A multidimensional framework for rating health system performance and sustainability: A nine plus one ranking system.

BACKGROUND: Health Care provision in terms of prevention, detection and treatment is primarily dependent on the quality of the hosting Health System. In its health report 2000, the WHO's attempt to assess and rank health systems' quality Worldwide was heavily criticized. We propose a novel framework for health system performance and ranking using three indicators for three domains; general health system performance, clinical outcome of treatment applied to the main causes of death and health system sustainability domains. METHODS: Each domain was rated as "A - high", "B - intermediate" or "C - poor" according to the aggregate score values of its three indicators. Hence the highest rank a health system can achieve is "AAA" and the lowest is "CCC". If there is a need to define a "numerical rank" to further differentiate health systems with similar rating from one another, the total health expenditure per capita per year was used as an additional "number 10" indicator to achieve that level of differentiation. The framework was applied to Health Systems serving most of the World population including China, India, Brazil, USA, Russia, Germany, Japan, UK, France, Singapore and Switzerland. Data pertinent to each indicator was captured from published reports in peer-reviewed journals and/or from official websites. A Delphi survey was conducted for data not available online. RESULTS: Among the 11 health systems tested, no one scored AAA, Switzerland, France, Germany and Japan scored AAB, Singapore scored ABB, UK scored BBB, USA, Russia and China scored BBC, Brazil scored BCC while India scored CCC. Total health expenditure per capita per year lead to ranking Switzerland first followed by France, Germany, and Japan. CONCLUSION: This novel ranking system is a practical and an applicable tool that test health system performance and sustainability. It can be utilized to guide all organizations, people and actions whose primary intent is to promote, restore or maintain health to achieve their targets. An International Health System Ranking database that will be hosted by the Institute of Global, Health, Faculty of Medicine, University of Geneva, Switzerland.

COVID-19 on the Nile: Review on the Management and Outcomes of the COVID-19 Pandemic in the Arab Republic of Egypt from February to August 2020.

As the world fights the coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the World Health Organization (WHO) reports that over 17 million people globally were infected with SARS-CoV-2 as of 1 August 2020. Although infections are asymptomatic in 80% of cases, severe respiratory illness occurs in 20% of cases, requiring hospitalization and highly specialized intensive care. The WHO, under the International Health Regulations, declared this pandemic a public health emergency of international concern; it has affected nearly all health systems worldwide. The health system in Egypt, similar to many others, was severely challenged when confronted with the need for urgent and major expansion required to manage such a significant pandemic. This review uses publicly available data to provide an epidemiological summary of the COVID-19 pandemic behavior during the first wave of the outbreak in Egypt. The article covers mathematical modeling predictions, Egypt's healthcare system, economic and social impacts of COVID-19, as well as national responses that were crucial to the initial containment of the pandemic. We observed how the government managed the outbreak by enhancing testing capacity, contact tracing, announcing public health and social measures (PHSMs), as well as allocating extra funds and human resources to contain SARS-COV-2. Prospectively, economic losses from major sources of revenues-tourism, travel, and trade-may be reflected in future timelines, as Egypt continues to control cases and loss of life from COVID-19. Overall, trends indicate that the spread of COVID-19 in Egypt was initially contained. Revalidation of prediction models and follow-up studies may reveal the aftermath of the pandemic and how well it was managed in Egypt.

Consultation on the Libyan health systems: towards patient-centred services.

The extra demand imposed upon the Libyan health services during and after the Libyan revolution in 2011 led the ailing health systems to collapse. To start the planning process to re-engineer the health sector, the Libyan Ministry of Health in collaboration with the World Health Organisation (WHO) and other international experts in the field sponsored the National Health Systems Conference in Tripoli, Libya, between the 26th and the 30th of August 2012. The aim of this conference was to study how health systems function at the international arena and to facilitate a consultative process between 500 Libyan health experts in order to identify the problems within the Libyan health system and propose potential solutions. The scientific programme adopted the WHO health care system framework and used its six system building blocks: i) Health Governance; ii) Health Care Finance; iii) Health Service Delivery; iv) Human Resources for Health; v) Pharmaceuticals and Health Technology; and vi) Health Information System. The experts used a structured approach starting with clarifying the concepts, evaluating the current status of that health system block in Libya, thereby identifying the strengths, weaknesses, and major deficiencies. This article summarises the 500 health expert recommendations that seized the opportunity to map a modern health systems to take the Libyan health sector into the 21st century.

