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Implantation of a left ventricular assist device to provide long-term support for end-stage Duchenne muscular dystrophy-associated cardiomyopathy.

Sat, 08/05/2017 - 12:45
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Implantation of a left ventricular assist device to provide long-term support for end-stage Duchenne muscular dystrophy-associated cardiomyopathy.

ESC Heart Fail. 2017 Aug;4(3):379-383

Authors: Stoller D, Araj F, Amin A, Fitzsimmons C, Morlend R, Thibodeau JT, Ramaciotti C, Drazner MH, Meyer DM, Mammen PPA

Abstract
A young man with Duchenne muscular dystrophy presented to the UT Southwestern Neuromuscular Cardiomyopathy Clinic with advanced heart failure. Despite maximal medical therapy, his cardiac function continued to decline requiring initiation of inotrope therapy. Given the patient's clinical deterioration, a left ventricular assist device (LVAD) was implanted as destination therapy after undergoing a multidisciplinary assessment. The patient tolerated the surgical implantation of the LVAD without any significant complications, and he has had a relatively unremarkable course 38 months post-LVAD implantation. A critical factor contributing to the long-term success of this patient was the decision to select an LVAD that would not disrupt the diaphragm and thus preserve the respiratory muscle strength. This case demonstrates that permanent mechanical LVADs should be considered for appropriately selected Duchenne muscular dystrophy patients with medically refractory end-stage cardiomyopathy.

PMID: 28772036 [PubMed]

ACE inhibitor-associated intestinal angioedema in orthotopic heart transplantation.

Sat, 08/05/2017 - 12:45
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ACE inhibitor-associated intestinal angioedema in orthotopic heart transplantation.

ESC Heart Fail. 2017 Aug;4(3):384-386

Authors: Srinivasan D, Strohbehn GW, Cascino T

Abstract
Angiotensin-converting enzyme inhibitor induced angioedema commonly involves the head and neck area. We report a case of angiotensin-converting enzyme inhibitor induced intestinal angioedema in a heart transplant recipient on mTOR immunosuppression. A 36-year-old Caucasian woman with history of heart transplantation on sirolimus, tacrolimus and prednisone presented to the Emergency Department with abdominal pain, one day following lisinopril initiation. A computer tomography scan demonstrated diffuse bowel wall thickening consistent with pancolitis and edema. She was subsequently diagnosed with angiotensin-converting enzyme inhibitor induced angioedema. Patients on mTOR immunosuppression are at higher risk for this potentially life-threatening side effect. Knowledge of this interaction is critical for providers prescribing mTOR agents.

PMID: 28772029 [PubMed]

Quantification of transplant-derived circulating cell-free DNA in absence of a donor genotype.

Sat, 08/05/2017 - 12:45
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Quantification of transplant-derived circulating cell-free DNA in absence of a donor genotype.

PLoS Comput Biol. 2017 Aug;13(8):e1005629

Authors: Sharon E, Shi H, Kharbanda S, Koh W, Martin LR, Khush KK, Valantine H, Pritchard JK, De Vlaminck I

Abstract
Quantification of cell-free DNA (cfDNA) in circulating blood derived from a transplanted organ is a powerful approach to monitoring post-transplant injury. Genome transplant dynamics (GTD) quantifies donor-derived cfDNA (dd-cfDNA) by taking advantage of single-nucleotide polymorphisms (SNPs) distributed across the genome to discriminate donor and recipient DNA molecules. In its current implementation, GTD requires genotyping of both the transplant recipient and donor. However, in practice, donor genotype information is often unavailable. Here, we address this issue by developing an algorithm that estimates dd-cfDNA levels in the absence of a donor genotype. Our algorithm predicts heart and lung allograft rejection with an accuracy that is similar to conventional GTD. We furthermore refined the algorithm to handle closely related recipients and donors, a scenario that is common in bone marrow and kidney transplantation. We show that it is possible to estimate dd-cfDNA in bone marrow transplant patients that are unrelated or that are siblings of the donors, using a hidden Markov model (HMM) of identity-by-descent (IBD) states along the genome. Last, we demonstrate that comparing dd-cfDNA to the proportion of donor DNA in white blood cells can differentiate between relapse and the onset of graft-versus-host disease (GVHD). These methods alleviate some of the barriers to the implementation of GTD, which will further widen its clinical application.

PMID: 28771616 [PubMed - in process]

Prophylactic levosimendan for the prevention of low cardiac output syndrome and mortality in paediatric patients undergoing surgery for congenital heart disease.

