Aims:The aim of this investigation was to explore and characterize alterations in coronary circulatory function in function of increasing body weight with medically controlled cardiovascular risk factors and, thus, "metabolically" unhealthy obesity. Materials and Methods:We prospectively enrolled 106 patients with suspected CAD but with normal stress-rest myocardial perfusion on 13 N-ammonia PET/CT and with medically controlled or no cardiovascular risk factors. 13 N-ammonia PET/CT concurrently determined myocardial blood flow (MBF) during pharmacologically induced hyperaemia and at rest. Based on body mass index (BMI), patients were grouped into normal weight (BMI: 20.0-24.9 kg/m 2 , n = 22), overweight (BMI: 25.0-29.9 kg/m 2 , n = 27), obese (BMI: 30.0-39.9 kg/m 2 , n = 31), and morbidly obese (BMI ≥ 40kg/m 2 , n = 26). Results:Resting MBF was comparable among groups (1.09 ± 0.18 vs. 1.00 ± 0.15 vs. 0.96 ± 0.18 vs.. 1.06 ± 0.31 ml/g/min; p = .279 by ANOVA). Compared to normal weight individuals, the hyperaemic MBF progressively decreased in in overweight and obese groups, respectively (2.54 ± 0.48 vs. 2.02 ± 0.27 and 1.75 ± 0.39 ml/g/min; p < .0001), while it increased again in the group of morbidly obese individuals comparable to normal weight (2.44 ± 0.41 vs. 2.54 ± 0.48 ml/g/ min, p = .192). The BMI of the study population correlated with the hyperaemic MBF in a quadratic or U-turn fashion (r = .34, SEE = 0.46; p ≤ .002). Conclusions:The U-turn of hyperaemic MBF from obesity to morbid obesity is likely to reflect contrasting effects of abdominal versus subcutaneous adipose tissue on coronary circulatory function indicative of two different disease entities, but needing further investigations.

Objectives: To define the care cascade for patients with serious injection drug use related infections (SIRI) in a tertiary hospital system and compare outcomes of those who did and did not participate in an opioid use disorder (OUD) treatment referral program. Methods: The medical records of patients admitted with both OUD and SIRI including endocarditis, osteomyelitis, septic arthritis, epidural abscess, thrombophlebitis, myositis, bacteremia, and fungemia from 2016-2019 were retrospectively reviewed. Patient demographics, clinical covariates, 90-day readmission rates, and outcomes data were collected. We compared data from those who were successfully referred to outpatient care through Engaging Patients in Care Coordination (EPICC), a peer recovery specialist-run OUD treatment referral program, to those who did not receive outpatient referral. Results: During the study period 334 persons who inject opioids were admitted with SIRI. Fourteen admitted patients died and were excluded from the analysis. The all-cause readmission rate was lower among patients referred to the EPICC program (18/76 [23.7%]) compared to those not referred to EPICC (100/244 [41.0%]) (OR 0.44; 95% CI 0.25-0.80). Conclusion: An OUD care cascade evaluation for patients with SIRI demonstrated that referral to peer recovery services with outpatient OUD treatment was associated with reduced 90-day readmission rate.

