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Delivery of biotinylated IGF-1 with biotinylated self-assembling peptides combined with bone marrow stem cell transplantation promotes cell therapy for myocardial infarction.

Thu, 10/19/2017 - 12:45

Delivery of biotinylated IGF-1 with biotinylated self-assembling peptides combined with bone marrow stem cell transplantation promotes cell therapy for myocardial infarction.

Exp Ther Med. 2017 Oct;14(4):3441-3446

Authors: Zhang M, Ai WW, Mei ZL, Hu YH, Zhang ZL

Abstract
Cell therapy is a promising approach for cardiac repair. The aim of the present study was to determine the feasibility of using biotinylated insulin-like growth factor 1 (IGF-1) with biotinylated self-assembling peptides (tethered IGF-1) combined with bone marrow stem cells (BMSCs) transplantation for the treatment of heart failure. Tethered IGF-1 was synthesized and its effect on H9c2 cells was analyzed. Reverse transcription-quantitative polymerase chain reaction and western blot assays demonstrated that tethered IGF-1 did not significantly affect the expression and phosphorylation of AKT, whereas it significantly increased the expression of cardiac troponin T (P<0.01). A rabbit myocardial infarction model was constructed and rabbits were divided into four groups: Control group (no treatment), group 1 (G1; BMSC transplantation), group 2 (G2; BMSCs + non-biotinylated IGF-1) and group 3 (G3; BMSCs + tethered IGF-1). At 4 weeks after modeling, cardiac tissues were obtained for analysis. In the control group, myocardial fibers were disordered, a large number of inflammatory cells infiltrated the cardiac tissues, and apoptosis occurred in ~50% of cells. However, in G1, G2 and G3, muscle cells were well ordered, and a lesser degree of myocardial degeneration and inflammatory cell infiltration was observed. Compared with the control group, the apoptosis rates of myocardial cells in G1-G3 were significantly decreased (P<0.01). Furthermore, compared with G1 and G2, tissue morphology was improved in G3and the number of apoptotic myocardial cells was significantly decreased (P<0.01). These results suggest that treatment with tethered IGF-1 + BMSCs significantly suppresses cell apoptosis and induces the expression of cardiac maturation proteins. These findings provide a novel insight into how the delivery of tethered IGF-1 with BMSCs could potentially enhance the prognosis of patients with heart failure treatment.

PMID: 29042931 [PubMed]

Bradycardia in a Pediatric Heart Transplant Recipient: Is It the Sugammadex?

Thu, 10/19/2017 - 12:45

Bradycardia in a Pediatric Heart Transplant Recipient: Is It the Sugammadex?

J Pediatr Pharmacol Ther. 2017 Sep-Oct;22(5):378-381

Authors: King A, Naguib A, Tobias JD

Abstract
Sugammadex is a novel pharmacologic agent that is used to selectively reverse the effects of the neuromuscular blocking agents rocuronium and vecuronium. Various advantages have been reported when comparing its reversal of neuromuscular blockade to that achieved with acetylcholinesterase inhibitors (neostigmine). In heart transplant recipients, bradycardia may occur following the administration of acetylcholinesterase inhibitors, due to the denervation of the heart. Theoretically, the combination of rocuronium and sugammadex could be advantageous in this clinical scenario to avoid the potential bradycardia resulting from neostigmine administration. We present a 10-year-old male who developed profound bradycardia immediately following the administration of intravenous sugammadex. The options for reversal of neuromuscular blockade in heart transplant recipients is discussed, previous reports of bradycardia following sugammadex are presented, and the role of sugammadex in the bradycardia in our patient is reviewed.

PMID: 29042841 [PubMed]

Risk of cancer after lung transplantation for COPD.

Thu, 10/19/2017 - 12:45

Risk of cancer after lung transplantation for COPD.

Int J Chron Obstruct Pulmon Dis. 2017;12:2841-2847

Authors: Ekström M, Riise GC, Tanash HA

Abstract
BACKGROUND: The risk of cancer is increased and affects survival after lung transplantation (LTx), but has not been well characterized in COPD. We aimed to evaluate the incidence and prognosis of cancer following LTx for COPD.
METHODS: A prospective, population-based study of patients undergoing LTx for end-stage COPD at the two transplantation centers in Sweden between 1990-2013, with follow-up for incident cancer and death, using national registers. The excess risk of cancer was calculated as standardized incidence ratios compared with the general population matched for age, sex, and calendar year. Risk factors for cancer were analyzed using Fine-Gray regression, and survival after cancer diagnosis with Kaplan-Meier.
RESULTS: In total, 331 patients (mean age 55.4 years; 64% women; 97% former smokers) were included. At a median follow-up of 2.8 years, 35% of patients had developed cancer and the risk was increased more than 10-fold ([95% CI] 8.1-11.8). The highest excess risks were for non-Hodgkin lymphoma (20.8-66.7), skin cancer (20.3-35.2), lung (11.7-31.2), liver (3.6-51.6), and colorectal cancer (6.1-19.5). Median survival was longer for skin cancer (8 years; 95% CI, 3-15) compared with non-skin cancer (4 years; 95% CI, 2.8-4.8; p<0.001).
CONCLUSION: The cancer risk is markedly increased after LTx for COPD. It could not be predicted by the factors evaluated, but contributed significantly to a negative prognosis.

