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Clonal Hematopoiesis and Risk of Atherosclerotic Cardiovascular Disease.

Thu, 06/22/2017 - 12:45
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Clonal Hematopoiesis and Risk of Atherosclerotic Cardiovascular Disease.

N Engl J Med. 2017 Jun 21;:

Authors: Jaiswal S, Natarajan P, Silver AJ, Gibson CJ, Bick AG, Shvartz E, McConkey M, Gupta N, Gabriel S, Ardissino D, Baber U, Mehran R, Fuster V, Danesh J, Frossard P, Saleheen D, Melander O, Sukhova GK, Neuberg D, Libby P, Kathiresan S, Ebert BL

Abstract
Background Clonal hematopoiesis of indeterminate potential (CHIP), which is defined as the presence of an expanded somatic blood-cell clone in persons without other hematologic abnormalities, is common among older persons and is associated with an increased risk of hematologic cancer. We previously found preliminary evidence for an association between CHIP and atherosclerotic cardiovascular disease, but the nature of this association was unclear. Methods We used whole-exome sequencing to detect the presence of CHIP in peripheral-blood cells and associated such presence with coronary heart disease using samples from four case-control studies that together enrolled 4726 participants with coronary heart disease and 3529 controls. To assess causality, we perturbed the function of Tet2, the second most commonly mutated gene linked to clonal hematopoiesis, in the hematopoietic cells of atherosclerosis-prone mice. Results In nested case-control analyses from two prospective cohorts, carriers of CHIP had a risk of coronary heart disease that was 1.9 times as great as in noncarriers (95% confidence interval [CI], 1.4 to 2.7). In two retrospective case-control cohorts for the evaluation of early-onset myocardial infarction, participants with CHIP had a risk of myocardial infarction that was 4.0 times as great as in noncarriers (95% CI, 2.4 to 6.7). Mutations in DNMT3A, TET2, ASXL1, and JAK2 were each individually associated with coronary heart disease. CHIP carriers with these mutations also had increased coronary-artery calcification, a marker of coronary atherosclerosis burden. Hypercholesterolemia-prone mice that were engrafted with bone marrow obtained from homozygous or heterozygous Tet2 knockout mice had larger atherosclerotic lesions in the aortic root and aorta than did mice that had received control bone marrow. Analyses of macrophages from Tet2 knockout mice showed elevated expression of several chemokine and cytokine genes that contribute to atherosclerosis. Conclusions The presence of CHIP in peripheral-blood cells was associated with nearly a doubling in the risk of coronary heart disease in humans and with accelerated atherosclerosis in mice. (Funded by the National Institutes of Health and others.).

PMID: 28636844 [PubMed - as supplied by publisher]

Prognostic significance of improvement in right ventricular systolic function during cardiac resynchronization therapy.

Thu, 06/22/2017 - 12:45
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Prognostic significance of improvement in right ventricular systolic function during cardiac resynchronization therapy.

Acta Cardiol. 2017 Mar 31;:1-9

Authors: Helsen F, Van De Bruaene A, Gabriels C, Claeys M, Troost E, Vörös G, Willems R, Voigt JU, Budts W

Abstract
Objectives There is conflicting evidence concerning the role of right ventricular (RV) systolic dysfunction in the long-term clinical outcome after cardiac resynchronization therapy (CRT). Therefore we aimed to assess evolution of RV systolic function during CRT, covariates associated with its improvement, and its impact on outcome. Methods and results All CRT device implantations (Jan 2009-Dec 2011) in our institution were reviewed. Records of 69 patients (25% female, mean age 62.8 ± 9.2 years, mean left ventricular (LV) ejection fraction 27 ± 8%) were analyzed. Baseline RV fractional area change (FAC) < 35% was present in 37 patients (54%). At one year, 24 of them (65%) improved in RV FAC. LV remodeling and mitral regurgitation were significantly associated with the likelihood of RV FAC improvement (OR 4.80, 95% CI 1.13-20.46, P = 0.034 and OR 0.32, 95% CI 0.12-0.89, P = 0.029, respectively). The composite endpoint of death or heart transplantation occurred in 23 patients (33%) over a mean follow-up of 2.8 ± 1.4 years. RV FAC at one year (HR 0.90, 95% CI 0.86-0.94, P < .001) was, independently of NYHA class and LV remodeling, associated with clinical outcome. Conclusions RV systolic function might improve during CRT. This seems mainly due to changed left-sided hemodynamics and LV remodeling. Good RV systolic function is independently related with better outcome.