Management-oriented classification of mitral valve regurgitation.

Mitral regurgitation (MR) has previously been classified into rheumatic, primary, and secondary MR according to the underlying disease process. Carpentier's/Duran functional classifications are apt in describing the mechanism(s) of MR. Modern management of MR, however, depends primarily on the severity of MR, status of the left ventricular function, and the presence or absence of symptoms, hence the need for a management-oriented classification of MR. In this paper we describe a classification of MR into 4 phases according to LV function: phase I = MR with normal left ventricle, phase II = MR with normal ejection fraction (EF) and indirect signs of LV dysfunction such as pulmonary hypertension and/or recent onset atrial fibrillation, phase III = EF ≥ 30%-< 50% and/or mild to moderate LV dilatation (ESID 40-54 mm), and phase IV = EF < 30% and/or severe LV dilatation (ESDID ≥ 55 mm). Each phase is further subdivided into three stages: stage "A" with an effective regurgitant orifice (ERO) < 20 mm, stage "B" with an ERO = 20-39 mm, and stage "C" with an ERO ≥ 40 mm. Evidence-based indications and outcome of intervention for MR will also be discussed.

Exosome secreted by MSC reduces myocardial ischemia/reperfusion injury.

Human ESC-derived mesenchymal stem cell (MSC)-conditioned medium (CM) was previously shown to mediate cardioprotection during myocardial ischemia/reperfusion injury through large complexes of 50-100 nm. Here we show that these MSCs secreted 50- to 100-nm particles. These particles could be visualized by electron microscopy and were shown to be phospholipid vesicles consisting of cholesterol, sphingomyelin, and phosphatidylcholine. They contained coimmunoprecipitating exosome-associated proteins, e.g., CD81, CD9, and Alix. These particles were purified as a homogeneous population of particles with a hydrodynamic radius of 55-65 nm by size-exclusion fractionation on a HPLC. Together these observations indicated that these particles are exosomes. These purified exosomes reduced infarct size in a mouse model of myocardial ischemia/reperfusion injury. Therefore, MSC mediated its cardioprotective paracrine effect by secreting exosomes. This novel role of exosomes highlights a new perspective into intercellular mediation of tissue injury and repair, and engenders novel approaches to the development of biologics for tissue repair.

Derivation and characterization of human fetal MSCs: an alternative cell source for large-scale production of cardioprotective microparticles.

The therapeutic effects of mesenchymal stem cells (MSCs) transplantation are increasingly thought to be mediated by MSC secretion. We have previously demonstrated that human ESC-derived MSCs (hESC-MSCs) produce cardioprotective microparticles in pig model of myocardial ischemia/reperfusion (MI/R) injury. As the safety and availability of clinical grade human ESCs remain a concern, MSCs from fetal tissue sources were evaluated as alternatives. Here we derived five MSC cultures from limb, kidney and liver tissues of three first trimester aborted fetuses and like our previously described hESC-derived MSCs; they were highly expandable and had similar telomerase activities. Each line has the potential to generate at least 10(16-19) cells or 10(7-10) doses of cardioprotective secretion for a pig model of MI/R injury. Unlike previously described fetal MSCs, they did not express pluripotency-associated markers such as Oct4, Nanog or Tra1-60. They displayed a typical MSC surface antigen profile and differentiated into adipocytes, osteocytes and chondrocytes in vitro. Global gene expression analysis by microarray and qRT-PCR revealed a typical MSC gene expression profile that was highly correlated among the five fetal MSC cultures and with that of hESC-MSCs (r(2)>0.90). Like hESC-MSCs, they produced secretion that was cardioprotective in a mouse model of MI/R injury. HPLC analysis of the secretion revealed the presence of a population of microparticles with a hydrodynamic radius of 50-65 nm. This purified population of microparticles was cardioprotective at approximately 1/10 dosage of the crude secretion.

Extended application of percutaneous pulmonary valve implantation.