PMID: 29042765 [PubMed - in process]

Predictors of Death in Adults With Duchenne Muscular Dystrophy-Associated Cardiomyopathy.

Thu, 10/19/2017 - 12:45

Predictors of Death in Adults With Duchenne Muscular Dystrophy-Associated Cardiomyopathy.

J Am Heart Assoc. 2017 Oct 17;6(10):

Authors: Cheeran D, Khan S, Khera R, Bhatt A, Garg S, Grodin JL, Morlend R, Araj FG, Amin AA, Thibodeau JT, Das S, Drazner MH, Mammen PPA

Abstract
BACKGROUND: Duchenne muscular dystrophy (DMD) is frequently complicated by development of a cardiomyopathy. Despite significant medical advances provided to DMD patients over the past 2 decades, there remains a group of DMD patients who die prematurely. The current study sought to identify a set of prognostic factors that portend a worse outcome among adult DMD patients.
METHODS AND RESULTS: A retrospective cohort of 43 consecutive patients was followed in the adult UT Southwestern Neuromuscular Cardiomyopathy Clinic. Clinical data were abstracted from the electronic medical record to generate baseline characteristics. The population was stratified by survival to time of analysis and compared with characteristics associated with death. The DMD population was in the early 20s, with median follow-up times over 2 years. All the patients had developed a cardiomyopathy, with the majority of the patients on angiotensin-converting enzyme inhibitors (86%) and steroids (56%), but few other guideline-directed heart failure medications. Comparison between the nonsurviving and surviving cohorts found several poor prognostic factors, including lower body mass index (17.3 [14.8-19.3] versus 25.8 [20.8-29.1] kg/m(2), P<0.01), alanine aminotransferase levels (26 [18-42] versus 53 [37-81] units/L, P=0.001), maximum inspiratory pressures (13 [0-30] versus 33 [25-40] cmH2O, P=0.03), and elevated cardiac biomarkers (N-terminal pro-brain natriuretic peptide: 288 [72-1632] versus 35 [21-135] pg/mL, P=0.03].
CONCLUSIONS: The findings demonstrate a DMD population with a high burden of cardiomyopathy. The nonsurviving cohort was comparatively underweight, and had worse respiratory profiles and elevated cardiac biomarkers. Collectively, these factors highlight a high-risk cardiovascular population with a worse prognosis.

PMID: 29042427 [PubMed - in process]

Comparison of glomerular filtration rate estimating equations derived from creatinine and cystatin C: validation in the Age, Gene/Environment Susceptibility-Reykjavik elderly cohort.

Thu, 10/19/2017 - 12:45
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Comparison of glomerular filtration rate estimating equations derived from creatinine and cystatin C: validation in the Age, Gene/Environment Susceptibility-Reykjavik elderly cohort.

Nephrol Dial Transplant. 2017 Oct 05;:

Authors: Björk J, Grubb A, Gudnason V, Indridason OS, Levey AS, Palsson R, Nyman U

Abstract
Background: Validation studies comparing glomerular filtration rate (GFR) equations based on standardized creatinine and cystatin C assays in the elderly are needed. The Icelandic Age, Gene/Environment Susceptibility-Kidney cohort was used to compare two pairs of recently developed GFR equations, the revised Lund-Malmö creatinine equation (LMRCr) and the arithmetic mean of the LMRCr and Caucasian, Asian, Paediatric and Adult cystatin C equations (MEANLMR+CAPA), as well as the Full Age Spectrum creatinine equation (FASCr) and its combination with cystatin C (FASCr+Cys), with the corresponding pair of Chronic Kidney Disease Epidemiology Collaboration equations (CKD-EPICr and CKD-EPICr+Cys).
Methods: A total of 805 individuals, 74-93 years of age, underwent measurement of GFR (mGFR) using plasma clearance of iohexol. Four metrics were used to compare the performance of the GFR equations: bias, precision, accuracy [including the percentage of participants with estimated GFR (eGFR) within 30% of mGFR (P30)] and the ability to detect mGFR <60 mL/min/1.73 m2.
Results: All equations had a P30 >90%. LMRCr and FASCr yielded significantly higher precision and P30 than CKD-EPICr, while bias was significantly worse. LMRCr, FASCr and CKD-EPICr showed similar ability to detect mGFR <60 mL/min/1.73 m2 based on the area under the receiver operating characteristic curves. MEANLMR+CAPA, FASCr+Cys and CKD-EPICr+Cys all exhibited consistent improvements compared with the corresponding creatinine-based equations.
Conclusion: None of the creatinine-based equations was clearly superior overall in this community-dwelling elderly cohort. The addition of cystatin C improved all of the creatinine-based equations.

