Longitudinal Outcomes Associated With Metabolic Dysfunction-Associated Steatotic Liver Disease: A Meta-analysis of 129 Studies.

BACKGROUND & AIMS: The progression of metabolic dysfunction-associated steatotic liver disease (MASLD) has been found to manifest in a series of hepatic and extrahepatic complications. A comprehensive meta-analysis of the longitudinal outcomes associated with MASLD has yet to be conducted. METHODS: To investigate the longitudinal outcomes associated with MASLD, Medline and Embase databases were searched to identify original studies that evaluated the longitudinal risks of incident clinical outcomes among MASLD patients compared with non-MASLD individuals. DerSimonian Laird random-effects meta-analysis was performed. Pooled effect estimates were calculated, and heterogeneity among studies was evaluated. RESULTS: One hundred twenty-nine studies were included in the meta-analysis. Meta-analysis revealed a significant increase in the risk of cardiovascular outcomes (hazard ratio [HR], 1.43; 95% confidence interval [CI], 1.27-1.60; P < .01), various metabolic outcomes such as incident hypertension (HR, 1.75; 95% CI, 1.46-2.08; P < .01), diabetes (HR, 2.56; 95% CI, 2.10-3.13; P < .01), pre-diabetes (HR, 1.69; 95% CI, 1.22-2.35; P < .01), metabolic syndrome (HR, 2.57; 95% CI, 1.13-5.85; P = .02), chronic kidney disease (HR, 1.38; 95% CI, 1.27-1.50; P < .01), as well as all cancers (HR, 1.54; 95% CI, 1.35-1.76; P < .01) among MASLD patients compared with non-MASLD individuals. By subgroup analysis, MASLD patients with advanced liver disease (HR, 3.60; 95% CI, 2.10-6.18; P < .01) were also found to be associated with a significantly greater risk (P = .02) of incident diabetes than those with less severe MASLD (HR, 1.63; 95% CI, 1.0-2.45; P = .02) when compared with non-MASLD. CONCLUSIONS: The present study emphasizes the association between MASLD and its clinical outcomes including cardiovascular, metabolic, oncologic, and other outcomes. The multisystemic nature of MASLD found in this analysis requires treatment targets to reduce systemic events and end organ complications.

Global prevalence, clinical characteristics, surveillance, treatment allocation, and outcomes of alcohol-associated hepatocellular carcinoma.

BACKGROUND AND AIMS: Although the burden of alcohol-associated hepatocellular carcinoma (HCC) is increasing with rising alcohol consumption, clinical presentation and outcomes of alcohol-associated HCC have not been systematically assessed. We aimed to determine the prevalence, clinical characteristics, surveillance rates, treatment allocation, and outcomes of alcohol-associated HCC. METHODS: Medline and Embase were searched from inception to January 2023. Proportional data were analyzed using a generalized linear mixed model. The odds ratio (OR) or mean difference comparing alcohol-associated HCC and other causes was obtained with pairwise meta-analysis. Survival outcomes were evaluated using a pooled analysis of hazard ratios. RESULTS: Of 4,824 records identified, 55 articles (86,345 patients) were included. Overall, 30.4% (CI: 24.0%-37.7%) of HCC were alcohol-associated, with the highest proportion in Europe and the lowest in the Americas. People with alcohol-associated HCC were more likely male, but similar in age and comorbidities, compared to other causes. 20.8% (CI: 11.4%-34.9%) of people with alcohol-associated HCC underwent surveillance compared to 35.0%, 31.6%, and 21.4% in hepatitis B virus, hepatitis C virus, and metabolic dysfunction-associated HCC, respectively (all P<0.05). Alcohol-associated HCC had a lower likelihood of BCLC stage (0/A) (OR: 0.7, CI: 0.6-0.9; P=0.018) and curative therapy (24.5% vs 33.9%; OR 0.7, CI: 0.5-0.9; P=0.003), and higher mortality (HR: 1.3, CI: 1.1-1.5, P=0.012) when compared to other causes. CONCLUSIONS: Alcohol-associated HCC is associated with lower surveillance rates, more advanced BCLC stage, lower likelihood of receiving curative therapy, and poorer survival. These data call for measures to reduce heavy alcohol consumption and improve strategies for effective HCC surveillance in high-risk individuals.