OBJECTIVES: This study was designed to report a novel indication for percutaneous pulmonary valve implantation in patients with previous right ventricular outflow tract (RVOT) patch. BACKGROUND: Current indications for percutaneous pulmonary valve implantation are limited to patients who had pulmonary valve stenosis and/or regurgitation in a right ventricle-to-pulmonary artery conduit. Percutaneous pulmonary valve implantation has not been previously reported in patients with severe pulmonary valve regurgitation following repair of tetralogy of Fallot (TOF) using RVOT patch. METHODS: After assessment of the RVOT patch in multiple projections, a catheter was placed in a distal pulmonary artery branch. In patients with an RVOT patch, sizing of the narrowest diameter of the RVOT patch by manual inflation of a sizing balloon was performed; a stent was placed into the RVOT patch at the level of the narrowest area to anchor the stent and to create an artificial conduit to place the Melody valve. The percutaneous valve was then implanted. RESULTS: Seven females and 6 males with a mean age of 14.3 years and mean body weight 45 kg had successful percutaneous implantation of the Melody valve. Four patients had previous repair of TOF using RVOT patch. All patients were discharged within 2 days after the procedure without complications. After a mean of 4 months follow-up all patients were alive and well. Transthoracic echocardiography showed competent pulmonary valve. Chest X-ray showed no stent migration or fracture. CONCLUSIONS: Percutaneous pulmonary valve implantation can be performed in patients with pulmonary valve regurgitation, including those with previous RVOT patch using pre-stenting techniques, with satisfactory results.

Late complex biventricular repair after bidirectional cavopulmonary shunt.

A child diagnosed with transposition of great arteries, multiple (Swiss cheese) ventricular septal defects, and a small right ventricle underwent pulmonary artery banding and patent ductus arteriosus ligation at the age of six months. At the age of three years bidirectional cavopulmonary shunt was performed as a first stage for univentricular repair. However, the patient was lost follow-up for four years, following which further evaluation showed that the right ventricle was reasonably adequate to support pulmonary circulation if the ventricular septal defects (VSDs) were closed using percutaneous techniques. Four VSDs were then closed using Amplatzer devices (AGA Medical Corporation, Plymouth, MN, USA). At the age of eight years she underwent complex biventricular repair in the form of arterial switch, closure of atrial septal defect, take down of Glenn shunt, and reanastomosis of the distal end of the superior vena cava to the distal superior vena cava stump on the right atrium. One year later the patient is alive and well. In conclusion; biventricular repair may be considered before completion of Fontan whenever cardiac anatomy allows.

Minimally invasive transventricular implantation of pulmonary xenograft.

Minimally invasive valve replacement is now a clinical reality. A number of ingenious techniques have been described for percutaneous aortic and pulmonary valve replacement as well as transventricular aortic valve replacement. We describe a technique for transventricular pulmonary valve replacement utilizing off-the-shelf bovine tissue valve, vascular stents, and simplified delivery system. After median sternotomy with limited exposure of the right ventricle, Contegra 200 pulmonary valve (Medtronic, Inc., Minneapolis, MN, USA) is transfixed inside a CP stent (NuMed, Inc., Hopkinton, NY, USA) using multiple 5/0 prolene sutures. The valve/stent composite is crimped on a Cristal balloon catheter (Balt, Montmorency, France). The valve/stent and the balloon are then introduced via a small purse-string placed at the RVOT. The stent/valve composite is then expanded in the pulmonary valve position.

Severity scoring system for ventricular septal defect.

INTRODUCTION: Residual ventricular septal defect (RVSD) occurs in one-third of patients undergoing patch closure of congenital VSD. Indications for re-intervention are often based on either patient's symptoms or echocardiographic or hemodynamic studies. We report a novel scoring system for RVSD that takes into account all of the above criteria. METHODS: RVSD size, Qp:Qs ratio, RV to LV pressure ratio, and heart failure symptoms are scored as follows: (A) RVSD size is subdivided into three categories: <3 mm, 3 to <4 mm, and >/=4 mm; (B) Qp:Qs ratio is also subdivided into three categories: <1.5, 1.5 to <2, and >/=2.0; (C) The right and left ventricular pressure ratio is subdivided into the following: <0.5, 0.5 to <0.75, and >/=0.75; (D) Heart failure symptoms are subdivided into three categories: NYHA class II/III, NYHA class IV, and pulmonary edema requiring assisted ventilation. Each of these categories is given a score value of one (less severe), two (intermediate severity), and three (severe). Intra-operative severity score of RVSD is calculated by adding the total score of A, B, and C. For post-operative RVSD severity, the score values of A, B, C, and D are added. According to the total score, the clinical significance of an intra-operative RVSD is then defined as mild, moderate, or severe for a score of /=6, respectively. Similarly, post-operative RVSD is then labeled as mild, moderate, or severe for a score of /=8, respectively. CONCLUSION: From our experience and review of literature, severe RVSD (and moderate VSD post Tetrology of Fallot (TOF) repair) require immediate closure of RVSD. Other patients with mild or moderate RVSD need close follow-up with a repeat of transesophageal echocardiography (TEE) before discharge, and six months after surgery. This scoring system, however, needs further prospective evaluation to assess its potential role in decision-making in the management of RVSD.

