and specialization, funding sources, and expansion plans.Participants-Surveys were received from 14 (74%) of 19 identified centers that performed 200 to 400 kidney, liver, pancreas, simultaneous kidney/pancreas, heart, and lung transplants in 2010, representing 55 transplant pharmacists.Results-A mean of 325 transplants were performed in 2010 at the surveyed centers. The mean number of pharmacist FTEs was 4.25, which yielded a transplant-to-pharmacist ratio of 76.5. Nine centers (64%) practiced in a pharmacy specialist-only model, 12 (86%) practiced in a service-based fashion, and 10 (71%) saw patients in clinic. Fifty-four pharmacists (98%) had obtained a PharmD degree, 45 (82%) had completed 1 postgraduate year, and 28 (51%) had completed 2 postgraduate years of training. Nine centers (64%) funded FTEs solely through the pharmacy department. Ten centers (71%) plan to expand transplant pharmacist staff by a mean of 1.4 FTEs.Conclusions-Large comprehensive transplant centers use multiple transplant pharmacists to perform patient care in the inpatient and outpatient environments. Most centers plan to expand FTEs. Further characterization of transplant pharmacists appears warranted.

PMID: 23448816 [PubMed - in process]

The chicken HS4 core insulator blocks promoter interference in lentiviral vectors.

Sat, 03/02/2013 - 12:48

The chicken HS4 core insulator blocks promoter interference in lentiviral vectors.

Hum Gene Ther Methods. 2013 Mar 1;

Authors: Uchida N, Hanawa H, Yamamoto M, Shimada T

Abstract
Lentiviral vectors including double internal promoters can be utilized to express two transgenes in a single vector construct; however, transcriptional activities from double internal promoters are often inhibited by promoter interference. To determine whether the chicken hypersensitivity site 4 insulator (cHS4) could block promoter interference, lentiviral vectors including an MSCV-U3 promoter (Mp) and an EF1α promoter (Ep) were generated, and transgene expression was evaluated among transduced cells. In the Ep-Mp configuration, transcriptional activity from Mp was much lower, while Mp-Ep had similar transcription levels from both promoters. The cHS4 core insulator increased expression levels from Mp in HeLa cells, hematopoietic cell lines, and mouse peripheral blood cells following hematopoietic stem cell transplantation transduced with the Mp-Ep configured vector. This blocking function was mainly mediated by barrier activity regions in the insulator but not CTCF binding site. CpG methylation did not contribute to this barrier activity. In summary, combining the cHS4 insulator in double promoter vectors can improve transgene expression levels in various cell lines and mouse hematopoietic repopulating cells. These findings are useful for developing hematopoietic stem cell gene therapy.

PMID: 23448496 [PubMed - as supplied by publisher]

Prevalence of renal dysfunction in tacrolimus-treated pediatric transplant recipients: A systematic review.

Sat, 03/02/2013 - 12:48

Prevalence of renal dysfunction in tacrolimus-treated pediatric transplant recipients: A systematic review.

Pediatr Transplant. 2013 Feb 28;

Authors: Gijsen VM, Hesselink DA, Croes K, Koren G, de Wildt SN

Abstract
Renal dysfunction after non-renal transplantation in adult tacrolimus-treated transplant patients is well documented. Little is known about its prevalence in children. Age-related changes in both disposition and effect of tacrolimus as well as renal function may preclude extrapolation of adult data to children. To systematically review the literature on renal dysfunction in non-renal pediatric transplant recipients treated with tacrolimus. PubMed/Medline, Embase, and Google were searched from their inception until April 19, 2012, with the search terms "tacrolimus," "renal function," "transplantation," and "children." Eighteen of 385 retrieved papers were considered relevant. Twelve dealt with liver, four with heart transplant, one with heart and lung transplant, and one with intestinal recipients. Reported prevalences of mild and severe chronic kidney disease ranged from 0% to 39% and 0% to 71.4%, respectively, for liver, and from 22.7% to 40% and 6.8% to 46%, respectively, for heart and/or lung transplant recipients. Ranges remained wide after adjusting for follow-up time and disease severity. Possible explanations are inclusion bias and definitions used for renal dysfunction. A considerable proportion of pediatric non-renal transplant patients who receive tacrolimus-based immunosuppression, appear to suffer from chronic kidney disease. This conclusion warrants further research into the real risk, its risk factors, and individualization of immunosuppressant therapy.

PMID: 23448292 [PubMed - as supplied by publisher]

Management of dialysis access-associated "steal" syndrome with DRIL procedure: challenges and clinical outcomes.

