Risk Factors for Development of Incisional Hernia after Aortic Aneurysm Repair: Secondary Analysis of the OVER Randomized Controlled Trial.

BACKGROUND: Since the risk of mortality from rupture is elevated, elective repair of abdominal aortic aneurysms (AAAs) is often recommended. Currently, over 80% of elective repairs are carried out using an endovascular approach. While open repair has similar late survival and fewer reintervention outcomes when compared to endovascular repair, incisional hernia is a frequent complication with morbidity and cost implications. The Open versus Endovascular Repair (OVER) trial was the largest randomized trial of endovascular versus open repair of AAA in the United States. The purpose of this study was to determine risk factors associated with incisional hernia development following AAA repair via secondary analysis of the OVER data. METHODS: This was a multisite trial conducted within the Veterans Affairs health-care system. Study participants (N = 881) were enrolled from 2002 to 2008 and followed until 2011 with additional administrative data collection until 2016. Eligible patients had AAA for which elective repair was planned and randomized 1:1 to either open or endovascular repair. Incisional hernia was a prespecified end point in the OVER protocol, specifically assessed at each protocol follow-up visit. Technical details were extracted from each operative report, repair case report form(s), and adverse event form(s). Patient demographics, comorbid conditions, reported preoperative activity level, and operative details including initial approach, blood loss, and closure methods were analyzed using Bayesian hierarchical Weibull survival regression modeling. RESULTS: Incisional hernias were recorded among 46 participants (5.2%). The average time to hernia diagnosis was 3.5 years. Of the 437 participants randomized to open treatment, 427 received an open repair including crossovers from endovascular treatment assignment. Transperitoneal repair was performed in 81%, running suture in 96%, and absorbable suture in 71% of cases. Randomization to endovascular repair was associated with reduced risk of hernia (hazard ratio [HR] 0.70, 95% credible interval [CI] 0.49-0.94). Higher activity level was associated with increased hernia risk (HR 1.39, 95% CI 1.06-1.84). Approach, suture closure techniques, body mass index, diabetes, and smoking status were not associated with increased risk of hernia development. CONCLUSIONS: Incisional hernia is a frequent complication associated with open repair of abdominal aortic aneurysm and commonly required reintervention. Endovascular repair was associated with reduced risk of hernia. Patients with increased activity experienced a higher incidence of hernia. However, no other modifiable patient, operative, or technical factors were found to be associated with hernia development.

Effect of preservation of antegrade hypogastric flow on development of claudication following aortoiliac aneurysm repair.

OBJECTIVE: The objective of this study was to compare the rate of development of buttock claudication in patients undergoing aortoiliac aneurysm repair with and without exclusion of antegrade hypogastric arterial flow. In the absence of convincing data, questions remain regarding the best management of hypogastric arterial flow to prevent the theoretical risk of buttock claudication. METHODS: The Veterans' Affairs Open Versus Endovascular Repair (OVER) Cooperative Study prospectively collected information on buttock claudication. Trial participants were specifically prompted both pre- and postoperatively to report the development of claudication symptoms at several anatomic levels. Of note, trial investigators were specifically trained to occlude the trunk hypogastric arterial, preserving the anterior and posterior divisions. Bayesian survival models were created to evaluate time to development of left, right, or bilateral buttock claudication according to the presence/absence of antegrade hypogastric perfusion. RESULTS: A total of 881 patients from the OVER trial with information regarding status of hypogastric flow were included in the analysis. Of these, 788 patients maintained bilateral antegrade hypogastric arterial perfusion, 63 had right hypogastric coverage/occlusion, and 27 had left hypogastric coverage/occlusion, whereas 3 patients had bilateral hypogastric coverage/occlusion. Just under 5% of all patients (n = 41) developed buttock claudication. After adjustment for smoking, chronic obstructive pulmonary disease, medications, study arm, preoperative activity level, body mass index, age, and diabetes, intervention-related changes to hypogastric perfusion had no effect on time to development of buttock claudication. A Maximum A Posteriori Kullback- Leibler misfit χ2 was 14.45 with 24 degrees of freedom, resulting in a goodness of fit P-value of P = .94, indicative of a good fit. CONCLUSIONS: OVER is the largest aneurysm treatment study to prospectively collect data related to the development of claudication as well as hypogastric preservation status. Despite this, we were unable to find evidence to support the assertion that preservation of antegrade hypogastric flow decreases the rate of development of buttock claudication symptoms. The low rate of development of buttock claudication overall and in the subgroups is striking.

