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.

Prognostic implications of pre-existing medical comorbidity in Takotsubo cardiomyopathy.

Takotsubo cardiomyopathy (TC) is associated with significant short-term morbidity and mortality. Several risk factors for poor outcomes have been identified; however, the prognostic implications of pre-existing comorbidity in TC are poorly delineated. We sought to assess the association of aggregate pre-existing comorbidity with short-term outcomes in TC. We performed a retrospective observational study of adult subjects diagnosed with TC at two academic tertiary care hospitals between 2005 and 2018. Overall burden of medical comorbidity was estimated using the Charlson comorbidity index (CCI). Multivariable logistic regression was used to test for independent association of CCI with 30-day mortality and severe shock at index presentation. Multivariable poisson regression was performed to assess the association of CCI with duration of hospitalization. Five-hundred and thirty-eight subjects were diagnosed with TC during the study period. The median CCI score of all subjects was 2 (IQR 1-4). Among subjects with physical triggers of TC, the median CCI score was 2 (IQR 1-4) compared to a median CCI score of 1 (IQR 0-1) in subjects with non-physical triggers of TC (P < 0.001). Seventy-six (14%) subjects died within 30 days of index diagnosis and 185 (34%) subjects experienced severe shock. The median duration of hospitalization was 7 days (IQR 3-14 days). In multivariable logistic regression, CCI was not associated with 30-day mortality or severe shock. In multivariable Poisson regression, CCI (IRR 1.17, 95% CI 1.16-1.18, P < 0.001) was associated with duration of hospitalization. Increased burden of pre-existing medical comorbidity was not independently associated with 30-day mortality or severe shock at index presentation, but was associated with increased duration of hospitalization after diagnosis of TC.

Initial changes in peak aortic jet velocity and mean gradient predict progression to severe aortic stenosis.

BACKGROUND: There is significant interindividual variability in the rate of aortic stenosis (AS) progression that is not accounted for in the current surveillance algorithms. We sought to examine the association between changes in peak aortic jet velocity (Vmax) and mean gradient (MG) among patients with mild or moderate AS and risk of progression to severe disease. METHODS: Adult subjects referred for echocardiography at a single academic referral center with a diagnosis of mild or moderate AS and ≥2 additional surveillance echocardiograms were included in the study. Changes in Vmax and MG between the first two echocardiograms were indexed to time and tested for association with future progression to severe AS. RESULTS: Among three hundred and sixty-four subjects, the median time between first and second echocardiograms was 1.3 years and initial changes in Vmax and MG indexed to time were +0.16 m/s per year and +1.44 mmHg per year, respectively. Fifty-three (15%) and fifty-six (15%) subjects progressed to severe AS defined by Vmax and MG, respectively. In multivariable logistic regression, initial increase in Vmax (OR = 4.19, 95% CI 1.93-9.10, p < 0.001) and initial increase in MG (OR = 1.12, 95% CI 1.06-1.18, p < 0.001) were associated with progression to severe AS. CONCLUSIONS: Initial changes in Vmax and MG among patients with mild or moderate AS are strongly associated with risk of progression to severe AS and may help guide individualized surveillance strategies.

Psychiatric Illness in Takotsubo (Stress) Cardiomyopathy: A Review.

BACKGROUND: Takotsubo cardiomyopathy (TC), also known as stress-induced cardiomyopathy, has been increasingly described in relation to psychiatric illness. METHODS: We performed a literature review to identify the key findings related to psychiatric illness in TC that may be relevant to the practice of mental health and other health care providers. RESULTS: The association of psychiatric illness with TC in addition to the spectrum of psychiatric illness found in TC, the role of exacerbation or treatment of psychiatric illness in triggering TC, different modes of presentation, prognostic implications, and long-term management of psychiatric illness in TC are discussed. Additionally, we review the limitations of the pre-existing literature and suggest areas of future research. CONCLUSIONS: There is a strong association between pre-existing psychiatric illness, particularly anxiety and mood spectrum disorders, and TC. Acute exacerbation of psychiatric illness, rapid uptitration or overdose of certain psychotropic agents, and electroconvulsive therapy may trigger TC. Further studies are needed to better evaluate the prognostic significance and long-term management of psychiatric illness in TC.