PMID: 29040701 [PubMed - as supplied by publisher]

Mortality risk in patients on hemodiafiltration versus hemodialysis: a 'real-world' comparison from the DOPPS.

Thu, 10/19/2017 - 12:45
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Mortality risk in patients on hemodiafiltration versus hemodialysis: a 'real-world' comparison from the DOPPS.

Nephrol Dial Transplant. 2017 Oct 11;:

Authors: Locatelli F, Karaboyas A, Pisoni RL, Robinson BM, Fort J, Vanholder R, Rayner HC, Kleophas W, Jacobson SH, Combe C, Port FK, Tentori F

Abstract
Background: With its convective component, hemodiafiltration (HDF) provides better middle molecule clearance compared with hemodialysis (HD) and is postulated to improve survival. A previous analysis of Dialysis Outcomes and Practice Patterns Study (DOPPS) data in 1998-2001 found lower mortality rates for high replacement fluid volume HDF versus HD. Randomized controlled trials have not shown uniform survival advantage for HDF; in secondary (non-randomized) analyses, better outcomes were observed in patients receiving the highest convection volumes.
Methods: In a 'real-world' setting, we analyzed patients on dialysis >90 days from seven European countries in DOPPS Phases 4 and 5 (2009-15). Adjusted Cox regression was used to study HDF (versus HD) and mortality, overall and by replacement fluid volume.
Results: Among 8567 eligible patients, 2012 (23%) were on HDF, ranging from 42% in Sweden to 12% in Germany. Median follow-up was 1.5 years during which 1988 patients died. The adjusted mortality hazard ratio (95% confidence interval) was 1.14 (1.00-1.29) for any HDF versus HD and 1.08 (0.92-1.28) for HDF >20 L replacement fluid volume versus HD. Similar results were found for cardiovascular and infection-related mortality. In an additional analysis aiming to avoid treatment-by-indication bias, we did not observe lower mortality rates in facilities using more HDF (versus HD).
Conclusions: Our results do not support the notion that HDF provides superior patient survival. Further trials designed to test the effect of high-volume HDF (versus lower volume HDF versus HD) on clinical outcomes are needed to adequately inform clinical practices.

PMID: 29040687 [PubMed - as supplied by publisher]

Frailty syndrome: an emerging clinical problem in the everyday management of clinical arrhythmias. The results of the European Heart Rhythm Association survey.

Thu, 10/19/2017 - 12:45
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Frailty syndrome: an emerging clinical problem in the everyday management of clinical arrhythmias. The results of the European Heart Rhythm Association survey.

Europace. 2017 Oct 10;:

Authors: Fumagalli S, Potpara TS, Bjerregaard Larsen T, Haugaa KH, Dobreanu D, Proclemer A, Dagres N

Abstract
The age of patients presenting with complex arrhythmias is increasing. Frailty is a multifaceted syndrome characterized by an increased vulnerability to stressors and a decreased ability to maintain homeostasis. The prevalence of frailty is associated with age. The aims of this European Heart Rhythm Association (EHRA) EP Wire survey were to evaluate the proportion of patients with frailty and its influence on the clinical management of arrhythmias. A total of 41 centres-members of the EHRA Electrophysiology Research Network-in 14 European countries completed the web-based questionnaire in June 2017. Patients over 70 years represented 53% of the total treated population, with the proportion of frail elderly individuals reaching approximately 10%; 91.7% of the responding centres reported treating frail subjects in the previous year. The respondents usually recognized frailty based on the presence of problems of mobility, nutrition, and cognition and inappropriate loss of body weight and muscle mass. Renal failure, dementia, disability, atrial fibrillation, heart failure, falls, and cancer were reported to characterize the elderly frail individuals. Atrial fibrillation was considered the prevalent arrhythmia associated with frailty by 72% of the responding centres, and for stroke prevention, non-vitamin K antagonist oral anticoagulants were preferred. None of the respondents considered withholding the prevention of thrombo-embolic events in subjects with a history of falls. All participants have agreed that cardiac resynchronization therapy exerts positive effects including improvement in cardiac, physical, and cognitive performance and quality of life. The majority of respondents preferred an Arrhythmia Team to manage this special population of elderly patients, and many would like having a simple tool to quickly assess the presence of frailty to guide their decisions, particularly on the use of complex cardiac implantable electrical devices (CIEDs). In conclusion, the complex clinical condition in frail patients presenting with arrhythmias warrants an integrated multidisciplinary approach both for the management of rhythm disturbances and for the decision on using CIEDs.

