Directional Endothelial Communication by Polarized Extracellular Vesicle Release.

BACKGROUND: Extracellular vesicles (EVs) contain bioactive cargo including miRNAs and proteins that are released by cells during cell-cell communication. Endothelial cells (ECs) form the innermost lining of all blood vessels, interfacing with cells in the circulation and vascular wall. It is unknown whether ECs release EVs capable of governing recipient cells within these 2 separate compartments. Given their boundary location, we propose ECs use bidirectional release of distinct EV cargo in quiescent (healthy) and activated (atheroprone) states to communicate with cells within the circulation and blood vessel wall. METHODS: EVs were isolated from primary human aortic ECs (plate and transwell grown; ±IL [interleukin]-1ß activation), quantified, visualized, and analyzed by miRNA transcriptomics and proteomics. Apical and basolateral EC-EV release was determined by miRNA transfer, total internal reflection fluorescence and electron microscopy. Vascular reprogramming (RNA sequencing) and functional assays were performed on primary human monocytes or smooth muscle cells±EC-EVs. RESULTS: Activated ECs increased EV release, with miRNA and protein cargo related to atherosclerosis. EV-treated monocytes and smooth muscle cells revealed activated EC-EV altered pathways that were proinflammatory and atherogenic. ECs released more EVs apically, which increased with activation. Apical and basolateral EV cargo contained distinct transcriptomes and proteomes that were altered by EC activation. Notably, activated basolateral EC-EVs displayed greater changes in the EV secretome, with pathways specific to atherosclerosis. In silico analysis determined compartment-specific cargo released by the apical and basolateral surfaces of ECs can reprogram monocytes and smooth muscle cells, respectively, with functional assays and in vivo imaging supporting this concept. CONCLUSIONS: Demonstrating that ECs are capable of polarized EV cargo loading and directional EV secretion reveals a novel paradigm for endothelial communication, which may ultimately enhance the design of endothelial-based therapeutics for cardiovascular diseases such as atherosclerosis where ECs are persistently activated.

Endothelial ACKR1 is induced by neutrophil contact and down-regulated by secretion in extracellular vesicles.

Atypical chemokine receptor-1 (ACKR1), previously known as the Duffy antigen receptor for chemokines, is a widely conserved cell surface protein that is expressed on erythrocytes and the endothelium of post-capillary venules. In addition to being the receptor for the parasite causing malaria, ACKR1 has been postulated to regulate innate immunity by displaying and trafficking chemokines. Intriguingly, a common mutation in its promoter leads to loss of the erythrocyte protein but leaves endothelial expression unaffected. Study of endothelial ACKR1 has been limited by the rapid down-regulation of both transcript and protein when endothelial cells are extracted and cultured from tissue. Thus, to date the study of endothelial ACKR1 has been limited to heterologous over-expression models or the use of transgenic mice. Here we report that exposure to whole blood induces ACKR1 mRNA and protein expression in cultured primary human lung microvascular endothelial cells. We found that contact with neutrophils is required for this effect. We show that NF-κB regulates ACKR1 expression and that upon removal of blood, the protein is rapidly secreted by extracellular vesicles. Finally, we confirm that endogenous ACKR1 does not signal upon stimulation with IL-8 or CXCL1. Our observations define a simple method for inducing endogenous endothelial ACKR1 protein that will facilitate further functional studies.

Endothelial cells secrete small extracellular vesicles bidirectionally containing distinct cargo to uniquely reprogram vascular cells in the circulation and vessel wall.

Rationale: Extracellular vesicles (EVs) contain bioactive cargo including microRNAs (miRNAs) and proteins that are released by cells as a form of cell-cell communication. Endothelial cells (ECs) form the innermost lining of all blood vessels and thereby interface with cells in the circulation as well as cells residing in the vascular wall. It is unknown whether ECs have the capacity to release EVs capable of governing recipient cells within two separate compartments, and how this is affected by endothelial activation commonly seen in atheroprone regions. Objective: Given their boundary location, we propose that ECs utilize bidirectional release of distinct EV cargo in quiescent and activated states to communicate with cells within the circulation and blood vessel wall. Methods and Results: EVs were isolated from primary human aortic endothelial cells (ECs) (+/-IL-1ß activation), quantified, and analysed by miRNA transcriptomics and proteomics. Compared to quiescent ECs, activated ECs increased EV release, with miRNA and protein cargo that were related to atherosclerosis. RNA sequencing of EV-treated monocytes and smooth muscle cells (SMCs) revealed that EVs from activated ECs altered pathways that were pro-inflammatory and atherogenic. Apical and basolateral EV release was assessed using ECs on transwells. ECs released more EVs apically, which increased with activation. Apical and basolateral EV cargo contained distinct transcriptomes and proteomes that were altered by EC activation. Notably, basolateral EC-EVs displayed greater changes in the EV secretome, with pathways specific to atherosclerosis. In silico analysis determined that compartment-specific cargo released by the apical and basolateral surfaces of ECs can reprogram monocytes and SMCs, respectively. Conclusions: The demonstration that ECs are capable of polarized EV cargo loading and directional EV secretion reveals a novel paradigm for endothelial communication, which may ultimately enhance our ability to design endothelial-based therapeutics for cardiovascular diseases such as atherosclerosis where ECs are persistently activated.

