Bone marrow and plasma FGF-23 in heart failure patients: novel insights into the heart-bone axis.

Aims: Fibroblast growth factor 23 (FGF-23) is known to be elevated in patients with congestive heart failure (CHF). As FGF-23 is expressed in the bone but can also be expressed in the myocardium, the origin of serum FGF-23 in CHF remains unclear. It is also unclear if FGF-23 expressed in the bone is associated with outcome in CHF.

Minute Myocardial Injury as Measured by High-Sensitive Troponin T Serum Levels Predicts the Response to Intracoronary Infusion of Bone Marrow-Derived Mononuclear Cells in Patients With Stable Chronic Post-Infarction Heart Failure: Insights From the TOPCARE-CHD Registry.

Rationale: Cell-based therapies are a promising option in patients with chronic postinfarction heart failure (ischemic cardiomyopathy [ICM]). However, the responses after intracoronary infusion of autologous bone marrow-derived mononuclear cells (BMCs) are heterogeneous, which may be related to impaired cell retention in patients with ICM. Ischemic injury is associated with upregulation of prototypical chemoattractant cytokines mediating retention and homing of circulating cells.

Metabolism Regulates Cellular Functions of Bone Marrow-Derived Cells used for Cardiac Therapy.

Administration of bone marrow-derived mononuclear cells (BMC) may increase cardiac function after myocardial ischemia. However, the functional capacity of BMC derived from chronic heart failure (CHF) patients is significantly impaired. As modulation of the energy metabolism allows cells to match the divergent demands of the environment, we examined the regulation of energy metabolism in BMC from patients and healthy controls (HC).

The challenges of autologous cell therapy: systemic anti-thrombotic therapies interfering with serum coagulation may disable autologous serum-containing cell products for therapeutical use.

Cell therapy of acute myocardial infarction (AMI) with bone marrow-derived mononuclear cells (BMC) resulted in a modest improvement of cardiac function, but clinical trial results were heterogeneous. After isolation, BMC are maintained in medium supplemented with complements such as autologous serum to maintain optimal cell viability until administration. In the REPAIR-AMI trial, serum was prepared using tubes containing coagulation accelerators, but the regulatory agency recommended using additive-free tubes for the pivotal BAMI trial.

Complications associated with the prehospital use of laryngeal tubes--a systematic analysis of risk factors and strategies for prevention.

Objective: With the increasing spread of laryngeal tubes (LT) in emergency medicine, complications and side-effects are observed. We sought to identify complications associated with the use of LTs in emergency medicine, and to develop strategies to prevent these incidents.

Methods: In a prospective clinical study, all patients who had their airways managed in the field with a LT and who were admitted through the emergency department of the Frankfurt University Hospital during a 6 year period were evaluated using anonymised data collection sheets.

Does the integration of personalized ultrasound change patient management in critical care medicine? Observational trials.

Objective. To test the influence of personalized ultrasound (PersUS) on patient management in critical care. Design of the Study.

Thorax, trachea, and lung ultrasonography in emergency and critical care medicine: assessment of an objective structured training concept.

Background and Study objective. Focused lung ultrasound (LUS) examinations are important tools in critical care medicine. There is evidence that LUS can be used for the detection of acute thoracic lesions.

MicroRNAs in stem cell function and regenerative therapy of the heart.

MicroRNAs are small noncoding RNAs that posttranscriptionally control gene expression by targeting mRNAs. Distinct microRNAs regulate stem and progenitor cell functions, thereby modulating cell survival and homing or controlling differentiation and maturation. Experimental studies additionally show that microRNAs regulate endogenous repair and might potentially be useful to enhance the regeneration of the heart.

Impact of intracoronary reinfusion of bone marrow-derived mononuclear progenitor cells on cardiopulmonary exercise capacity in patients with chronic postinfarction heart failure.

Introduction: Intracoronary infusion of bone marrow-derived progenitor cells (BMC) in patients with chronic ischaemic heart failure (CHF) is associated with improvement in left ventricular ejection fraction (LVEF), reduction of NT-proBNP levels and improved prognosis. However, effects of this therapy on cardiopulmonary exercise capacity have not been investigated separately so far.

Patients And Methods: One hundred and fifty-four patients with ischaemic heart failure (mean LVEF 40.

Effect of shock wave-facilitated intracoronary cell therapy on LVEF in patients with chronic heart failure: the CELLWAVE randomized clinical trial.

