Citations

Purpose: The role of erectile dysfunction (ED) has recently shown an association with the risk of stroke and coronary heart disease (CHD) via the atherosclerotic pathway. Cardiovascular disease (CVD)/stroke risk has been widely understood with the help of carotid artery disease (CTAD), a surrogate biomarker for CHD. The proposed study emphasizes artificial intelligence-based frameworks such as machine learning (ML) and deep learning (DL) that can accurately predict the severity of CVD/stroke risk using carotid wall arterial imaging in ED patients. Methods: Using the PRISMA model, 231 of the best studies were selected. The proposed study mainly consists of two components: (i) the pathophysiology of ED and its link with coronary artery disease (COAD) and CHD in the ED framework and (ii) the ultrasonic-image morphological changes in the carotid arterial walls by quantifying the wall parameters and the characterization of the wall tissue by adapting the ML/DL-based methods, both for the prediction of the severity of CVD risk. The proposed study analyzes the hypothesis that ML/DL can lead to an accurate and early diagnosis of the CVD/stroke risk in ED patients. Our finding suggests that the routine ED patient practice can be amended for ML/DL-based CVD/stroke risk assessment using carotid wall arterial imaging leading to fast, reliable, and accurate CVD/stroke risk stratification. Summary: We conclude that ML and DL methods are very powerful tools for the characterization of CVD/stroke in patients with varying ED conditions. We anticipate a rapid growth of these tools for early and better CVD/stroke risk management in ED patients.

540 Background: The 3-arm, open-label, phase 3 KEYNOTE-361 study (NCT02853305) evaluated first-line pembro ± chemo vs chemo in advanced UC regardless of PD-L1 status. The trial did not meet its primary end points of superior PFS and OS with pembro + chemo vs chemo and thus analysis of pembro monotherapy (mono) vs chemo was exploratory. We explored the association of TMB status and PD-L1 combined positive score (CPS) with clinical outcomes in KEYNOTE-361. Methods: In pts with TMB and/or PD-L1 data, the association between TMB (via whole exome sequencing) and PD-L1 (via PD-L1 IHC 22C3 pharmDx) and clinical outcomes (ORR, PFS, and OS) was evaluated. In each treatment arm, the hypotheses regarding the associations were evaluated using logistic regression (ORR) and Cox proportional hazards regression (PFS; OS), and 1-sided (pembro; pembro + chemo) and 2-sided (chemo) P values were calculated; significance was prespecified at α = 0.05 without multiplicity adjustment. Clinical utility was assessed using prespecified cutoffs of 175 mut/exome (TMB) and CPS 10 (PD-L1). Clinical data cutoff was April 29, 2020. Results: 820/993 pts (82.6%) had evaluable TMB data (pembro, 252; pembro + chemo, 282; chemo, 286). TMB (log10) was significantly positively associated with ORR, PFS, and OS for pembro ( P < 0.001, < 0.001, and 0.007, respectively) and PFS and OS for pembro + chemo ( P= 0.007 and 0.010, respectively). The area under the receiver operating characteristics (AUROC) curve (95% CI) for discriminating response was 0.64 (0.56-0.71) for pembro, 0.53 (0.46-0.60) for pembro + chemo, and 0.52 (0.45-0.59) for chemo. Efficacy by TMB cutoff is reported in the Table. All 993 pts had PD-L1 data (pembro, 302; pembro + chemo, 349; chemo, 342). PD-L1 was significantly positively associated with PFS for pembro ( P= 0.006) and ORR for pembro + chemo ( P= 0.042) but not chemo. Efficacy by PD-L1 CPS is reported in the Table. Conclusions: Strong associations were observed between TMB and all 3 clinical outcomes (ORR, PFS, and OS) with pembro mono in the first-line setting and a reduced association was observed between TMB and clinical outcomes with pembro + chemo. No consistent associations were observed between PD-L1 and clinical outcomes with pembro mono or pembro + chemo. Clinical trial information: NCT02853305. [Table: see text]