PMID: 28636525 [PubMed - as supplied by publisher]

Impact of growing cohorts of adults with con-genital heart disease on clinical workload: a 20-year experience at a tertiary care centre.

Thu, 06/22/2017 - 12:45
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Impact of growing cohorts of adults with con-genital heart disease on clinical workload: a 20-year experience at a tertiary care centre.

Swiss Med Wkly. 2017 Jun 21;147:w14443

Authors: Padrutt M, Bracher I, Bonassin F, Santos Lopes B, Gruner C, Stämpfli SF, Wolber T, Kretschmar O, Oxenius A, De Pasquale G, Seeliger T, Lüscher TF, Attenhofer Jost C, Greutmann M

Abstract
BACKGROUND: Population based studies show a steady increase in adult patients with congenital heart defects. The aim of this study was to assess the evolution of such a patient cohort and its burden on clinical care at a dedicated tertiary care centre.
METHODS: All patients with congenital heart disease followed up by a dedicated multidisciplinary team at our institution were identified (n = 1725). Disease characteristics, the increase in patient numbers and interventions and the increase in selected complications were analysed and compared between the first (1996-2005) and second (2006-2015) decades of the study period.
RESULTS: Between the two decades of the study period, the number of patients in follow-up increased by 109%, the number of patients who died or underwent transplantation more than doubled and the number of outpatient visits increased by 195%. One fourth of all patients underwent at least one surgical procedure and 14% had at least one percutaneous intervention. The increase in surgical procedures between the two decades was 27% and the increase in percutaneous interventions 159%. Between the two decades the number of patients requiring direct current cardioversion increased from 32 to 95 (+197%), the number of patients requiring admission for infective endocarditis increased from 7 to 29 (+314%) and the number of women followed up during pregnancy increased from 18 to 115 (+539%).
CONCLUSION: As a result of the increasing number and complexity of adult survivors with congenital heart disease more resources will be needed to cope with the demands of this novel cohort of complex patients in adult cardiology.

PMID: 28634971 [PubMed - in process]

The role of frontline autologous stem cell transplantation for primary plasma cell leukemia: a retrospective multicenter study (KMM160).

Thu, 06/22/2017 - 12:45
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The role of frontline autologous stem cell transplantation for primary plasma cell leukemia: a retrospective multicenter study (KMM160).

Oncotarget. 2017 Jun 16;:

Authors: Jung SH, Lee JJ, Kim K, Suh C, Yoon DH, Min CK, Sohn SK, Choi CW, Lee HS, Kim HJ, Shin HJ, Bang SM, Yoon SS, Park SK, Yhim HY, Kim MK, Jo JC, Mun YC, Lee JH, Kim JS, Korean Multiple Myeloma Working Party

Abstract
Primary plasma cell leukemia (pPCL) is a rare and aggressive plasma cell neoplasm, with rapidly progressing clinical course. We evaluated the treatment status and survival outcomes of 69 Korean patients with pPCL. Of them, 59 patients were treated; 15 (25.4%) were treated initially with novel agent-based regimens with upfront autologous stem cell transplantation (ASCT), 7 (11.9%) with conventional chemotherapy with upfront ASCT, 21 (35.6%) with novel agent-based regimens only, and 16 (27.1%) were treated with conventional chemotherapy alone. Overall response rates after initial therapy were significantly higher in patients treated with novel agent-based regimens compared with those treated with conventional chemotherapies (75% vs. 43.4%, P = 0.026). Median progression-free survival (PFS) and overall survival (OS) were 12.2 months and 16.1 months, respectively. The median PFS of the four treatment groups-conventional chemotherapy alone, novel agents alone, conventional chemotherapy with ASCT, and novel agents with ASCT-were 1.2, 9.0, 10.5, and 26.4 months, respectively (P < 0.001); the median OS of the four treatment groups were 2.9, 12.3, 14.1, and 31.1 months, respectively (P < 0.001). The median OS was also significantly better in the patients with novel agents with ASCT versus other patients. In a multivariate analysis, an increased lactate dehydrogenase level, low albumin (< 3.5 g/dL), and non-CR after front-line treatment were independently associated with poor PFS and OS. In conclusion, the use of novel agent-based therapy with ASCT and achieving a deep response to front-line treatment are important in expecting improved PFS and OS in patients with pPCL.

PMID: 28634317 [PubMed - as supplied by publisher]

Blood pressure-independent renoprotection in diabetic rats treated with AT1 receptor-neprilysin inhibition compared with AT1 receptor blockade alone.