Importance: The modest effects of clinical studies using intracoronary administration of autologous bone marrow-derived mononuclear cells (BMCs) in patients with chronic postinfarction heart failure may be attributed to impaired homing of BMCs to the target area. Extracorporeal shock wave treatment has been experimentally shown to increase homing factors in the target tissue, resulting in enhanced retention of applied BMCs.

Objective: To test the hypothesis that targeted cardiac shock wave pretreatment with subsequent application of BMCs improves recovery of left ventricular ejection fraction (LVEF) in patients with chronic heart failure.

Comparison of the Seattle heart failure model and cardiopulmonary exercise capacity for prediction of death in patients with chronic ischemic heart failure and intracoronary progenitor cell application.

Background: Despite many therapeutic advances, the prognosis of patients with chronic heart failure (CHF) remains poor. Therefore, reliable identification of high-risk patients with poor prognosis is of utmost importance. Cardiopulmonary exercise testing (CPET) provides important prognostic information by peak O2 uptake (peak VO2 ), maximal oxygen pulse (O2 Pmax), O2 uptake efficiency slope (OUES), and VE/VCO2 slope (VE/VCO2 ).

Procedural safety and predictors of acute outcome of intracoronary administration of progenitor cells in 775 consecutive procedures performed for acute myocardial infarction or chronic heart failure.

Background: Cell-based therapies are a promising option in patients with acute myocardial infarction or chronic heart failure (CHF). However, administration of cells requires intracoronary or intracardiac instrumentation, which is potentially associated with periprocedural risks. Therefore, we analyzed periprocedural complications and 30-day outcome in 775 consecutive procedures of intracoronary administration of progenitor cells using the stop-flow technique.

Immunosenescence-associated microRNAs in age and heart failure.

Aims: Ageing of the immune system, immunosenescence, is characterized by impaired lymphopoiesis, especially B-lymphocyte maturation, and is a hallmark of chronic heart failure (CHF). MicroRNAs (miRNAs) are non-coding, small RNAs, which post-transcriptionally control gene expression of multiple target genes. The miR-181 family is known to control haematopoietic lineage differentiation.

G-CSF stimulation and coronary reinfusion of mobilized circulating mononuclear proangiogenic cells in patients with chronic ischemic heart disease:five-year results of the TOPCARE-G-CSF trial.

Prognosis of patients with heart failure remains poor despite improved conventional and interventional treatment regimens. The improvement of neovascularization and repair processes by administration of bone marrow-derived cells modestly improved the recovery after acute myocardial infarction. However, circulating patient-derived cells are reduced in number and function particularly in chronic heart failure.

Elevated levels of the mediator of catabolic bone remodeling RANKL in the bone marrow environment link chronic heart failure with osteoporosis.

Background: Chronic heart failure (CHF) is associated with a 4-fold increased risk for osteoporotic fractures. Therefore, we sought to identify the pathophysiological link between chronic heart failure and catabolic bone remodeling.

Methods And Results: In a total cohort of 153 subjects (123 patients with CHF, 30 patients with coronary artery disease and preserved cardiac function) as well as mice with heart failure, bone marrow (BM) plasma levels of the catabolic receptor activator of NF-κB ligand (RANKL), and its antagonist, osteoprotegerin were measured.

Simplistic approach to prognosis after cardiopulmonary resuscitation-value of pH and lactate.

Purpose: The purpose was to determine the prognostic value of broadly available clinical parameters such as pH and lactate for early stratification of outcome after cardiopulmonary resuscitation.

Methods: We analyzed patients with status postresuscitation who were admitted to the Frankfurt University hospital. Arterial pH and serum lactate levels were dichotomized as "high" or "low.

Heparin disrupts the CXCR4/SDF-1 axis and impairs the functional capacity of bone marrow-derived mononuclear cells used for cardiovascular repair.

Rationale: Cell therapy is a promising option for the treatment of acute or chronic myocardial ischemia. The intracoronary infusion of cells imposes the potential risk of cell clotting, which may be prevented by the addition of anticoagulants. However, a comprehensive analysis of the effects of anticoagulants on the function of the cells is missing.

Micro-RNA-34a contributes to the impaired function of bone marrow-derived mononuclear cells from patients with cardiovascular disease.

Objectives: This study evaluated the regulation and function of micro-RNAs (miRs) in bone marrow-mononuclear cells (BMCs).

