Thrombectomy Outcomes With General vs Nongeneral Anesthesia: A Pooled Patient-Level Analysis From the EXTEND-IA Trials and SELECT Study

BACKGROUND AND OBJECTIVES: The effect of anesthesia choice on endovascular thrombectomy (EVT) outcomes is unclear. Collateral status on perfusion imaging may help identify the optimal anesthesia choice. METHODS: In a pooled patient-level analysis of EXTEND-IA, EXTEND-IA TNK, EXTEND-IA TNK part II, and SELECT, EVT functional outcomes (modified Rankin Scale score distribution) were compared between general anesthesia (GA) vs non-GA in a propensity-matched sample. Furthermore, we evaluated the association of collateral flow on perfusion imaging, assessed by hypoperfusion intensity ratio (HIR) - Tmax \u3e 10 seconds/Tmax \u3e 6 seconds (good collaterals - HIR \u3c 0.4, poor collaterals - HIR ≥ 0.4) on the association between anesthesia type and EVT outcomes. RESULTS: Of 725 treated with EVT, 299 (41%) received GA and 426 (59%) non-GA. The baseline characteristics differed in presentation National Institutes of Health Stroke Scale score (median [interquartile range] GA: 18 [13-22], non-GA: 16 [11-20], DISCUSSION: GA was associated with worse functional outcomes after EVT, particularly in patients with poor collaterals in a propensity score-matched analysis from a pooled patient-level cohort from 3 randomized trials and 1 prospective cohort study. The confounding by indication may persist despite the doubly robust nature of the analysis. These findings have implications for randomized trials of GA vs non-GA and may be of utility for clinicians when making anesthesia type choice. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that use of GA is associated with worse functional outcome in patients undergoing EVT. TRIAL REGISTRATION INFORMATION: EXTEND-IA: ClinicalTrials.gov (NCT01492725); EXTEND-IA TNK: ClinicalTrials.gov (NCT02388061); EXTEND-IA TNK part II: ClinicalTrials.gov (NCT03340493); and SELECT: ClinicalTrials.gov (NCT02446587)

Thrombectomy Outcomes With General vs Nongeneral Anesthesia: A Pooled Patient-Level Analysis From the EXTEND-IA Trials and SELECT Study

Background and Objectives The effect of anesthesia choice on endovascular thrombectomy (EVT) outcomes is unclear. Collateral status on perfusion imaging may help identify the optimal anesthesia choice. Methods In a pooled patient-level analysis of EXTEND-IA, EXTEND-IA TNK, EXTEND-IA TNK part II, and SELECT, EVT functional outcomes (modified Rankin Scale score distribution) were compared between general anesthesia (GA) vs non-GA in a propensity-matched sample. Furthermore, we evaluated the association of collateral flow on perfusion imaging, assessed by hypoperfusion intensity ratio (HIR) – Tmax \u3e 10 seconds/Tmax \u3e 6 seconds (good collaterals – HIR \u3c 0.4, poor collaterals – HIR ≥ 0.4) on the association between anesthesia type and EVT outcomes. Results Of 725 treated with EVT, 299 (41%) received GA and 426 (59%) non-GA. The baseline characteristics differed in presentation National Institutes of Health Stroke Scale score (median [interquartile range] GA: 18 [13–22], non-GA: 16 [11–20], p \u3c 0.001) and ischemic core volume (GA: 15.0 mL [3.2–38.0] vs non-GA: 9.0 mL [0.0–31.0], p \u3c 0.001). In addition, GA was associated with longer last known well to arterial access (203 minutes [157–267] vs 186 minutes [138–252], p = 0.002), but similar procedural time (35.5 minutes [23–59] vs 34 minutes [22–54], p = 0.51). Of 182 matched pairs using propensity scores, baseline characteristics were similar. In the propensity score–matched pairs, GA was independently associated with worse functional outcomes (adjusted common odds ratio [adj. cOR]: 0.64, 95% CI: 0.44–0.93, p = 0.021) and higher neurologic worsening (GA: 14.9% vs non-GA: 8.9%, aOR: 2.10, 95% CI: 1.02–4.33, p = 0.045). Patients with poor collaterals had worse functional outcomes with GA (adj. cOR: 0.47, 95% CI: 0.29–0.76, p = 0.002), whereas no difference was observed in those with good collaterals (adj. cOR: 0.93, 95% CI: 0.50–1.74, p = 0.82), pinteraction: 0.07. No difference was observed in infarct growth overall and in patients with good collaterals, whereas patients with poor collaterals demonstrated larger infarct growth with GA with a significant interaction between collaterals and anesthesia type on infarct growth rate (pinteraction: 0.020). Discussion GA was associated with worse functional outcomes after EVT, particularly in patients with poor collaterals in a propensity score–matched analysis from a pooled patient-level cohort from 3 randomized trials and 1 prospective cohort study. The confounding by indication may persist despite the doubly robust nature of the analysis. These findings have implications for randomized trials of GA vs non-GA and may be of utility for clinicians when making anesthesia type choice. Classification of Evidence This study provides Class III evidence that use of GA is associated with worse functional outcome in patients undergoing EVT. Trial Registration Information EXTEND-IA: ClinicalTrials.gov (NCT01492725); EXTEND-IA TNK: ClinicalTrials.gov (NCT02388061); EXTEND-IA TNK part II: ClinicalTrials.gov (NCT03340493); and SELECT: ClinicalTrials.gov (NCT02446587)