MiR-30 promotes fatty acid beta-oxidation and endothelial cell dysfunction and is a circulating biomarker of coronary microvascular dysfunction in pre-clinical models of diabetes.

BACKGROUND: Type 2 diabetes (T2D) is associated with coronary microvascular dysfunction, which is thought to contribute to compromised diastolic function, ultimately culminating in heart failure with preserved ejection fraction (HFpEF). The molecular mechanisms remain incompletely understood, and no early diagnostics are available. We sought to gain insight into biomarkers and potential mechanisms of microvascular dysfunction in obese mouse (db/db) and lean rat (Goto-Kakizaki) pre-clinical models of T2D-associated diastolic dysfunction. METHODS: The microRNA (miRNA) content of circulating extracellular vesicles (EVs) was assessed in T2D models to identify biomarkers of coronary microvascular dysfunction/rarefaction. The potential source of circulating EV-encapsulated miRNAs was determined, and the mechanisms of induction and the function of candidate miRNAs were assessed in endothelial cells (ECs). RESULTS: We found an increase in miR-30d-5p and miR-30e-5p in circulating EVs that coincided with indices of coronary microvascular EC dysfunction (i.e., markers of oxidative stress, DNA damage/senescence) and rarefaction, and preceded echocardiographic evidence of diastolic dysfunction. These miRNAs may serve as biomarkers of coronary microvascular dysfunction as they are upregulated in ECs of the left ventricle of the heart, but not other organs, in db/db mice. Furthermore, the miR-30 family is secreted in EVs from senescent ECs in culture, and ECs with senescent-like characteristics are present in the db/db heart. Assessment of miR-30 target pathways revealed a network of genes involved in fatty acid biosynthesis and metabolism. Over-expression of miR-30e in cultured ECs increased fatty acid ß-oxidation and the production of reactive oxygen species and lipid peroxidation, while inhibiting the miR-30 family decreased fatty acid ß-oxidation. Additionally, miR-30e over-expression synergized with fatty acid exposure to down-regulate the expression of eNOS, a key regulator of microvascular and cardiomyocyte function. Finally, knock-down of the miR-30 family in db/db mice decreased markers of oxidative stress and DNA damage/senescence in the microvascular endothelium. CONCLUSIONS: MiR-30d/e represent early biomarkers and potential therapeutic targets that are indicative of the development of diastolic dysfunction and may reflect altered EC fatty acid metabolism and microvascular dysfunction in the diabetic heart.

Endovascular repair of abdominal aortic aneurysm in octogenarians: clinical outcomes and complications.

Background: Endovascular aneurysm repair (EVAR) is associated with decreased perioperative morbidity and mortaliy in comparison with open repair, and thus octagenarians are traditionally offered EVAR given their age and medical comorbidities. The aim of this study was to investigate outcomes and predictors of complications associated with EVAR in octogenarians. Methods: We conducted a retrospective chart review of consecutive patients aged 80 years and older who received an EVAR between August 2010 and January 2017 at a single centre in Toronto, Ontario. We conducted univariate comparisons and then completed logistic regression to determine predictors of complications. We used Kaplan-Meier analysis to explore survival times. Results: A total of 154 octogenarians underwent an EVAR during the study period for an infrarenal aneurysm with a mean size of 64.8 (standard deviation [SD] 12.7) mm. The mean age of the patients was 84.1 (SD 3.7) years, and most patients (81%) were men. Eighteen patients presented with a ruptured abdominal aortic aneurysm (AAA). Ninety-five (62%) patients sustained a complication. Fifty percent of patients experienced an intraoperative complication. A majority of these (77%) resulted in an endoleak, with type II endoleaks requiring no further intervenion being the most common (58%, n = 45). The remaining complications (n = 70) occurred postoperatively, with myocardial ischemia (n = 24) and dysrhythmias (n = 10) being the most common. Past aortic surgery (χ2 = 8.62, p = 0.014, Cramer V = 0.27) was found to be a multivariate predictor of complications. Most patients (88%) continued follow-up to an average of 20.9 months. Twenty-one patients (13%) died. Nine of these deaths (43%) occurred during the index admission and involved a ruptured AAA. Past aortic surgery was the only predictor of vascular complications. The mean survival time after EVAR was 57.63 months for patients without events. Conclusion: Endovascular aneurysm repair in octogenarians is a suitable form of therapy with acceptable short- and long-term results in the elective setting. Past aortic surgery was a predictor of complications in this population.

