The complex regulation of eNOS (endothelial nitric oxide synthase) in cardiovascular physiology occurs at multiple stages. eNOS mRNA levels are controlled both at the transcriptional and ...post-transcriptional phases, and epigenetic mechanisms appear to modulate tissue-specific eNOS expression. The eNOS enzyme reversibly associates with a diverse family of protein partners that regulate eNOS sub-cellular localization, catalytic function, and biological activity. eNOS enzyme activity and sub-cellular localization are intimately controlled by post-translational modifications including phosphorylation, nitrosylation, and acylation. The multiple extra-cellular stimuli affecting eNOS function coordinate their efforts through these key modifications to dynamically control eNOS and NO bioactivity in the vessel wall. This review will focus on the biochemical partners and perturbations of the eNOS protein as this vital enzyme undergoes modulation by diverse signal transduction pathways in the vascular endothelium.
Multidisciplinary Pulmonary Embolism Response Teams Dudzinski, David M; Piazza, Gregory
Circulation (New York, N.Y.),
2016-January-5, 2016-Jan-05, 2016-01-05, 20160105, Letnik:
133, Številka:
1
Journal Article
Nitric oxide (NO) is a small, diffusible, lipophilic free radical gas that mediates significant and diverse signaling functions in nearly every organ system in the body. The endothelial isoform of ...nitric oxide synthase (eNOS) is a key source of NO found in the cardiovascular system. This review summarizes the pharmacology of NO and the cellular regulation of endothelial NOS (eNOS). The molecular intricacies of the chemistry of NO and the enzymology of NOSs are discussed, followed by a review of the biological activities of NO. This information is then used to develop a more global picture of the pharmacological control of NO synthesis by NOSs in both physiologic conditions and pathophysiologic states.
Integrating newly developed tests and treatments for severe pulmonary embolism (PE) into clinical care requires coordinated multispecialty collaboration. To meet this need, we developed a new ...paradigm: a multidisciplinary Pulmonary Embolism Response Team (PERT). In this report, we provide the first longitudinal analysis of patients treated by a PERT.
Our PERT includes specialists in cardiovascular medicine and surgery, emergency medicine, hematology, pulmonary/critical care, and radiology, and is organized as a rapid response team. We prospectively captured clinical, therapeutic, and outcome data at PERT activation and during follow-up periods up to 365 days. We analyzed data collectively, and as five mutually exclusive 6-month periods. We performed Fisher exact tests and regression analysis to test for trend.
In 30 months, there were 394 unique PERT activations, 314 (80%) for confirmed PE. PERT activations increased by 16% every 6 months. Most confirmed PEs were submassive (n = 143, 46%) or massive (n = 80, 26%). The PERT treated a relatively large proportion of patients with PE and systemic or catheter-directed thrombolysis (n = 35, 11%), though the most common treatment was anticoagulation alone (n = 215, 69%). Hemorrhagic complications were rare overall, especially among patients treated with catheter-directed thrombolysis. The all-cause 30-day mortality of PERT patients with confirmed PE was 12%.
We report our initial 30-month experience with a novel multidisciplinary PERT that rapidly engages multiple specialists to deliver efficient, organized, and evidence-based care to patients with high-risk PE. The PERT paradigm was rapidly adopted and may become a new standard of care for patients with PE.
Pulmonary embolism (PE) is the third leading cause of cardiovascular mortality in the United States. Unfortunately, significant gaps exist in outcome data around many interventional therapies, a fact ...that is reflected in the low strength of management recommendations found in consensus major society guidelines. In addition to careful risk stratification, therapeutic anticoagulation generally should be an early part of PE management in all cases. For patients presenting with acute high-risk PE or intermediate-risk PE with higher risk features, consideration should be given to systemic thrombolysis after careful evaluation for potential bleeding complications. In patients with contraindications to systemic thrombolysis, failure of this therapy, or significant ongoing cardiopulmonary distress, consideration should be given to interventional therapies like catheter-directed lysis, catheter-directed embolectomy, surgical embolectomy, and mechanical circulatory support. Until more robust comparative outcome data are put forward, pulmonary embolism response teams (PERT) should be considered for multi-disciplinary patient evaluation and management.
prosthetic valve endocarditis (PVE) remains among the most morbid bacterial infections, with mortality estimates ranging from 40% to 80%. The proportion of PVE cases due to methicillin-resistant
...(MRSA) has grown in recent decades, to account for more than 15% of cases of
PVE and 6% of all cases of PVE. Because no large studies or clinical trials for PVE have been published, most guidelines on the diagnosis and management of MRSA PVE rely upon expert opinion and data from animal models or related conditions (e.g., coagulase-negative
infection). We performed a review of the literature on MRSA PVE to summarize data on pathogenic mechanisms and updates in epidemiology and therapeutic management and to inform diagnostic strategies and priority areas where additional clinical and laboratory data will be particularly useful to guide therapy. Major updates discussed in this review include novel diagnostics, indications for surgical management, the utility of aminoglycosides in medical therapy, and a review of newer antistaphylococcal agents used for the management of MRSA PVE.
