Fate of the unoperated ascending thoracic aortic aneurysm: three-decade experience from the Aortic Institute at Yale University.

AIMS: This study aims to outline the 'true' natural history of ascending thoracic aortic aneurysm (ATAA) based on a cohort of patients not undergoing surgical intervention. METHODS AND RESULTS: The outcomes, risk factors, and growth rates of 964 unoperated ATAA patients were investigated, over a median follow-up of 7.9 (maximum of 34) years. The primary endpoint was adverse aortic events (AAE), including dissection, rupture, and aortic death. At aortic sizes of 3.5-3.9, 4.0-4.4, 4.5-4.9, 5.0-5.4, 5.5-5.9, and ≥6.0 cm, the average yearly risk of AAE was 0.2%, 0.2%, 0.3%, 1.4%, 2.0%, and 3.5%, respectively (P < 0.001), and the 10-year survival free from AAE was 97.8%, 98.2%, 97.3%, 84.6%, 80.4%, and 70.9%, respectively (P < 0.001). The risk of AAE was relatively flat until 5 cm of aortic size, at which it began to increase rapidly (P for non-linearity <0.001). The mean annual growth rate was estimated to be 0.10 ± 0.01 cm/year. Ascending thoracic aortic aneurysms grew in a very slow manner, and aortic growth over 0.2 cm/year was rarely seen. Multivariable Cox regression identified aortic size [hazard ratio (HR): 1.78, 95% confidence interval (CI): 1.50-2.11, P < 0.001] and age (HR: 1.02, 95% CI: 1.00-1.05, P = 0.015) as significant independent risk factors for AAE. Interestingly, hyperlipidemia (HR: 0.46, 95% CI: 0.23-0.91, P = 0.025) was found to be a significant protective factor for AAE in univariable Cox regression. CONCLUSION: An aortic size of 5 cm, rather than 5.5 cm, may be a more appropriate intervention criterion for prophylactic ATAA repair. Aortic growth may not be an applicable indicator for intervention.

Burnout and psychological distress among Hispanic nurses across Illinois and New York hospitals: Implications for structural and person-centered solutions.

BACKGROUND: Despite high levels of burnout and psychological distress among nurses, few studies have evaluated these outcomes among Hispanic nurses. PURPOSE: To evaluate the differences in job-related and psychological well-being outcomes for Hispanic and non-Hispanic White nurses and the association of nurse work environments. METHODS: Cross-sectional analysis of the 2021 RN4CAST-New York-Illinois nurse survey. Multilevel logistic regression models examined the association between nurse ethnicity and job-related outcomes and psychological well-being. DISCUSSION: Our sample included 798 (10.7%) Hispanic and 6,642 (89.3%) non-Hispanic White nurses in 249 hospitals. In unadjusted models, Hispanic ethnicity was associated with higher odds of burnout (odds ratio (OR) 1.21, 95% confidence interval (CI): 1.03-1.42), which diminished when considering the work environment (OR 1.16, 95% CI: 1.01-1.35) and nurse characteristics (i.e., age) (OR 1.01, 95% CI: 0.83-1.21). CONCLUSION: Equity-driven solutions to support the well-being of Hispanic nurses should consider a focus on the needs of young Hispanic nurses and include increased support in work environments.

Enhanced cognitive interference during visuomotor tasks may cause eye-hand dyscoordination.

In complex visuomotor tasks, such as cooking, people make many saccades to continuously search for items before and during reaching movements. These tasks require cognitive resources, such as short-term memory and task-switching. Cognitive load may impact limb motor performance by increasing demands on mental processes, but mechanisms remain unclear. The Trail-Making Tests, in which participants sequentially search for and make reaching movements to 25 targets, consist of a simple numeric variant (Trails-A) and a cognitively challenging variant that requires alphanumeric switching (Trails-B). We have previously shown that stroke survivors and age-matched controls make many more saccades in Trails-B, and those increases in saccades are associated with decreases in speed and smoothness of reaching movements. However, it remains unclear how patients with neurological injuries, e.g., stroke, manage progressive increases in cognitive load during visuomotor tasks, such as the Trail-Making Tests. As Trails-B trial progresses, switching between numbers and letters leads to progressive increases in cognitive load. Here, we show that stroke survivors with damage to frontoparietal areas and age-matched controls made more saccades and had longer fixations as they progressed through the 25 alphanumeric targets in Trails-B. Furthermore, when stroke survivors made saccades during reaching movements in Trails-B, their movement speed slowed down significantly. Thus, damage to frontoparietal areas serving cognitive motor functions may cause interference between oculomotor, visual, and limb motor functions, which could lead to significant disruptions in activities of daily living. These findings augment our understanding of the mechanisms that underpin cognitive-motor interference during complex visuomotor tasks.

