Liquid-biopsy proteomics combined with AI identifies cellular drivers of eye aging and disease in vivo.

Single-cell analysis in living humans is essential for understanding disease mechanisms, but it is impractical in non-regenerative organs, such as the eye and brain, because tissue biopsies would cause serious damage. We resolve this problem by integrating proteomics of liquid biopsies with single-cell transcriptomics from all known ocular cell types to trace the cellular origin of 5,953 proteins detected in the aqueous humor. We identified hundreds of cell-specific protein markers, including for individual retinal cell types. Surprisingly, our results reveal that retinal degeneration occurs in Parkinson's disease, and the cells driving diabetic retinopathy switch with disease stage. Finally, we developed artificial intelligence (AI) models to assess individual cellular aging and found that many eye diseases not associated with chronological age undergo accelerated molecular aging of disease-specific cell types. Our approach, which can be applied to other organ systems, has the potential to transform molecular diagnostics and prognostics while uncovering new cellular disease and aging mechanisms.

Comparing the Long-Term Cardiovascular Outcomes of Lumbo-Peritoneal, Ventriculo-Peritoneal, or Non-Shunting Treatment after Idiopathic Normal Pressure Hydrocephalus: A Nationwide Retrospective Cohort Study.

Purpose: With advances in medical technology, the average lifespan has increased, leading to a growing significance of idiopathic normal pressure hydrocephalus (iNPH), particularly in the elderly population. Most patients with iNPH have been treated either with ventriculo-peritoneal shunts (VPS) or conservative measures. However, lumbo-peritoneal shunts (LPS) have emerged as an alternative treatment option for iNPH in recent decades, extensive research still lacks comparing outcomes with LPS to those with VPS or non-surgical treatment. The aim of the resent study is to disclose the long-term therapeutic outcomes of LPS, VPS, and non-shunting in patients with iNPH. Methods: We used the National Health Insurance Research Database in Taiwan to assess the long-term outcomes of these treatment options. We enrolled 5,537 iNPH patients who received shunting surgery, of which 5,254 were VPS and 283 were LPS. To compare the difference between each group, matching was conducted by propensity score matching using a 1:1 ratio based on LPS patients. Primary outcomes included death and major adverse cardiovascular events (MACEs) Results: Our findings show that VPS resulted in significantly more MACEs than non-surgical treatment (Odds ratio: 1.83, 95% confidence interval: 1.16-2.90). In addition, both VPS and LPS groups had significantly lower overall mortality rates than non-shunting group. Moreover, LPS had lower overall mortality but similar MACEs rates to VPS. Conclusions: Based on these findings, we propose that the LPS is preferable to the VPS, and surgical treatment should be considered the primary choice over conservative treatment unless contraindications are present.

A comparative effectiveness study of carotid intervention for long-term stroke prevention in patients with severe asymptomatic stenosis from a large integrated health system.

OBJECTIVE: The results of current prospective trials comparing the effectiveness of carotid endarterectomy (CEA) vs standard medical therapy for long-term stroke prevention in patients with asymptomatic carotid stenosis (ACS) will not be available for several years. In this study, we compared the observed effectiveness of CEA and standard medical therapy vs standard medical therapy alone to prevent ipsilateral stroke in a contemporary cohort of patients with ACS. METHODS: This cohort study was conducted in a large integrated health system in adult subjects with 70% to 99% ACS (no neurologic symptom within 6 months) with no prior ipsilateral carotid artery intervention. Causal inference methods were used to emulate a conceptual randomized trial using data from January 1, 2008, through December 31, 2017, for comparing the event-free survival over 96 months between two treatment strategies: (1) CEA within 12 months from cohort entry vs (2) no CEA (standard medical therapy alone). To account for both baseline and time-dependent confounding, inverse probability weighting estimation was used to derive adjusted hazard ratios, and cumulative risk differences were assessed based on two logistic marginal structural models for counterfactual hazards. Propensity scores were data-adaptively estimated using super learning. The primary outcome was ipsilateral anterior ischemic stroke. RESULTS: The cohort included 3824 eligible patients with ACS (mean age: 73.7 years, 57.9% male, 12.3% active smokers), of whom 1467 underwent CEA in the first year, whereas 2297 never underwent CEA. The median follow-up was 68 months. A total of 1760 participants (46%) died, 445 (12%) were lost to follow-up, and 158 (4%) experienced ipsilateral stroke. The cumulative risk differences for each year of follow-up showed a protective effect of CEA starting in year 2 (risk difference = 1.1%, 95% confidence interval: 0.5%-1.6%) and persisting to year 8 (2.6%, 95% confidence interval: 0.3%-4.8%) compared with patients not receiving CEA. CONCLUSIONS: In this contemporary cohort study of patients with ACS using rigorous analytic methodology, CEA appears to have a small but statistically significant effect on stroke prevention out to 8 years. Further study is needed to appropriately select the subset of patients most likely to benefit from intervention.

Risk for surgical interventions following endovascular aneurysm repair with Endologix AFX or AFX2 Endovascular AAA Systems compared with other devices.