Aims The aim of this study is to evaluate whether post‐acute sequelae of COVID‐19 cardiovascular syndrome (PASC‐CVS) is associated with alterations in coronary circulatory function. Materials and Methods In individuals with PASC‐CVS but without known cardiovascular risk factors ( n = 23) and in healthy controls (CON, n = 23), myocardial blood flow (MBF) was assessed with 13 N‐ammonia and PET/CT in mL/g/min during regadenoson‐stimulated hyperemia, at rest, and the global myocardial flow reserve (MFR) was calculated. MBF was also measured in the mid and mid‐distal myocardium of the left ventricle (LV). The Δ longitudinal MBF gradient (hyperemia minus rest) as a reflection of an impairment of flow‐mediated epicardial vasodilation, was calculated. Results Resting MBF was significantly higher in PASC‐CVS than in CON (1.29 ± 0.27 vs. 1.08 ± 0.20 ml/g/min, p ≤ .024), while hyperemic MBFs did not differ significantly among groups (2.46 ± 0.53 and 2.40 ± 0.34 ml/g/min, p = .621). The MFR was significantly less in PASC‐CVS than in CON (1.97 ± 0.54 vs. 2.27 ± 0.43, p ≤ .031). In addition, there was a Δ longitudinal MBF gradient in PASC‐CVS, not observed in CON (−0.17 ± 0.18 vs. 0.04 ± 0.11 ml/g/min, p < .0001). Conclusions Post‐acute sequelae of COVID‐19 cardiovascular syndrome may be associated with an impairment of flow‐mediated epicardial vasodilation, while reductions in coronary vasodilator capacity appear predominantly related to increases in resting flow in women deserving further investigations.

Cell migration is an important process occurring during normal animal development but also in the early stages of metastatic cancer when cells invasively migrate out of the primary tumor. It is therefore likely that some of the same genes function in both migrations. Although transcriptional profiling has identified many genes differentially expressed between metastases and primary tumors, we do not understand the function of most of these genes in either normal or disease states. Our goal has been to identify conserved genes used in migration of mammalian metastasis and normal C. elegans development to further characterize their function in both systems. From two published transcriptional profile datasets1,2, we selected genes that were upregulated in metastases compared to primary tumors, and then identified the C. elegans orthologs of those genes to generate a list of 107 genes. We further narrowed our selection to 87 genes based on the gene's expression in the linker cell, a migratory C. elegans cell that we had previously transcriptionally profiled3. We used RNAi by feeding to reduce the function of these genes in three migratory cell types in C. elegans. The male linker cell and hermaphrodite distal tip cell are both somatic gonadal cells that migrate long distances while pulling along attached, non-motile gonadal cells, yet differ in their gender and in their migratory path. The sex myoblast migrates individually and for a short distance. We scored defects in migratory path, cell shape, and speed. 19 genes affected the migration of the linker cell and 16 genes that of the distal tip cell. Six genes overlapped between these two cell migrations, including SNTB2/syntrophin, an adaptor protein in the dystrophin pathway, and ATP6V0A1, a vacuolar proton-translocating ATPase. The sex myoblast screen is still ongoing, but only one of 25 genes affects its migration, showing even fewer overlapping genes with the other two cells. Among the genes that have penetrant but cell-specific defects are UTRN/utrophin, CAP1/ adenylate cyclase-associated protein, STXBP2/syntaxin binding protein, and MYL12A/myosin light chain regulatory subunit. Our results indicate that different cells use different genes for their migration, and suggest that different cancer cell types may also. This underscores the importance of characterizing the function of diverse genes to both understand their role in metastasis and identify cell type-specific drug targets. 1. Alonso, S.R. et al. (2007) A high-throughput study in melanoma identifies epithelial-mesenchymal transition as a major determinant of metastasis. Cancer Res. 67:3450-3460. 2. Patsialou, A. et al. (2012) Selective gene-expression profiling of migratory tumor cells in vivo predicts clinical outcome in breast cancer patients. Breast Cancer Res. 14:R139. 3. Schwarz, E.M.*, Kato, M*. Sternberg, P.W. (2012) Functional transcriptomics of a migrating cell in Caenorhabditis elegans. Proc. Natl. Acad. Sci.109: 16246-51. Citation Format: Mihoko Kato, Jonathan Liu, Olivia Box Power, Anand Upadhyaya, John Yim, Paul Sternberg. Comparison of genes upregulated in metastasis with three C. elegans cell migrations. [abstract]. In: Proceedings of the AACR Special Conference: The Translational Impact of Model Organisms in Cancer; Nov 5-8, 2013; San Diego, CA. Philadelphia (PA): AACR; Mol Cancer Res 2014;12(11 Suppl):Abstract nr A46.