Analysis of Repair Type and Hypogastric Artery Antegrade Perfusion and Erectile Function following Repair of Abdominal Aortic Aneurysms.

BACKGROUND: Published reports suggest that exclusion of antegrade hypogastric artery flow may have deleterious effects on erectile function after abdominal aortic aneurysm (AAA) repair. Off-label and open surgical hybrid procedures and, more recently, purpose-built branched devices have been developed to maintain antegrade pelvic perfusion in patients undergoing endovascular repair. Maintaining antegrade perfusion may reduce a spectrum of risks, including buttock claudication, colorectal ischemia, and spinal cord ischemia when patients undergo subsequent thoracic aortic procedures, as well as erectile dysfunction (ED). This project specifically focuses on erectile function, and analyzes baseline associations and relationships of hypogastric artery exclusion on changes in erectile function following aneurysm repair. METHODS: Male patients in the Veterans Affairs Open Versus Endovascular Repair (CSP#498; OVER) Trial had erectile function assessed preoperatively and postoperatively by administration of the International Index of Erectile Function-5 questionnaire. Bayesian mixed-effects regression models were created with the outcome variable (erectile function) treated as a latent variable. Primary effects of differences in erectile function between groups with and without preservation of bilateral antegrade hypogastric flow were compared. RESULTS: 876 men (442 randomized to endovascular repair) were enrolled in the trial and included in the analysis comparing treatment assignment. There is significant ED in elderly men with aortic aneurysm at baseline. Over 5 years of follow-up, there is modest decrease in erectile function and the endovascular group has improved function compared to open repair (0.082; 95% credible interval (CI) 0.008 and 0.155). A fifth of patients did not have bilateral preservation of antegrade hypogastric artery perfusion, with no difference in erectile function by univariate analysis. A more detailed regression analysis was applied--and after adjustment for baseline score, age, beta blocker use, diabetes, activity level, ejection fraction, preoperative ankle-brachial indices and time--preservation of both antegrade hypogastric arteries' perfusion showed transient improvement in survey scores compared to occlusion of at least 1 hypogastric artery at 6 months and 12 months after treatment, although this was not sustained at 60 months (score change: 0.046; 95% CI: -0.123, 0.215). Retesting this model in the cohort with complete data as a sensitivity analysis did not meaningfully change the conclusions. CONCLUSIONS: In this large prospective aneurysm treatment trial with systematic measurement of erectile function with a validated instrument, endovascular repair is associated with improved erectile function. Preservation of antegrade hypogastric flow with any repair is associated with early improved erectile function; however, it is not a sustained benefit. There is limited benefit of maintaining bilateral hypogastric artery perfusion for this specific indication in unselected men undergoing AAA repair.

Machine learning as a new paradigm for characterizing localization and lateralization of neuropsychological test data in temporal lobe epilepsy.

