Mas-related G protein-coupled receptor type D antagonism improves portal hypertension in cirrhotic rats.

Splanchnic vasodilatation contributes to the development and aggravation of portal hypertension (PHT). We previously demonstrated that in cirrhosis, angiotensin- mediates splanchnic vasodilatation through the Mas receptor (MasR). In this study, we investigated whether the recently characterized second receptor for angiotensin-(1-7), Mas-related G protein-coupled receptor type D (MrgD), contributes to splanchnic vasodilatation in cirrhotic and noncirrhotic PHT. Splanchnic vascular hemodynamic and portal pressure were determined in two rat models of cirrhotic PHT and a rat model with noncirrhotic PHT, treated with either MrgD blocker D-Pro7 -Ang-(1-7) (D-Pro) or MasR blocker A779. Gene and protein expression of MrgD and MasR were measured in splanchnic vessels and livers of cirrhotic and healthy rats and in patients with cirrhosis and healthy subjects. Mesenteric resistance vessels isolated from cirrhotic rats were used in myographs to study their vasodilatory properties. MrgD was up-regulated in cirrhotic splanchnic vessels but not in the liver. In cirrhotic rats, treatment with D-Pro but not A779 completely restored splanchnic vascular resistance to a healthy level, resulting in a 33% reduction in portal pressure. Mesenteric vessels pretreated with D-Pro but not with A779 failed to relax in response to acetylcholine. There was no splanchnic vascular MrgD or MasR up-regulation in noncirrhotic PHT; thus, receptor blockers had no effect on splanchnic hemodynamics. Conclusion: MrgD plays a major role in the development of cirrhotic PHT and is a promising target for the development of novel therapies to treat PHT in cirrhosis. Moreover, neither MrgD nor MasR contributes to noncirrhotic PHT.

A blueprint for building an emergency department quality improvement and patient safety committee.

The field of quality improvement and patient safety (QIPS) has matured significantly in emergency medicine over the past decade. From standalone, strategically misaligned, and incoherently designed QIPS projects years ago, emergency department (ED) leaders have now recognized that developing a more robust QIPS infrastructure helps prioritize and organize projects for a greater likelihood of success and impact for patients and the system. This process includes the development of a well-defined, accountable, and supported departmental QIPS committee. This can be achieved effectively using a deliberate and structured approach, such as the one described by Harvard Business School Professor John Kotter in his seminal work, "Leading Change." Herein, we present a blueprint using this framework and include practical examples from our experience developing a robust and successful ED QIPS committee and infrastructure. The steps include how to develop a "burning platform," select a guiding coalition of leaders, develop a strategic vision and initiatives, recruit a volunteer army of members, enable actions for the committee, generate short-term successes, sustain the pace of change, and, finally, enable the infrastructure to support ongoing improvements. This road map can be replicated by ED teams of variable sizes and settings to structure, prioritize, and operationalize their QIPS activities and ultimately improve the outcomes of their patients.

RéSUMé: Le domaine de l'amélioration de la qualité de la pratique clinique et de la sécurité des patients (AQSP) s'est considérablement développé en médecine d'urgence au cours de la dernière décennie. Alors qu'il y a quelques années, les projets d'AQSP étaient autonomes, mal alignés sur le plan stratégique et conçus de manière incohérente, les responsables des services d'urgence (SU) reconnaissent aujourd'hui que la mise en place d'une infrastructure d'AQSP plus solide permet de hiérarchiser et d'organiser les projets pour qu'ils aient plus de chances de réussir et d'avoir un impact sur les patients et le système. Ce processus comprend le développement d'un comité d'AQSP départemental bien défini, responsable et soutenu. On peut y parvenir efficacement en utilisant une approche délibérée et structurée, comme celle décrite par le professeur John Kotter de la Harvard Business School dans son ouvrage phare intitulé « Leading Change ¼. Dans le présent document, nous présentons un plan à l'aide de ce cadre et incluons des exemples pratiques tirés de notre expérience de l'élaboration d'un comité et d'une infrastructure d'AQSP de SU solides et réussis. Les étapes comprennent la façon d'élaborer une « plateforme brûlante ¼, de sélectionner une coalition de dirigeants, d'élaborer une vision et des initiatives stratégiques, de recruter une armée de membres bénévoles, de permettre des actions pour le comité, de générer des succès à court terme, de maintenir le rythme du changement et enfin, permettre à l'infrastructure de soutenir les améliorations en cours. Cette feuille de route peut être reproduite par des équipes d'urgence de tailles et de contextes différents pour structurer, hiérarchiser et rendre opérationnelles leurs activités d'AQSP et, en fin de compte, améliorer les résultats de leurs patients.