Background: Although cell therapy with BMCs may represent a therapeutic option to treat patients with heart disease, the impaired functionality of patient-derived cells remains a major challenge. Small noncoding miRs post-transcriptionally control gene expression patterns and play crucial roles in modulating cell survival and function.

Early remodeling processes as predictors of diastolic function 5 years after reperfused acute myocardial infarction and intracoronary progenitor cell application.

Aims: Ischemia-induced left ventricular (LV) diastolic dysfunction (DD) is increasingly recognized as a therapeutic challenge. While DD during acute myocardial infarction (AMI) determines patients' prognosis, it is unknown how LV remodeling after AMI affects the development of DD. Therefore, we aimed to identify AMI characteristics, which determine diastolic function after 5 years.

Transplantation of progenitor cells and regeneration enhancement in acute myocardial infarction (TOPCARE-AMI): final 5-year results suggest long-term safety and efficacy.

Background: Limited data is available for investigating the long-term safety and effects of intracoronary progenitor cell therapy in patients with acute myocardial infarction (AMI).

Objective: To assess the clinical course, NT-proBNP and MRI data as objective markers of cardiac function of the TOPCARE-AMI patients at 5-year follow-up.

Design: The TOPCARE-AMI trial was the first randomized study investigating the effects of intracoronary infusion of circulating (CPC) or bone marrow-derived progenitor cells (BMC) in 59 patients with successfully reperfused AMI.

Focused echocardiographic evaluation in life support and peri-resuscitation of emergency patients: a prospective trial.

Purpose Of The Study: Focused ultrasound is increasingly used in the emergency setting, with an ALS-compliant focused echocardiography algorithm proposed as an adjunct in peri-resuscitation care (FEEL). The purpose of this study was to evaluate the feasibility of FEEL in pre-hospital resuscitation, the incidence of potentially treatable conditions detected, and the influence on patient management.

Patients, Materials And Methods: A prospective observational study in a pre-hospital emergency setting in patients actively undergoing cardio-pulmonary resuscitation or in a shock state.

Peri-resuscitation echocardiography: training the novice practitioner.

Aims: Echocardiography performed in an ALS-compliant manner provides a tool whereby some of the potentially reversible causes of cardiac arrest can be diagnosed in real time by minimally trained practitioners. One of the major concerns this raises is how to deliver effective training to the required standard. The objective of this study was to determine the effectiveness of number of different educational methods used teach echocardiography to novices.

Kruppel-like factor 2 improves neovascularization capacity of aged proangiogenic cells.

Aims: Coronary artery disease (CAD) patients have less circulating proangiogenic cells (PACs), formerly known as endothelial progenitor cells, which exhibit impaired neovascularization properties. Inverse correlations were also found between PAC function and risk factors like age. Krüppel-like factor 2 (KLF2) is expressed by mature endothelial cells (ECs), is induced by both shear stress and statins, and provokes endothelial functional differentiation.

Red blood cell contamination of the final cell product impairs the efficacy of autologous bone marrow mononuclear cell therapy.

Objectives: The aim of this study was to identify an association between the quality and functional activity of bone marrow-derived progenitor cells (BMCs) used for cardiovascular regenerative therapies and contractile recovery in patients with acute myocardial infarction included in the placebo-controlled REPAIR-AMI (Reinfusion of Enriched Progenitor cells And Infarct Remodeling in Acute Myocardial Infarction) trial.

Background: Isolation procedures of autologous BMCs might affect cell functionality and therapeutic efficacy.

Methods: Quality of cell isolation was assessed by measuring the total number of isolated BMCs, CD34+ and CD133+ cells, their colony-forming unit (CFU) and invasion capacity, cell viability, and contamination of the final BMC preparation with thrombocytes and red blood cells (RBCs).

Intracarotid administration of human bone marrow mononuclear cells in rat photothrombotic ischemia.

Background: Increasing evidence suggests that cell therapy improves functional recovery in experimental models of stroke and myocardial infarction. So far only small pilot trials tested the effects of cell therapy in stroke patients, whereas large clinical trials were conducted in patients with ischemic heart disease. To investigate the therapeutic benefit of cell therapy to improve the recovery after stroke, we determined the efficacy of bone marrow derived mononuclear cells, which were shown to improve the recovery in experimental and clinical acute myocardial infarction studies, in a rat stroke model.