Exploring the Activities of RBPMS Proteins in Myocardial Biology.

Numerous RNA-binding proteins (RBPs) are expressed in the heart, and mutations in several RBPs have been implicated in cardiovascular disease through genetic associations, animal modeling, and mechanistic studies. However, the functions of many more cardiac RBPs, and their relevance to disease states, remain to be elucidated. Recently, we have initiated studies to characterize the functions of the RBPs RBPMS and RBPMS2 in regulating myocardial biology in zebrafish and higher vertebrate species.

Comparison of Outcomes in Elective Endovascular Aortic Repair vs Open Surgical Repair of Abdominal Aortic Aneurysms.

Importance: Knowledge regarding the long-term outcomes of elective treatment of abdominal aortic aneurysm (AAA) using endovascular aortic repair (EVAR) is increasing. However, data with greater than 10 years' follow-up remain sparse and are lacking from population-based studies.

Objective: To determine the long-term outcomes of EVAR compared with open surgical repair (OSR) for elective treatment of AAA.

Factors associated with in-hospital complications and long-term implications of these complications in elderly patients undergoing endovascular aneurysm repair.

Objective: Perioperative complications in elderly patients undergoing endovascular aneurysm repair (EVAR) occur frequently. Although perioperative mortality has been well-described in the elderly patient population, factors associated with in-hospital complications and their impact on long-term survival remain poorly characterized.

Methods: We identified all patients undergoing elective EVAR for infrarenal AAA within the Vascular Quality Initiative registry (2003-2018) and compared in-hospital complication rates between elderly (age ≥75) and nonelderly patients (<75).

Lumbar Spine MRI: Missed Opportunities for Abdominal Aortic Aneurysm Detection.

Purpose: The US Preventive Services Task Force (USPSTF) recommends 1-time sonographic screening for abdominal aortic aneurysms (AAAs) in male smokers ages 65-75 and other selected individuals in this age group based on risk factors. Patients in this age range are frequent utilizers of lumbar spine MRI, in which the abdominal aorta is typically fully imaged. The purpose of this study was to assess the potential detection rate of AAAs on lumbar spine MRI performed in the USPSTF screening age range with systematic aortic measurement and the frequency with which AAAs are currently reported in practice.

Identification of a novel class of RIP1/RIP3 dual inhibitors that impede cell death and inflammation in mouse abdominal aortic aneurysm models.

Receptor interacting protein kinase-1 and -3 (RIP1 and RIP3) are essential mediators of cell death processes and participate in inflammatory responses. Our group recently demonstrated that gene deletion of Rip3 or pharmacological inhibition of RIP1 attenuated pathogenesis of abdominal aortic aneurysm (AAA), a life-threatening degenerative vascular disease characterized by depletion of smooth muscle cells (SMCs), inflammation, negative extracellular matrix remodeling, and progressive expansion of aorta. The goal of this study was to develop drug candidates for AAA and other disease conditions involving cell death and inflammation.

Critical questions in ovarian cancer research and treatment: Report of an American Association for Cancer Research Special Conference.

Substantial progress has been made in understanding ovarian cancer at the molecular and cellular level. Significant improvement in 5-year survival has been achieved through cytoreductive surgery, combination platinum-based chemotherapy, and more effective treatment of recurrent cancer, and there are now more than 280,000 ovarian cancer survivors in the United States. Despite these advances, long-term survival in late-stage disease has improved little over the last 4 decades.

Prevalence of Elective and Ruptured Abdominal Aortic Aneurysm Repairs by Age and Sex From 2003 to 2016 in Ontario, Canada.

Importance: Age and sex are important considerations in assessing and individualizing therapy for abdominal aortic aneurysm (AAA) repair.

Objective: To determine the prevalence of open and endovascular elective AAA (EAAA) and ruptured AAA (RAAA) repair by age and sex.

Design, Setting, And Participants: In this retrospective, population-based, cross-sectional, time-series analysis in Ontario, Canada, from April 1, 2003, to March 31, 2016, all patients undergoing AAA repair who were older than 39 years were included.