Sat, 08/05/2017 - 12:45
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Prophylactic levosimendan for the prevention of low cardiac output syndrome and mortality in paediatric patients undergoing surgery for congenital heart disease.

Cochrane Database Syst Rev. 2017 Aug 02;8:CD011312

Authors: Hummel J, Rücker G, Stiller B

Abstract
BACKGROUND: Low cardiac output syndrome remains a serious complication, and accounts for substantial morbidity and mortality in the postoperative course of paediatric patients undergoing surgery for congenital heart disease. Standard prophylactic and therapeutic strategies for low cardiac output syndrome are based mainly on catecholamines, which are effective drugs, but have considerable side effects. Levosimendan, a calcium sensitiser, enhances the myocardial function by generating more energy-efficient myocardial contractility than achieved via adrenergic stimulation with catecholamines. Thus potentially, levosimendan is a beneficial alternative to standard medication for the prevention of low cardiac output syndrome in paediatric patients after open heart surgery.
OBJECTIVES: To review the efficacy and safety of the postoperative prophylactic use of levosimendan for the prevention of low cardiac output syndrome and mortality in paediatric patients undergoing surgery for congenital heart disease.
SEARCH METHODS: We identified trials via systematic searches of CENTRAL, MEDLINE, Embase, and Web of Science, as well as clinical trial registries, in June 2016. Reference lists from primary studies and review articles were checked for additional references.
SELECTION CRITERIA: We only included randomised controlled trials (RCT) in our analysis that compared prophylactic levosimendan with standard medication or placebo, in infants and children up to 18 years of age, who were undergoing surgery for congenital heart disease.
DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and assessed risk of bias according to a pre-defined protocol. We obtained additional information from all but one of the study authors of the included studies. We used the five GRADE considerations (study limitations, consistency of effect, imprecision, indirectness, and publication bias) to assess the quality of evidence from the studies that contributed data to the meta-analyses for the prespecified outcomes. We created a 'Summary of findings' table to summarise the results and the quality of evidence for each outcome.
MAIN RESULTS: We included five randomised controlled trials with a total of 212 participants in the analyses. All included participants were under five years of age. Using GRADE, we assessed there was low-quality evidence for all analysed outcomes. We assessed high risk of performance and detection bias for two studies due to their unblinded setting. Levosimendan showed no clear effect on risk of mortality (risk ratio (RR) 0.47, 95% confidence interval (CI) 0.12 to 1.82; participants = 123; studies = 3) and no clear effect on low cardiac output syndrome (RR 0.64, 95% CI 0.39 to 1.04; participants = 83; studies = 2) compared to standard treatments. Data on time-to-death were not available from any of the included studies.There was no conclusive evidence on the effect of levosimendan on the secondary outcomes. The length of intensive care unit stays (mean difference (MD) 0.33 days, 95% CI -1.16 to 1.82; participants = 188; studies = 4), length of hospital stays (MD 0.26 days, 95% CI -3.50 to 4.03; participants = 75; studies = 2), duration of mechanical ventilation (MD -0.04 days, 95% CI -0.08 to 0.00; participants = 208; studies = 5), and the risk of mechanical circulatory support or cardiac transplantation (RR 1.49, 95% CI 0.19 to 11.37; participants = 60; studies = 2) did not clearly differ between the groups. Published data about adverse effects of levosimendan were limited. A meta-analysis of hypotension, one of the most feared side effects of levosimendan, was not feasible because of the heterogeneous expression of blood pressure values.
AUTHORS' CONCLUSIONS: The current level of evidence is insufficient to judge whether prophylactic levosimendan prevents low cardiac output syndrome and mortality in paediatric patients undergoing surgery for congenital heart disease. So far, no significant differences have been detected between levosimendan and standard inotrope treatments in this setting.The authors evaluated the quality of evidence as low, using the GRADE approach. Reasons for downgrading were serious risk of bias (performance and detection bias due to unblinded setting of two RCTs), serious risk of inconsistency, and serious to very serious risk of imprecision (small number of included patients, low event rates).

PMID: 28770972 [PubMed - as supplied by publisher]

Discovery and replication of SNP-SNP interactions for quantitative lipid traits in over 60,000 individuals.

Sat, 08/05/2017 - 12:45
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Discovery and replication of SNP-SNP interactions for quantitative lipid traits in over 60,000 individuals.

