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Identification of novel risk loci for restless legs syndrome in genome-wide association studies in individuals of European ancestry: a meta-analysis.

Tue, 10/17/2017 - 12:45
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Identification of novel risk loci for restless legs syndrome in genome-wide association studies in individuals of European ancestry: a meta-analysis.

Lancet Neurol. 2017 Nov;16(11):898-907

Authors: Schormair B, Zhao C, Bell S, Tilch E, Salminen AV, Pütz B, Dauvilliers Y, Stefani A, Högl B, Poewe W, Kemlink D, Sonka K, Bachmann CG, Paulus W, Trenkwalder C, Oertel WH, Hornyak M, Teder-Laving M, Metspalu A, Hadjigeorgiou GM, Polo O, Fietze I, Ross OA, Wszolek Z, Butterworth AS, Soranzo N, Ouwehand WH, Roberts DJ, Danesh J, Allen RP, Earley CJ, Ondo WG, Xiong L, Montplaisir J, Gan-Or Z, Perola M, Vodicka P, Dina C, Franke A, Tittmann L, Stewart AFR, Shah SH, Gieger C, Peters A, Rouleau GA, Berger K, Oexle K, Di Angelantonio E, Hinds DA, Müller-Myhsok B, Winkelmann J, 23andMe Research Team, DESIR study group

Abstract
BACKGROUND: Restless legs syndrome is a prevalent chronic neurological disorder with potentially severe mental and physical health consequences. Clearer understanding of the underlying pathophysiology is needed to improve treatment options. We did a meta-analysis of genome-wide association studies (GWASs) to identify potential molecular targets.
METHODS: In the discovery stage, we combined three GWAS datasets (EU-RLS GENE, INTERVAL, and 23andMe) with diagnosis data collected from 2003 to 2017, in face-to-face interviews or via questionnaires, and involving 15 126 cases and 95 725 controls of European ancestry. We identified common variants by fixed-effect inverse-variance meta-analysis. Significant genome-wide signals (p≤5 × 10(-8)) were tested for replication in an independent GWAS of 30 770 cases and 286 913 controls, followed by a joint analysis of the discovery and replication stages. We did gene annotation, pathway, and gene-set-enrichment analyses and studied the genetic correlations between restless legs syndrome and traits of interest.
FINDINGS: We identified and replicated 13 new risk loci for restless legs syndrome and confirmed the previously identified six risk loci. MEIS1 was confirmed as the strongest genetic risk factor for restless legs syndrome (odds ratio 1·92, 95% CI 1·85-1·99). Gene prioritisation, enrichment, and genetic correlation analyses showed that identified pathways were related to neurodevelopment and highlighted genes linked to axon guidance (associated with SEMA6D), synapse formation (NTNG1), and neuronal specification (HOXB cluster family and MYT1).
INTERPRETATION: Identification of new candidate genes and associated pathways will inform future functional research. Advances in understanding of the molecular mechanisms that underlie restless legs syndrome could lead to new treatment options. We focused on common variants; thus, additional studies are needed to dissect the roles of rare and structural variations.
FUNDING: Deutsche Forschungsgemeinschaft, Helmholtz Zentrum München-Deutsches Forschungszentrum für Gesundheit und Umwelt, National Research Institutions, NHS Blood and Transplant, National Institute for Health Research, British Heart Foundation, European Commission, European Research Council, National Institutes of Health, National Institute of Neurological Disorders and Stroke, NIH Research Cambridge Biomedical Research Centre, and UK Medical Research Council.

PMID: 29029846 [PubMed - in process]

Throwing out the good with the bad: Declining potential donor hearts with left ventricular dysfunction.

Tue, 10/17/2017 - 12:45
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Throwing out the good with the bad: Declining potential donor hearts with left ventricular dysfunction.

J Heart Lung Transplant. 2017 Sep 25;:

Authors: Moayedi Y, Khush KK

PMID: 29029801 [PubMed - as supplied by publisher]

More than 20 years' experience of left ventricular assist device implantation at a non-transplant Centre.

Tue, 10/17/2017 - 12:45
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More than 20 years' experience of left ventricular assist device implantation at a non-transplant Centre.

