Citations

Background Computed tomography (CT) angiography collateral score (CTA-CS) is an important clinical outcome predictor following mechanical thrombectomy for ischemic stroke with large vessel occlusion (LVO). The present multireader study aimed to evaluate the performance of e-CTA software for automated assistance in CTA-CS scoring. Materials and Methods Brain CTA images of 56 patients with anterior LVO were retrospectively processed. Twelve readers of various clinical training, including junior neuroradiologists, senior neuroradiologists, and neurologists graded collateral flow using visual CTA-CS scale in two sessions separated by a washout period. Reference standard was the consensus of three expert readers. Duration of reading time, inter-rater reliability, and statistical comparison of readers’ performance metrics were analyzed between the e-CTA assisted and unassisted sessions. Results e-CTA assistance resulted in significant increase in mean accuracy (58.6% to 67.5%, p = 0.003), mean F1 score (0.574 to 0.676, p = 0.002), mean precision (58.8% to 68%, p = 0.007), and mean recall (58.7% to 69.9%, p = 0.002), especially with slight filling deficit (CTA-CS 2 and 3). Mean reading time was reduced across all readers (103.4 to 59.7 s, p = 0.001), and inter-rater agreement in CTA-CS assessment was increased (Krippendorff's alpha 0.366 to 0.676). Optimized occlusion laterality detection was also noted with mean accuracy (92.9% to 96.8%, p = 0.009). Conclusion Automated assistance for CTA-CS using e-CTA software provided helpful decision support for readers in terms of improving scoring accuracy and reading efficiency for physicians with a range of experience and training backgrounds and leading to significant improvements in inter-rater agreement.

Background: Heart disease is linked to worse acute outcomes after coronavirus disease 2019 (COVID-19), although long-term outcomes and prognostic factor data are lacking. We aim to characterize the outcomes and the impact of underlying heart diseases after surviving COVID-19 hospitalization. Methods: We conducted an analysis of the prospective registry HOPE-2 (Health Outcome Predictive Evaluation for COVID-19-2, NCT04778020). We selected patients discharged alive and considered the primary end-point all-cause mortality during follow-up. As secondary main end-points, we included any readmission or any post-COVID-19 symptom. Clinical features and follow-up events are compared between those with and without cardiovascular disease. Factors with p < 0.05 in the univariate analysis were entered into the multivariate analysis to determine independent prognostic factors. Results: HOPE-2 closed on 31 December 2021, with 9299 patients hospitalized with COVID-19, and 1805 died during this acute phase. Finally, 7014 patients with heart disease data were included in the present analysis, from 56 centers in 8 countries. Heart disease (+) patients were older (73 vs. 58 years old), more frequently male (63 vs. 56%), had more comorbidities than their counterparts, and suffered more frequently from post-COVID-19 complications and higher mortality (OR heart disease: 2.63, 95% CI: 1.81–3.84). Vaccination was found to be an independent protector factor (HR all-cause death: 0.09; 95% CI: 0.04–0.19). Conclusions: After surviving the acute phase, patients with underlying heart disease continue to present a more complex clinical profile and worse outcomes including increased mortality. The COVID-19 vaccine could benefit survival in patients with heart disease during follow-up.

Abstract Neurofilament light chain, a putative measure of neuronal damage, is measurable in blood and CSF and is predictive of cognitive function in individuals with Alzheimer’s disease. There has been limited prior work linking neurofilament light and functional connectivity, and no prior work has investigated neurofilament light associations with functional connectivity in autosomal dominant Alzheimer’s disease. Here, we assessed relationships between blood neurofilament light, cognition, and functional connectivity in a cross-sectional sample of 106 autosomal dominant Alzheimer’s disease mutation carriers and 76 non-carriers. We employed an innovative network-level enrichment analysis approach to assess connectome-wide associations with neurofilament light. Neurofilament light was positively correlated with deterioration of functional connectivity within the default mode network and negatively correlated with connectivity between default mode network and executive control networks, including the cingulo-opercular, salience, and dorsal attention networks. Further, reduced connectivity within the default mode network and between the default mode network and executive control networks was associated with reduced cognitive function. Hierarchical regression analysis revealed that neurofilament levels and functional connectivity within the default mode network and between the default mode network and the dorsal attention network explained significant variance in cognitive composite scores when controlling for age, sex, and education. A mediation analysis demonstrated that functional connectivity within the default mode network and between the default mode network and dorsal attention network partially mediated the relationship between blood neurofilament light levels and cognitive function. Our novel results indicate that blood estimates of neurofilament levels correspond to direct measurements of brain dysfunction, shedding new light on the underlying biological processes of Alzheimer’s disease. Further, we demonstrate how variation within key brain systems can partially mediate the negative effects of heightened total serum neurofilament levels, suggesting potential regions for targeted interventions. Finally, our results lend further evidence that low-cost and minimally invasive blood measurements of neurofilament may be a useful marker of brain functional connectivity and cognitive decline in Alzheimer’s disease.

