Explantation of infected thoracic endovascular aortic repair

Prosthetic graft infection is a rare and serious complication of thoracic endovascular aortic repair associated with high mortality and posing unique challenges for treatment. The prosthetic graft infection is often identified late as patients present with mild nonspecific symptoms. We describe the successful medical management and surgical explantation of an infected thoracic endograft with an aorta-bronchial fistula, using an inline reconstruction with an antibiotic-soaked synthetic graft. In this report, we provide an example of a patient with an infected thoracic endograft and how inline reconstruction combined with appropriate medical management is an acceptable treatment strategy

Expression profile of CREB knockdown in myeloid leukemia cells.

BackgroundThe cAMP Response Element Binding Protein, CREB, is a transcription factor that regulates cell proliferation, differentiation, and survival in several model systems, including neuronal and hematopoietic cells. We demonstrated that CREB is overexpressed in acute myeloid and leukemia cells compared to normal hematopoietic stem cells. CREB knockdown inhibits leukemic cell proliferation in vitro and in vivo, but does not affect long-term hematopoietic reconstitution.MethodsTo understand downstream pathways regulating CREB, we performed expression profiling with RNA from the K562 myeloid leukemia cell line transduced with CREB shRNA.ResultsBy combining our expression data from CREB knockdown cells with prior ChIP data on CREB binding we were able to identify a list of putative CREB regulated genes. We performed extensive analyses on the top genes in this list as high confidence CREB targets. We found that this list is enriched for genes involved in cancer, and unexpectedly, highly enriched for histone genes. Furthermore, histone genes regulated by CREB were more likely to be specifically expressed in hematopoietic lineages. Decreased expression of specific histone genes was validated in K562, TF-1, and primary AML cells transduced with CREB shRNA.ConclusionWe have identified a high confidence list of CREB targets in K562 cells. These genes allow us to begin to understand the mechanisms by which CREB contributes to acute leukemia. We speculate that regulation of histone genes may play an important role by possibly altering the regulation of DNA replication during the cell cycle

CREB is a critical regulator of normal hematopoiesis and leukemogenesis

The cAMP-responsive element binding protein (CREB) is a 43-kDa nuclear transcription factor that regulates cell growth, memory, and glucose homeostasis. We showed previously that CREB is amplified in myeloid leukemia blasts and expressed at higher levels in leukemia stem cells from patients with myeloid leukemia. CREB transgenic mice develop myeloproliferative disease after 1 year, but not leukemia, suggesting that CREB contributes to but is not sufficient for leukemogenesis. Here, we show that CREB is most highly expressed in lineage negative hematopoietic stem cells (HSCs). To understand the role of CREB in hematopoietic progenitors and leukemia cells, we examined the effects of RNA interference (RNAi) to knock down CREB expression in vitro and in vivo. Transduction of primary HSCs or myeloid leukemia cells with lentiviral CREB shRNAs resulted in decreased proliferation of stem cells, cell- cycle abnormalities, and inhibition of CREB transcription. Mice that received transplants of bone marrow transduced with CREB shRNA had decreased committed progenitors compared with control mice. Mice injected with Ba/F3 cells expressing either Bcr-Abl wild-type or T315I mutation with CREB shRNA had delayed leukemic infiltration by bioluminescence imaging and prolonged median survival. Our results suggest that CREB is critical for normal myelopoiesis and leukemia cell proliferation

Managing Central Venous Access during a Healthcare Crisis

INTRODUCTION: During the COVID-19 pandemic, central venous access line teams were implemented at many hospitals throughout the world to provide access for critically ill patients. The objective of this study was to describe the structure, practice patterns and outcomes of these vascular access teams during the COVID-19 pandemic. METHODS: We conducted a cross sectional, self-reported study of central venous access line teams in hospitals afflicted with the COVID-19 pandemic. In order to participate in the study, hospitals were required to meet one of the following criteria: a) development of a formal plan for a central venous access line team during the pandemic, b) implementation of a central venous access line team during the pandemic, c) placement of central venous access by a designated practice group during the pandemic as part of routine clinical practice, or d) management of an iatrogenic complication related to central venous access in a patient with COVID-19. RESULTS: Participants from 60 hospitals in 13 countries contributed data to the study. Central venous line teams were most commonly composed of vascular surgery and general surgery attending physicians and trainees. Twenty sites had 2,657 lines placed by their central venous access line team or designated practice group. During that time, there were 11 (0.4%) iatrogenic complications associated with central venous access procedures performed by the line team or group at those 20 sites. Triple lumen catheters, Cordis(R) catheters and non-tunneled hemodialysis catheters were the most common types of central venous lines placed by the teams. Eight (14%) sites reported experience placing central venous lines in prone, ventilated patients with COVID-19. A dedicated line cart was used by 35 (59%) of hospitals. Less than 50% (24, 41%) of the participating sites reported managing thrombosed central lines in COVID-patients. Twenty-three of the sites managed 48 iatrogenic complications in patients with COVID-19 (including complications caused by providers outside of the line team or designated practice group). CONCLUSIONS: Implementation of a dedicated central venous access line team during a pandemic or other healthcare crisis is a way by which physicians trained in central venous access can contribute their expertise to a stressed healthcare system. A line team composed of physicians with vascular skill sets provides relief to resource-constrained ICU, ward, and emergency medicine teams with a low rate of iatrogenic complications relative to historical reports. We recommend that a plan for central venous access line team implementation be in place for future healthcare crises