Scand Cardiovasc J. 2017 Oct 13;:1-6

Authors: Holmberg E, Ahn H, Peterzén B

Abstract
OBJECTIVES: Over recent decades implantable left ventricular assist devices (LVAD) have increased the possibility of improved survival in patients with advanced heart failure who also benefit from a better quality of life. The aim of this retrospective survey was to review the clinical results of LVAD implantation at a low-volume non-transplant centre (Linköping, Sweden) between 1993 and 2016. Our aim was also to assess the mortality and morbidity rates associated with implantation of three LVAD versions at our centre, and to compare our results with those from transplant centres.
DESIGN: A retrospective cohort study was performed examining the medical records of patients who had a HeartMate(®) (HMI, HMII, HMIII) LVAD implanted as a bridge to heart transplantation (BTT) or as destination therapy (DT) at the University Hospital, Linköping.
RESULTS: Our main finding was a survival to heart transplantation rate of 82% among our BTT LVAD patients. The most common adverse event among our patients was infection. A higher frequency of temporary dialysis was seen in the HMII group compared to the HMI group, and the frequency of right ventricular failure was higher in our HMII material.
CONCLUSIONS: Our data suggests that patients requiring long-term LVAD support can safely have their device implanted and cared for at a non-transplant centre.

PMID: 29029567 [PubMed - as supplied by publisher]

Prolonged EVLP Using OCS Lung: Cellular and Acellular Perfusates.

Tue, 10/17/2017 - 12:45
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Prolonged EVLP Using OCS Lung: Cellular and Acellular Perfusates.

Transplantation. 2017 Oct;101(10):2303-2311

Authors: Loor G, Howard BT, Spratt JR, Mattison LM, Panoskaltsis-Mortari A, Brown RZ, Iles TL, Meyer CM, Helms HR, Price A, Iaizzo PA

Abstract
BACKGROUND: We report the ability to extend lung preservation up to 24 hours (24H) by using autologous whole donor blood circulating within an ex vivo lung perfusion (EVLP) system. This approach facilitates donor lung reconditioning in a model of extended normothermic EVLP. We analyzed comparative responses to cellular and acellular perfusates to identify these benefits.
METHODS: Twelve pairs of swine lungs were retrieved after cardiac arrest and studied for 24H on the Organ Care System (OCS) Lung EVLP platform. Three groups (n = 4 each) were differentiated by perfusate: (1) isolated red blood cells (RBCs) (current clinical standard for OCS); (2) whole blood (WB); and (3) acellular buffered dextran-albumin solution (analogous to STEEN solution).
RESULTS: Only the RBC and WB groups met clinical standards for transplantation at 8 hours; our primary analysis at 24H focused on perfusion with WB versus RBC. The WB perfusate was superior (vs RBC) for maintaining stability of all monitored parameters, including the following mean 24H measures: pulmonary artery pressure (6.8 vs 9.0 mm Hg), reservoir volume replacement (85 vs 1607 mL), and PaO2:FiO2 ratio (541 vs 223). Acellular perfusion was limited to 6 hours on the OCS system due to prohibitively high vascular resistance, edema, and worsening compliance.
CONCLUSIONS: The use of an autologous whole donor blood perfusate allowed 24H of preservation without functional deterioration and was superior to both RBC and buffered dextran-albumin solution for extended lung preservation in a swine model using OCS Lung. This finding represents a potentially significant advance in donor lung preservation and reconditioning.

PMID: 28009782 [PubMed - indexed for MEDLINE]

Engineered Biomaterials to Enhance Stem Cell-Based Cardiac Tissue Engineering and Therapy.

Tue, 10/17/2017 - 12:45
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Engineered Biomaterials to Enhance Stem Cell-Based Cardiac Tissue Engineering and Therapy.

Macromol Biosci. 2016 Jul;16(7):958-77

Authors: Hasan A, Waters R, Roula B, Dana R, Yara S, Alexandre T, Paul A

Abstract
Cardiovascular disease is a leading cause of death worldwide. Since adult cardiac cells are limited in their proliferation, cardiac tissue with dead or damaged cardiac cells downstream of the occluded vessel does not regenerate after myocardial infarction. The cardiac tissue is then replaced with nonfunctional fibrotic scar tissue rather than new cardiac cells, which leaves the heart weak. The limited proliferation ability of host cardiac cells has motivated investigators to research the potential cardiac regenerative ability of stem cells. Considerable progress has been made in this endeavor. However, the optimum type of stem cells along with the most suitable matrix-material and cellular microenvironmental cues are yet to be identified or agreed upon. This review presents an overview of various types of biofunctional materials and biomaterial matrices, which in combination with stem cells, have shown promises for cardiac tissue replacement and reinforcement. Engineered biomaterials also have applications in cardiac tissue engineering, in which tissue constructs are developed in vitro by combining stem cells and biomaterial scaffolds for drug screening or eventual implantation. This review highlights the benefits of using biomaterials in conjunction with stem cells to repair damaged myocardium and give a brief description of the properties of these biomaterials that make them such valuable tools to the field.