PMID: 29040554 [PubMed - as supplied by publisher]

Physiological and Perceptual Responses to Nordic Walking in a Natural Mountain Environment.

Thu, 10/19/2017 - 12:45
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Physiological and Perceptual Responses to Nordic Walking in a Natural Mountain Environment.

Int J Environ Res Public Health. 2017 Oct 17;14(10):

Authors: Grainer A, Zerbini L, Reggiani C, Marcolin G, Steele J, Pavei G, Paoli A

Abstract
Background: Interest around Nordic Walking (NW) has increased in recent years. However, direct comparisons of NW with normal walking (W), particularly in ecologically valid environments is lacking. The aim of our study was to compare NW and W, over long distances in a natural mountain environment. Methods: Twenty one subjects (13 male/8 female, aged 41 ± 12 years, body mass index BMI 24.1 ± 3.7), walked three distinct uphill paths (length 2.2/3.4/7 km) with (NW) or without (W) walking poles over two separate days. Heart rate (HR), energy expenditure (EE), step length (SL), walking speed (WS), total steps number (SN) and rating of perceived exertion (RPE) were monitored. Results: HR (+18%) and EE (+20%) were higher in NW than in W whilst RPE was similar. SN (-12%) was lower and SL (+15%) longer in NW. WS was higher (1.64 vs. 1.53 m s(-1)) in NW. Conclusions: Our data confirm that, similarly to previous laboratory studies, differences in a range of walking variables are present between NW and W when performed in a natural environment. NW appears to increase EE compared to W, despite a similar RPE. Thus, NW could be a useful as aerobic training modality for weight control and cardiorespiratory fitness.

PMID: 29039775 [PubMed - in process]

[Corrigendum] Farnesoid X receptor deletion improves cardiac function, structure and remodeling following myocardial infarction in mice.

Thu, 10/19/2017 - 12:45
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[Corrigendum] Farnesoid X receptor deletion improves cardiac function, structure and remodeling following myocardial infarction in mice.

Mol Med Rep. 2017 Oct 03;:

Authors: Gao J, Liu X, Wang B, Xu H, Xia Q, Lu T, Wang F

Abstract
Following the publication of this article, an interested reader drew to our attention that we had incorrectly reported (in the Materials and methods section, 'Western blot analysis', on p. 674) that the anti-farnesoid X receptor (FXR) antibody of Cell Signalling Technology, Inc., cat. no. #12295, had been used in this study to probe for FXR. In fact, the antibodies used in the above-mentioned study were a gift from the group of Dr Xin-Liang Ma at Thomas Jefferson University (Philadelphia, PA, USA), as referenced in the following article: [Pul J, Yuan A, Shan P, Gao E, Wang X, Wang Y, Lau WB, Koch W, Xin-Ma XL and He B: Cardiomyocyte-expressed farnesoid-X-receptor is a novel apoptosis mediator and contributes to myocardial ischaemia/reperfusion injury. Eur Heart J 34: 1834-1845, 2013]. The antibody that was used for the western blotting analysis was raised against the C-terminus of FXR (C-20; cat. no. sc-1204, Santa Cruz Biotechnology, San Diego, CA, USA). We sincerely apologize for this mistake, and thank the reader of our article who drew this matter to our attention. The error made in our incorrect referencing of the antibody did not affect the conclusions reported in this study. Furthermore, we regret the inconvenience that this mistake caused. [the original article was published in the Molecular Medicine Reports 16: 673-679, 2017; DOI: 10.3892/mmr.2017.6643].

PMID: 29039548 [PubMed - as supplied by publisher]

Blood vessel control of macrophage maturation promotes arteriogenesis in ischemia.

Thu, 10/19/2017 - 12:45
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Blood vessel control of macrophage maturation promotes arteriogenesis in ischemia.

Nat Commun. 2017 Oct 16;8(1):952

Authors: Krishnasamy K, Limbourg A, Kapanadze T, Gamrekelashvili J, Beger C, Häger C, Lozanovski VJ, Falk CS, Napp LC, Bauersachs J, Mack M, Haller H, Weber C, Adams RH, Limbourg FP

Abstract
Ischemia causes an inflammatory response that is intended to restore perfusion and homeostasis yet often aggravates damage. Here we show, using conditional genetic deletion strategies together with adoptive cell transfer experiments in a mouse model of hind limb ischemia, that blood vessels control macrophage differentiation and maturation from recruited monocytes via Notch signaling, which in turn promotes arteriogenesis and tissue repair. Macrophage maturation is controlled by Notch ligand Dll1 expressed in vascular endothelial cells of arteries and requires macrophage canonical Notch signaling via Rbpj, which simultaneously suppresses an inflammatory macrophage fate. Conversely, conditional mutant mice lacking Dll1 or Rbpj show proliferation and transient accumulation of inflammatory macrophages, which antagonizes arteriogenesis and tissue repair. Furthermore, the effects of Notch are sufficient to generate mature macrophages from monocytes ex vivo that display a stable anti-inflammatory phenotype when challenged with pro-inflammatory stimuli. Thus, angiocrine Notch signaling fosters macrophage maturation during ischemia.Molecular mechanisms of macrophage-mediated regulation of artery growth in response to ischemia are poorly understood. Here the authors show that vascular endothelium controls macrophage maturation and differentiation via Notch signaling, which in turn promotes arteriogenesis and ischemic tissue recovery.

