End-Stage Acute Thoracic Aortic Care Patients’ Interventions and Two-Year Survival: the New York State Experience

BACKGROUND: Scarce US-based regional or State-specific reports exist recording the incidence, prevalence, or post-diagnosis clinical outcomes for end-stage thoracic aortic aneurysmal (TAA) disease. This retrospective cohort study of New York State (NYS) patients with newly diagnosed ruptured or dissected thoracic aortic aneurysms (TAA-RD) documents two-year follow-up after elective and emergent procedures. METHODS: Using hospital billing codes, NYS first-time TAA-RD encounters were extracted. As the primary study endpoint, the two-year composite included all-cause death, subsequent rupture or dissection, or non-elective intervention; individual composite sub-components were secondary study endpoints. Multivariable logistic regression models estimated two-year intervention and composite outcome risks. Using multivariable regression models created for the composite endpoints, post-discharge elective TAA procedural impact was evaluated. RESULTS: Of the 5,789 NYS residents identified, 49.92% reached the two-year composite endpoint with 23.98% two-year deaths. Only 1902 (32.86%) of TAA-RD patients had an index intervention. Post-discharge elective TAA interventions dramatically reduced adverse outcome risk (odds ratio [O.R.] = 0.36; 95% confidence interval [C.I.] = 0.26 - 0.51). Multivariable regression models identified patient characteristics associated with the two-year adverse composite outcome including urgent/emergent status, increased Elixhauser comorbidity score, non-rheumatic aortic regurgitation, and carotid disease. CONCLUSIONS: Nearly 50% of NYS TAA-RD patients reached the two-year adverse endpoint. Post-2014, the TAA-RD diagnosis rates increased but emergent thoracic aortic surgery rates decreased. Surprisingly, under 50% of NYS TAA-RD patients received an index admission procedure; this rate is lower than anticipated. Beyond traditional morphologic metrics, “at risk” TAA patient-characteristics were identified. Post-discharge survivors had excellent post-procedural two-year durability rates

Atrial fibrillation in mechanical circulatory support patients

Atrial fibrillation (AF) is known to be one of the most common arrhythmias noted in cardiac procedures and is frequently associated with heart failure. As frequent interventions for patients with heart failure involve implantation of mechanical circulatory assist devices (e.g., left ventricular assist devices), it is timely to review the role this arrhythmia has on adverse clinical outcomes. A comprehensive literature search was conducted for PubMed. Relevant medical subject heading (MeSH) terms used in the initial literature search include “Heart-Assist Devices”, “Extracorporeal Membrane Oxygenation”, “Atrial Fibrillation”, “Heart Failure”, “Mortality”, “Hospital Readmission”, “stroke”, “Postoperative Complications”. In this review, the relevant literature was highlighted to identify the incidence, clinical impacts, and management of AF surrounding mechanical circulatory support implantation. The incidence of AF in this mechanical circulatory support device population was similar to that of patients with other cardiac procedures (10%-40%). Moreover, in most studies, preoperative AF was not significantly associated with adverse outcomes. In contrast, however, it appears that postoperative atrial fibrillation may predispose patients to increased risk for thromboembolic events and adverse long-term outcomes

A literature review: pre-/post-operative atrial fibrillation for thoracic aortic aneurysm procedures

Atrial fibrillation (AF) is among the most frequent cardiac surgical arrhythmias documented. The global AF prevalence is estimated at over 33 million cases, with estimates ranging up to 6.1 million cases in the United States. Among cardiac surgical patients, the risk factors for new-onset post-operative AF (POAF) include Caucasian race with increased prevalence documented in older men. Due to trends of earlier thoracic aortic aneurysm (TAA) detection and treatment, it is timely to review the AF association with adverse TAA clinical outcomes. Towards this goal, a comprehensive PubMed literature review was performed. For this initial Medline literature search, the MeSH search strategy included “thoracic aortic aneurysm” and “atrial fibrillation”. Based on the pertinent articles identified, the limited literature available for preoperative TAA AF and the predictors of POAF following TAA procedures were reviewed. Given only a handful of publications addressing these pre-/post-operative AF topics were identified using this very broad initial search approach, a knowledge chasm exists–as very little is known about TAA patients with pre-operative or new-onset post-operative AF. Given the paucity of evidence-based information available, clinically relevant TAA-specific research questions have been raised to guide future TAA AF-related investigations

