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Background: Three-dimensional echocardiography (3DE) allows accurate and reproducible measurements of right ventricular (RV) size and function. However, widespread implementation of 3DE in routine clinical practice is limited because the existing software packages are relatively time-consuming and skill demanding. The aim of this study was to test the accuracy and reproducibility of new machine learning- (ML-) based, fully automated software for three-dimensional quantification of RV size and function., Methods: Fifty-six unselected patients with a wide range of RV size and function and image quality, referred for clinically indicated cardiac magnetic resonance (CMR) imaging, underwent a transthoracic 3DE exam on the same day. End-systolic and end-diastolic RV volumes (ESV, EDV) and ejection fraction (EF) were measured using the ML-based algorithm and compared with CMR reference values using Bland-Altman and linear regression analyses., Results: RV function quantification by echocardiography was feasible in all patients. The automatic approach was accurate in 32% patients with analysis time of 15 ± 1 seconds and 100% reproducible. Endocardial contour editing was necessary after the automated postprocessing in the remaining 68% patients, prolonging analysis time to 114 ± 71 seconds. With these minimal adjustments, RV volumes and EF measurements were accurate in comparison with CMR reference (biases: EDV, -25.6 ± 21.1 mL; ESV, -7.4 ± 16 mL; EF, -3.3% ± 5.2%) and showed excellent reproducibility reflected by coefficients of variation <7% and intraclass correlations ≥0.95 for all measurements., Conclusions: The new ML-based 3DE algorithm provided accurate and completely reproducible RV volume and EF measurements in one-third of unselected patients without any boundary editing. In the remaining patients, quick minimal editing resulted in reasonably accurate measurements with excellent reproducibility. This approach provides a promising solution for fast three-dimensional quantification of RV size and function., (Copyright © 2019 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.)

Aims: Studies have demonstrated the ability of a new automated algorithm for volumetric analysis of 3D echocardiographic (3DE) datasets to provide accurate and reproducible measurements of left ventricular and left atrial (LV, LA) volumes at end-systole and end-diastole. Recently, this methodology was expanded using a machine learning (ML) approach to automatically measure chamber volumes throughout the cardiac cycle, resulting in LV and LA volume-time curves. We aimed to validate ejection and filling parameters obtained from these curves by comparing them to independent well-validated reference techniques., Methods and Results: We studied 20 patients referred for cardiac magnetic resonance (CMR) examinations, who underwent 3DE imaging the same day. Volume-time curves were obtained for both LV and LA chambers using the ML algorithm (Philips HeartModel), and independently conventional 3DE volumetric analysis (TomTec), and CMR images (slice-by-slice, frame-by-frame manual tracing). Automatically derived LV and LA volumes and ejection/filling parameters were compared against both reference techniques. Minor manual correction of the automatically detected LV and LA borders was needed in 4/20 and 5/20 cases, respectively. Time required to generate volume-time curves was 35 ± 17 s using ML algorithm, 3.6 ± 0.9 min using conventional 3DE analysis, and 96 ± 14 min using CMR. Volume-time curves obtained by all three techniques were similar in shape and magnitude. In both comparisons, ejection/filling parameters showed no significant inter-technique differences. Bland-Altman analysis confirmed small biases, despite wide limits of agreement., Conclusion: The automated ML algorithm can quickly measure dynamic LV and LA volumes and accurately analyse ejection/filling parameters. Incorporation of this algorithm into the clinical workflow may increase the utilization of 3DE imaging., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2018. For permissions, please email: journals.permissions@oup.com.)