In this study, we employed a kernel support vector machine to predict epilepsy localization and lateralization for patients with a diagnosis of epilepsy (n = 228). We assessed the accuracy to which indices of verbal memory, visual memory, verbal fluency, and naming would localize and lateralize seizure focus in comparison to standard electroencephalogram (EEG). Classification accuracy was defined as models that produced the least cross-validated error (CVϵ). In addition, we assessed whether the inclusion of norm-based standard scores, demographics, and emotional functioning data would reduce CVϵ. Finally, we obtained class probabilities (i.e., the probability of a particular classification for each case) and produced receiver operating characteristic (ROC) curves for the primary analyses. We obtained the least error assessing localization data with the Gaussian radial basis kernel function (RBF; support vectors = 157, CVϵ = 0.22). There was no overlap between the localization and lateralization models, such that the poorest localization model (the hyperbolic tangent kernel function; support vectors = 91, CVϵ = 0.36) outperformed the strongest lateralization model (RBF; support vectors = 201, CVϵ = 0.39). Contrary to our hypothesis, the addition of norm, demographics, and emotional functioning data did not improve the accuracy of the models. Receiver operating characteristic curves suggested clinical utility in classifying epilepsy lateralization and localization using neuropsychological indicators, albeit with better discrimination for localizing determinations. This study adds to the existing literature by employing an analytic technique with inherent advantages in generalizability when compared to traditional single-sample, not cross-validated models. In the future, class probabilities extracted from these and similar analyses could supplement neuropsychological practice by offering a quantitative guide to clinical judgements.

Cognition Mediates the Association Between Cerebrospinal Fluid Biomarkers of Amyloid and P-Tau and Neuropsychiatric Symptoms.

Background: Neuropsychiatric symptoms (NPS) can be an early manifestation of Alzheimer's disease (AD). However, the associations among NPS, cognition, and AD biomarkers across the disease spectrum are unclear. Objective: We analyzed cross-sectional mediation pathways between cerebrospinal fluid (CSF) biomarkers of AD (Aß1-42, p-tau181), cognitive function, and NPS. Methods: Primary models included 781 participants from the National Alzheimer's Coordinating Center (NACC) data set who had CSF analyzed for AD biomarkers using Lumipulse. NPS were assessed with the Neuropsychiatric Inventory Questionnaire (NPI-Q). We assessed cognition with the harmonized MMSE/MoCA, as well as neuropsychological tests sensitive to AD pathology: story recall, naming, animal fluency, and Trails B. The Clinical Dementia Rating (CDR®) scale assessed dementia severity. Mediation models were estimated with Kemeny metric covariance in a structural equation model framework, controlling for age, education, sex, and APOEɛ4. Results: The sample was older adults (M = 73.85, SD = 6.68; 49.9% male, 390; 27.9% dementia, 218) who were predominantly white (n = 688, 88.1%). Higher p-tau181/Aß1-42 ratio predicted higher NPI-Q, which was partially mediated by the MMSE/MoCA and, in a second model, story recall. No other pathway was statistically significant. Both the MMSE/MoCA and NPI-Q independently mediated the association between p-tau181/Aß1-42 ratio and CDR global impairment. With dementia excluded, p-tau181/Aß1-42 ratio was no longer associated with the NPI-Q. Conclusions: NPS may be secondary to cognitive impairment and AD pathology through direct and indirect pathways. NPS independently predict dementia severity in AD. However, AD pathology likely plays less of a role in NPS in samples without dementia.

Trajectories of Cognitive Decline in Brain Donors With Autopsy-Confirmed Alzheimer Disease and Cerebrovascular Disease.