Comparison of Heparin and Bivalirudin in Patients Undergoing Orbital Atherectomy.

OBJECTIVE: We compared the angiographic and clinical outcomes of heparin and bivalirudin in patients who underwent orbital atherectomy for severely calcified coronary lesions. BACKGROUND: Severely calcified coronary lesions are associated with increased ischemic complications. Orbital atherectomy modifies calcified plaque, thereby facilitating stent delivery and stent expansion. The ideal antithrombotic agent during orbital atherectomy is unknown. Previous studies reported that bivalirudin was associated with lower bleeding rates compared with heparin plus glycoprotein IIb/IIa inhibitors during percutaneous coronary intervention. METHODS: This retrospective multicenter analysis included 458 consecutive real-world patients with severely calcified coronary arteries who underwent orbital atherectomy. Patients were stratified based on the antithrombotic agent that was used. The primary safety endpoint was the 30-day rate of major adverse cardiac and cerebrovascular events, defined as death, myocardial infarction, target-vessel revascularization, and stroke. RESULTS: Heparin was used in 356/458 cases (77.2%) and bivalirudin was used in 102/458 cases (22.8%). The primary endpoint was similar in the heparin and bivalirudin groups (2% vs 3%; P=.55), as were the 30-day rates of death (1% vs 2%; P=.51), myocardial infarction (1% vs 1%; P=.90), target-vessel revascularization (0% vs 0%; P>.99), and stroke (0% vs 0%; P=.59). Angiographic complication, stent thrombosis, and major bleeding complication rates were similarly low in both groups. CONCLUSION: Both heparin and bivalirudin were safe and effective antithrombotic agents for patients who underwent orbital atherectomy. A randomized trial is needed to determine the antithrombotic agent of choice for orbital atherectomy.

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.

Temporal Pattern and Prognostic Significance of Hypokalemia in Patients Undergoing Targeted Temperature Management Following Cardiac Arrest.

Hypokalemia has been consistently reported as a common occurrence during targeted temperature management (TTM) in comatose survivors of cardiac arrest. We sought to better describe changes in serum potassium throughout the different stages of TTM and to assess for any prognostic significance. We analyzed a prospectively collected cohort of 240 patients treated with TTM following cardiac arrest at a tertiary care hospital between 2007 and 2014. The primary outcome was poor neurologic outcome at hospital discharge, defined as a Cerebral Performance Category score >2. Secondary outcomes included death and recurrent ventricular arrhythmia before hospital discharge. Multivariable logistic regression was used to assess for association of hypokalemia and hyperkalemia with the designated outcomes. During all phases of TTM, hypokalemia and hyperkalemia occurred in 207 (86%) and 77 (32%) of patients, respectively. Hypokalemia occurred in 203 (85%) patients at target temperature, and 25 (10%) patients were hyperkalemic following normothermia. In multivariable logistic regression, hypokalemia was not associated with poor neurologic outcomes or recurrent ventricular arrhythmia. Hypokalemia was associated with reduced odds of death before hospital discharge (odds ratio = 0.36, 95% confidence interval 0.13 to 0.97, p = 0.044). Hyperkalemia was not associated with poor neurologic outcomes, death, or recurrent ventricular arrhythmia.

Pre-existing Psychiatric Illness is Associated With Increased Risk of Recurrent Takotsubo Cardiomyopathy.

BACKGROUND: The increased prevalence of psychiatric illness among patients with takotsubo cardiomyopathy (TC) has been previously described. OBJECTIVES: We sought to assess the effect of pre-existing psychiatric illness on clinical outcomes following the diagnosis of TC. METHODS: Adults diagnosed with TC at Vanderbilt University Medical Center between 1999 and 2015 were included in the study. Medical records were retrospectively reviewed to identify any pre-existing mood, anxiety, or schizophrenia-spectrum illness before TC presentation. Multivariable logistic regression was used to test for independent association of pre-existing psychiatric illness with 30-day mortality and recurrent TC; Cox proportional hazard analysis was used to evaluate for association with long-term mortality. RESULTS: Among 306 patients diagnosed with TC during the study period, 114 (37%) had a pre-existing psychiatric illness. In all, 43 (14%) and 88 (29%) patients died within 30 days of index diagnosis and as of last medical record review, respectively. Of the 269 who survived their index hospitalization, 19 (7%) had a confirmed recurrent episode of TC. In multivariable analyses, pre-existing psychiatric illness was not associated with increased 30-day (P = 0.320) or long-term (P = 0.621) mortality. Pre-existing psychiatric illness was associated with higher risk of recurrent TC (odds ratio = 7.44, 95% CI: 2.30-24.01, P < 0.001). CONCLUSIONS: Pre-existing psychiatric illness was associated with an increased risk of recurrent TC. No significant association was noted between pre-existing psychiatric illness and survival.