Sat, 03/02/2013 - 12:48
Related Articles

Management of dialysis access-associated "steal" syndrome with DRIL procedure: challenges and clinical outcomes.

J Vasc Access. 2012 Jul-Sep;13(3):299-304

Authors: Anaya-Ayala JE, Pettigrew CD, Ismail N, Diez-De Sollano AL, Syed FA, Ahmed FG, Davies MG, Peden EK

Abstract
PURPOSE: The distal revascularization interval-ligation (DRIL) procedure has demonstrated efficacy in the management of dialysis access-associated steal syndrome (DASS); however, this has not been widely used because of concerns about complexity, risk of ligating a native artery, and lack of long-term outcomes.
METHODS: Retrospective review of all patients with DASS who underwent DRIL procedure from March 2005 to August 2011. Indications, clinical considerations, bypass grafts, and patency rates were determined; complications, reinterventions, and factors influencing their outcomes were studied.
RESULTS: 33 patients, (70% women, mean age of 56 ± 13) with DASS underwent a DRIL. Indications were ischemic pain alone in 12 (36%) patients, loss of neurologic function in 7 (21%), both ischemic pain and loss of neurologic function in 4 (12%) tissue loss in 7 (21%), pain during hemodialysis in one (3%), and "prophylactic" DRIL during a femoral vein transposition (FVt) fistula in two (6%). Technical success was 100%; Ischemic symptoms fully resolved by DRIL in 24 of the 31 symptomatic patients (77%) and during the follow up period DASS did not develop in the subjects we judged at high risk and underwent DRIL during FVt. One serious complication occurred because of early bypass thrombosis causing worsening hand gangrene requiring transmetacarpal amputation. The primary, assisted-primary, and secondary patency rates of the arterial bypass at 12 months were 65%, 75%, and 95% respectively. AV access primary, assisted-primary, and secondary patency were 29%, 85%, and 94% at 12 months.
CONCLUSIONS: DRIL procedure is effective at relieving symptoms in carefully selected patients, but does have potential complications such as bypass failure and worsened ischemia. DASS remains a complex clinical entity in that it is not fully understood, and deserves further study.

PMID: 22266588 [PubMed - indexed for MEDLINE]

Surgical technique for heart transplantation: a strategy for congenital heart disease.

Fri, 03/01/2013 - 12:19

Surgical technique for heart transplantation: a strategy for congenital heart disease.

Eur J Cardiothorac Surg. 2013 Feb 27;

Authors: Hosseinpour AR, González-Calle A, Adsuar-Gómez A, Cuerpo G, Greco R, Borrego-Domínguez JM, Ordoñez A, Wallwork J

Abstract
The standard techniques for orthotopic heart transplantation often require certain adjustments when the procedure is carried out for complex congenital heart disease. This is because of both the unusual anatomy and possible distortions caused by previous surgery. Such technical adjustments have been described in various published reports over the years. Those reports, when combined, do cover the full spectrum of the technical difficulties that may be encountered, whether the defects are in their original form or altered by surgery, such that no cardiac malformation or distortion would prohibit transplantation. However, those reports are comprehensive only when combined. None of the individual reports addresses all the possible technical challenges. Consequently, the available information is somewhat fragmented. In addition, the generic aspect of the described technical strategies is not always given the emphasis that it deserves. Indeed, occasionally a technique may be presented as a specific solution for a specific malformation, without necessarily pointing out that the same technique may be applied to other hearts with different overall pathologies but which share that specific malformation. The aim of this review article was to combine all the available published information in one article in a manner that constructs a simple but comprehensive and generic system of decision-making that may be applied to any heart in order to determine the exact technical adjustments needed for transplantation in each case. Such a strategy is possible for two reasons. First, only a few anatomical sites are technically significant, namely the points of anastomosis between the donor's organ and the recipient. The rest of the intracardiac morphology does not affect the operation and may be ignored. Second, each of those anatomical sites can present difficulties in only a few ways, and each of those few difficulties has a well-described and published solution already. Therefore, the exact technical adjustments required in each case may be worked out by the sequential assessment of the anastomotic sites alone.

PMID: 23447472 [PubMed - as supplied by publisher]

Therapeutic effect of eNOS-transfected endothelial progenitor cells on hemodynamic pulmonary arterial hypertension.

Fri, 03/01/2013 - 12:19

Therapeutic effect of eNOS-transfected endothelial progenitor cells on hemodynamic pulmonary arterial hypertension.