PMID: 26953627 [PubMed - indexed for MEDLINE]

Atrioventricular conduction disturbances immediately after hepatic graft reperfusion and their outcomes in patients undergoing liver transplantation.

Tue, 10/17/2017 - 12:45
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Atrioventricular conduction disturbances immediately after hepatic graft reperfusion and their outcomes in patients undergoing liver transplantation.

Liver Transpl. 2016 Jul;22(7):956-67

Authors: Kim SH, Moon YJ, Lee S, Jeong SM, Song JG, Hwang GS

Abstract
Hemodynamic perturbation during hepatic graft reperfusion in patients undergoing liver transplantation (LT) is challenging and is frequently accompanied by bradyarrhythmia and even asystole. However, detailed data on electrocardiographic (ECG) changes during reperfusion are almost nonexistent, although the correct diagnosis by record is important for the treatment. We aimed to identify ECG rhythm disturbances during graft reperfusion and to investigate risk factors and outcomes. Data from 1065 consecutive patients who underwent adult LT were analyzed. The incidence, type, and detailed characteristics of ECG changes immediately after graft reperfusion were assessed using an electronically archived intraoperative ECG database. We analyzed risk factors, postoperative outcomes including major cardiovascular events, 30-day and 1-year mortalities of recipients based on the occurrence of atrioventricular (AV) block, and asystole during reperfusion. The typical pattern of postreperfusion bradyarrhythmia was progressive PR interval prolongation until a Mobitz type 1 AV block occurred. The overall incidence of AV block was 5.0% (53/1065), and 30.2% of them (16/53) had initiated as AV block and then progressed into ventricular asystole. Fulminant hepatic failure was a significant predictor for occurrence of AV block (odds ratio [OR], 7.20; 95% confidence interval, 3.38-15.32; P < 0.001). Patients with AV block showed significantly higher incidence of postoperative major cardiovascular events (P < 0.001) and 30-day mortality (P = 0.002) than those without AV block, whereas the 1-year mortality was not different between the 2 groups (P = 0.10). The postreperfusion asystole was consistently preceded by a Mobitz type 1 AV block. The occurrence of AV block and asystole appears to be an important prognosticator. Therefore, maintaining an optimal range of physiological status and gradual unclamping of the vena cava to avoid sudden atrial distension are recommended in high-risk patients during reperfusion period. Liver Transplantation 22 956-967 2016 AASLD.

PMID: 26850221 [PubMed - indexed for MEDLINE]

Sirt1-Positive Lymphocytes in Acute Cellular Cardiac Allograft Rejection: Contributor to Pathogenesis and a Therapeutic Target.

Tue, 10/17/2017 - 12:45
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Sirt1-Positive Lymphocytes in Acute Cellular Cardiac Allograft Rejection: Contributor to Pathogenesis and a Therapeutic Target.

ASAIO J. 2016 May-Jun;62(3):349-53

Authors: Welsh KJ, Zhao B, Buja LM, Brown RE

Abstract
Cardiac allograft rejection remains a problem, despite advances with immunosuppressants. Understanding the mechanisms behind rejection is essential for developing targeted therapies. The goal of this investigation is to explore Sirtuin 1 (Sirt1) as a therapeutic target for cardiac allograft rejection. Thirteen endomyocardial biopsy specimens with acute cellular rejection (grade 2R or 3R) were selected. CD3, CD4, CD8, CD20, CD68, T-cell intracytoplasmic antigen (TIA-1), and Sirt1 expressions were determined by immunohistochemical stains. Comparison of Sirt1 expression was made with 10 cases of grade 0R and grade 1R. Quantitative image analysis was performed. There were 2 cases of grade 3R and 11 cases of grade 2R acute cellular rejection. Sirtuin 1 expression was present in the majority of mononuclear cells (median percentage, 73.5; interquartile range, 51.2-100%); staining was also observed in cardiomyocytes. Twelve of the 13 cases (92.3%) had an elevated CD8/FoxP3 ratio, coinciding with acute cellular rejection. Sirtuin 1 expression in the nuclei of FoxP3+ cells can lead to deacetylation and inactivation of FoxP3 rendering the T-suppressor cells inactive and promoting acute cellular rejection. The use of a Sirt1 inhibitor may be a therapeutic option in expanding the functionality of the FoxP3+ T-suppressor cells and moderating the severity of such rejection.

PMID: 26771391 [PubMed - indexed for MEDLINE]

Cerebral strokes in children on intracorporeal ventricular assist devices: analysis of the EUROMACS Registry.

