Immune Checkpoint Therapies and Atherosclerosis: Mechanisms and Clinical Implications: JACC State-of-the-Art Review.

Immune checkpoint inhibitor therapy has revolutionized the treatment of advanced malignancies in recent years. Numerous reports have detailed the myriad of possible adverse inflammatory effects of immune checkpoint therapies, including within the cardiovascular system. However, these reports have been largely limited to myocarditis. The critical role of inflammation and adaptive immunity in atherosclerosis has been well characterized in preclinical studies, and several emerging clinical studies indicate a potential role of immune checkpoint targeting therapies in the development and exacerbation of atherosclerosis. In this review, we provide an overview of the role of T-cell immunity in atherogenesis and describe the molecular effects and clinical associations of both approved and investigational immune checkpoint therapy on atherosclerosis. We also highlight the role of cholesterol metabolism in oncogenesis and discuss the implications of these associations on future treatment and monitoring of atherosclerotic cardiovascular disease in the oncologic population receiving immune checkpoint therapy.

Vaping Instead of Cigarette Smoking: A Panacea or Just Another Form of Cardiovascular Risk?

Since 2007, the electronic cigarette (EC), with its increasingly diverse array of device options, has gained popularity both among long-term tobacco cigarette (TC) smokers and among never-smoking youth. The absence of a number of known toxic by-products of TC smoking has helped cultivate the perception that ECs are healthy. However, an expanding literature has provided concerning evidence that a number of EC constituents, including nicotine, and their thermal degradation by-products may have adverse effects, including cardiovascular effects. In this review, we discuss the cardiovascular risks associated with EC vaping and compare this risk profile with TC smoking. Acknowledging the dynamic nature of EC vaping, we will focus on the latest developments, including the introduction of the pod-like device, which is the most popular EC device used today. We discuss the implications of a new, unique, nicotine chemistry that mimics the efficient and addictive nicotine delivery of TCs. Furthermore, we touch on the outbreak of the lethal lung disease associated with ECs, which exposed the lack of quality control in the EC industry. Along the way, we will identify the limitations of current knowledge and provide suggestions for future research. Overall, we conclude that although ECs may once have held promise as part of a harm-reduction strategy in people who smoke lethal TCs, this role has been largely offset by the unconscionable marketing to our youth, in addition to a failure of regulation and enforcement, leading to significant harm, especially in never-smokers who use them.

Outcomes of Patients With a History of Coronary Artery Bypass Grafting Who Underwent Orbital Atherectomy for Severe Coronary Artery Calcification.

OBJECTIVE: We assess the angiographic and clinical outcomes of patients with a history of coronary artery bypass graft (CABG) surgery who underwent orbital atherectomy for the treatment of severely calcified coronary lesions. BACKGROUND: The presence of severe coronary artery calcification (CAC) increases the complexity of percutaneous coronary intervention (PCI) and is associated with worse clinical outcomes. Patients with a history of CABG who undergo PCI often have comorbidities and are at higher risk for ischemic complications. METHODS: Of the 458 patients who underwent orbital atherectomy, 77 patients (17%) had a history of CABG and 381 (83%) did not. The primary endpoint was rate of 30-day major adverse cardiac and cerebrovascular events (MACCE), comprised of cardiac death, myocardial infarction (MI), target-vessel revascularization (TVR), and stroke. RESULTS: The CABG group had a higher prevalence of hypertension, chronic renal insufficiency, history of PCI, and unstable angina. The primary endpoint was similar in the CABG and non-CABG groups (1% vs 2%; P=.56), as were the individual endpoints of cardiac death (0% vs 2%; P=.27), MI (1% vs 1%; P=.85), TVR (0% vs 0%; P>.99), and stroke (0% vs 0%; P=.65). The rates of angiographic complications and stent thrombosis were similarly low in both groups. CONCLUSION: Despite a higher-risk baseline profile, patients with a history of CABG had similar angiographic and clinical outcomes compared with patients who had no previous history of CABG. Further studies are needed to clarify the role of orbital atherectomy in these patients.

Type 2 diabetes is an independent negative prognostic factor in patients undergoing surgical resection of a WHO grade I meningioma.

OBJECTIVES: In recent years, there has been increased recognition of the relationship between type 2 diabetes mellitus (DM) and poor outcomes following a variety of surgical procedures. We sought to study the role of type 2 DM as a prognostic factor affecting the long-term survival of patients undergoing surgical resection of a WHO Grade I meningioma. METHODS: We conducted a retrospective cohort study on 196 patients who had a WHO Grade I meningioma resected at our institution between 2001 and 2013. The medical record was reviewed to identify a pre-existing diagnosis of type 2 DM. Patient mortality was reviewed by medical record and Social Security Death Index (SSDI). Variables associated with survival in a univariate analysis were included in the multivariate Cox model if P<0.10. Variables with probability values >0.05 were then removed from the multivariate model in a step-wise fashion. RESULTS: 33 (17%) patients had pre-existing diagnoses of type 2 DM prior to clinical presentation. Mean survival time in diabetic patients was 52.1 months compared to 160.9 months in non-diabetics. The decreased survival rate and time in patients with type 2 DM were found to be statistically significant (p=0.008 and p<0.0001, respectively). In a multivariate Cox analysis, a pre-existing history of type 2 DM was independently associated with decreased survival following the resection of a WHO Grade I meningioma (HR=2.6, p=0.045). CONCLUSIONS: A pre-existing diagnosis of type 2 DM is an independent negative prognostic indicator following the resection of a WHO Grade I meningioma.