The incidence of adverse outcome in donors after living donor liver transplantation: A meta-analysis of 60,829 donors.

The scarcity of liver grafts has prompted developments in living donor liver transplantations (LDLT), with previous literature illustrating similar outcomes in recipients compared to deceased donor transplants. However, significant concerns regarding living donor morbidity and mortality have yet to be examined comprehensively. This study aims to provide estimates of the incidence of various outcomes in living liver donors. In this meta-analysis, Medline and Embase were searched from inception to July 2022 for articles assessing the incidence of outcomes in LDLT donors. Complications in the included studies were classified into respective organ systems. Analysis of incidence was conducted using a generalized linear mixed model with Clopper-Pearson intervals. Eighty-seven articles involving 60,829 living liver donors were included. The overall pooled incidence of complications in LDLT donors was 24.7% (CI: 21.6%-28.1%). The incidence of minor complications was 17.3% (CI: 14.7%-20.3%), while the incidence of major complications was lower at 5.5% (CI: 4.5%-6.7%). The overall incidence of donor mortality was 0.06% (CI: 0.0%-0.1%) in 49,027 individuals. Psychological complications (7.6%, CI: 4.9%-11.5%) were the most common among LDLT donors, followed by wound-related (5.2%, CI: 4.4%-6.2%) and respiratory complications (4.9%, CI: 3.8%-6.3%). Conversely, cardiovascular complications had the lowest incidence among the subgroups at 0.8% (CI: 0.4%-1.3%). This study presents the incidence of post-LDLT outcomes in living liver donors, illustrating significant psychological, wound-related, and respiratory complications. While significant advancements in recent decades have contributed towards decreased morbidity in living donors, our findings call for targeted measures and continued efforts to ensure the safety and quality of life of liver donors post-LDLT.

Dual Layer vs Single Layer Woven EndoBridge Device in the Treatment of Intracranial Aneurysms: A Propensity Score-Matched Analysis.

BACKGROUND: The Woven EndoBridge (WEB) devices have been used for treating wide neck bifurcation aneurysms (WNBAs) with several generational enhancements to improve clinical outcomes. The original device dual-layer (WEB DL) was replaced by a single-layer (WEB SL) device in 2013. This study aimed to compare the effectiveness and safety of these devices in managing intracranial aneurysms. METHODS: A multicenter cohort study was conducted, and data from 1,289 patients with intracranial aneurysms treated with either the WEB SL or WEB DL devices were retrospectively analyzed. Propensity score matching was utilized to balance the baseline characteristics between the two groups. Outcomes assessed included immediate occlusion rate, complete occlusion at last follow-up, retreatment rate, device compaction, and aneurysmal rupture. RESULTS: Before propensity score matching, patients treated with the WEB SL had a significantly higher rate of complete occlusion at the last follow-up and a lower rate of retreatment. After matching, there was no significant difference in immediate occlusion rate, retreatment rate, or device compaction between the WEB SL and DL groups. However, the SL group maintained a higher rate of complete occlusion at the final follow-up. Regression analysis showed that SL was associated with higher rates of complete occlusion (OR: 0.19; CI: 0.04 to 0.8, p = 0.029) and lower rates of retreatment (OR: 0.12; CI: 0 to 4.12, p = 0.23). CONCLUSION: The WEB SL and DL devices demonstrated similar performances in immediate occlusion rates and retreatment requirements for intracranial aneurysms. The SL device showed a higher rate of complete occlusion at the final follow-up.

Treatment of large intracranial aneurysms using the Woven EndoBridge (WEB): a propensity score-matched analysis.