Development of Product Recyclability Index Utilizing Design for Assembly and Disassembly Principles

Designing products for recyclability is driven by environmental and economic goals. Several design for assembly (DFA) rules and parameters can be used to gauge the recyclability index of product designs. These indices can be used for comparative analysis of the recyclability of different products. This assists the designer in making design choices related to the product's end of life. However, many of the existing recyclability indices are only available after design and manufacturing decisions are made. If such design decisions could be made earlier in the design process, when the design space is less bound, recyclability could be considered earlier. A case study is performed to determine if DFA parameters could be utilized to determine product recyclability. The parameters were obtained from existing DFA time estimate tables. The results of the study indicated that the recyclability of the product, as defined by established recyclability metrics, could be predicted through DFA measures. A negative correlation was realized between recyclability and insertion time. Components that required greater time to mate during assembly adversely affected the recyclability of the product. Conversely, handing time was found to have no predictive capability on product recyclability. These findings are used to develop a recyclability index that utilizes the DFA measures, allowing designers and engineers to determine recyclability earlier in the design process.</jats:p

Utilizing Design for Assembly Principles to Predict Product Recyclability

Designing products for recyclability is driven by environmental and economic goals. Several Design for Assembly rules and parameters can be used to gauge the recyclability index of product designs. These indices can then be used for comparative analysis of the recyclability of different products. This would assist the designer in making design choices related to the end of the product’s life cycle. Further, such design decisions could be made earlier in the design process, when the design space is less bound. A case study was conducted for different products to compare their recyclability indices. The parameters were obtained from existing Design for Assembly time estimate tables. The results of the study indicated the recyclability of the product, as defined by established recyclability metrics, could be predicted through design for assembly measures. A statistically significant negative correlation was realized between recyclability and insertion time. Effectively, components that required greater time to mate during assembly adversely affected the recyclability of the product. Conversely, handing time was found to have no predictive capability to product recyclability.</jats:p

Drill Hole Optimization for Augmenting Structural Integrity

Structures develop cracks during the course of there life resulting in catastrophic failures. This can be reduced by drilling holes near the crack tip. Here the aspect of optimal position and size of the drill hole has been analysed. Additionally the effect of supplementary hole has also been made. Finite element code ANSYS was used for the analysis. To verify the fracture capabilities of ANSYS the results were corroborated using photoelastic techniques. It was observed that reduction in stress intensity factor to a great extent depends upon the position of the stop hole. Also it was observed that as the radius of the crack was increased the stress intensity factor increased. Creating supplementary hole further reduced the stress intensity factor. So it can be concluded that for employing the concept of drill hole its position and size should be accurately determined.</jats:p