Abstract Introduction: Mammographic breast density is among the strongest risk factors for breast cancer. However, breast density is typically assessed subjectively by the radiologist according to the Breast Imaging Reporting and Data System (BI-RADS) based on 2 dimensional (2D) digital mammography (DM) images. Digital breast tomosynthesis (DBT) is quickly replacing DM and allows more detailed volumetric imaging of the breast. Advances in radiomics, the high-throughput extraction of radiologic features, has enabled characterization of breast parenchymal complexity beyond breast density alone. The purpose of this study was to compare the performance of volumetric parenchymal pattern analysis from DBT and DM with conventional breast density measurement with respect to breast cancer risk estimation. Methods: We performed a case control study among women with concurrent DM and DBT screening (Selenia Dimensions, Hologic Inc.) at our institution between 3/2011-12/2014. Cases were diagnosed with breast cancer within 1 year of screening; controls were confirmed negative or benign at 1 year follow-up, matched on race (Black, White, other/unknown) and age (5-year bins). After exclusions for imaging artifacts, craniocaudal (CC) and mediolateral oblique (MLO) views for 187 cases and 737 controls, in six image formats were assessed: 1) raw (“FOR PROCESSING”) DM; 2) processed (“FOR PRESENTATION”) DM; 3) raw DBT central projection; 4) processed DBT central projection; 5) DBT central reconstructed slice; and 6) DBT reconstructed stack. For cases, we analyzed the breast contralateral to cancer diagnosis; for controls the same breast as the matched case. We extracted radiomic features using a lattice-based approach with the publicly available CaPTk software, averaging features for each breast over CC and MLO views. We examined 3 lattice window sizes (6.4, 12.8, and 25.6 mm) and 23 resolutions for image resampling (0.075 - 2mm). We performed PCA on the resulting 487 features for each combination of window size and resolution and built conditional logistic regression models to assess the association of the first 7 principal components with breast cancer, with models including age, BMI, and BI-RADS density. For each image type we calculated the model C-statistic at all window sizes and resolutions, for a total of 2304 experimental conditions. Results: Features from reconstructed DBT scans had on average higher C-statistics across all experimental conditions. A model using only age, BMI, and BI-RADS density had a C-statistic of 0.61. Models using radiomic features plus age, BMI, and BI-RADS density had mean C-statistic of 0.68 (IQR 0.68, 0.69) for reconstructed DBT scans; for all other image types, the mean C-statistic ranged from 0.64 to 0.66. Conclusions: Incorporating volumetric breast parenchymal patterns from DBT improves breast cancer risk estimation beyond markers derived from DM and beyond conventional BI-RADS density. Citation Format: Eric A. Cohen, Omid Haji Maghsoudi, Raymond Acciavatti, Lauren Pantalone, Walter Mankowski, Alex A Nguyen, Christopher G. Scott, Stacey Winham, Andrew D. Maidment, Anne Marie McCarthy, Celine M Vachon, Emily F Conant, Despina Kontos. Volumetric parenchymal pattern analysis for breast cancer risk estimation. [abstract]. In: Proceedings of the AACR Special Conference: Precision Prevention, Early Detection, and Interception of Cancer; 2022 Nov 17-19; Austin, TX. Philadelphia (PA): AACR; Can Prev Res 2023;16(1 Suppl): Abstract nr P070.