The Woven EndoBridge (WEB) device is primarily used for treating wide-neck intracranial bifurcation aneurysms under 10 mm. Limited data exists on its efficacy for large aneurysms. We aim to assess angiographic and clinical outcomes of the WEB device in treating large versus small aneurysms. We conducted a retrospective review of the WorldWide WEB Consortium database, from 2011 to 2022, across 30 academic institutions globally. Propensity score matching (PSM) was employed to compare small and large aneurysms on baseline characteristics. A total of 898 patients were included. There was no significant difference observed in clinical presentations, smoking status, pretreatment mRS, presence of multiple aneurysms, bifurcation location, or prior treatment between the two groups. After PSM, 302 matched pairs showed significantly lower last follow-up adequate occlusion rates (81% vs 90%, p = 0.006) and higher retreatment rates (12% vs 3.6%, p < 0.001) in the large aneurysm group. These findings may inform treatment decisions and patient counseling. Future studies are needed to further explore this area.

Off-Label Use of Woven EndoBridge Device for Intracranial Brain Aneurysm Treatment: Modeling of Occlusion Outcome.

INTRODUCTION: The Woven EndoBridge (WEB) device is emerging as a novel therapy for intracranial aneurysms, but its use for off-label indications requires further study. Using machine learning, we aimed to develop predictive models for complete occlusion after off-label WEB treatment and to identify factors associated with occlusion outcomes. METHODS: This multicenter, retrospective study included 162 patients who underwent off-label WEB treatment for intracranial aneurysms. Baseline, morphological, and procedural variables were utilized to develop machine-learning models predicting complete occlusion. Model interpretation was performed to determine significant predictors. Ordinal regression was also performed with occlusion status as an ordinal outcome from better (Raymond Roy Occlusion Classification [RROC] grade 1) to worse (RROC grade 3) status. Odds ratios (OR) with 95% confidence intervals (CI) were reported. RESULTS: The best performing model achieved an AUROC of 0.8 for predicting complete occlusion. Larger neck diameter and daughter sac were significant independent predictors of incomplete occlusion. On multivariable ordinal regression, higher RROC grades (OR 1.86, 95% CI 1.25-2.82), larger neck diameter (OR 1.69, 95% CI 1.09-2.65), and presence of daughter sacs (OR 2.26, 95% CI 0.99-5.15) were associated with worse aneurysm occlusion after WEB treatment, independent of other factors. CONCLUSION: This study found that larger neck diameter and daughter sacs were associated with worse occlusion after WEB therapy for aneurysms. The machine learning approach identified anatomical factors related to occlusion outcomes that may help guide patient selection and monitoring with this technology. Further validation is needed.

Ethnic disparities in waitlist outcomes of patients with nonalcoholic steatohepatitis listed for liver transplantation in the US.

NASH is the fastest-growing cause of liver cirrhosis and is the leading indication for liver transplantation (LT). However, significant racial and ethnic disparities in waitlist outcomes and LT allocation may unfairly disadvantage minorities. Our aim was to characterize racial and ethnic disparities in waitlist mortality and transplantation probability among patients with NASH. This is a retrospective analysis of the United Network for Organ Sharing registry data of LT candidates from January 1, 2000 to December 31, 2021. Outcomes analysis was performed using competing risk analysis with the Fine and Gray model. The multivariable adjustment was conducted, and mixed-effect regression was used to compare the model for end-stage liver disease scores at listing and removal. Of 18,562 patients with NASH cirrhosis, there were 14,834 non-Hispanic Whites, 349 African Americans, 2798 Hispanics, 312 Asians, and 269 of other races/ethnicities; African American (effect size: 2.307, 95% CI: 1.561-3.053, and p < 0.001) and Hispanic (effect size: 0.332, 95% CI: 0.028-0.637, p = 0.032) patients were found to have a significantly higher model for end-stage liver disease scores at the time of listing than non-Hispanic Whites. African Americans had a higher probability of receiving LT relative to non-Hispanic Whites (subdistribution HR: 1.211, 95% CI: 1.051-1.396, and p = 0.008). However, Hispanic race/ethnicity was associated with a lower transplantation probability (subdistribution HR: 0.793, 95% CI: 0.747-0.842, and p < 0.001) and increased waitlist mortality (subdistribution HR: 1.173, CI: 1.052-1.308, and p = 0.004) compared with non-Hispanic Whites. There are significant racial and ethnic disparities in waitlist outcomes of patients with NASH in the US. Hispanic patients are less likely to receive LT and more likely to die while on the waitlist compared with non-Hispanic Whites despite being listed with a lower model for end-stage liver disease scores.

