Trasplante cardíaco

Endoglin: a novel target for therapeutic intervention in acute leukemias revealed in xenograft mouse models.

Blood. 2017 Mar 28;:

Authors: Dourado KM, Baik J, Oliveira VK, Beltrame M, Yamamoto A, Theuer CP, Figueiredo CA, Verneris MR, Perlingeiro RC

Abstract
Endoglin (CD105), a receptor of the transforming growth factor-β (TGF-β) superfamily, has been reported to identify functional long-term repopulating hematopoietic stem cells, and has been detected in certain sub-types of acute leukemias. Whether this receptor plays a functional role in leukemogenesis remains unknown. We identified endoglin expression on the majority of blasts from patients with acute myeloid leukemia (AML) and acute B-lymphoblastic leukemia (B-ALL). Using a xenograft model, we find that CD105(+) blasts are endowed with superior leukemogenic activity compared to the CD105(-) population. We test the effect of targeting this receptor using the monoclonal antibody TRC105, and find that in AML, TRC105 prevented the engraftment of primary AML blasts and inhibited leukemia progression following disease establishment, but in B-ALL, TRC105 alone was ineffective due to the shedding of soluble CD105. However, in both B-ALL and AML, TRC105 synergized with reduced intensity myeloablation to inhibit leukemogenesis, indicating that TRC105 may represent a novel therapeutic option for B-ALL and AML.

PMID: 28351936 [PubMed - as supplied by publisher]

British Lung Foundation/United Kingdom Primary Immunodeficiency Network Consensus Statement on the Definition, Diagnosis, and Management of Granulomatous-Lymphocytic Interstitial Lung Disease in Common Variable Immunodeficiency Disorders.

J Allergy Clin Immunol Pract. 2017 Mar 25;:

Authors: Hurst JR, Verma N, Lowe D, Baxendale HE, Jolles S, Kelleher P, Longhurst HJ, Patel SY, Renzoni EA, Sander CR, Avery GR, Babar JL, Buckland MS, Burns S, Egner W, Gompels MM, Gordins P, Haddock JA, Hart SP, Hayman GR, Herriot R, Hoyles RK, Huissoon AP, Jacob J, Nicholson AG, Rassl DM, Sargur RB, Savic S, Seneviratne SL, Sheaff M, Vaitla PM, Walters GI, Whitehouse JL, Wright PA, Condliffe AM

Abstract
A proportion of people living with common variable immunodeficiency disorders develop granulomatous-lymphocytic interstitial lung disease (GLILD). We aimed to develop a consensus statement on the definition, diagnosis, and management of GLILD. All UK specialist centers were contacted and relevant physicians were invited to take part in a 3-round online Delphi process. Responses were graded as Strongly Agree, Tend to Agree, Neither Agree nor Disagree, Tend to Disagree, and Strongly Disagree, scored +1, +0.5, 0, -0.5, and -1, respectively. Agreement was defined as greater than or equal to 80% consensus. Scores are reported as mean ± SD. There was 100% agreement (score, 0.92 ± 0.19) for the following definition: "GLILD is a distinct clinico-radio-pathological ILD occurring in patients with [common variable immunodeficiency disorders], associated with a lymphocytic infiltrate and/or granuloma in the lung, and in whom other conditions have been considered and where possible excluded." There was consensus that the workup of suspected GLILD requires chest computed tomography (CT) (0.98 ± 0.01), lung function tests (eg, gas transfer, 0.94 ± 0.17), bronchoscopy to exclude infection (0.63 ± 0.50), and lung biopsy (0.58 ± 0.40). There was no consensus on whether expectant management following optimization of immunoglobulin therapy was acceptable: 67% agreed, 25% disagreed, score 0.38 ± 0.59; 90% agreed that when treatment was required, first-line treatment should be with corticosteroids alone (score, 0.55 ± 0.51).

PMID: 28351785 [PubMed - as supplied by publisher]

Keratose Hydrogels Promote Vascular Smooth Muscle Differentiation from C-kit Positive Human Cardiac Stem Cells.