OBJECTIVE: To evaluate the risk for 90-day returns to care and long-term subsequent surgical interventions after primary endovascular aneurysm repair (EVAR) with an Endologix AFX Endovascular AAA System compared with three other high-volume endograft devices. METHODS: We conducted a matched cohort study using data from Kaiser Permanente's Endovascular Stent Graft Registry. Patients aged ≥18 years who underwent primary EVAR for AAA in the health care system from January 1, 2011, to December 31, 2017, comprised the eligible study sample. The treatment group included patients who received an Endologix AFX or AFX2 device (n = 470). Patients who received one of three other high-volume endograft devices used within the health care system comprised the eligible comparison group (n = 2122). These patients were 2:1 propensity score matched without replacement to patients who received an Endologix device based on a number of patient and procedural characteristics. After the application of matching, conditional logistic regression was used to evaluate the likelihood for 90-day emergency department visit and readmission. Cause-specific Cox regression was used to evaluate the long-term risk of endoleak, graft revision, secondary reintervention (not including revision), conversion to open repair, and rupture during follow-up. Cox proportional hazards regression was used to evaluate the risk of mortality (overall and aneurysm related). RESULTS: The final matched study sample included 470 patients who received an Endologix AFX or AFX2 device and 940 patients who received a different high-volume device. compared with the other devices, AFX/AFX2 had a higher risk for type III endoleak (hazard ratio [HR], 38.79; 95% confidence interval [CI], 14.51-103.67), revision surgery >1 year after the primary EVAR (HR, 4.50; 95% CI, 3.10-6.54), rupture (HR, 6.52; 95% CI, 1.73-24.63), and aneurysm-related mortality (HR, 2.43; 95% CI, 1.32-4.47) was observed with the use of AFX/AFX2. CONCLUSIONS: In our matched cohort study, patients who received an Endologix AFX System during their primary EVAR had a higher risk for several adverse longitudinal outcomes, as well as aneurysm-related mortality, when compared with patients who received other high-volume devices. Patients who have received these devices should be monitored closely after EVAR.

Tribology of Pore-Textured Hard Surfaces under Physiological Conditions: Effects of Texture Scales.

Micro- and nanotexturing on hard biomaterials have shown advantages for tissue engineering and antifouling applications. However, a growing number of studies have also shown that texturing may cause an increase in friction, demanding further research on the tribological effects of texturing under physiological conditions. This study investigates the tribological effects of micro- and nanopore patterns on hard hydrophilic silicon sliding against soft hydrophobic polydimethylsiloxane (PDMS) immersed in aqueous liquids with various viscosities, simulating the sliding of a textured implant surface against soft tissues. The experimental results show that silicon surfaces with pore textures at both micro- and nanoscale feature sizes confer a higher coefficient of friction (COF) than an untextured one. It is attributed to the texture's edge effect caused by the periodic pore patterns between the two sliding objects with a large difference in material stiffness. For the same solid area fraction, nanopored surfaces show a higher COF than micropored surfaces because of the significantly higher texture edge length per unit area. For micropored surfaces with a similar length of texture edge length per unit area, the COF increases more significantly with the increase in pore size because of the greater stress at the rims of the larger pores. The COFs of both micro- and nanoscale pores generally decrease from ∼10 to 0.1 with an increase in the surrounding aqueous viscosity, indicating the transition from a boundary lubrication to a mixed lubrication regime while mostly remaining in boundary lubrication. In contrast, the COF of an untextured surface decreases from ∼1 to 0.01, indicating that it mostly remains in the mixed lubrication regime while showing the tendency toward hydrodynamic lubrication. Compared to a hydrophilic hard probe sliding against a textured hydrophobic soft substrate, the hydrophobic soft probe sliding against a textured hydrophilic hard substrate produces a significantly higher COF under similar physiological conditions due to the larger edge effect.

Design of Low-Complexity Convolutional Neural Network Accelerator for Finger Vein Identification System.

In the biometric field, vein identification is a vital process that is constrained by the invisibility of veins as well as other unique features. Moreover, users generally do not wish to have their personal information uploaded to the cloud, so edge computing has become popular for the sake of protecting user privacy. In this paper, we propose a low-complexity and lightweight convolutional neural network (CNN) and we design intellectual property (IP) for shortening the inference time in finger vein recognition. This neural network system can operate independently in client mode. After fetching the user's finger vein image via a near-infrared (NIR) camera mounted on an embedded system, vein features can be efficiently extracted by vein curving algorithms and user identification can be completed quickly. Better image quality and higher recognition accuracy can be obtained by combining several preprocessing techniques and the modified CNN. Experimental data were collected by the finger vein image capture equipment developed in our laboratory based on the specifications of similar products currently on the market. Extensive experiments demonstrated the practicality and robustness of the proposed finger vein identification system.

Natural History of Asymptomatic Moderate Carotid Artery Stenosis in a Large Community-Based Cohort.