Hypertens Res. 2013 Feb 28;

Authors: Wei L, Zhu W, Xia L, Yang Y, Liu H, Shen J, Zhu J, Xu Y, Yang Z, Wang C

Abstract
Hemodynamic pulmonary arterial hypertension (HPAH) is a common symptom in congenital heart disease (CHD) patients with a left-to-right shunt. Endothelial NO synthase (eNOS) and endothelial-like progenitor cells result in significant improvement of right ventricular systolic pressure in established pulmonary arterial hypertension (PAH) models. We hypothesized that bone marrow (BM)-derived endothelial progenitor cells (EPCs) and eNOS would prevent HPAH in a newly established rat model. The heNOS gene was cloned into a PSUCMV vector, and a high-titer adenovirus was generated. Mononuclear cells (MNCs) from rat BM were differentiated into EPCs by treatment with various cytokines, and a high purity of EPCs (>70%) was confirmed using the markers DiI ac-LDL, UEA-1, vWF and Flk-1. An ideal rat HPAH model was successfully established based on right lung lobectomy, and was confirmed by pressure measurement and histological staining. heNOS was successfully transfected into EPCs, which were then transplanted into HPAH rats. Two weeks after transplantation, the systolic pulmonary arterial blood pressure (sPAP) was significantly reduced by heNOS-EPCs treatment and by transplantation of control EPCs. The high number of muscular pulmonary arteries and the thickness of the muscular coat characteristic of HPAH rats were clearly reversed or even restored to normal levels following transplantation of EPCs, particularly eNOS-EPCs. These findings indicate a critical role of eNOS in HPAH treatment and suggest that eNOS-transfected EPCs may provide an effective strategy for HPAH treatment in CHD patients.Hypertension Research advance online publication, 28 February 2013; doi:10.1038/hr.2012.217.

PMID: 23446773 [PubMed - as supplied by publisher]

HLA compatibility index: does it have a role in patients after heart transplantation?

Fri, 03/01/2013 - 12:19

HLA compatibility index: does it have a role in patients after heart transplantation?

Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2013 Feb 15;

Authors: Bedanova H, Orban M, Ondrasek J, Stepanova R, Nemec P

Abstract
AIMS: To determine the impact of HLA compatibility measured by the Compatibility Index, on survival, rate of rejections, malignancies and infections in patients after heart transplantation (HTx). METHODS: We carried out a retrospective analysis of 182 consecutive patients who underwent heart transplantation in our center from January 2001 to April 2010. According to degree of HLA-A, B and DR matching (Compatibility Index, CI) the patients were divided in two groups, Group A (n=83) with an IC 0-17 and group B (n=99) with an IC 18-26. There was no significant difference in demographic parameters between recipients and donors. RESULTS: We found no difference in rates of rejections or infections between Group A and Group B (AR: 22 (26.5%) vs. 34 (34.3%), P=0.2539; infections: 21 (25.3%) vs. 27 (27%) P=0.7637). The distribution of infections in terms of type (bacterial, viral, fungal, including Aspergillus) was similar in both groups. The incidence of malignant tumours was infrequent (3 (3.6%) vs. 4 (4.0%), P=0.8817). We found trend toward lower level of tacrolimus in Group A. Long term survival was similar in both groups. CONCLUSIONS: Based on the results of our single-center trial, we found no impact of higher degree of HLA-A,-B, and -DR matching on survival, rejection episodes or infection. Further large studies are necessary to confirm our hypothesis that subjects with better HLA compatibility could require lower dose immunosuppression.

PMID: 23446213 [PubMed - as supplied by publisher]

Comparison of left ventricular geometry after HeartMate II and HeartWare left ventricular assist device implantation.

Fri, 03/01/2013 - 12:19

Comparison of left ventricular geometry after HeartMate II and HeartWare left ventricular assist device implantation.

J Cardiothorac Surg. 2013 Feb 28;8(1):31

Authors: Hosseini MT, Popov AF, Simon AR, Amrani M, Bahrami T

Abstract
BACKGROUND: HeartMate II (HM II) and HeartWare (HW) Left Ventricular Assist Devices have been successfully used in end-stage heart failure patients as a bridge to transplantation, recovery, or decision. We set out to compare their effect in off-loading the left ventricle and its geometry. METHODS: The left ventricular end diastolic (LVEDD) and end systolic (LVESD) diameters were compared between first time HM II (n = 25) and HW implantations (n = 24) before and after the operation at 1, 3, and 6 months. A p value of less than 0.05 was considered as significant. RESULTS: Post-operative LVEDD and LVESD at 1, 3, and 6 months were significantly reduced in comparison with pre-operative values in both HM II and HW groups. No significant difference was found comparing HM II and HW groups together before and after the operation. CONCLUSIONS: Our study shows that both HM II and HW can significantly reduce the left ventricular systolic and diastolic dimensions and off-load the left ventricle. The miniaturized nature of HW does not affect its performance and it could be as effective as HM II.