Continued Infarction Growth and Penumbral Consumption After Reperfusion in Vaccine-Naive Patients With COVID-19: A Case-Control Study.

BACKGROUND. Neurologic sequelae of SARS-CoV-2 include potentially malignant cerebrovascular events arising from complex hemodynamic, hematologic, and inflammatory processes occurring in concert. OBJECTIVE. This study concerns the hypothesis that despite angiographic reperfusion COVID-19 promotes continued consumption of at-risk tissue volumes after acute ischemic stroke (AIS), yielding critical insights into prognostication and monitoring paradigms in vaccine-naive patients experiencing AIS. METHODS. This retrospective study compared 100 consecutive COVID-19 patients with AIS presenting between March 2020 and April 2021 with a contemporaneous cohort of 282 AIS patients without COVID-19. Reperfusion classes were dichotomized into positive (extended thrombolysis in cerebral ischemia [eTICI] score = 2c-3) and negative (eTICI score < 2c) groups. All patients underwent endovascular therapy after initial CT perfusion imaging (CTP) to document infarction core and total hypoperfusion volumes. RESULTS. Ten COVID-positive (mean age ± SD, 67 ± 12 years; seven men, three women) and 144 COVID-negative patients (mean age, 71 ± 16 years; 76 men, 68 women) undergoing endovascular reperfusion, with antecedent CTP and follow-up imaging, comprised the final dataset. Initial infarction core and total hypoperfusion volumes (mean ± SD) were 1.5 ± 18 mL and 85 ± 100 mL in COVID-negative patients and 30.5 ± 34 mL and 117 ± 80.5 mL in COVID-positive patients, respectively. Final infarction volumes were significantly larger in patients with COVID-19, with median volumes of 77.8 mL versus 18.2 mL among control patients (p = .01), as were normalized measures of infarction growth relative to baseline infarction volume (p = .05). In adjusted logistic parametric regression models, COVID positivity emerged as a significant predictor for continued infarct growth (OR, 5.10 [95% CI, 1.00-25.95]; p = .05). CONCLUSION. These findings support the potentially aggressive clinical course of cerebrovascular events in patients with COVID-19, suggesting greater infarction growth and ongoing consumption of at-risk tissues, even after angiographic reperfusion. CLINICAL IMPACT. SARS-CoV-2 infection may promote continued infarction progression despite angiographic reperfusion in vaccine-naive patients with large-vessel occlusion AIS. The findings carry potential implications for prognostication, treatment selection, and surveillance for infarction growth among revascularized patients in future waves of infection by novel viral strains.

Imaging Intracranial Aneurysms in the Endovascular Era: Surveillance and Posttreatment Follow-up.

While most intracranial aneurysms (IAs) remain asymptomatic over a patient's lifetime, those that rupture can cause devastating outcomes. The increased usage and quality of neuroimaging has increased detection of unruptured IAs and driven an increase in surveillance and treatment of these lesions. Standard practice is to treat incidentally discovered unruptured IAs that confer high rupture risk as well as ruptured IAs to prevent rehemorrhage. IAs are increasingly treated with coil embolization instead of microsurgical clipping; more recently, flow diversion and intrasaccular flow disruption have further expanded the versatility and utility of endovascular IA treatment. Imaging is increasingly used for posttreatment IA follow-up in the endovascular era. While cerebral angiography remains the standard for IA characterization and treatment planning, advances in CT and CT angiography and MR angiography have improved the diagnostic accuracy of noninvasive imaging for initial diagnosis and surveillance. IA features including size, dome-to-neck ratio, location, and orientation allow rupture risk stratification and determination of optimal treatment strategy and timing. The radiologist should be familiar with the imaging appearance of common IA treatment devices and the expected imaging findings following treatment. In distinction to clipping and coil embolization, flow diversion and intrasaccular flow disruption induce progressive aneurysm obliteration over months to years. Careful assessment of the device; the treated IA; adjacent brain, bone, meninges; and involved extracranial and intracranial vasculature is crucial at posttreatment follow-up imaging to confirm aneurysm obliteration and identify short-term and long-term posttreatment complications. An invited commentary by Chatterjee is available online. Online supplemental material and the slide presentation from the RSNA Annual Meeting are available for this article. ©RSNA, 2022.