"Big Data" Analyses Underlie Clinical Discoveries at the Aortic Institute.

This issue of the Yale Journal of Biology and Medicine (YJBM) focuses on Big Data and precision analytics in medical research. At the Aortic Institute at Yale New Haven Hospital, the vast majority of our investigations have emanated from our large, prospective clinical database of patients with thoracic aortic aneurysm (TAA), supplemented by ultra-large genetic sequencing files. Among the fundamental clinical and scientific discoveries enabled by application of advanced statistical and artificial intelligence techniques on these clinical and genetic databases are the following: From analysis of Traditional "Big Data" (Large data sets). 1. Ascending aortic aneurysms should be resected at 5 cm to prevent dissection and rupture. 2. Indexing aortic size to height improves aortic risk prognostication. 3. Aortic root dilatation is more malignant than mid-ascending aortic dilatation. 4. Ascending aortic aneurysm patients with bicuspid aortic valves do not carry the poorer prognosis previously postulated. 5. The descending and thoracoabdominal aorta are capable of rupture without dissection. 6. Female patients with TAA do more poorly than male patients. 7. Ascending aortic length is even better than aortic diameter at predicting dissection. 8. A "silver lining" of TAA disease is the profound, lifelong protection from atherosclerosis. From Modern "Big Data" Machine Learning/Artificial Intelligence analysis: 1. Machine learning models for TAA: outperforming traditional anatomic criteria. 2. Genetic testing for TAA and dissection and discovery of novel causative genes. 3. Phenotypic genetic characterization by Artificial Intelligence. 4. Panel of RNAs "detects" TAA. Such findings, based on (a) long-standing application of advanced conventional statistical analysis to large clinical data sets, and (b) recent application of advanced machine learning/artificial intelligence to large genetic data sets at the Yale Aortic Institute have advanced the diagnosis and medical and surgical treatment of TAA.

UNav: An Infrastructure-Independent Vision-Based Navigation System for People with Blindness and Low Vision.

Vision-based localization approaches now underpin newly emerging navigation pipelines for myriad use cases, from robotics to assistive technologies. Compared to sensor-based solutions, vision-based localization does not require pre-installed sensor infrastructure, which is costly, time-consuming, and/or often infeasible at scale. Herein, we propose a novel vision-based localization pipeline for a specific use case: navigation support for end users with blindness and low vision. Given a query image taken by an end user on a mobile application, the pipeline leverages a visual place recognition (VPR) algorithm to find similar images in a reference image database of the target space. The geolocations of these similar images are utilized in a downstream task that employs a weighted-average method to estimate the end user's location. Another downstream task utilizes the perspective-n-point (PnP) algorithm to estimate the end user's direction by exploiting the 2D-3D point correspondences between the query image and the 3D environment, as extracted from matched images in the database. Additionally, this system implements Dijkstra's algorithm to calculate a shortest path based on a navigable map that includes the trip origin and destination. The topometric map used for localization and navigation is built using a customized graphical user interface that projects a 3D reconstructed sparse map, built from a sequence of images, to the corresponding a priori 2D floor plan. Sequential images used for map construction can be collected in a pre-mapping step or scavenged through public databases/citizen science. The end-to-end system can be installed on any internet-accessible device with a camera that hosts a custom mobile application. For evaluation purposes, mapping and localization were tested in a complex hospital environment. The evaluation results demonstrate that our system can achieve localization with an average error of less than 1 m without knowledge of the camera's intrinsic parameters, such as focal length.

Real-Time Loosely Coupled 3DMA GNSS/Doppler Measurements Integration Using a Graph Optimization and Its Performance Assessments in Urban Canyons of New York.