PMID: 23445831 [PubMed - as supplied by publisher]

Drug-related problems and hospital admissions in cardiac transplant recipients.

Fri, 03/01/2013 - 12:19
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Drug-related problems and hospital admissions in cardiac transplant recipients.

Ann Pharmacother. 2012 Oct;46(10):1299-307

Authors: Repp KL, Hayes C, Woods TM, Allen KB, Kennedy K, Borkon MA

Abstract
BACKGROUND: Drug-related problems (DRPs) in the general population account for 15% of all hospital admissions, of which approximately 30% are preventable. Cardiac transplant patients may be at increased risk for DRPs because of their complicated medication regimens that include drugs with a narrow therapeutic index.
OBJECTIVE: To determine the incidence and preventability of DRPs causing hospital admission in cardiac transplant patients at a single institution.
METHODS: Between November 2009 and January 2010, a prospective longitudinal study investigated the incidence and preventability of DRPs in a single cardiac transplant center. Three independent reviewers used validated scoring systems to determine the incidence and preventability of drug-related hospital admissions. DRPs were classified by type, pharmacologic class, and impact on length of stay.
RESULTS: During the 3-month study period, 48 cardiac transplant patients were hospitalized. DRPs accounted for 40% (19/48) of these admissions and 58% (11/19) were adjudicated to be preventable. Common DRPs included supratherapeutic (32%) and subtherapeutic (16%) dosage, adverse drug reaction (32%), drug interaction (5%), and nonadherence (5%). Pharmacologic classes implicated included immunosuppressant (63%), antimicrobial (11%), electrolyte/fluid (11%), and anticoagulant (5%). Average length of stay in drug-related compared to non-drug-related admissions was 11.4 versus 8.5 days (p = 0.458). When annualized, 44 hospitalizations or 500 hospital days may have been prevented.
CONCLUSIONS: Hospital admissions following cardiac transplantation are often drug related (40%) and preventable (58%). Incorporating this insight into the multidisciplinary transplant team may improve outcomes, assist in meeting national quality mandates by the United Network for Organ Sharing and Centers for Medicare Services, and lead to new benchmarks for transplant centers.

PMID: 23032656 [PubMed - indexed for MEDLINE]

Donor Brain Death Exacerbates Complement-Dependent Ischemia Reperfusion Injury in Transplanted Hearts.

Thu, 02/28/2013 - 12:19

Donor Brain Death Exacerbates Complement-Dependent Ischemia Reperfusion Injury in Transplanted Hearts.

Circulation. 2013 Feb 26;

Authors: Atkinson C, Floerchinger B, Qiao F, Casey S, Williamson T, Moseley E, Stoica S, Goddard M, Ge X, Tullius SG, Tomlinson S

Abstract
BACKGROUND: Brain death (BD) can immunologically prime the donor organ and is thought to lead to exacerbated ischemia reperfusion injury (IRI) post-transplantation. Using a newly developed mouse model of BD, we investigated the effect of donor BD on post transplant cardiac IRI. We further investigated the therapeutic effect of a targeted complement inhibitor in recipients of BD donor hearts, and addressed the clinical relevance of these studies by analysis of human heart biopsies from BD and domino (living) donors. METHODS AND RESULTS: Hearts from living or brain dead donor C57BL/6 mice were transplanted into C57BL/6 or BALB/c recipients. Recipient mice were treated with the complement inhibitor CR2-Crry or vehicle control (n=6). Isografts were analyzed 48 hours post-transplant for injury, inflammation and complement deposition, and allografts monitored for graft survival. Human cardiac biopsies were analyzed for complement deposition and inflammatory cell infiltration. In the murine model, donor BD exacerbated IRI and graft rejection as demonstrated by increased myocardial injury, serum cardiac troponin, cellular infiltration, inflammatory chemokine and cytokine levels, complement deposition, and decreased graft survival. CR2-Crry treatment of recipients significantly reduced all measured outcomes in grafts from both BD and living donors compared to controls. Analysis of human samples documented the relevance of our experimental findings and revealed exacerbated complement deposition and inflammation in grafts from BD donors compared to grafts from living donors. CONCLUSIONS: BD exacerbates post-transplant cardiac IRI in mice and humans, and decreases survival of mouse allografts. Further, targeted complement inhibition in recipient mice ameliorates BD-exacerbated IRI.