AbstractPlasmablastic lymphoma (PBL) is a rare entity, commonly associated with immunosuppressed states such as human immunodeficiency virus (HIV) infection or solid organ transplant. The clinical course is characterized by high relapse rates and a poor prognosis, leading some clinicians to recommend aggressive frontline therapy. However, a specific review of limited stage (LS) PBL patients is not available to evaluate outcomes and justify treatment recommendations. We performed a retrospective review of LS PBL cases to provide insight into this rare disease. Our cohort consisted of 80 stage I or II PBL patients from 13 US academic centers. With a median follow up of 34 months (1–196), the 3‐year progression‐free survival (PFS) and overall survival (OS) of the entire cohort were 72% (95% CI 62, 83) and 79% (95% CI 70, 89), respectively. The 3‐year PFS and OS of patients treated with frontline chemotherapy alone was 65% (95% CI 50, 84) and 71% (95% CI 56, 89), respectively, compared to 85% (95% CI 72, 100) and 96% (95% CI 89, 100), respectively, in patients treated with combined frontline chemotherapy with radiation consolidation. Our data demonstrate favorable outcomes in LS PBL with no improvements in outcome from aggressive frontline treatment including Hyper‐CVAD or auto‐SCT consolidation. Multivariate regression analysis (MRA) demonstrated improved PFS for patients receiving EPOCH based frontline therapy versus CHOP (HR: 0.23; p = 0.029). Frontline chemotherapy followed by radiation consolidation versus chemotherapy alone appeared to be associated with improved relapse and survival outcomes but did not show statistical significance in MRA.

Abstract The microbiota present on every mucosal surface of the body is imperative for the development and maintenance of the immune system. Disruption of the microbiota from environmental factors can affect immune components in both the mucosal and the systemic immune compartments. Following birth in mammals including humans and mice, the microbiota rapidly develops and matures into a composition generally seen in adults when infants are weaned. Gut microbiota composition is directly affected by feeding type, breast-fed vs formula-feeding, in humans, and the microbiota associated with breastfeeding has been shown to promote intestinal health. As the composition of breastmilk changes throughout lactation, we hypothesize maternal provided factors within breastmilk support the development of the microbiota in a temporally sensitive manner. To address this question we asynchronously cross-fostered (ACF) litters born on day 1 to dams who had delivered 2 weeks earlier. Gut microbiota composition was assessed by 16S analysis of stool samples at the time of weaning, and while the microbiota of synchronous cross-fostered pups resembled the microbiota of their foster dam, the microbiota of ASF mice was different from both their foster dam and the healthy microbiota seen in weanling mice. ACF mice had a significant reduction in bacteroides and firmicute species, species that generally represent the majority of the bacteria within a healthy microbiota, and expansion in prevotella species, which include clinically important opportunistic pathogens, suggesting ACF mice contain a dysbiotic microbiota. Future work will explore and identify what temporally dependent components in breast milk support the development of a healthy microbiota.

Abstract Late-onset neonatal sepsis (LOS), a significant cause of morbidity and mortality in prematurely born infants, results from a bloodstream infection of gut-originating bacteria. It remains unclear how such bacteria translocate from the intestine, though it has been repeatedly observed that breastfed infants, particularly those fed mother’s own milk (MOM), have reduced risk of LOS compared to formula fed infants. Epidermal growth factor (EGF) promotes intestinal barrier function in infants and is present at high concentrations in breast milk post-partum and decreases throughout lactation. We found reduced concentrations of EGF in the stool of premature formula-fed infants compared to MOM-fed infants, and observed a similar decrease in EGF concentrations of stool of neonatal mice asynchronously cross-fostered (ACF) to dams that had delivered two weeks prior. LOS bloodstream isolates of E. coli colonized the tracts of all pups but translocated and disseminated systemically only in ACF mice resulting in bacteremia and rapid death. Goblet cell intrinsic sensing of EGF via the epidermal growth factor receptor (EGFR) limited bacterial translocation from the colon. Oral gavage of recombinant EGF reduced bacteria translocation and prevented the development of systemic disease in ACF mice. Thus, disruption of maternally delivered EGF in ACF mice results in translocation of pathogens from the gut, and a sepsis-like disease. In conclusion we have identified a mechanism whereby a gut-residing pathogen gains systemic access and have developed a novel animal model replicating this mechanism to explore the protective effect of breastmilk and EGF in LOS.