PMID: 29038527 [PubMed - in process]

Regulation of T cell alloimmunity by PI3Kγ and PI3Kδ.

Thu, 10/19/2017 - 12:45
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Regulation of T cell alloimmunity by PI3Kγ and PI3Kδ.

Nat Commun. 2017 Oct 16;8(1):951

Authors: Uehara M, McGrath MM, Ohori S, Solhjou Z, Banouni N, Routray S, Evans C, DiNitto JP, Elkhal A, Turka LA, Strom TB, Tullius SG, Winkler DG, Azzi J, Abdi R

Abstract
Phosphatidylinositol-3-kinases (PI3K) γ and δ are preferentially enriched in leukocytes, and defects in these signaling pathways have been shown to impair T cell activation. The effects of PI3Kγ and PI3Kδ on alloimmunity remain underexplored. Here, we show that both PI3Kγ (-/-) and PI3Kδ (D910A/D910A) mice receiving heart allografts have suppression of alloreactive T effector cells and delayed acute rejection. However, PI3Kδ mutation also dampens regulatory T cells (Treg). After treatment with low dose CTLA4-Ig, PI3Kγ (-/-) , but not PI3Κδ (D910A/D910A) , recipients exhibit indefinite prolongation of heart allograft survival. PI3Kδ (D910A/D910A) Tregs have increased apoptosis and impaired survival. Selective inhibition of PI3Kγ and PI3Kδ (using PI3Kδ and dual PI3Kγδ chemical inhibitors) shows that PI3Kγ inhibition compensates for the negative effect of PI3Kδ inhibition on long-term allograft survival. These data serve as a basis for future PI3K-based immune therapies for transplantation.Phosphatidylinositol-3-kinases (PI3K) γ and δ are key regulators of T cell signaling. Here the author show, using mouse heart allograft transplantation models, that PI3Kγ or PI3Kδ deficiency prolongs graft survival, but selective inhibition of PI3Kγ or PI3Kδ reveals alternative transplant survival outcomes post CTLA4-Ig treatment.

PMID: 29038423 [PubMed - in process]

Effect of Age and Renal Function on Survival After Left Ventricular Assist Device Implantation.

Thu, 10/19/2017 - 12:45
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Effect of Age and Renal Function on Survival After Left Ventricular Assist Device Implantation.

Am J Cardiol. 2017 Sep 20;:

Authors: Muslem R, Caliskan K, Akin S, Yasar YE, Sharma K, Gilotra NA, Kardys I, Houston B, Whitman G, Tedford RJ, Hesselink DA, Bogers AJJC, Manintveld OC, Russell SD

Abstract
Left ventricular assist devices (LVAD) are increasingly used, especially as destination therapy in in older patients. The aim of this study was to evaluate the effect of age on renal function and mortality in the first year after implantation. A retrospective multicenter cohort study was conducted, evaluating all LVAD patients implanted in the 2 participating centers (age ≥18 years). Patients were stratified according to the age groups <45, 45-54, 55-64, and ≥65 years old. Overall, 241 patients were included (mean age 52.4 ± 12.9 years, 76% males, 33% destination therapy). The mean estimated Glomerular Filtration Rate (eGFR) at 1 year was 85, 72, 69, and 49 mL/min per 1.73 m(2) in the age groups <45(n = 65, 27%), 45-54(n = 52, 22%), 55-64(n = 87, 36%), and ≥65 years (n = 37, 15%) p <0.001)), respectively. Older age and lower eGFR at baseline (p <0.01) were independent predictors of worse renal function at 1 year. The 1-year survival post-implantation was 79%,84%, 68%, and 54% for those in the age group <45, 45-54, 55-64 and ≥65 years (Log-rank p = 0.003). Older age, lower eGFR and, INTERMACS class I were independent predictors of 1-year mortality. Furthermore, older patients (age > 60 years) with an impaired renal function (eGFR <55 mL/min per 1.73 m(2)) had a 5-fold increased hazard ratio for mortality during the first year after implantation (p <0.001). In conclusion, age >60 years is an independent predictor for an impaired renal function and mortality. Older age combined with reduced renal function pre-implantation had a cumulative adverse effect on survival in patients receiving a LVAD.

PMID: 29037445 [PubMed - as supplied by publisher]

Transplantation of Isl1(+) cardiac progenitor cells in small intestinal submucosa improves infarcted heart function.