Background: Although 3D echocardiography (3DE) circumvents many limitations of 2D echocardiography by allowing direct measurements of left ventricular (LV) mass, it is seldom used in clinical practice due to time-consuming analysis. A recently developed 3DE machine learning (ML) approach allows automated determination of LV mass. We aimed to evaluate the accuracy of this new approach by comparing it to cardiac magnetic resonance (CMR) reference and to conventional 3DE volumetric analysis., Methods: We prospectively studied 23 patients who underwent 3DE (Philips EPIQ) and CMR imaging on the same day. Single-beat wide-angle 3D datasets of the left ventricle were acquired. LV mass was quantified using the new automated software (Philips HeartModel) with manual corrections when necessary and using conventional volumetric analysis (TomTec). CMR analysis was performed by manual slice-by-slice tracing of LV endo- and epicardial boundaries. Reproducibility of the ML approach was assessed using repeated measurements and quantified by intra-class correlation (ICC) and coefficients of variation (CoV)., Results: Automated LV mass measurements were feasible in 20 patients (87%). The results were similar to CMR-derived values (Bland-Altman bias 5 g, limits of agreement ±37 g) and also to the conventional 3DE analysis (bias 7 g, ±27 g). Processing time was considerably shorter: 1.02 ± 0.24 minutes (CMR: 2.20 ± 0.13 minutes; TomTec: 2.36 ± 0.09 minutes), although manual corrections were performed in most patients. Repeated measurements showed high reproducibility: ICC = 0.99; CoV = 4 ± 5%., Conclusions: 3D Echocardiography analysis of LV mass using novel ML-based algorithm is feasible, fast, and accurate and may thus facilitate the incorporation of 3DE measurements of LV mass into clinical practice., (© 2018 Wiley Periodicals, Inc.)

Objectives: The goal of this study was to test the feasibility and accuracy of an automated algorithm that simultaneously quantifies 3-dimensional (3D) transthoracic echocardiography (TTE)-derived left atrial (LA) and left ventricular (LV) volumes and left ventricular ejection fraction (LVEF). Conventional manual 3D TTE tracings and cardiac magnetic resonance (CMR) images were used as a reference for comparison., Background: Cardiac chamber quantification from 3D TTE is superior to 2D TTE measurements. However, integration of 3D quantification into clinical practice has been limited by time-consuming workflow and the need for 3D expertise. A novel automated software was developed that provides LV and LA volumetric quantification from 3D TTE datasets that reflect real-life manual 3-dimensional echocardiography measurements and values comparable to CMR., Methods: A total of 159 patients were studied in 2 separate protocols. In protocol 1, 94 patients underwent 3D TTE imaging (EPIQ, iE33, X5-1, Philips Healthcare, Andover, Massachusetts) covering the left atrium and left ventricle. LA and LV volumes and LVEF were obtained using the automated software (HeartModel, Philips Healthcare) with and without contour correction, and compared with the averaged manual 3D volumetric measurements from 3 readers. In protocol 2, automated measurements from 65 patients were compared with a CMR reference. The Pearson correlation coefficient, Bland-Altman analysis, and paired Student t tests were used to assess inter-technique agreement., Results: Correlations between the automated and manual 3D TTE measurements were strong (r = 0.87 to 0.96). LVEF was underestimated and automated LV end-diastolic, LV end-systolic, and LA volumes were overestimated compared with manual measurements. Agreement between the automated analysis and CMR was also strong (r = 0.84 to 0.95). Test-retest variability was low., Conclusions: Automated simultaneous quantification of LA and LV volumes and LVEF is feasible and requires minimal 3D software analysis training. The automated measurements are not only comparable to manual measurements but also to CMR. This technique is highly reproducible and timesaving, and it therefore promises to facilitate the integration of 3D TTE-based left-heart chamber quantification into clinical practice., (Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Aims: Speckle tracking echocardiography has already demonstrated its clinical potential. However, its use in routine practice is jeopardized by recent reports on high inter-vendor variability of the measurements. As such, the European Association of CardioVascular Imaging (EACVI) and the American Society of Echocardiography (ASE) set up a standardization task force, which was joined by all manufacturers of echocardiographic equipment as well as by companies offering software solutions only, with the ambition to tackle this problem by standardization and quality assurance (QA)., Methods and Results: In this study, a first step towards QA of all commercially available tracking solutions based on computer-generated ultrasound images is presented. The accuracy of the products was acceptable with relative errors below 10% and intra-vendor reproducibility within 5%., Conclusion: Whether these results can be extrapolated to the clinical setting is the topic of an ongoing study of the EACVI/ASE/Industry Task Force to standardize deformation imaging. This study was an important first step in the development of generally accepted tools for QA of speckle tracking echocardiography., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.)