PMID: 23443736 [PubMed - as supplied by publisher]

Association of a Change in Immunosuppressive Regimen with Hemodynamic and Inflammatory Markers of Cardiovascular Disease After Kidney Transplantation.

Thu, 02/28/2013 - 12:19

Association of a Change in Immunosuppressive Regimen with Hemodynamic and Inflammatory Markers of Cardiovascular Disease After Kidney Transplantation.

Am J Hypertens. 2013 Feb 26;

Authors: Yong K, Nguyen HD, Hii L, Chan DT, Boudville N, Messineo A, Lim EM, Dogra GK, Lim WH

Abstract
BackgroundAlthough rejection rates and short-term graft survival have significantly improved in kidney transplantation with the introduction of calcineurin inhibitor (CNI), cardiovascular disease (CVD) and metabolic complications are being increasingly recognized as important causes of morbidity and mortality. We hypothesize that non-CNI proliferation signal inhibitor (PSI)-based immunosuppressive regimen is associated with improved arterial stiffness after kidney transplantation compared with CNI-based immunosuppressive regimens.MethodsThis is a prospective, single-center study of renal transplant (RT) recipients comparing the metabolic, cardiovascular (pulse wave velocity and aortic augmentation index (AI) adjusted for heart rate (AI × 75)), inflammatory cytokines (interleukins (ILs) 6, 12, and 18) and graft-related outcomes at 3 and 15 months posttransplantation between RT recipients maintained on CNI- (CNI-CNI) or PSI-based (CNI-PSI) regimens including sirolimus and everolimus.ResultsFifty and 17 RT recipients maintained on CNI-CNI and CNI-PSI, respectively, were included in this study. Median time to PSI conversion from CNI was 5 months. Compared with CNI-CNI recipients, CNI-PSI recipients had significantly lower fasting blood glucose in nondiabetics (coefficient = -16.2; 95% confidence interval (CI) = -14.4 to -18.0; P < 0.01), lower IL-18 levels (coefficient = -229.16; 95% CI = -343.94 to -114.38; P < 0.01), and lower AI × 75 (coefficient = -5.14; 95% CI = -9.99 to -0.28; P = 0.04) at 15 months posttransplant in the multivariable models.ConclusionsOur study suggests from the elimination of CNI for PSI may lower AIx75 and IL-18, both surrogate markers of CVD, but adequately powered, randomized, controlled studies are required to establish the causal relationship between immunosuppressive agents and CVD risk.

PMID: 23443728 [PubMed - as supplied by publisher]

A heart transplant candidate with severe pulmonary hypertension and extremely high pulmonary vascular resistance.

Thu, 02/28/2013 - 12:19

A heart transplant candidate with severe pulmonary hypertension and extremely high pulmonary vascular resistance.

J Artif Organs. 2013 Feb 27;

Authors: Sato T, Seguchi O, Morikawa N, Hieda M, Watanabe T, Sunami H, Murata Y, Yanase M, Hata H, Fujita T, Nakatani T

Abstract
Fixed pulmonary hypertension (PH) is a contraindication for heart transplantation (HTx). Several studies showed that use of a left ventricular assist device (LVAD) in patients with fixed PH who were initially deemed ineligible for HTx effectively decreased pulmonary arterial pressure (PAP), thus permitting HTx. We recently encountered a candidate for HTx who had severe PH with extremely high pulmonary vascular resistance (PVR). A 27-year-old female who had been diagnosed with dilated-phase hypertrophic cardiomyopathy and who was approved for HTx at age 25 was referred to our institute because of severe fatigability with moderate dyspnea even at rest due to severe bilateral heart failure. Despite continuous inotrope infusion, the patient's symptoms were not relieved. Right heart catheterization (RHC) disclosed a PAP of 62/40 mmHg with severely reduced cardiac output (1.8 l/min). A PVR of 15.9 Wood units suggested progressive worsening of left ventricular function with almost irreversible remodeling of the pulmonary vasculature, and the patient was thought to be contraindicated for HTx. Following 3 weeks of aggressive medical treatment, repeat RHC demonstrated PVR lowering to 8.16 Wood units. This suggested it was likely that PVR could be reversed, and the patient underwent LVAD implantation. RHC performed after LVAD implantation showed a fall in PVR from the initial, extremely high measurement of 15.9 Wood units to 3.4 Wood units at 2 months postoperatively, and to 2.2 Wood units at 1 year. The patient is currently awaiting HTx with favorable LVAD support.