Stem Cells Dev. 2017 Mar 28;:

Authors: Ledford BT, Simmons J, Chen M, Fan H, Barron C, Liu Z, Van Dyke M, He JQ

Abstract
Stem cell-based therapies have demonstrated great potential for the treatment of cardiac diseases, <i>e.g.,</i> myocardial infarction; however, low cell viability, low retention/engraftment, and uncontrollable in vivo differentiation after transplantation are still major limitations, which lead low therapeutic efficiency. Biomaterials provide a promising solution to overcome these issues due to their biocompatibility, biodegradability, low/non-immunogenicity, and low/non-cytotoxicity. The present study aims to investigate the impacts of Keratose (KOS) hydrogel biomaterial on cellular viability, proliferation, and differentiation of c-kit⁺ human cardiac stem cells (hCSCs). Briefly, hCSCs were cultured on both KOS hydrogel-coated dishes and regular tissue culture dishes (Blank control). Cell viability, stemness, proliferation, cellular morphology, and cardiac lineage differentiation were compared between KOS hydrogel and the Blank control at different time points. We found that KOS hydrogel is effective in maintaining hCSCs without any observable toxic effects, although cell size and proliferation rate appeared smaller on the KOS hydrogel compared to the Blank control. To our surprise, KOS hydrogel significantly promoted vascular smooth muscle cell (VSMC) differentiation (~72%), while on the Blank control dishes, most of the hCSCs (~78%) became cardiomyocytes. Further, we also observed "endothelial cell tube-like" microstructures formed by differentiated VSMCs only on KOS hydrogel, suggesting a potential capability of the hCSC-derived VSMCs for <i>in vitro </i>angiogenesis. To the best of our knowledge, this is the first report to discover the preferred differentiation of hCSCs toward VSMCs on KOS hydrogel. The underlying mechanism remains unknown. This innovative methodology may offer a new approach to generate a robust number of VSMCs simply by culturing hCSCs on KOS hydrogel, and the resulting VSMCs may be used in animal studies and clinical trials in combination with an injectable KOS hydrogel to treat cardiovascular diseases.

PMID: 28351290 [PubMed - as supplied by publisher]

Current status of mechanical circulatory support for treatment of advanced end-stage heart failure: successes, shortcomings and needs.

Expert Rev Cardiovasc Ther. 2017 Mar 29;:

Authors: Sunagawa G, Koprivanac M, Karimov JH, Moazami N, Fukamachi K

Abstract
INTRODUCTION: Heart failure remains a major global burden in terms of morbidity and mortality. Despite advances in pharmacological and resynchronization device therapy, many patients worsen to end-stage heart failure. Although the gold-standard treatment for such patients is heart transplantation, there will always be a shortage of donor hearts. Areas covered: A left ventricular assist device (LVAD) is a valuable option for these patients as a bridge measure (to recovery, to candidacy for transplant, or to transplant itself) or as destination therapy. This review describes the current indications for and complications of the most commonly implanted LVADs. In addition, we review the potential and promising new LVADs, including the HeartMate 3, MVAD, and other LVADs. Studies investigating each were identified through a combination of online database and direct extraction of studies cited in previously identified articles. Expert commentary: The goal of LVADs has been to fill the gap between patients with end-stage HF who would likely not benefit from heart transplantation and those who could benefit from a donor heart. As of now, the use of LVADs has been limited to patients with end-stage HF, but next-generation LVAD therapy may improve both survival and quality of life in less sick patients.

PMID: 28351172 [PubMed - as supplied by publisher]

Extended surgery for T4 lung cancer: a 30 years' experience.

Gen Thorac Cardiovasc Surg. 2017 Mar 27;:

Authors: Dartevelle PG, Mitilian D, Fadel E

Abstract
T4 non-small cell lung carcinomas (NSCLC) were deemed unresectable. Advances in surgery have challenged this dogma. We describe technical aspects and result on superior vena cava (SVC), carinal, thoracic inlet tumor surgeries, and resection under cardiopulmonary bypass (CPB). SVC reconstruction requires hemodynamic control to reverse SVC clamping cerebral effects and excellent cephalic venous bed patency. Among 50 SVC resections, including 25 carinal pneumonectomies, post-operative mortality rate was 8%. In the N0-N1 group, 5- and 10-year survival rates were 46.6 and 37.7%, respectively. Right carinal pneumonectomy was performed through right thoracotomy. Sternotomy was favored for left carinal pneumonectomy or carinal resection alone. Among 138 carinal resections, including eight right upper lobectomies, 123 right pneumonectomies, four left pneumonectomies, and three isolated carinal resections, the post-operative mortality rate was 9.4%. In the N0-N1 patients, 5-year survival rate was 47%. 191 patients underwent resections of thoracic inlet tumors through a transclavicular cervicothoracic anterior approach combined in 63 patients with a posterior midline incision for limited spine invasion. In N0-N1 group, 5- and 10-year survival rates were 41.5 and 29.7%, respectively. CPB allowed resection of tumors invading the heart or great vessels in 13 patients. R0 resection and post-operative mortality rate were 94.4 and 5.5%, respectively. In this series of 388 T4 NSCLC, the post-operative mortality rate was 4%. In the R0 and N0-N1 groups, the 5-year survival rates were 44 and 41%, respectively. Surgical resection of T4 locally advanced NSCLC is worth being performed in selected N0-N1 patients, provided that a radical resection is expected.

PMID: 28349384 [PubMed - as supplied by publisher]

Anticoagulation therapy for a LVAD patient with acquired warfarin resistance.

J Artif Organs. 2017 Mar 27;:

Authors: Yoshioka D, Toda K, Hidaka T, Yasuda S, Saito S, Domae K, Sawa Y

Abstract
Anticoagulation therapy with warfarin is essential for postoperative management in patients with left ventricular assist device (LVAD). In this manuscript, we report the case of a patient who developed warfarin resistance after LVAD implantation. Although we administered a novel anticoagulant drug in addition to warfarin and aspirin therapy, the patient developed a major stroke. The patient needed continuous intravenous heparinization until heart transplantation for approximately 2 years. Meticulous management of anticoagulation therapy is essential for a LVAD with warfarin resistance. To our best knowledge, our case is the first case of warfarin resistance in a patient with LVAD.

PMID: 28349222 [PubMed - as supplied by publisher]

Total artificial heart implantation for biventricular failure due to eosinophilic myocarditis.

J Artif Organs. 2017 Mar 27;:

Authors: Kawabori M, Kurihara C, Miller Y, Heck KA, Bogaev RC, Civitello AB, Cohn WE, Frazier OH, Morgan JA

Abstract
Idiopathic hypereosinophilic syndrome is a condition of unknown etiology characterized by proliferation of eosinophils and their infiltration into tissues. Although cardiac involvement is rare, eosinophilic myocarditis can lead to life-threating fulminant congestive heart failure. Treatment of patients with eosinophilic myocarditis is challenging as heart failure can be caused by biventricular dysfunction. To our knowledge, this is the first case reported in the literature describing a patient with acute severe biventricular heart failure caused by eosinophilic myocarditis with mural left ventricular apical thrombus who was successfully treated with implantation of a total artificial heart as a bridge to heart transplant.

PMID: 28349221 [PubMed - as supplied by publisher]

Impact of advanced medical therapy for the outcome of an adult patient with Eisenmenger syndrome.

Respir Med Case Rep. 2017;21:16-20

Authors: Ereminienė E, Kinderytė M, Miliauskas S

Abstract
Eisenmenger syndrome (ES) is the most severe form of pulmonary arterial hypertension (PAH) associated with congenital heart disease. It is an extremely devastating condition with a serious impact on patients' life. Classical therapy of ES remains directed to avoid complications, such as erythrocytosis, treatment of congestive heart failure, prevention of infection, and secondary haematological abnormalities such as iron deficiency and coagulation disorders. However, the only effective treatment is heart-lung transplantation; still, morbidity and mortality after transplantation remain substantially high. Furthermore, waiting lists for heart-lung transplantation are long. Recent studies examining the use of advanced medical treatment in patients with ES have shown that it may have beneficial effects in patients with ES; however, additional studies need to be done to confirm its efficacy and appropriate clinical use. A 41-year-old female admitted to the Hospital of Lithuanian University of Health Sciences due to progressive dyspnea on minimal effort, heart failure symptoms leading to NYHA functional class III-IV. After clinical and instrumental investigations, ES secondary to unrepaired patent ductus arteriosus with severe PAH was diagnosed. Treatment with sildenafil was initiated together with the standard pharmacological therapy, and the patient was added to the waiting list for the heart and lung transplantation. After 24 months of stable condition, her clinical status deteriorated, and combination therapy (sildenafil and ambrisentan) was initiated. Clinical symptoms and exercise capacity improved, and she has been stable for 4 years thereafter. Our experience of the management of an adult patient with ES showed the benefits of treatment with advanced therapy with pulmonary vasodilators that improved the patient's quality of life and delayed the need for heart and lung transplantation.

