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These results suggest blood group-dependent (re)shaping of lipoprotein metabolism in healthy subjects, which may provide relevant information to explain the differential susceptibility to certain diseases observed in different blood groups.Heart failure (HF), type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD) are some of the most important health problems of this century, and these three conditions often coexist, one worsening the prognosis of the other two. No disease is more important than the others in the composition of risk, which is significantly increased by their overlap. Thus, it would be more appropriate to refer to this cluster as cardio-nephro-metabolic syndrome. The aim of this review is to promote the development of an integrated multidisciplinary approach to the treatment of HF, T2DM and CKD in a perspective of paradigm shift from an individual management among different specialists to a shared one. Nowadays, this is achievable thanks to telemedicine and optimized therapy consisting in the new drugs with pleiotropic effect available today. The need is to have technological solutions, which also include telemedicine, for the management of patients affected by all three diseases to consider their fragility, sometimes due to a wrong, partial, or incomplete treatment. Multicentric, multidisciplinary trials on cardio-nephro-metabolic syndrome and new telemedicine/telemonitoring technologies could help place the chronic and fragile patient at the center of such multidimensionally integrated care.

We aimed to investigate predictors for long-term survival of in-hospital patients with medical emergency team (MET) consultation with or without in-hospital cardiac arrest (IHCA) in Austria's largest medical center.

Data of patients, who needed an intervention of a MET between 01/2014 and 03/2020 were reviewed for this retrospective analysis.

In total, 708 MET calls were analyzed. The minimum follow-up was 7 months, the maximum 6.2 years. The main MET indications were circulatory failure (63%) followed by respiratory failure (27.1%), and bleeding events (3.5%). IHCA with subsequent cardiopulmonary resuscitation (CPR) was experienced by 425 (60%) patients. Of those, 274 (64%) reached return of spontaneous circulation (ROSC), and 221 (52%) survived the first 24-hours (median survival 146 days) and 22.1% the first year. After adjustment for potential confounders, age (p<0.001), time to ROSC (p<0.001), a non-shockable rhythm (p=0.041), chronic kidney disease (CKD, p=0.041), peak lactate levels (p<0ies, and cardiac arrest-related parameters. A better characterization of MET call populations and their outcome might help to improve clinical decision making.

Acute coronary syndromes (ACS) are a major cause of morbidity and mortality. SC75741 As cytomegalovirus (CMV) may contribute to Cardio-Vascular (CV) manifestations, we sought to provide a proof-of-concept for the involvement of coronary and/or systemic CMV-reactivation as a possible ACS trigger.

We prospectively enrolled consecutive patients undergoing a coronary angiography for ACS (acute-cases, N=136), or non-ACS reasons (chronic-cases, N=57). Matched coronary and peripheral blood-samples were processed for quantification of CMV-DNAemia (RT-PCR), CMVIgG/ IgM, and CMV-IgG avidity (ELISA). Peripheral-blood samples from 17 healthy subjects were included as controls.