PMID: 23443326 [PubMed - as supplied by publisher]

Right heart morphology and function in heart transplantation recipients.

Thu, 02/28/2013 - 12:19

Right heart morphology and function in heart transplantation recipients.

J Cardiovasc Med (Hagerstown). 2013 Feb 25;

Authors: D'Andrea A, Riegler L, Nunziata L, Scarafile R, Gravino R, Salerno G, Amarelli C, Maiello C, Limongelli G, Di Salvo G, Caso P, Bossone E, Calabrò R, Pacileo G, Russo MG

Abstract
BACKGROUND: The right heart is a major determinant of prognosis in cardiac transplant recipient patients. AIM: To investigate right ventricular morphology and function and their relationship with exercise capacity in cardiac transplant recipient patients using standard tranthoracic echocardiography and a new three-dimensional echocardiographic software adapted for right ventricular analysis. METHODS: One hundred fifteen relatively stable cardiac transplant recipient patients (71 men; 58.3 ± 5.8 years; 7.8 ± 4.5 years after transplantation) and 80 healthy age-comparable and sex-comparable controls underwent standard echocardiography, tissue Doppler imaging (TDI), and three-dimensional echocardiography, focused on the right ventricular analysis. Along with left heart parameters, right ventricular measurements included end-diastolic diameters at basal and mid-cavity level; base-to-apex length; tricuspid annulus plane systolic excursion (TAPSE); TDI right ventricular systolic peak velocity (Sm); and three-dimensional ejection fraction. Using the peak systolic tricuspid regurgitation velocity (TRV) and the end-diastolic pulmonary regurgitation velocity, the modified Bernoulli equation was used to calculate the pulmonary artery systolic (PASP) and diastolic pressures. Pulmonary artery vascular conductance (PAVC) was estimated by left ventricular stroke volume/4 × (TRV - pulmonary regurgitation velocity). RESULTS: Left ventricular diameters and ejection fraction did not significantly differ between the two groups, whereas mass index was increased in cardiac transplant recipient patients (P < 0.01). Right ventricular diameters were significantly increased (P < 0.001), whereas TAPSE and right ventricular Sm were significantly lower in cardiac transplant recipient patients. Conversely, in cardiac transplant recipient patients, three-dimensional right ventricular ejection fraction (RVEF) was not significantly reduced (P < 0.001), whereas both PASP and PAVC were impaired. By multivariable analysis, age at transplantation (P < 0.01) and pulmonary artery mean pressure (P < 0.001) were the only independent determinants of right ventricular diameters and RVEF in cardiac transplant. Furthermore, RVEF measured by real-time three-dimensional echocardiography was a powerful independent determinant of functional capacity in cardiac transplant recipient patients. CONCLUSION: Despite the reduction of right ventricular performance along the long axis suggested by TAPSE and right ventricular Sm, the increased right ventricular diameters along with absence of a decrease in three-dimensional RVEF support the hypothesis of geometrical rather than functional changes of the right ventricle in cardiac transplant recipient patients.

PMID: 23442808 [PubMed - as supplied by publisher]

Current devices for pediatric extracorporeal life support and mechanical circulatory support systems in the United States.

Thu, 02/28/2013 - 12:19

Current devices for pediatric extracorporeal life support and mechanical circulatory support systems in the United States.

Biomed Mater Eng. 2013 Jan 1;23(1):57-62

Authors: Undar A, Wang S

Abstract
Extracorporeal life support (ECLS) and mechanical circulatory support (MCS) have become indispensable treatment tools for pediatric patients with congenital heart defects undergoing peri-operative or end-stage heart and/or lung failure. ECLS and MCS can serve as bridges to recovery, transplantation (heart or lung), destination therapy, or "bridge to bridge" long-term MCS. Dependent on patient condition, venoarterial ECMO (V-A ECMO) for heart and lung support, venovenous ECMO (V-V ECMO) for respiratory support, and MCS for uni- and biventricular support can be selected properly. Considering small patient body size, the access sites and cannulation should be selected carefully to obtain adequate blood flow, minimum injury, and easy management. The applying equipment, including tubing, cannulae, oxygenator and blood pump, need to be selected optimally in order to enable rapid setup and priming, successful cannulation and early support, and to reduce the risk of device-related morbidity and mortality. The aim of this review manuscript was to discuss briefly the current devices for pediatric ECLS and MCS available in US.