PMID: 28348949 [PubMed - in process]

Acute Onset Significant Muscle Weakness in a Patient Awaiting Liver Transplantation: Look for Statins.

J Clin Exp Hepatol. 2017 Mar;7(1):66-67

Authors: Choudhary NS, Saigal S, Saraf N, Soin AS

Abstract
Statins are commonly used drugs in patients with liver and cardiac disease. Statin-induced severe myopathy is a very uncommon presentation and rhabdomyolysis may occur in extreme cases which leads to renal failure. Patients with comorbidities like diabetes, hypothyroidism, and liver disease have higher chances of development of statin-induced myopathy. We describe a case of Child's C cirrhosis wherein the patient had acute onset significant muscle weakness and improved on statin discontinuation.

PMID: 28348473 [PubMed - in process]

Influence of Drugs Carried in Lipid Nanoparticles in Coronary Disease of Rabbit Transplanted Heart.

Ann Thorac Surg. 2017 Mar 24;:

Authors: Barbieri LR, Lourenço-Filho DD, Tavares ER, Carvalho PO, Gutierrez PS, Maranhão RC, Stolf NA

Abstract
BACKGROUND: Coronary allograft vasculopathy is an inflammatory-proliferative process that compromises the long-term success of heart transplantation and currently has no effective prevention and treatment. Lipid nanoparticles, termed LDE can carry chemotherapeutic agents in the circulation and concentrates them in the heart.
METHODS: Twenty-eight rabbits fed a cholesterol-rich diet and submitted to heterotopic heart transplantation were treated with cyclosporine A (10 mg/kg daily) and allocated to four groups of 7 animals treated with intravenous LDE-methotrexate (MTX; 4 mg/kg weekly), with LDE-paclitaxel (PACLI; 4 mg/kg weekly), or with LDE-PACLI (4 mg/kg weekly) and LDE-MTX (4 mg/kg weekly). A control group was treated with only weekly intravenous saline solution. Animals were euthanized 6 weeks later for morphometric, histologic, immunohistochemical, and gene expression analysis of the graft and native hearts.
RESULTS: Compared with controls, grafts of rabbits treated with LDE-PACLI showed 50% reduction of coronary stenosis, and in the LDE-MTX and LDE-MTX/PACLI stenosis was approximately 18% less than in control, but this difference was not statistically significant. In the three treatment groups, macrophage infiltration was decreased. In the LDE-MTX group, gene expression of proinflammatory factors tumor necrosis factor-α, monocyte chemoattractant protein 1, interleukin 18, vascular cellular adhesion molecule 1, and matrix metalloproteinase 12 was strongly diminished, whereas expression of antiinflammatory interleukin 10 increased. In the LDE-PACLI and LDE-PACLI/MTX groups, proinflammatory and antiinflammatory gene expressions were not consistently changed by the treatments.
CONCLUSIONS: LDE-PACLI promoted strong improvement of cardiac allograft vasculopathy, but the decrease in coronary stenosis by LDE-MTX and LDE-MTX/PACLI was not significant. All three treatments decreased macrophage infiltration in the graft. These results may encourage future clinical trials to test this new therapeutic approach to coronary allograft vasculopathy.

PMID: 28347533 [PubMed - as supplied by publisher]

Surgical management of interventricular septal rupture.