BACKGROUND: Moderate carotid artery stenosis is a poorly defined risk factor for ischemic stroke. As such, practice recommendations are lacking. In this study, we describe the long-term risk of stroke in patients with moderate asymptomatic stenosis in an integrated health care system. METHODS: All adult patients with asymptomatic moderate (50%-69%) internal carotid artery stenosis between 2008 and 2012 were identified, with follow-up through 2017. The primary outcome was acute ischemic stroke attributed to the ipsilateral carotid artery. Stroke rates were calculated using competing risk analysis. Secondary outcomes included disease progression, ipsilateral intervention, and long-term survival. RESULTS: Overall, 11 614 arteries with moderate stenosis in 9803 patients were identified. Mean age was 74.2±9.9 years with 51.4% women. Mean follow-up was 5.1±2.9 years. There were 180 ipsilateral ischemic strokes (1.6%) identified (crude annual risk, 0.31% [95% CI, 0.21%-0.41%]), of which thirty-one (17.2%) underwent subsequent intervention. Controlling for death and intervention as competing risks, the cumulative incidence of stroke was 1.2% (95% CI, 1.0%-1.4%) at 5 years and 2.0% (95% CI, 1.7%-2.4%) at 10 years. Of identified strokes, 50 (27.8%) arteries had progressed to severe stenosis or occlusion. During follow-up, there were 17 029 carotid studies performed in 5951 patients, revealing stenosis progression in 1674 (14.4%) arteries, including 1614 (13.9%) progressing to severe stenosis and 60 (0.5%) to occlusion. The mean time to stenosis progression was 2.6±2.1 years. Carotid intervention occurred in 708 arteries (6.1%). Of these, 66.1% (468/708) had progressed to severe stenosis. The overall mortality rate was 44.5%, with 10.5% of patients lost to follow-up. CONCLUSIONS: In this community-based sample of patients with asymptomatic moderate internal carotid artery stenosis followed for an average of 5 years, the cumulative incidence of stroke is low out to 10 years. Future research is needed to optimize management strategies for this population.

Decreasing trends in reintervention and readmission after endovascular aneurysm repair in a multiregional implant registry.

OBJECTIVE: As endovascular aortic aneurysm repair (EVAR) matures into its third decade, measures such as long-term reintervention and readmission have become a focus of quality improvement efforts. Within a large United States integrated health care system, we describe time trends in the rates of long-term reinterventions utilization measures. METHODS: Data from a United States multiregional EVAR registry was used to perform a descriptive study of 3891 adults who underwent conventional infrarenal EVAR for infrarenal abdominal aortic aneurysm between 2010 and 2019. Three-year follow-up was 96.7%. Outcomes included 1-, 3-, and 5-year graft revision (defined as a procedure involving placement of a new endograft component), secondary interventions (defined as a procedure necessary for maintenance of EVAR integrity [eg, coil embolization and balloon angioplasty/stenting]), conversion to open, interventions for type II endoleaks alone, and 90-day readmission. Crude cause-specific reintervention probabilities were calculated by operative year using the Aalen-Johansen estimator, with death as a competing risk and December 31, 2020 as the study end date. RESULTS: Excluding interventions for type II endoleak alone, 1-year secondary intervention incidence decreased from 5.9% for EVARs in 2010 to 2.0% in 2019 (P < .001) and 3-year incidence decreased from 7.2% to 3.6% from 2010 to 2017 (P = .03). The 3-year incidences of graft revision (mean incidence, 3.4%) and conversion to open remained fairly stable (mean incidence, 0.6%) over time. The 3-year incidence of interventions for type II endoleak alone also decreased from 3.4% in 2010 to 0.7% in 2017 (P = .01). Ninety-day readmission rates decreased from 19.3% for index EVAR in 2010 to 9.2% in 2019 (P = .03). CONCLUSIONS: Comprehensive data from a multiregional health care system demonstrates decreasing long-term secondary intervention and readmission rates over time in patients undergoing EVAR. These trends are not explained by evolving management of type II endoleaks and suggest improving graft durability, patient selection, or surgical technique. Further study is needed to define implant and anatomic predictors of different types of long-term reintervention.

The natural history of large abdominal aortic aneurysms in patients without timely repair.