BioData Min. 2017;10:25

Authors: Holzinger ER, Verma SS, Moore CB, Hall M, De R, Gilbert-Diamond D, Lanktree MB, Pankratz N, Amuzu A, Burt A, Dale C, Dudek S, Furlong CE, Gaunt TR, Kim DS, Riess H, Sivapalaratnam S, Tragante V, van Iperen EPA, Brautbar A, Carrell DS, Crosslin DR, Jarvik GP, Kuivaniemi H, Kullo IJ, Larson EB, Rasmussen-Torvik LJ, Tromp G, Baumert J, Cruickshanks KJ, Farrall M, Hingorani AD, Hovingh GK, Kleber ME, Klein BE, Klein R, Koenig W, Lange LA, Mӓrz W, North KE, Charlotte Onland-Moret N, Reiner AP, Talmud PJ, van der Schouw YT, Wilson JG, Kivimaki M, Kumari M, Moore JH, Drenos F, Asselbergs FW, Keating BJ, Ritchie MD

Abstract
BACKGROUND: The genetic etiology of human lipid quantitative traits is not fully elucidated, and interactions between variants may play a role. We performed a gene-centric interaction study for four different lipid traits: low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), total cholesterol (TC), and triglycerides (TG).
RESULTS: Our analysis consisted of a discovery phase using a merged dataset of five different cohorts (n = 12,853 to n = 16,849 depending on lipid phenotype) and a replication phase with ten independent cohorts totaling up to 36,938 additional samples. Filters are often applied before interaction testing to correct for the burden of testing all pairwise interactions. We used two different filters: 1. A filter that tested only single nucleotide polymorphisms (SNPs) with a main effect of p < 0.001 in a previous association study. 2. A filter that only tested interactions identified by Biofilter 2.0. Pairwise models that reached an interaction significance level of p < 0.001 in the discovery dataset were tested for replication. We identified thirteen SNP-SNP models that were significant in more than one replication cohort after accounting for multiple testing.
CONCLUSIONS: These results may reveal novel insights into the genetic etiology of lipid levels. Furthermore, we developed a pipeline to perform a computationally efficient interaction analysis with multi-cohort replication.

PMID: 28770004 [PubMed]

Anti-Interleukin-6 Promotes Allogeneic Bone Marrow Engraftment and Prolonged Graft Survival in an Irradiation-Free Murine Transplant Model.

Sat, 08/05/2017 - 12:45
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Anti-Interleukin-6 Promotes Allogeneic Bone Marrow Engraftment and Prolonged Graft Survival in an Irradiation-Free Murine Transplant Model.

Front Immunol. 2017;8:821

Authors: Granofszky N, Farkas AM, Muckenhuber M, Mahr B, Unger L, Maschke S, Pilat N, Holly R, Wiletel M, Regele H, Wekerle T

Abstract
Transfer of recipient regulatory T cells (Tregs) induces mixed chimerism and tolerance in an irradiation-free bone marrow (BM) transplantation (BMT) model involving short-course co-stimulation blockade and mTOR inhibition. Boosting endogenous Tregs pharmacologically in vivo would be an attractive alternative avoiding the current limitations of performing adoptive cell therapy in the routine clinical setting. Interleukin-6 (IL-6) potently inhibits Treg differentiation and its blockade was shown to increase Treg numbers in vivo. Therefore, we investigated whether IL-6 blockade can replace adoptive Treg transfer in irradiation-free allogeneic BMT. Treatment with anti-IL-6 instead of Treg transfer led to multi-lineage chimerism (persisting for ~12 weeks) in recipients of fully mismatched BM and significantly prolonged donor skin (MST 58 days) and heart (MST > 100 days) graft survival. Endogenous Foxp3(+) Tregs expanded in anti-IL-6-treated BMT recipients, while dendritic cell (DC) activation and memory CD8(+) T cell development were inhibited. Adding anti-IL-17 to anti-IL-6 treatment increased Treg frequencies, but did not further prolong donor skin graft survival significantly. These results demonstrate that IL-6 blockade promotes BM engraftment and donor graft survival in non-irradiated recipients and might provide an alternative to Treg cell therapy in the clinical setting.

PMID: 28769930 [PubMed]

C-C Chemokine Receptor Type 5 (CCR5)-Mediated Docking of Transferred Tregs Protects Against Early Blood-Brain Barrier Disruption After Stroke.

Sat, 08/05/2017 - 12:45
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C-C Chemokine Receptor Type 5 (CCR5)-Mediated Docking of Transferred Tregs Protects Against Early Blood-Brain Barrier Disruption After Stroke.