Coron Artery Dis. 2016 Nov;27(7):618-20

Authors: Alkhalil I, Barrett T, Tandan S, Hamlin MP, Schmoker JD, Hopkins WE

PMID: 27363002 [PubMed - indexed for MEDLINE]

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Apigenin Reduces NF-κB and Subsequent Cytokine Production as Protective Effect in a Rodent Animal Model of Lung Ischemia-Reperfusion Injury.

J Invest Surg. 2017 Mar 24;:1-11

Authors: Bougioukas I, Didilis V, Emmert A, Jebran AF, Waldmann-Beushausen R, Stojanovic T, Schoendube FA, Danner BC

Abstract
PURPOSE: Lung ischemia-reperfusion injury (LIRI) can complicate lung transplantation or cardiac surgery with cardiopulmonary bypass, increasing morbidity and mortality. In LIRI, pro-inflammatory cytokines are activated, reactive oxygen species are generated and nuclear factor-κB (NF-κB) is up-regulated, altering lung mechanics. We tested the effect of the flavonoid apigenin on a rodent model of LIRI.
METHODS: Thirty-seven Wistar rats were subjected to LIRI with or without a single or double dose of apigenin. Induction of LIRI involved sternotomy and clamping of either the left lung hilum or the pulmonary artery alone for 30 min, followed by 60 min of reperfusion. Control groups consisted of LIRI plus NaCl, a sham group and a baseline group. At the end of the experiments, both lungs were analyzed by RT-PCR, Western blot, and light microscopy.
RESULTS: In placebos, the expression levels of pro-inflammatory markers were increased in both lungs significantly, whereas NF-κB was markedly up-regulated. Administration of apigenin reduced the activation of NF-κB and the expression of TNFα, iNOS, and IL-6. These effects were observed in total lung ischemia. Histology showed greater hemorrhage and exudation in the pulmonary periphery of all groups, whereby damage was practically absent in the central lung regions of the apigenin animals. A second dose of apigenin did not outclass a single one.
CONCLUSIONS: We conclude that apigenin given intraperitoneally can reduce activation of NF-κB and also attenuate the expression of TNFα, IL-6, and iNOS in a surgical model of LIRI. The surgical procedure itself can induce significant damage to the lungs.

PMID: 28340319 [PubMed - as supplied by publisher]

The evolution and benefit of device therapy in patients listed for heart transplant.

Europace. 2017 Mar 09;:

Authors: Vandenberk B, Hinderks M, Voros G, Garweg C, Vanhaecke J, Willems R

Abstract
Aims: The latest 2015 ESC Guidelines on the prevention of sudden cardiac death make a Class IIa recommendation for ICD implantation in patients listed for heart transplantation. This recommendation was based on expert consensus in view of the sparsity of data.
Methods and results: All patients listed for heart transplantation at the University Hospitals of Leuven from 2002 until 2014 were studied retrospectively. Exclusion criteria were age <16 years, cardiac disease other than ischaemic or dilated cardiomyopathy and re-transplantation. A total of 286 patients were included, of which 140 (49.0%) received an ICD. There was a historical increase of the time on the waiting list before transplantation (P < 0.001) together with an increase of the use of ICDs (P < 0.001) and left ventricular assist devices (LVADs) (P < 0.001). The proportion of patients reaching heart transplant remained unchanged (P = 0.700). The annual appropriate shock rate in patients with ICD was 28.0%/y on the active waiting list. Patients with ICD showed a trend to improved survival (P = 0.070). Independent predictors of mortality or removal from the transplant list because of clinical deterioration were the need for LVAD (HR 4.38, 95%CI 2.11-9.01), a history of stroke (HR 2.95, 95%CI 1.61-5.40), older age (HR 1.03, 95%CI 1.01-1.05) and a worse renal function (HR 1.15, 95%CI 1.00-1.33).
Conclusion: The time on the waiting list for heart transplantation significantly increased together with an increased use of device therapy in this population. The proportion of patients reaching transplant remained unchanged. This patient group is prone to life-threatening arrhythmias and the use of an ICD may improve survival.

PMID: 28340197 [PubMed - as supplied by publisher]

Identification of cardiac hemo-vascular precursors and their requirement of sphingosine-1-phosphate receptor 1 for heart development.