Thu, 06/22/2017 - 12:45
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Blood pressure-independent renoprotection in diabetic rats treated with AT1 receptor-neprilysin inhibition compared with AT1 receptor blockade alone.

Clin Sci (Lond). 2016 Jul 01;130(14):1209-20

Authors: Roksnoer LC, van Veghel R, van Groningen MC, de Vries R, Garrelds IM, Bhaggoe UM, van Gool JM, Friesema EC, Leijten FP, Hoorn EJ, Danser AH, Batenburg WW

Abstract
ARNI [dual AT1 (angiotensin II type 1) receptor-neprilysin inhibition] exerts beneficial effects on blood pressure and kidney function in heart failure, compared with ARB (AT1 receptor blockade) alone. We hypothesized that ARNI improves cardiac and kidney parameters in diabetic TGR(mREN2)27 rats, an angiotensin II-dependent hypertension model. Rats were made diabetic with streptozotocin for 5 or 12 weeks. In the final 3 weeks, rats were treated with vehicle, irbesartan (ARB) or irbesartan+thiorphan (ARNI). Blood pressure, measured by telemetry in the 5-week group, was lowered identically by ARB and ARNI. The heart weight/tibia length ratio in 12-week diabetic animals was lower after ARNI compared with after ARB. Proteinuria and albuminuria were observed from 8 weeks of diabetes onwards. ARNI reduced proteinuria more strongly than ARB, and a similar trend was seen for albuminuria. Kidneys of ARNI-treated animals showed less severe segmental glomerulosclerosis than those of ARB-treated animals. After 12 weeks, no differences between ARNI- and ARB-treated animals were found regarding diuresis, natriuresis, plasma endothelin-1, vascular reactivity (acetylcholine response) or kidney sodium transporters. Only ARNI-treated rats displayed endothelin type B receptor-mediated vasodilation. In conclusion, ARNI reduces proteinuria, glomerulosclerosis and heart weight in diabetic TGR(mREN2)27 rats more strongly than does ARB, and this occurs independently of blood pressure.

PMID: 27129187 [PubMed - indexed for MEDLINE]

Reduced intensity conditioning allogeneic transplantation after salvage treatment with DT-PACE in myeloma patients relapsing early after autologous transplant.

Wed, 06/21/2017 - 21:45

Reduced intensity conditioning allogeneic transplantation after salvage treatment with DT-PACE in myeloma patients relapsing early after autologous transplant.

Eur J Haematol. 2017 Jun 20;:

Authors: Randall K, Kaparou M, Xenou E, Paneesha S, Kishore B, Kanellopoulos A, Lovell R, Holder K, Suhr J, Baker L, Ryan L, Nikolousis E

Abstract
OBJECTIVE: In this retrospective single center study we have looked into the transplant outcomes(overall survival OS, progression free survival PFS,GvHD) and the role of chimerism, DLI and pre-transplant characteristics in patients who had a suboptimal response (<12 months)to an autologous stem cell transplant for myeloma and underwent an Alemtuzumab T-cell depleted reduced intensity allograft(RIC).
METHODS: 24 patients were salvaged with 2 cycles of DT-PACE and received a RIC transplant with Fludarabine, Melphalan and Alemtuzumab. All the patients received PBSC grafts, 8 patients had a sibling donor and 16 had a graft from a fully matched unrelated donor. The median follow up was 65.3 months (6-132 months).
RESULTS: The median overall survival 55.4 months. DLI administration was associated with a trend towards better overall survival (p:0.05).Disease status at allo-HCT, PR or VGPR,ISS score and CMV serostatus were not significant predictors of OS and PFS. Full donor whole blood chimerism (>= 98%) at 3 months post-transplant was associated with PFS (p:0.04) but did not have a significant impact on OS(p:0.45).
CONCLUSION: Reduced intensity alemtuzumab conditioned allografts for myeloma after DT-PACE salvage chemotherapy is an efficient and low toxicity treatment for those who had a suboptimal response post autologous stem cell transplant for myeloma. This article is protected by copyright. All rights reserved.

PMID: 28632322 [PubMed - as supplied by publisher]

UK consensus statement on the use of plerixafor to facilitate autologous Peripheral Blood Stem Cell collection to support high-dose chemoradiotherapy for patients with malignancy.

Wed, 06/21/2017 - 21:45

UK consensus statement on the use of plerixafor to facilitate autologous Peripheral Blood Stem Cell collection to support high-dose chemoradiotherapy for patients with malignancy.