Quality improvement initiative for improved patient communication in an ED rapid assessment zone.

INTRODUCTION: Patient-clinician communication in the Emergency Department (ED) faces challenges of time and interruptions, resulting in negative effects on patient satisfaction with communication and failure to relieve anxiety. Our aim was to improve patient satisfaction with communication and to decrease related patient anxiety. METHODS: A multistage quality improvement (QI) initiative was conducted in the ED of Toronto General Hospital, a quaternary care centre in Ontario, Canada, from January to May 2018. We engaged stakeholders widely including clinicians, allied health and patients. We developed a 5-point Likert scale survey to measure patient and clinician rating of their communication experience, along with open-ended questions, and a patient focus group. Inductive analyses yielded interventions that were introduced through three Plan-Do-Study-Act (PDSA) cycles: (1) a clinician communication tool called Acknowledge-Empathize-Inform; (2) patient information pamphlets; and (3) a multimedia solution displaying patient-directed material. Our primary outcome was to improve patient satisfaction with communication and decrease anxiety by at least one Likert scale point over 6 months. Our secondary outcome was clinician-perceived interruptions by patients. We used statistical process control (SPC) charts to identify special cause variation and two-tailed Mann-Whitney U tests to compare means (statistical significance p<0.05). RESULTS: A total of 232 patients and 104 clinicians were surveyed over baseline and three PDSA cycles. Communication about wait times, ED process, timing of next steps and directions to patient areas were the most frequently identified gaps, which informed our interventions. Measurements at baseline and during PDSA 3 showed: patient satisfaction increased from 3.28 (5 being best; n=65) to 4.15 (n=59, p<0.0001). Patient anxiety decreased from 2.96 (1 being best; n=65) to 2.31 (n=59, p<0.001). Clinician-perceived interruptions by patients changed from 4.33 (5 being highest; n=30) to 4.18 (n=11, p=0.98) and did not meet significance. SPC charts showed special cause variation temporally associated with our interventions. CONCLUSIONS: Our pragmatic low-cost QI initiative led to statistically significant improvement in patient satisfaction with communication and decreased patient anxiety while narrowly missing our a priori improvement aim of one full Likert scale point.

Activation of the Alternate Renin-Angiotensin System Correlates with the Clinical Status in Human Cirrhosis and Corrects Post Liver Transplantation.

INTRODUCTION: Recent animal studies have shown that the alternate renin-angiotensin system (RAS) consisting of angiotensin-converting enzyme 2 (ACE2), angiotensin-(1⁻7) (Ang-(1⁻7)) and the Mas receptor is upregulated in cirrhosis and contributes to splanchnic vasodilatation and portal hypertension. To determine the potential relevance of these findings to human liver disease, we evaluated its expression and relationship to the patients' clinical status in subjects with cirrhosis. METHODS: Blood sampling from peripheral and central vascular beds was performed intra-operatively for cirrhotic patients at the time of liver transplantation (LT) or trans-jugular intra-hepatic portosystemic shunt (TIPS) procedures to measure angiotensin II (Ang II) and Ang-(1⁻7) peptide levels and ACE and ACE2 enzyme activity. Relevant clinical and hemodynamic data were recorded pre-operatively for all subjects and peripheral blood sampling was repeated 3 months or later post-operatively. RESULTS: Ang-(1⁻-7) and ACE2 activity were up-regulated more than twofold in cirrhotic subjects both at the time of LT and TIPS and levels returned to comparable levels as control subjects post-transplantation. Ang-(1⁻7) levels correlated positively with the degree of liver disease severity, as measured by the model for an end-stage liver disease (MELD) and also with clinical parameters of pathological vasodilatation including cardiac output (CO). There were strong correlations found between the ACE2:ACE and the Ang-(1⁻7):Ang II ratio highlighting the inter-dependence of the alternate and classical arms of the RAS and thus their potential impact on vascular tone. CONCLUSIONS: In human cirrhosis, the alternate RAS is markedly upregulated and the activation of this system is associated strongly with features of the hyperdynamic circulation in advanced human cirrhosis.

