Readmissions Following Endovascular Thoracic and Thoracoabdominal Aortic Repairs in the Vascular Implant Surveillance and Interventional Outcomes Network (VISION).

Background: Investigate readmission rates, diagnoses associated with readmission, and associations with mortality through 90 days postoperatively after elective endovascular thoracic and thoracoabdominal aortic repair overall and by extent of coverage.

Methods: A cohort of index elective nontraumatic endovascular thoracic and thoracoabdominal aortic cases from 2010 to 2018 was derived from the Vascular Implant Surveillance and Interventional Outcomes Network. Cohort readmissions within 90 days postoperative were examined both overall and by Crawford extent (CE) of aortic coverage.

A patient-centered textbook outcome measure effectively discriminates contemporary elective open abdominal aortic aneurysm repair quality.

Background: There is persistent controversy surrounding the merit of surgical volume benchmarks being used solely as a sufficient proxy for assessing the quality of open abdominal aortic aneurysm (AAA) repair. Importantly, operative volume quotas may fail to reflect a more nuanced and comprehensive depiction of surgical outcomes most relevant to patients. Accordingly, we herein propose a patient-centered textbook outcome (TO) for AAA repair that is analogous to other large magnitude extirpative operations performed in other surgical specialties, and test its feasibility to discriminate hospital performance using Society for Vascular Surgery (SVS) volume guidelines.

Treatment Location Variation for Chronic Limb-Threatening Ischemia in Patients With Kidney Failure.

Introduction: End-stage kidney disease (ESKD) is an established risk factor for chronic limb-threatening ischemia (CLTI). Procedural location for ESKD patients has not been well described. This study aims to examine variation in index procedural location in ESKD versus non-ESKD patients undergoing peripheral vascular intervention for CLTI and identify preoperative risk factors for tibial interventions.

Interventions in Carotid Artery Surgery: An Overview of Current Management and Future Implications.

Atherosclerotic carotid artery disease has been well studied over the last half-century by multiple randomized controlled trials attempting to elucidate the appropriate modality of therapy for this disease process. Surgical techniques have evolved from carotid artery endarterectomy and transfemoral carotid artery stenting to the development of hybrid techniques in transcarotid artery revascularization. In this article, the authors provide a review of the available literature regarding operative and medical management of carotid artery disease.

Accidental central venous catheter cannulation into aberrant arterial anatomy requiring endovascular intervention.

Central venous catheter placement continues to be an extremely common procedure throughout hospital systems. Although ultrasound guidance can mitigate some placement risks, misplacement of lines into neighboring structures, such as arteries, remains an unfortunate complication. In this report, we will discuss an 83-year-old female with aberrant left subclavian artery and right sided arch, which provided for successful stent graft coverage of arterial injury secondary to accidental subclavian artery cannulation with a central venous catheter with preservation of the right common carotid artery and avoidance of a potentially morbid sternotomy.

Differences in Long-Term Outcomes in End-Stage Kidney Disease Patients with Chronic Limb-Threatening Ischemia.

Background: End-stage kidney disease (ESKD) is a risk factor for peripheral arterial disease and major adverse limb events following infra-inguinal bypass. Despite comprising an important patient population, ESKD patients are rarely analyzed as a subgroup and are underrepresented in vascular surgery guidelines. This study aims to compare the long-term outcomes of patients with and without ESKD undergoing endovascular peripheral vascular intervention (PVI) for chronic limb-threatening ischemia (CLTI).

Investigating glycemic control in patients undergoing lower extremity bypass within an enhanced recovery pathway at a single institution.

Background: Enhanced recovery pathways (ERPs) aim to lower perioperative stress to facilitate recovery. Limited fasting combined with carbohydrate loading is a common ERP element. The effect of limited fasting has not been elucidated in patients with diabetes.

Aortic visceral segment instability is evident following thoracic endovascular aortic repair for acute and subacute type B aortic dissection.