Smart health applications have received significant attention in recent years. Novel applications hold significant promise to overcome many of the inconveniences faced by persons with disabilities throughout daily living. For people with blindness and low vision (BLV), environmental perception is compromised, creating myriad difficulties. Precise localization is still a gap in the field and is critical to safe navigation. Conventional GNSS positioning cannot provide satisfactory performance in urban canyons. 3D mapping-aided (3DMA) GNSS may serve as an urban GNSS solution, since the availability of 3D city models has widely increased. As a result, this study developed a real-time 3DMA GNSS-positioning system based on state-of-the-art 3DMA GNSS algorithms. Shadow matching was integrated with likelihood-based ranging 3DMA GNSS, generating positioning hypothesis candidates. To increase robustness, the 3DMA GNSS solution was then optimized with Doppler measurements using factor graph optimization (FGO) in a loosely-coupled fashion. This study also evaluated positioning performance using an advanced wearable system's recorded data in New York City. The real-time forward-processed FGO can provide a root-mean-square error (RMSE) of about 21 m. The RMSE drops to 16 m when the data is post-processed with FGO in a combined direction. Overall results show that the proposed loosely-coupled 3DMA FGO algorithm can provide a better and more robust positioning performance for the multi-sensor integration approach used by this wearable for persons with BLV.

Dysfunctional mode switching between fixation and saccades: collaborative insights into two unusual clinical disorders.

Voluntary rapid eye movements (saccades) redirect the fovea toward objects of visual interest. The saccadic system can be considered as a dual-mode system: in one mode the eye is fixating, in the other it is making a saccade. In this review, we consider two examples of dysfunctional saccades, interrupted saccades in late-onset Tay-Sachs disease and gaze-position dependent opsoclonus after concussion, which fail to properly shift between fixation and saccade modes. Insights and benefits gained from bi-directional collaborative exchange between clinical and basic scientists are emphasized. In the case of interrupted saccades, existing mathematical models were sufficiently detailed to provide support for the cause of interrupted saccades. In the case of gaze-position dependent opsoclonus, existing models could not explain the behavior, but further development provided a reasonable hypothesis for the mechanism underlying the behavior. Collaboration between clinical and basic science is a rich source of progress for developing biologically plausible models and understanding neurological disease. Approaching a clinical problem with a specific hypothesis (model) in mind often prompts new experimental tests and provides insights into basic mechanisms.

How sandbag-able are concussion sideline assessments? A close look at eye movements to uncover strategies.

Background: Sideline diagnostic tests for concussion are vulnerable to volitional poor performance ("sandbagging") on baseline assessments, motivated by desire to subvert concussion detection and potential removal from play. We investigated eye movements during sandbagging versus best effort on the King-Devick (KD) test, a rapid automatized naming (RAN) task.Methods: Participants performed KD testing during oculography following instructions to sandbag or give best effort.Results: Twenty healthy participants without concussion history were included (mean age 27 ± 8 years). Sandbagging resulted in longer test times (89.6 ± 39.2 s vs 48.2 ± 8.5 s, p < .001), longer inter-saccadic intervals (459.5 ± 125.4 ms vs 311.2 ± 79.1 ms, p < .001) and greater numbers of saccades (171.4 ± 47 vs 138 ± 24.2, p < .001) and reverse saccades (wrong direction for reading) (21.2% vs 11.3%, p < .001). Sandbagging was detectable using a logistic model with KD times as the only predictor, though more robustly detectable using eye movement metrics.Conclusions: KD sandbagging results in eye movement differences that are detectable by eye movement recordings and suggest an invalid test score. Objective eye movement recording during the KD test shows promise for distinguishing between best effort and post-injury performance, as well as for identifying sandbagging red flags.

Detection of normal and slow saccades using implicit piecewise polynomial approximation.