J Clin Apher. 2017 Jun 20;:

Authors: Douglas KW, Gilleece M, Hayden P, Hunter H, Johnson PRE, Kallmeyer C, Malladi RK, Paneesha S, Pawson R, Quinn M, Raj K, Richardson D, Robinson S, Russell N, Snowden J, Sureda A, Tholouli E, Thomson K, Watts M, Wilson KM

Abstract
Plerixafor is a CXC chemokine receptor (CXCR4) antagonist that mobilizes stem cells in the peripheral blood. It is indicated (in combination with granulocyte-colony stimulating factor [G-CSF]) to enhance the harvest of adequate quantities of cluster differentiation (CD) 34+ cells for autologous transplantation in patients with lymphoma or multiple myeloma whose cells mobilize poorly. Strategies for use include delayed re-mobilization after a failed mobilization attempt with G-CSF, and rescue or pre-emptive mobilization in patients in whom mobilization with G-CSF is likely to fail. Pre-emptive use has the advantage that it avoids the need to re-schedule the transplant procedure, with its attendant inconvenience, quality-of-life issues for the patient and cost of additional admissions to the transplant unit. UK experience from 2 major centers suggests that pre-emptive plerixafor is associated with an incremental drug cost of less than £2000 when averaged over all patients undergoing peripheral blood stem cell (PBSC) transplant. A CD34+ cell count of <15 µl(-1) at the time of recovery after chemomobilization or after four days of G-CSF treatment, or an apheresis yield of <1 × 10(6) CD34+ cells/kg on the first day of apheresis, could be used to predict the need for pre-emptive plerixafor.

PMID: 28631842 [PubMed - as supplied by publisher]

Coronary artery bypass grafting to treat coronary arterial occlusion incurred during orthotopic heart transplantation.

Wed, 06/21/2017 - 21:45
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Coronary artery bypass grafting to treat coronary arterial occlusion incurred during orthotopic heart transplantation.

J Card Surg. 2017 Jun 19;:

Authors: Rajagopal K, Rajapreyar I, Kar B, Loyalka P, Gregoric ID

Abstract
We report a case of left circumflex coronary artery occlusion sustained during orthotopic heart transplantation. Emergent coronary artery bypass grafting was performed, with recovery of cardiac function. The etiology and management of this complication are reviewed.

PMID: 28631410 [PubMed - as supplied by publisher]

An innovative biologic system for photon-powered myocardium in the ischemic heart.

Wed, 06/21/2017 - 21:45
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An innovative biologic system for photon-powered myocardium in the ischemic heart.

Sci Adv. 2017 Jun;3(6):e1603078

Authors: Cohen JE, Goldstone AB, Paulsen MJ, Shudo Y, Steele AN, Edwards BB, Patel JB, MacArthur JW, Hopkins MS, Burnett CE, Jaatinen KJ, Thakore AD, Farry JM, Truong VN, Bourdillon AT, Stapleton LM, Eskandari A, Fairman AS, Hiesinger W, Esipova TV, Patrick WL, Ji K, Shizuru JA, Woo YJ

Abstract
Coronary artery disease is one of the most common causes of death and disability, afflicting more than 15 million Americans. Although pharmacological advances and revascularization techniques have decreased mortality, many survivors will eventually succumb to heart failure secondary to the residual microvascular perfusion deficit that remains after revascularization. We present a novel system that rescues the myocardium from acute ischemia, using photosynthesis through intramyocardial delivery of the cyanobacterium Synechococcus elongatus. By using light rather than blood flow as a source of energy, photosynthetic therapy increases tissue oxygenation, maintains myocardial metabolism, and yields durable improvements in cardiac function during and after induction of ischemia. By circumventing blood flow entirely to provide tissue with oxygen and nutrients, this system has the potential to create a paradigm shift in the way ischemic heart disease is treated.

PMID: 28630913 [PubMed - in process]

Chest X-ray of a patient with history of pleural effusion.

Wed, 06/21/2017 - 21:45
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Chest X-ray of a patient with history of pleural effusion.

BMJ Case Rep. 2017 Jun 18;2017:

Authors: Konik E, Schirger J

Abstract
The presented chest X-ray depicts the thoracic duct anatomy of a 50-year-old man who underwent heart transplantation. His postoperative course was complicated by Candida mediastinitis, treated with débridements and closure of the anterior chest wound with myocutaneous flaps. Postoperatively, he had persistent output from a right-sided chest tube. The fluid appeared milky and its triglycerides level was elevated at 254 mg/dL. The drainage persisted despite a low fat diet. The interventional radiologist identified a leak in the upper thoracic duct. It was embolised with coil and onyx. After the procedure, the chylous pleural effusions resolved. The thoracic duct has been visualised on subsequent chest X-rays (figures 1 and 2).

