No abstract

Background Over 70 million Americans inherit the strongest genetic risk factor for Alzheimer’s disease (AD), apolipoprotein E4 (APOE4), but have no course for reducing their risk. The association of non-steroidal anti-inflammatory drug (NSAID) use with reduced risk of AD for APOE4-carriers suggests that NSAIDs may be useful in AD prevention. Methods We identified phenotypes associated with APOE4 in APOE knock-in mice in order to define modifiable measures that correlate with risk of AD. Results APOE4 mouse brains showed altered post-translational modifications and biochemical distribution of APOE compared to APOE3 mice; these differences were also observed in brains of human APOE4 carriers. Two-month treatment with ibuprofen significantly altered the expression pattern of APOE in APOE4 mice to that of APOE3 mice; PPAR-γ agonist pioglitazone also had a significant effect. APOE4 mice also show deficits in dendritic spine density, and ibuprofen and pioglitazone significantly increased dendritic spine density. Conclusions We report new phenotypes associated with APOE4 in control human and APOE knock-in mice and their mitigation with NSAID treatment, through COX-2 inhibition and PPAR-γ activation.

The utility of Thoracic EndoVascular Aortic Repair (TEVAR) continues to progress at a very rapid rate. Initially implemented for the treatment of thoracic aortic aneurysms, TEVAR has evolved to treat a variety of aortic pathologies and reduce overall morbidity and mortality rates compared with traditional open surgical repair.Given the rapidly evolving nature of endovascular thoracic intervention, we hereby briefly review the current literature on the evolving applications of TEVAR.TEVAR continues to rapidly evolve and is being applied to a growing number of aortic pathologies. Given the perioperative, short- and mid-term morbidity and mortality rates, TEVAR is quickly surpassing traditional open surgical intervention as the ideal procedure for patients undergoing intervention of the descending thoracic aorta and applicability to ascending and arch pathologies is being explored. However, as more data becomes available TEVAR may be associated with higher rates of reoperative requirements. Data remains limited on the long-term efficacy of the intervention and should continue to be investigated.

No abstract

The complex pathophysiology of pulmonary embolism (PE) involves hemostatic activation, inflammatory processes, cellular dysfunction, and hemodynamic derangements. Due to the heterogeneity of this disease, risk stratification and diagnosis remains challenging. Biochip-array technology provides an integrated high throughput method for analyzing blood plasma samples for the simultaneous measurement of multiple biomarkers for potential risk stratification. Using biochip-array method, this study aimed to quantify the inflammatory biomarkers such as interleukin (IL)-1α, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, vascular endothelial growth factor (VEGF), interferon gamma (IFN-γ), tumor necrosis factor alpha (TNF-α), monocyte chemoattractant protein-1 (MCP-1), and epidermal growth factor (EGF) in 109 clinically confirmed PE patients in comparison to the control group comprised of plasma samples collected from 48 healthy subjects. Cytokines IL-4, IL-6, IL-8, IL-10, IL-1β, and MCP-1 demonstrated varying level of significant increase ( P < 0.05) in massive-risk PE patients compared to submassive- and low-risk PE patients. The upregulation of inflammatory cytokines in PE patients observed in this study suggest that inflammation plays an important role in the overall pathophysiology of this disease. The application of biochip-array technology may provide a useful approach to evaluate these biomarkers to understand the pathogenesis and risk stratification of PE patients.

Background: Pulmonary embolism may cause cardiac arrest secondary to obstruction of blood flow. Traditional treatment strategies include anticoagulation, thrombolysis, and mechanical extraction. Some advocate for support with extra corporeal membrane oxygenation; however, surgical therapies are contraindicated following thrombolytics. Methods: We describe the emergent use of peripheral extra corporeal membrane oxygenation following thrombolytic therapy for a saddle pulmonary embolism associated with multiple episodes of cardiac arrest. Results: The patient was stabilized with peripheral extra corporeal membrane oxygenation, anticoagulated and subsequently weaned from extra corporeal membrane oxygenation without any major bleeding complications. Conclusion:The administration of thrombolytics should not be a contraindication for extra corporeal membrane oxygenation in patients with massive pulmonary embolism associated with hemodynamic instability.

Background: Recent years have seen a trend towards utilizing a video-assisted thoracic surgery (VATS) approach for treatment of thymoma. Although increasing in practice, intermediate-and long-term oncologic outcome data is lacking for the VATS approach. There is no oncologic data for the uniportal VATS approach. We sought to evaluate the feasibility and impact on patient survival of uniportal VATS thymectomy for early-stage thymoma. Method: The clinical outcomes for 17 patients with Masaoka stage I to II thymomas treated between January of 2009 and July of 2014 at a single institution were collected retrospectively. Primary endpoint was overall survival (OS) and secondary endpoint was recurrence-free survival (RFS). Results: Ten women and seven men underwent uniportal VATS thymectomy; eleven had stage I thymoma and six had stage II thymoma. There were no conversions to open surgery. Operative mortality was zero.Mean tumor size was 3.8±1.0 centimeters, with a range of 1.9 to 6.0 centimeters. All patients underwent a R0 resection. Five-year survival was 100%, and the estimated RFS was 100%. Conclusions: Our findings suggest that uniportal VATS thymectomy for early-stage thymoma is feasible, and the intermediate-term oncologic outcomes are comparable to historic standards for open and multiincision VATS thymectomy. However, additional follow-up is required to evaluate for long-term oncologic outcomes.

Pulmonary embolism is the third most common cardiovascular syndrome with an estimated up to 25% of patients presenting with sudden death. For those who survive, a mainstay of management for patients with hemodynamic stability is anticoagulation; however, recommendations and options are rapidly changing for patients with submassive or massive pulmonary embolism with hemodynamic instability. Catheter-based and surgical approaches offer efficacious management options for unstable patients or patients with contraindications to anticoagulation; however, both approaches have inherent benefits and risk. This article seeks to offer a brief review on the recommendations and options for management of pulmonary embolism from both surgical and catheter-based perspectives.