The quantitative analysis of saccades in eye movement data unveils information associated with intention, cognition, and health status. Abnormally slow saccades are indicative of neurological disorders and often imply a specific pathological disturbance. However, conventional saccade detection algorithms are not designed to detect slow saccades, and are correspondingly unreliable when saccades are unusually slow. In this article, we propose an algorithm that is effective for the detection of both normal and slow saccades. The proposed algorithm is partly based on modeling saccadic waveforms as piecewise-quadratic signals. The algorithm first decreases noise in acquired eye-tracking data using optimization to minimize a prescribed objective function, then uses velocity thresholding to detect saccades. Using both simulated saccades and real saccades generated by healthy subjects and patients, we evaluate the performance of the proposed algorithm and 10 other detection algorithms. We show the proposed algorithm is more accurate in detecting both normal and slow saccades than other algorithms.

Natural history and management of Kommerell's diverticulum in a single tertiary referral center.

OBJECTIVE: The Kommerell diverticulum (KD) is an extremely rare developmental abnormality of the aorta related to an aberrant subclavian artery (ASCA). The objective of our study was to review the natural history of KD and ASCA using our single-center experience in diagnosing and managing KD and ASCA. METHODS: A retrospective review of the Yale radiological database from January 1999 to December 2016 was performed. Only patients with KD/ASCA and a computed tomography (CT) scan of the chest were selected for review. The primary goal was to examine the natural history of KD and ASCA and the secondary goals were to review the management and outcomes of those patients treated for KD and ASCA. RESULTS: There were 75 patients with KD/ASCA identified, with a mean age of 63 ± 19 years; 49 were female (65%). On CT scans, left- and right-sided aortas were present in 47 (63%) and 28 (37%) patients. A right ASCA or a left ASCA were present in 47 (63%) and 28 (37%) patients. Six patients were symptomatic on presentation. Symptoms included dysphagia, chest or back pain, and emboli to the fingers. The mean KD diameter was 21.8 ± 6.0 mm and the distance to the opposite aortic wall (DAW) was 48.3 ± 10.8 mm. Sixty-six patients were followed for a mean of 31.7 ± 32.5 months. One patient ruptured without repair. Nine patients underwent operative intervention, including eight open and one endovascular repair. Complications from operative intervention included ischemic stroke with hemorrhagic transformation, deep vein thrombosis and pneumonia. The mean growth rate for KD and DAW was 1.45 ± 0.39 mm/year and 2.29 ± 0.47 mm/year, respectively. On multivariable regression analysis, hypertension was a predictor of growth of DAW (P = .03). CONCLUSIONS: KD is uncommon and shows a female predominance. The diverticulum grows, albeit slowly (KD and DAW growth rates of 1.45 ± 0.39 mm/year and 2.29 ± 0.47 mm/year). Most patients are asymptomatic, but dysphagia, chest/back pain, and distal emboli may occur. Rupture is rare. Symptomatic patients should be operated. Asymptomatic patients can be followed with serial CT scans.

Eye Movement Recordings: Practical Applications in Neurology.

Accurate detection and interpretation of eye movement abnormalities often guides differential diagnosis, discussions on prognosis and disease mechanisms, and directed treatment of disabling visual symptoms and signs. A comprehensive clinical eye movement examination is high yield from a diagnostic standpoint; however, skillful recording and quantification of eye movements can increase detection of subclinical deficits, confirm clinical suspicions, guide therapeutics, and generate expansive research opportunities. This review encompasses an overview of the clinical eye movement examination, provides examples of practical diagnostic contributions from quantitative recordings of eye movements, and comments on recording equipment and related challenges.

Facile synthesis of 2-azaspiro[3.4]octane.

Our annulation strategy utilized for the synthesis of 2-azaspiro[3.4]octane is explained. Three successful routes for the synthesis were developed. One of the approaches involved annulation of the cyclopentane ring and the remaining two approaches involved annulation of the four membered ring. All three approaches employ readily available starting materials with conventional chemical transformations and minimal chromatographic purifications to afford the title compound. The merits and limitations of the three approaches are also discussed.

History and Future Directions of Vision Testing in Head Trauma.