OBJECTIVE: Contemporary data on the natural history of large abdominal aortic aneurysms (AAAs) in patients undergoing delayed or no repair are lacking. In this study, we examine the impact of large AAA size on the incidence of rupture and mortality. METHODS: From a prospectively maintained aneurysm surveillance registry, patients with an unrepaired, large AAA (≥5.5 cm in men and ≥5.0 cm in women) at baseline (ie, index imaging) or who progressed to a large size from 2003 to 2017 were included, with follow-up through March 2020. Outcomes of interest obtained by manual chart review included rupture (confirmed by imaging/autopsy), probable rupture (timing/findings consistent with rupture without more likely cause of death), repair, reasons for either no or delayed (>1 year after diagnosis of large AAA) repair and total mortality. Cumulative incidence of rupture was calculated using a nonparametric cumulative incidence function, accounting for the competing events of death and aneurysm repair and was stratified by patient sex. RESULTS: Of the 3248 eligible patients (mean age, 83.6 ± 9.1 years; 71.2% male; 78.1% white; and 32.0% current smokers), 1423 (43.8%) had large AAAs at index imaging, and 1825 progressed to large AAAs during the follow-up period, with a mean time to qualifying size of 4.3 ± 3.4 years. In total, 2215 (68%) patients underwent repair, of which 332 were delayed >1 year; 1033 (32%) did not undergo repair. The most common reasons for delayed repair were discrepancy in AAA measurement between surgeon and radiologist (34%) and comorbidity (20%), whereas the most common reasons for no repair were patient preference (48%) and comorbidity (30%). Among patients with delayed repair (mean time to repair, 2.6 ± 1.8 years), nine (2.7%) developed symptomatic aneurysms, and an additional 11 (3.3%) ruptured. Of patients with no repair, 94 (9.1%) ruptured. The 3-year cumulative incidence of rupture was 3.4% for initial AAA size 5.0 to 5.4 cm (women only), 2.2% for 5.5 to 6.0 cm, 6.0% for 6.1 to 7.0 cm, and 18.4% for >7.0 cm. Women with AAA size 6.1 to 7.0 cm had a 3-year cumulative incidence of rupture of 12.8% (95% confidence interval, 7.5%-19.6%) compared with 4.5% (95% confidence interval, 3.0%-6.5%) in men (P = .002). CONCLUSIONS: In this large cohort of AAA registry patients over 17 years, annual rupture rates for large AAAs were lower than previously reported, with possible increased risk in women. Further analyses are ongoing to identify those at increased risk for aneurysm rupture and may provide targeted surveillance regimens and improve patient counseling.

Society for Vascular Surgery clinical practice guidelines for management of extracranial cerebrovascular disease.

Management of carotid bifurcation stenosis in stroke prevention has been the subject of extensive investigations, including multiple randomized controlled trials. The proper treatment of patients with carotid bifurcation disease is of major interest to vascular surgeons and other vascular specialists. In 2011, the Society for Vascular Surgery published guidelines for the treatment of carotid artery disease. At the time, several randomized trials, comparing carotid endarterectomy (CEA) and carotid artery stenting (CAS), were reported. Since the 2011 guidelines, several studies and a few systematic reviews comparing CEA and CAS have been reported, and the role of medical management has been reemphasized. In the present publication, we have updated and expanded on the 2011 guidelines with specific emphasis on five areas: (1) is CEA recommended over maximal medical therapy for low-risk patients; (2) is CEA recommended over transfemoral CAS for low surgical risk patients with symptomatic carotid artery stenosis of >50%; (3) the timing of carotid intervention for patients presenting with acute stroke; (4) screening for carotid artery stenosis in asymptomatic patients; and (5) the optimal sequence of intervention for patients with combined carotid and coronary artery disease. A separate implementation document will address other important clinical issues in extracranial cerebrovascular disease. Recommendations are made using the GRADE (grades of recommendation assessment, development, and evaluation) approach, as was used for other Society for Vascular Surgery guidelines. The committee recommends CEA as the first-line treatment for symptomatic low-risk surgical patients with stenosis of 50% to 99% and asymptomatic patients with stenosis of 70% to 99%. The perioperative risk of stroke and death in asymptomatic patients must be <3% to ensure benefit for the patient. In patients with recent stable stroke (modified Rankin scale score, 0-2), carotid revascularization is considered appropriate for symptomatic patients with >50% stenosis and should be performed as soon as the patient is neurologically stable after 48 hours but definitely <14 days after symptom onset. In the general population, screening for clinically asymptomatic carotid artery stenosis in patients without cerebrovascular symptoms or significant risk factors for carotid artery disease is not recommended. In selected asymptomatic patients with an increased risk of carotid stenosis, we suggest screening for clinically asymptomatic carotid artery stenosis as long as the patients would potentially be fit for and willing to consider carotid intervention if significant stenosis is discovered. For patients with symptomatic carotid stenosis of 50% to 99%, who require both CEA and coronary artery bypass grafting, we suggest CEA before, or concomitant with, coronary artery bypass grafting to potentially reduce the risk of stroke and stroke/death. The sequencing of the intervention depends on the clinical presentation and institutional experience.

Gendered Expectations: the Impact of Gender, Evaluation Language, and Clinical Setting on Resident Trainee Assessment of Faculty Performance.