PMID: 28630248 [PubMed - in process]

Comparative Analysis of Four Scores to Stratify Patients With Heart Failure and Reduced Ejection Fraction.

Wed, 06/21/2017 - 21:45
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Comparative Analysis of Four Scores to Stratify Patients With Heart Failure and Reduced Ejection Fraction.

Am J Cardiol. 2017 May 11;:

Authors: Freitas P, Aguiar C, Ferreira A, Tralhão A, Ventosa A, Mendes M

Abstract
There are several prognostic risk scores available for patients with heart failure with reduced ejection fraction (HFrEF) that can aid in the decision of listing candidates for heart transplant (HTx). A direct comparison between these scores has not been performed. Therefore, our objective was to evaluate the calibration and discriminative power of 4 contemporary HF scores. A retrospective analysis of 259 patients with HFrEF who underwent cardiopulmonary exercise test was conducted. The Heart Failure Survival Score (HFSS), Seattle Heart Failure Model (SHFM), Meta-analysis Global Group in Chronic Heart Failure (MAGGIC), and Metabolic Exercise Cardiac Kidney Index (MECKI) were compared. During the first year, 7 deaths occurred (6 cardiovascular) and 25 patients were submitted to HTx (8 urgent). Over a 2-year period, 14 deaths occurred (10 cardiovascular) and 34 patients received an HTx (8 urgent). Calibration analysis showed that SHFM and HFSS tended to underestimate event occurrence, whereas MAGGIC and MECKI tended to overestimate risk, especially in the highest risk subgroups. Interestingly, MECKI score at 1 year was well calibrated (expected similar to observed events). Overall, the MECKI score consistently showed better discrimination ability for all studied end points (areas under the curve between 0.8 and 0.9). In conclusion, along with HFSS and SHFM, the MECKI score can also be used to aid treatment decisions, such as HTx listing with the advantage of being very well calibrated at 1-year intervals, which might allow us to avoid the pitfalls of under/overestimation of risk.

PMID: 28629552 [PubMed - as supplied by publisher]

Psychiatric and cognitive characteristics of individuals with Danon disease (LAMP2 gene mutation).

Tue, 06/20/2017 - 12:45
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Psychiatric and cognitive characteristics of individuals with Danon disease (LAMP2 gene mutation).

Am J Med Genet A. 2017 Jun 19;:

Authors: Yardeni M, Weisman O, Mandel H, Weinberger R, Quarta G, Salazar-Mendiguchía J, Garcia-Pavia P, Lobato-Rodríguez MJ, Simon LF, Dov F, Arad M, Gothelf D

Abstract
Danon disease (DD) is a rare X-linked disorder caused by loss-of-function mutations in the LAMP2 gene, which encodes lysosome-associated membrane protein. It is characterized by the triad of hypertrophic cardiomyopathy, myopathy, and intellectual disability. Whereas the molecular and pathophysiological mechanisms underlying this disorder have been previously reported and continue to be explored, the cognitive deficits and psychiatric comorbidities manifested in DD remain an understudied topic. We systematically assessed cognitive abilities and psychiatric comorbidities in 13 males and females. Most of the participants in our cohort (n = 9; 75%) had an IQ score within the normal range, while only one participant had intellectual disability. Participants' performance on the Cognitive Neuropsychiatric Battery (CNB) showed only mildly impaired cognitive abilities in most modules, except in the executive functioning test, which was low compared to healthy controls. Of note, 69% of the participants met criteria for at least one psychiatric disorder, mainly mood and anxiety disorders, occurring alone or in combination in the same patient. The results of the present study challenge earlier reports suggesting that mental retardation is a core constituent in DD. Of importance, it underscores the need to refer Danon patients to psychiatric assessment.

PMID: 28627787 [PubMed - as supplied by publisher]

Lentiviral vector-mediated co-overexpression of VEGF and Bcl-2 improves mesenchymal stem cell survival and enhances paracrine effects in vitro.

Tue, 06/20/2017 - 12:45
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Lentiviral vector-mediated co-overexpression of VEGF and Bcl-2 improves mesenchymal stem cell survival and enhances paracrine effects in vitro.