BACKGROUND AND OBJECTIVES: Cerebrovascular disease (CBVD) is frequently comorbid with autopsy-confirmed Alzheimer disease (AD), but its contribution to the clinical presentation of AD remains unclear. We leveraged the National Alzheimer's Coordinating Center (NACC) uniform and neuropathology datasets to compare the cognitive and functional trajectories of AD+/CBVD+ and AD+/CBVD- brain donors. METHODS: The sample included NACC brain donors with autopsy-confirmed AD (Braak stage ≥3, Consortium to Establish a Registry for Alzheimer's Disease score ≥2) and complete Uniform Data Set (UDS) evaluations between 2005 and 2019, with the most recent UDS evaluation within 2 years of autopsy. CBVD was defined as moderate to severe arteriosclerosis or atherosclerosis. We used propensity score weighting to isolate the effects of comorbid AD and CBVD. This method improved the balance of covariates between the AD+/CBVD+ and AD+/CBVD- groups. Longitudinal mixed-effects models were assessed with robust bayesian estimation. UDS neuropsychological test and the Clinical Dementia Rating Scale Sum of Boxes (CDR-SB) scores were primary outcomes. RESULTS: Of 2,423 brain donors, 1,476 were classified as AD+/CBVD+. Compared with AD+/CVBD- donors, the AD+/CBVD+ group had accelerated decline (i.e., group × time effects) on measures of processing speed (ß = -0.93, 95% CI -1.35, -0.51, Bayes factor [BF] 130.75), working memory (ß = 0.05, 95% CI 0.02, 0.07, BF 3.59), verbal fluency (ß = 0.10, 95% CI 0.04, 0.15, BF 1.28), naming (ß = 0.09, 95% CI 0.03, 0.16, BF = 0.69), and CDR-SB (ß = -0.08, 95% CI -0.12, -0.05, BF 18.11). Effects ranged from weak (BFs <3.0) to strong (BFs <150). We also found worse performance in the AD+/CBVD+ group across time on naming (ß = -1.04, 95% CI -1.83, -0.25, BF 2.52) and verbal fluency (ß = -0.73, 95% CI -1.30, -0.15, BF 1.34) and more impaired CDR-SB scores (ß = 0.45, 95% CI 0.01, 0.89, BF 0.33). DISCUSSION: In brain donors with autopsy-confirmed AD, comorbid CBVD was associated with an accelerated functional and cognitive decline, particularly on neuropsychological tests of attention, psychomotor speed, and working memory. CBVD magnified effects of AD neuropathology on semantic-related neuropsychological tasks. Findings support a prominent additive and more subtle synergistic effect for comorbid CBVD neuropathology in AD.

Inattention in misophonia: Difficulties achieving and maintaining alertness.

Introduction: Misophonia is marked by abnormal negative reactions to specific and idiosyncratic sounds. Despite unclear etiology and diagnostic conceptualization, neuropsychology may be able to help characterize the syndrome. In the current study, we administered the Attention Network Test (ANT) under symptom provocation conditions, as well as secondary measures of concept formation, perseveration, processing speed, and frustration tolerance. We assessed treatment seeking individuals with misophonia and non-clinical controls. We hypothesized higher alerting, orienting, and conflict effects on the ANT suggesting overall poorer performance for the misophonia group.Methods: The sample consisted of symptomatic individuals recruited from a randomized treatment trial prior to the mandatory waitlist (n = 11) and age, gender matched controls (n = 11). Symptomatic individuals were screened with the Misophonia Questionnaire, as well as a number of additional self-report and diagnostic measures.Results: Robust Bayesian estimation in multi-level models suggested worse alerting attention for symptomatic individuals, ßMedian = 2.766, ßSD = 1.253, 95% CI [0.322, 5.2876], Bayes factor = 31.41. There were no effects respective to block (i.e., blocks before versus during and after symptom provocation) or interaction effects. There were also no effects particular to executive functioning measures but some evidence this domain should be further explored (e.g., ANT conflict effects, perseveration, and serial math accuracy).Conclusions: We propose that symptom provocation alone does not explain the observed group difference in alerting attention, which could reflect a long-standing neuropsychological weakness. Future studies should attempt to characterize misophonia with more comprehensive neuropsychological batteries and larger samples.

A theoretical and empirical modeling of anxiety integrated with RDoC and temporal dynamics.

The newly launched Research Domain Criteria (RDoC) emphasize specific mechanisms over diagnostic categories of psychopathology. In our view, RDoC provides a useful heuristic for mental health disorders, but does not capture the complexity of psychological data when proposed mechanisms are viewed as static entities. However, temporal and complex system dynamics may advance RDoC's utility. By investigating temporal patterns within trajectories and the interaction of complex networks, we propose that dynamic modeling provides comprehensive methods with which to investigate the etiopathology and maintenance of mental health disorders. We examine applications of dynamical systems to periphery physiology, an RDoC construct that has been widely used in psychological science. A review of the literature suggests methodological problems with aggregate and reductive models. We present a dynamical systems modeling of anxiety which suggests avenues for future biomarker research. This model appears congruent with RDoC and recent learning theory.