Effects of angiotensin-(1-7) and angiotensin II on vascular tone in human cirrhotic splanchnic vessels.

Evidence suggests that the renin angiotensin system (RAS) may play a role in the pathological splanchnic vasodilatation that leads to a hyperdynamic circulation in cirrhosis. An impaired contractile response to the angiotensin II peptide of the classical RAS system has been described in animal models of cirrhosis and in vivo in cirrhotic subjects. Furthermore, in experimental cirrhosis, the so-called alternate arm of the RAS was found to be upregulated and its effector peptide, angiotensin-(1-7) was shown to attenuate splanchnic vascular tone. The aim of this study was to explore the relevance of these findings to human disease. Omental arteries from cirrhotic and controls subjects were studied in isolation using a wire myograph. Varied protocols to evaluate the vasoactivity of RAS mediators were enacted. The contractile response to angiotensin II was comparable in cirrhotic vs control splanchnic arteries (61 ± 9 vs 68 ± 11% KPSS, respectively). Despite this, however, arterial contractility of the cirrhotic vessels correlated negatively with Child Pugh score (p = 0.0003, r=-0.83) and there was evidence that angiotensin II-induced contractility was increased in early cirrhosis. Angiotensin II-induced contractility was attenuated by angiotensin-(1-7) in cirrhotic and control arteries, however, adrenergic responses were not affected by angiotensin-(1-7). Contractile responses to angiotensin II are preserved in narrow lumen human cirrhotic splanchnic arteries and are comparatively augmented in early disease. Angiotensin-(1-7) had no vasodilatory effect on adrenergic tone, however, attenuated angiotensin II-induced contractility, possibly through an Ang-(1-7)-AT1R interaction, and thus may contribute to pathological vasodilatation in human cirrhosis.

A prospective evaluation of the role of transient elastography for the detection of hepatic fibrosis in type 2 diabetes without overt liver disease.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is a major risk factor for the development of non-alcoholic fatty liver disease (NAFLD) and subsequently hepatic fibrosis. Transient elastography (TE) is a rapid, reproducible non-invasive test that may be appropriate as a screening tool for the presence of hepatic fibrosis. AIM: Assess the utility of TE as a screening tool for the presence of hepatic fibrosis in a T2DM population with no known liver disease. METHODS: T2DM patients without known liver disease were included. Patients were assessed with TE in addition to biochemical parameters. RESULTS: A successful TE evaluation could be obtained in 74 of 81 (91%) included subjects. Of these, 26 (35%) had a liver stiffness measurement (LSM) ≥ 7.65 kPa. Sixteen of these subjects had confirmatory liver biopsies with significant (≥ F2 fibrosis) present in 12 (75%) and cirrhosis diagnosed in 2 subjects. 15/16 (94%) had histological steatohepatitis. Compared with those with a lower LSM, subjects with an LSM ≥ 7.65 kPa had higher ALT levels (38.0 ± 21.7 vs 26.1 ± 11.1 U/L, p = 0.021) and increased prevalence of hepatic steatosis by ultrasound (85% vs 63%, p = 0.005). CONCLUSION: Significant hepatic fibrosis in the T2DM population is frequently under-recognized. TE may be a feasible tool for the screening of T2DM patients for the presence of hepatic fibrosis.

The origin and evolution of seahorses (genus Hippocampus): a phylogenetic study using the cytochrome b gene of mitochondrial DNA.

Phylogenetic relationships among 93 specimens of 22 species of seahorses (genus Hippocampus) from the Atlantic and Indo-Pacific Oceans were analysed using cytochrome b gene sequence data. A maximum sequence divergence of 23.2% (Kimura 2-parameter model) suggests a pre-Tethyan origin for the genus. Despite a greater number of seahorse species in the Indo-Pacific than in the Atlantic Ocean, there was no compelling genetic evidence to support an Indo-Pacific origin for the genus Hippocampus. The phylogenetic data suggest that high diversity in the Indo-Pacific results from speciation events dating from the Pleistocene to the Miocene, or earlier. Both vicariance and dispersal events in structuring the current global distribution of seahorses. The results suggested that several species designations need re-evaluating, and further phylogeographic studies are required to determine patterns and processes of seahorse dispersal.