Predictors and risk-adjusted outcomes of new-onset postoperative atrial fibrillation in repeat surgical and valve-in-valve transcatheter aortic valve replacement

Aim: New-onset postoperative atrial fibrillation/flutter (POAF/AFL) complications have not been well studied for repeat aortic valve replacements (r-AVR); this study identified risk factors predisposing to POAF/AFL and POAF/AFL’s effect upon risk-adjusted outcomes.Methods: Using New York State’s Statewide Planning and Research Cooperative System records (2005-2018), multivariable forward selection models identified risks predictive of POAF/AFL. To identify POAF/AFL’s impact upon risk-adjusted mortality/morbidity (MM) and 30-day readmission (READMIT), forward selection logistic regression models applied Firth bias correction to address data sparsity.Results: Of the 242 r-AVR patients, 147 underwent repeat surgical aortic valve replacements (r-SAVR) and 95 underwent valve-in-valve transcatheter aortic valve replacements (ViV-TAVR); 39.46% of r-SAVR and 43.16% of ViV-TAVR patients had POAF/AFL. R-SAVR patients with POAF/AFL were older (69.7 ± 11.1 vs. 56.7 ± 13.2 years, P < 0.01) compared to R-SAVR patients without POAF/AFL. Multivariable models identified an enhanced POAF/AFL risk for elderly (OR: 1.05, 95%CI: 1.03-1.07, P < 0.01) and cerebral vascular disease (OR: 2.18, 95%CI: 1.05-4.55, P = 0.04) patients. Bivariately, POAF/AFL was associated with READMIT, but not MM. Correspondingly, multivariable models found POAF/AFL increased READMIT (OR: 3.12, 95%CI: 1.46-6.65, P < 0.01), but not MM. However, black race (OR: 4.97, 95%CI: 1.61-15.37, P < 0.01) and Elixhauser score (OR: 1.05, 95%CI: 1.02-1.08, P < 0.01) increased risk for MM.Conclusion: More common in older and cerebrovascular disease patients, 41% of r-AVR patients with POAF/AFL had increased READMIT risk; thus, future investigations should focus on improving POAF/AF r-AVR patients’ post-discharge continuity of care

Elucidation of Exosome Migration Across the Blood–Brain Barrier Model In Vitro

The delivery of therapeutics to the central nervous system (CNS) remains a major challenge in part due to the presence of the blood-brain barrier (BBB). Recently, cell-derived vesicles, particularly exosomes, have emerged as an attractive vehicle for targeting drugs to the brain, but whether or how they cross the BBB remains unclear. Here, we investigated the interactions between exosomes and brain microvascular endothelial cells (BMECs) in vitro under conditions that mimic the healthy and inflamed BBB in vivo. Transwell assays revealed that luciferase-carrying exosomes can cross a BMEC monolayer under stroke-like, inflamed conditions (TNF-α activated) but not under normal conditions. Confocal microscopy showed that exosomes are internalized by BMECs through endocytosis, co-localize with endosomes, in effect primarily utilizing the transcellular route of crossing. Together, these results indicate that cell-derived exosomes can cross the BBB model under stroke-like conditions in vitro. This study encourages further development of engineered exosomes as drug delivery vehicles or tracking tools for treating or monitoring neurological diseases

Guidelines for the use and interpretation of assays for monitoring autophagy

In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field

Guidelines for the use and interpretation of assays for monitoring autophagy

In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field