BACKGROUND: Concussion leads to neurophysiologic changes that may result in visual symptoms and changes in ocular motor function. Vision-based testing is used increasingly to improve detection and assess head injury. This review will focus on the historical aspects and emerging data for vision tests, emphasizing rapid automatized naming (RAN) tasks and objective recording techniques, including video-oculography (VOG), as applied to the evaluation of mild traumatic brain injury. METHODS: Searches on PubMed were performed using combinations of the following key words: "concussion," "mild traumatic brain injury," "rapid automatized naming," "King-Devick," "mobile universal lexicon evaluation system," "video-oculography," and "eye-tracking." Additional information was referenced from web sites of vendors of commercial eye-tracking systems and services. RESULTS: Tests of rapid number, picture, or symbol naming, termed RAN tasks, have been used in neuropsychological studies since the early 20th century. The visual system contains widely distributed networks that are readily assessed by a variety of functionally distinct RAN tasks. The King-Devick test, a rapid number naming assessment, and several picture-naming tests, such as the Mobile Universal Lexicon Evaluation System (MULES) and the modified Snodgrass and Vanderwart image set, show capacity to identify athletes with concussion. VOG has gained widespread use in eye- and gaze-tracking studies of head trauma from which objective data have shown increased saccadic latencies, saccadic dysmetria, errors in predictive target tracking, and changes in vergence in concussed subjects. Performance impairments on RAN tasks and on tasks recorded with VOG are likely related to ocular motor dysfunction and to changes in cognition, specifically to attention, memory, and executive functioning. As research studies on ocular motor function after concussion have expanded, so too have commercialized eye-tracking systems and assessments. However, these commercial services are still investigational and all vision-based markers of concussion require further validation. CONCLUSIONS: RAN tasks and VOG assessments provide objective measures of ocular motor function. Changes in ocular motor performance after concussion reflect generalized neurophysiologic changes affecting a variety of cognitive processes. Although these tests are increasingly used in head injury assessments, further study is needed to validate them as adjunctive diagnostic aids and assessments of recovery.

Natural history and management of splanchnic artery aneurysms in a single tertiary referral center.

OBJECTIVE: Splanchnic artery aneurysms (SAAs) are rare, and little is known about their natural history and management. We reviewed our single-center experience in managing this population of patients. METHODS: A retrospective review of the Yale radiologic database from January 1999 to December 2016 was performed. Only patients with an SAA and a computed tomography scan of the abdomen were selected for review. Demographics of the patients, aneurysm characteristics, management, postoperative complications, and follow-up data were collected. Our primary outcomes included aneurysm growth rate and risk of rupture in those patients managed nonoperatively and morbidity and mortality of those SAA patients who underwent operative intervention. RESULTS: There were 122 patients with 138 SAAs identified; 77 were male (62%), with a mean age of 66 years (range, 25-94 years). On computed tomography, 56 (45%) had previously diagnosed or concomitant aneurysms elsewhere. Of the patients managed nonoperatively, 101 patients (79%) had 108 SAAs; in the operative intervention group, 25 (21%) patients had 30 SAAs. The mean overall vessel diameter was 1.76 ± 0.83 cm. The diameter of observed and operatively repaired SAAs was 1.58 ± 0.56 cm and 2.41 ± 1.23 cm, respectively (P = .00001). Mean follow-up was 50 ± 42 months for nonoperative management without any adverse events related to SAA, including 10 patients with SAA >2.0 cm. The mean observed growth rate for SAA was 0.064 ± 0.18 cm/y. All symptomatic patients who presented with severe abdominal pain (n = 11 [44%]) underwent operative intervention. Five patients presented with a ruptured SAA (3.6%; range, 2.3-5.0 cm); all of them except one underwent operative intervention. Other indications for repair included large size in seven, rapid growth in two, other open abdominal surgical procedures in two, multiple aneurysms in one, and desire to pursue fertility treatment in one. Operative repair included 14 (56%) endovascular embolizations and 11 (44%) open abdominal operations. After endovascular embolization, two patients underwent abdominal operation for hemorrhage and splenectomy. Open repairs included bypasses in six, splenectomy in two, resection in two, and plication in one. Two patients had postoperative acute kidney injury that resolved and one died of multisystem organ failure. One bypass occluded without sequelae. On multivariable regression analysis, female sex (P = .02) was associated with faster growth rate, and a history of smoking (P = .04) was associated with slower growth rate. CONCLUSIONS: It seems reasonable to observe asymptomatic patients with an SAA <2.0 cm because of the slow growth rate (0.064 ± 0.18 cm/y) and benign behavior. When intervention is needed, both open and endovascular options should be considered.