Sky Cargo: Self-Navigating Delivery Drone

&lt;p&gt;The rapid growth of e-commerce and the increasing demand for efficient, sustainable, reliable, economical delivery solutions have driven the development of autonomous delivery drones. The "Sky &nbsp;Cargo Self-Navigating Delivery Drone," has a cutting- edge technology designed to revolutionize the logistics &nbsp;and transportation industry. The system has a predefined path between its starting point to its delivery location based. The system ensures the precision landing at the receiver end by verification at the delivery location by the uniquely generated Aruco marker. An optimal path is given to the drone by performing the mathematical calculations between the starting point to its delivery point&lt;/p&gt;&lt;p&gt;Keywords:- Autonomous drone, Self-Navigating, precision landing, Aruco marker, optimal path.&lt;/p&gt

Abstract P2-12-24: Exosomal metabolic signatures are associated with differential response to neoadjuvant chemotherapy in patients with breast cancer

Abstract Background: Neoadjuvant chemotherapy (NAC) is becoming the standard of care for aggressive breast cancer (BC). In patients with BC, NAC can increase eligibility for breast-conserving surgery, lower the excision volume, and assist in evaluating the disease course. NAC may shrink (residual disease, RD) or even eliminate (pathologic complete response, pCR) the tumor. Patients with RD often have a poor long-term prognosis. In contrast, pCR is associated with better long-term survival outcomes. Approximately 30% of patients with BC show pCR after NAC, while the rest exhibit RD. A critical barrier to improving NAC outcomes in patients with BC is the lack of precise molecular targets and limited understanding of the molecular mechanisms underlying differential treatment outcomes in patients with BC receiving NAC. Thus, there is an urgent clinical need to elucidate the underlying molecular regulation associated with NAC resistance. Studies have shown that cellular stress induces the release of small extracellular vesicles known as exosomes, contributing to drug resistance. In this study, we evaluated the ability of exosomal metabolic profiles to predict NAC response in BC patients. Methods: We collected blood samples of 16 patients with BC who received NAC at Grady Memorial Hospitals, USA. Further, total exosomes were isolated from plasma by an ultracentrifugation method and characterized for their concentration (number/ml), size distribution, and exosomal content. Exosome sizes were validated using nanoparticle tracking analysis. RNA, proteins, and metabolites were isolated from exosomes to perform deep multiplatform analyses (viz. miRNA seq, proteomics, and metabolomics) of exosomal cargo to identify various potential biological determinants of NAC response and evaluate their contributions to the risk of RD in patients with BC after NAC. KEGG and HMDB IDs were used for metabolomics data analyses. Various analyses viz. enriched metabolomic pathway analysis, MS peak to pathway analysis (using GSEA and Mummichog), and network explorer analysis were performed using Metaboanalyst online portal to reveal the metabolic signatures in exosomes of BC patients who exhibited pCR and RD after NAC treatment. Results: Among the 16 patients with BC who received NAC, eight patients attained pCR, and eight had RD. Interestingly, we found that patients with pCR secreted 61% fewer exosomes but had 24% larger-sized exosomes than patients with RD following NAC. Furthermore, significant differences in the loading of exosomal cargo were observed between the two groups. Based on these results, we proposed that the differential RNA, protein, and metabolite profile of exosomes might contribute to the higher drug sensitivity in patients with pCR. Our proteomics and miRNA-seq analyses of exosomes from patients with pCR and RD after NAC did not show any significant differences between the groups. However, metabolite set enrichment analysis using MetaboAnalyst revealed that compared to exosomes from patients with pCR, patients with RD were significantly enriched in various metabolic pathways. These pathways included valine, leucine, and isoleucine biosynthesis; phenylalanine metabolism; one-carbon pool folate; and inositol phosphate metabolism. Additionally, MS peak to pathway analysis revealed differential enrichment of various other metabolic pathways, particularly in patients with RD.Conclusions: These data strongly suggest that exosomal metabolic signatures are associated with differential NAC outcomes in patients with BC. We believe that in-depth studies of these metabolite signatures will give essential clues about differential NAC response in patients with BC. Citation Format: Shriya Joshi, Chakravarthy Garalapati, Shristi Bhattarai, Darshan Shimoga Chandrashekar, Sooryanarayana Varambally, Gagan Deep, Ritu Aneja. Exosomal metabolic signatures are associated with differential response to neoadjuvant chemotherapy in patients with breast cancer [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P2-12-24.</jats:p