Sci Rep. 2017 Mar 24;7:45205

Authors: Hu Y, Belyea BC, Li M, Göthert JR, Gomez RA, Sequeira-Lopez ML

Abstract
The cardiac endothelium plays a crucial role in the development of a functional heart. However, the precise identification of the endocardial precursors and the mechanisms they require for their role in heart morphogenesis are not well understood. Using in vivo and in vitro cell fate tracing concomitant with specific cell ablation and embryonic heart transplantation studies, we identified a unique set of precursors which possess hemogenic functions and express the stem cell leukemia (SCL) gene driven by its 5' enhancer. These hemo-vascular precursors give rise to the endocardium, atrioventricular cushions and coronary vascular endothelium. Furthermore, deletion of the sphingosine-1-phosphate receptor 1 (S1P1) in these precursors leads to ventricular non-compaction cardiomyopathy, a poorly understood condition leading to heart failure and early mortality. Thus, we identified a distinctive population of hemo-vascular precursors which require S1P1 to exert their functions and are essential for cardiac morphogenesis.

PMID: 28338096 [PubMed - in process]

Improving on the diagnostic characteristics of echocardiography for pulmonary hypertension.

Int J Cardiovasc Imaging. 2017 Mar 24;:

Authors: Broderick-Forsgren K, Davenport CA, Sivak JA, Hargett CW, Foster MC, Monteagudo A, Armour A, Rajagopal S, Arges K, Velazquez EJ, Samad Z

Abstract
This retrospective study evaluated the diagnostic characteristics of a combination of echocardiographic parameters for pulmonary hypertension (PH). Right ventricular systolic pressure (RVSP) estimation by echocardiography (echo) is used to screen for PH. However, the sensitivity of this method is suboptimal. We hypothesized that RVSP estimation in conjunction with other echo parameters would improve the value of echo for PH. The Duke Echo database was queried for adult patients with known or suspected PH who had undergone both echo and right heart catheterization (RHC) within a 24 h period between 1/1/2008 and 12/31/2013. Patients with complex congenital heart disease, heart transplantation, ventricular assist device, or on mechanical ventilation at time of study were excluded. Diagnostic characteristics of several echo parameters (right atrial enlargement, pulmonary artery (PA) enlargement, RV enlargement, RV dysfunction, and RVSP) for PH (mean PA pressure 25 mmHg on RHC) were evaluated among 1007 patients. RVSP ≥40 had a sensitivity of 77% (accuracy 77), while RVSP ≥35 had the highest sensitivity at 88% (81% accuracy). PA enlargement had the lowest sensitivity at 17%. The area under the curve (AUC) for RVSP was 0.844. A model including RVSP, RA, PA, RV enlargement and RV dysfunction had a higher AUC (AUC = 0.87) than RVSP alone. The value of echo as a screening test for PH is improved by a model incorporating a lower RVSP in addition to other right heart parameters. These findings need to be validated in prospective cohorts.

PMID: 28337558 [PubMed - as supplied by publisher]

Cold preservation with hyperbranched polyglycerol-based solution improves kidney functional recovery with less injury at reperfusion in rats.

Am J Transl Res. 2017;9(2):429-441

Authors: Li S, Liu B, Guan Q, Chafeeva I, Brooks DE, Nguan CY, Kizhakkedathu JN, Du C

Abstract
Minimizing donor organ injury during cold preservation (including cold perfusion and storage) is the first step to prevent transplant failure. We recently reported the advantages of hyperbranched polyglycerol (HPG) as a novel substitute for hydroxyethyl starch in UW solution for both cold heart preservation and cold kidney perfusion. This study evaluated the functional recovery of the kidney at reperfusion after cold preservation with HPG solution. The impact of HPG solution compared to conventional UW and HTK solutions on tissue weight and cell survival at 4°C was examined using rat kidney tissues and cultured human umbilical vein endothelial cells (HUVECs), respectively. The kidney protection by HPG solution was tested in a rat model of cold kidney ischemia-reperfusion injury, and was evaluated by histology and kidney function. Here, we showed that preservation with HPG solution prevented cell death in cultured HUVECs and edema formation in kidney tissues at 4°C similar to UW solution, whereas HTK solution was less effective. In rat model of cold ischemia-reperfusion injury, the kidneys perfused and subsequently stored 1-hour with cold HPG solution showed less leukocyte infiltration, less tubular damage and better kidney function (lower levels of serum creatinine and blood urea nitrogen) at 48 h of reperfusion than those treated with UW or HTK solution. In conclusion, our data show the superiority of HPG solution to UW or HTK solution in the cold perfusion and storage of rat kidneys, suggesting that the HPG solution may be a promising candidate for improved donor kidney preservation prior to transplantation.