J Am Heart Assoc. 2017 Aug 02;6(8):

Authors: Li P, Wang L, Zhou Y, Gan Y, Zhu W, Xia Y, Jiang X, Watkins S, Vazquez A, Thomson AW, Chen J, Yu W, Hu X

Abstract
BACKGROUND: Despite recent evidence demonstrating a potent protective effect of adoptively transferred regulatory T cells (Tregs) in ischemic stroke, the mechanism for Treg mobilization and activation in the ischemic brain is, remarkably, unknown. This study determines the role of C-C chemokine receptor type 5 (CCR5) in mediating the docking and activation of transferred Tregs in their protection of early blood-brain barrier disruption after stroke.
METHODS AND RESULTS: Adoptive transfer of CCR5(-/-) Tregs failed to reduce brain infarct or neurological deficits, indicating an indispensable role of CCR5 in Treg-afforded protection against cerebral ischemia. Two-photon live imaging demonstrated that CCR5 was critical for Treg docking at the injured vessel wall, where they interact with blood-borne neutrophils/macrophages after cerebral ischemic injury. CCR5 deficiency on donor Tregs deprived of their early protection against blood-brain barrier damage. Using flow cytometry, real-time polymerase chain reaction, and immunostaining, we confirmed that the expression of CCL5, a CCR5 ligand, was significantly elevated on the injured endothelium after cerebral ischemia, accompanied by CCR5 upregulation on circulating Tregs. In a Treg-endothelial cell coculture, CCR5 expression was induced on Tregs on their exposure to ischemia-injured endothelial cells. Furthermore, CCR5 induction on Tregs enhanced expression of the inhibitory molecule programmed death ligand 1, which in turn inhibited neutrophil-derived matrix metallopeptidase 9.
CONCLUSIONS: These results suggest that CCR5 is a critical molecule for Treg-mediated blood-brain barrier protection and a potential target to optimize Treg therapy for stroke.

PMID: 28768648 [PubMed - in process]

Muir-Torre syndrome: multiple sebaceous neoplasms and visceral malignancy manifesting after cardiac transplantation and iatrogenic immunosuppression.

Sat, 08/05/2017 - 12:45
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Muir-Torre syndrome: multiple sebaceous neoplasms and visceral malignancy manifesting after cardiac transplantation and iatrogenic immunosuppression.

Int J Dermatol. 2017 Feb;56(2):e26-e27

Authors: Shaw KC, Altmayer SA, Driscoll MS

PMID: 27868185 [PubMed - indexed for MEDLINE]

Stem cells differentiation and probing their therapeutic applications in hematological disorders: a critical review.

Sat, 08/05/2017 - 12:45
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Stem cells differentiation and probing their therapeutic applications in hematological disorders: a critical review.

Eur Rev Med Pharmacol Sci. 2016 Oct;20(20):4390-4400

Authors: Ali F, Taresh S, Al-Nuzaily M, Mok PL, Ismail A, Ahmad S

Abstract
Numerous lines of evidence support that bone marrow is a rich source of stem cells that can be used for research purposes and to treat some complex blood diseases and cancers. Stem cells are a potential source for regenerative medicine and tissue replacement after injury or disease, and mother cells that possess the capacity to become any type of cell in the body. They are cells without specific structure and characterized by their ability to self-renew or multiply while maintaining the potential to develop into other types of cells. Stem cells can normally become cells of the blood, heart, bones, skin, muscles or brain. Although, there are different sources of stem cells, all types of stem cells have the same capacity to develop into multiple types of cells. Stem cells are generally described as unspecialized cells with unlimited proliferation capacity that can divide (through mitosis) to produce more stem cells. Several types of adult stem cells have been characterized and can be cultured in vitro, including neural stem cells, hematopoietic stem cells, mesenchymal stem cells, cardiac stem cells and epithelial stem cells. They are valuable as research tools and might, in the future, be used to treat a wide range of diseases such as hematological hereditary diseases, Parkinson's disease, diabetes mellitus, heart disease and many other diseases. Currently, two types of stem cells have been identified based on their origins, namely embryonic stem cells and adult stem cells. Collectively, although many kinds of literature have been studying stem cell application in terms of clinical practice, stem cell-based therapy is still in its infancy stage.

PMID: 27831631 [PubMed - indexed for MEDLINE]

Steroids can reduce warm ischemic reperfusion injury in a porcine donation after circulatory death model with ex vivo lung perfusion evaluation.

Sat, 08/05/2017 - 12:45
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Steroids can reduce warm ischemic reperfusion injury in a porcine donation after circulatory death model with ex vivo lung perfusion evaluation.