BACKGROUND: Gender inequity is pervasive in academic medicine. Factors contributing to these gender disparities must be examined. A significant body of literature indicates men and women are assessed differently in teaching evaluations. However, limited data exist on how faculty gender affects resident evaluation of faculty performance based on the skill being assessed or the clinical practice settings in which the trainee-faculty interaction occurs. OBJECTIVE: Evaluate for gender-based differences in the assessment of general internal medicine (GIM) faculty physicians by trainees in inpatient and outpatient settings. DESIGN: Retrospective cohort study SUBJECTS: Inpatient and outpatient GIM faculty physicians in an Internal Medicine residency training program from July 1, 2015, to December 31, 2018. MAIN MEASURES: Faculty scores on trainee teaching evaluations including overall teaching ability and Accreditation Council for Graduate Medical Education (ACGME) competencies (medical knowledge [MK], patient care [PC], professionalism [PROF], interpersonal and communication skills [ICS], practice-based learning and improvement [PBLI], and systems-based practice [SBP]) based on the institutional faculty assessment form. KEY RESULTS: In total, 3581 evaluations by 445 trainees (55.1% men, 44.9% women) assessing 161 GIM faculty physicians (50.3% men, 49.7% women) were included. Male faculty were rated higher in overall teaching ability (male=4.69 vs. female=4.63, p=0.003) and in four of the six ACGME competencies (MK, PROF, PBLI, and SBP) based on our institutional evaluation form. In the inpatient setting, male faculty were rated more favorably for overall teaching (male = 4.70, female = 4.53, p=<0.001) and across all ACGME competencies. The only observed gender difference in the outpatient setting favored female faculty in PC (male = 4.65, female = 4.71, p=0.01). CONCLUSIONS: Male and female GIM faculty performance was assessed differently by trainees. Gender-based differences were impacted by the setting of evaluation, with the greatest difference by gender noted in the inpatient setting.

Patient Personality and Illness Perceptions in Relation to Follow-Up Appointment Adherence in Neuro-Ophthalmology.

BACKGROUND: Improving patient attendance at medical follow-up visits may have a notable impact on disease and overall health outcomes. Understanding factors contributing to poor attendance is important for identifying at-risk patients and designing interventions to improve clinical outcomes. Our objective was to identify personality and illness perception factors associated with attendance at recommended follow-up visits in a neuro-ophthalmology practice. METHODS: New or established patients (≥18 years) with scheduled neuro-ophthalmology (study) or glaucoma (comparison) appointments at a tertiary care academic medical center completed the Brief Illness Perception Questionnaire and Ten-Item Personality Inventory. Physician recommendations made during the visit were recorded (medications, referrals, follow-up, testing, and procedures). A chart review was performed 18 months after enrollment to assess attendance at follow-up appointment and adherence with other physician recommendations. Multiple variable logistic regression models studied associations between follow-up appointment attendance and demographic factors, appointment factors, and survey responses. RESULTS: Among 152 respondents (97% response rate (152 of 157), aged 19-97 years, 58% female, 34% new, 80 neuro-ophthalmology, 72 glaucoma), neuro-ophthalmology subjects were younger, more likely to be White, non-Hispanic, female and new to the practice than subjects with glaucoma. They reported higher emotional impact, identity, and consequences related to their illness (P = 0.001-0.03). Neuro-ophthalmology physician recommendations included more referrals to other services (17.5% vs 1.4%, P = 0.001, chi-square) and more radiology studies (15% vs 0%, P = 0.001, chi-square), but fewer follow-up visits (75% vs 97%, P < 0.0005, chi-square). Among those with recommended follow-up visits, neuro-ophthalmology subjects had lower rates of on-time appointment attendance (55% vs 77%, P = 0.009, chi-square). In a multiple variable model, on-time follow-up attendance was associated with shorter recommended follow-up interval (≤90 days, P < 0.0005), established (vs new) patient status at enrollment visit (P = 0.04), and glaucoma (P = 0.08), but not subject demographics, illness perception, or personality factors. CONCLUSIONS: Patient demographics, illness perception, and personality traits were not associated with follow-up appointment attendance and therefore unlikely to be useful for identifying patients at risk of being lost to follow-up. New neuro-ophthalmology patients with a follow-up recommended ≥90 days in advance may benefit from targeted interventions to improve follow-up appointment adherence.

Drowsiness Detection System Based on PERCLOS and Facial Physiological Signal.

Accidents caused by fatigue occur frequently, and numerous scholars have devoted tremendous efforts to investigate methods to reduce accidents caused by fatigued driving. Accordingly, the assessment of the spirit status of the driver through the eyes blinking frequency and the measurement of physiological signals have emerged as effective methods. In this study, a drowsiness detection system is proposed to combine the detection of LF/HF ratio from heart rate variability (HRV) of photoplethysmographic imaging (PPGI) and percentage of eyelid closure over the pupil over time (PERCLOS), and to utilize the advantages of both methods to improve the accuracy and robustness of drowsiness detection. The proposed algorithm performs three functions, including LF/HF ratio from HRV status judgment, eye state detection, and drowsiness judgment. In addition, this study utilized a near-infrared webcam to obtain a facial image to achieve non-contact measurement, alleviate the inconvenience of using a contact wearable device, and for use in a dark environment. Furthermore, we selected the appropriate RGB channel under different light sources to obtain LF/HF ratio from HRV of PPGI. The main drowsiness judgment basis of the proposed drowsiness detection system is the use of algorithm to obtain sympathetic/parasympathetic nervous balance index and percentage of eyelid closure. In the experiment, there are 10 awake samples and 30 sleepy samples. The sensitivity is 88.9%, the specificity is 93.5%, the positive predictive value is 80%, and the system accuracy is 92.5%. In addition, an electroencephalography signal was used as a contrast to validate the reliability of the proposed method.