Int J Mol Med. 2017 Jun 12;:

Authors: Ni X, Ou C, Guo J, Liu B, Zhang J, Wu Z, Li H, Chen M

Abstract
Mesenchymal stem cell (MSC) transplantation has emerged as a promising therapy for ischemic heart disease; however, the low survival rate of transplanted cells limits their therapeutic efficacy. The aim of this study was to investigate whether the dual genetic modification of vascular endothelial growth factor (VEGF) and B‑cell lymphoma‑2 (Bcl‑2) confers a higher expression level of the target genes, better survival and a stronger paracrine effect in MSCs in an adverse environment than the modification of the individual genes. For this purpse, a lentiviral vector was constructed by using a self‑cleaving T2A peptide sequence to link and achieve the co‑overexpression of VEGF and Bcl‑2. Rat MSCs were transfected to obtain cell lines that exhibited a stable overexpression. An in vitro model of oxygen glucose deprivation (OGD) was applied to mimic the ischemic microenvironment, and cell apoptosis, autophagy and the paracrine effects were then determined. Compared with the MSCs in which individual genes were modified and the control MSCs, the MSCs which were subjected to dual genetic modification had a higher expression level of the target genes, a more rapid proliferation, reduced apoptosis, decreased autophagy and an enhanced paracrine effect. Furthermore, the suppression of autophagy was found to contribute to the inhibition of apoptosis in this in vitro OGD model. On the whole, these data indicate that the co‑overexpression of VEGF and Bcl‑2 protects MSCs in an ischemic environment by inhibiting apoptosis, suppressing autophagy and enhancing the paracrine effects.

PMID: 28627637 [PubMed - as supplied by publisher]

A Multicenter Retrospective Analysis Stressing Importance of Long-Term Follow Up after Hematopoietic Cell Transplantation for Β-Thalassemia.

Tue, 06/20/2017 - 12:45
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A Multicenter Retrospective Analysis Stressing Importance of Long-Term Follow Up after Hematopoietic Cell Transplantation for Β-Thalassemia.

Biol Blood Marrow Transplant. 2017 Jun 13;:

Authors: Chaudhury S, Ayas M, Rosen C, Ma M, Viqaruddin M, Parikh S, Kharbanda S, Chiang KY, Haight A, Bhatia M, Guilcher G, Thompson A, Shenoy S

Abstract
Allogeneic hematopoietic cell transplantation (HCT) is curative in patients with β-thalassemia major. However, the majority of reports on HCT outcomes lack long-term follow-up data with the exception of single center reports. An international multicenter retrospective data collection and analysis was conducted in 176 β-Thalassemia patients who were 1 year or beyond after first HCT to evaluate follow up methods and outcomes at 7 centers- Median age at HCT was 5.5 years (range, 0.6- 18.5) and median follow-up was 7 years (range, 1-20). HCT was predominantly from HLA-matched related donors (91%) with bone marrow as stem cell source (91%) and myeloablative conditioning regimens (88%). Late mortality or persistent chronic graft versus host disease (GVHD) were rare (<2%). Graft rejection was reported in 23% (24% of these occurred beyond 1 year) post-HCT. Of 119 patients with donor chimerism results available for ≥4yrs post HCT, 50% had >95%, 22% had 50-95%, 7% had 20-50% and 25 (21%) had <20% donor chimerism. Organ dysfunction was identified in 10% pre-HCT and in 20% post-HCT even without complete clinical details on all patients. Hypogonadism and elevated creatinine for age were most commonly reported and significantly higher in recipients ≥ 7years at the time of HCT (p=0.007), and in those with pre-existing morbidity before HCT (p=0.02). Outcomes were unaffected by pre- HCT ferritin or GVHD. Mean z-scores for height and weight were low at baseline and remained low post-HCT (79%), confirming that growth impairment from disease lacked recovery post-HCT during this follow-up period.
CONCLUSION: HCT for β-thalassemia has a high rate of cure and low mortality especially in the young, and from HLA-matched related donors. Half the number of recipients live with mixed chimerism that requires continued follow-up due to a risk of late graft rejection (14%). Organ function following HCT when <7 years of age was generally preserved. Hypogonadism, renal dysfunction and growth impairment that failed to correct were late complications identified most frequently in older transplant recipients. Systematic follow-up of individual organs such as lung and heart were inadequate but important. These data support the development of simple measures of uniformly tracking long-term HCT outcomes and organ functions in children and adolescents who undergo HCT for thalassemia, allowing for systematic identification and implementation of standardized surveillance strategies and interventions.

PMID: 28627425 [PubMed - as supplied by publisher]

Accepting Hearts From Hepatitis C Positive Donor: Can We Expand the Donor Pool?