Thu, 10/19/2017 - 12:45
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Transplantation of Isl1(+) cardiac progenitor cells in small intestinal submucosa improves infarcted heart function.

Stem Cell Res Ther. 2017 Oct 16;8(1):230

Authors: Wang L, Meier EM, Tian S, Lei I, Liu L, Xian S, Lam MT, Wang Z

Abstract
BACKGROUND: Application of cardiac stem cells combined with biomaterial scaffold is a promising therapeutic strategy for heart repair after myocardial infarction. However, the optimal cell types and biomaterials remain elusive.
METHODS: In this study, we seeded Isl1(+) embryonic cardiac progenitor cells (CPCs) into decellularized porcine small intestinal submucosa extracellular matrix (SIS-ECM) to assess the therapeutic potential of Isl1(+) CPCs and the biocompatibility of SIS-ECM with these cells.
RESULTS: We observed that SIS-ECM supported the viability and attachment of Isl1(+) CPCs. Importantly, Isl1(+) CPCs differentiated into cardiomyocytes and endothelial cells 7 days after seeding into SIS-ECM. In addition, SIS-ECM with CPC-derived cardiomyocytes showed spontaneous contraction and responded to β-adrenergic stimulation. Next, patches of SIS-ECM seeded with CPCs for 7 days were transplanted onto the outer surface of infarcted myocardium in mice. Four weeks after transplantation, the patches were tightly attached to the surface of the host myocardium and remained viable. Transplantation of patches improved cardiac function, decreased the left ventricular myocardial scarring area, and reduced fibrosis and heart failure.
CONCLUSIONS: Transplantation of Isl1(+) CPCs seeded in SIS-ECM represents an effective approach for cell-based heart therapy.

PMID: 29037258 [PubMed - in process]

Ten-year results of the Freedom Solo stentless heart valve: excellent haemodynamics but progressive valve dysfunction in the long term.

Thu, 10/19/2017 - 12:45
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Ten-year results of the Freedom Solo stentless heart valve: excellent haemodynamics but progressive valve dysfunction in the long term.

Interact Cardiovasc Thorac Surg. 2017 May 01;24(5):663-669

Authors: Sponga S, Barbera MD, Pavoni D, Lechiancole A, Mazzaro E, Valente M, Nucifora G, Thiene G, Livi U

Abstract
OBJECTIVES: Freedom Solo (FS) is a pericardial stentless heart valve showing excellent haemodynamic performance at mid-term. The aim of this study was to evaluate the long-term performance of such bioprostheses.
METHODS: Between December 2004 and November 2009, 109 patients (31 men; mean age 76 ± 6 years) underwent aortic valve replacement with FS. Preoperatively, the mean NYHA class was 2.5 ± 0.7, the mean EuroSCORE II, 2.8 ± 2.5. Mean prosthesis size was 22.7 ± 1.9 mm; concomitant procedures were performed in 65 patients. Structural valve deterioration (SVD) was diagnosed according to the Valve Academic Research Consortium-2 definition.
RESULTS: Two patients (1.8%) died within 30 days. Follow-up (72 ± 36 months) was 100% completed. The 1-, 5- and 10-year actuarial survival rates were 89, 73 and 42%, respectively, with 8 valve-related deaths; the actuarial freedom from SVD was 99, 93 and 76%. During 61 ± 39 months of follow-up, echocardiographic findings worsened progressively: At discharge, 3-5 and 7-9 years, the mean gradient was 8 ± 4, 12 ± 11 and 19 ± 19 mmHg ( P  < 0.01); the indexed effective orifice area was 1.0 ± 0.2, 0.9 ± 0.2 and 0.8 ± 0.3 cm 2 /m 2 ( P  < 0.01). Of the 13 patients who developed SVD, it was due to aortic stenosis in 11. SVD was a predictor of cardiovascular mortality at univariate analysis (HR 2.87, 1.12-7.29); 2 explanted prostheses showed massive calcium deposits with mean calcium and phosphorus contents of 234 ± 16 and 116 ± 7 mg/g dry weight, respectively.
CONCLUSIONS: The FS bioprosthesis shows excellent mid-term clinical and haemodynamic results and offers an alternative to other valves, particularly in the case of a small aortic annulus. Worsening of FS performance was observed at late follow-up because of progressive SVD with stenosis, questioning whether it should be used in patients with a long life expectancy.

PMID: 28329194 [PubMed - indexed for MEDLINE]

Repair of left ventricular rupture in a patient with mitral annular calcification.

Thu, 10/19/2017 - 12:45
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Repair of left ventricular rupture in a patient with mitral annular calcification.