Respiratory inhalers constitute a large percentage of hospital pharmacy expenditures. Metered-dose inhaler (MDI) canisters usually contain enough medication to last 2 to 4 weeks, while the average hospital stay for acute hospitalizations of respiratory illnesses is only 4-5 days. Hospital pharmacies are often unable to operationalize relabeling of inhalers at discharge to meet regulatory requirements. This dilemma produces drug wastage. The common canister (CC) approach is a method some hospitals implemented in an effort to minimize the costs associated with this issue. The CC program uses a shared inhaler, an individual one-way valve holding chamber, and a cleaning protocol. This approach has been the subject of considerable controversy. Proponents of the CC approach reported considerable cost savings to their institutions. Opponents of the CC approach are not convinced the benefits outweigh even a minimal risk of cross-contamination since adherence to protocols for hand washing and disinfection of the MDI device cannot be guaranteed to be 100% (pathogens from contaminated devices can enter the respiratory tract through inhalation). Other cost containment strategies, such as unit dose nebulizers, may be useful to realize similar reductions in pharmacy drug costs while minimizing the risks of nosocomial infections and their associated medical costs. The CC strategy may be appropriate for some hospital pharmacies that face budget constraints, but a full evaluation of the risks, benefits, and potential costs should guide those who make hospital policy decisions.

Public health professionals face many challenges in infectious disease cluster case identification and partner notification (PN), especially in populations using social media as a primary communication venue. We present a method using Facebook and social network diagram illustration to identify, link, and notify individuals in a cluster of syphilis cases in young black men who have sex with men (MSM). Use of Facebook was crucial in identifying two of 55 individuals with syphilis, and the cooperation of socially connected individuals with traditional PN methods yielded a high number of contacts per case. Integration of PN services for HIV and sexually transmitted diseases, as well as collaboration between the city and state information systems, assisted in the cluster investigation. Given that rates of syphilis and HIV infection are increasing significantly in young African American MSM, the use of social media can provide an additional avenue to facilitate case identification and notification.

The World Organisation for Animal Health (OIE) Aquatic Animal Health Code recommends that programmes forthe monitoring and surveillance of antimicrobial resistance in microorganisms associated with aquatic animals be initiated by the appropriate authorities. This paper discusses the classes of bacteria to be studied in such programmes and the methods of sample collection to be employed. It also discusses the susceptibility test protocols appropriate for use in such programmes, the interpretive criteria that should be applied to the data they generate and the form in which the output of such programmes should be reported. The authors argue that it is essential that all monitoring and surveillance programmes should employ standardised and internationally harmonised susceptibility test methods to the greatest extent possible. With respect to bacteria capable of infecting aquatic animals, it is recommended that the set of consensus-based standards and guidelines published by the Clinical and Laboratory Standards Institute be adopted as the basis for international harmonisation of test protocols, as they are significantly more developed than any alternatives. It is further recommended that, for the purpose of evaluating antimicrobial resistance trends, such as emerging resistance, the data generated by these protocols should be interpreted by the application of epidemiological cut-off values. However, as yet, internationally agreed cut-off values have been produced for only one species. Thus, for many species, authorities will be obliged to set their own local and laboratory-specific cut-off values. It is recommended that laboratories use a statistical and standardised method of establishing such local cut-off values. Internationally harmonised standard test protocols and interpretive criteria have, to a large extent, been developed to monitor antimicrobial resistance in bacterial species capable of infecting humans. These methods can also be applied to microorganisms capable of infecting humans that are isolated from aquatic animals reared for human consumption or for sale as companion animals.