Sun, 10/15/2017 - 18:48

Cerebral strokes in children on intracorporeal ventricular assist devices: analysis of the EUROMACS Registry.

Eur J Cardiothorac Surg. 2017 Sep 25;:

Authors: Schweiger M, Miera O, de By TMMH, Hübler M, Berger F, Özbaran M, Loforte A, Seifert B, Gargiulo G, Gummert J, Mohacsi P, EUROMACS members

Abstract
OBJECTIVES: Little is known about cerebral strokes in paediatric patients supported by intracorporeal continuous-flow ventricular assist devices.
METHODS: We retrospectively investigated patients younger than 19 years of age who were treated with an intracorporeal continuous-flow ventricular assist device in the European Registry for Patients with Mechanical Circulatory Support (EUROMACS) database. The patients were stratified by body surface area in Group 1 [<1.2 m2 (n = 13)] and Group 2 [≥1.2 m2 (n = 38)]. Cerebral strokes, both ischaemic and haemorrhagic, were studied.
RESULTS: Of the 2941 patients with ventricular assist device (VAD) implants listed in the database, 124 (4%) patients were less than 19 years of age. Fifty-one of them (2%) were supported with a continuous-flow ventricular assist device. Group 1 (6 female and 7 male) had a mean age (±SD) of 9 ± 2.3 years compared with 15.6 ± 1.8 years in Group 2 (21 female and 17 male). Three (23%) patients died in Group 1 on VAD support, whereas 5 (13%) patients died in Group 2 (P = 0.21; log-rank test). Seven (54%) patients with a VAD in Group 1 and 17 (45%) patients in Group 2 underwent transplantation (P = 0.29); of these, 1 (8%) patient recovered (Group 1) with subsequent device explantation. The other patients, 2 in Group 1 and 16 in Group 2, were still on device support at the time of the analysis. There were no cerebral strokes in Group 1, but 4 cerebral strokes (11% of Group 2, 8% of a total of 51 patients in Groups 1 and 2 combined) occurred in Group 2 (3 patients died; P = 0.26; log-rank test). Taken together, the incidence of cerebral strokes in this paediatric cohort of patients with an intracorporeal VAD was 0.1 per patient-year.
CONCLUSIONS: The incidence of cerebral strokes in children with intracorporeal VADs (0.1 per patient-year) seems to be low irrespective of the body surface area.

PMID: 29029180 [PubMed - as supplied by publisher]

Comparative performance of transcatheter aortic valve-in-valve implantation versus conventional surgical redo aortic valve replacement in patients with degenerated aortic valve bioprostheses: systematic review and meta-analysis.

Sun, 10/15/2017 - 18:48

Comparative performance of transcatheter aortic valve-in-valve implantation versus conventional surgical redo aortic valve replacement in patients with degenerated aortic valve bioprostheses: systematic review and meta-analysis.

Eur J Cardiothorac Surg. 2017 Sep 08;:

Authors: Gozdek M, Raffa GM, Suwalski P, Kolodziejczak M, Anisimowicz L, Kubica J, Navarese EP, Kowalewski M, SIRIO-TAVI group

Abstract
The objective of this report was to directly compare, by means of a systematic review and meta-analysis, redo surgical aortic valve replacement (re-sAVR) with valve-in-valve transcatheter aortic valve implantation (ViV TAVI) for patients with failed degenerated aortic bioprostheses. Multiple databases were screened for all available reports comparing ViV TAVI with re-sAVR in patients with failing degenerated aortic bioprostheses. The primary outcome was all-cause mortality determined from the longest available survival data. Five observational studies (n = 342) were included in the meta-analysis; patients in the ViV TAVI group were older and had a higher baseline risk compared to those in the re-sAVR group. Although there was no statistical difference in procedural mortality [risk ratio (RR) 0.74, 95% confidence interval (CI) 0.18-2.97; P = 0.67], 30-day mortality (RR 1.29, 95% CI 0.44-3.78; P = 0.64) and cardiovascular mortality (RR 0.91, 95% CI 0.30-2.70; P = 0.86) at a mean follow-up period of 18 months, cumulative survival analysis favoured surgery with borderline statistical significance (ViV TAVI versus re-sAVR: hazard ratio 1.91, 95% CI 1.03-3.57; P = 0.039). ViV TAVI was associated with a significantly lower rate of permanent pacemaker implantations (RR 0.37, 95% CI 0.20-0.68; P = 0.002) and shorter intensive care unit (P < 0.001) and hospital stays (P = 0.020). In contrast, re-sAVR offered superior echocardiographic outcomes: lower incidence of patient-prosthesis mismatch (P = 0.008), fewer paravalvular leaks (P = 0.023) and lower mean postoperative aortic valve gradients in the prespecified analysis (P = 0.017). The ViV TAVI approach is a safe and feasible alternative to re-sAVR that may offer an effective, less invasive treatment for patients with failed surgical aortic valve bioprostheses who are inoperable or at high risk. Re-sAVR should remain the standard of care, particularly in the low-risk population, because it offers superior haemodynamic outcomes with low mortality rates.