Incidence of Ischemic Stroke in Patients With Asymptomatic Severe Carotid Stenosis Without Surgical Intervention.

Importance: Optimal management of patients with asymptomatic severe carotid stenosis is uncertain, due to advances in medical care and a lack of contemporary data comparing medical and surgical treatment. Objective: To estimate stroke outcomes among patients with medically treated asymptomatic severe carotid stenosis who did not undergo surgical intervention. Design, Setting, and Participants: Retrospective cohort study that included 3737 adult participants with asymptomatic severe (70%-99%) carotid stenosis diagnosed between 2008 and 2012 and no prior intervention or ipsilateral neurologic event in the prior 6 months. Participants received follow-up through 2019, and all were members of an integrated US regional health system serving 4.5 million members. Exposures: Imaging diagnosis of asymptomatic carotid stenosis of 70% to 99%. Main Outcomes and Measures: Occurrence of ipsilateral carotid-related acute ischemic stroke. Censoring occurred with death, disenrollment, or ipsilateral intervention. Results: Among 94 822 patients with qualifying imaging studies, 4230 arteries in 3737 (mean age, 73.8 [SD 9.5 years]; 57.4% male) patients met selection criteria including 2539 arteries in 2314 patients who never received intervention. The mean follow-up in this cohort was 4.1 years (SD 3.6 years). Prior to any intervention, there were 133 ipsilateral strokes with a mean annual stroke rate of 0.9% (95% confidence interval [CI], 0.7%-1.2%). The Kaplan-Meier estimate of ipsilateral stroke by 5 years was 4.7% (95% CI, 3.9%-5.7%). Conclusions and Relevance: In a community-based cohort of patients with asymptomatic severe carotid stenosis who did not undergo surgical intervention, the estimated rate of ipsilateral carotid-related acute ischemic stroke was 4.7% over 5 years. These findings may inform decision-making regarding surgical and medical treatment for patients with asymptomatic severe carotid artery stenosis.

Validation of natural language processing to determine the presence and size of abdominal aortic aneurysms in a large integrated health system.

OBJECTIVE: Previous studies of the natural history of abdominal aortic aneurysms (AAAs) have been limited by small cohort sizes or heterogeneous analyses of pooled data. By quickly and efficiently extracting imaging data from the health records, natural language processing (NLP) has the potential to substantially improve how we study and care for patients with AAAs. The aim of the present study was to test the ability of an NLP tool to accurately identify the presence or absence of AAAs and detect the maximal abdominal aortic diameter in a large dataset of imaging study reports. METHODS: Relevant imaging study reports (n = 230,660) from 2003 to 2017 were obtained for 32,778 patients followed up in a prospective aneurysm surveillance registry within a large, diverse, integrated healthcare system. A commercially available NLP algorithm was used to assess the presence of AAAs, confirm the absence of AAAs, and extract the maximal diameter of the abdominal aorta, if stated. A blinded expert manual review of 18,000 randomly selected imaging reports was used as the reference standard. The positive predictive value (PPV or precision), sensitivity (recall), and the kappa statistics were calculated. RESULTS: Of the randomly selected 18,000 studies that underwent expert manual review, 48.7% were positive for AAAs. In confirming the presence of an AAA, the interrater reliability of the NLP compared with the expert review showed a kappa value of 0.84 (95% confidence interval [CI], 0.83-0.85), with a PPV of 95% and sensitivity of 88.5%. The NLP algorithm showed similar results for confirming the absence of an AAA, with a kappa of 0.79 (95% CI, 0.799-0.80), PPV of 77.7%, and sensitivity of 91.9%. The kappa, PPV, and sensitivity of the NLP for correctly identifying the maximal aortic diameter was 0.88 (95% CI, 0.87-0.89), 88.8%, and 88.2% respectively. CONCLUSIONS: The use of NLP software can accurately analyze large volumes of radiology report data to detect AAA disease and assemble a contemporary aortic diameter-based cohort of patients for longitudinal analysis to guide surveillance, medical management, and operative decision making. It can also potentially be used to identify from the electronic medical records pre- and postoperative AAA patients "lost to follow-up," leverage human resources engaged in the ongoing surveillance of patients with AAAs, and facilitate the construction and implementation of AAA screening programs.

Establishing a carotid artery stenosis disease cohort for comparative effectiveness research using natural language processing.