Contractile and vasorelaxant effects of hydrogen sulfide and its biosynthesis in the human internal mammary artery.

This study aimed to test these hypotheses: cystathionine gamma-lyase (CSE) is expressed in a human artery, it generates hydrogen sulfide (H(2)S), and H(2)S relaxes a human artery. H(2)S is produced endogenously in rat arteries from cysteine by CSE. Endogenously produced H(2)S dilates rat resistance arteries. Although CSE is expressed in rat arteries, its presence in human blood vessels has not been described. In this study, we showed that both CSE mRNA, determined by reverse transcription-polymerase chain reaction, and CSE protein, determined by Western blotting, apparently occur in the human internal mammary artery (internal thoracic artery). Artery homogenates converted cysteine to H(2)S, and the H(2)S production was inhibited by dl-propargylglycine, an inhibitor of CSE. We also showed that H(2)S relaxes phenylephrine-precontracted human internal mammary artery at higher concentrations but produces contraction at low concentrations. The latter contractions are stronger in acetylcholine-prerelaxed arteries, suggesting inhibition of nitric oxide action. The relaxation is partially blocked by glibenclamide, an inhibitor of K(ATP) channels. The present results indicate that CSE protein is expressed in human arteries, that human arteries synthesize H(2)S, and that higher concentrations of H(2)S relax human arteries, in part by opening K(ATP) channels. Low concentrations of H(2)S contract the human internal mammary artery, possibly by reacting with nitric oxide to form an inactive nitrosothiol. The possibility that CSE, and the H(2)S it generates, together play a physiological role in regulating the diameter of arteries in humans, as has been demonstrated in rats, should be considered.

PI3 K/Akt/mTOR-mediated translational control regulates proliferation and differentiation of lineage-restricted RoSH stem cell lines.

BACKGROUND: We have previously derived highly similar lineage-restricted stem cell lines, RoSH and E-RoSH cell lines from mouse embryos and CD9hi SSEA-1- differentiated mouse embryonic stem cells, respectively. These cell lines are not pluripotent and differentiate readily into endothelial cells in vitro and in vivo. RESULTS: We investigated the signaling pathway that maintains proliferation of these cells in an undifferentiated state, and demonstrate that PI3 K/Akt/mTOR, but not Raf/MEK/Erk, signaling in these cells was active during proliferation and was downregulated during endothelial differentiation. Inhibition of PI3 K/Akt/mTOR signaling, but not Raf/MEK/Erk, reduced proliferation and induced expression of endothelial specific proteins. During differentiation or inhibition of PI3 K/Akt/mTOR signaling, cyclinD2 transcript abundance in ribosome-enriched RNA but not in total RNA was reduced with a corresponding reduction in protein level. In contrast, transcript abundance of endothelial-specific genes e.g. Kdr, Tek and Pdgfralpha in ribosome-enriched RNA fraction was not reduced and their protein levels were increased. Together these observations suggested that translational control mediated by PI3K/Akt/mTOR signaling was critical in regulating proliferation and endothelial differentiation of lineage-restricted RoSH-like stem cell lines. CONCLUSION: This study highlights translation regulation as a critical regulatory mechanism during proliferation and differentiation in stem cells.

Elucidating the secretion proteome of human embryonic stem cell-derived mesenchymal stem cells.