PMID: 23442237 [PubMed - in process]

Risk factors for impaired quality of life and psychosocial adjustment after pediatric heart, kidney, and liver transplantation.

Thu, 02/28/2013 - 12:19

Risk factors for impaired quality of life and psychosocial adjustment after pediatric heart, kidney, and liver transplantation.

Pediatr Transplant. 2013 Feb 26;

Authors: Haavisto A, Korkman M, Sintonen H, Holmberg C, Jalanko H, Lipsanen J, Qvist E

Abstract
Few studies compare HRQOL and PSA in children who have undergone different types of solid organ Tx. In this cross-sectional study, HRQOL and PSA were assessed in 74 Tx patients (16 heart, 44 kidney, 14 liver) at a mean age of 11.5 (range 6.3-16.7), 7.2 yr post-Tx (range 1.0-15.0). HRQOL was self-assessed using standardized health utility questionnaires (15D-17D). The patients' PSA was evaluated using the Child Behavior Checklist for parents, Youth Self-Report for patients aged 11-16 yr, and Teacher Report Form. Outcomes did not differ significantly between Tx groups. Preadolescents (8-11 yr) reported poorer HRQOL compared with same-age peers (p = 0.020). In contrast, adolescents reported similar HRQOL and PSA compared to the general population. Proxy-reports revealed more PSA problems compared with age expectations (p < 0.01), mainly in internalizing behavior (p < 0.01). Lower HRQOL was associated with shorter follow-up time since Tx, congenital disease, and a psychiatric or neurological diagnosis. PSA problems were associated with family-related variables, neurological diagnosis, shorter follow-up time, and in teacher-reports longer disease duration before Tx. Different pediatric Tx groups have similar outcome. Neurological comorbidity and shorter follow-up time are important risk factors, but the impact of family-related variables on PSA indicate the need of family interventions.

PMID: 23442166 [PubMed - as supplied by publisher]

Ten yr of pediatric heart transplantation: A report from the Pediatric Heart Transplant Study.

Thu, 02/28/2013 - 12:19

Ten yr of pediatric heart transplantation: A report from the Pediatric Heart Transplant Study.

Pediatr Transplant. 2013 Mar;17(2):99-111

Authors: Dipchand AI, Kirk R, Mahle WT, Tresler MA, Naftel DC, Pahl E, Miyamoto SD, Blume E, Guleserian KJ, White-Williams C, Kirklin JK

Abstract
The PHTS was founded in 1991 as a not-for-profit organization dedicated to the advancement of the science and treatment of children during listing for and following heart transplantation. Now, 21 yr later, the PHTS has contributed significantly to the field, most notably in the form of outcomes analyses and risk factor assessment, in addition to amassing the most detailed dataset on pediatric heart transplant recipients worldwide. The purpose of this report is to review the last decade of pediatric patients listed for heart transplantation (January 1, 2000-December 31, 2009) and summarize the changes, trends, outcomes, and lessons learned.

PMID: 23442098 [PubMed - in process]

Single-center analysis of biopsy-confirmed posttransplant lymphoproliferative disorder: incidence, clinico-pathological characteristics and prognostic factors.

Thu, 02/28/2013 - 12:19

Single-center analysis of biopsy-confirmed posttransplant lymphoproliferative disorder: incidence, clinico-pathological characteristics and prognostic factors.

Leuk Lymphoma. 2013 Feb 27;

Authors: Dierickx D, Tousseyn T, Sagaert X, Fieuws S, Wlodarska I, Morscio J, Brepoels L, Kuypers D, Vanhaecke J, Nevens F, Verleden G, Van Damme-Lombaerts R, Renard M, Pirenne J, De Wolf-Peeters C, Verhoef G

Abstract
Abstract Hematopoietic stem cell and solid organ transplant recipients diagnosed with biopsy-confirmed posttransplant lymphoproliferative disorder (PTLD) at our institution from 1989 to 2010 were identified. Patient-, transplantation- and disease-related characteristics, prognostic factors and outcome were collected and analyzed. One hundred-forty biopsy-proven PTLD cases were included. Overall incidence in the transplant population was 2.12% with heart transplant recipients carrying the highest risk. Most PTLDs were monomorphic (83.6%) with diffuse large B cell lymphoma being the most frequent subtype. The majority of cases (70.7%) occurred > 1 year posttransplantation, whereas 66% were Epstein Barr virus positive. Following initial therapy overall response rate was 68.5%. Three-year relapse-free and overall survival were 59% and 49%, respectively. At last follow-up 44% of the patients were alive. Multivariable analysis identified several classical lymphoma-specific poor prognostic factors for the different outcome measures. The value of the International Prognostic Index was confirmed in our analysis.