Frequency of 30-Day Readmission and Its Causes After Endovascular Aneurysm Intervention of Abdominal Aortic Aneurysm (from the Nationwide Readmission Database).

Endovascular aneurysm intervention (EVAI) is one of the most commonly performed vascular interventions for abdominal aortic aneurysm (AAA). Data regarding 30-day readmission rates after EVAI are poorly reported in the literature. We used the United States Nationwide Readmission Database from 2010 to 2014 to identify all patients ≥18 years who were readmitted within 30 days after a hospital discharge for EVAI of the AAA.

Fenestrated endovascular aneurysm repair is associated with lower perioperative morbidity and mortality compared with open repair for complex abdominal aortic aneurysms.

Objective: The Zenith Fenestrated Endovascular Graft (ZFEN; Cook Medical, Bloomington, Ind) has expanded the anatomic eligibility of endovascular aneurysm repair (EVAR) for complex abdominal aortic aneurysms (AAAs). Current data on ZFEN mainly consist of single-institution experiences and show conflicting results. Therefore, we compared perioperative outcomes after repair using ZFEN with open complex AAA repair and infrarenal EVAR in a nationwide multicenter registry.

Hospital Volume Matters: The Volume-Outcome Relationship in Open Juxtarenal AAA Repair.

Objective: We studied whether the volume-outcome relationship would persist in more complex aortic operations.

Background: Despite the added complexity of the involvement of the renal arteries in open juxtarenal abdominal aortic aneurysm (AAA) repair, the volume effect in these difficult operations has yet to be defined.

Methods: We identified all patients in the Vascular Quality Initiative (VQI) who underwent open AAA repair from 2003 to 2016.

Current status of the treatment of infrarenal abdominal aortic aneurysms.

Aortic aneurysms are the 13 leading cause of death in the United States. While aneurysms can occur along the entire length of the aorta, the infrarenal location is the most common. Targeted ultrasound screening has been found to be an effective and economical means of preventing aortic aneurysm rupture.

Advanced endografting techniques: snorkels, chimneys, periscopes, fenestrations, and branched endografts.

The anatomy of aortic aneurysms from the proximal neck to the access vessels may create technical challenges for endovascular repair. Upwards of 30% of patients with abdominal aortic aneurysms (AAA) have unsuitable proximal neck morphology for endovascular repair. Anatomies considered unsuitable for conventional infrarenal stent grafting include short or absent necks, angulated necks, conical necks, or large necks exceeding size availability for current stent grafts.

Complications of endovascular aneurysm repair of the thoracic and abdominal aorta: evaluation and management.

In recent decades, endovascular aneurysm repair or endovascular aortic repair (EVAR) has become an acceptable alternative to open surgery for the treatment of thoracic and abdominal aortic aneurysms and other aortic pathologies such as the acute aortic syndromes (e.g., penetrating aortic ulcer, intramural hematoma, dissection).

Abdominal aortic aneurysm screening: concepts and controversies.

Abdominal aortic aneurysms (AAAs) are a leading cause mortality and morbidity but often go undiagnosed until late stages unless imaging is performed. In 2005, the United States Preventive Services Task Force (USPSTF) for the first time recommended one-time ultrasound screening for elderly male smokers and selective screening in other populations. These guidelines were reaffirmed and updated in 2014; a proposal for potential further revisions is now in early planning stages.

ACR Appropriateness Criteria Abdominal Aortic Aneurysm: Interventional Planning and Follow-Up.

Abdominal aortic aneurysms (AAAs) are a relatively common vascular problem that can be treated with either open, surgical repair or endovascular aortic aneurysm repair (EVAR). Both approaches to AAA repair require dedicated preoperative imaging to minimize adverse outcomes. After EVAR, cross-sectional imaging has an integral role in confirming the successful treatment of the AAA and early detection of complications related to EVAR.