Tue, 06/20/2017 - 12:45
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Accepting Hearts From Hepatitis C Positive Donor: Can We Expand the Donor Pool?

J Card Fail. 2017 Jun 13;:

Authors: Grinstein J, Lourenco LM, Te HS, Renz JF, Jeevanandam V, Uriel N

Abstract
BACKGROUND: Until recently, transplantation from hepatitis C positive donors was relatively contraindicated as eradication of active hepatitis C previously required an interferon-based regimen which has been associated with rejection in solid organ transplantation. New interferon-free treatment regimens for hepatitis C have fewer adverse events and higher cure rates than interferon-based regimens. Interferon-free regimens have been shown to be safe in the liver transplantation literature but little is known about the safety and efficacy of treatment in heart transplantation.
CASE DESCRIPTION AND DISCUSSION: Here we report a case of successful eradication of hepatitis C with a non-interferon based regimen using Ledipasvir-sofosbuvir following combined orthotopic heart and liver transplantation. Based on the prevalence of hepatitis C in the general population, inclusion of hepatitis C positive donors for heart transplantation can expand this component of the donor pool 3-6 fold.
CONCLUSIONS: In carefully selected patients and recipients, inclusion of hepatitis C positive donors may allow for expansion of the donor pool.

PMID: 28627403 [PubMed - as supplied by publisher]

Landmark cure rate models with time-dependent covariates.

Tue, 06/20/2017 - 12:45
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Landmark cure rate models with time-dependent covariates.

Stat Methods Med Res. 2017 Jan 01;:962280217708681

Authors: Shi H, Yin G

Abstract
We propose a class of landmark cure rate models by incorporating time-dependent covariates. The landmark approach enables us to obtain dynamic predictions of a patient's survival probabilities as new clinical information emerges during the follow-up time. The proposed method extends the landmark model for failure time data with a possible cure fraction. We specify a series of landmark time points, and for each of time point, we construct a landmark data set consisting of only those at-risk individuals at the landmark time. The time-dependent covariates can be fixed at the values evaluated at the landmark time point. Through landmarking, our framework accommodates the Cox proportional hazards model, accelerated failure time model and censored quantile regression model in the presence of a cure proportion. We conduct simulation studies to assess the estimation accuracy of the proposed method, and illustrate it with data from a heart transplant study.

PMID: 28627311 [PubMed - as supplied by publisher]

Donor-specific antibodies are associated with micro- and macrovascular coronary disease, restrictive myocardial damage, and poor outcome in heart-transplanted patients.

Tue, 06/20/2017 - 12:45
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Donor-specific antibodies are associated with micro- and macrovascular coronary disease, restrictive myocardial damage, and poor outcome in heart-transplanted patients.

Clin Transplant. 2017 Jun 19;:

Authors: Clemmensen TS, Koefoed-Nielsen P, Jensen LA, Poulsen SH, Holm NR, Løgstrup BB, Christiansen EH, Dijkstra J, Valen KPB, Eiskjaer H

Abstract
AIMS: We examined the relationship between donor-specific HLA antibody (DSA) presence and graft function, hemodynamics, cardiac allograft vasculopathy (CAV), and major adverse cardiac events (MACE) in stable long-term heart-transplanted (HTx) patients.
METHODS: Sera from 79 patients (median 7.5 years after HTx) were analyzed for DSA presence. Graft function was evaluated by echocardiography and right heart catheterization. CAV-burden was determined by coronary angiography, optical coherence tomography (OCT), and coronary flow velocity reserve (CFVR). Patients were prospectively followed after DSA assessment. MACE included significant CAV progression, heart failure, treated rejection, and cardio-vascular death.
RESULTS: Sixty patients had no DSA and 19 patients were sensitized. The vasculopathy burden by angiography, OCT, and CFVR were more pronounced in DSA-positive patients than in DSA-negative patients. DSA-positive patients had higher pulmonary capillary wedge pressure (16 [8;21] versus 9 mmHg [7;11], p<0.05) and right atrial pressure (8 [6;9] versus 4 mmHg [2;6], p<0.01) and lower global longitudinal strain (-13% [-10;-15] versus -16% [-14;-17], p<0.01) than DSA-negative patients. DSA presence was a strong MACE predictor (HR 4.7 (95% CI 2.0-11.4), p<0.001).
CONCLUSIONS: DSA-positive patients had higher vasculopathy burden, higher filling pressures, and lower longitudinal myocardial deformation than DSA-negative patients. The DSA presence was a strong MACE predictor. This article is protected by copyright. All rights reserved.