Transplantation of mesenchymal stem cells (MSCs) has been used to treat a wide range of diseases, and the mechanism of action is postulated to be mediated by either differentiation into functional reparative cells that replace injured tissues or secretion of paracrine factors that promote tissue repair. To complement earlier studies that identified some of the paracrine factors, we profiled the paracrine proteome to better assess the relevance of MSC paracrine factors to the wide spectrum of MSC-mediated therapeutic effects. To evaluate the therapeutic potential of the MSC paracrine proteome, a chemically defined serum-free culture medium was conditioned by MSCs derived from human embryonic stem cells using a clinically compliant protocol. The conditioned medium was analyzed by multidimensional protein identification technology and cytokine antibody array analysis and revealed the presence of 201 unique gene products. 86-88% of these gene products had detectable transcript levels by microarray or quantitative RT-PCR assays. Computational analysis predicted that these gene products will significantly drive three major groups of biological processes: metabolism, defense response, and tissue differentiation including vascularization, hematopoiesis, and skeletal development. It also predicted that the 201 gene products activate important signaling pathways in cardiovascular biology, bone development, and hematopoiesis such as Jak-STAT, MAPK, Toll-like receptor, transforming growth factor-beta, and mTOR (mammalian target of rapamycin) signaling pathways. This study identified a large number of MSC secretory products that have the potential to act as paracrine modulators of tissue repair and replacement in diseases of the cardiovascular, hematopoietic, and skeletal tissues. Moreover our results suggest that human embryonic stem cell-derived MSC-conditioned medium has the potency to treat a variety of diseases in humans without cell transplantation.

Total arterial coronary revascularization using arterial bypass circle with multiple inflows.

Coronary artery bypass techniques, currently applied to maximize the benefits of multiple arterial coronary conduits, render the newly constructed myocardial flow dependent on a single source "inflow" of blood. We describe a technique for total arterial coronary revascularization with multiple inflows; the distal end of the pedicled right internal thoracic artery is anastomosed to the distal end of a free radial artery, and the other end of the radial artery is then connected to the ascending aorta. This vascular circle, passed in a retro-cardiac fashion, is used to revascularize the inferio-lateral surface of the heart using multiple side-to-side anastomoses. The "sacred" left internal thoracic artery is reserved to revascularize the anterior wall of the myocardium, independent of the arterial circle.

Derivation of clinically compliant MSCs from CD105+, CD24- differentiated human ESCs.

Adult tissue-derived mesenchymal stem cells (MSCs) have demonstrated therapeutic efficacy in treating diseases or repairing damaged tissues through mechanisms thought to be mediated by either cell replacement or secretion of paracrine factors. Characterized, self-renewing human ESCs could potentially be an invariable source of consistently uniform MSCs for therapeutic applications. Here we describe a clinically relevant and reproducible manner of generating identical batches of hESC-derived MSC (hESC-MSC) cultures that circumvents exposure to virus, mouse cells, or serum. Trypsinization and propagation of HuES9 or H1 hESCs in feeder- and serum-free selection media generated three polyclonal, karyotypically stable, and phenotypically MSC-like cultures that do not express pluripotency-associated markers but displayed MSC-like surface antigens and gene expression profile. They differentiate into adipocytes, osteocytes, and chondrocytes in vitro. Gene expression and fluorescence-activated cell sorter analysis identified CD105 and CD24 as highly expressed antigens on hESC-MSCs and hESCs, respectively. CD105+, CD24- monoclonal isolates have a typical MSC gene expression profiles and were identical to each other with a highly correlated gene expression profile (r(2) > .90). We have developed a protocol to reproducibly generate clinically compliant and identical hESC-MSC cultures.

Reduction of myocardial infarct size by human mesenchymal stem cell conditioned medium.

Although paracrine effects of mesenchymal stem cells (MSCs) have been suggested previously, cardioprotection by human MSC secretions has never been demonstrated. Human MSC-conditioned medium (CM) was collected by following a clinically compliant protocol. In a porcine model of ischemia and reperfusion injury, intravenous and intracoronary MSC-CM treatment significantly reduced myocardial nuclear oxidative stress as determined by immunostaining for 8-hydroxy-2'-deoxyguanosine. In addition, expression levels of phospho-SMAD2 and active caspase 3 were diminished following CM treatment, suggesting that TGF-beta signaling and apoptosis were reduced. This was associated with a 60% reduction in infarct size and marked improvement of systolic and diastolic cardiac performance as assessed with echocardiography and pressure volume loops. Fractionation studies revealed that only the fraction of the CM containing products >1000 kDa (100-220 nm) provided cardioprotection in a mouse model of ischemia and reperfusion injury. This indicates that the responsible paracrine factor of human MSCs is likely a large complex rather than a single small molecule. These data identify human MSC-CM as a promising therapeutic option to reduce myocardial infarct size in patients with acute MI and suggest that the use of stem cell secretions could extend the applicability of stem cells for therapeutic purposes.