Contexte: La réparation endovasculaire de l'anévrisme (REVA) est associée à une diminution de la morbidité et de la mortalité périopératoires comparativement à la chirurgie ouverte, c'est pourquoi on offre habituellement la REVA aux octogénaires, compte tenu de leur âge et de leurs comorbidités. Le but de cette étude était d'analyser l'issue de la REVA et les prédicteurs de complications chez les octogénaires. Méthodes: Nous avons procédé à une analyse rétrospective des dossiers de patients de 80 ans et plus consécutifs soumis à une REVA entre août 2010 et janvier 2017 dans un établissement de Toronto, en Ontario. Nous avons effectué des comparaisons univariées, puis une analyse de régression logistique pour dégager les prédicteurs de complications. C'est l'analyse de Kaplan­Meier qui a permis d'explorer la survie. Résultats: En tout, pendant la période de l'étude, 154 octogénaires ont subi une REVA pour un anévrisme infrarénal dont la dimension moyenne était de 64,8 mm (écart-type [É.-T.] 12,7 mm). L'âge moyen des patients était de 84,1 ans (É.-T. 3,7 ans) et la majorité des patients (81 %) étaient des hommes. Dix-huit patients ont présenté une rupture d'anévrisme de l'aorte abdominale (AAA). Quatre-vingt-quinze patients (62 %) ont connu une complication. Cinquante pour cent des patients ont eu une complication peropératoire. Une majorité des complications (77 %) ont causé des endofuites, le plus fréquemment de type II, ne nécessitant pas d'autres interventions (58 %, n = 45). Les autres complications (n = 70) sont survenues en période postopératoire et les plus fréquentes ont été l'ischémie myocardique (n = 24) et la dysrythmie (n = 10). Des antécédents de chirurgie à l'aorte (χ2 = 8,62, p = 0,014, test V de Cramer = 0,27) se sont révélés être un prédicteur multivarié de complications. La plupart des patients (88 %) ont maintenu le suivi pendant une durée moyenne de 20,9 mois. Vingt-et-un patients (13 %) sont décédés. Neuf de ces décès (43 %) se sont produits pendant l'admission index et impliquaient une rupture de l'AAA. Des antécédents de chirurgie à l'aorte ont été le seul prédicteur des complications vasculaires. La survie moyenne après la REVA a été de 57,63 mois pour les patients n'ayant présenté aucune complication. Conclusion: La REVA est une forme de traitement qui convient aux octogénaires et qui donne des résultats acceptables à court et à long terme dans un contexte de chirurgie non urgente. Des antécédents de chirurgie à l'aorte se sont révélés être un prédicteur de complications dans cette population.

Overcoming Barriers: The Endothelium As a Linchpin of Coronavirus Disease 2019 Pathogenesis?

OBJECTIVE: Coronavirus disease 2019 (COVID-19) is a global pandemic involving >5 500 000 cases worldwide as of May 26, 2020. The culprit is the severe acute respiratory syndrome coronavirus-2, which invades cells by binding to ACE2 (angiotensin-converting enzyme 2). While the majority of patients mount an appropriate antiviral response and recover at home, others progress to respiratory distress requiring hospital admission for supplemental oxygen. In severe cases, deterioration to acute respiratory distress syndrome necessitating mechanical ventilation, development of severe thrombotic events, or cardiac injury and dysfunction occurs. In this review, we highlight what is known to date about COVID-19 and cardiovascular risk, focusing in on the putative role of the endothelium in disease susceptibility and pathogenesis. Approach and Results: Cytokine-driven vascular leak in the lung alveolar-endothelial interface facilitates acute lung injury in the setting of viral infection. Given that the virus affects multiple organs, including the heart, it likely gains access into systemic circulation by infecting or passing from the respiratory epithelium to the endothelium for viral dissemination. Indeed, cardiovascular complications of COVID-19 are highly prevalent and include acute cardiac injury, myocarditis, and a hypercoagulable state, all of which may be influenced by altered endothelial function. Notably, the disease course is worse in individuals with preexisting comorbidities that involve endothelial dysfunction and may be linked to elevated ACE2 expression, such as diabetes mellitus, hypertension, and cardiovascular disease. CONCLUSIONS: Rapidly emerging data on COVID-19, together with results from studies on severe acute respiratory syndrome coronavirus-1, are providing insight into how endothelial dysfunction may contribute to the pandemic that is paralyzing the globe. This may, in turn, inform the design of biomarkers predictive of disease course, as well as therapeutics targeting pathogenic endothelial responses.