Natural history and management of renal artery aneurysms in a single tertiary referral center.

OBJECTIVE: Although renal artery aneurysms (RAAs) are uncommon, several large reports have been published indicating their benign natural history. The objective of our study was to review our single-center experience managing this disease entity. METHODS: A retrospective review of the Yale radiologic database from January 1999 to December 2016 was performed. Only patients with RAA and a computed tomography scan of the abdomen were selected for review. Demographics of the patients, aneurysm characteristics, management, postoperative complications, and follow-up data were collected. RESULTS: There were 241 patients with 259 RAAs identified, with a mean age of 69 years (range, 35-100 years); 147 were female (61%). On computed tomography, aneurysms were solitary and right sided in 224 (86%) and 159 (61%), respectively; 64 (27%) patients had aneurysms elsewhere. The breakdown of RAAs by location was as follows: renal bifurcation in 84 (32%), renal pelvis in 77 (30%), distal renal artery in 58 (22%), mid renal artery in 34 (13%), and proximal renal artery in 6 (2%). Five patients had symptoms that were attributed to the RAA and underwent operative repair; all others were observed without an operation. Symptoms in the operative repair group included flank pain in four and uncontrolled hypertension in one. The mean overall diameter of the RAAs was 1.22 ± 0.49 cm. The diameter of operatively repaired and observed RAAs was 1.84 ± 0.55 cm and 1.21 ± 0.48 cm, respectively (P = .002). Operative repair included four coil embolizations and one open resection. There were no renal function changes in any of these patients after operation and no other complications. Mean follow-up was 41 ± 35 months for patients in the group that was observed; 18 of these RAAs were >2 cm, and none ruptured. On multivariable regression analysis, female sex (P = .0001), smoking history (P = .00007), left-sided RAA (P = .03), and main renal artery location (P = .03) were inversely related to growth, whereas a history of hypertension was directly related to growth rate (P = .01). The mean growth rate for RAAs was 0.017 ± 0.052 cm/y. CONCLUSIONS: RAAs tend to have a benign natural history. Although previous reports have not identified any factors that contribute to RAA growth, we observed that RAA location, sex, smoking history, and hypertension may have an impact on growth rates. No ruptures were observed. Operative repair at our institution was rare, with no morbidity or mortality. Observation of RAAs over time seems feasible in the asymptomatic patient with a small RAA.

Natural history of aneurysmal aortic arch branch vessels in a single tertiary referral center.

OBJECTIVE: Little is known about the natural history and management of aneurysmal aortic arch branch vessels (AABVs). The objectives of this study were to assess the natural history of aneurysmal AABVs and to examine the outcomes of operative intervention. METHODS: A retrospective review of the Yale radiologic database from 1999 to 2016 was performed. Only those patients with an aneurysmal AABV and a computed tomography scan were selected for review. Patients' demographics, aneurysm characteristics, management, and follow-up information were collected. RESULTS: There were 105 patients with 147 aneurysmal AABVs; 76 were male (72%), with a mean age of 70 years (range, 17-93 years). We identified 63 innominate, 50 left subclavian, 30 right subclavian, and 4 common carotid artery aneurysms. On computed tomography, 65 (62%) had aortic aneurysms and six (6%) had suffered an aortic dissection. Most were asymptomatic (104 [99%]); one had chest pain and an enlarging swollen mass. Twelve (11%) patients underwent operative repair (OR) for 12 aneurysmal AABVs because of symptoms, growth, or concomitant aortic operations; 93 (89%) were observed in the no operative repair (NOR) group with cross-sectional imaging. The overall mean vessel diameter was 2.08 ± 0.68 cm. The mean diameters in the OR and NOR groups were 3.32 ± 1.24 cm and 1.97 ± 0.46 cm, respectively (P = .002). OR included nine bypasses with resection, two stent grafts, and one resection without reconstruction. Two patients developed postoperative hemorrhage requiring re-exploration, one patient developed stent thrombosis, and one patient required pseudoaneurysm repair 20 years after index operation. Mean follow-up was 52 ± 51 months for the NOR group, with no ruptures or emboli. The growth rate was 0.04 ± 0.10 cm/y. On multivariable regression analysis, a descending aortic aneurysm (P = .041) and a left subclavian artery aneurysm (P = .016) were associated with higher growth rates, whereas height was associated with a lower growth rate (P = .001). CONCLUSIONS: Aneurysmal AABVs tend to have a benign natural history with slow growth rates and low rates of complications, including rupture and embolization. We recommend expectant observational management for small, incidentally detected aneurysms.