Interact Cardiovasc Thorac Surg. 2017 Jun 01;24(6):972-973

Authors: Okamoto K, Tazume H, Koga A, Fukui T

Abstract
Left ventricular free wall rupture is a complication following acute myocardial infarction or mitral valve replacement. We report the case of a 56-year-old female patient with idiopathic left ventricular rupture confirmed by contrast-enhanced computed tomography (CT). CT also showed no coronary artery obstruction and severe mitral annular calcification. Left ventricular rupture was successfully repaired internally with bovine pericardium. Mitral valve replacement with annular decalcification was also performed.

PMID: 28329152 [PubMed - indexed for MEDLINE]

Single leaflet reconstruction of pulmonic valve with decellurized bovine pericardium.

Thu, 10/19/2017 - 12:45
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Single leaflet reconstruction of pulmonic valve with decellurized bovine pericardium.

Interact Cardiovasc Thorac Surg. 2017 Jun 01;24(6):969-971

Authors: Tomasko JM, Rankin JS, Malaisrie SC

Abstract
A patient presented with a complex mass seen extending from the lumen of the aorta to the lumen of the pulmonary artery. Papillary fibroelastoma was identified at resection, however the left pulmonary valve leaflet required resection to fully remove the mass. The leaflet was reconstructed using the bovine pericardial extracellular matrix. Valve function and flow characteristics were excellent following repair.

PMID: 28329102 [PubMed - indexed for MEDLINE]

Perioperative outcomes of off-pump minimally invasive coronary artery bypass grafting with bilateral internal thoracic arteries under direct vision†.

Thu, 10/19/2017 - 12:45
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Perioperative outcomes of off-pump minimally invasive coronary artery bypass grafting with bilateral internal thoracic arteries under direct vision†.

Interact Cardiovasc Thorac Surg. 2017 May 01;24(5):696-701

Authors: Kikuchi K, Chen X, Mori M, Kurata A, Tao L

Abstract
OBJECTIVES: We previously introduced techniques to harvest and use the right internal thoracic artery in minimally invasive coronary artery bypass grafting (CABG) via a single left thoracotomy for revascularization with bilateral internal thoracic arteries (BITA). We report our short-term outcomes of patients who underwent minimally invasive CABG using BITA and a single internal thoracic artery (SITA).
METHODS: Consecutive patients who underwent minimally invasive CABG using BITA or SITA at a Japanese medical center between February 2012 and December 2015 were reviewed retrospectively. Preoperative, intraoperative and 30-day postoperative outcomes were analysed. Perioperative data for the SITA cohort is presented to provide a context in which the outcomes of the BITA cohort can be evaluated.
RESULTS: A total of 25 and 37 patients underwent BITA and SITA revascularization, respectively. The mean duration of the operation was longer in the BITA group than in the SITA group (265 ± 104 vs 336 ± 73 min). There were no deaths in the BITA group and one death in the SITA group. There were no strokes in either cohort, and new haemodialysis was required in one patient in each group. All BITA grafts were harvested without major complications and were all patent on computed tomography angiograms 1 week following the operations.
CONCLUSIONS: BITA can be safely harvested in a reproducible manner under direct vision via a small left thoracotomy. The potential advantages of minimally invasive CABG using BITA, although yet to be established, include a long-term survival benefit conferred by BITA grafts and elimination of the risk of sternal wound infection, in addition to the established advantages of minimally invasive coronary artery surgery. This approach has the potential for further optimization with hybrid revascularization strategies.

PMID: 28329064 [PubMed - indexed for MEDLINE]

Heparin improves BMSC cell therapy: Anticoagulant treatment by heparin improves the safety and therapeutic effect of bone marrow-derived mesenchymal stem cell cytotherapy.

Thu, 10/19/2017 - 12:45
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Heparin improves BMSC cell therapy: Anticoagulant treatment by heparin improves the safety and therapeutic effect of bone marrow-derived mesenchymal stem cell cytotherapy.

Theranostics. 2017;7(1):106-116

Authors: Liao L, Shi B, Chang H, Su X, Zhang L, Bi C, Shuai Y, Du X, Deng Z, Jin Y

Abstract
Systemic infusion of bone marrow-derived mesenchymal stem cells (BMSCs) has become a promising strategy for disease treatment and tissue regeneration. Strategies to enhance the efficiency of BMSC cell therapy are crucial to promote its clinical application. Here, we aimed to improve BMSC cell therapy by inhibiting the BMSC-induced coagulation reaction. Intravenous injection of gradient BMSCs into mice showed that BMSCs were not fully compatible with blood. Large doses of BMSCs induced a series of symptoms of respiratory failure and heart failure. Histological and homeostasis analysis confirmed that large doses of BMSCs induced disseminated intravascular thrombosis, exhaustion of platelets and coagulation factors, and prolonged prothrombin time (PT) and activated partial thromboplastin time (APTT). Similar to mouse BMSCs, goat and human BMSCs also induced coagulation reactions in vitro and in vivo. The coagulation was induced mostly by tissue factor, the overexpression of which enhanced the procoagulant activity of BMSCs during in vitro culture. Notably, clinical doses of BMSCs in cell therapy also induced mild and reversible coagulation, which increased BMSC lung embolism and clearance. Anticoagulation treatment by heparin (400 U/kg) prevented BMSC-induced coagulation and the acute adverse effects of large-dose BMSCs infusion efficiently. Importantly, heparin treatment led to decreased BMSC lung embolism and enhanced migration and maintenance of BMSCs to target organs in cell therapy. Based on an experimental colitis model, we confirmed that heparin treatment enhanced the effect of BMSC therapy efficiently to reduce mortality, prevent weight loss, suppress inflammation reaction and alleviate tissue injury. In conclusion, BMSCs possess procoagulant activity that could induce disseminated coagulation and thrombosis in recipients. Anticoagulation treatment by heparin is a practical strategy to improve both the safety and therapeutic effect of BMSC therapy.