PMID: 29029105 [PubMed - as supplied by publisher]

Intralobar pulmonary sequestration with an aortic aneurysm.

Sun, 10/15/2017 - 18:48

Intralobar pulmonary sequestration with an aortic aneurysm.

Eur J Cardiothorac Surg. 2017 Oct 04;:

Authors: Menager JB, Mercier O

PMID: 29029028 [PubMed - as supplied by publisher]

Coronary vasospasm: a silent enemy in orthotopic heart transplant.

Sun, 10/15/2017 - 18:48

Coronary vasospasm: a silent enemy in orthotopic heart transplant.

Coron Artery Dis. 2017 Oct 12;:

Authors: Omondi A, Briceno D, Villablanca PA

PMID: 29028740 [PubMed - as supplied by publisher]

Individualized Biventricular Epicardial Augmentation Technology in a Drug-Induced Porcine Failing Heart Model.

Sun, 10/15/2017 - 18:48

Individualized Biventricular Epicardial Augmentation Technology in a Drug-Induced Porcine Failing Heart Model.

ASAIO J. 2017 Oct 12;:

Authors: Jagschies L, Hirschvogel M, Matallo J, Maier A, Mild K, Brunner H, Hinkel R, Gee MW, Radermacher P, Wildhirt SM, Hafner S

Abstract
For treatment of advanced heart failure, current strategies include cardiac transplantation or blood-contacting pump technology associated with complications, including stroke and bleeding. This study investigated an individualized biventricular epicardial augmentation technology in a drug-induced porcine failing heart model. A total of 11 pigs were used, for the assessment of hemodynamics and cardiac function under various conditions of support pressures and support durations (n = 4), to assess device positioning and function by in vivo computer tomographic imaging (n = 3) and to investigate a minimally invasive implantation on the beating heart (n = 4). Support pressures of 20-80 mm Hg gradually augmented cardiac function parameters in this animal model as indicated by increased left ventricular stroke volume, end-systolic pressures, and decreased end-diastolic pressures. Strong evidence was found regarding the necessity of mechanical synchronization of support end with the isovolumetric relaxation phase of the heart. In addition, the customized, self-expandable implant enabled a marker-guided minimally invasive implantation through a 4 cm skin incision using fluoroscopy. Correct positioning was confirmed in computer tomographic images. Continued long-term survival investigations will deliver preclinical evidence for further development of this concept.

PMID: 29028694 [PubMed - as supplied by publisher]

The Development of Pulmonary Hypertension Results in Decreased Post-Transplant Survival.

Sun, 10/15/2017 - 18:48

The Development of Pulmonary Hypertension Results in Decreased Post-Transplant Survival.

ASAIO J. 2017 Oct 10;:

Authors: Schumer EM, Gallo M, Rogers MP, Trivedi JR, Black MC, Massey HT, Slaughter MS

Abstract
The effects of pulmonary hypertension (PAH) on survival after heart transplantation are debated, especially for patients with left ventricular assist devices (LVAD). The United Network of Organ Sharing database was retrospectively queried from January 2005 to June 2015 to identify adult patients who underwent heart transplantation. Four groups were defined: patients without PAH, persistent PAH, resolved PAH, and developed PAH between listing and transplant. A total of 15,914 patients underwent heart transplant of which 4,662 (29%) were implanted with an LVAD. Of the total population, 10,872 (68%) had PAH at time of listing and 9,661 (61%) had PAH at time of transplant. Long-term survival was significantly worse for patients with an LVAD than for those without who had PAH at time of transplant (p = 0.010). Kaplan-Meier analysis showed a trend of worse long-term survival for patients with an LVAD who developed PAH by the time of transplant but improved survival for patients with resolved PAH while on LVAD therapy (p = 0.052). PAH at time of transplant results in worse long-term survival for patients with an LVAD. Furthermore, the development of PAH while on LVAD therapy may negatively impact long-term post-transplant survival, while resolution of PAH improves long-term survival.