Pre-existing medical comorbidity is not associated with neurological outcomes in patients undergoing targeted temperature management following cardiac arrest.

The prognostic significance of chronic medical illness in comatose survivors of cardiac arrest who undergo targeted temperature management (TTM) remains largely unknown. We sought to assess the association between overall burden of pre-existing medical comorbidity and neurological outcomes in survivors of cardiac arrest undergoing TTM. We analyzed a prospectively collected cohort of 314 patients treated with TTM following cardiac arrest at a tertiary care hospital between 2007 and 2014. Overall burden of medical comorbidity was approximated with the use of the Charlson Comorbidity Index (CCI). Poor neurological outcome at hospital discharge, defined as a cerebral performance category (CPC) score >2, was the primary outcome. Secondary outcomes included death prior to hospital discharge and at 1 year following cardiac arrest. Multivariable logistic regression was used to assess the association between CCI scores and outcomes. A poor neurological outcome at hospital discharge was observed in 193 (61%) patients. One hundred and seventy-nine (57%) patients died prior to hospital discharge and a total of 195 (62%) patients had died at 1-year post-arrest. In multivariable logistic regression, elevated CCI scores were not associated with increased odds of poor neurological outcomes (OR 1.04, 95% CI 0.90-1.19, p = 0.608) or death (OR 0.99, 95% CI 0.86-1.13, p = 0.816) at hospital discharge. No association was seen between CCI scores and death at 1-year post-arrest (OR 1.09, 95% CI 0.95-1.26, p = 0.220). Increasing burden of medical comorbidity, as defined by CCI scores, is not associated with neurological outcomes or survival in patients treated with TTM.

Prognostic Significance of Early Rehospitalization After Takotsubo Cardiomyopathy.

Short-term complications, particularly rehospitalization, after a diagnosis of takotsubo cardiomyopathy (TTC) are poorly described. We sought to characterize the rates, causes, clinical associations, and prognostic implications of early rehospitalization in this patient population. We performed a retrospective observational study of all adult subjects diagnosed with TTC at an academic tertiary care hospital from 2005 to 2015. The primary outcome was rehospitalization within 30 days of index discharge. Multivariable logistic regression was used to test for association between clinical variables and rehospitalization. Association between rehospitalization and survival after index discharge was assessed as a secondary outcome using a multivariable Cox proportional hazard model. Two hundred sixty-three subjects met the inclusion criteria for the study. There were 38 rehospitalizations among 32 subjects (12%). Ninety-five percent of rehospitalizations were due to nonheart failure causes, and 76% were related to noncardiovascular complaints. In multivariable analysis, recent hospitalization before TTC diagnosis and increased length of index hospitalization were associated with greater risk of rehospitalization (odds ratio 4.58, 95% CI 1.97 to 10.65, p <0.001 and odds ratio 1.05, 95% CI 1.01 to 1.10, p = 0.026, respectively). Early rehospitalization after TTC was associated with decreased survival (hazard ratio 3.17, 95% CI 1.53 to 6.56, p = 0.002).

Temperature variability during targeted temperature management is not associated with neurological outcomes following cardiac arrest.