Purpose: The goals of this study were to optimize radiolabeling of renal lineages differentiated from human embryonic stem (hES) cells and use noninvasive imaging (positron emission tomography (PET) and bioluminescence imaging (BLI)) to detect the cells in fetal monkeys post-transplant., Procedures: hES cells expressing firefly luciferase (5 × 10(6)) were radiolabeled with the optimized concentration of 10 μCi/ml (64)Cu-PTSM then transplanted under ultrasound guidance into early second trimester fetal monkey kidneys. Fetuses were imaged in utero with PET and tissues collected for analysis 3 days post-transplant. Fetal kidneys were imaged ex vivo (PET and BLI) post-tissue harvest, and serial kidney sections were assessed by PCR for human-specific DNA sequences, fluorescent in situ hybridization (FISH) for human-specific centromere probes, and immunohistochemistry (IHC) to assess engrafted cells., Results: Transplanted cells were readily imaged in vivo and identified at the site of injection; tissue analyses confirmed the imaging findings. Using a semi-quantitative method, one in approximately 650 cells in the kidney was shown to be of human origin by PCR and FISH., Conclusions: These studies suggest that hES cells differentiated toward renal lineages can be effectively radiolabeled, transplanted into fetal monkey kidneys under ultrasound guidance, monitored with PET post-transplant, and identified by PET, BLI, PCR, FISH, and IHC post-tissue harvest.

Introduction: We have identified a novel hierarchy of human endothelial colony-forming cells (ECFCs) that are functionally defined by their proliferative and clonogenic potential and in vivo vessel-forming ability. The rhesus monkey provides an excellent model in which to examine the changes in circulating concentrations and functions of ECFCs since this nonhuman primate possesses a long lifespan and has been used extensively to model age-related processes that occur in humans., Results: Endothelial cells (ECs) derived from rhesus monkey ECFCs share a cell-surface phenotype similar to human cord blood ECFCs, rapidly form capillary-like structures in vitro, and form endothelial-lined vessels in vivo upon implantation in immunodeficient mice in an age-dependent manner. Of interest, although ECFCs from the oldest monkeys formed capillary-like structures in vitro, the cells failed to form inosculating vessels when implanted in vivo and displayed a deficiency in cytoplasmic vacuolation in vitro; a critical first step in vasculogenesis., Discussion: Utilizing previously established clonogenic assays for defining different subpopulations of human ECFCs, we have shown that a hierarchy of ECFCs, identical to human cells, can be isolated from the peripheral blood of rhesus monkeys, and that the frequency of the circulating cells varies with age. These studies establish the rhesus monkey as an important preclinical model for evaluating the role and function of circulating ECFCs in vascular homeostasis and aging., Methods: Peripheral blood samples were collected from 40 healthy rhesus monkeys from birth to 24 years of age for ECFC analysis including immunophenotyping, clonogenic assays, and in vivo vessel formation.

Circulating endothelial progenitor cells (EPCs) in adult human peripheral blood were originally identified in 1997 by Asahara et al., which challenged the paradigm that vasculogenesis is a process restricted to embryonic development. Since their original identification, EPCs have been extensively studied as biomarkers to assess the risk of cardiovascular disease in human subjects and as a potential cell therapeutic for vascular regeneration. Endothelial colony-forming cells (ECFCs), which are a subtype of EPCs, were recently identified from circulating adult and human umbilical cord blood. In contrast to other types of EPCs, which display various monocyte/macrophage phenotypes and functions, ECFCs are characterized by robust proliferative potential, secondary and tertiary colony formation upon replating, and de novo blood vessel formation in vivo when transplanted into immunodeficient mice. In this unit, we describe detailed methodologies for isolation and characterization of ECFCs from both human peripheral and umbilical cord blood.

Endothelial progenitor cells (EPCs) are used for angiogenic therapies and as biomarkers of cardiovascular disease. Human umbilical cord blood (UCB) is a rich source of endothelial colony forming cells (ECFCs), which are EPCs with robust proliferative potential that may be useful for clinical vascular regeneration. Previous studies show that hematopoietic progenitor cells are increased in premature UCB compared with term controls. Based on this paradigm, we hypothesized that premature UCB would be an enriched source of ECFCs. Thirty-nine UCB samples were obtained from premature infants (24-37 wk gestational age (GA)) and term controls. ECFC colonies were enumerated, clonally isolated, and identified by expression of endothelial cell surface antigens and functional analysis. GA of 33-36 wk UCB yielded predominantly ECFC colonies at equivalent numbers to term infants. UCB from 24 to 28 wk GA infants had significantly fewer ECFCs. Surprisingly, 24-28 wk GA UCB yielded predominantly mesenchymal stem cell (MSC) colonies, capable of differentiating into adipocytes, chondrocytes, and osteocytes. MSCs were rarely identified in 37-40 wk GA UCB. These studies demonstrate that circulating MSCs and ECFCs appear at different GA in the human UCB, and that 24-28 wk GA UCB may be a novel source of MSCs for therapeutic use in human diseases.