PMID: 29028693 [PubMed - as supplied by publisher]

Myocardial Expression of Macrophage Migration Inhibitory Factor in Patients with Heart Failure.

Sun, 10/15/2017 - 18:48

Myocardial Expression of Macrophage Migration Inhibitory Factor in Patients with Heart Failure.

J Clin Med. 2017 Oct 13;6(10):

Authors: Pohl J, Hendgen-Cotta UB, Stock P, Luedike P, Baba HA, Kamler M, Rassaf T

Abstract
Macrophage migration inhibitory factor (MIF) is a pleiotropic inflammatory protein and contributes to several different inflammatory and ischemic/hypoxic diseases. MIF was shown to be cardioprotective in experimental myocardial ischemia/reperfusion injury and its expression is regulated by the transcription factor hypoxia-inducible factor (HIF)-1α. We here report on MIF expression in the failing human heart and assess myocardial MIF in different types of cardiomyopathy. Myocardial tissue samples from n = 30 patients were analyzed by quantitative Real-Time PCR. MIF and HIF-1α mRNA expression was analyzed in myocardial samples from patients with ischemic (ICM) and non-ischemic cardiomyopathy (NICM) and from patients after heart transplantation (HTX). MIF expression was elevated in myocardial samples from patients with ICM compared to NICM. Transplanted hearts showed lower MIF levels compared to hearts from patients with ICM. Expression of HIF-1α was analyzed and was shown to be significantly increased in ICM patients compared to patients with NICM. MIF and HIF-1α mRNA is expressed in the human heart. MIF and HIF-1α expression depends on the underlying type of cardiomyopathy. Patients with ICM show increased myocardial MIF and HIF-1α expression.

PMID: 29027966 [PubMed]

The Prognostic Significance of Measurable ("Minimal") Residual Disease in Acute Myeloid Leukemia.

Sun, 10/15/2017 - 18:48

The Prognostic Significance of Measurable ("Minimal") Residual Disease in Acute Myeloid Leukemia.

Curr Hematol Malig Rep. 2017 Oct 13;:

Authors: Buccisano F, Hourigan CS, Walter RB

Abstract
PURPOSE OF REVIEW: The purpose of this review was to evaluate recent literature on detection methodologies for, and prognostic significance of, measurable ("minimal") residual disease (MRD) in acute myeloid leukemia (AML).
RECENT FINDINGS: There is no "one-fits-all" approach to MRD testing in AML. Most exploited to date are methods relying on immunophenotypic aberrancies (identified via multiparameter flow cytometry) or genetic abnormalities (identified via PCR-based assays). Current methods have important shortcomings, including the lack of assay platform standardization/harmonization across laboratories. In parallel to refinements of existing technologies and data analysis/interpretation, new methodologies (e.g., next-generation sequencing-based assays) are emerging that eventually may complement or replace existing ones. This dynamic evolution of MRD testing has complicated comparisons between individual studies. Nonetheless, an ever-growing body of data demonstrates that a positive MRD test at various time points throughout chemotherapy and hematopoietic cell transplantation identifies patients at particularly high risks of disease recurrence and short survival even after adjustment for other risk factors.

PMID: 29027628 [PubMed - as supplied by publisher]

Correlation between endothelial dysfunction and myocardial damage in acute phase of Tako-Tsubo cardiomyopathy: brachial flow mediated dilation as a potential marker for assessment of patient with Tako-Tsubo.

Sun, 10/15/2017 - 18:48

Correlation between endothelial dysfunction and myocardial damage in acute phase of Tako-Tsubo cardiomyopathy: brachial flow mediated dilation as a potential marker for assessment of patient with Tako-Tsubo.

Heart Vessels. 2017 Oct 13;:

Authors: Carbonara R, Giardinelli F, Pepe M, Luzzi G, Panettieri I, Vulpis V, Bortone AS, Ciccone MM