PMID: 23442063 [PubMed - as supplied by publisher]

Functional role of matrix metalloproteinase-8 in stem/progenitor cell migration and their recruitment into atherosclerotic lesions.

Thu, 02/28/2013 - 12:19
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Functional role of matrix metalloproteinase-8 in stem/progenitor cell migration and their recruitment into atherosclerotic lesions.

Circ Res. 2013 Jan 4;112(1):35-47

Authors: Xiao Q, Zhang F, Lin L, Fang C, Wen G, Tsai TN, Pu X, Sims D, Zhang Z, Yin X, Thomaszewski B, Schmidt B, Mayr M, Suzuki K, Xu Q, Ye S

Abstract
RATIONALE: Accumulating evidence indicates that stem/progenitor cells (SPCs) represent an important source of cells in atheromas and contribute to lesion formation and progression.
OBJECTIVE: We investigated whether matrix metalloproteinase-8 (MMP8) played a role in SPC migration and their recruitment into atheromas.
METHODS AND RESULTS: We found that SPCs in atheromas expressed MMP8 and that MMP8 knockout significantly reduced SPC numbers in atherosclerotic lesions in apolipoprotein E (ApoE)-deficient mice fed a Western diet. Further in vivo experiments showed that ApoE(-/-)/MMP8(-/-) mice injected with stem cells isolated from bone marrows of ApoE(-/-)/MMP8(-/-) mice had fewer SPCs in atheromas and smaller lesions than ApoE(-/-)/MMP8(-/-) mice injected with stem cells isolated from bone marrows of ApoE(-/-)/MMP8(+/+) mice. Ex vivo experiments showed that MMP8 deficiency inhibited the ability of SPCs to migrate from the arterial lumen and the adventitia into atherosclerotic lesions. In vitro assays indicated that MMP8 facilitated SPC migration across endothelial cells and through Matrigel or collagen I. We also found that MMP8 cleaved a-disintegrin-and-metalloproteinase-domain-10 and that MMP8 deficiency reduced mature a-disintegrin-and-metalloproteinase-domain-10 on SPCs. Knockdown of MMP8 or incubation with the a-disintegrin-and-metalloproteinase-domain-10 inhibitor GI254023X decreased E-cadherin shedding on SPCs. The decrease in migratory ability of SPCs with MMP8 knockdown was reduced by incubation of such cells with culture supernatant from SPCs without MMP8 knockdown, and this compensatory effect was abolished by an antibody against soluble E-cadherin.
CONCLUSIONS: MMP8 plays an important role in SPC migration and their recruitment into atherosclerotic lesions.

PMID: 23071158 [PubMed - indexed for MEDLINE]

New cell therapies in cardiology.

Thu, 02/28/2013 - 12:19
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New cell therapies in cardiology.

Expert Rev Cardiovasc Ther. 2012 Aug;10(8):1023-37

Authors: Pal SN, Kofidis T

Abstract
Even today, cardiovascular disease remains the leading cause of death globally. Cardiological conditions such as myocardial infarction, ischemic injury and chronic cardiomyopathy result in permanent cardiac tissue damage followed by heart failure. Current therapies primarily aim to trigger the pathological remodeling that occurs after cardiac injury and also to reduce risk factors involved in cardiovascular diseases. Animal model studies over the last decade indicate that the systematic administration of autologous and allogeneic stem cells possesses therapeutic potential to improve overall cardiac functions. This evidence robustly indicates that cardiac tissue has the potential to undergo a systematic repair process. The past few years have also witnessed a splurge in clinical research that particularly aims to explore the regenerative properties of the naive stem cells to restore cardiac functions. The mechanisms involved in stem cell therapy remain unclear. The magnitude of benefit demonstrated in animal models is yet to be completely translated into humans. The future of cardiac research will require tangible synchrony between clinicians and basic scientists to unravel the precise mechanism of stem cell therapy. It is also pivotal to define an ideal cell type and a suitable cell delivery technique that provide maximum benefit, while eliminating the grey areas in translational cardiology research. In this article, the authors review the properties and therapeutic potential of the stem cell plethora reported for cardiac repair and regeneration, recent stem cell therapies, mode of action, their delivery techniques, recent clinical developments and the future for these stem cell therapies in cardiology.

PMID: 23030292 [PubMed - indexed for MEDLINE]

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