Abstract Stroke represents a considerable burden of disease for both men and women. However, a growing body of literature suggests clinically relevant sex differences in the underlying causes, presentations and outcomes of acute ischaemic stroke. In a recent study, we reported sex divergences in lesion topographies: specific to women, acute stroke severity was linked to lesions in the left-hemispheric posterior circulation. We here determined whether these sex-specific brain manifestations also affect long-term outcomes. We relied on 822 acute ischaemic patients [age: 64.7 (15.0) years, 39% women] originating from the multi-centre MRI-GENIE study to model unfavourable outcomes (modified Rankin Scale &gt;2) based on acute neuroimaging data in a Bayesian hierarchical framework. Lesions encompassing bilateral subcortical nuclei and left-lateralized regions in proximity to the insula explained outcomes across men and women (area under the curve = 0.81). A pattern of left-hemispheric posterior circulation brain regions, combining left hippocampus, precuneus, fusiform and lingual gyrus, occipital pole and latero-occipital cortex, showed a substantially higher relevance in explaining functional outcomes in women compared to men [mean difference of Bayesian posterior distributions (men – women) = −0.295 (90% highest posterior density interval = −0.556 to −0.068)]. Once validated in prospective studies, our findings may motivate a sex-specific approach to clinical stroke management and hold the promise of enhancing outcomes on a population level.

Abstract While chronological age is one of the most influential determinants of post-stroke outcomes, little is known of the impact of neuroimaging-derived biological brain age. We here first examine whether radiomics analysis of the texture of brain T2-FLAIR MRI images can be used to predict brain age in stroke patients. We then assess the clinical determinants of accelerated brain aging and, finally, its impact on post-stroke functional outcomes. Leveraging a multisite cohort of 4,163 ischemic stroke patients, we show that older-appearing patients have more hypertension, diabetes mellitus, prior strokes, and smoking history and are more likely to develop worse post-stroke outcomes than their younger-appearing counterparts. Our results strengthen the importance of preventive medicine for maintaining brain health in stroke patients as they age and suggest a novel methodology to capture previously undescribed prognostic information available on commonly acquired MRI sequences during routine stroke care.

Abstract Cirrhosis, highly prevalent worldwide, develops after years of hepatic inflammation triggering progressive fibrosis. Currently, the main etiologies of cirrhosis are non‐alcoholic fatty liver disease and alcohol‐related liver disease, although chronic hepatitis B and C infections are still major etiological factors in some areas of the world. Recent studies have shown that liver fibrosis can be assessed with relatively high accuracy noninvasively by serological tests, transient elastography, and radiological methods. These modalities may be utilized for screening for liver fibrosis in at‐risk populations. Thus far, a limited number of population‐based studies using noninvasive tests in different areas of the world indicate that a significant percentage of subjects without known liver disease (around 5% in general populations and a higher rate −18% to 27%‐in populations with risk factors for liver disease) have significant undetected liver fibrosis or established cirrhosis. Larger international studies are required to show the harms and benefits before concluding that screening for liver fibrosis should be applied to populations at risk for chronic liver diseases. Screening for liver fibrosis has the potential for changing the current approach from diagnosing chronic liver diseases late when patients have already developed complications of cirrhosis to diagnosing liver fibrosis in asymptomatic subjects providing the opportunity of preventing disease progression.

AbstractDespite the fact that the choice of bearing design has been thought to influence the functional outcomes and longevity of unicompartimental knee arthroplasty (UKA), there is a lack of clinical evidence supporting the decision‐making process in patients who have undergone high tibial osteotomy (HTO). A systematic review of studies was carried out that reported the outcomes of fixed‐bearing (FB) or mobile‐bearing (MB) medial UKA in patients with a previous HTO. A random effect meta‐analysis using a generalized linear mixed‐effects model to calculate revision rates was done. Seven retrospective cohort studies were included for this study. Regarding the fixation method, 40 were the FB‐UKA and 47 were MB‐UKA. For both groups, the mean post‐operative follow‐up was 5.8 years. The survival rates were 92% for the FB‐UKA with a mean follow‐up of 10 years. For the MB‐UKA, it ranged from 35.7 to 93%, with a mean follow‐up of 4.2 years. For the FB, the time to revision was reported as 9.3 years, while 1.2, 2.5 and 2.91 years was reported for the MB. The results of the meta‐analysis showed that the revision rate for the patients receiving a FB‐UKA after failed HTO was 8%, compared to 17% in those who received an MB‐UKA. The results of the review suggest that the use of the FB‐UKA is associated with lower revision rates and a longer survival time than the MB‐UKA and have similar functional ability scores.Level of evidence: III (systematic review of level‐III studies).