Transpl Int. 2016 Nov;29(11):1237-1246

Authors: Martens A, Boada M, Vanaudenaerde BM, Verleden SE, Vos R, Verleden GM, Verbeken EK, Van Raemdonck D, Schols D, Claes S, Neyrinck AP

Abstract
Donation after circulatory death (DCD) is being used to increase the number of transplantable organs. The role and timing of steroids in DCD donation and ex vivo lung perfusion (EVLP) has not been thoroughly investigated. In this study, we investigated the effect of steroids on warm ischemic injury in a porcine model (n = 6/group). Following cardiac arrest, grafts were left untouched in the donor (90-min warm ischemia). Graft function was assessed after 6 h of EVLP. In the MP group, 500 mg methylprednisolone was given prior to cardiac arrest and during EVLP. In the CONTR group, no steroids were added. Median lung compliance (13 ml/cmH2 0) was significantly better preserved in the CONTR group than in the MP group (30.5 ml/cmH2 0). Also, median wet-to-dry weight (6.11 vs. 6.94) and CT density (182.5 vs. 352.9 g/l) were significantly better in the MP group than in the CONTR group, respectively. There was no difference in oxygenation and pulmonary vascular resistance. Perfusate cytokine analysis showed a significant reduction in IL-1β, IL-8, IFN-α, IL-10, TNF-α, and IFN-γ in MP. Cytokines in bronchoalveolar lavage were not decreased except for IFN-gamma. We demonstrated that warm ischemic injury in DCD donation can be attenuated by steroids when given prior to warm ischemia and during EVLP. Ethical context of donor preconditioning should be discussed further.

PMID: 27514498 [PubMed - indexed for MEDLINE]

A multidisciplinary team-based process improves outpatient anticoagulation quality with continuous-flow left-ventricular assist devices.

Sat, 08/05/2017 - 12:45
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A multidisciplinary team-based process improves outpatient anticoagulation quality with continuous-flow left-ventricular assist devices.

Int J Cardiol. 2016 Sep 01;218:118-9

Authors: Kuyumjian YM, Miyares MA, Leverock J, Chaparro S, Baker WL, Jennings DL

PMID: 27232922 [PubMed - indexed for MEDLINE]

Comparison of the ability of two continuous cardiac output monitors to measure trends in cardiac output: estimated continuous cardiac output measured by modified pulse wave transit time and an arterial pulse contour-based cardiac output device.

Sat, 08/05/2017 - 12:45
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Comparison of the ability of two continuous cardiac output monitors to measure trends in cardiac output: estimated continuous cardiac output measured by modified pulse wave transit time and an arterial pulse contour-based cardiac output device.

J Clin Monit Comput. 2016 Oct;30(5):621-7

Authors: Terada T, Oiwa A, Maemura Y, Robert S, Kessoku S, Ochiai R

Abstract
Estimated continuous cardiac output (esCCO), a noninvasive technique for continuously measuring cardiac output (CO), is based on modified pulse wave transit time, which in turn is determined by pulse oximetry and electrocardiography. However, its trending ability has never been evaluated in patients undergoing non-cardiac surgery. Therefore, this study examined esCCO's ability to detect the exact changes in CO, compared with currently available arterial waveform analysis methods, in patients undergoing kidney transplantation. CO was measured using an esCCO system and arterial pressure-based CO (APCO), and compared with a corresponding intermittent bolus thermodilution CO (ICO) method. Percentage error and statistical methods, including concordance analysis and polar plot analysis, were used to analyze results from 15 adult patients. The difference in the CO values between esCCO and ICO was -0.39 ± 1.15 L min(-1) (percentage error, 35.6 %). And corrected precision for repeated measures was 1.16 L min(-1) (percentage error for repeated measures, 36.0 %). A concordance analysis showed that the concordance rate was 93.1 %. The mean angular bias was -1.8° and the radial limits of agreement were ±37.6°. The difference between the APCO and ICO CO values was 0.04 ± 1.37 L min(-1) (percentage error, 42.4 %). And corrected precision for repeated measures was 1.37 L min(-1) (percentage error for repeated measures, 42.5 %). The concordance rate was 89.7 %, with a mean angular bias of -3.3° and radial limits of agreement of ±42.2°. This study demonstrated that the trending ability of the esCCO system is not clinically acceptable, as judged by polar plots analysis; however, its trending ability is clinically acceptable based on a concordance analysis, and is comparable with currently available arterial waveform analysis methods.

PMID: 26370094 [PubMed - indexed for MEDLINE]

Novel technique for airless connection of artificial heart to vascular conduits.