Prevention of Aortic Dissection Suggests a Diameter Shift to a Lower Aortic Size Threshold for Intervention.

BACKGROUND: Multiple studies have quantified the relationship between aortic size and risk of dissection. However, these studies estimated the risk of dissection without accounting for any increase in aortic size from the dissection process itself. OBJECTIVES: This study aims to compare aortic size before and after dissection and to evaluate the change in size consequent to the dissection itself. METHODS: Fifty-five consecutive patients (29 type A; 26 type B) with aortic dissection and incidental imaging studies prior to dissection were identified and compared to a control group of aneurysm patients (n = 205). The average time between measurement at and prior to dissection was 1.7 ± 1.9 years (1.9 ± 2.0 years mean inter-image time in the control group). A multivariate regression model controlling for growth rate, age, and gender was created to estimate the effect of dissection itself on aortic size. RESULTS: The mean aortic sizes at and prior to dissection were 54.2 ± 7.0 and 45.1 ± 5.7 mm for the ascending aorta, and 47.1 ± 13.8 and 39.5 ± 13.1 mm for the descending aorta, respectively. The multivariable analysis revealed a significant impact of the dissection itself (p < 0.001) and estimated an increase in size of 7.65 mm (ascending aorta) and 6.38 mm (descending aorta). Thus, a proportional estimate of 82.8% (ascending aorta) and 80.8% (descending aorta) of dissections are made at a size lower than the guideline-recommended threshold (55 mm). CONCLUSIONS: The aortic diameter increases substantially due to aortic dissection itself and, thus, aortas are being dissected at clinically meaningfully smaller sizes than natural history analyses have previously suggested. These findings have important implications regarding the size at which the risk of dissection is increased.

Evolution of Visual Outcomes in Clinical Trials for Multiple Sclerosis Disease-Modifying Therapies.

: BACKGROUND:: The visual pathways are increasingly recognized as an ideal model to study neurodegeneration in multiple sclerosis (MS). Low-contrast letter acuity (LCLA) and optical coherence tomography (OCT) are validated measures of function and structure in MS. In fact, LCLA was the topic of a recent review by the Multiple Sclerosis Outcome Assessments Consortium (MSOAC) to qualify this visual measure as a primary or secondary clinical trial endpoint with the Food and Drug Administration (FDA) and other regulatory agencies. This review focuses on the use of LCLA and OCT measures as outcomes in clinical trials to date of MS disease-modifying therapies. METHODS: A Pubmed search using the specific key words "optical coherence tomography," "low-contrast letter acuity," "multiple sclerosis," and "clinical trials" was performed. An additional search on the clinicaltrials.gov website with the same key words was used to find registered clinical trials of MS therapies that included these visual outcome measures. RESULTS: As demonstrated by multiple clinical trials, LCLA and OCT measures are sensitive to treatment effects in MS. LCLA has been used in many clinical trials to date, and findings suggest that 7 letters of LCLA at the 2.5% contrast level are meaningful change. Few clinical trials using the benefits of OCT have been performed, although results of observational studies have solidified the ability of OCT to assess change in retinal structure. Continued accrual of clinical trial and observational data is needed to validate the use of OCT in clinical trials, but preliminary work suggests that an intereye difference in retinal nerve fiber layer thickness of 5-6 µm is a clinically meaningful threshold that identifies an optic nerve lesion in MS. CONCLUSIONS: Visual impairment represents a significant component of overall disability in MS. LCLA and OCT enhance the detection of visual pathway injury and can be used as measures of axonal and neuronal integrity. Continued investigation is ongoing to further incorporate these vision-based assessments into clinical trials of MS therapies.