MicroRNAs as sentinels and protagonists of carotid artery thromboembolism.

Stroke is the leading cause of serious disability in the world and a large number of ischemic strokes are due to thromboembolism from unstable carotid artery atherosclerotic plaque. As it is difficult to predict plaque rupture and surgical treatment of asymptomatic disease carries a risk of stroke, carotid disease continues to present major challenges with regard to clinical decision-making and revascularization. There is therefore an imminent need to better understand the molecular mechanisms governing plaque instability and rupture, as this would allow for the development of biomarkers to identify at-risk asymptomatic carotid plaque prior to disease progression and stroke. Further, it would aid in creation of therapeutics to stabilize carotid plaque. MicroRNAs (miRNAs) have been implicated as key protagonists in various stages of atherosclerotic plaque initiation, development and rupture. Notably, they appear to play a crucial role in carotid artery thromboembolism. As the molecular pathways governing the role of miRNAs are being uncovered, we are learning that their involvement is complex, tissue- and stage-specific, and highly selective. Notably, miRNAs can be packaged and secreted in extracellular vesicles (EVs), where they participate in cell-cell communication. The measurement of EV-encapsulated miRNAs in the circulation may inform disease mechanisms occurring in the plaque itself, and therefore may serve as sentinels of unstable plaque as well as therapeutic targets.

Vascular Complications and Procedures Following Transcatheter Aortic Valve Implantation.

OBJECTIVES: Vascular complications (VCs) remain a significant cause of morbidity in transcatheter aortic valve implantation (TAVI) patients and are associated with worse outcomes. This research analysed the incidence, impact, and predictors of VCs in transfemoral cases. METHODS: A retrospective chart review was performed of 388 consecutive TAVI patients between January 2007 and April 2015, which included 237 transfemoral cases. Major and minor VCs were characterised according to the Valve Academic Research Consortium (VARC) guidelines. Logistic regression was completed to identify predictors of VCs. RESULTS: While VCs occurred in 68 (28.7%) cases, only seven (3.38%) were classified as major complications. Twenty-six (10.9%) of these complications occurred intra-operatively, with four being major (1.6%) and 22 minor (9.3%). Post-operative VCs occurred in 42 cases (17.2%), with three (1.3%) being major. Procedures to correct VCs occurred in 10 (4.2%) cases, with the majority (90%) being surgical and the remainder being treated by endovascular techniques. Nine surgical procedures, predominantly embolectomy, were performed to correct post-operative complications. Female gender was a predictor of all major VCs (B = -2.1, p < .006). Further, a logistic regression analysis found that when the largest sheath was located on the left side, there were increased minor post-operative complications (B = -0.99, p = .007). Dissections and haematomas made up the majority of VCs. Thirty day mortality was six patients (n = 2.5%), and peri-operative VCs were significantly correlated with 30 day mortality (p = .001, R = 0.21). The 30 day readmission rate comprised nine patients (3.8%), with three (1.3%) due to VCs, including haematomas and groin infections. CONCLUSIONS: VCs contribute to operative morbidity in TAVI patients. This study demonstrated low major VC rates over an eight year period. Left sided location of largest sheath size and female gender were predictors of VC.

Development of a cumulative teaching score for tracking surgeon performance in undergraduate medical education

Background: Surgeon educators are important in undergraduate medical education (UME). However, teaching activities are undervalued and under-recognized compared with research, resulting in poorer quantity and quality of surgeon teaching. The purpose of this study was to investigate teaching roles available to surgeons and the amount of effort involved. Methods: A comprehensive review of all possible roles surgeons may take in UME at our institution was assembled. Delphi committee members were asked to evaluate each teaching role on the amount of effort needed per hour. Results were analyzed using descriptive statistics, and a Cronbach α of 0.60 or higher was the threshold to declare consensus. Results: Twenty-five participants, including physicians, residents and medical students, completed the study. Consensus was reached on the amount of effort needed for each teaching role. These values were used to prototype a cumulative teaching score that can be used to qualitatively quantify surgeon teaching. Conclusion: Surgeon teaching is important in UME, but not tracked and thus not valued. To improve the quantity and quality of surgeon teaching in UME, we need to track, reward and recognize surgeon teaching activities. The "effort score" we developed to objectively and transparently qualify teaching was able to determine the relative effort needed for each teaching activity in UME at the University of Toronto. Combining the effort score and time committed to each teaching activity will produce a cumulative teaching score for each instructor.