OBJECTIVE: Investigation of asymptomatic carotid stenosis treatment is hindered by the lack of a contemporary population-based disease cohort. We describe the use of natural language processing (NLP) to identify stenosis in patients undergoing carotid imaging. METHODS: Adult patients with carotid imaging between 2008 and 2012 in a large integrated health care system were identified and followed through 2017. An NLP process was developed to characterize carotid stenosis according to the Society of Radiologists in Ultrasound (for ultrasounds) and North American Symptomatic Carotid Endarterectomy Trial (NASCET) (for axial imaging) guidelines. The resulting algorithm assessed text descriptors to categorize normal/non-hemodynamically significant stenosis, moderate or severe stenosis as well as occlusion in both carotid ultrasound (US) and axial imaging (computed tomography and magnetic resonance angiography [CTA/MRA]). For US reports, internal carotid artery systolic and diastolic velocities and velocity ratios were assessed and matched for laterality to supplement accuracy. To validate the NLP algorithm, positive predictive value (PPV or precision) and sensitivity (recall) were calculated from simple random samples from the population of all imaging studies. Lastly, all non-normal studies were manually reviewed for confirmation for prevalence estimates and disease cohort assembly. RESULTS: A total of 95,896 qualifying index studies (76,276 US and 19,620 CTA/MRA) were identified among 94,822 patients including 1059 patients who underwent multiple studies on the same day. For studies of normal/non-hemodynamically significant stenosis arteries, the NLP algorithm showed excellent performance with a PPV of 99% for US and 96.5% for CTA/MRA. PPV/sensitivity to identify a non-normal artery with correct laterality in the CTA/MRA and US samples were 76.9% (95% confidence interval [CI], 74.1%-79.5%)/93.1% (95% CI, 91.1%-94.8%) and 74.7% (95% CI, 69.3%-79.5%)/94% (95% CI, 90.2%-96.7%), respectively. Regarding cohort assembly, 15,522 patients were identified with diseased carotid artery, including 2674 exhibiting equal bilateral disease. This resulted in a laterality-specific cohort with 12,828 moderate, 5283 severe, and 1895 occluded arteries and 326 diseased arteries with unknown stenosis. During follow-up, 30.1% of these patients underwent 61,107 additional studies. CONCLUSIONS: Use of NLP to detect carotid stenosis or occlusion can result in accurate exclusion of normal/non-hemodynamically significant stenosis disease states with more moderate precision with lesion identification, which can substantially reduce the need for manual review. The resulting cohort allows for efficient research and holds promise for similar reporting in other vascular diseases.

Long-term stroke risk with carotid endarterectomy in patients with severe carotid stenosis.

OBJECTIVE: Informed debate regarding the optimal use of carotid endarterectomy (CEA) for stroke risk reduction requires contemporary assessment of both long-term risk and periprocedural risk. In this study, we report long-term stroke and death risk after CEA in a large integrated health care system. METHODS: All patients with documented severe (70%-99%) stenosis from 2008 to 2012 who underwent CEA were identified and stratified by asymptomatic or symptomatic indication. Those with prior ipsilateral interventions were excluded. Patients were followed up through 2017 for the primary outcomes of any stroke/death within 30 days of intervention and long-term ipsilateral ischemic stroke; secondary outcomes were any stroke and overall survival. RESULTS: Overall, 1949 patients (63.2% male; mean age, 71.3 ± 8.9 years) underwent 2078 primary CEAs, 1196 (58%) for asymptomatic stenosis and 882 (42%) for symptomatic stenosis. Mean follow-up was 5.5 ± 2.7 years. Median time to surgery was 72.0 (interquartile range, 38.5-198.0) days for asymptomatic patients and 21.0 (interquartile range, 5.0-55.0) days for symptomatic patients (P < .001). Most of the patients' demographics and characteristics were similar in both groups. Controlled blood pressure rates were similar at the time of CEA. Baseline statin use was seen in 60.5% of the asymptomatic group compared with 39.9% in the symptomatic group (P < .001), and statin adherence by 80% medication possession ratio was 19.3% asymptomatic vs 12.4% symptomatic (P < .001). The crude overall 30-day any stroke/death rates were 0.9% and 1.5% for the asymptomatic group and the symptomatic group, respectively. The 5-year risk of ipsilateral stroke and a combined end point of any stroke/death by Kaplan-Meier survival analysis were 2.5% and 28.7% for the asymptomatic group and 4.0% and 31.4% for the symptomatic group, respectively. Unadjusted cumulative all-cause survival was 74.2% for the asymptomatic group and 71.8% for the symptomatic group at 5 years. CONCLUSIONS: In a contemporary review of CEA, outcomes for either operative indication show low adverse events perioperatively and low long-term stroke risk up to 5 years. These results are well within consensus guidelines and published trial outcomes and should help inform the discussion around optimal CEA use for severe carotid stenosis.

Midterm outcomes for 605 patients receiving Endologix AFX or AFX2 Endovascular AAA Systems in an integrated healthcare system.