Background: Anatomic remodeling within the thoracic aorta following thoracic endovascular aortic repair (TEVAR) for type B aortic dissection (TBAD) has been well documented. However, less is known about the response of the untreated visceral aorta. In the present study, we investigated the visceral aortic behavior after TEVAR for acute or subacute TBAD to identify any associations with the clinical outcomes.

An approach to induction of tolerance to pig cardiac xenografts in neonates.

There is a continuing need for donor hearts for infants with complex congenital heart defects. The transplantation of hearts from neonatal pigs would be an alternative to human organs, particularly if donor-specific immunological tolerance could be achieved. The great majority of infant humans do not make natural (preformed) antibodies against triple-knockout (TKO) pigs (that do not express any of the three known pig antigens against which humans have natural anti-pig antibodies).

Schizosaccharomyces pombe Pol II transcription elongation factor ELL functions as part of a rudimentary super elongation complex.

ELL family transcription factors activate the overall rate of RNA polymerase II (Pol II) transcription elongation by binding directly to Pol II and suppressing its tendency to pause. In metazoa, ELL regulates Pol II transcription elongation as part of a large multisubunit complex referred to as the Super Elongation Complex (SEC), which includes P-TEFb and EAF, AF9 or ENL, and an AFF family protein. Although orthologs of ELL and EAF have been identified in lower eukaryotes including Schizosaccharomyces pombe, it has been unclear whether SEC-like complexes function in lower eukaryotes.

Advancement of mass spectrometry-based proteomics technologies to explore triple negative breast cancer.

Understanding the complexity of cancer biology requires extensive information about the cancer proteome over the course of the disease. The recent advances in mass spectrometry-based proteomics technologies have led to the accumulation of an incredible amount of such proteomic information. This information allows us to identify protein signatures or protein biomarkers, which can be used to improve cancer diagnosis, prognosis and treatment.

TNIP2 is a Hub Protein in the NF-κB Network with Both Protein and RNA Mediated Interactions.

The NF-κB family of transcription factors is pivotal in controlling cellular responses to environmental stresses; abnormal nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling features in many autoimmune diseases and cancers. Several components of the NF-κB signaling pathway have been reported to interact with the protein TNIP2 (also known as ABIN2), and TNIP2 can both positively and negatively regulate NF-κB- dependent transcription of target genes. However, the function of TNIP2 remains elusive and the cellular machinery associating with TNIP2 has not been systematically defined.

SONAR Discovers RNA-Binding Proteins from Analysis of Large-Scale Protein-Protein Interactomes.

RNA metabolism is controlled by an expanding, yet incomplete, catalog of RNA-binding proteins (RBPs), many of which lack characterized RNA binding domains. Approaches to expand the RBP repertoire to discover non-canonical RBPs are currently needed. Here, HaloTag fusion pull down of 12 nuclear and cytoplasmic RBPs followed by quantitative mass spectrometry (MS) demonstrates that proteins interacting with multiple RBPs in an RNA-dependent manner are enriched for RBPs.

WDR76 Co-Localizes with Heterochromatin Related Proteins and Rapidly Responds to DNA Damage.

Proteins that respond to DNA damage play critical roles in normal and diseased states in human biology. Studies have suggested that the S. cerevisiae protein CMR1/YDL156w is associated with histones and is possibly associated with DNA repair and replication processes.

Proteomic and Genomic Analyses of the Rvb1 and Rvb2 Interaction Network upon Deletion of R2TP Complex Components.

The highly conserved yeast R2TP complex, consisting of Rvb1, Rvb2, Pih1, and Tah1, participates in diverse cellular processes ranging from assembly of protein complexes to apoptosis. Rvb1 and Rvb2 are closely related proteins belonging to the AAA+ superfamily and are essential for cell survival. Although Rvbs have been shown to be associated with various protein complexes including the Ino80 and Swr1chromatin remodeling complexes, we performed a systematic quantitative proteomic analysis of their associated proteins and identified two additional complexes that associate with Rvb1 and Rvb2: the chaperonin-containing T-complex and the 19S regulatory particle of the proteasome complex.

Proteins interacting with cloning scars: a source of false positive protein-protein interactions.