PMID: 28337272 [PubMed]

Total Artificial Heart Implantation After Undifferentiated High-Grade Sarcoma Excision.

Med Sci Monit Basic Res. 2016 Nov 02;22:128-131

Authors: Kremer J, Farag M, Arif R, Brcic A, Sabashnikov A, Schmack B, Popov AF, Karck M, Dohmen PM, Ruhparwar A, Weymann A

Abstract
BACKGROUND Total artificial heart (TAH) implantation in patients with aggressive tumor infiltration of the heart can be challenging. CASE REPORT We report on a patient with a rare primary undifferentiated high-grade spindle cell sarcoma of the mitral valve and in the left atrium, first diagnosed in 2014. The referring center did a first resection in 2014. In the course of 17 months, computer tomography (CT) scan again showed massive invasion of the mitral valve and left atrium. Partial resection and mitral valve replacement was not an option. We did a subtotal heart excision with total artificial heart implantation. In this report we discuss complications, risk factors, and perioperative management of this patient. CONCLUSIONS Patients with aggressive tumors of the heart can be considered for TAH implantation.

PMID: 27803495 [PubMed - indexed for MEDLINE]

Total Arterial Revascularization: Bypassing Antiquated Notions to Better Alternatives for Coronary Artery Disease.

Med Sci Monit Basic Res. 2016 Oct 04;22:107-114

Authors: Samak M, Fatullayev J, Sabashnikov A, Zeriouh M, Schmack B, Ruhparwar A, Karck M, Popov AF, Dohmen PM, Weymann A

Abstract
Total arterial revascularization is the leading trend in coronary artery bypass grafting (CABG) for the treatment of coronary artery disease (CAD). Adding to its superiority to vein conduits, arteries allow for a high degree of versatility and long-term patency, while minimizing the need for reintervention. This is especially important for patients with multi-vessel coronary artery disease, as well as young patients. However, arterial revascularization has come a long way before being widely appreciated, with some yet unresolved debates, and advances that never cease to impress. In this review, we discuss the evolution of this surgical technique and its clinical success, as well as its most conspicuous limitations in light of accumulated published date from decades of experience.

PMID: 27698339 [PubMed - indexed for MEDLINE]

MLL-AF9 Expression in Hematopoietic Stem Cells Drives a Highly Invasive AML Expressing EMT-Related Genes Linked to Poor Outcome.

Cancer Cell. 2016 07 11;30(1):43-58

Authors: Stavropoulou V, Kaspar S, Brault L, Sanders MA, Juge S, Morettini S, Tzankov A, Iacovino M, Lau IJ, Milne TA, Royo H, Kyba M, Valk PJ, Peters AH, Schwaller J

Abstract
To address the impact of cellular origin on acute myeloid leukemia (AML), we generated an inducible transgenic mouse model for MLL-AF9-driven leukemia. MLL-AF9 expression in long-term hematopoietic stem cells (LT-HSC) in vitro resulted in dispersed clonogenic growth and expression of genes involved in migration and invasion. In vivo, 20% LT-HSC-derived AML were particularly aggressive with extensive tissue infiltration, chemoresistance, and expressed genes related to epithelial-mesenchymal transition (EMT) in solid cancers. Knockdown of the EMT regulator ZEB1 significantly reduced leukemic blast invasion. By classifying mouse and human leukemias according to Evi1/EVI1 and Erg/ERG expression, reflecting aggressiveness and cell of origin, and performing comparative transcriptomics, we identified several EMT-related genes that were significantly associated with poor overall survival of AML patients.

PMID: 27344946 [PubMed - indexed for MEDLINE]