Contexte: Les chirurgiens formateurs jouent un rôle important pendant les études de premier cycle en médecine. Toutefois, les tâches d'enseignement sont sousévaluées et elles ne sont pas suffisamment reconnues comparativement aux activités de recherche, et cela nuit quantitativement et qualitativement à l'enseignement en chirurgie. Cette étude avait pour but d'analyser les divers rôles assumés par les chirurgiens formateurs et l'effort requis. Méthodes: Nous avons procédé à une revue complète de tous les rôles possibles assumés par les chirurgiens durant les études de premier cycle en médecine dans notre établissement. Les membres d'un comité Delphi ont été invités à évaluer chaque rôle de formateur au plan de l'effort requis par heure. Les résultats ont été analysés à l'aide de statistiques descriptives; et un coefficient α de Cronbach de 0,60 ou plus a servi de seuil consensuel. Résultats: Vingt-cinq participants, dont des médecins, des résidents et des étudiants en médecine, ont participé à l'étude. Un consensus a été atteint pour ce qui est de l'effort requis pour chaque rôle de formateur. Ces valeurs ont servi à élaborer le prototype d'un score cumulatif propre à l'enseignement qui peut être utilisé pour quantifier qualitativement l'enseignement par les chirurgiens. Conclusion: L'enseignement par les chirurgiens est important au premier cycle de la formation en médecine, mais ne fait l'objet ni d'un suivi ni d'une évaluation. Pour améliorer quantitativement et qualitativement l'enseignement en chirurgie au premier cycle, nous devons suivre, récompenser et reconnaître les diverses activités d'enseignement dans cette spécialité. L'« indice d'effort ¼ que nous avons élaboré pour qualifier de manière objective et transparente l'enseignement a permis de déterminer l'effort relatif requis pour chaque activité d'enseignement au premier cycle à l'Université de Toronto. En combinant l'indice d'effort et le temps consacré à chaque activité d'enseignement, on obtient un score cumulatif d'enseignement pour chaque instructeur.

Temporal Trends of Pediatric Hospitalizations with Acute Disseminated Encephalomyelitis in the United States: An Analysis from 2006 to 2014 using National Inpatient Sample.

OBJECTIVE: To determine the temporal trends in the epidemiology of acute disseminated encephalomyelitis (ADEM) and hospitalization outcomes in the US from 2006 through 2014. STUDY DESIGN: Pediatric (≤18 years of age) hospitalizations with ADEM discharge diagnosis were identified from the National (Nationwide) Inpatient Sample (NIS) for years 2006 through 2014. Trends in the incidence of ADEM with respect to age, sex, race, and region were examined. Outcomes of ADEM in terms of mortality, length of stay (LOS), cost of hospitalization, and seasonal variation were analyzed. NIS includes sampling weight. These weights were used to generate national estimates. P value of < .05 was considered significant. RESULTS: Overall incidence of ADEM associated pediatric hospitalizations from 2006 through 2014 was 0.5 per 100 000 population. Between 2006 through 2008 and 2012 through 2014, the incidence of ADEM increased from 0.4 to 0.6 per 100 000 (P-trend <.001). Black and Hispanic children had a significantly increased incidence of ADEM during the study period (0.2-0.5 per 100 000 population). There was no sex preponderance and 67% of ADEM hospitalizations were in patients <9 years old. From 2006 through 2008 to 2012 through 2014 (1.1%-1.5%; P-trend 0.07) and median LOS (4.8-5.5 days; Ptrend = .3) remained stable. However, median inflation adjusted cost increased from $11 594 in 2006 through 2008 to $16 193 in 2012 through 2014 (Ptrend = .002). CONCLUSION: In this large nationwide cohort of ADEM hospitalizations, the incidence of ADEM increased during the study period. Mortality and LOS have remained stable over time, but inflation adjusted cost of hospitalizations increased.

Association Between Statin Use and Cardiovascular Events After Carotid Artery Revascularization.