Out of the 193 cases included, 18.1% were aged ≤55 years, 92.5% were Central-European, and 100% immunocompetent. CMV-IgG seroprevalence was 91.7% (95%CI 87.8-95.6), significantly higher than in healthy-controls (52.9% [95%CI 29.2-76.5]; p<0.001), yet consistent across age-groups (p=0.602), male/females (p=0.765), and acute/chronic-cases (p=0.157).rculation during an ACS, with increased prevalence in older subjects and in absence of CV risk-factors, identifying possible areas for novel interventions.Mobilization or egress of stem cells from bone marrow (BM) into peripheral blood (PB) is an evolutionary preserved and important mechanism in an organism for self-defense and regeneration. BM-derived stem cells circulate always at steady-state conditions in PB, and their number increases during stress situations related to (a) infections, (b) tissue organ injury, (c) stress, and (d) strenuous exercise. Stem cells also show a circadian pattern of their PB circulating level with peak in early morning hours and nadir late at night. The number of circulating in PB stem cells could be pharmacologically increased after administration of some drugs such as cytokine granulocyte colony-stimulating factor (G-CSF) or small molecular antagonist of CXCR4 receptor AMD3100 (Plerixafor) that promote their egress from BM into PB and lymphatic vessels. Circulating can be isolated from PB for transplantation purposes by leukapheresis. This important homeostatic mechanism is governed by several intrinsic complementary pathways. In this chapter, we will discuss the role of purinergic signaling and extracellular nucleotides in regulating this process and review experimental strategies to study their involvement in mobilization of various types of stem cells that reside in murine BM.The hematopoietic system is one of the most sensitive tissues to ionizing radiation, and radiation doses from 2 to 10 gray can result in death from bleeding and infection if left untreated. Reviewing the range of radiation doses reported in the literature that result in similar lethality highlights the need for a more consistent model that would allow a better comparison of the hematopoietic acute radiation syndrome (H-ARS) studies carried out in different laboratories. Developing a murine model of H-ARS to provide a platform suited for efficacy testing of medical countermeasures (MCM) against radiation should include a review of the Food and Drug Administration requirements outlined in the Animal Rule. The various aspects of a murine H-ARS model found to affect consistent performance will be described in this chapter including strain, sex, radiation type and dose, mouse restraint, and husbandry.The zebrafish as a model organism is well known for its versatile genetics, rapid development, and straightforward live imaging. It is an excellent model to study hematopoiesis because of its highly conserved ontogeny and gene regulatory networks. Recently developed highly specific transgenic reporter lines have allowed direct imaging and tracking of hematopoietic stem and progenitor cells (HSPCs) in live zebrafish. These reporter lines can also be used for fluorescence-activated cell sorting (FACS) of HSPCs. Similar to mammalian models, HSPCs can be transplanted to reconstitute the entire hematopoietic system of zebrafish recipients. However, the zebrafish provides unique advantages to study HSPC biology, such as transplants into embryos and high-throughput chemical screening. This chapter will outline the methods needed to identify, isolate, and transplant HSPCs in zebrafish.Experimental hematopoietic stem cell transplantation (HSCT) is an invaluable tool in determining the function and characteristics of hematopoietic stem cells (HSC) from experimental mouse and human donor groups. These groups could include, but are not limited to, genetically altered populations (gene knockout/knockin models), ex vivo manipulated cell populations, or in vivo modulated cell populations. The basic fundamentals of this process involve taking cells from a mouse/human donor source and putting them into another mouse (recipient) after preconditioning of the recipient with either total body irradiation (TBI) for mouse donor cells or into sublethally irradiated immune-deficient mice for human donor cells. Then, at pre-determined time points post-transplant, sampling a small amount of peripheral blood (PB) and at the termination of the evalaution, bone marrow (BM) to determine donor contribution and function by phenotypic analysis. Exploiting the congenic mouse strains of C57BL/6 (CD45.1- CD45.2+), BoyJ (CD45.1+ CD45.2-), and their F1-crossed hybrid C57BL/6 × BoyJ (CD45.1+ CD45.2+), we are able to quantify donor, competitor, and recipient mouse cell contributions to the engraftment state. Human donor cell engraftment (e.g., from the cord blood [CB], mobilized PB, or BM) is assessed by human cell phenotyping in sublethally irradiated immune-deficient mouse recipients (e.g., NOD scid gamma mice that are deficient in B cells, T cells, and natural killer cells and have defective dendritic cells and macrophages). Engraftment of cells from primary mouse recipients into secondary mice allows for an estimation of the self-renewal capacity of the original donor HSC. This chapter outlines concepts, methods, and techniques for mouse and human cell models of HSCT and for assessment of donor cells collected and processed in hypoxia versus ambient air.T cells go through most of their maturation in the thymus, and the stromal constituents of the thymus are therefore essential for T cell differentiation. The thymic stroma secretes the factors that recruit and sustain T cell progenitors, and they also partake in the shaping of a functional and tolerant T cell receptor repertoire. The damage incurred to the thymic stromal compartment by bone marrow conditioning regimens as well as by the natural aging process impairs T cell production. Yet little is known of how to prevent or reverse this damage. The development of high-throughput, single-cell analysis technologies has enabled better characterization of thymic stromal cells. This does however require tissue dissociation protocols optimized for stromal cell isolation. In this chapter, we detail the methodology of harvesting thymus stromal cells from human and murine tissue for downstream applications such as flow cytometric analysis and single-cell RNA sequencing.Mesenchymal stromal cells (MSCs) are the crucial component of the hematopoietic stem and progenitor cell (HSPC) niche in the bone marrow. Therefore, an ex vivo culture system that recapitulates the marrow microenvironment is important to understanding the niche's regulatory role on HSPC function and improving ex vivo HSPC expansion for clinical transplantation. Herein, a procedure for ex vivo expansion of MSCs from human bone marrow cells and their identification and characterization is described. In addition, a protocol for MSC and HSPC coculture assay is presented. This MSC-HSPC coculture assay can be used for ex vivo expansion of HSPC. Furthermore, this assay is also useful for qualitative analysis of MSCs capable of supporting hematopoiesis.The bone marrow (BM) has traditionally been a difficult tissue to access because it is embedded deep within the bone matrix. It is home to the hematopoietic stem cells (HSCs) that give rise to all blood cells in the body. It is also the site of origin for malignant blood cells such as leukemia and multiple myeloma, as well as a frequent site of metastasis for many solid tumors including prostate and breast cancer. The following chapter describes how laser micromachining of bone can be used to improve both optical and physical access to the BM. For example, laser thinning of the overlying bone can improve optical access, enabling deeper imaging into the BM as well as enhancing optical resolution by reducing scattering and aberration. Laser micromachining can also be used to provide physical access into the BM by creating access ports for micropipette insertion and delivery of cells to precise locations in the BM, as well as for the extraction of BM cells and interstitial fluid, all under image guidance. This chapter provides a detailed protocol for installing a laser-micromachining capability for users with an existing multiphoton microscope.

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