The antibiotic cyclomarin blocks arginine-phosphate-induced millisecond dynamics in the N-terminal domain of ClpC1 from .

can remain dormant in the host, an ability that explains the failure of many current tuberculosis treatments. Recently, the natural products cyclomarin, ecumicin, and lassomycin have been shown to efficiently kill persisters. Their target is the N-terminal domain of the hexameric AAA+ ATPase ClpC1, which recognizes, unfolds, and translocates protein substrates, such as proteins containing phosphorylated arginine residues, to the ClpP1P2 protease for degradation.

Use of an Assistant Surgeon Does not Mitigate the Effect of Lead Surgeon Volume on Outcomes Following Open Repair of Intact Abdominal Aortic Aneurysms.

Objective/background: While higher lead surgeon volume has been associated with lower mortality following open abdominal aortic aneurysm (AAA) repair, little is known about the impact of using an attending surgeon as assistant surgeon. The aim of this study was to determine whether the presence of an assistant surgeon, particularly a high volume assistant, mitigates the relationship between lead surgeon volume and outcomes.

Methods: All Medicare beneficiaries who underwent intact, open AAA repair between 2003 and 2008 were evaluated and nested regression models were constructed to evaluate the relationship between surgeon and assistant volume and peri-operative mortality, adjusting for comorbid conditions and hospital volume.

Mortality after endovascular treatment of infrarenal abdominal aortic aneurysms - the newer the better?

Although endovascular repair of infrarenal abdominal aortic aneurysms (EVAR) presents a delicate alternative treatment for abdominal aortic aneurysms (AAA) with lower perioperative mortality, its long-term efficacy remains a matter of concern. The purpose of this study was to evaluate the currently reported mortality evidence after EVAR and to examine the possible effect of aneurysm status and the study period on mortality rates. The PubMed and Cochrane bibliographical databases were thoroughly searched for studies reporting on more than 1 000 patients with non-ruptured or ruptured infrarenal AAA, treated with EVAR from August 1991 to September 2016.

Early reintervention after open and endovascular abdominal aortic aneurysm repair is associated with high mortality.

Objective: Although reinterventions are generally considered more common after endovascular aneurysm repair (EVAR) than after open surgical repair (OSR), less is known about reintervention in the early postoperative period. Furthermore, there are few data regarding the impact of early reintervention on 30-day mortality. We sought to evaluate the rates and types of reintervention after abdominal aortic aneurysm (AAA) repair and the impact of reintervention on postoperative mortality.

The p97 Inhibitor CB-5083 Is a Unique Disrupter of Protein Homeostasis in Models of Multiple Myeloma.

Inhibition of the AAA ATPase, p97, was recently shown to be a novel method for targeting the ubiquitin proteasome system, and CB-5083, a first-in-class inhibitor of p97, has demonstrated broad antitumor activity in a range of both hematologic and solid tumor models. Here, we show that CB-5083 has robust activity against multiple myeloma cell lines and a number of multiple myeloma models. Treatment with CB-5083 is associated with accumulation of ubiquitinated proteins, induction of the unfolded protein response, and apoptosis.

Mutation in human elevates levels of aminolevulinate synthase and protoporphyrin IX to promote erythropoietic protoporphyria.

Loss-of-function mutations in genes for heme biosynthetic enzymes can give rise to congenital porphyrias, eight forms of which have been described. The genetic penetrance of the porphyrias is clinically variable, underscoring the role of additional causative, contributing, and modifier genes. We previously discovered that the mitochondrial AAA+ unfoldase ClpX promotes heme biosynthesis by activation of δ-aminolevulinate synthase (ALAS), which catalyzes the first step of heme synthesis.

Abdominal Aortic Aneurysm Screening Practices: Impact of the 2014 U.S. Preventive Services Task Force Recommendations.

Purpose: To assess changes in abdominal aortic aneurysm (AAA) ultrasound screening associated with the release of revised U.S. Preventive Services Task Force (USPSTF) recommendations on June 24, 2014.