Background Statins are commonly used for the prevention of cardiovascular events; however, statins are underutilized in patients with noncoronary atherosclerosis. We sought to establish the rates of statin use in patients with carotid artery disease and to examine the association between statin therapy and outcomes after carotid revascularization. Methods and Results In this population-level retrospective cohort study, we identified all individuals aged ≥66 years who underwent carotid endarterectomy or stenting in Ontario, Canada (2002-2014). The primary outcome was a composite of 1-year stroke, myocardial infarction, or death (major adverse cardiac and cerebrovascular events). Five-year risks were also examined. Adjusted hazard ratios were computed using inverse probability of treatment weighting based on propensity scores. A total of 7893 of 10 723 patients (73.6%) who underwent carotid revascularization were on preprocedural statin therapy; moderate- or high-dose therapy was utilized by 7384 patients (68.9%). The composite rate of 1-year major adverse cardiac and cerebrovascular events was lower among statin users (adjusted hazard ratio: 0.76; 95% confidence interval, 0.70-0.83). Patients who were on persistent long-term statin therapy after the carotid procedure continued to experience significantly lower risk of major adverse cardiac and cerebrovascular events at 5 years (adjusted hazard ratio: 0.75, 95% confidence interval, 0.71-0.80). The beneficial associations with statin use were observed regardless of type of carotid revascularization procedure, carotid artery symptom status, or statin dose. Conclusions Continuous statin therapy was associated with a 25% lower risk of long-term adverse cardiovascular events in patients with significant carotid disease. Along with other supportive evidence, statins should be considered in patients undergoing carotid revascularization, and efforts are required to increase statin use in this undertreated population.

Perioperative mortality rates in low-income and middle-income countries: a systematic review and meta-analysis.

INTRODUCTION: The Lancet Commission on Global Surgery proposed the perioperative mortality rate (POMR) as one of the six key indicators of the strength of a country's surgical system. Despite its widespread use in high-income settings, few studies have described procedure-specific POMR across low-income and middle-income countries (LMICs). We aimed to estimate POMR across a wide range of surgical procedures in LMICs. We also describe how POMR is defined and reported in the LMIC literature to provide recommendations for future monitoring in resource-constrained settings. METHODS: We did a systematic review of studies from LMICs published from 2009 to 2014 reporting POMR for any surgical procedure. We extracted select variables in duplicate from each included study and pooled estimates of POMR by type of procedure using random-effects meta-analysis of proportions and the Freeman-Tukey double arcsine transformation to stabilise variances. RESULTS: We included 985 studies conducted across 83 LMICs, covering 191 types of surgical procedures performed on 1 020 869 patients. Pooled POMR ranged from less than 0.1% for appendectomy, cholecystectomy and caesarean delivery to 20%-27% for typhoid intestinal perforation, intracranial haemorrhage and operative head injury. We found no consistent associations between procedure-specific POMR and Human Development Index (HDI) or income-group apart from emergency peripartum hysterectomy POMR, which appeared higher in low-income countries. Inpatient mortality was the most commonly used definition, though only 46.2% of studies explicitly defined the time frame during which deaths accrued. CONCLUSIONS: Efforts to improve access to surgical care in LMICs should be accompanied by investment in improving the quality and safety of care. To improve the usefulness of POMR as a safety benchmark, standard reporting items should be included with any POMR estimate. Choosing a basket of procedures for which POMR is tracked may offer institutions and countries the standardisation required to meaningfully compare surgical outcomes across contexts and improve population health outcomes.

Long-term use of left ventricular assist devices: a report on clinical outcomes.

BACKGROUND: The literature examining clinical outcomes and readmissions during extended (> 1 yr) left ventricular assist device (LVAD) support is scarce, particularly in the era of continuous-flow LVADs. METHODS: We completed a retrospective cohort study on consecutive LVAD patients from June 2006 to March 2015, focusing on those who received more than 1 year of total LVAD support time. Demographic characteristics, clinical outcomes and readmissions were analyzed using standard statistical methods. All readmissions were categorized as per the Interagency Registry for Mechanically Assisted Circulatory Support 2015 guidelines. RESULTS: Of the 103 patients who received LVADs during the study period, 37 received LVAD support for more than 1 year, with 18 receiving support for more than 2 years. Average support time was 786 ± 381 days, with total support time reaching 80 patient-years. During a median follow-up of 2 years, 27 patients died, with 1-year conditional survival of 74%. Median freedom from first readmission was 106 days (range 1-603 d), with an average length of stay of 6 days. Readmissions resulted in an average of 41 ± 76 days in hospital per patient. Reasons for readmission were major infection (24%), major bleeding (19%) and device malfunction/thrombus (13%). There were a total of 112 procedures completed during the readmissions, with 60% of procedures being done in 13% (n = 5) of patients. CONCLUSION: Continuous-flow LVADs provide excellent long-term survival. The present study describes marked differences in reasons for readmissions between the general LVAD population and those supported for more than 1 year. Prolonged LVAD support resulted in decreased susceptibility to major bleeds and increased susceptibility to infection.