Abstract
Takotsubo cardiomyopathy (TTC) is characterized by transient systolic ventricular dysfunction. It is supposed to be caused by a cathecolaminergic wave which leads to myocardial stunning through a massive action on beta2-adrenoreceptor. Moreover, beta2-receptor hyperactivity negatively influences endothelial function. It can be detected by brachial flow mediated dilation (b-FMD) which assesses endothelium regulated vasomotility. The study aim is to analyze the b-FMD variability during hospitalization in 50 patients admitted with TTC. In addition, we investigated a possible correlation between b-FMD at admission and both length of hospital stay (LOHS) and troponin I peak. We detected b-FMD by measuring the hypoxic induced vasoreactivity through assessing brachial artery dilation after 5 min of iatrogenic ischemia obtained by inflating a sphygmomanometer cuff. Artery diameter modifications were assessed by high-resolution ultrasound, and a dedicated software calculated accurately the percentage of dilation after ischemia by comparing it to the basal. These values were measured at admission and on discharge. The obtained values were compared for each patient to explore their variability during hospitalization. Moreover, the correlation between the b-FMD at admission and both the troponin I peak and the LOHS was investigated. There was a statistical significant difference between mean FMD measured at admission and at discharge (respectively 1.54 ± 0.34 and 8.92 ± 2.48%; p < 0.001). Moreover, we found a significant negative correlation between troponin I peak and FMD values at admission (r = - 0.7645; p < 0.001) and a significant inverse correlation between FMD at admission and LOHS (r = - 0.7543; p < 0.001). There is a significant improvement of b-FMD during hospitalization in patients admitted for Tako-Tsubo Cardiomyopathy. Moreover, for the first time, a direct correlation among b-FMD, troponin I peak and LOHS has been detected.

PMID: 29027587 [PubMed - as supplied by publisher]

Multiply adjusted comparisons: A meta-analysis method to compare single-arm clinical-trial data to literature results regarding a competitor.

Sun, 10/15/2017 - 18:48

Multiply adjusted comparisons: A meta-analysis method to compare single-arm clinical-trial data to literature results regarding a competitor.

Stat Methods Med Res. 2017 Jan 01;:962280217733776

Authors: Boethig D, Hecker H

Abstract
Prospective randomized controlled trials are difficult to obtain if a promising new therapy has to be tested against seemingly obsolete alternatives. One method to address this problem is to compare the results of (multicentre) trials to literature results. However, previous treatment-era changes and population-dependent results complicate objective comparisons. The presented approach describes a method to objectify such comparisons in cases in which individual raw data regarding a new therapy have to be compared to summary results regarding a conventional alternative published in the literature. The chosen example is the introduction of bovine neck veins as a substitute for dysfunctional human pulmonary valves, and the conventional therapeutic alternative is pulmonary-artery homografts. Literature research, subgroup identification, filtering, endpoint remodelling, weighting and, if necessary, confidence-limit calculation yield adjusted comparisons. These individual comparisons are then aggregated, first by article and then over several articles (similar to meta-analyses), resulting in a differentiated panel of answers (Multiply Adjusted Comparisons). In situations in which extensive raw data regarding a new therapeutic alternative but no randomized controlled trials and no raw data from previous studies using the conventional therapeutic alternative are available, the proposed method identifies the best evidence and is by far superior to unadjusted direct comparisons or gut feelings.

PMID: 29027509 [PubMed - as supplied by publisher]

Ginsenoside Rb1 prevents homocysteine-induced EPC dysfunction via VEGF/p38MAPK and SDF-1/CXCR4 activation.

Sun, 10/15/2017 - 18:48
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Ginsenoside Rb1 prevents homocysteine-induced EPC dysfunction via VEGF/p38MAPK and SDF-1/CXCR4 activation.

Sci Rep. 2017 Oct 12;7(1):13061

Authors: Lan TH, Xu DP, Huang MT, Song JX, Wu HL, Li M

Abstract
Hyperhomocystinemia (HHcy) is known as an independent risk factor for cardiovascular disease. Our previous study showed that ginsenoside Rb1, the major active constituent of ginseng, prevents homocysteine (Hcy)-induced endothelial damage. However, the role of ginsenoside Rb1 in Hcy-induced dysfunction in endothelial progenitor cells (EPCs) remains unknown. In the study, we found that ginsenoside Rb1 reversed the Hcy-induced impairment of adhesive and migratory ability in EPCs which were significantly abolished by CXCR4 antagonist AMD3100 and VEGFR2 inhibitor SU5416. Ginsenoside Rb1 significantly reversed Hcy-induced SDF-1 reduction in the supernatant and in the serum. Ginsenoside Rb1 reversed downregulation of SDF-1 and VEGFR2 protein expression, inhibition of p38MAPK phosphorylation induced by Hcy. Re-endothelialization in balloon-injured carotid arteries significantly increased with EPCs transplant, and was even better with Rb1 treatment. This effect was significantly abolished by AMD3100. AMD3100 also decreased the number of CM-DiI labeled EPCs in injured arteries. Here we show for the first time that Rb1 prevents Hcy-induced EPC dysfunction via VEGF/p38MAPK and SDF-1/CXCR4 activation. These findings demonstrate a novel mechanism of the action of Rb1 that may have value in prevention of HHcy associated cardiovascular disease.