PMID: 28042320 [PubMed - indexed for MEDLINE]

Distribution of human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) in canines after intracerebroventricular injection.

Thu, 10/19/2017 - 12:45
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Distribution of human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) in canines after intracerebroventricular injection.

Neurobiol Aging. 2016 Nov;47:192-200

Authors: Park SE, Jung NY, Lee NK, Lee J, Hyung B, Myeong SH, Kim HS, Suh YL, Lee JI, Cho KR, Kim DH, Choi SJ, Chang JW, Na DL

Abstract
In this study, we investigated the distribution of human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) administered via intracerebroventricular (ICV) injection in a canine model. Ten beagles (11-13 kg per beagle) each received an injection of 1 × 10(6) cells into the right lateral ventricle and were sacrificed 7 days after administration. Based on immunohistochemical analysis, hUCB-MSCs were observed in the brain parenchyma, especially along the lateral ventricular walls. Detected as far as 3.5 mm from the cortical surface, these cells migrated from the lateral ventricle toward the cortex. We also observed hUCB-MSCs in the hippocampus and the cervical spinal cord. According to real-time polymerase chain reaction results, most of the hUCB-MSCs were found distributed in the brain and the cervical spinal cord but not in the lungs, heart, kidneys, spleen, and liver. ICV administered hUCB-MSCs also enhanced the endogenous neural stem cell population in the subventricular zone. These results highlighted the ICV delivery route as an optimal route to be performed in stem cell-based clinical therapies for neurodegenerative diseases.

PMID: 27614113 [PubMed - indexed for MEDLINE]

Pediatric cardiorespiratory failure successfully managed with venoarterial-venous extracorporeal membrane oxygenation: a case report.

Thu, 10/19/2017 - 12:45
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Pediatric cardiorespiratory failure successfully managed with venoarterial-venous extracorporeal membrane oxygenation: a case report.

BMC Pulm Med. 2016 Aug 12;16(1):119

Authors: Kyo M, Ohshimo S, Kida Y, Shimatani T, Torikoshi Y, Suzuki K, Yamaga S, Hirohashi N, Shime N

Abstract
BACKGROUND: Venoarterial-venous extracorporeal membrane oxygenation (VAV ECMO) configuration is a combined procedure of extracorporeal membrane oxygenation (ECMO). The proportion of cardiac and respiratory support can be controlled by adjusting arterial and venous return. Therefore, VAV ECMO can be applicable as a bridging therapy in the transition from venoarterial (VA) to venovenous (VV) ECMO.
CASE PRESENTATION: We present an 11-year-old girl with chemotherapy-induced myocarditis requiring extracorporeal cardiorespiratory support. She showed progressive hypotension, tachycardia, hyperlactemia, and tachypnea under support of catecholamines. Echocardiography showed severe left ventricular hypokinesis with an ejection fraction of 30 %. She was placed on VA ECMO with a drainage catheter from the right femoral vein (19.5 Fr) and a return catheter to the right femoral artery (16.5 Fr). Extracorporeal circulation was initiated at a blood flow of 2.0 L/min (59 mL/kg/min). On day 31, although cardiac function had improved, persistent pulmonary failure made weaning from VA ECMO difficult. We planned transition from VA ECMO to VAV ECMO to ensure gradual tapering of extracorporeal cardiac support while evaluating cardiopulmonary function. An additional return cannula (13.5 Fr) was inserted from the right internal jugular vein, which was connected to the circuit branch from the original returning cannula. We then gradually shifted the blood from the femoral artery to the right internal jugular vein over 24 h. She was successfully switched from VA to VV ECMO via VAV ECMO.
CONCLUSIONS: VAV ECMO might be an option in ensuring oxygenation to the coronary circulation and allowing time to adequately evaluate cardiac function during transition from VA to VV ECMO. Further investigations using larger cohorts are necessary to validate the efficacy of VAV ECMO as a bridging therapy in the transition from VA to VV ECMO.

PMID: 27519601 [PubMed - indexed for MEDLINE]

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