CONTEXTE: La documentation sur les résultats cliniques et les réadmissions reliés au recours prolongé (> 1 an) à un dispositif d'assistance ventriculaire gauche (DAVG) est peu abondante, particulièrement en ce qui concerne les DAVG à flux continu. MÉTHODES: Nous avons procédé à une étude de cohorte rétrospective sur une série de patients consécutifs à qui on a implanté un DAVG entre juin 2006 et mars 2015, en nous attardant plus particulièrement à ceux qui ont bénéficié du DAVG pendant une durée totale de plus d'un an. Les caractéristiques démographiques, les résultats cliniques et les réadmissions ont été analysés au moyen de méthodes statistiques standard. Toutes les réadmissions ont été catégorisées selon les lignes directrices 2015 du Registre INTERMACS (Interagency Registry for Mechanically Assisted Circulatory Support). RÉSULTATS: Parmi les 103 patients chez qui un DAVG a été implanté durant la période de l'étude, 37 en ont bénéficié pendant plus d'un an et 18 pendant plus de 2 ans. La durée moyenne d'utilisation a été de 786 ± 381 jours, la durée totale de l'assistance ainsi fournie atteignant 80 années-patients. Pendant la période de suivi médiane de 2 ans, 27 patients sont décédés, ce qui correspond à une survie conditionnelle d'un an chez 74 % des participants. L'intervalle médian avant une première réadmission a été de 106 jours (éventail 1-603 jours), et la durée médiane des séjours a été de 6 jours. Les réadmissions ont en moyenne été suivies d'un séjour hospitalier de 41 ± 76 jours par patient. Les raisons des réadmissions ont été infection grave (24 %), hémorragie majeure (19 %) et dysfonction du dispositif/thrombus (13 %). En tout, 112 interventions ont été effectuées lors des réadmissions, 60 % d'entre elles chez 13 % des patients (n = 5). CONCLUSION: Les DAVG à flux continu donnent lieu à une excellente survie à long terme. La présente étude décrit les différences marquées en ce qui concerne les raisons des réadmissions entre la population générale porteuse d'un DAVG et la population ayant bénéficié du dispositif pendant plus d'un an. Le recours prolongé à un DAVG a été associé à une diminution du risque d'hémorragie majeure et à une augmentation du risque d'infection.

External jugular vein thrombosis secondary to deep tissue neck massage.

An 85-year-old man presented with an acute asymptomatic lateral neck mass in the context of deep tissue neck massages during the past year. He was referred to vascular surgery after an ultrasound examination of the neck revealed a thrombus in the external jugular vein. His past medical history and comorbidities were noncontributory. A multidisciplinary team of vascular surgeons and hematologists did not recommend any anticoagulation, given that the patient did not have any risk factors for thrombosis as well as normal D-dimer levels. The patient was maintained on his previous dose of aspirin (81 mg daily).

MRTF-A signaling regulates the acquisition of the contractile phenotype in dedifferentiated chondrocytes.

Chondrocyte culture as a monolayer for cell number expansion results in dedifferentiation whereby expanded cells acquire contractile features and increased actin polymerization status. This study determined whether the actin polymerization based signaling pathway, myocardin-related transcription factor-a (MRTF-A) is involved in regulating this contractile phenotype. Serial passaging of chondrocytes in monolayer culture to passage 2 resulted in increased gene and protein expression of the contractile molecules alpha-smooth muscle actin, transgelin and vinculin compared to non-passaged, primary cells. This resulted in a functional change as passaged 2, but not primary, chondrocytes were capable of contracting type I collagen gels in a stress-relaxed contraction assay. These changes were associated with increased actin polymerization and MRTF-A nuclear localization. The involvement of actin was demonstrated by latrunculin B depolymerization of actin which reversed these changes. Alternatively cytochalasin D which activates MRTF-A increased gene and protein expression of α-smooth muscle actin, transgelin and vinculin, whereas CCG1423 which deactivates MRTF-A decreased these molecules. The involvement of MRTF-A signaling was confirmed by gene silencing of MRTF or its co-factor serum response factor. Knockdown experiments revealed downregulation of α-smooth muscle actin and transgelin gene and protein expression, and inhibition of gel contraction. These findings demonstrate that passaged chondrocytes acquire a contractile phenotype and that this change is modulated by the actin-MRTF-A-serum response factor signaling pathway.