INTRODUCTION: Recent studies on comatose survivors of cardiac arrest undergoing targeted temperature management (TTM) have shown similar outcomes at multiple target temperatures. However, details regarding core temperature variability during TTM and its prognostic implications remain largely unknown. We sought to assess the association between core temperature variability and neurological outcomes in patients undergoing TTM following cardiac arrest. METHODS: We analyzed a prospectively collected cohort of 242 patients treated with TTM following cardiac arrest at a tertiary care hospital between 2007 and 2014. Core temperature variability was defined as the statistical variance (i.e. standard deviation squared) amongst all core temperature recordings during the maintenance phase of TTM. Poor neurological outcome at hospital discharge, defined as a Cerebral Performance Category (CPC) score>2, was the primary outcome. Death prior to hospital discharge was assessed as the secondary outcome. Multivariable logistic regression was used to examine the association between temperature variability and neurological outcome or death at hospital discharge. RESULTS: A poor neurological outcome was observed in 147 (61%) patients and 136 (56%) patients died prior to hospital discharge. In multivariable logistic regression, increased core temperature variability was not associated with increased odds of poor neurological outcomes (OR 0.38, 95% CI 0.11-1.38, p=0.142) or death (OR 0.43, 95% CI 0.12-1.53, p=0.193) at hospital discharge. CONCLUSION: In this study, individual core temperature variability during TTM was not associated with poor neurological outcomes or death at hospital discharge.

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.

Publication misrepresentation among neurosurgery residency applicants: an increasing problem.

OBJECT Misrepresentation of scholarly achievements is a recognized phenomenon, well documented in numerous fields, yet the accuracy of reporting remains dependent on the honor principle. Therefore, honest self-reporting is of paramount importance to maintain scientific integrity in neurosurgery. The authors had observed a trend toward increasing numbers of publications among applicants for neurosurgery residency at Vanderbilt University and undertook this study to determine whether this change was a result of increased academic productivity, inflated reporting, or both. They also aimed to identify application variables associated with inaccurate citations. METHODS The authors retrospectively reviewed the residency applications submitted to their neurosurgery department in 2006 (n = 148) and 2012 (n = 194). The applications from 2006 were made via SF Match and those from 2012 were made using the Electronic Residency Application Service. Publications reported as "accepted" or "in press" were verified via online search of Google Scholar, PubMed, journal websites, and direct journal contact. Works were considered misrepresented if they did not exist, incorrectly listed the applicant as first author, or were incorrectly listed as peer reviewed or published in a printed journal rather than an online only or non-peer-reviewed publication. Demographic data were collected, including applicant sex, medical school ranking and country, advanced degrees, Alpha Omega Alpha membership, and USMLE Step 1 score. Zero-inflated negative binomial regression was used to identify predictors of misrepresentation. RESULTS Using univariate analysis, between 2006 and 2012 the percentage of applicants reporting published works increased significantly (47% vs 97%, p < 0.001). However, the percentage of applicants with misrepresentations (33% vs 45%) also increased. In 2012, applicants with a greater total of reported works (p < 0.001) and applicants from unranked US medical schools (those not ranked by US News & World Report) were more likely to have erroneous citations (p = 0.038). CONCLUSIONS The incidence of legitimate and misrepresented scholarly works reported by applicants to the authors' neurosurgery residency program increased during the past 6 years. Misrepresentation is more common in applicants from unranked US medical schools and those with a greater number of reported works on their application. This trend is concerning in a profession where trustworthiness is vital. To preserve integrity in the field, programs should consider verifying citations prior to submitting their rank lists.

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.

Identification of obscure yet conserved actin-associated proteins in Giardia lamblia.

Consistent with its proposed status as an early branching eukaryote, Giardia has the most divergent actin of any eukaryote and lacks core actin regulators. Although conserved actin-binding proteins are missing from Giardia, its actin is utilized similarly to that of other eukaryotes and functions in core cellular processes such as cellular organization, endocytosis, and cytokinesis. We set out to identify actin-binding proteins in Giardia using affinity purification coupled with mass spectroscopy (multidimensional protein identification technology [MudPIT]) and have identified >80 putative actin-binding proteins. Several of these have homology to conserved proteins known to complex with actin for functions in the nucleus and flagella. We validated localization and interaction for seven of these proteins, including 14-3-3, a known cytoskeletal regulator with a controversial relationship to actin. Our results indicate that although Giardia lacks canonical actin-binding proteins, there is a conserved set of actin-interacting proteins that are evolutionarily indispensable and perhaps represent some of the earliest functions of the actin cytoskeleton.