Background: Considerable disagreement exists among experts regarding the appropriate extent of diagnostic testing after ischemic stroke (IS). Evidence-based data guiding stroke evaluation for individual patients according to the underlying phenotype are unknown. We sought to determine the yield of cardiac and arterial evaluations for identifying an alternative major stroke etiology in patients with a given phenotype in the NINDS Stroke Genetics Network (SiGN). Methods: SiGN is a consortium of IS studies at 22 US and European sites aiming to identify stroke susceptibility genes. Adjudicators certified in Causative Classification of Stroke (CCS) system determined major etiologic stroke phenotypes based on chart review. All diagnostic data entered into the CCS software were stored in a confidential database. We determined the probability of identifying an alternative major abnormality based on cardiac (history, EKG, echocardiography) and arterial [intracranial (IC), extracranial (EC)] evaluations in 3 stroke phenotypes: lacunar infarct (LI), large artery atherosclerosis (LAA), and cardiac embolism (CE). Proportions of alternative major etiologies were calculated in patients with complete evaluations in each phenotype. Results: The analyses included 15720 patients. Among these, 2299 had phenotypic subtype of LI (1660 with cardiac and 1691 with arterial evaluations); 4228 had CE (2451 with arterial evaluation); and 2613 had LAA (2047 with cardiac evaluation). Cardiac evaluation revealed a major cardiac source of embolism in 12.3% of patients with LI and 20.3% with LAA. Echocardiography demonstrated an additional major structural cardiac source not seen by history/examination/EKG in 1.9% and 1.6% in LI and LAA respectively. Arterial evaluation led to the identification of ≥50%ipsilateral stenosis in 13.5% (IC: 8.9%, EC: 5.8%) of patients with LI and 17% (IC: 8.1%, EC: 11.3%) of those with CE. In LI patients with complete cardiac and vascular evaluations, 24.1% had an alternative major stroke etiology. Conclusions: A considerable proportion of IS patients with LI, LAA, and CE harbor an alternative major etiology. In the future, these results can be used to generate evidence-based and cost-effective evaluation and management strategies.

Background: Fundamental advances in stroke care will require pooling imaging phenotype data from multiple centers, to complement the current aggregation of genomic, environmental, and clinical information. Sharing clinically acquired MRI data from multiple hospitals is challenging due to inherent heterogeneity of clinical data, where the same MRI series may be labeled differently depending on vendor and hospital. Furthermore, the de-identification process may remove data describing the MRI series, requiring human review. However, manually annotating the MRI series is not only laborious and slow but prone to human error. In this work, we present a recurrent convolutional neural network (RCNN) for automated classification of the MRI series. Methods: We randomly selected 1000 subjects from the MRI-GENetics Interface Exploration study and partitioned them into 800 training, 100 validation and 100 testing subjects. We categorized the MRI series into 24 groups (see Table). The RCNN used a modified AlexNet to extract features from 2D slices. AlexNet was pretrained on ImageNet photographs. Since clinical MRI are 3D and 4D, a gated recurrent unit neural network was used to aggregate information from multiple 2D slices to make the final prediction. Results: We achieved a classification accuracy (correct/total cases) of 99.8%, 98.5% and 97.5% on the training, validation and testing set, respectively. The averaged F1-score (percent overlap between predicted cases and actual cases) over all categories were 99.8% 98.2% and 94.4% on the training, validation and testing set. Conclusion: We showed that automated annotation of MRI series by repurposing deep-learning techniques used for photographic image recognition tasks is feasible. Such methods can be used to facilitate high throughput curation of MRI data acquired across multiple centers and enable scientifically productive collaboration by researchers and, ultimately enhancing big data stroke research.

Introduction: Genetic studies of early-onset disease have been an effective strategy to identify novel pathways and drug targets relevant to later-onset disease. Few studies have investigated the role of common genetic variation in the etiology of early-onset ischemic stroke (IS). Methods: We performed a GWAS meta-analysis of 38 studies from 10 countries, comprised of 5,847 IS cases of European ancestry under age 60 and 32,533 controls. Results: We identified two genome-wide significant (p< 5 x 10 -8 ) loci (see Figure). The ABO locus has previously been associated with venous thrombosis and ischemic stroke in predominantly older adults, but the effect size of our top SNP (OR 1.18; p = 9.1 x 10 -12 ) is larger than the effect size for this same SNP in MEGASTROKE (OR: 1.05; p = 6.5 x 10 -5 ). The lead SNP at the BCL7A/MLXIP locus is a novel GWAS finding for stroke (OR 1.14, 95% CI 1.08-1.19; p = 1.7 x 10 -8 ) and is noteworthy because of prior reports linking SNPs in these genes to BMI and blood pressure. Conclusions: We identified a novel locus that is near variants associated with BMI and blood pressure. Further studies are needed to confirm this locus, examine subtype specificity, and determine its function. The larger effect size observed at the ABO in this early-onset IS sample compared to older-onset IS samples is consistent with a larger role for prothrombotic mechanisms in early-onset IS.