Wed, 08/02/2017 - 10:00
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Novel technique for airless connection of artificial heart to vascular conduits.

J Artif Organs. 2017 Jul 31;:

Authors: Karimov JH, Gao S, Dessoffy R, Sunagawa G, Sinkewich M, Grady P, Sale S, Moazami N, Fukamachi K

Abstract
Successful implantation of a total artificial heart relies on multiple standardized procedures, primarily the resection of the native heart, and exacting preparation of the atrial and vascular conduits for pump implant and activation. Achieving secure pump connections to inflow/outflow conduits is critical to a successful outcome. During the connection process, however, air may be introduced into the circulation, traveling to the brain and multiple organs. Such air emboli block blood flow to these areas and are detrimental to long-term survival. A correctly managed pump-to-conduit connection prevents air from collecting in the pump and conduits. To further optimize pump-connection techniques, we have developed a novel connecting sleeve that enables airless connection of the Cleveland Clinic continuous-flow total artificial heart (CFTAH) to the conduits. In this brief report, we describe the connecting sleeve design and our initial results from two acute in vivo implantations using a scaled-down version of the CFTAH.

PMID: 28761992 [PubMed - as supplied by publisher]

Posterior Reversible Encephalopathy Syndrome after Heart Transplantation: Diagnosis and Immunosuppressive Therapy.

Wed, 08/02/2017 - 10:00
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Posterior Reversible Encephalopathy Syndrome after Heart Transplantation: Diagnosis and Immunosuppressive Therapy.

Tex Heart Inst J. 2017 Jun;44(3):205-208

Authors: Kapoor A, Birks E, Lenneman A, McCants K

Abstract
Posterior reversible encephalopathy syndrome, an infrequent neurotoxicity associated with the use of tacrolimus, was first described in 1996, as a reversible syndrome manifested by headache, altered mental function, seizures, and visual disturbances. We describe the case of a 37-year-old woman who developed neurologic symptoms consistent with encephalopathy after treatment with tacrolimus, which was prescribed to maintain immunosuppression after orthotopic heart transplantation. This report also discusses the imaging methods used in the diagnosis of posterior reversible encephalopathy and highlights the difficulty of maintaining immunosuppression and managing medication-related adverse effects, while taking into account the risk of acute rejection after transplantation.

PMID: 28761402 [PubMed - in process]

Retained cardiac implantable electronic device fragments are not associated with magnetic resonance imaging safety issues, morbidity, or mortality after orthotopic heart transplant.

Wed, 08/02/2017 - 10:00
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Retained cardiac implantable electronic device fragments are not associated with magnetic resonance imaging safety issues, morbidity, or mortality after orthotopic heart transplant.

Am Heart J. 2017 Aug;190:46-53

Authors: Austin CO, Landolfo K, Parikh PP, Patel PC, Venkatachalam KL, Kusumoto FM

Abstract
BACKGROUND: Cardiac implantable electronic device therapy (CIED) has revolutionized treatment for advanced heart failure. Most patients considered for orthotopic heart transplantation (OHT) are treated with implantable cardioverter defibrillators, cardiac resynchronization therapy, or both. These CIEDs are surgically extracted at the time of transplant. Occasionally, CIEDs are incompletely removed. Little is known about the outcomes of post-OHT patients with retained CIED fragments.
METHODS: We identified 200 consecutive patients that underwent OHT at our institution between April 2006 and December 2014 and performed a retrospective analysis of available radiographic images and clinical records. Chest radiographs prior to and following OHT were reviewed for the presence of CIED or retained CIED fragments. The outcomes of patients with retained CIED fragments that had subsequent magnetic resonance imaging (MRI) studies performed were further investigated.
RESULTS: One hundred eighty of 200 patients were identified as having CIED prior to OHT, of which 29 had retained CIED fragments after OHT. Most retained CIED fragments originated from superior vena cava defibrillator coils. There were no adverse events in the retained CIED fragment cohort, and survival was unaffected. Ten patients with retained CIED fragments safely underwent a total of 28 MRIs after OHT, all of diagnostic quality.
CONCLUSION: Retained CIED fragments are not associated with adverse events or increased mortality after OHT. Diagnostic MRI has been safely performed in patients with retained CIED fragments after incomplete device extraction. Retrieval of these fragments prior to MRI does not appear warranted given the demonstrated safety and preserved image quality in this population.

PMID: 28760213 [PubMed - in process]

County socioeconomic characteristics and heart transplant outcomes in the United States.

Wed, 08/02/2017 - 10:00
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County socioeconomic characteristics and heart transplant outcomes in the United States.