Factors Associated with Low Socioeconomic Status Predict Poor Postoperative Follow-up after Meningioma Resection.

Objectives To quantify the rates of loss of follow-up after meningioma resection and to identify any key demographical associations. Design Retrospective cohort. Setting Vanderbilt University Medical Center, 2001-2013. Participants A total of 281 patients surgically treated for an intracranial meningioma at a single institution between 2001 and 2013. Main Outcome Measures Patient clinical follow-up within the first postoperative year. Results A history of tobacco use (p < 0.0001), ongoing alcohol abuse at time of presentation (p = 0.0014), Medicaid coverage (p < 0.0001), and lack of a college degree (p < 0.0001) were all found to be predictors of loss of follow-up at a statistically significant level. Conclusions Several factors associated with low socioeconomic status are predictors of poor clinical follow-up after meningioma resection. The health risk of poor follow-up in this patient population is significant, and increased measures are needed to ensure regular appointment attendance.

Early postoperative emergency department presentation predicts poor long-term outcomes in patients surgically treated for meningioma.

Previous authors have identified a number of factors that predict morbidity, mortality, and recurrence in patients undergoing resection of a meningioma. We sought to study a novel potential prognostic indicator: early postoperative visit to the emergency department (ED). We conducted a retrospective cohort study on 239 patients who underwent a meningioma resection at our institution between 2001 and 2013 with over 3 months of follow-up postoperatively. All postoperative entries in the medical record were reviewed to identify any ED visit with a neurologic or wound-related complaint within a 90 day postoperative period. The relationships between ED presentation, tumor grade, and extent of surgical resection with future risk of operative recurrence and mortality were analyzed using Fisher's exact test. Variables associated with increased risks of mortality or operative recurrence in a univariate analysis were then included in the multivariate logistic regression model. Patients with a postoperative ED visit were found to be significantly more likely to die during the follow-up period (23.0% versus 4.85%, p<0.0001) or develop an eventual operative recurrence (12.2% versus 3.0%, p=0.0131). Postoperative ED presentation was found to be associated with a higher risk of mortality and operative recurrence independent of pathological tumor grade (p<0.0001 and p=0.0102, respectively). Presentation to the ED is associated with significantly higher rates of future operative recurrence and mortality in patients with recent meningioma resections. This poor prognostic relationship is independent of tumor pathological grade. Increased vigilance and follow-up may be warranted in such patients.

Short-term postoperative surveillance imaging may be unnecessary in elderly patients with resected WHO Grade I meningiomas.

The optimal timing and frequency of postoperative imaging surveillance after a meningioma resection are not well-established. The low recurrence rates and slow growth of World Health Organization (WHO) Grade I meningiomas in particular have raised doubts about the utility of postoperative imaging surveillance. We sought to analyze the cost and utility of asymptomatic surveillance imaging in elderly patients after the resection of a WHO Grade I meningioma. We conducted a retrospective cohort study on 45 patients who had a primary WHO Grade I meningioma resected at our institution between 2001-2013 at or above the age of 60 with a minimum of 2 years of follow-up. All postoperative clinic notes were reviewed alongside imaging results to verify that patients were asymptomatic during the surveillance period. MRI and CT scan costs (all $USD) were estimated at $599.61 and $334.31 respectively based on the Centers for Medicare and Medicaid national averages. During an average follow-up period of 4.5 years, the average number of total imaging studies performed per asymptomatic patient was 3.58 with an average total cost of $2086.30 per patient. Forty-two (93%) patients had no new abnormal findings on any of their imaging. Three (7%) patients demonstrated either a new meningioma or progressive growth of the postoperative residual tumor on imaging. No asymptomatic patient underwent a reoperation. Our data suggest that elderly patients with resected WHO Grade I meningiomas are at low risk for recurrence and may not need asymptomatic surveillance imaging for the first several postoperative years.

Imaging of Resected Nonfunctioning Pituitary Adenomas: The Cost of Surveillance.

Objectives To determine the cost of annual magnetic resonance imaging (MRI) surveillance after resection of nonfunctioning pituitary adenomas (NFPAs) and its effectiveness in reducing visual compromise due to tumor recurrence. Design Retrospective case series. Setting Vanderbilt University Medical Center (2003-2011). Participants A total of 120 patients underwent primary transsphenoidal resection and surveillance of NFPAs between 2003 and 2011. Main Outcome Measures Time from initial surgery to most recent imaging or progression. Surveillance MRI costs according to Centers for Medicare and Medicaid database and visual field deficits. Results Patients received 382 surveillance scans at a total cost of $218,477.30. The median follow-up was 47 months (interquartile range [IQR]: 26-76), and the median interval between scans was 357 days (IQR: 225-434). Overall, 50 scans (13%) revealed tumor growth. The cost per scan revealing growth was $4,369.55. The cost to identify 19 patients (16%) with clinically significant growth was $11,498.80 per patient. A total of 5 of 19 patients (26%) experienced new visual deficits prior to intervention. Patients with visual decline tended to have longer scan intervals than those with preserved vision (mean: 239 versus 794 days; p = 0.0584). No patient with annual surveillance imaging experienced visual decline. Conclusions Annual MRI scans are a sensitive and cost-conscious method to identify NFPA recurrence prior to visual decline.