Automated Processing of Head CT Perfusion Imaging for Ischemic Stroke Triage: A Practical Guide to Quality Assurance and Interpretation.

Recent successful trials of thrombectomy launched a shift to imaging-based patient selection for stroke intervention. Many centers have adopted CT perfusion imaging (CTP) as a routine part of stroke workflow, and the demand for emergent CTP interpretation is growing. Fully automated CTP postprocessing software that rapidly generates standardized color-coded CTP summary maps with minimal user input and with easy accessibility of the software output is increasingly being adopted. Such automated postprocessing greatly streamlines clinical workflow and CTP interpretation for radiologists and other frontline physicians. However, the straightforward interface overshadows the computational complexity of the underlying postprocessing workflow, which, if not carefully examined, predisposes the interpreting physician to diagnostic errors. Using case examples, this article aims to familiarize the general radiologist with interpreting automated CTP software data output in the context of contemporary stroke management, providing a discussion of CTP acquisition and postprocessing, a stepwise guide for CTP quality assurance and troubleshooting, and a framework for avoiding clinically significant pitfalls of CTP interpretation in commonly encountered clinical scenarios. Interpreting radiologists should apply the outlined approach for quality assurance and develop a comprehensive search pattern for the identified pitfalls, to ensure accurate CTP interpretation and optimize patient selection for reperfusion.

Characterization of novel conformation-selective α-synuclein antibodies as potential immunotherapeutic agents for Parkinson's disease.

Parkinson's disease (PD) and dementia with Lewy bodies (DLB) are progressive neurodegenerative diseases for which there is no disease-modifying treatment. PD and DLB are characterized by aggregation of the synaptic protein α-synuclein, and there is compelling evidence to suggest that progression of these diseases is associated with the trans-cellular spread of pathogenic α-synuclein through the brains of afflicted individuals. Therapies targeting extracellular, pathogenic α-synuclein may therefore hold promise for slowing or halting disease progression. In this regard, it has been suggested that highly-selective antibodies can be administered as therapeutic agents targeting pathogenic proteins. In the current study, we screened a series of antibodies using multiple selection criterion to identify those that selectively bind pathogenic α-synuclein and show potent inhibition of pathology seeding in a neuronal model of α-synucleinopathy. A lead antibody was tested in a mouse model of PD, and it was able to reduce the spread of α-synuclein pathology in the brain and attenuate dopamine reductions in the striatum. This study highlights the therapeutic potential of α-synuclein immunotherapy for the treatment of PD and DLB, and provides a framework for screening of α-synuclein antibodies to identify those with preferred properties.

Unbiased Proteomics of Early Lewy Body Formation Model Implicates Active Microtubule Affinity-Regulating Kinases (MARKs) in Synucleinopathies.

Parkinson's disease (PD) patients progressively accumulate intracytoplasmic inclusions formed by misfolded α-synuclein known as Lewy bodies (LBs). LBs also contain other proteins that may or may not be relevant in the disease process. To identify proteins involved early in LB formation, we performed proteomic analysis of insoluble proteins in a primary neuron culture model of α-synuclein pathology. We identified proteins previously found in authentic LBs in PD as well as several novel proteins, including the microtubule affinity-regulating kinase 1 (MARK1), one of the most enriched proteins in this model of LB formation. Activated MARK proteins (MARKs) accumulated in LB-like inclusions in this cell-based model as well as in a mouse model of LB disease and in LBs of postmortem synucleinopathy brains. Inhibition of MARKs dramatically exacerbated α-synuclein pathology. These findings implicate MARKs early in synucleinopathy pathogenesis and as potential therapeutic drug targets.SIGNIFICANCE STATEMENT Neurodegenerative diseases are diagnosed definitively only in postmortem brains by the presence of key misfolded and aggregated disease proteins, but cellular processes leading to accumulation of these proteins have not been well elucidated. Parkinson's disease (PD) patients accumulate misfolded α-synuclein in LBs, the diagnostic signatures of PD. Here, unbiased mass spectrometry was used to identify the microtubule affinity-regulating kinase family (MARKs) as activated and insoluble in a neuronal culture PD model. Aberrant activation of MARKs was also found in a PD mouse model and in postmortem PD brains. Further, inhibition of MARKs led to increased pathological α-synuclein burden. We conclude that MARKs play a role in PD pathogenesis.