Explantation of infected thoracic endovascular aortic repair

Prosthetic graft infection is a rare and serious complication of thoracic endovascular aortic repair associated with high mortality and posing unique challenges for treatment. The prosthetic graft infection is often identified late as patients present with mild nonspecific symptoms. We describe the successful medical management and surgical explantation of an infected thoracic endograft with an aorta-bronchial fistula, using an inline reconstruction with an antibiotic-soaked synthetic graft. In this report, we provide an example of a patient with an infected thoracic endograft and how inline reconstruction combined with appropriate medical management is an acceptable treatment strategy

A review of acute limb ischemia in COVID-positive patients.

This literature review discusses the current evidence on acute limb ischemia (ALI) in patients with COVID-19. Throughout the pandemic, these patients have been at increased risk of arterial thrombotic events and subsequent mortality as a result of a hypercoagulable state. The exact mechanism of thrombosis is unknown; however arterial thrombosis may be due to invasion of endothelial cells via angiotensin-converting enzyme 2 (ACE2) receptors, endothelial injury from inflammation, or even free-floating aortic thrombus. Multiple studies have been performed evaluating the medical and surgical management of these patients; the decision to proceed with operative intervention is dependent on the patient's clinical status as it relates to COVID-19 and morbidity of that disease. The interventions afforded typically include anticoagulation in patients undergoing palliation; alternatively, thrombectomy (endovascular and open) is utilized in other patients. There is a high risk of rethrombosis, despite anticoagulation, given persistent endothelial injury from the virus. Postoperative mortality can be high in these patients

Carotid Duplex Velocity Criteria Recommended by the Society of Radiologists in Ultrasound and Endorsed by the Intersocietal Accreditation Commission Lack Predictive Ability for Identifying High-Grade Carotid Artery Stenosis.

BACKGROUND: Carotid duplex is the first-line imaging modality for characterizing degree of carotid stenosis. The Intersocietal Accreditation Commission (IAC), in published guideline documents, has endorsed use of the Society of Radiologists in Ultrasound (SRU) criteria to characterize ≥70% stenosis: peak systolic velocity (PSV) ≥230 cm/s. We sought to perform a validation of the SRU criteria using computed tomography (CT) angiography as a gold standard imaging modality and to perform a sensitivity analysis to determine optimal velocity criteria for identifying ≥80% stenosis. METHODS: We queried all carotid duplex examinations performed at our institution between 2008 and 2017. Patients with ≥70% carotid stenosis, based on previous criteria, were identified. Of these patients, those who also had a CT angiogram of the neck within one year formed the study cohort. Patients who underwent carotid revascularization between the 2 imaging dates were excluded. Degree of stenosis, as reported from the CT angiogram, was considered the true degree of stenosis. Receiver operating characteristic (ROC) curves were generated to evaluate the SRU criteria and to identify the optimal discrimination threshold for high-grade carotid stenosis. RESULTS: Of 37,204 carotid duplex examinations, 3,478 arteries met criteria for ≥70% stenosis. Of these, 344 patients had a CT angiogram within 1 year of the carotid duplex (mean time between studies, 55 days, SD 6.5) and 240 (69.8%) were consistent with ≥80% carotid stenosis. The predictive ability of the SRU criteria to identify ≥70% stenosis was poor, with an area under the ROC curve (AUC) of 0.51. A sensitivity analysis to identify ≥80% stenosis demonstrated the optimal discrimination threshold to be PSV ≥450 cm/s or end diastolic velocity (EDV) ≥120 cm/s, with an AUC of 0.66. CONCLUSIONS: In this validation study, the SRU criteria, endorsed by the IAC, to identify ≥70% carotid stenosis had no predictive value. For detection of ≥80% stenosis, the optimal criteria are a PSV ≥450 cm/s or EDV ≥120 cm/s. This study demonstrates the critical importance of carotid duplex examination validation