PMID: 29026158 [PubMed - in process]

Effect of erdosteine on the rate and duration of COPD exacerbations: the RESTORE study.

Sun, 10/15/2017 - 18:48
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Effect of erdosteine on the rate and duration of COPD exacerbations: the RESTORE study.

Eur Respir J. 2017 Oct;50(4):

Authors: Dal Negro RW, Wedzicha JA, Iversen M, Fontana G, Page C, Cicero AF, Pozzi E, Calverley PMA, RESTORE group, RESTORE study

Abstract
Oxidative stress contributes to chronic obstructive pulmonary disease (COPD) exacerbations and antioxidants can decrease exacerbation rates, although we lack data about the effect of such drugs on exacerbation duration.The RESTORE (Reducing Exacerbations and Symptoms by Treatment with ORal Erdosteine in COPD) study was a prospective randomised, double-blind, placebo-controlled study, enrolling patients aged 40-80 years with Global Initiative for Chronic Obstructive Lung Disease stage II/III. Patients received erdosteine 300 mg twice daily or placebo added to usual COPD therapy for 12 months. The primary outcome was the number of acute exacerbations during the study.In the pre-specified intention-to-treat population of 445 patients (74% male; mean age 64.8 years, forced expiratory volume in 1 s 51.8% predicted) erdosteine reduced the exacerbation rate by 19.4% (0.91 versus 1.13 exacerbations·patient(-1)·year(-1) for erdosteine and placebo, respectively; p=0.01), due to an effect on mild events; the reduction in the rate of mild exacerbations was 57.1% (0.23 versus 0.54 exacerbations·patient(-1)·year(-1) for erdosteine and placebo, respectively; p=0.002). No significant difference was observed in the rate of moderate and severe exacerbations (0.68 versus 0.59 exacerbations·patient(-1)·year(-1) for erdosteine and placebo, respectively; p=0.054) despite a trend in favour of the comparison group. Erdosteine decreased the exacerbation duration irrespective of event severity by 24.6% (9.55 versus 12.63 days for erdosteine and placebo, respectively; p=0.023). Erdosteine significantly improved subject and physician subjective severity scores (p=0.022 and p=0.048, respectively), and reduced the use of reliever medication (p<0.001), but did not affect the St George's Respiratory Questionnaire score or the time to first exacerbation.In patients with COPD, erdosteine can reduce both the rate and duration of exacerbations. The percentage of patients with adverse events was similar in both the placebo and erdosteine treatment groups.

PMID: 29025888 [PubMed - in process]

Remote Monitoring of Automated Peritoneal Dialysis Patients: Assessing Clinical and Economic Value.

Fri, 10/13/2017 - 12:45

Remote Monitoring of Automated Peritoneal Dialysis Patients: Assessing Clinical and Economic Value.

Telemed J E Health. 2017 Oct 12;:

Authors: Makhija D, Alscher MD, Becker S, D'Alonzo S, Mehrotra R, Wong L, McLeod K, Danek J, Gellens M, Kudelka T, Sloand JA, Laplante S

Abstract
BACKGROUND: For chronic kidney disease patients who progress to end-stage renal disease, survival is dependent on renal replacement therapy in the form of kidney transplantation or chronic dialysis. Peritoneal dialysis (PD), which can be performed at home, is both more convenient and less costly than hemodialysis that requires three 4-h visits per week to the dialysis facility and complicated equipment. Remote therapy management (RTM), technologies that collect medical information and transmit it to healthcare providers for patient management, has the potential to improve the outcomes of patients receiving automated peritoneal dialysis (APD) at home.
OBJECTIVE: Estimate through a simulation study the potential impact of RTM on APD patients use of healthcare resources and costs in the United States, Germany, and Italy.
METHODS: Twelve APD patient profiles were developed to reflect potential clinical scenarios of APD therapy. Two versions of each profile were created to simulate healthcare resource use, one assuming use of RTM and one with no RTM. Eleven APD teams (one nephrologist, one nurse) estimated resources that would be used.
RESULTS: Results from U.S., German, and Italian clinicians found that RTM could avoid use of 59, 49, and 16 resources over the 12 profiles, respectively. Estimated reduced utilization across the three countries ranged from one to two hospitalizations, one to four home visits, two to five emergency room visits, and four to eight unplanned clinic visits. Total savings across all scenarios were $23,364 in the United States, $11,477 in Germany, and $7,088 in Italy.
CONCLUSION: In a simulated environment, early intervention enabled by RTM reduced healthcare resource utilization and associated costs.

PMID: 29024613 [PubMed - as supplied by publisher]

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