Am Heart J. 2017 Aug;190:104-112

Authors: Tumin D, Horan J, Shrider EA, Smith SA, Tobias JD, Hayes D, Foraker RE

Abstract
BACKGROUND: Geographic disparities in survival after heart transplantation have received mixed support in prior studies, and specific geographic characteristics that might be responsible for these differences are unclear. We tested for differences in heart transplant outcomes across United States (US) counties after adjustment for individual-level covariates. Our secondary aim was to evaluate whether specific county-level socioeconomic characteristics explained geographic disparities in survival.
METHODS: Data on patients aged ≥18 years undergoing a first-time heart transplant between July 2006 and December 2014 were obtained from the United Network for Organ Sharing. Residents of counties represented by <5 patients were excluded. Patient survival (censored in March 2016) was analyzed using multivariable Cox regression. Shared frailty models were used to test for residual differences in overall all-cause mortality across counties after adjusting for recipient and donor characteristics. Measures of county economic disadvantage, inequality, and racial segregation were obtained from US Census data and coded into quintiles. A likelihood ratio test determined whether adjusting for each county measure improved the fit of the Cox model.
RESULTS: Multivariable analysis of 10,879 heart transplant recipients found that, adjusting for individual-level characteristics, there remained statistically significant variation in mortality hazard across US counties (P=.004). Adjusting for quintiles of community disadvantage, economic inequality, or racial segregation did not significantly improve model fit (likelihood ratio test P=.092, P=.273, and P=.107, respectively) and did not explain residual differences in patient survival across counties.
CONCLUSIONS: Heart transplantation outcomes vary by county, but this difference is not attributable to county-level socioeconomic disadvantage.

PMID: 28760203 [PubMed - in process]

Severe Plantar Warts in an Immunocompromised Patient.

Wed, 08/02/2017 - 10:00
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Severe Plantar Warts in an Immunocompromised Patient.

N Engl J Med. 2017 Jul 20;377(3):267

Authors: D'Souza GF, Zins JE

PMID: 28723340 [PubMed - indexed for MEDLINE]

Neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio as predictors of survival after heart transplantation.

Tue, 08/01/2017 - 21:53
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Neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio as predictors of survival after heart transplantation.

ESC Heart Fail. 2017 Jul 31;:

Authors: Seropian IM, Romeo FJ, Pizarro R, Vulcano NO, Posatini RA, Marenchino RG, Berrocal DH, Belziti CA

Abstract
AIMS: The aim of this study was to evaluate whether neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) predict outcome in heart failure (HF) patients undergoing heart transplantation (HTX).
METHODS AND RESULTS: Data from 111 HF patients undergoing HTX 2010-2015 were retrospectively reviewed. NLR and PLR were calculated before HTX, immediately after HTX, and at 6 and 24 hours. Primary endpoint was in-hospital mortality, and secondary endpoints were 1 year mortality and renal replacement therapy (RRT). Prognostic factors were assessed by multivariate analysis, and the predictive values of NLR and PLR for mortality were compared. The discriminatory performance for predicting in-hospital mortality was better for NLR [area under the receiver operating characteristic curve (AUC) = 0.644, 95% confidence interval 0.492-0.797] than for PLR (AUC = 0.599, 95% confidence interval 0.423-0.776). Best cut-off value was 2.41 for NLR (sensitivity 86%, specificity 67%) and 92.5 for PLR (sensitivity 86%, specificity 68%). When divided according to best cut-off value, in-hospital mortality was significantly higher in the high NLR group (17.5% vs. 3.2%, P < 0.05), but not in the high PLR group (16.5% vs. 6.3%, P = ns). One year mortality was not significantly higher for either group (37.5% vs. 6.5% for NLR; 36.7% vs. 9.4% for PLR, P = ns for both), while RRT was significantly higher in both the NLR and PLR high groups (33.8% vs. 0%; 32.9% vs. 3.1%, respectively, P < 0.001). Multivariate analysis indicated that only high NLR (hazard ratio = 3.403, P < 0.05) and pre-transplant diabetes (hazard ratio = 3.364, P < 0.05) were independent prognostic factors for 1 year mortality.
CONCLUSIONS: High NLR was a predictor for in-hospital mortality, and an independent prognostic factor for 1 year mortality. Both high NLR and high PLR were predictors for RRT.

PMID: 28758719 [PubMed - as supplied by publisher]

Cardiopulmonary Exercise Test in Leukemia Patients After Chemotherapy: A Feasibility Study.