A common approach for exploring the interactome, the network of protein-protein interactions in cells, uses a commercially available ORF library to express affinity tagged bait proteins; these can be expressed in cells and endogenous cellular proteins that copurify with the bait can be identified as putative interacting proteins using mass spectrometry. Control experiments can be used to limit false-positive results, but in many cases, there are still a surprising number of prey proteins that appear to copurify specifically with the bait. Here, we have identified one source of false-positive interactions in such studies.

Controlling for gene expression changes in transcription factor protein networks.

The development of affinity purification technologies combined with mass spectrometric analysis of purified protein mixtures has been used both to identify new protein-protein interactions and to define the subunit composition of protein complexes. Transcription factor protein interactions, however, have not been systematically analyzed using these approaches. Here, we investigated whether ectopic expression of an affinity tagged transcription factor as bait in affinity purification mass spectrometry experiments perturbs gene expression in cells, resulting in the false positive identification of bait-associated proteins when typical experimental controls are used.

Affinity purification of protein complexes for analysis by multidimensional protein identification technology.

Characterizing protein complexes and identifying their subunits promote our understanding of the machinery involved in many in vivo processes. Proteomic studies can identify a protein's binding partners, and this can provide insight into how protein complexes function and how they are regulated. In addition, the composition of a protein complex within an organism can be investigated as a function of time, as a function of location, or during the response of an organism to a change in environment.

Human mediator subunit MED26 functions as a docking site for transcription elongation factors.

Promoter-proximal pausing by initiated RNA polymerase II (Pol II) and regulated release of paused polymerase into productive elongation has emerged as a major mechanism of transcription activation. Reactivation of paused Pol II correlates with recruitment of super-elongation complexes (SECs) containing ELL/EAF family members, P-TEFb, and other proteins, but the mechanism of their recruitment is an unanswered question. Here, we present evidence for a role of human Mediator subunit MED26 in this process.

Distinct ubiquitin ligases act sequentially for RNA polymerase II polyubiquitylation.

The proteasome degrades proteins modified by polyubiquitylation, so correctly controlled ubiquitylation is crucial to avoid unscheduled proteolysis of essential proteins. The mechanism regulating proteolysis of RNAPII has been controversial since two distinct ubiquitin ligases (E3s), Rsp5 (and its human homologue NEDD4) and Elongin-Cullin complex, have both been shown to be required for its DNA-damage-induced polyubiquitylation. Here we show that these E3s work sequentially in a two-step mechanism.

Identification and Characterization of a Schizosaccharomyces pombe RNA Polymerase II Elongation Factor with Similarity to the Metazoan Transcription Factor ELL.

ELL family transcription factors activate the rate of transcript elongation by suppressing transient pausing by RNA polymerase II at many sites along the DNA. ELL-associated factors 1 and 2 (EAF1 and EAF2) bind stably to ELL family members and act as strong positive regulators of their transcription activities. Orthologs of ELL and EAF have been identified in metazoa, but it has been unclear whether such RNA polymerase II elongation factors are utilized in lower eukaryotes.

ELL-associated factors 1 and 2 are positive regulators of RNA polymerase II elongation factor ELL.

In human cells, the ELL family of transcription factors includes at least three members, which are all capable of stimulating the overall rate of elongation by RNA polymerase II by suppressing transient pausing by the enzyme at many sites along DNA. In this report, we identify the ELL-associated factors (EAF)1 and EAF2 as strong positive regulators of ELL elongation activity. Our findings provide insights into the structure and function of ELL family transcription factors, and they bring to light direct roles for the EAF proteins in regulation of RNA polymerase II transcription.

The mammalian Mediator complex.

The multiprotein Mediator (Med) complex is an evolutionarily conserved transcriptional regulator that plays important roles in activation and repression of RNA polymerase II transcription. Prior studies identified a set of more than twenty distinct polypeptides that compose the Saccharomyces cerevisiae Mediator. Here we discuss efforts to characterize the subunit composition and associated activities of the mammalian Med complex.