PMID: 28627046 [PubMed - as supplied by publisher]

Inefficacy of Platelet Transfusion in a Heart Transplant Patient Under Continuous Ticagrelor.

Tue, 06/20/2017 - 12:45
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Inefficacy of Platelet Transfusion in a Heart Transplant Patient Under Continuous Ticagrelor.

J Cardiothorac Vasc Anesth. 2017 Feb 20;:

Authors: Filaire L, Pham DT, d'Ostrevy N, Tran HT, Camilleri L, Azarnoush K

PMID: 28625754 [PubMed - as supplied by publisher]

Decline in peak oxygen consumption over time predicts death or transplantation in adults with a Fontan circulation.

Tue, 06/20/2017 - 12:45
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Decline in peak oxygen consumption over time predicts death or transplantation in adults with a Fontan circulation.

Am Heart J. 2017 Jul;189:184-192

Authors: Cunningham JW, Nathan AS, Rhodes J, Shafer K, Landzberg MJ, Opotowsky AR

Abstract
Peak oxygen consumption (pVO2) measured by cardiopulmonary exercise test (CPET) predicts mortality in adults with a Fontan circulation. The purpose of this study was to assess the additive prognostic value of change in pVO2 over time.
METHODS: We analyzed a cohort of adults (≥18 years old) with a Fontan circulation who underwent at least 2 maximal CPETs separated by 6-30 months at Boston Children's Hospital between 2000 and 2015. Survival analysis was performed to determine whether changes in CPET variables, including pVO2 between consecutive tests, were associated with subsequent clinical events. The primary outcome was transplant-free survival.
RESULTS: The study included 130 patients with 287 CPET test pairs. Average age was 26.6±9.5 years. Baseline pVO2 averaged 22.0±5.7 mL/kg/min or 60.9%±13.7% predicted. In the cohort overall, there was no change in mean pVO2 between sequential CPETs. Eleven patients died and 2 underwent transplant. On average, pVO2 declined for patients who subsequently died or underwent transplant but remained stable among those who did not (-9.8%±14.6% vs 0.0±13.0%, P<.01). Those with a decline in pVO2 between CPETs were at greater risk of death or transplantation (per 10% decrease in pVO2: HR=2.0, 95% CI 1.2-3.1, P=.004). Change in pVO2 remained a significant predictor of death or transplant after adjusting for pVO2 at first CPET (per 10% decline in pVO2: HR=2.5, 95% CI 1.5-4.2, P<.001).
CONCLUSIONS: A decline in pVO2 between consecutive CPETs predicts increased risk for death or transplant in adults with a Fontan circulation independent of baseline pVO2. These results support the additive clinical value of serial CPET in this population.

PMID: 28625375 [PubMed - in process]

Two and a Half Hours of Cardiopulmonary Resuscitation in a Deceased Brain Dead Donor before Liver Transplantation - A Good Idea to Accept?

Tue, 06/20/2017 - 12:45
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Two and a Half Hours of Cardiopulmonary Resuscitation in a Deceased Brain Dead Donor before Liver Transplantation - A Good Idea to Accept?

Chirurgia (Bucur). 2017 Jan-Feb;112(1):46-49

Authors: Hoyer DP, Kaiser GM, Paul A, Machairas N, Molmenti EP, Sotiropoulos GC, -

Abstract
The sequelae of cardiac arrest (CA) and cardiopulmonary resuscitation (CPR) in organ donors potentially results in ischemic organ injury and graft dysfunction after transplantation. Thresholds of resuscitation times in brain dead liver donors have not been established so far. We report the case of a brain dead liver donor who experienced 2.5 hours of CPR whose liver was successfully transplanted. A 75-year-old male experienced CA and was treated by CPR with streptokinase application for 2.5 hours until stabilization of cardiac function. Brain death was diagnosed at the day of admission and organ donation carried out within 24 hours. The DRI was 2.2 with a CIT of 8.8 hours. The liver was transplanted into a 64-year-old recipient suffering from alcoholic liver cirrhosis and a MELD-score of 10 non representative for severity of disease. During follow up of 4 years ERCP and stenting was performed regularly for biliary anastomosis stenosis. The patient remained in a very good overall state of health without any signs of liver dysfunction. This case demonstrates that an extensive period of CPR is not an obligatory exclusion criterion for liver donation. Thresholds of CPR times as well as predictive factors in donors with CA should be established.

PMID: 28266292 [PubMed - indexed for MEDLINE]

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