Graphical Abstract
Abstract
Aims
Right ventricular (RV) failure causes death from acute pulmonary embolism (PE), due to a mismatch between RV systolic function and increased RV afterload. We ...hypothesized that an echocardiographic ratio of this mismatch RV systolic function by tricuspid annular plane systolic excursion (TAPSE) divided by pulmonary arterial systolic pressure (PASP) would predict adverse outcomes better than each measurement individually, and would be useful for risk stratification in intermediate-risk PE.
Methods and results
This was a retrospective analysis of a single academic centre Pulmonary Embolism Response Team registry from 2012 to 2019. All patients with confirmed PE and a formal transthoracic echocardiogram performed within 2 days were included. All echocardiograms were analysed by an observer blinded to the outcome. The primary endpoint was a 7-day composite outcome of death or haemodynamic deterioration. Secondary outcomes were 7- and 30-day all-cause mortality. A total of 627 patients were included; 135 met the primary composite outcome. In univariate analysis, the TAPSE/PASP was associated with our primary outcome odds ratio = 0.028, 95% confidence interval (CI) 0.010–0.087; P < 0.0001, which was significantly better than either TAPSE or PASP alone (P = 0.017 and P < 0.0001, respectively). A TAPSE/PASP cut-off value of 0.4 was identified as the optimal value for predicting adverse outcome in PE. TAPSE/PASP predicted both 7- and 30-day all-cause mortality, while TAPSE and PASP did not.
Conclusion
A combined echocardiographic ratio of RV function to afterload is superior in prediction of adverse outcome in acute intermediate-risk PE. This ratio may improve risk stratification and identification of the patients that will suffer short-term deterioration after intermediate-risk PE.
Clot in transit (CIT) represents a rare and life-threatening manifestation of venous thromboembolism of which we have limited understanding. This study describes the risk factors, clinical ...characteristics, and outcomes associated with the development of CIT as well as death following CIT diagnosis.
We analyzed patients enrolled in our institutional Pulmonary Embolism Response Team (PERT) registry and compared 57 patients who had a CIT to 608 pulmonary embolism (PE) patients who did not have a CIT. We performed univariate and multivariate logistic regression to identify factors associated with CIT (vs PE without CIT) among patients who had an echocardiogram, as well as factors associated with 7-day death after CIT diagnosis.
CIT was present in (57) 8.6% of patients who had an echocardiogram. Multivariate analysis showed heart failure (OR 2.8, 95% CI 1.2–6.5, P = 0.01), a pre-existing central venous catheter (OR 2.5, 95% CI 1.1–5.7, P = 0.03), and hypotension (OR 2.1, 95% CI 1.1–3.7, P = 0.02) to be independently associated with CIT. All-cause mortality by 7 days was higher in CIT patients (12.5% vs 5.1%, P = 0.02). CIT patients who died were more likely to have presented with hemodynamic collapse (57.1% vs 14.0%, P = 0.02), mental status change (100% vs 22.0%, P < 0.001), and to be intubated (100% vs 36.0%, P = 0.001).
The presence of heart failure, a central venous catheter, and hypotension should alert physicians to patients who may require an echocardiogram to diagnose CIT. The mortality of CIT is high, even relative to a population with severe PE.
•Clot in transit (CIT) is present in 9% of pulmonary embolism response team patients.•Specific risk factors (e.g. HF) should alert clinicians to the possibility of CIT.•CIT is associated with high 7-day mortality compared to pulmonary embolism alone.•Mental status changes and hemodynamic collapse are associated with mortality in CIT.
Ischemic mitral regurgitation is an important consequence of LV remodeling after myocardial infarction. Echocardiographic diagnosis and assessment of ischemic mitral regurgitation are critical to ...gauge its adverse effects on prognosis and to attempt to tailor rational treatment strategy. There is no single approach to the echocardiographic assessment of ischemic mitral regurgitation: standard echocardiographic measures of mitral regurgitation severity and of LV dysfunction are complemented by assessments of displacement of the papillary muscles and quantitative indices of mitral valve deformation. Development of novel approaches to understand mitral valve geometry by echocardiography may improve understanding of the mechanism, clinical trajectory, and reparability of ischemic mitral regurgitation.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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