Progressive proximal-to-distal reduction in expression of the tight junction complex in colonic epithelium of virally-suppressed HIV+ individuals.

Effective antiretroviral therapy (ART) dramatically reduces AIDS-related complications, yet the life expectancy of long-term ART-treated HIV-infected patients remains shortened compared to that of uninfected controls, due to increased risk of non-AIDS related morbidities. Many propose that these complications result from translocated microbial products from the gut that stimulate systemic inflammation--a consequence of increased intestinal paracellular permeability that persists in this population. Concurrent intestinal immunodeficiency and structural barrier deterioration are postulated to drive microbial translocation, and direct evidence of intestinal epithelial breakdown has been reported in untreated pathogenic SIV infection of rhesus macaques. To assess and characterize the extent of epithelial cell damage in virally-suppressed HIV-infected patients, we analyzed intestinal biopsy tissues for changes in the epithelium at the cellular and molecular level. The intestinal epithelium in the HIV gut is grossly intact, exhibiting no decreases in the relative abundance and packing of intestinal epithelial cells. We found no evidence for structural and subcellular localization changes in intestinal epithelial tight junctions (TJ), but observed significant decreases in the colonic, but not terminal ileal, transcript levels of TJ components in the HIV+ cohort. This result is confirmed by a reduction in TJ proteins in the descending colon of HIV+ patients. In the HIV+ cohort, colonic TJ transcript levels progressively decreased along the proximal-to-distal axis. In contrast, expression levels of the same TJ transcripts stayed unchanged, or progressively increased, from the proximal-to-distal gut in the healthy controls. Non-TJ intestinal epithelial cell-specific mRNAs reveal differing patterns of HIV-associated transcriptional alteration, arguing for an overall change in intestinal epithelial transcriptional regulation in the HIV colon. These findings suggest that persistent intestinal epithelial dysregulation involving a reduction in TJ expression is a mechanism driving increases in colonic permeability and microbial translocation in the ART-treated HIV-infected patient, and a possible immunopathogenic factor for non-AIDS related complications.

Expression and processing of fluorescent fusion proteins of amyloid precursor protein (APP).

Processing of ß-amyloid precursor protein (APP) by ß- and γ-secretases in neurons produces amyloid-ß (Aß), whose excess accumulation leads to Alzheimer's disease (AD). Knowledge on subcellular trafficking pathways of APP and its fragments is important for the understanding of AD pathogenesis. We designed fusion proteins comprising a C-terminal fragment of APP (app) and fluorescent proteins GFP (G) and DsRed (D) to permit the tracking of the fusion proteins and fragments in cells. CAD cells expressing these proteins emitted colocalized green and red fluorescence and produce ectodomains, sGapp and sRapp, and Aß, whose level was reduced by inhibitors of ß- and γ-secretases. The presence of GappR in endosomes was observed via colocalization with Rab5. These observations indicated that the fusion proteins were membrane inserted, transported in vesicles and proteolytically processed by the same mechanism for APP. By attenuating fusion protein synthesis with cycloheximide, individual fluorescent colors from the C-terminus of the fusion proteins appeared in the cytosol which was strongly suppressed by ß-secretase inhibitor, suggesting that the ectodomains exit the cell rapidly (t1/2 about 20min) while the C-terminal fragments were retained longer in cells. In live cells, we observed the fluorescence of the ectodomains located between parental fusion proteins and plasma membrane, suggesting that these ectodomain positions are part of their secretion pathway. Our results indicate that the native ectodomain does not play a decisive role for the key features of APP trafficking and processing and the new fusion proteins may lead to novel insights in intracellular activities of APP.

Venous Anatomy of the Central Nervous System.