Tue, 08/01/2017 - 21:53
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Cardiopulmonary Exercise Test in Leukemia Patients After Chemotherapy: A Feasibility Study.

Ann Rehabil Med. 2017 Jun;41(3):456-464

Authors: Kim S, Song IC, Jee S

Abstract
OBJECTIVE: To explore the feasibility of cardiopulmonary exercise test (CPET) in leukemia patients after chemotherapy.
METHODS: Leukemia patients with histologically confirmed hematologic malignancies were reviewed. We evaluated for CPET, between receiving chemotherapy and undergoing stem cell transplantation after 2 weeks. We recorded exercise testing and physiologic parameters during CPET between January 2013 to May 2015. All patients were subjected to symptoms limited to exercise testing, according to the Modified Bruce Protocol. We considered that if respiratory exchange ratio achieved was over 1.10, participants had successfully completed CPET. We dichotomized all participants into two groups (normal group, normal range of resting heart rate; higher group, over 100 per minute of heart rate).
RESULTS: 30 patients were finally enrolled. All participants had no adverse effects during the exercise test. Mean peak double product was 26,998.60 mmHg·beats/min (range, 15,481-41,004), and mean peak oxygen consumption (VO2 peak) was 22.52±4.56 mL/kg/min. Significant differences were observed in the normal group with VO2 peak (mean, 24.21 mL/kg/min; p=0.027) and number of prior intensive chemotherapy, compared to the higher group (mean, 1.95; p=0.006).
CONCLUSION: Our results indicate that CPET in leukemia patients before stem cell transplantation was very safe, and is an efficient method to screen for patients with poor cardiac functions. As CPET presents the parameters which reveal the cardiopulmonary functions, including VO2 peak, double product and exercise capacity, this exercise test would help to predict the physical performance or general condition of the leukemia patients.

PMID: 28758084 [PubMed]

Long Non-coding RNA-mRNA Correlation Analysis Reveals the Potential Role of HOTAIR in Pathogenesis of Sporadic Thoracic Aortic Aneurysm.

Tue, 08/01/2017 - 21:53
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Long Non-coding RNA-mRNA Correlation Analysis Reveals the Potential Role of HOTAIR in Pathogenesis of Sporadic Thoracic Aortic Aneurysm.

Eur J Vasc Endovasc Surg. 2017 Jul 27;:

Authors: Guo X, Chang Q, Pei H, Sun X, Qian X, Tian C, Lin H

Abstract
OBJECTIVE/BACKGROUND: Long non-coding RNA (lncRNA) play important roles in many diseases. However, their roles in sporadic thoracic aortic aneurysm (STAA) are unclear. Therefore, the objective of this study was to construct an lncRNA-mRNA network and dissect lncRNAs that might contribute to the pathogenesis of STAA.
METHODS: Differentially expressed lncRNAs and mRNAs between four ascending aortic specimens derived from STAA and four controls from patients who had undergone coronary artery bypass graft (CABG) were identified by microarray analysis. Gene Ontology (GO) enrichment and lncRNA-mRNA correlation analysis were implemented with differentially expressed genes. An lncRNA in the correlation network HOX transcript antisense intergenic RNA (HOTAIR) was selected as a candidate. HOTAIR expression was examined by quantitative real time polymerase chain reaction in STAA (n = 24) and controls (n = 24 [CABG, n = 22; heart transplant donors, n = 2]). HOTAIR expression was knocked down with siRNA in order to evaluate its role in apoptosis, cell proliferation, and expression of collagen types I and III.
RESULTS: Five percent of lncRNAs were significantly differentially expressed in STAA patient samples compared with controls. GO enrichment analysis suggested differentially expressed genes were significantly enriched in the process of extracellular matrix organisation and leukocyte migration. lncRNA-mRNA interaction network revealed HOTAIR was associated with genes involved in extracellular matrix organisation. Moreover, HOTAIR expression was significantly decreased in STAA specimens and it negatively correlated with aortic diameter. HOTAIR knockdown induced early and late apoptosis and reduced cell proliferation. Furthermore, both mRNA and protein levels of collagen types I and III expression were suppressed after HOTAIR knockdown.
CONCLUSION: Transcriptomic and lncRNA-mRNA correlation analysis revealed HOTAIR was downregulated in STAA and associated with genes involved in extracellular matrix remodelling. In vitro experiments confirmed that knockdown of HOTAIR could induce apoptosis and suppress collagen types I and III expression in human aortic smooth muscle cells.

PMID: 28757056 [PubMed - as supplied by publisher]

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