Treatment of a pseudoaneurysm of the ascending aorta in association with aortopulmonary fistula following acute Type A dissection.

This report describes a rare case of aortic pseudoaneurysm with an aortopulmonary fistula in a 69-year-old woman two years following repair of a Type A aortic dissection. The patient presented with NYHA Class IV symptoms having deteriorated rapidly over a course of six weeks. We describe our successful surgical repair following a failed attempt of percutaneous closure with an atrial septal occlusion device.

Readmissions Following Implantation of a Continuous-Flow Left Ventricular Assist Device.

OBJECTIVE: The objective of this study is to review and analyze readmission data for patients who received a continuous flow left ventricular assist device (LVAD). METHODS: A retrospective review of 88 patients implanted with a continuous-flow LVAD between June 2006 and June 2014 was performed. Reason for readmission, frequency, length of stay, and procedures performed during each readmission were recorded. All patients were followed in our LVAD clinic and all readmissions were reported to our program. RESULTS: Sixty-seven patients (76%) were discharged following their hospitalization for LVAD implant. In these patients, indication for LVAD support consisted of bridge to transplant (78%) and destination therapy (22%). Total device support time was 30,482 days, with an average support time of 455 ± 376 days. Forty-two patients (63%) were readmitted at least once, with an average length of readmission stay of nine days (median = 6). There were 129 readmissions totaling 1264 hospital days. The main reason for readmission was infection (17%). Despite this relatively high readmission rate, patients spent 86% of their time outside the hospital. CONCLUSION: Although common, LVAD readmissions can be appropriately managed with patients spending the majority of their support time at home. doi: 10.1111/jocs.12744 (J Card Surg 2016;31:361-364).

Importance of patient-centred signage and navigation guide in an orthopaedic and plastics clinic.

Gulshan & Nanji Orthopaedic and Plastics Center at the North York General Hospital is the second busiest site after the emergency department serving more than 26,000 patients annually. Increase in patient flow, overworked staff, and recent renovations to the hospital have resulted in patients experiencing long wait times, and thusly patient dissatisfaction and stress. Several factors contribute to patient dissatisfaction and stress: i) poor and unfriendly signage; ii) inconsistent utilization of the numbering system; and iii) difficulty navigating to and from the imaging center. A multidisciplinary QI team was assembled to improve the patient experience. We developed a questionnaire to assess patient stress levels at the baseline. Overall, more than half of the patients (54.8%) strongly agreed or agreed to having a stressful waiting experience. Subsequently, based on patient feedback and staff perspectives, we implemented two PDSA cycles. For PDSA 1, we placed a floor graphic (i.e. black tape) to assist patients in navigating from the clinic to the imaging centre and back. For PDSA 2, we involved creating a single 21"×32" patient-friendly sign at the entrance to welcome patients, with clear instructions outlining registration procedures. Surveys were re-administered to assess patient stress levels. A combination of both interventions caused a statistically significant reduction in patient stress levels based on the Kruskal-Wallis and Mann-Whitney U Tests. The present project highlighted the importance of involving stakeholders as well as frontline staff when undertaking quality improvement projects as a way to identify bottlenecks as well as establish sustainable solutions. Additionally, the team recognized the importance of incorporating empirical based solutions and involving experts in the field to optimize results. The present project successfully implemented strategies to improve patient satisfaction and reduce stress in a high flow community clinic. These endpoints were achieved by incorporating patient friendly signage, as well as improving patient flow directors.

Expression of type I collagen and tenascin C is regulated by actin polymerization through MRTF in dedifferentiated chondrocytes.

This study examined actin regulation of fibroblast matrix genes in dedifferentiated chondrocytes. We demonstrated that dedifferentiated chondrocytes exhibit increased actin polymerization, nuclear localization of myocardin related transcription factor (MRTF), increased type I collagen (col1) and tenascin C (Tnc) gene expression, and decreased Sox9 gene expression. Induction of actin depolymerization by latrunculin treatment or cell rounding, reduced MRTF nuclear localization, repressed col1 and Tnc expression, and increased Sox9 gene expression in dedifferentiated chondrocytes. Treatment of passaged chondrocytes with MRTF inhibitor repressed col1 and Tnc expression, but did not affect Sox9 expression. Our results show that actin polymerization regulates fibroblast matrix gene expression through MRTF in passaged chondrocytes.