BACKGROUND: Endologix issued important safety updates for the AFX Endovascular AAA System in 2016 and 2018 owing to the risk of type III endoleaks. Outcomes with these devices are limited to small case series with short-term follow-up. We describe the midterm outcomes for a large cohort of patients who received an Endologix AFX or AFX2 device. STUDY DESIGN: Data from an integrated healthcare system's implant registry, which prospectively monitors all patients after endovascular aortic repair, was used for this descriptive study. Patients undergoing endovascular aortic repair with three AFX System variations (Strata [AFX-S], Duraply [AFX-D], and AFX2 with Duraply [AFX2]) were identified (2011-2017). Crude cumulative event probabilities for endoleak (types I and III), major reintervention, conversion to open, rupture, and mortality (aneurysm related and all cause) were estimated. RESULTS: Among 605 patients, 375 received AFX-S, 197 received AFX-D, and 33 received AFX2. Median follow-up for the cohort was 3.9 (interquartile range, 2.5-5.1) years. The crude 2-year incidence of overall endoleak, any subsequent reintervention or conversion, and mortality was 8.8% (95% confidence interval [CI], 6.3-12.3), 12.0% (95% CI, 9.1-15.9), and 8.8% (95% CI, 6.3-12.2) for AFX-S. Respective estimates for AFX-D were 7.9% (95% CI, 4.8-13.0), 10.6% (95% CI, 6.9-16.1), and 9.7% (95% CI, 6.3-14.7); for AFX2, they were 14.1% (95% CI, 4.7-38.2), 16.2% (95% CI, 6.4-37.7), and 21.2% (95% CI, 10.7-39.4). CONCLUSIONS: The midterm outcomes of a large U.S. patient cohort with an Endologix AFX or AFX2 System demonstrate a concerning rate of adverse postoperative events. Patients with these devices should receive close clinical surveillance to prevent device-related adverse events.

Long-term freedom from aneurysm-related mortality remains favorable after endovascular abdominal aortic aneurysm repair in a 15-year multicenter registry.

OBJECTIVE: Endovascular aneurysm repair (EVAR) has become the preferred approach to abdominal aortic aneurysm (AAA) because of lower early morbidity and mortality than open repair. However, the ability of EVAR to prevent long-term aneurysm-related mortality (ARM) has been questioned in light of recent trial data. We have updated our long-term EVAR experience in a large multicenter registry to further examine this issue. METHODS: Between 2000 and 2010, 1736 patients with AAA underwent EVAR in a large integrated regional healthcare system. We extended follow-up in this previously reported cohort through 2015 and identified predictors associated with ARM and need for major reintervention. The primary outcome was ARM. Secondary outcomes were all-cause mortality, delayed aneurysm rupture, major adverse event, major reintervention, sac growth of more than 5 mm, and type I or III endoleak. End points were analyzed for the whole cohort and compared for patients who underwent EVAR during the earlier (2000-2005) and latter (2006-2010) halves of the enrollment period to assess for changes in outcomes over time of repair. RESULTS: The overall follow-up rate was 96.3%, and median follow-up was 5.5 years (interquartile range, 2.8-7.7 years). During the study period, 958 patients died, of whom 63 experienced ARM (6.6%). Overall crude rate of freedom from ARM was 96.4%. Delayed aneurysm rupture was seen in 1.3% (n = 23), with a median time to event of 4.1 years (interquartile range, 1.7-7.2 years). Major adverse events occurred in 12.4% of patients, and major reintervention was performed in 10.3%. Overall freedom from major adverse event or major reintervention was seen in 84.0%. Significant predictors of ARM included female sex, age 80 to 89 years, urgent EVAR, and any major reintervention. The unadjusted cumulative probability of all-cause survival was significantly higher in the late group than the early group at 5 years (66.8% vs 59.8%; P = .01, log-rank test); however, freedom from ARM at 5 years was not significantly different (96.5% and 97.1%, respectively; P = .67, log-rank test). CONCLUSIONS: Our results demonstrate favorable long-term freedom from major adverse event or major reintervention after EVAR and extremely low rates of ARM and delayed rupture. Our findings support EVAR as a safe, long-term solution for managing patients with AAA and provide insight into clinical parameters that can be used to stratify patients' post-EVAR surveillance and need for reintervention.

Aggregation control in natural brush-printed conjugated polymer films and implications for enhancing charge transport.

Shear-printing is a promising processing technique in organic electronics for microstructure/charge transport modification and large-area film fabrication. Nevertheless, the mechanism by which shear-printing can enhance charge transport is not well-understood. In this study, a printing method using natural brushes is adopted as an informative tool to realize direct aggregation control of conjugated polymers and to investigate the interplay between printing parameters, macromolecule backbone alignment and aggregation, and charge transport anisotropy in a conjugated polymer series differing in architecture and electronic structure. This series includes (i) semicrystalline hole-transporting P3HT, (ii) semicrystalline electron-transporting N2200, (iii) low-crystallinity hole-transporting PBDTT-FTTE, and (iv) low-crystallinity conducting PEDOT:PSS. The (semi-)conducting films are characterized by a battery of morphology and microstructure analysis techniques and by charge transport measurements. We report that remarkably enhanced mobilities/conductivities, as high as 5.7×/3.9×, are achieved by controlled growth of nanofibril aggregates and by backbone alignment, with the adjusted R2 (R2adj) correlation between aggregation and charge transport as high as 95%. However, while shear-induced aggregation is important for enhancing charge transport, backbone alignment alone does not guarantee charge transport anisotropy. The correlations between efficient charge transport and aggregation are clearly shown, while mobility and degree of orientation are not always well-correlated. These observations provide insights into macroscopic charge transport mechanisms in conjugated polymers and suggest guidelines for optimization.