AbstractBackgroundThere is a critical need for tau PET radiotracers that accurately detect non‐Alzheimer’s disease (AD) tau pathology. We aim to evaluate [18F]PI‐2620 PET tracer retention in patients with non‐AD, 4R tau‐related clinical syndromes, including progressive supranuclear palsy (PSP) with Richardson’s syndrome (PSP‐RS) and with predominant parkinsonism (PSP‐P), corticobasal syndrome (CBS), and nonfluent/agrammatic variant of primary progressive aphasia (nfvPPA).Method38 participants underwent amyloid and [18F]PI‐2620 PET (Table 1). 5 mCi ± 10% of [18F]PI‐2620 was administered. [18F]PI‐2620 PET SUVR images were generated using an inferior cerebellar gray matter reference from PET data acquired 30‐60 minutes post‐injection. Mean SUVR values were extracted from each participant in neuroanatomical structures that have elevated tau burden in PSP and CBS due to corticobasal degeneration (regions of interest in Table 2). Comparison between each diagnostic group and healthy controls (HCs) was performed using a one‐tailed, independent‐samples t‐test. Spearman correlation was used to evaluate the relationship between tracer binding (SUVR) and disease severity (PSP rating scale) in patients with PSP‐RS.ResultPatients with PSP‐RS had increased tracer retention in the left globus pallidus internus and externus, left subthalamic nucleus, and left dorsolateral prefrontal cortex compared to HCs (all p < 0.05). CBS and nfvPPA patients did not have increased tracer retention at any ROIs compared to HCs, but there were low numbers of patients in these groups (Table 2, Figures 1‐3). PSP rating scale values did not correlate with tracer binding in PSP‐RS (no correlations in any regions, rs < 0.44, p > 0.05 uncorrected).Conclusion[18F]PI‐2620 PET 30‐60 minute SUVR images may have limited ability to distinguish PSP from HCs, especially on visual read, and tracer uptake did not correlate with PSP disease severity. Other post‐injection PET acquisition windows (e.g., 30‐40 minute SUVR, 0‐60 minute DVR) will be evaluated to determine if they can maximize differences between PSP and HCs. A limitation of this preliminary study is the modest number of patients and controls, with most controls provided from a different study. Additional participants are being scanned in the multicenter 4RTNI study to understand the utility of this tracer as a neuroimaging biomarker for 4R tauopathies.

AbstractBackgroundThe relationship between CINV duration and recurrence in subsequent cycles is largely unstudied. Our objective was to determine if patients experiencing CINV in their first cycle of chemotherapy (C1) would face increased risk of CINV in later cycles and whether the duration of the CINV would predict increased risk of recurrence.Patients and MethodsUsing data from a previously reported phase III trial, we assessed patients’ recurrence of breakthrough CINV after antiemetic prophylaxis for anthracycline+cyclophosphamide (AC) for breast cancer, comparing C1 short CINV vs. extended CINV as a secondary analysis. Complete response (CR) and CINV duration were primary and secondary endpoints, respectively. CR was considered prophylaxis success; lack of CR was considered treatment failure (TF).ResultsAmong 402 female patients, 99 (24.6%) had TF in C1 (TF1). The remaining 303 patients (CR1) had ≥93% CR rates in each subsequent cycle, while the 99 patients with TF1 had TF rates of 49.8% for cycles 2-4 (P &lt; .001). The 51 patients with extended TF (≥3 days) in C1 had recurrent TF in 73/105 later cycles (69.5%, P &lt; .001), while the 48 patients with short TF (1-2 days) in C1 had recurrent TF in 33/108 later cycles (30.6%). The relative risk of recurrence after C1 extended TF was 2.28 (CI 1.67-3.11; P &lt; .001) compared to short TF.ConclusionsProphylaxis success in C1 led to &gt;90% repeat success across cycles of AC-based chemotherapy. For patients with breakthrough CINV, extended duration strongly predicted recurrent CINV. The duration of CINV should be closely monitored, and augmenting antiemetic prophylaxis considered for future cycles when extended CINV occurs.