Objective: Endothelial progenitor cells (EPCs) are used for angiogenic therapies or as biomarkers to assess cardiovascular disease risk. However, there is no uniform definition of an EPC, which confounds EPC studies. EPCs are widely described as cells that coexpress the cell-surface antigens CD34, AC133, and vascular endothelial growth factor receptor-2 (VEGFR-2). These antigens are also expressed on primitive hematopoietic progenitor cells (HPCs). Remarkably, despite their original identification, CD34+AC133+VEGFR-2+ cells have never been isolated and simultaneously plated in hematopoietic and endothelial cell (EC) clonogenic assays to assess the identity of their clonal progeny, which are presumably the cellular participants in vascular regeneration., Methods: CD34+AC133+VEGFR-2+ cells were isolated from human umbilical cord blood (CB) or granulocyte colony-stimulating factor-mobilized peripheral blood and assayed for either EPCs or HPCs., Results: CD34+AC133+VEGFR-2+ cells did not form EPCs and were devoid of vessel forming activity. However, CD34+AC133+VEGFR-2+ cells formed HPCs and expressed the hematopoietic lineage-specific antigen, CD45. We next tested whether EPCs could be separated from HPCs by immunoselection for CD34 and CD45. CD34+CD45+ cells formed HPCs but not EPCs, while CD34+CD45- cells formed EPCs but not HPCs., Conclusions: Therefore, CD34+AC133+VEGFR-2+ cells are HPCs that do not yield EC progeny, and the biological mechanism for their correlation with cardiovascular disease needs to be reexamined.

The limited vessel-forming capacity of infused endothelial progenitor cells (EPCs) into patients with cardiovascular dysfunction may be related to a misunderstanding of the biologic potential of the cells. EPCs are generally identified by cell surface antigen expression or counting in a commercially available kit that identifies "endothelial cell colony-forming units" (CFU-ECs). However, the origin, proliferative potential, and differentiation capacity of CFU-ECs is controversial. In contrast, other EPCs with blood vessel-forming ability, termed endothelial colony-forming cells (ECFCs), have been isolated from human peripheral blood. We compared the function of CFU-ECs and ECFCs and determined that CFU-ECs are derived from the hematopoietic system using progenitor assays, and analysis of donor cells from polycythemia vera patients harboring a Janus kinase 2 V617F mutation in hematopoietic stem cell clones. Further, CFU-ECs possess myeloid progenitor cell activity, differentiate into phagocytic macrophages, and fail to form perfused vessels in vivo. In contrast, ECFCs are clonally distinct from CFU-ECs, display robust proliferative potential, and form perfused vessels in vivo. Thus, these studies establish that CFU-ECs are not EPCs and the role of these cells in angiogenesis must be re-examined prior to further clinical trials, whereas ECFCs may serve as a potential therapy for vascular regeneration.

The cytologic and histologic features of 2 intracranial and 2 spinal (extramedullary cervical) canine meningiomas were compared. Cerebrospinal fluid analysis in 2 cases revealed mild, mixed cell pleocytosis, primarily composed of small lymphocytes and monocytoid cells, with a moderate increase in total protein concentration. Cytologic features suggestive of meningioma included cells with both epithelial and mesenchymal characteristics and a tendency towards cell clustering. Tumor location also was useful in making a diagnosis. The 4 meningiomas differed histologically from one another, and included angioblastic, psammomatous, meningotheliomatous, and microcystic anaplastic types, which conformed to a classification scheme for human meningiomas. The classification scheme could not be applied to cytologic specimens.