Comprehensive understanding of venous anatomy is a key factor in the approach to a multitude of conditions. Moreover, the venous system has become the center of attention as a new frontier for treatment of diseases such as idiopathic intracranial hypertension (IIH), arteriovenous malformation (AVM), pulsatile tinnitus, hydrocephalus, and cerebrospinal fluid (CSF) venous fistulas. Its knowledge is ever more an essential requirement of the modern brain physician. In this article, the authors explore the descriptive and functional anatomy of the venous system of the CNS in 5 subsections: embryology, dural sinuses, cortical veins, deep veins, and spinal veins.

Comprehensive Analysis of Post-Pipeline Endothelialization and Remodeling.

BACKGROUND AND PURPOSE: Successful post-flow-diverter endoluminal reconstruction is widely believed to require endothelial overgrowth of the aneurysmal inflow zone. However, endothelialization/neointimal overgrowth is a complex process, over which we currently have very limited influence. Less emphasized is vascular remodeling of the target arterial segment, the dynamic response of the vessel to flow-diverter implantation. This process is distinct from flow modifications in covered branches. It appears that basic angiographic methods allow simple and useful observations. The purpose of this article was to quantitatively evaluate observable postimplantation changes in target vessels following deployment of Pipeline endoluminal constructs. MATERIALS AND METHODS: One hundred consecutive adults with unruptured, previously untreated, nondissecting aneurysms treated with the Pipeline Embolization Device with Shield Technology and the availability of follow-up conventional angiography were studied with 2D DSA imaging. Target vessel size; Pipeline Embolization Device diameter; endothelial thickness; and various demographic, antiplatelet, and device-related parameters were recorded and analyzed. RESULTS: The thickness of neointimal overgrowth (mean, 0.3 [SD, 0.1] mm; range, 0.1-0.7 mm) is inversely correlated with age and is independent of vessel size, smoking status, sex, and degree of platelet inhibition. The decrease in lumen diameter caused by neointimal overgrowth, however, appears counteracted by outward remodeling (dilation) of the target arterial segment. This leads to an increase in the diameter with a corresponding decrease in length (foreshortening) of the implanted Pipeline Embolization Device. This physiologic remodeling process affects optimally implanted devices and is not a consequence of stretching, device migration, vasospasm, and so forth. A direct, linear, statistically significant relationship exists between the degree of observed outward remodeling and the diameter of the implanted Pipeline Embolization Device relative to the target vessel. Overall, remodeled arterial diameters were reduced by 15% (SD, 10%) relative to baseline and followed a normal distribution. Clinically relevant stenosis was not observed. CONCLUSIONS: Vessel healing involves both outward remodeling and neointimal overgrowth. Judicial oversizing could be useful in specific settings to counter the reduction in lumen diameter due to postimplant neointimal overgrowth; however, this overszing needs to be balanced against the decrease in metal coverage accompanying the use of oversized devices. Similar analysis for other devices is essential.

Use of Carotid Web Angioarchitecture for Stroke Risk Assessment.

OBJECTIVE: To examine the usefulness of carotid web (CW), carotid bifurcation and their combined angioarchitectural measurements in assessing stroke risk. METHODS: Anatomic data on the internal carotid artery (ICA), common carotid artery (CCA), and the CW were gathered as part of a retrospective study from symptomatic (stroke) and asymptomatic (nonstroke) patients with CW. We built a model of stroke risk using principal-component analysis, Firth regression trained with 5-fold cross-validation, and heuristic binary cutoffs based on the Minimal Description Length principle. RESULTS: The study included 22 patients, with a mean age of 55.9 ± 12.8 years; 72.9% were female. Eleven patients experienced an ischemic stroke. The first 2 principal components distinguished between patients with stroke and patients without stroke. The model showed that ICA-pouch tip angle (P = 0.036), CCA-pouch tip angle (P = 0.036), ICA web-pouch angle (P = 0.036), and CCA web-pouch angle (P = 0.036) are the most important features associated with stroke risk. Conversely, CCA and ICA anatomy (diameter and angle) were not found to be risk factors. CONCLUSIONS: This pilot study shows that using data from computed tomography angiography, carotid bifurcation, and CW angioarchitecture may be used to assess stroke risk, allowing physicians to tailor care for each patient according to risk stratification.